Prostaglandins, Leukotrienes and Essential Fatty Acids,Magnetic Resonance Materials in Physics, Biology and Medicine,Philosophical Studies,Genetics,Earth Science,Immunogenetics, Otolaryngology,Quaternary Geochronology

Quaternary Geochronology Assessing the dead carbon proportion of a modern speleothem from central Brazil Publication date: June 2019 Source: Quaternary Geochronology, Volume 52 Author(s): K.D. Macario, N.M. Stríkis, F.W. Cruz, I. Hammerschlag, E.Q. Alves, V.F. Novello, L. Edwards, H. Cheng, F.R.D. Andrade, P.F.S.M. Buarque, J.A.S. Garbelim Abstract Geographic and temporal variations in atmospheric carbon isotopic ratios are recorded in environmental proxies. In temperate regions, this may assist in the construction of datasets for the calibration of radiocarbon ages. Over the tropics, the high growth rate of speleothems combined with high precision 230Th dating provides potential records for atmospheric 14C reconstruction. In this preliminary work, we investigate the isotopic composition (δ18O and δ13C) of a speleothem from central Brazil, precisely dated by the multi-collector inductively coupled plasma mass spectrometry technique (MC-ICP-MS). Radiocarbon Accelerator Mass Spectrometry (AMS) measurements were compared to the 14C concentration in the atmosphere during the nuclear tests period based on the Bomb13SH1-2 curve. Our results show that the speleothem dead carbon proportion is less than 20% between 1932 and 1992 AD while δ13C values vary between −14 and −9‰. Given that the empirical radiocarbon calibration curves for the Southern Hemisphere were constructed based on limited records, we discuss the potential and limitations of Brazilian speleothems for the evaluation of atmospheric 14C concentrations over the last millennia. Geochemical characterisation of the Late Quaternary widespread Japanese tephrostratigraphic markers and correlations to the Lake Suigetsu sedimentary archive (SG06 core) Publication date: June 2019 Source: Quaternary Geochronology, Volume 52 Author(s): Paul G. Albert, Victoria C. Smith, Takehiko Suzuki, Danielle McLean, Emma L. Tomlinson, Yasuo Miyabuchi, Ikuko Kitaba, Darren F. Mark, Hiroshi Moriwaki, SG06 Project Members, Takeshi Nakagawa Abstract Large Magnitude (6–8) Late Quaternary Japanese volcanic eruptions are responsible for widespread ash (tephra) dispersals providing key isochrons suitable for the synchronisation and dating of palaeoclimate archives across East Asia, the NW Pacific and beyond. The transfer of geochronological information using these eruption deposits demands robust tephra correlations underpinned by detailed and precise volcanic glass geochemical data. Presented here is a major (electron microprobe; EMP) and trace element (Laser ablation inductively coupled plasma mass spectrometry; LA-ICP-MS) characterisation of near-source deposits from a series of large magnitude Japanese eruptions spanning approximately the last 150 ka. These data offer new insights into diagnostic compositional variations of the investigated volcanic sources spanning the Japanese islands. Whilst in the case of the highly productive Aso caldera (Kyushu), we are able to explore compositional variations through successive large magnitude eruptions (50–135 ka). These near-source volcanic glass data are used to validate and refine the visible tephrostratigraphy of the intensely dated Lake Suigetsu sedimentary record (SG06 core), Honshu Island, whilst also illustrating key tephrostratigraphic tie points to other East Asian palaeoclimate records (e.g. Lake Biwa). The identification of widespread Japanese tephrostratigraphic markers in the SG06 sediment record enables us to place chronological constraints on these ash dispersals, and consequently explosive volcanism at source volcanoes situated along the Kyushu Arc, including Kikai, Ata and Aso calderas. The proximal Aso-4 Ignimbrite (Magnitude 7.7) deposit is dated here by 40Ar/39Ar at 86.4 ± 1.1 ka (2σ), and provides a chronological anchor (SG06-4963) for the older sediments of the Lake Suigetsu record. Finally, trace element glass data verify visible ash fall layers derived from other compositionally distinct source regions of Japanese volcanism, including activity along the northern Izu-Bonin arc and North East Japan Arcs. These findings underline the Lake Suigetsu record as central node in the Japanese tephrostratigraphic framework. Cosmogenic and nucleogenic 21Ne in quartz in a 28-meter sandstone core from the McMurdo Dry Valleys, Antarctica Publication date: June 2019 Source: Quaternary Geochronology, Volume 52 Author(s): Greg Balco, Pierre-Henri Blard, David L. Shuster, John O.H. Stone, Laurent Zimmermann Abstract We measured concentrations of Ne isotopes in quartz in a 27.6-m sandstone core from a low-erosion-rate site at 2183 m elevation at Beacon Heights in the Antarctic Dry Valleys. Surface concentrations of cosmogenic 21Ne indicate a surface exposure age of at least 4.1 Ma and an erosion rate no higher than ca. 14 cm Myr−1 21Ne concentrations in the upper few centimeters of the core show evidence for secondary spallogenic neutron escape effects at the rock surface, which is predicted by first-principles models of cosmogenic-nuclide production but is not commonly observed in natural examples. We used a model for 21Ne production by various mechanisms fit to the observations to distinguish cosmic-ray-produced 21Ne from nucleogenic 21Ne produced by decay of trace U and Th present in quartz, and also constrain rates of subsurface 21Ne production by cosmic-ray muons. Core samples have a quartz (U-Th)/Ne closure age, reflecting cooling below approximately 95 °C, near 160 Ma, which is consistent with existing apatite fission-track data and the 183 Ma emplacement of nearby Ferrar dolerite intrusions. Constraints on 21Ne production by muons derived from model fitting are consistent with a previously proposed value of 0.79 mb at 190 GeV for the cross-section for 21Ne production by fast muon interactions, but indicate that 21Ne production by negative muon capture is likely negligible. U-Th and radiocarbon dating of calcite speleothems from gypsum caves (Emilia Romagna, North Italy) Publication date: June 2019 Source: Quaternary Geochronology, Volume 52 Author(s): Andrea Columbu, Russell Drysdale, John Hellstrom, Jon Woodhead, Hai Cheng, Quan Hua, Jian-xin Zhao, Paolo Montagna, Edwige Pons-Branchu, R. Lawrence Edwards Abstract High-resolution U-Th and 14C dating of two calcite flowstones (RTf: Last Interglacial; RTy: Late Holocene) from the Re Tiberio – Monte Tondo karst system (North Italy) is presented to investigate the palaeoclimate potential of speleothems from gypsum caves. To date, there is a lack of information regarding the dating potential of calcite speleothems that have grown in such gypsum karst environment (e.g. no pseudokarst). High-resolution U-Th dating, aimed at establishing if these speleothems can provide robust radiometric age sequences, is first presented. Although both samples show promise for reliable radiometric dating, about 20% of the ages in the RTf dataset were excluded from the age-model as outliers. These outliers are best explained by post-depositional diagenetic processes affecting the U-Th system rather than anything specific to gypsum karst environment conditions. In contrast, outliers were not detected in the RTy sample, but U-Th analysis was not able to constrain its relatively young age (∼600 years before present, B.P.). Consequently, radiocarbon measurements were undertaken, and combined with the U-Th ages to build an age-model. The latter allowed the estimation of "dead carbon fraction" (DCF), which yields a constant value through time, and a magnitude comparable to other sites where climate is similar to Monte Tondo. Soils were considered the main source of carbon, because bedrock dissolution acted predominantly under open-system conditions, and soil organic matter (SOM) turnover rate appears above average compared to sites studied elsewhere. Evaluating the potential of tree-ring methodology for cross-dating of three annually laminated stalagmites from Zoolithencave (SE Germany) Publication date: June 2019 Source: Quaternary Geochronology, Volume 52 Author(s): Dana F.C. Riechelmann, Jens Fohlmeister, Tobias Kluge, Klaus Peter Jochum, Detlev K. Richter, Michael Deininger, Ronny Friedrich, Norbert Frank, Denis Scholz Abstract Three small stalagmites from Zoolithencave (southern Germany) show visible laminae, which consist of a clear and a brownish, pigmented layer pair. This potentially provides the opportunity to construct precise chronologies by counting annual laminae. The growth period of the three stalagmites was constrained by the 14C bomb peak in the youngest part of all three stalagmites and 14C-dating of a piece of charcoal in the consolidated base part of stalagmite Zoo-rez-2. These data suggest an age of AD 1970 for the top laminae and a lower age limit of AD 1973–1682 or AD 1735–1778. Laminae were counted and their thickness determined on scanned thin sections of all stalagmites. On stalagmites Zoo-rez-1 and -2, three tracks were measured near the growth axes, each separated into three sections at prominent anchor laminae (I, II, III). Each section was replicated three times (a, b, c). For Zoo-rez-3, only one track was measured. The total number of laminae counted for Zoo-rez-1 ranges from 138 to 177, for Zoo-rez-2 from 119 to 145, and for Zoo-rez-3 from 159 to 166. The numbers agree well with the range constrained by the bomb peak and the age of the charcoal, which supports the annual origin of the laminae. The replicated measurements of the different tracks as well as the three different tracks on the stalagmites Zoo-rez-1 and -2 were cross-dated using the TSAP-Win® tree-ring software. This software is very useful for cross-dating because it enables to insert or delete missing or false laminae as well as identifying common pattern by shifting the series back and forth in time. However, visual inspection of the thin sections was necessary to confirm detection of missing or false laminae by TSAP-Win®. For all three Zoo-rez speleothems, cross-dating of the mean lamina thickness series was not possible due to a missing common pattern. The cross-dating procedure results in three refined chronologies for the three Zoo-rez stalagmites of ranging from AD 1821–1970 (Zoo-rez-1), AD 1835–1970 (Zoo-rez-2), and AD 1808–1970 (Zoo-rez-3). Guidelines for reporting and archiving 210Pb sediment chronologies to improve fidelity and extend data lifecycle Publication date: June 2019 Source: Quaternary Geochronology, Volume 52 Author(s): Colin J. Courtney Mustaphi, Janice Brahney, Marco A. Aquino-López, Simon Goring, Kiersten Orton, Alexandra Noronha, John Czaplewski, Quinn Asena, Sarah Paton, Johnny Panga Brushworth Abstract Radiometric dating methods are essential for developing geochronologies to study Late Quaternary environmental change and 210Pb dating is commonly used to produce age-depth models from recent (within 150 years) sediments and other geoarchives. The past two centuries are marked by rapid environmental socio-ecological changes frequently attributed to anthropogenic land-use activities, modified biogeochemical cycles, and climate change. Consequently, historical reconstructions over this recent time interval have high societal value because analyses of these datasets provide understanding of the consequences of environmental modifications, critical ecosystem thresholds, and to define desirable ranges of variation for management, restoration, and conservation. For this information to be used more broadly, for example to support land management decisions or to contribute data to regional analyses of ecosystem change, authors must report all of the useful age-depth model information. However, at present there are no guidelines for researchers on what information should be reported to ensure 210Pb data are fully disclosed, reproducible, and reusable; leading to a plethora of reporting styles, including inadequate reporting that reduces potential reusability and shortening the data lifecycle. For example, 64% of the publications in a literature review of 210Pb dated geoarchives did not include any presentation of age uncertainty estimates in modeled calendar ages used in age-depth models. Insufficient reporting of methods and results used in 210Pb dating geoarchives severely hampers reproducibility and data reusability, especially in analyses that make use of databased palaeoenvironmental data. Reproducibility of data is fundamental to further analyses of the number of palaeoenvironmental data and the spatial coverage of published geoarchives sites. We suggest, and justify, a set of minimum reporting guidelines for metadata and data reporting for 210Pb dates, including an IEDA (Interdisciplinary Earth Data Alliance), LiPD (Linked Paleo Data) and generic format data presentation templates, to contribute to improvements in data archiving standards and to facilitate the data requirements of researchers analyzing datasets of several palaeoenvironmental study sites. We analyse practices of methods, results and first order interpretation of 210Pb data and make recommendations to authors on effective data reporting and archiving to maximize the value of datasets. We provide empirical evidence from publications and practitioners to support our suggested reporting guidelines. These guidelines increase the scientific value of 210Pb by expanding its relevance in the data lifecycle. Improving quality and fidelity of environmental datasets broadens interdisciplinary use, lengthens the potential lifecycle of data products, and achieves requirements applicable for evidenced-based policy support. Increased radiocarbon dating resolution of ombrotrophic peat profiles reveals periods of disturbance which were previously undetected Publication date: June 2019 Source: Quaternary Geochronology, Volume 52 Author(s): Piotr Kołaczek, Mariusz Gałka, Mariusz Lamentowicz, Katarzyna Marcisz, Katarzyna Kajukało-Drygalska, Monika Karpińska-Kołaczek Abstract We tested the robustness of three previously published age-depth models by supplementing them with five new 14C AMS dates. The age-models were calculated for profiles retrieved from ombrotrophic peatlands in northern Poland (Bagno Kusowo, Gązwa, and Mechacz Wielki bogs). For the Bagno Kusowo and Mechacz Wielki bogs, the addition of new dates did not significantly change the shape of the age-depth models. In the topmost sections of these peat profiles the new dates did not conform with previously published models. The updated age-depth model from the Gązwa bog profile revealed the presence of 14C date inversions, which led to multiple chronology scenarios. The section of the Gązwa profile with the outliers was characterised by (i) a higher amplitude of reconstructed water table fluctuations in comparison with the lower peat layers and (ii) a higher frequency of layers with macrocharcoal (indicating local fires). However, no relationship was found between the presence/absence of Arcella discoides, Eriophorum vaginatum (hydrological disturbances), and coprophilous fungi (presence of herbivores or omnivores) and peat layers under and above the section with 14C date inversions. Moreover, a section with outlying 14C dates did not differ in terms of disturbance indicator content compared with the profiles from Bagno Kusowo and Mechacz Wielki. Although our study does not give a clear explanation for the presence of the section rich in outlying dates in the Gązwa profile, it proves that with low-resolution dating it might be very difficult to detect sections of peat disturbance. In addition, obtaining the most accurate reconstruction of the vertical depth range of post-bomb dates in a peat core may improve age-depth models for the youngest peat layers. Seismic history from in situ 36Cl cosmogenic nuclide data on limestone fault scarps using Bayesian reversible jump Markov chain Monte Carlo Publication date: June 2019 Source: Quaternary Geochronology, Volume 52 Author(s): J. Tesson, L. Benedetti Abstract Constraining the past seismic activity and the slip-rates of faults over several millennials is crucial for seismic hazard assessment. Chlorine 36 (36Cl) in situ produced cosmogenic nuclide is increasingly used to retrieve past earthquakes histories on seismically exhumed limestone normal fault-scarps. Here we present a new methodology to retrieve the exhumation history based on a Bayesian transdimensional inversion of the 36Cl data and using the latest muon production calculation method. This procedure uses the reversible jump Markov chains Monte-Carlo algorithm (RJ-MCMC, Green 1995) which enables 1-exploring the parameter space (number of events, age and slip of the events), 2-finding the most probable scenarios, and 3- quantifying the associated uncertainties. Through a series of synthetic tests, the algorithm revealed a great capacity to constrain event slips and ages in a short computational time (several days) with a precision that can reach 0.1 ky and 0.5 m for the age and slip of exhumation event, respectively. In addition, our study show that the amount of 36Cl accumulated when the sampled fault-plane was still buried under the colluvial wedge, prior its exhumation, might represents up to 35% of the total 36Cl. Additional sampling under the colluvial is necessary to constrain this contribution. Temporal variability of 14C reservoir effects and sedimentological chronology analysis in lake sediments from Chibuzhang Co, North Tibet (China) Publication date: June 2019 Source: Quaternary Geochronology, Volume 52 Author(s): Hao Chen, Liping Zhu, Jianting Ju, Junbo Wang, Qingfeng Ma Abstract Chronological analysis is the basic premise for paleoenvironmental research on lake sediment cores. It mainly employs bulk organic matter as a mixed dating material, although terrestrial plant remains are believed to provide reliable radiocarbon (14C) ages. 14C reservoir effects (REs) are generally problematic in establishing a final chronology and are usually recorded in aquatic macrophytes by the incorporation of dissolved inorganic carbon in high-altitude lakes of the Tibetan Plateau. We present a typical case of a 5.48 m-long core sampled from Chibuzhang Co, a lake in north Tibet, China, which contained two obvious obstacles: high REs and age reversals. The 14C RE was recently as much as ∼3500 years in the upper part according to total organic carbon (TOC) 14C ages and related dating from 210Pbex activity. It notably changed during the climatic transition to the Holocene due to carbonate input from catchment erosion and glacial meltwater, resulting in reversed 14C ages in the lower section of the core. 14C-dead carbon (or old carbon) dissolved in lake water was incorporated in the dating materials, as inferred from the 14C ages of plant samples. By combining data on grain size and carbonate content changes, two sedimentary units were identified with a boundary at 390 cm depth. These were used to estimate individual sediment accumulation rates (SARs) for the final age-depth models, instead of using a constant RE-corrected chronology. Our results provide an environmental history of ∼12.7 kyr in a long sediment core, based on an optimized SAR model of conventional 14C ages, which is supported by related lacustrine records and Bacon models. Use of separate 14C SAR analyses can solve the problem of age inversion in sediment cores, as sedimentological chronology analysis. Changes in the optically stimulated luminescence (OSL) sensitivity of single grains of quartz during the measurement of natural OSL: Implications for the reliability of optical ages Publication date: Available online 20 May 2019 Source: Quaternary Geochronology Author(s): Naveen Chauhan, A.K. Singhvi Abstract Single Aliquot Regeneration (SAR) protocol has been routinely used to estimate palaeodose for sediment samples. However, it was observed that significant changes in the OSL sensitivity occur during read out of the natural OSL and that the current SAR protocol does not take into account these changes (Singhvi et al., 2011). It was suggested that if not corrected, this change of OSL sensitivity would lead to substantive systematic offsets in ages based on the conventional SAR protocol. To circumvent this issue of sensitivity change of OSL, a natural correction factor based SAR (NCF-SAR) measurement protocol and a correction procedure was suggested by Singhvi et al. (2011) with an implicit but a reasonable assumption that the sensitivity of 110 °C TL peak of quartz correlates with the OSL sensitivity. Use of this correction resulted in reduced over-dispersion in paleodoses and additionally provided a satisfactory way to deal with samples, where natural signal was significantly higher than the saturation value of the regenerated signal. As a logical extension of this work, similar sensitivity changes in the OSL from single grains of quartz were examined and, their impact on the accuracy and reliability of single grain based SAR ages is discussed in this contribution. About ∼200 single grains each from 9 samples of diverse depositional environments were analysed and the NCF of each grain was measured. The single grain NCF' [=(1/NCF)] values varied from 0.7 to 20. Of these ∼50% grains had sensitivity changes in the range of 0.7–1.3. The results indicated that, 1) the brighter grains (photon counts > 1000 c/s in a standard Risoe reader) had NCF′ closer to 1, though significant outliers did exist, 2) the distribution of NCF′ was positively skewed with significant number of values greater than one and, 3) the averaged single grain and multigrain NCF' values were different, suggesting that in the case of multigrain aliquots, sensitivity changes of dim grains, on account of their larger numbers, collectively contributed significantly to the light sum in OSL.

Otolaryngology https://www.sciencedirect.com/journal/american-journal-of-otolaryngology/articles-in-press Research articleAbstract only New wand coblation turbinator vs coblation radiofrequency Yuce Islamoglu, Gulın Gokcen Kesici, Kadır Sınası Bulut, Ebubekır Alper Ozer, ... Mehmet Ali Babademez In Press, Accepted Manuscript, Available online 21 May 2019 Purchase PDFArticle preview Abstract Abstract Introduction İnferior turbinate hypertrophy is a common reason of nasal obstruction. One of the most preferred surgical metod is radiofrequency tecnique. Coblation submucosal reduction turbinator (SCT);new surgical device; started to use recently. Since the method is new, very few study has been done yet. We compare coblation radiofrequency (CR) with SCT. Material and methods Patients with only inferior turbinate hypertrophy but no other diseases included in study. Paranasal CT was made to all patient to rule out turbinate bone hypertrophy. Group 1 32 patient; performed CR. Group 2 25 patients performed SCT. To all patients preoperative and 3 weeks later post operative mucosiliary activity test was performed. Nasal flow was measured with nasal flow meter preoperatively and 3 weeks post operatively. VAS and NOSE was measured. Results compared between two groups. SCT performed under general; CR performed under local anesthesia. Results There was significant nasal flow changes in CR group. (p < 0.001) There was no difference in pre-and-post operatively saccharin test results in CR group. (p = 0.385) There was slightly nasal flow gain in SCT group but this was not statistically significant. (p < 0.192) Also there was no statistically significant changes in pre-and-post operatively saccharin test results in SCT group. (p = 0.167) There was no difference between two groups in terms of post operative nasal flow values and mucociliary activity. (respectively p = 0.562, p = 0.355). (Table 2). Both two tecnique has significant increase in VAS and NOSE scores. (p < 0.001). Conclusions According to our study two tecnique is suitable and safe for nasal mucociliary activity. Tecniques has positive effect on nasal flow, VAS and NOSE scores. select article Post-operative treatment patterns after functional endoscopic sinus surgery: A survey of the American Rhinologic Society Research articleNo access Post-operative treatment patterns after functional endoscopic sinus surgery: A survey of the American Rhinologic Society Samuel N. Helman, Benjamin M. Laitman, Mingyang Gray, Brian Deutsch, ... Anthony Del Signore In Press, Accepted Manuscript, Available online 21 May 2019 Purchase PDF select article Comparison of the effects of the temperature of intratympanic dexamethasone injections on vertigo Research articleAbstract only Comparison of the effects of the temperature of intratympanic dexamethasone injections on vertigo Nurdoğan Ata, Kayhan Öztürk, Bahri Gezgin In Press, Accepted Manuscript, Available online 20 May 2019 Purchase PDFArticle preview Abstract Abstract Objective This study aimed to compare if vertigo improved in patients when the dexamethasone used in the intratympanic (IT) injection was applied at body temperature or at room temperature. Methods The study included 54 patients who had undergone intratympanic treatment due to sudden hearing loss and tinnitus. The IT injection was administered to all patients, 2 times with 1-day intervals. Two different IT injection techniques were used for each patient: injecting dexamethasone at room temperature and injecting it at body temperature. Patients were asked to report the vertigo they felt immediately, and at 15 min after the injection using the visual analogue scale (VAS) and the four-point categorical rating scale (CRS-4). Results The level of vertigo immediately after injection was lower when the dexamethasone was injected at body temperature rather that at room temperature for both the VAS and CRS-4 (p < 0.05). However, no statistical differences in the VAS and CRS-4 self-report values between the two methods were found 15 min after the injection (p > 0.05). Conclusion Vertigo due to IT decreases within minutes. When the IT drugs are administered at body temperature, temporal vertigo due to injection is lower than when they are administered at room temperature. select article Craniofacial injuries related to motorized scooter use: A rising epidemic Research articleAbstract only Craniofacial injuries related to motorized scooter use: A rising epidemic Amishav Bresler, Curtis Hanba, Peter Svider, Michael A. Carron, ... Boris Paskhover In Press, Accepted Manuscript, Available online 20 May 2019 Purchase PDFArticle preview Abstract Abstract Objectives Over the last decade, there has been increased interest in utilizing motorized scooters for transportation. The limited regulation of this modernized vehicle raises numerous safety concerns. This analysis examines a national database to describe the yearly incidence of craniofacial injuries and patterns of injury related to motorized scooter use. Methods The Consumer Product Safety Commission's National Electronic Injury Surveillance system was queried for craniofacial injuries associated with motorized scooter use. Patient demographics, injury type, anatomic location, injury pattern, and helmet status were extracted for analysis. Results From 2008 to 2017, there were 990 recorded events for craniofacial injuries secondary to motorized scooters extrapolating to an estimated 32,001 emergency department (ED) visits. The annual incidence was noted to triple over that 10-year period. The majority of patients were male (62.1%) and the common age groups at presentation were young children 6–12 years old (33.3%), adolescents 13–18 years old (16.1%) and young adults 19–40 years old (18.0%). The most common injury pattern was a closed head injury (36.1%) followed by lacerations (20.5%). Facial fractures were only present in 5.2% of cases. In cases in which helmet use was recorded, 66% of the patients were not helmeted. Conclusion The incidence of motorized scooter related craniofacial trauma is rising, resulting in thousands of ED visits annually. Many patients are experiencing morbid traumatic injuries and may not be wearing appropriate protective equipment. This study highlights the importance of public awareness and policy to improve safety and primarily prevent craniofacial trauma. select article Buteyko breathing technique for obstructive Eustachian tube dysfunction: Preliminary results from a randomized controlled trial Research articleAbstract only Buteyko breathing technique for obstructive Eustachian tube dysfunction: Preliminary results from a randomized controlled trial Haicang Zeng, Xiaoxin Chen, Yaodong Xu, Yiqing Zheng, Hao Xiong In Press, Accepted Manuscript, Available online 17 May 2019 Purchase PDFArticle preview Abstract Abstract Purpose To assess the effectiveness of Buteyko breathing technique in patients with obstructive Eustachian tube dysfunction (ETD). Materials and methods Fifty-one patients (77 ears) aged between 21 and 62 years were randomized to Buteyko breathing in conjunction with medical management (nasal steroid) group or medical management alone group. The Eustachian Tube Dysfunction Questionnaire (ETDQ-7) symptom scores, tympanogram, positive Valsalva maneuver were evaluated at baseline, 6-week and 12-week follow-up. Results Normalization of ETDQ-7 symptom scores at 6-week follow-up was observed in 30.0% (12/40) of the Buteyko breathing group versus 16.2% (6/37) of the controls (P > 0.05). At 12-week follow-up, the ratio rose to 50.0% (20/40) in the Buteyko breathing group and 24.3% (9/37) in the controls (P < 0.05). Tympanogram normalization at 12-week follow-up was observed in 53.6% (15/28) of the Buteyko breathing group versus 26.9% (7/26) of the controls (P < 0.05). The Buteyko breathing group showed slight improvement in positive Valsalva maneuver at 6- and 12-week follow-up (P > 0.05). Conclusions Our study shows that Buteyko breathing technique might be an effective adjunctive intervention in treatment of obstructive ETD, especially for those patients who are refractory to medical treatment and cannot afford Eustachian tube balloon dilation surgery. select article Commentary on Surgical management of patients with Eagle syndrome CorrespondenceNo access Commentary on Surgical management of patients with Eagle syndrome Zhengcai- Lou In Press, Accepted Manuscript, Available online 17 May 2019 Purchase PDF select article Prognostic factors and survival for malignant conjunctival melanoma and squamous cell carcinoma over four decades Research articleAbstract only Prognostic factors and survival for malignant conjunctival melanoma and squamous cell carcinoma over four decades Nicholas B. Abt, Jiawei Zhao, Yuru Huang, Allen O. Eghrari In Press, Corrected Proof, Available online 15 May 2019 Purchase PDFArticle preview Abstract Abstract Purpose To determine the epidemiology and survival of primary conjunctival malignant neoplasms. Methods Retrospective analysis of primary malignant conjunctival neoplasms using Surveillance, Epidemiology, and End Results database from 1973 to 2012. Results Of 1661 cases, the most common neoplasms are squamous cell carcinoma (SCC) at 54.8% and melanoma at 38.8%. Mean diagnostic age for melanoma was 62.1 compared to 65.5 years for SCC (p = 0.002). 52.2% of melanoma are male versus 77.4% of SCC (p < 0.001). For SCC only age (HR: 1.09, 95% CI:1.04–1.14) is a predictor of survival. For melanoma, age (HR: 1.07, 95% CI: 1.05–1.10), male sex (HR: 2.04, 95% CI: 1.16–3.60), T4 tumors (HR: 3.38, 95% CI: 1.17–9.80) and N1 status (HR: 8.69, 95% CI: 2.75–27.42) are all survival predictors. The 5 and 10-year overall survival (OS) estimates are not significantly different between SCC and melanoma, with 70% and 50% respectively for SCC, and 71% and 50% respectively for melanoma. Median survival time is worse for blacks (52 months) compared to whites (118 months) and Asians/Native Americans/Pacific Islanders (145 months), however race was not found to be a significant prognostic factor in multivariate analysis. Five-year survival are similar between decades 1973–1982 (66.2%), 1983–1992 (69.2%), 1993–2002 (71.3%) and 2003–2012 (70.2%). Conclusion Age at diagnosis is a determinant of survival for both conjunctival SCC and melanoma. Male sex, T4 and N1 staging are also important prognostic factors for melanoma. With respect to overall survival, SCC and melanoma did not differ significantly. select article Barometric pressure and the incidence of benign paroxysmal positional vertigo Research articleAbstract only Barometric pressure and the incidence of benign paroxysmal positional vertigo Jonathan Korpon, Roy Sabo, Daniel H. Coelho In Press, Accepted Manuscript, Available online 15 May 2019 Purchase PDFArticle preview Abstract Abstract Objectives To investigate the relationship between barometric pressure and the incidence of benign paroxysmal positional vertigo (BPPV). Methods 181 patients diagnosed with classic BPPV seen between 2011 and 2016 were identified. Demographic information, data of onset, and date of presentation were recorded. Historical barometric data for each of the 60 months were recorded. In addition, monthly counts of other atmospheric, infectious, and allergic variables for that time period were recorded. Correlation analysis compared monthly incidence of BPPV with absolute and relative changes in atmospheric conditions. Results The incidence of BPPV onset demonstrated a statistically significant positive correlation with barometric pressure, where every one-unit increase in barometric pressure leads to an expected increase of 6.1 diagnoses (p = 0.0008). The correlation coefficient (r) between barometric pressure and BPPV diagnoses was 0.66 (95% CI 0.14–0.90) with a p-value of 0.0131. Other seasonal variables demonstrated correlation, though none as strong as barometric pressure. Conclusions Barometric pressure has been long been associated with conditions of the inner ear, though its relationship to the pathogenesis of BPPV has not been investigated. Monthly changes in barometric pressure, rather than the absolute value, may be responsible for the observed changes in incidence. These findings demonstrate a clear association between barometric pressure and BPPV that may help to explain both the etiology of BPPV and its possible connection to migraine-related conditions. select article Thermal injury to common operating room materials by fiber optic light sources and endoscopes Research articleAbstract only Thermal injury to common operating room materials by fiber optic light sources and endoscopes Earl Harley, Raluca Tavaluc, Navin Prasad In Press, Accepted Manuscript, Available online 15 May 2019 Purchase PDFArticle preview Abstract Abstract Purpose To determine the thermal energy damage potential by heat sources, such as endoscopes and fiber optic light cables, in contact with materials commonly placed around an operating room (OR) table. Materials and method Injury by xenon and halogen light sources were tested by direct and indirect contact using fiber optic light bundle cables and scopes at light intensities between ranging from Standby to 100%. The scopes had diameters ranging from 2.7 mm to 10 mm and were set at varying angles. The materials tested were surgical drapes, cotton towels, child shirts, child pants, lap sponges, X-ray detectable sponges, and Mayo covers. The damage potential was determined qualitatively by presence of smoking or smell of burning. Results Permutations involving direct contact were able to cause thermal injury, while permutations involving indirect contact, endoscopes, or halogen lamp were not. The xenon light source with the fiber optic light cable created thermal injury at light intensities of 50%, 75%, and 100%. Time to injury increased as light intensity was decreased. Only the surgical drape, child shorts, and cotton towel showed evidence of burn injury. Conclusions This report supports the potential for thermal injury to the patient secondary to fiber optic light sources, although this potential may be limited in extent. The injury risk can be reduced by avoiding direct contact to materials overlying the patient, confirming standby mode or 25% light intensity, and maintaining the endoscope connected to the fiber optic cable at all times. select article 3D-real IR MRI of Meniere's disease with partial endolymphatic hydrops Research articleAbstract only 3D-real IR MRI of Meniere's disease with partial endolymphatic hydrops Suming Shi, Feng Zhou, Wuqing Wang In Press, Corrected Proof, Available online 15 May 2019 Purchase PDFArticle preview Abstract Abstract Objectives A three-dimensional inversion-recovery sequence with real reconstruction (3D-real IR) sequence 4 h after intravenous gadolinium injection (IV) has been used to visualize the endolymphatic hydrops (ELH) in Meniere's disease (MD). This study was designed to explore the pathology of MD with partial ELH. Methods We collected 338 patients with definite MD, all of whom underwent the IV method. Patients who were found to have partial ELH (vestibular or cochlear) were enrolled. The hearing thresholds of the enrolled patients were analyzed, the regions of interest of the cochlear perilymph and the cerebellum white matter were determined, and the signal intensity ratio in the former to the latter (CC ratio) for both sides in the patients was subsequently evaluated. Results Of the 338 collected patients with definite MD, 19 patients (5.6%) had unilateral vestibular ELH (N = 18) or cochlear ELH (N = 1), and 4 patients (1.2%) with bilateral ELH had contralateral cochlear ELH. The CC ratio of the affected side (1.44 ± 0.46) was higher than that of the unaffected side (1.15 ± 0.33, P < 0.05) in the 19 patients with unilateral ELH. Conversely, there was no difference between the ratio of the contralateral side (1.18 ± 0.16) and the unaffected side (P > 0.05) in the 4 patients with bilateral ELH. Conclusions Partial vestibular ELH was more common than partial cochlear ELH in MD. Moreover, vestibular ELH, rather than cochlear ELH, may correlate with the elevated contrast effect in the affected side, which may better reflect the pathologic mechanism of MD. select article Plunging ranula with lingual nerve tether: Case report and literature review Case reportAbstract only Plunging ranula with lingual nerve tether: Case report and literature review Krish Suresh, Allen L. Feng, Mark A. Varvares In Press, Corrected Proof, Available online 15 May 2019 Purchase PDFArticle preview Abstract Abstract Plunging ranulas are most often treated surgically; various surgical approaches may be necessary depending on the unique characteristics of each case. Here, we present the case of a plunging ranula noted on imaging to have a cordlike tether, which was revealed intraoperatively to be the lingual nerve. This case illustrates the importance of preoperative imaging for surgical planning, and when a transcervical approach may be the best choice for plunging ranulas. select article Teaching nasal analysis to otolaryngology residents Research articleAbstract only Teaching nasal analysis to otolaryngology residents Katie Geelan-Hansen, Douglas Farquhar, Gita Fleischman, J. Madison Clark, William W. Shockley In Press, Accepted Manuscript, Available online 15 May 2019 Purchase PDFArticle preview Abstract Abstract Purpose This prospective cohort study was completed to evaluate a systematic approach for teaching nasal analysis to otolaryngology-head and neck surgery residents. Methods Residents from each post graduate year (PGY) were randomized to the control group or study group. Residents in the study group were given a 10-slide PowerPoint (Microsoft Corp) instruction on nasal analysis using the standard sequence of photographs and anatomic elements to describe in each view. All residents were given the standard sequence of photographs of 3 patients for assessment on nasal analysis. Then 12–14 weeks later all residents were re-evaluated using photographs of 3 new patients. The results were blinded and graded using an 18 point scale modified from a previous publication [1]. Results Twenty otolaryngology-head and neck surgery residents completed the study. Analysis was performed with and without multivariate regression modeling to adjust for PGY, gender, and number of rhinoplasties performed. The study group had overall higher scores in both the initial and follow up assessment, specifically with subsite-specific dorsal deviation, tip projection, and nostril symmetry. Neither group obtained high scores in facial symmetry, skin thickness, tip shape and contour, and radix position at initial or re-assessment. Conclusion Nasal analysis is a complex task. A lecture on a systemic approach to facial analysis given to a group of residents, who performed significantly better on facial analysis cases than controls. Further research in providing feedback, periods of rehearsal or testing, or focused selected elements with serial exposure can be considered. select article The prognostic effect of anatomic subsite in HPV-positive oropharyngeal squamous cell carcinoma Research articleAbstract only The prognostic effect of anatomic subsite in HPV-positive oropharyngeal squamous cell carcinoma Tristan Tham, Michael Wotman, Ansley Roche, Dennis Kraus, Peter Costantino In Press, Corrected Proof, Available online 15 May 2019 Purchase PDFArticle preview Abstract Abstract Background Since most HPV-associated disease occurs in the tonsillar-related areas (TRA) – palatine and lingual tonsils, the effect of HPV on survival in non-tonsillar oropharyngeal subsites (nTRA) is not well established. The objective of this study was to use a large population-based cohort to investigate the survival impact of HPV in nTRA subsites versus TRA subsites. Methods This SEER database study was conducted by stratifying the HPV-positive oropharyngeal cancer cohort into two primary groups, TRA and nTRA. Results HPV-positive squamous cell cancer was significantly more common in TRAs (73%) compared to nTRAs (31.2%, p < 0.001). After controlling for age, treatment, stage, race, and income, patients with HPV-positive disease in nTRAs had a worse cause-specific survival (CSS) than individuals with HPV-positive disease in TRAs (HR = 2.16, 95% CI 1.20–3.86, p = 0.01). Conclusion Patients with HPV-positive OPSCC in nTRAs had poorer survival outcomes compared to patients with HPV-positive OPSCC in TRAs. select article Post-operative epiphora following the transcutaneous medial canthal incision Research articleAbstract only Post-operative epiphora following the transcutaneous medial canthal incision Mark A. Prendes, John Mittel, Peter J. Timoney, Christopher J. Compton, ... H.B. Harold Lee In Press, Corrected Proof, Available online 14 May 2019 Purchase PDFArticle preview Abstract Abstract Purpose The safety profile of the transcutaneous medial canthal incision for access to the medial orbit is assessed with a focus on the risk of post-operative iatrogenic epiphora. Methods A retrospective chart review of patients undergoing medial orbitotomy via the transcutaneous medial canthal incision was performed. Patients with a minimum of 3 months of follow-up were included and post-operative complications were assessed and characterized. Results One-hundred-fifty patients were included in the study. A total of 4 complications were identified, including one each of the following: nasolacrimal duct obstruction, hypertrophic scar, suture granuloma and soft tissue infection. Only the nasolacrimal duct obstruction required surgical intervention. Discussion Access to the medial orbit has been achieved through a variety of approaches, each with their own benefits and risk profile. The transcaruncular approach has increased in usage as a means to avoid a visible cutaneous scar and decrease the risk of iatrogenic epiphora, however, there are specific patients who may have relative contraindications to this approach. The current study demonstrates the low risk profile of the transcutaneous medial canthal incision, specifically the minimal risk of iatrogenic damage to the nasolacrimal outflow system. This approach is another useful tool which orbit surgeons should be familiar with to offer as an option to patients requiring medial orbitotomy. select article Efficacy analysis of medical and surgical treatments in chronic kidney disease patients with secondary hyperparathyroidism Research articleAbstract only Efficacy analysis of medical and surgical treatments in chronic kidney disease patients with secondary hyperparathyroidism Yajing Huang, Hao Wu, Yaqun Wu, Zhiyong Luo In Press, Accepted Manuscript, Available online 14 May 2019 Purchase PDFArticle preview Abstract Abstract Purpose To investigate the effects of surgical and medical treatments on chronic kidney disease (CKD) patients with secondary hyperparathyroidism (SHPT). Materials and methods A total of 198 CKD patients with SHPT were identified at Tongji Hospital from January 2013 to June 2017. Results Surgical group (53 patients) received maintenance dialysis for 78.0 ± 4.9 months, while medical group (84 patients) for 62.0 ± 6.4 months. The serum intact parathyroid hormone (iPTH) in surgical group reduced apparently compared with medical group (P = 0.015) and maintained satisfied result during three years of follow-up (67.4 ± 7.4 pg/ml). The recurrence rate in surgical group was 7.5% and in medical group was 15.5% (P = 0.024). Beyond that, 5 (5.9%) patients suffered persistent hyperparathyroidism in medical group. Conclusion Although the progress of medical treatment is changing rapidly, surgical treatment is still an effective way to control serum iPTH and calcium chronically for SHPT patients. Complex SHPT patients can also receive satisfied effect by surgical treatment, without apparently increasing the risk of complications. select article The case of the eyelid silicone granulomas Case reportAbstract only The case of the eyelid silicone granulomas Jacqueline A. Wulu, Laura Garcia-Rodriguez, Andrey Prilutskiy, Jeffrey Spiegel In Press, Accepted Manuscript, Available online 14 May 2019 Purchase PDFArticle preview Abstract Abstract Foreign body granulomas can develop even several years after autologous fat or filler injection. In some instances the foreign body granulomas have been found at sites other than the original injection site. We present a case of a 48-year-old male with reported "hyaluronic acid fillers" injected into his upper and lower eyelids several years prior. He subsequently developed periorbital swelling with negative allergic and rheumatologic workup. The patient ultimately underwent a blepharoplasty for improvement of the swelling. Histopathology suggested silicone granulomas of the upper and lower eyelid. This case illustrates the importance of keeping foreign body granulomas on the differential for all patients with a history of facial dermal filler injections. Although hyaluronic acid is the most common dermal filler, providers should suspect the use of other dermal fillers including those not FDA approved particularly when common conservative treatment methods are not sufficient. select article Herpes simplex virus of the nose masquerading as invasive fungal sinusitis: A pediatric case series Case reportAbstract only Herpes simplex virus of the nose masquerading as invasive fungal sinusitis: A pediatric case series Neha A. Patel, Rachel Kessel, Gerald Zahtz In Press, Corrected Proof, Available online 14 May 2019 Purchase PDFArticle preview Abstract Abstract The management of invasive fungal sinusitis differs greatly from the management of herpes simplex virus (HSV) of the nose in immunocompromised patients. However, the diagnosis may be uncertain and a delay in treatment can lead to mortality. Here we describe the successful medical management of a series of immunocompromised pediatric patients with HSV lesions of the nose with the initial concern for invasive fungal sinusitis. The diagnosis of HSV herpes was supported by positive polymerase chain reaction (PCR) testing of the nasal lesion. To our knowledge, these are the first cases described in the pediatric literature, emphasizing the need to include this entity on the differential. select article Heterogeneity in the clinical presentation, diagnosis, and treatment initiation of p16-positive oropharyngeal cancer Research articleAbstract only Heterogeneity in the clinical presentation, diagnosis, and treatment initiation of p16-positive oropharyngeal cancer Anish Raman, Neilayan Sen, Ethan Ritz, Mary Jo Fidler, ... Samer Al-khudari In Press, Accepted Manuscript, Available online 14 May 2019 Purchase PDFArticle preview Abstract Abstract Background Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has a patient demographic, presentation, and clinical treatment response distinct from HPV-unassociated OPSCC. The heterogeneity in presentation and diagnosis within a patient population with HPV-positive OPSCC and its impact on times to presentation, diagnosis, and treatment have yet to be characterized. Participants Patients with biopsy-proven p16-positive OPSCC seen and/or treated at our institution between 2008 and 2018. Of 136 patients with OPSCC seen and/or treated at our institution, 101 met criteria for inclusion. Methods Patients were grouped by several parameters including presenting symptom category (asymptomatic neck mass, neck mass with primary-site symptoms, or primary-site symptoms without a neck mass), p16 status on fine-needle aspiration (FNA), and date of presentation. Median time intervals between presentation to imaging, biopsy, and treatment were compared within each parameter using the Kruskal-Wallis test with a significance level of 0.05. Results Sixty-five of the 101 study patients presented with a neck mass. Patients without a neck mass had a longer interval from presentation to imaging than patients with a neck mass (median 4 vs 0 days, p = 0.025). Initial FNA obtained on 61 patients was positive for p16 in 19 patients. Unknown or negative p16 status on FNA was associated with shorter intervals from initial imaging to treatment initiation (39 vs 46.5 days, p = 0.045). Patients presenting in the final three years had a longer interval from presentation to treatment initiation (55 vs 41 days, p = 0.024). Conclusion A neck mass is absent from the clinical picture of a substantial proportion of HPV-associated OPSCC patients. Primary-site symptom category and regional metastasis were not associated with differences in times to diagnosis or treatment initiation at this major referral center. The increased awareness and complexity of treatment decisions related to OPSCC may contribute to the delays in treatment initiation observed in patients with p16-positive FNAs and those who presented in more recent years. select article Impact of metabolic syndrome on recovery of idiopathic sudden sensorineural hearing loss Research articleAbstract only Impact of metabolic syndrome on recovery of idiopathic sudden sensorineural hearing loss Yilong Zhou, Shuyao Qiu, Dabo Liu In Press, Corrected Proof, Available online 14 May 2019 Purchase PDFArticle preview Abstract Abstract Purpose Metabolic syndrome (MetS) was reported to a risk factor of developing idiopathic sudden sensorineural hearing loss (ISSNHL), but limited data exist on its effect on the recovery. The purpose of this study was to evaluate the impact of (MetS) and its components on recovery of patients with ISSNHL. Material and methods 228 ISSNHL patients were divided into MetS group and Non-MetS group according to the diagnostic criteria of MetS, and demographic and clinical characteristics and hearing recovery were reviewed between two groups. Results In total, 86 (37.7%) patients in MetS group, and 142 (62.3%) patients in Non-MetS group. The rate of hypertension, diabetes mellitus, low HDL-C, high TG and obesity were significantly higher in the MetS group than those in the Non-MetS group (P < 0.05). The complete recovery rate and partial recovery rate were significantly lower in the MetS group than those in the Non-MetS group. According to the multivariate analysis, MetS was significantly associated with a poor prognosis; high initial hearing threshold and presence of diabetes mellitus were correlated with a poor prognosis (P < 0.05). Conclusions These results suggest that MetS has a negative impact on the hearing recovery of ISSNHL. High initial hearing threshold and diabetes mellitus were indictors of a poor prognosis of ISSNHL. select article Impact of habitual marijuana and tobacco smoke on severity of chronic rhinosinusitis Research articleAbstract only Impact of habitual marijuana and tobacco smoke on severity of chronic rhinosinusitis Osama G. Abdel-Naby Awad In Press, Corrected Proof, Available online 14 May 2019 Purchase PDFArticle preview Abstract Abstract Purpose Health concerns around cannabis (marijuana) use have focused on the possible relationship with psychosis and lower airway health, however; the effect of cannabis smoking on upper airway health has received less attention. The aim of this study is to investigate difference between exclusive tobacco cigarettes smoking compared with tobacco plus cannabis smoking regarding severity of chronic rhinosinusitis (CRS). Material and methods A prospective cross-sectional study with two groups of CRS patients recruited (Group 1: tobacco cigarettes smokers; 100 patients and group 2: tobacco cigarettes smokers and also cannabis users; 100 patients). Recruitment occurred in a general practice in Egypt. Cannabis use was recorded by self-report. Severity of CRS was assessed and compared between 2 groups using SNOT-20 questionnaire, Lund-Mackay CT score and Lund-Kennedy (LK) endoscopy Score. Results Group 2 patients (tobacco plus cannabis smokers) had significantly higher mean of assessment cores (SNOT-20 (P = 0.005), Lund-Mackay CT score (P = 0.006) and Lund-Kennedy (LK) endoscopy Score (P = 0.005)). Group 2 patients also had significantly higher mean of facial pain/pressure, difficulty sleep, and wake at night, lack of sleep, wake up tired, fatigue, reduced productivity, reduced concentration, frustration/restless/irritable, sad and embarrassed compared to patients in group 1. Conclusion Adult patients who smoked tobacco cigarettes plus cannabis mixed with tobacco had greater health related quality of life burden and more severe CRS compared to patients who smoked tobacco cigarettes only.

ImmunoGenetics Correction to: HLA-F*01:01 presents peptides with N-terminal flexibility and a preferred length of 16 residues The original version of this article contained errors. The Article Title, Figures 1 and 3, and Electronic Supplementary Materials were incorrectly shown in the wrong version. The original article has been corrected. Characterisation of major histocompatibility complex class IIa haplotypes in an island sheep population Abstract The ovine MHC class IIa is known to consist of six to eight loci located in close proximity on chromosome 20, forming haplotypes that are typically inherited without recombination. Here, we characterise the class IIa haplotypes within the Soay sheep (Ovis aries) on St. Kilda to assess the diversity present within this unmanaged island population. We used a stepwise sequence-based genotyping strategy to identify alleles at seven polymorphic MHC class IIa loci in a sample of 118 Soay sheep from four cohorts spanning 15 years of the long-term study on St. Kilda. DRB1, the most polymorphic MHC class II locus, was characterised first in all 118 sheep and identified six alleles. Using DRB1 homozygous animals, the DQA (DQA1, DQA2 and DQA2-like) and DQB (DQB1, DQB2 and DQB2-like) loci were sequenced, revealing eight haplotypes. Both DQ1/DQ2 and DQ2/DQ2-like haplotype configurations were identified and a single haplotype carrying three DQB alleles. A test sample of 94 further individuals typed at the DRB1 and DQA loci found no exceptions to the eight identified haplotypes and a haplotype homozygosity of 21.3%. We found evidence of historic positive selection at DRB1, DQA and DQB. The limited variation at MHC class IIa loci in Soay sheep enabled haplotype characterisation but showed that no single locus could capture the full extent of the expressed variation in the region. Distribution of ancient α1 and α2 domain lineages between two classical MHC class I genes and their alleles in grass carp Abstract Major histocompatibility complex (MHC) class I molecules play a crucial role in the immune response by binding and presenting pathogen-derived peptides to specific CD8+ T cells. From cDNA of 20 individuals of wild grass carp (Ctenopharyngodon idellus), we could amplify one or two alleles each of classical MHC class I genes Ctid-UAA and Ctid-UBA. In total, 27 and 22 unique alleles of Ctid-UAA and Ctid-UBA were found. The leader, α1, transmembrane and cytoplasmic regions distinguish between Ctid-UAA and Ctid-UBA, and their encoded α1 domain sequences belong to the ancient lineages α1-V and α1-II, respectively, which separated several hundred million years ago. However, Ctid-UAA and Ctid-UBA share allelic lineage variation in their α2 and α3 sequences, in a pattern suggestive of past interlocus recombination events that transferred α2+α3 fragments. The allelic Ctid-UAA and Ctid-UBA variation involves ancient variation between domain lineages α2-I and α2-II, which in the present study was dated back to before the ancestral separation of teleost fish and spotted gar (> 300 million years ago). This is the first report with compelling evidence that recombination events combining different ancient α1 and α2 domain lineages had a major impact on the allelic variation of two different classical MHC class I genes within the same species. Convergent inactivation of the skin-specific C-C motif chemokine ligand 27 in mammalian evolution Abstract The appearance of mammalian-specific skin features was a key evolutionary event contributing for the elaboration of physiological processes such as thermoregulation, adequate hydration, locomotion, and inflammation. Skin inflammatory and autoimmune processes engage a population of skin-infiltrating T cells expressing a specific C-C chemokine receptor (CCR10) which interacts with an epidermal CC chemokine, the skin-specific C-C motif chemokine ligand 27 (CCL27). CCL27 is selectively produced in the skin by keratinocytes, particularly upon inflammation, mediating the adhesion and homing of skin-infiltrating T cells. Here, we examined the evolution and coding condition of Ccl27 in 112 placental mammalian species. Our findings reveal that a number of open reading frame inactivation events such as insertions, deletions, and start and stop codon mutations independently occurred in Cetacea, Pholidota, Sirenia, Chiroptera, and Rodentia, totalizing 18 species. The diverse habitat settings and lifestyles of Ccl27-eroded lineages probably implied distinct evolutionary triggers rendering this gene unessential. For example, in Cetacea, the rapid renewal of skin layers minimizes the need for an elaborate inflammatory mechanism, mirrored by the absence of epidermal scabs. Our findings suggest that the convergent and independent loss of Ccl27 in mammalian evolution concurred with unique adaptive roads for skin physiology. HLA-F*01:01 presents peptides with N-terminal flexibility and a preferred length of 16 residues Abstract HLA-F belongs to the non-classical HLA-Ib molecules with a marginal polymorphic nature and tissue-restricted distribution. HLA-F is a ligand of the NK cell receptor KIR3DS1, whose activation initiates an antiviral downstream immune response and lead to delayed disease progression of HIV-1. During the time course of HIV infection, the expression of HLA-F is upregulated while its interaction with KIR3DS1 is diminished. Understanding HLA-F peptide selection and presentation is essential to a comprehensive understanding of this dynamic immune response and the molecules function. In this study, we were able to recover stable pHLA-F*01:01 complexes and analyze the characteristics of peptides naturally presented by HLA-F. These HLA-F-restricted peptides exhibit a non-canonical length without a defined N-terminal anchor. The peptide characteristics lead to a unique presentation profile and influence the stability of the protein. Furthermore, we demonstrate that almost all source proteins of HLA-F-restricted peptides are described to interact with HIV proteins. Understanding the balance switch between HLA-Ia and HLA-F expression and peptide selection will support to understand the role of HLA-F in viral pathogenesis. Identification and characterization of the lamprey cathepsin genes Abstract Cathepsins are key mammalian proteases that play an important role in the immune response. Several studies have revealed the versatile and critical functions of cathepsins. Here, we obtained ten kinds of cathepsin homologs and identified seven homologs with complete coding sequences. Phylogenetic analysis verified their identities and supported the classification of cathepsins into seven families, which is similar to other vertebrates. Tissue-specific expression analysis showed that all lamprey cathepsins (L-cathepsins) are present in the supraneural body (SB), kidney, gill, intestine, brain, heart, and liver, but their relative abundance varied among tissues. Additionally, we focused on the lamprey cathepsin L (L-cathepsin L) and used recombinant L-cathepsin L protein (rL-cathepsin L) to prepare anti rL-cathepsin L polyclonal antibodies, which were used to detect its distribution in lamprey tissues. The L-cathepsin L protein was primarily detected in the SB, kidney, gill, intestine, brain, and liver via western blot and immunohistochemistry assays. Importantly, quantitative real-time PCR (RT-PCR) revealed that the expression level of L-cathepsins mRNA significantly increased after exposure to three different stimuli (poly I:C, Staphylococcus aureus (S.a) and Vibro anguilarum (V.an)). This suggested that L-cathepsins may participate in defense processes. These results revealed that L-cathepsins may play key roles in the immune response to exogenous stimuli. The findings provide important information for future studies aiming to understand the molecular mechanisms underlying the immune response to pathogen invasion in lamprey. Prolonged stable disease in a uveal melanoma patient with germline MBD4 nonsense mutation treated with pembrolizumab and ipilimumab Abstract There is currently no effective treatment for metastasised uveal melanoma (UM). Recently, it was reported that a UM patient was responsive to checkpoint inhibitor (CI) treatment, due to a high tumour mutation burden correlated with a germline loss-of-function MBD4 mutation. Here, we report on another UM patient who carried an MBD4 germline nonsense variant (p.Leu563Ter) and her tumour showed a fivefold higher than average mutation burden. We confirmed the association between germline loss-of-function variant in MBD4 and CI response. The patient experienced stable disease (10 months) and survived 2 years with metastatic disease, which is twice as long as median survival. Additionally, the frequency of MBD4 loss-of-function variants in reported UM cohorts was > 20 times higher than in an aggregated population genome database (P < 5 × 10−5), implying a potential role as UM predisposition gene. These findings provide a strong basis for the inclusion of MBD4 in the screening of potential UM-prone families as well as stratification of immunotherapy. Strong selection of the TLR2 coding region among the Lagomorpha suggests an evolutionary history that differs from other mammals Abstract Toll-like receptors (TLRs) are one of the first lines of defense against pathogens and are crucial for triggering an appropriate immune response. Among TLRs, TLR2 is functional in all vertebrates and has high ability in detecting bacterial and viral pathogen ligands. The mammals' phylogenetic tree of TLR2 showed longer branches for the Lagomorpha clade, raising the hypothesis that lagomorphs experienced an acceleration of the mutation rate. This hypothesis was confirmed by (i) Tajima's test of neutrality that revealed different evolutionary rates between lagomorphs and the remaining mammals with lagomorphs presenting higher nucleotide diversity; (ii) genetic distances were similar among lagomorphs and between lagomorphs and other mammals; and (iii) branch models reinforced the existence of an acceleration of the mutation rate in lagomorphs. These results suggest that the lagomorph TLR2 has been strongly involved in pathogen recognition, which probably caused a host-pathogen arms race that led to the observed acceleration of the mutation rate. Immune stimulation of rainbow trout reveals divergent regulation of MH class II-associated invariant chain isoforms Abstract Major histocompatibility complex (MHC) class II-associated invariant chain is a chaperone responsible for targeting the MHC class II dimer to the endocytic pathway, thus enabling the loading of exogenous antigens onto the MHC class II receptor. In the current study, in vivo and in vitro methods were used to investigate the regulation of the rainbow trout invariant chain proteins S25-7 and INVX, upon immune system activation. Whole rainbow trout and the macrophage/monocyte-like cell line RTS11 were treated with PMA at concentrations shown to induce IL-1β transcripts and homotypic aggregation of RTS11. S25-7 transcript levels remained unchanged in the gill, spleen, and liver and were found to be significantly decreased in head kidney beginning 24 h post-stimulation. Meanwhile, INVX transcript levels remained unchanged in all tissues studied. Both S25-7 and INVX proteins were produced in gill and spleen tissues but their expression was unaffected by immune system stimulation. Surprisingly, neither INVX nor S25-7 protein was detected in the secondary immune organ, the head kidney. Analysis of RTS11 cultures demonstrated that both INVX and S25-7 transcript levels significantly increased at 96 h and 120 h following PMA stimulation before returning to control levels at 168 h. Meanwhile, at the protein level in RTS11, S25-7 remained unchanged while INVX had a significant decrease at 168 h post-stimulation. These results indicate that neither INVX nor S25-7 is upregulated upon immune system activation; thus, teleosts have evolved a system of immune regulation that is different than that found in mammals. DLA class II haplotypes show sex-specific associations with primary hypoadrenocorticism in Standard Poodle dogs Abstract Addison's disease (AD) is a life-threatening endocrine disorder that occurs spontaneously in both humans and dogs. Associations between MHC class II genes and AD have been shown in several human studies. Our goal was to identify MHC class II associations with AD in a large population of Standard Poodles, a breed highly predisposed to AD. We sequenced exon 2 of the class II genes DLA-DRB1, DLA-DQA1, and DLA-DQB1 in 110 affected and 101 unaffected Standard Poodles and tested for association with AD. After correcting for population structure, two haplotypes were found to confer risk of developing AD in a sex-specific manner: DLA-DRB1*015:01-DQA1*006:01-DQB1*023:01 in males (x2p = 0.03, OR 2.1) and DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 in females (x2p = 0.02, OR 8.43). Sex-specific associations have been previously described in human populations, but this is the first report of this kind in dogs. Consistent with findings in other studies, we found the DLA-DQA1*006:01 allele (x2p = 0.04) to be associated with AD in males independent of haplotype. In females, the haplotype DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 confers a very high risk for developing AD, although its frequency was rare (9 of 124 females) in our study population. Further studies are warranted to validate the findings of this exploratory dataset and to assess the usefulness of this haplotype as a risk marker for AD in female Standard Poodles. Our results highlight the importance of evaluating MHC class II disease associations in large populations, and accounting for both biological sex and population structure.

Earth Sciences The 2015/16 El Niño-related glacier changes in the tropical Andes Abstract Significant changes in the area and snowline altitude of two glacierized mountains – Nevado Champara (Cordillera Blanca, Peru) and Cerro Tilata (Cordillera Real, Bolivia) – in the tropical Andes, before and after the recent El Niño in 2015/16 period, have been analysed using Sentinel 2A and Landsat data. It is seen that the recent El Niño has been accompanied by higher fluctuation in glacier coverage on Nevado Champara and the loss of glacier coverage on Cerro Tilata was very high during the past 16 years. Rise in snowline altitude of selected glaciers was very high after the 2015/16 El Niño. Increase in the area covered by snow and ice during the La Niña periods were not enough to cover the ice loss occurred during the previous El Niño events and the strongest El Niño in 2015/16 was followed by a significant loss of ice-covered areas in the tropical Andes. Freshwater resources in this region will be affected in the near future if the current trends in glacier decline continue. Adaptation strategies needs to be implemented to reduce the impacts of the continuing loss of glacierized on regional communities in the tropical Andean region. Ecological vulnerability analysis of Beidagang National Park, China Abstract Ecological vulnerability analysis (EVA) is vital for ecological protection, restoration, and management of wetland-type national parks. In this study, we assessed the ecological vulnerability of Beidagang National Park based upon remote sensing (RS) and geographic information system (GIS) technologies. To quantify the ecological vulnerability, 10 indices were collected by the 'exposure-sensitivity-adaptive capacity' model and spatial principal component analysis (SPCA) was then applied to calculate the ecological vulnerability degree (EVD). Based on the numerical values, EVD of the study area was classified into five levels: moderate, light, medium, strong, and extreme. Results showed that the average EVD value was approximately 0.39, indicating overall good ecological vulnerability in Beidagang National Park. To be specific, 80.42% of the whole area was assigned to a moderate level of EVD with the highest being the tourism developed areas and the lowest being the reservoirs and offshore areas. Ecological vulnerability of the region was determined to be affected by the natural environment and anthropogenic disturbance jointly. The primary factors included tourism disturbance, traffic interference, exotic species invasion, land use/land cover, and soil salinization. We expected to provide some insights of the sustainable development of Beidagang National Park and would like to extend the results to other wetland-type national parks in the future. Chemical and minero-petrographical changes on granulite rocks affected by weathering processes Abstract The purpose of this work is to study the weathering processes of the granulite rocks of the Serre Massif (southern Calabria, Italy) using a multidisciplinary approach based on field studies, geochemical modeling, and minero-petrographical analyses. The granulite rocks are plagioclase-rich with minor amphibole, clinopyroxene, orthopyroxene, biotite, and garnet and their texture are coarse-grained. The reaction path modeling was performed to simulate the evolution of groundwaters upon interaction with local granulite by means of the software package EQ3/6, version 8.0a. Simulations were performed in kinetic (time) mode under a closed system at a constant temperature of 11.5°C, (which reproduces the average temperature of local area) and fixing the fugacity of CO2 at 10–2.34 bar (mean value). During the most advanced stage of weathering the main mineralogical changes are: partial destruction and transformation of biotite and plagioclase associated with neoformation of ferruginous products and secondary clay minerals producing a change in the origin rock fabric. The secondary solid phases observed during the geochemical modeling (kaolinite, vermiculite and ferrihydrite) are similar to those found in this natural system. Thus, the soil-like material mainly characterized by mostly sand to gravel grain-size fractions is the final result of the weathering processes. Bias characterization of ATMS low-level channels under clear-sky and cloudy conditions Abstract The Advanced Technology Microwave Sounder (ATMS) onboard the Suomi National Polar-Orbiting Partnership satellite is a cross-track scanning instrument containing 22 sounding channels in total. In this study, the bias characteristics of channels 1–6, which could have significant cloud contamination in heavy precipitation, are first analyzed based on the differences between ATMS observations (O) and model simulations (B) under clear-sky conditions over oceans. Latitudinal dependencies of the biases of window channels 1–3 are greater than those of channels 4–6. Biases of all nadir-only observations examined in different latitudinal bands [μ1(φ)] are positive and no more than 7.0 K. Biases at higher latitudes are larger. Channels 1–5 have a generally symmetric scan bias pattern [μ2(α)]. The global distributions of brightness temperature differences after subtracting the biases, i.e., O-B-μ1(φ)-μ2(α), for channels 3–6 spatially match the liquid water path distributions. Excluding ice-affected observations, channel 3–6 O-B differences systematically increase as the liquid water path increases under cloudy conditions. Further investigation is needed to apply these findings for ATMS data assimilation under both clear-sky and cloudy conditions. Comparison of C- and L-band simulated compact polarized SAR in oil spill detection Abstract This paper presents the compact polarized (CP) pseudo quad-pol parameters for the detection of marine oil spills and segregation of lookalikes using simulated CP SAR data from full-polarized (FP) SAR imagery. According to the CP theory, 11 polarized parameters generally used for the detection of oil spills were derived from reconstructed pseudo quad-pol data for both C and L bands. In addition, the reconstruction performance between C and L bands was also compared by evaluating the reconstruction accuracy of retrieved polarized parameters. The results show that apart from σHV and RH, other polarized parameters of σHH, σVV, H, α, φH–V, r, ρH–V, and γ can be reconstructed with satisfactory accuracy for both C and L bands. Furthermore, C band has a higher reconstruction accuracy than L band, especially for φH–V. Moreover, the effect of reconstruction of polarized parameters on oil spill classification was also evaluated using the maximum likelihood classification (MLC) method. According to the evaluation of kappa coefficients and mapping accuracy, it is recommended to use σHH, σVV, H, ρH–V, and γ of the C band CP SAR for marine oil spill classification. Terrain relief periods of loess landforms based on terrain profiles of the Loess Plateau in northern Shaanxi Province, China Abstract The Loess Plateau is densely covered by numerous types of gullies which represent different soil erosion intensities. Therefore, research on topographic variation features of the loess gullies is of great significance to environmental protection and ecological management. Using a 5 m digital elevation model and data from a national geographic database, this paper studies different topographical areas of the Loess Plateau, including Shenmu, Suide, Yanchuan, Ganquan, Yijun, and Chunhua, to derive representative gully terrain profile data of the sampled areas. First, the profile data are standardized in MATLAB and then decomposed using the ensemble empirical mode decomposition method. Then, a significance test is performed on the results; the test confidence is 95% to 99%. The most reliable decomposition component is then used to calculate the relief period and size of the gullies. The results showed that relief periods of the Chunhua, Shenmu, Yijun, Yuanchuan, Ganquan, and Suide gullies are 1110.14 m, 1096.85 m, 1002.49 m, 523.48 m, 498.12 m, and 270.83 m, respectively. In terms of gully size, the loess landforms are sorted as loess fragmented tableland, aeolian and dune, loess tableland, loess ridge, loess hill and loess ridge, and loess hill, in descending order. Taken together, the gully terrain features of the sample areas and the results of the study are approximately consistent with the actual terrain profiles. Thus, we conclude that ensemble empirical mode decomposition is a reliable method for the study of the relief and topography of loess gullies. The relationships between urban-rural temperature difference and vegetation in eight cities of the Great Plains Abstract Interpreting the relationship between urban heat island (UHI) and urban vegetation is a basis for understanding the impacts of underlying surfaces on UHI. The calculation of UHI intensity (UHII) requires observations from paired stations in both urban and rural areas. Due to the limited number of paired meteorological stations, many studies have used remotely sensed land surface temperature, but these time-series land surface temperature data are often heavily affected by cloud cover and other factors. These factors, together with the algorithm for inversion of land surface temperature, lead to accuracy problems in detecting the UHII, especially in cities with weak UHII. Based on meteorological observations from the Oklahoma Mesonet, a world-class network, we quantified the UHII and trends in eight cities of the Great Plains, USA, where data from at least one pair of urban and rural meteorological stations were available. We examined the changes and variability in urban temperature, UHII, vegetation condition (as measured by enhanced vegetation index, EVI), and evapotranspiration (ET). We found that both UHI and urban cold islands (UCI) occurred among the eight cities during 2000–2014 (as measured by impervious surface area). Unlike what is generally considered, UHII in only three cities significantly decreased as EVI and ET increased (p<0.1), indicating that the UHI or UCI cannot be completely explained simply from the perspective of the underlying surface. Increased vegetative cover (signaled by EVI) can increase ET, and thereby effectively mitigate the UHI. Each study station clearly showed that the underlying surface or vegetation affects urban-rural temperature, and that these factors should be considered during analysis of the UHI effect over time. Effects of sea level rise on storm surge and waves within the Yangtze River Estuary Abstract Sea level rise (SLR) can cause water depth increase (WDI) and coastal inundation (CI). By applying the coupled FVCOM + SWAN model, this study investigates the potential impacts of WDI and CI, induced by a 1.0 m SLR, on storm surge and waves within the Yangtze River Estuary. A 1.0 m WDI decreases the maximum storm surge by 0.15 m and increases the maximum significant wave height by 0.35 m. The CI effect size is smaller when compared with WDI. CI decreases the maximum storm surge and significant wave height by 0.04 and 0.07 m, respectively. In the near-shore area, WDI significantly alters the local hydrodynamic environment, thereby stimulating changes in maximum storm surges and wave heights. Low-lying regions are negatively impacted by CI. Conversely, in deep-water areas, the relative change in water depth is minimal and the effect of CI is gradually enhanced. The combined effect of WDI and CI decreases the maximum surge by 0.31 m and increases the maximum significant wave height by 0.21 m. As a result, CI may be neglected when designing deep-water infrastructures. Nonetheless, the complex interactions between adoption and neglect of CI should be simulated to achieve the best seawall flood control standards and design parameters. Land use and land cover classification using Chinese GF-2 multispectral data in a region of the North China Plain Abstract The newly launched GF-2 satellite is now the most advanced civil satellite in China to collect high spatial resolution remote sensing data. This study investigated the capability and strategy of GF-2 multispectral data for land use and land cover (LULC) classification in a region of the North China Plain. The pixel-based and object-based classifications using maximum likelihood (MLC) and support vector machine (SVM) classifiers were evaluated to determine the classification strategy that was suitable for GF-2 multispectral data. The validation results indicated that GF-2 multispectral data achieved satisfactory LULC classification performance, and object-based classification using the SVM classifier achieved the best classification accuracy with an overall classification accuracy of 94.33% and kappa coefficient of 0.911. Therefore, considering the LULC classification performance and data characteristics, GF-2 satellite data could serve as a valuable and reliable high-resolution data source for land surface monitoring. Future works should focus on improving LULC classification accuracy by exploring more classification features and exploring the potential applications of GF-2 data in related applications. Evolution model of a modern delta fed by a seasonal river in Daihai Lake, North China: determined from ground-penetrating radar and trenches Abstract While deltas fed by seasonal rivers are common in modern sedimentary environments, their characteristics remain unclear as compared to those fed by perennial rivers. This study identifies a small delta discharged by a seasonal stream flowing into Daihai Lake, in northern China, which is driven by ephemeral and high-energy flood events. Detailed 3D facies architecture was analyzed using ground-penetrating radar (GPR) and sedimentary logs from outcrop and trenches. Four types of radar surfaces, including truncations of underlying inclined strata, weak reflections, and depositional surface of downlap and onlap, were identified. Six radar facies (high-angle oblique-tangential, low-angle subparallel, gently plane parallel, plane-parallel, chaotic, and continuous strong reflection) were identified based on distinctive reflections, including amplitude, continuity, dip, and termination patterns. Five depositional units (Unit A to E) were documented from proximal to distal delta. Seasonal discharge signatures include significant grain-size decrease over short distance, abundant Froude supercritical flow sedimentary structures, poorly developed barforms, and small-scale scour and fill structures. Records of lake-level and sediment budget were evaluated over the past 60 years. In highstand stage (1960–1980), amalgamated channel (Units A and B), and delta front (Unit C) were deposited. In slope stage (1980–1996), the lower deposits (Units A, B, C) were eroded by Unit D with a distinct truncation surface. In lowstand stage, most eroded sediments bypassed the incised channel and accumulated in the distal part, in which a new depositional unit was formed (Unit E). The model demonstrates that deltas fed by seasonal rivers tend to accumulate large amounts of sediments carried by high magnitude floods within short periods.

Political Science Correction to: Social Risk Management at AIIB – Chinese or International Characteristics? When transforming the references of this paper into a numerical system during the production process, some sources became wrongly related to authors of other references and one reference disappeared. These errors in the paper's bibliographical information were caused by Springer Nature. Rory Truex, Making Autocracy Work: Representation and Responsiveness in Modern China Bianco, Lucien, Translated by Krystyna Horko, Stalin and Mao: a Comparison of the Russian and Chinese Revolutions Jonathan Sullivan and Chun-Yi Lee, eds., A New Era in Democratic Taiwan: Trajectories and Turning Points in Politics and Cross-Strait Relations Becky Yang Hsu, Borrowing Together: Microfinance and Cultivating Social Ties Elizabeth C. Economy, The Third Revolution: Xi Jinping and the New Chinese State Beatriz Carrillo, Johanna Hood and Paul Kadetz, eds., Handbook of Welfare in China John F. Copper, Taiwan at a Tipping Point : the Democratic Progressive Party's Return to Power Sino-Western Cognitive Differences and Western Liberal Biases in Chinese Political Studies Abstract Many scholarly publications in the field of Chinese political studies show a strong Western liberal bias. Very often we find their descriptions and predictions on China to be inaccurate or false. To probe the problem of Western liberal bias, this study uses a multidisciplinary approach to analyze the Sino-Western cognitive habits and the cultural and historical roots of these differences. We find that there are some important cognitive differences between Chinese and Western people. These differences may derive from their linguistic, psychological, and genetic variations, and are closely associated with their different political values, preferences, and behavior patterns. The implication of these finding suggests that some of the Western liberal ideas may not be congruent with Chinese culture which emphasizes social harmony, rule of ethics, and respect to authority. Effort to promote Western liberal democracy as a universal value does not take into consideration of these important cognitive and cultural differences. Mapping the Knowledge Domain: Research on Service-Oriented Government in China Abstract Establishing a service-oriented government (SOG) that can satisfy the needs of the people is not only a critical research topic in the field of public administration, but also a strategic agenda officially proposed since the Nineteenth National Congress of the Communist Party of China (CPC). As SOG research increases, it is important to thoroughly review the topics and trajectory of research on SOG in China. This paper uses CiteSpace, a visual analysis software, to provide an up-to-date overview and systematic summary of the research topics, trajectory, and gaps in SOG research in China. SOG research in China is classified into four categories: SOG concepts, development paths, government reforms, and performance evaluations. This paper illustrates the underlying problems, such as unsystematic theoretical development, research perspectives, and deficiency of the integrated research on the development mechanism, prominent focuses, and practical applicability. We concluded by identifying new trends in SOG research in China regarding government–society relations and big data.

Genetics DNA Methylation in Yeast-Like Fungi of the Species Candida albicans Induced by Different Lengths of Exposure to Ozone Abstract The objective of the study was to determine global DNA methylation induced by lengths of exposure to ozone in Candida albicans isolates of human and animal origin. The level of global DNA methylation was tested as the relative methylation level in the samples in relation to a methylated control. The analysis revealed differences in the methylation level in the human and animal samples. Ozone had a significant effect on the DNA methylation process, and longer exposure substantially increased the level of total methylated DNA. As expected, the degree of methylation depended on the length of exposure to ozone. Structure and Variability of 5'UTR, Exon 1 and Fragment of Intron 1 of the Pax3 Gene in American Mink ( Neovison vison ) Abstract The expression product of the Pax3 gene is a transcription factor involved in the process of neural crest's stem cell differentiation into melanocytes during embryonic development. In individual life, the Pax3 gene expression is an element of the complex process of regulation the degree of melanoblasts differentiation. The state of melanoblasts (being a reservoir of renewable cells) differentiation depends on UV radiation, which stimulates the Pax3 gene expression. In the absence of radiation the expression of the Pax3 gene is inhibited, what stops the melanoblasts at the current level of diversity. Pax3 gene is one of the candidate genes responsible for animals coat color and its mutations are considered a possible cause for the occurrence of the color patterns: "splashed white" and "white spotting" in Quarter Horse breed. The 5'UTR exon 1 and the intron fragment 1 of the Pax3gene in the American mink were sequenced. Two variations were found: substitution c.-17G>A in the 5′ UTR and substitution c.+142C>G in intron 1. Investigations were carried out on 93 individuals, which were genotyped for polymorphisms in the 5'UTR region using the MTPA-PCR technique. It was established that the study group was in a state of genetic equilibrium, because there were no statistically significant differences between observed genotypes frequency and theoretically calculated according to the Hardy–Weinberg principle and it was found that there were no statistically significant relationship between the Pax3 gene polymorphism and the American mink coat color. Association of ABCB9 and COL22A1 Gene Polymorphism with Human Predisposition to Severe Forms of Tick-Borne Encephalitis Abstract Tick-borne encephalitis (TBE) is caused by a neurotropic RNA virus from the Flavivirus genus. TBE is characterized by a significant variability of clinical manifestations from nonparalytic forms (fever, meningitis) to severe paralytic (focal) forms (meningoencephalitis, poliomyelitis, polioencephalomyelitis). The result of interaction between a virus and a host (and, consequently, the viral disease course and outcome) largely depends on genetically determined ability of the host (particularly, human) organism immune system to suppress the development of viral infection. However, hereditary predisposition to TBE has been rather poorly studied in human populations. In this study, the results of whole exome sequencing of DNA samples from 22 Russian non-immunized TBE patients with severe TBE forms and 17 control individuals from the same populations are presented. Sixteen single nucleotide polymorphisms (SNPs) associated with predisposition to severe forms of TBE were identified. The genotype and allele frequencies for three of these SNPs localized in the ABCB9 (rs4148866, G/A, intron), COL22A1 (rs4909444, G/T, Ala938Asp), and ITGAL (rs1557672, G/A, intron) genes were then studied in larger samples of patients with different forms of TBE (n = 177) and in the control population (n = 215). As a result, the association of the ABCB9 and COL22A1 gene SNPs with the development of severe forms of TBE was for the first time demonstrated in the Russian population. The hypothesis regarding a possible mechanism of the effect of the ABCB9 gene intronic SNP on the process of human infection with TBE virus is considered. Genetic Consequences of Interspecific Hybridization, Its Role in Speciation and Phenotypic Diversity of Plants Abstract The review focuses on the genetic consequences of interspecific hybridization and discusses its role in speciation and increasing the genetic diversity of plants, including the diversity of species and varieties of cultivated crops and garden plants. The combination of two or more genomes of different origin in the first-generation hybrids is usually accompanied by a phenomenon referred to as genomic shock, which results in different genetic and epigenetic changes. As a result, a material appears which is unique in providing multiple variants for natural selection of organisms, in different degrees adapted to new environmental conditions. In isolated plant populations with various destabilized genomes of hybrid origin under the influence of natural selection and due to genetic drift, gene and chromosomal differences will accumulate, triggering new reproductive isolating mechanisms that increase genetic isolation of a new race or species. Progressive establishment of genome stabilization at the eupolyploid stage and subsequent repeated genome and karyotype diploidization facilitate the retention of selected new genomic and epigenomic combinations. It seems likely that the evolutionary history of all agricultural crops and garden plant varieties, as well as of many invasive alien species and the components of adventive flora, was marked by interspecific crossings purposefully carried out by breeders during the creation of modern varieties and crossings between previously geographically isolated plants that were unintentionally united in apothecary and botanical gardens, in fields and backyards, and on disturbed lands around settlements. At the same time, phenotypic and genetic diversity of cultivars not only results from the combination of different alleles that already existed in the genomes of the parental species but also is a consequence of the appearance in the first-generation hybrids of new genomic and epigenomic variants that are direct or distant effects of post-hybridization genomic shock, the creative role of which we would like to emphasize. Bioinformatic Analysis of the Sciatic Nerve Transcriptomes of Mice after 30-Day Spaceflight on Board the Bion-M1 Biosatellite Abstract Comparative bioinformatic analysis of sciatic nerve transcriptomes of C57BL/6J mice was carried out. Animals were divided into three groups: Flight, 30-day spaceflight; Recovery, 30-day spaceflight with subsequent 7-day readaptation; and Control. A significant pool of genes with an absolute difference in expression of more than 32 times compared to the control group was revealed in mice after the 30-day spaceflight (Flight and Recovery groups). Comparative analysis of the Flight and Recovery groups of murine transcriptomes did not reveal any significant differences in gene expression. In animals after spaceflight on board the biosatellite, using the KEGG database (Kyoto Encyclopedia of Genes and Genomes), we identified genes related to the state of metabolic and signaling pathways involved in actin cytoskeleton regulation, regulation of potential-dependent calcium, sodium, and potassium channels, and myelination of nerve fibers. Interrelation of EAST-Dependent and Su(Hw)-Dependent Repression in Transgenic Lines of Drosophila melanogaster Abstract In D. melanogaster, the nuclear matrix protein EAST functionally interacts with the Su(Hw)-dependent insulator complex. The y2 allele, in which the MDG4 retrotransposon is inserted between enhancers and the gene promoter, was previously described. The Su(Hw) insulator sequence is present in the regulatory region of MDG4. An increase in the EAST protein concentration or inactivation of the Mod(mdg4)-67.2 protein, which is part of the Su(Hw)-dependent complex, results in tissue-specific repression of the yellow gene in the y2 allele. In the present work, the degree of EAST-dependent and Su(Hw)-dependent repression in different regions of the genome was analyzed using transposition of transgenes containing long terminal repeat (LTR) sequences of the MDG4 retrotransposon and the Su(Hw) insulator. As a result of genetic experiments, it was shown for the first time that EAST-dependent repression of the yellow gene is observed in the same transgenic lines of D. melanogaster as Su(Hw)-dependent repression. The obtained data confirm our earlier suggestion that the regulatory complex, which is formed on the LTR sequence and functionally interacts with the EAST protein, transfers the transgene to the nucleus regions with a high concentration of factors that repress transcription. Genetic Diversity of atp6 and cox3 Gene in Wild Drosophila melanogaster Abstract Mitochondria are the energy factory in cells, and more than 95% of the energy in cells is produced by the mitochondrial oxidative phosphorylation (OXPHOS). Therefore, mitochondria likely plays an important role in the process of high-altitude adaptation. Wild Drosophila melanogaster population structure provides a good precondition to detect positive selection on mitochondrial genes related to environmental or climatic variation, specifically hypoxia and high altitudes. In this paper, we sequenced atp6 (ATPase synthase 6) from 27 individuals and cox3 (cytochrome c oxidase III) from 26 individuals of wild Drosophila melanogaster. The percent G+C content of atp6 and cox3 genes has a value of 24 and 29.3%, respectively, exhibiting an extreme bias in base composition. 5 single nucleotide polymorphisms (SNPs) were detected and 2 nonsynonymous substitutions (m.555T > A and m.577A > G) were detected in atp6, only one SNP (m.126C > T) was found from highland Drosophila melanogaster. 6 SNPs were detected in cox3, we found 2 nonsynonymous substitutions (m.745G > A and m.427G > A) of only one highland strain from Yun Nan province. Substitution rates and dN/dS ratios were relatively high for cox3 (ω = 0.34851) compared to atp6 (ω = 0.07329), both of them inferring is purifying selection by using PAML. Only one amino acid site 255I (p < 0.01) of the cox3 gene was found in one fly from low altitude Drosophila sample, which was generated by SNPs (m.763A > G and m.764T > C). From these analyses we conclude that selection may not have played a role in shaping Drosophila melanogaster regional mtDNA variation, the changes in selection is very likely due to some environmental stressors other than hypoxia and high altitudes, and more broadly, our results add to an emerging body of research in Drosophila. Genetic Differentiation of the Arctic Phylogenetic Group of Charr from Northeast Asia and North America Abstract A comparative analysis of the mitochondrial DNA variability in Salvelinus taranetzi (and closely related taxa) from Asia and Salvelinus alpinus erythrinus from the Northwest Territories (NWT), North America, representing the Arctic phylogenetic group of charrs of the genus Salvelinus, has been carried out. The estimated divergence of the combined nucleotide sequences of the mtDNA CoI and Cytb genes and CR region within the discussed phylogroup varies in the range of 0.001–0.003 and does not exceed the intraspecific variability of S. taranetzi. A genealogical analysis confirms the phylogenetic proximity of S. a. erythrinus from NWT and S. taranetzi from Asia. By assuming a common origin of S. taranetzi and S. a. erythrinus, we have shown a significant differentiation between the geographical populations as a result of probable fragmentation of their common ancestor's range. According to the hierarchical analysis of molecular variance (AMOVA), the intergroup component accounts for the major part (83% of variance) of the mtDNA variability (490 bp, CR) with a low genetic diversity within the groups (10%). The region of Anadyr–Kolyma Basin, which determines the heterogeneity of the phylogroups, stands out on a broad geographical scale. RT-qPCR Analysis of Host Defense-Related Genes in Nonhost Resistance: Wheat -Bgh Interaction Abstract Non-host resistance (NHR) is a plant defense system against the majority of microbial pathogens. Blumeria graminis f. sp. hordei (Bgh), is an obligate biotrophic ascomycete fungal pathogen that can grow and reproduce only on living cells of wild or domesticated barley (Hordeum sp.).‎ In this study, the expression pattern of eight defense-related genes including NPR1, PR2, PR5, PR1-2, Lipase, LTP, PAL and POX was assessed in bread wheat (Triticum aestivum cv. Darya) against the powdery mildew fungus Bgh. Hydrogen peroxide (H2O2) activity in leaf tissues was also detected histochemically with 3,3-diaminobenzidine (DAB) staining. Result showed that in response to virulence agent, Bgh spores, papillae and hypersensitive response (HR) were formed in the 53.9 and 40.1% of infected area, respectively while in the rest of the infected area (6%) spores were not germinated. According to the histochemical analysis, the wheat NHR against Bgh belongs to type IІ NHR and display a multi-layered feature including wax composition, pre-formed barriers, papilla formation, hypersensitive response. According to results of expression analysis, the Pox, PR5 and PR1-2 expression level were clearly upregulated 24 hours post inoculation (hpi) and LTP was identified as an early signaling response to Bgh. In this study NPR1 was down regulated during all given time points, thus we suggested that salicylic acid (SA) signaling pathway may be mediated by a NPR1-independent mechanism(s) in wheat-Bgh interaction. The coordinated induction of a set of so-called systemic acquired resistance (SAR) genes including POX, PR1-2 and PR5 was observed in wheat-Bgh interaction. Expression pattern of defense-related genes at the wheat-Bgh interaction can be taken as an indication of their functional relevance at different time points of tissue infection. The Role of Calcium-Dependent Protein Kinase Genes VaCPK1 and VaCPK26 in the Response of Vitis amurensis ( in vitro ) and Arabidopsis thaliana ( in vivo ) to Abiotic Stresses Abstract Calcium-dependent protein kinases (CDPK or CPK) are involved in protecting plants from abiotic stresses, but the properties and functions of CDPK are still poorly understood. Analysis of the Amur grape Vitis amurensisRupr. is of great interest, since it demonstrates high tolerance to adverse environmental conditions. It was demonstrated that exposure of V. amurensis to salt and, to a lesser extent, osmotic and cold stress resulted in a considerable increase in the VaCPK1 and VaCPK26 transcription level. The present study was focused on the analysis of the effect of constitutive expression of the recombinant VaCPK1 and VaCPK26 genes on the resistance of V. amurensis cell cultures and Arabidopsis thaliana plants to salt, osmotic, and temperature stresses. It was demonstrated that expression of recombinant VaCPK26, as well as to a lesser extent VaCPK1, led to a 1.2–1.7 times increase in biomass accumulation by V. amurensis cell cultures and to a 1.2–2.1 times increase in survival of A. thaliana plants under salt stress. In addition, VaCPK26-expressing lines of A. thaliana lines demonstrated a slight degree of drought tolerance and were characterized by increased expression of some stress-induced protective genes involved in the formation of salt and dehydration tolerance. The data obtained indicate that the VaCPK1 and VaCPK26 genes can act as positive regulators of plant response to salt stress.

Philosophical Studies Credal pragmatism In the original publication of the article, Table 1 was incorrectly published. The corrected table is give below. Laws and their instances Abstract I present an argument for the view that laws ground their instances. I then outline two important consequences that follow if we accept the conclusion of this argument. First, the claim that laws ground their instances threatens to undermine a prominent recent attempt to make sense of the explanatory power of Humean laws by distinguishing between metaphysical and scientific explanation. And second, the claim that laws ground their instances gives rise to a novel argument against the view that grounding relations are metaphysically necessary. On not getting out of bed Abstract This morning I intended to get out of bed when my alarm went off. Hearing my alarm, I formed the intention to get up now. Yet, for a time, I remained in bed, irrationally lazy. It seems I irrationally failed to execute my intention. Such cases of execution failure (as I call it) pose a challenge for Mentalists about rationality, who believe that facts about rationality supervene on facts about the mind. For, this morning, my mind was in order; it was my (in)action that apparently made me irrational. What, then, should Mentalists say about the phenomenon of execution failure? The phenomenon of execution failure, and the puzzle it raises for Mentalists, have rarely been discussed. This paper addresses the puzzle in two parts. First, it argues (against John Broome) that execution failure is a real phenomenon. It is possible for agents to irrationally fail to act on their present-directed intentions. It follows that Mentalists in the philosophy of action must solve the puzzle of explaining what is irrational about cases of execution failure. Second, this paper begins the search for such a solution. It considers six possible resolutions to the puzzle, arguing that none is obviously the most attractive. These resolutions include a requirement of overall conative consistency, an appeal to the norm of intention consistency, a form of Volitionalism, an appeal to factive mental states, and a proposal due to Garrett Cullity, and a novel requirement of proper functioning. Moral supervenience and distinctness: comments on Dreier Abstract Jamie Dreier has argued that the supervenience of the moral on the non-moral requires explanation, and that attempts by the non-naturalist to provide it, or to sidestep the issue, have so far failed. These comments on Dreier first examine the notion of distinctness at work in the idea that non-natural properties are distinct from natural ones, pointing out that distinctness cannot be understood in modal terms if supervenience is to be respected. It then suggests that Dreier's implicit commitment to the existence of infinite Boolean combinations of properties plays a significant role in the challenge to non-naturalism, and that the non-naturalist has some principled reasons for rejecting it. It also suggests that the real problem for non-naturalists isn't explaining supervenience, but is rather the well-known problem of explaining our capacity to know anything about non-natural properties. That is, if the latter epistemological problem can be solved, the former metaphysical one might well disappear, at least as a distinctive problem for non-naturalist realists about morality. Attributing error without taking a stand Abstract Moral error theory is the doctrine that our first-order moral commitments are pervaded by systematic error. It has been objected that this makes the error theory itself a position in first-order moral theory that should be judged by the standards of competing first-order moral theories (Here we are thinking, for example, of Dworkin (Philos Public Aff 25(2):87–139, 1996) and Kramer (Moral realism as a moral doctrine. New York: Wiley-Blackwell, 2009). Kramer: "the objectivity of ethics is itself an ethical matter that rests primarily on ethical considerations. It is not something that can adequately be contested or confirmed through non-ethical reasoning" [2009, 1]). This paper shows that error theorists can resist this charge if they adopt a particular understanding of the presuppositions of moral discourse. Moral perception, inference, and intuition Abstract Sarah McGrath argues that moral perception has an advantage over its rivals in its ability to explain ordinary moral knowledge. I disagree. After clarifying what the moral perceptualist is and is not committed to, I argue that rival views are both more numerous and more plausible than McGrath suggests: specifically, I argue that (a) inferentialism can be defended against McGrath's objections; (b) if her arguments against inferentialism succeed, we should accept a different rival that she neglects, intuitionism; and (c), reductive epistemologists can appeal to non-naturalist commitments to avoid McGrath's counterexamples. Credal pragmatism Abstract According to doxastic pragmatism, certain perceived practical factors, such as high stakes and urgency, have systematic effects on normal subjects' outright beliefs. Upholders of doxastic pragmatism have so far endorsed a particular version of this view, which we may call threshold pragmatism. This view holds that the sensitivity of belief to the relevant practical factors is due to a corresponding sensitivity of the threshold on the degree of credence necessary for outright belief. According to an alternative but yet unrecognised version of doxastic pragmatism, practical factors affect credence rather than the threshold on credence. Let's call this alternative view credal pragmatism. In this paper, I argue that credal pragmatism is more plausible than threshold pragmatism. I show that the former view better accommodates a cluster of intuitive and empirical data. I conclude by considering the issue of whether our doxastic attitudes' sensitivity to practical factors can be considered rational, and if yes, in what sense. Drop it like it's HOT: a vicious regress for higher-order thought theories Abstract Higher-order thought (HOT) theories of consciousness attempt to explain what it takes for a mental state to be conscious, rather than unconscious, by means of a HOT that represents oneself as being in the state in question. Rosenthal (in: Liu, Perry (eds) Consciousness and the self: new essays, Cambridge University Press, Cambridge, 2011) stresses that the way we are aware of our own conscious states requires essentially indexical self-reference. The challenge for defenders of HOT theories is to show that there is a way to explain the required reference-fixing mechanisms that is compatible with the theory. According to Rosenthal, the reference to oneself as such is grounded in the disposition to identify the individual the HOT refers to as the individual who has that HOT. I argue that this leads to a vicious infinite regress on the more than plausible assumption that our cognitive capacities are limited. This leaves such theories without a foundation, since self-reference is thought essential to consciousness. Value ascriptions: rethinking cognitivism Abstract This paper focuses on value as ascribed to what can be desired, enjoyed, cherished, admired, loved, and so on: value that putatively serves as ground for evaluating such attitudes and for justifying conduct. The main question of the paper is whether such value ascriptions are property ascriptions as traditional cognitivism claims. The paper makes the case that although the linguistic evidence favors traditional cognitivism over non-cognitivism about evaluative language, the main tenet of cognitivism is best restated as the thesis that evaluative terms are linguistically encoded classificatory devices. This opens up the theoretical possibility, for even inflationists about properties, to embrace cognitivism without inviting any metaphysical worries about the properties ascribed in evaluative language. Is there a supervenience problem for robust moral realism? Abstract The paper describes the problem for robust moral realism of explaining the supervenience of the moral on the non-moral, and examines five objections to the argument: (1) The moral does not supervene on the descriptive, because we may owe different obligations to duplicates. (2) If the supervenience thesis is repaired to block (1), it becomes trivial and easy to explain. (3) Supervenience is a moral doctrine and should get an explanation from within normative ethics rather than metaethics. (4) Supervenience is a conceptual truth and should be explained by the nature of our concepts rather than by a metaphysical theory. (5) The moral does not supervene on the descriptive, because moral principles are not metaphysically necessary. It concludes that none of these objections is successful, so Robust Realists do have an explanatory debt to worry about.

Prostaglandins, Leukotrienes and Essential Fatty Acids Variants in the CYSLTR2 are associated with asthma, atopy markers and helminths infections in the Brazilian population Publication date: June 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 145 Author(s): Talita dos S. Jesus, Ryan dos S. Costa, Neuza Maria Alcântara-Neves, Maurício L. Barreto, Camila Alexandrina Figueiredo Abstract Background Asthma is a chronic disease of the airways and its most common phenotype is characterized by a T2 type response with IgE production and inflammatory mediators in response to common allergens. Cysteinyl leukotrienes (CysLTs), LTC4, LTD4 and LTE4, are mediators known to possess important proinflammatory action. CysLTs can bind to the Cysteinyl leukotriene receptor type 2 (CysLTR2) and activate an inflammatory. Polymorphisms in CysLTR2 have been associated with asthma and atopy, although the mechanism is not clear. Objective To evaluate the association between genetic polymorphisms in CYSLTR2 with asthma phenotypes, atopy markers and helminth infection. Methods Genotyping was performed using a panel Illumina and carried out in 1245 participants of SCAALA program (Social Change, Asthma, Allergy in Latin American). Logistic regressions for asthma, helminth infections (Trichuris trichiura and Ascaris lumbricoides) and allergy markers (skin tests and IgE production) were performed using PLINK 1.9 software adjusted for sex, age, helminth infection and ancestry markers. Results The G allele of rs1323556 was negatively associated with asthma in the additive model (OR 0.74, 95% CI 0.59–0.93) and in the dominant model (OR 0.71, 95% CI 0.53–0.74). The G allele of rs1575464 was also negatively associated with asthma in two genetic models, additive (OR 0.77, 95% CI 0.62–0.96) and dominant (OR 0.73, 95% CI 0.55–0.97). The G allele of rs61735175 was positively associated with asthma severity in the additive model (OR 1.72, 95% CI 1.07–2.77) and in the dominant model (OR 1.77, 95% CI 1.09–2.85). Five SNVs were associated with atopy markers and four SNVs were associated with helminth infections. Conclusion Polymorphisms in the CYSLTR2 gene are associated with asthma, atopy markers and helminth infection in Brazilian individuals, which may lead to protection or risk for such conditions, however, more studies are needed to evaluate the functional of this variants here in described. Quantitating fatty acids in dried blood spots on a common collection card versus a novel wicking sampling device Publication date: June 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 145 Author(s): Jan Gunash, Juan J. Aristizabal-Henao, Ken D. Stark Abstract Blood biomarkers of n − 3 polyunsaturated fatty acids can serve as indicators of dietary intake and benefits and/or disease risk. The use of dried blood spots for fatty acid analyses is increasing but most of the reported data is qualitative (relative percentages of total fatty acids). The ability to quantitate concentrations of fatty acids on a common blood spot collection card and a novel wicking device designed to collect 10 µL of blood was compared with a wet blood sample in ten young adult participants. Prior to this comparison, the collection materials were screened for contaminants by gas chromatography with flame ionization and liquid chromatography/tandem mass spectrometry, and the blood volume and blood spot area relationship of the collection card was confirmed using technical replicates. Palmitate and stearate were detected as free fatty acids on both collection materials and as lysophosphatidylcholines on the wicking device. The low amounts (<1.0 µg) did not affect the quantitation of these fatty acids in either material. The relationship between blood volume and blood spot area was linear (r = 0.99, p < 0.001) and it was determined that a 6 mm hole punch contained 9.6 µL of blood. When compared with wet blood, the fatty acid determinations from the dried blood spots were largely similar although there were some minor differences in low abundant fatty acids. Quantitative fatty acid determinations of dried blood spots are possible and should be reported along with relative percentage data to improve interpretation in the future. Physical fitness is associated with prostaglandin F2α isomers during pregnancy Publication date: June 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 145 Author(s): Jean-François Bilodeau, Michèle Bisson, Jessica Larose, Etienne Pronovost, Mélanie Brien, Karine Greffard, Isabelle Marc Abstract Introduction Pregnancy and physical activity are associated with oxidative stress and immune changes. We hypothesized that pregnant women physically more active in early pregnancy will display a better oxidative stress management and inflammatory response later in pregnancy compared with less active pregnant women. Material and methods Maternal physical activity using accelerometry monitors for 1 week and cardiorespiratory fitness (VO2 at anaerobic threshold) were assessed at 14–18 weeks in 58 pregnant women. Plasma and erythrocytes membrane samples were obtained from maternal blood samples at 14–18 and 34–37 weeks of pregnancy. Pro-inflammatory prostaglandin (PG) F2α and oxidative stress-derived F2-isoprostanes were measured by high-performance liquid chromatography coupled to tandem mass spectrometry. Results Higher physical activity levels at 14–18 weeks measured by mean counts per minute, >30 min/d of moderate to vigorous activity or >6500 steps/d at 14–18 weeks of pregnancy were associated with lower levels of total plasmatic PGF2α later in pregnancy. Concentrations of 5 F2-isomers in erythrocyte membranes in late pregnancy were significantly higher in the third (17.5–19.5 mL kg−1 min−1) and/or fourth (19.6–27.7 mL kg−1 min−1) quartiles of cardio-respiratory fitness compared to the first quartile (13.9–15.9 mL kg−1 min−1). Conclusions Overall, higher cardio-respiratory fitness in early pregnancy is associated with enhanced erythrocyte membranes oxidation at 34–37 weeks reflecting a higher oxygen transfer capacity. Also, the most active women experienced lower circulating levels of pro-inflammatory PGF2α in plasma at 34–37 weeks, a marker associated with adverse antenatal inflammation-associated conditions. These results support the practice of physical activity by pregnant women. Relationship of Omega-3 Fatty Acids DHA and EPA with the Inflammatory Biomarker hs-CRP in Children with Sickle Cell Anemia Publication date: Available online 10 May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): B N Yamaja Setty, Suhita Gayen Betal, Robin E Miller, Dawn S Brown, Maureen Meier, Michele Cahill, Norma B Lerner, Nataly Apollonsky, Marie J Stuart Abstract Background Inflammation and vaso-occlusion play key roles in Sickle Cell Disease (SCD) pathophysiology. Lipoxygenase products of the omega-3 fatty acids (O3FAs), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, are potent anti-inflammatory mediators modulating pain. O3FAs decrease episodes of vaso-occlusion in SCD. Methods We assessed erythrocyte fatty acid composition in two major cell membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine, in children with SCD HbSS-disease (n=38) and age/race-matched HbAA-controls (n=18). Ratio of pro-inflammatory arachidonic acid (AA) to anti-inflammatory DHA and EPA (FA-Ratio), and its relationship to hs-CRP were evaluated. Results FA-Ratios were increased in both phosphatidylcholine and phosphatidylethanolamine in HbSS compared to controls. Correlations were noted in HbSS subjects between hs-CRP and FA-Ratios (p=0.011). FA-Ratios increased with age (p=0.0007) due to an increase in pro-inflammatory AA with a concomitant decrease in anti-inflammatory DHA. Conclusions Findings demonstrate relative deficiencies in HbSS of the anti-inflammatory precursor fatty acids DHA and EPA, which correlates positively with hs-CRP. Gestational age and maternal status of DHA and other polyunsaturated fatty acids in pregnancy: A systematic review Publication date: May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 144 Author(s): Nina A. Wilson, Evangeline Mantzioris, Philippa T. Middleton, Beverly S. Muhlhausler Abstract Introduction Maternal diet is important in determining omega-3 DHA status however there is limited knowledge of other factors influencing maternal omega-3 concentrations during pregnancy. The primary objective of this systematic review and meta-analysis was to evaluate whether maternal DHA status changed across gestation. Changes in levels of other key polyunsaturated fatty acids were also investigated. Materials and methods The Medline, Embase, Amed, and CINAHL databases were searched. Included studies reported measures of maternal omega-3 status in at least two pregnancy trimesters. Results Thirteen studies were included in the final analyses. Absolute omega-3 DHA concentrations increased across gestation, but decreased as a proportion of total lipids. Discussion Our findings are consistent with previous observations of increases in lipid mobilisation, coupled with preferential transfer of DHA to the fetus, with advancing gestation. However the number of eligible studies was small and further investigations are required. Associations of medium and long chain omega-3 polyunsaturated fatty acids with blood pressure in Hispanic and non-Hispanic smokers and nonsmokers Publication date: May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 144 Author(s): Kayla R. Zehr, Allison Segovia, Meera Shah, Mary T. Walsh-Wilcox, Barbara H. Brumbach, Joe R. Anderson, Mary K. Walker Summary Epidemiology studies and clinical trials have shown that omega-3 polyunsaturated fatty acids (n-3 PUFAs) are inversely associated with blood pressure. We sought to determine the influence of cigarette smoking and Hispanic ethnicity on this association. Age- and sex-matched smokers and nonsmokers (n = 98) 19–50 years old lacking cardiovascular disease were recruited. Systolic and diastolic blood pressure (SBP, DBP), heart rate, HbA1c, lipids, BMI, and RBC fatty acids were measured. The omega-3 index (percent eicosapentaenoic and docosahexaenoic acid, EPA+DHA, in RBCs) was significantly lower in smokers (Smokers: 3.19 ± 0.86%; Nonsmokers, 3.88 ± 1.05%, p = 0.001) and Hispanics (Hispanic 3.32 ± 0.93%; Non-Hispanic, 3.82 ± 1.03%, p = 0.006). DHA exhibited a significant inverse association with BP in both smokers and nonsmokers, while alpha-linolenic acid (ALA) exhibited a significant positive association with BP only in smokers. Multiple regression analyses showed that BMI, DHA, smoking status, and smoking status*ALA interaction significantly predicted SBP (p < 0.0001, R2 = 0.44) and DBP (p < 0.0001, R2 = 0.33), while ethnicity had no effect. The observed lower BP when DHA levels are high suggests a possible protective role of DHA on BP in normotensive smokers and nonsmokers. Additionally, the observed higher BP when ALA levels are high only in smokers suggests that ALA may influence the BP-lowering effects of chronic smoking. The association of maternal polyunsaturated fatty acids during pregnancy with social competence and problem behaviours at 7 years of age: The MEFAB cohort Publication date: May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 144 Author(s): E.C. Tore, M. Gielen, E.E. Antoniou, R.H.M. de Groot, R.W.L. Godschalk, T.R. Southwood, L. Smits, N. Stratakis, I.S.M. van de Wurff, M.P. Zeegers Abstract Background The prenatal exposure to maternal n-6 and n-3 polyunsaturated fatty acids (PUFAs) might influence the development of social competence and internalizing and externalizing behaviours of the child, because of the numerous functions of PUFAs within the nervous system. Methods To analyse the association of selected maternal PUFAs (i.e., AA, EPA, DHA, total n-6, total n-3, and the n-6:n-3 ratio) measured during gestation with childhood social competence and problem behaviours, we examined 311 mother-child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort. For each woman, PUFA-specific changes in relative concentrations were calculated by identifying the best-fitting curve of PUFA concentration by linear splines of gestational age. The associations of changes in maternal PUFAs in early and late pregnancy with childhood social competence, total problems, internalizing and externalizing behaviours, measured with the Child Behaviour Checklist 4/18 at age 7, were investigated with linear regression analyses adjusted for maternal and children's socio-demographic characteristics. Results In late gestation (i.e., from gestational week 30), an increase in AA was associated with higher social competence, while a decrease in total n-6 was associated with lower externalizing behaviours. No other significant associations were found. Discussion In this prospective study, increasing maternal AA and decreasing total n-6 were associated with improved social competence and externalizing behaviours, respectively, in 7-year old children. Nonetheless, the clinical significance of the identified associations is modest and further investigations are warranted to clarify the relationship between maternal AA and total n-6 during pregnancy and childhood social and behavioural development. Editorial Board Publication date: May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 144 Author(s): Dietary docosahexaenoic acid contributes to increased bone mineral accretion and strength in young female Sprague-Dawley rats Publication date: May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 144 Author(s): Zahra Farahnak, Marie Therese Freundorfer, Paula Lavery, Hope A. Weiler Abstract Growing evidence suggests that docosahexaenoic acid (DHA: 22:6n-3) enhances bone mineral content (BMC) and bone mineral density (BMD) in adulthood and during aging, however the effects during and after sexual maturation are unclear. The aim of this study was to examine the dose-response of BMC, BMD and microarchitectural properties of bone to dietary DHA in healthy growing female rats during acquisition of peak bone mass (PBM). Female Sprague-Dawley rats (n = 12/diet) were randomized to receive a control diet (AIN-93 M, 60 g soybean oil/kg diet) or an experimental diet containing 0.1, 0.4, 0.8 and 1.2% DHA (w/w of total diet) for 10 weeks. Dietary DHA increased the whole body, lumbar spine and long bone BMC compared to the control, in addition to higher aBMD and also BMD. Additionally, an increase in cortical bone microarchitecture parameters of lumbar spine as well as peak force were observed in dietary DHA diet groups. Dietary DHA contributes to PBM when consumed during and after sexual maturation, however higher doses of DHA do not provide further benefits. Changes to breast milk fatty acid composition during storage, handling and processing: a systematic review Publication date: Available online 1 May 2019 Source: Prostaglandins, Leukotrienes and Essential Fatty Acids Author(s): Chang Gao, Jacqueline Miller, Philippa F. Middleton, Yi-Chao Huang, Andrew J. McPhee, Robert A. Gibson Abstract This review evaluated the effect of various storage and handling conditions on the fat composition of expressed breast milk (EBM). Three databases PubMed, Embase and Scopus were searched in April 2019 with words from the three key components: human milk, handling process (i.e. storage and/or pasteurization), and fatty acid composition. The comparisons were EBM subjected to handling processes versus fresh EBM or versus EBM subjected to another handling processes. Both intervention and observational studies were included, and the outcomes measured included total fat and lipid classes of the EBM. We included 42 studies (43 reports), 40 of which were assessed to be of good quality. Relative changes to the fat composition of EBM subjected to handling processes were calculated based on the data provided in the included studies, and the results were synthesized narratively. The total fat content and total fatty acid composition of EBM was not generally influenced by storage and handling process, with most changes less than 10%, which is likely a result of methodological variation. A reduction in EBM triglyceride concentration and concomitant increase in free fatty acid concentration were seen after exposing to various conditions, probably due to endogenous lipase. Summary Our systematic review suggests that the total fat content of breast milk and its fatty acid composition are not affected by any storage or handling processes, where changes were seen they mostly less than 10% and likely due to methodological errors. However, the studies reviewed suggest that the lipid classes of breast milk are affected by storage, pasteurization, and various thawing and warming methods perhaps due to the presence of lipases. There are needs for developing clinical guidelines on handling expressed breast milk for better preserving the fat composition and developing modern technologies for more precise measurements of the changes to breast milk fat composition.

Magnetic Resonance Materials in Physics, Biology and Medicine Projection-based respiratory-resolved left ventricular volume measurements in patients using free-breathing double golden-angle 3D radial acquisition Abstract Objective To refine a new technique to measure respiratory-resolved left ventricular end-diastolic volume (LVEDV) in mid-inspiration and mid-expiration using a respiratory self-gating technique and demonstrate clinical feasibility in patients. Materials and methods Ten consecutive patients were imaged at 1.5 T during 10 min of free breathing using a 3D golden-angle radial trajectory. Two respiratory self-gating signals were extracted and compared: from the k-space center of all acquired spokes, and from a superior–inferior projection spoke repeated every 64 ms. Data were binned into end-diastole and two respiratory phases of 15% respiratory cycle duration in mid-inspiration and mid-expiration. LVED volume and septal–lateral diameter were measured from manual segmentation of the endocardial border. Results Respiratory-induced variation in LVED size expressed as mid-inspiration relative to mid-expiration was, for volume, 1 ± 8% with k-space-based self-gating and 8 ± 2% with projection-based self-gating (P = 0.04), and for septal–lateral diameter, 2 ± 2% with k-space-based self-gating and 10 ± 1% with projection-based self-gating (P = 0.002). Discussion Measuring respiratory variation in LVED size was possible in clinical patients with projection-based respiratory self-gating, and the measured respiratory variation was consistent with previous studies on healthy volunteers. Projection-based self-gating detected a higher variation in LVED volume and diameter during respiration, compared to k-space-based self-gating. Realization of 19 F MRI oximetry method using perfluorodecalin Abstract Objective To identify the technical aspects of the potential use of clinically approved perfluorodecalin (PFD, C10F18) for 19F magnetic resonance imaging (MRI) oximetry method at high magnetic field 7.05 T. Materials and methods 19F T1 measurements were made on a set of PFD samples with different oxygen contents (0%, 21%, and 100%) at room (21 °C) and body temperature (37 °C). In vivo MRI studies were carried out on one healthy rat and two rats with C6 brain glioma. Results The selective excitation of the magnetically equivalent 19F nuclei of CF2 groups of trans-isomer of PFD, which give a doublet at a frequency of about − 140 ppm (in relation the chemical shift of trifluoroacetic acid, which is − 76.55 ppm) should be done for correct implementation of 19F MRI oximetry method. The amount of PFD equal to 30 μl is the optimal for obtaining reliable data on the measured T1 values. In this case, the standard deviation of T1 does not exceed 5%. In vivo MRI studies showed that the values of the partial pressure of oxygen (pO2) decrease from normal values of about 38 mmHg (healthy brain) to almost 0 mmHg at the last stage of tumor growth. Conclusion The study showed the feasibility of the successful application of PFD for 19F MRI oximetry method. Precision of T1-relaxation time measurements in the hepatic portal vein: influence of measurement technique and sequence parameters Abstract Objective To investigate the effects of a range of parameter settings on T1 measurement stability in the portal vein using the T1-mapping sequences Look-Locker (LL) and Modified Look-Locker inversion recovery (MOLLI). Materials and methods Ten different versions of LL and MOLLI sequences were tested and compared to a reference sequence provided by the MR manufacturer. Ten healthy volunteers were imaged multiple times on two separate scan days at 3T. The mean T1 values and coefficient of variation (CoV) were calculated for each of the ten sequences and compared to the reference sequence. Results Six of the tested sequences had T1 values close to the reference sequence; among those, three sequences achieved lower CoV than the reference sequence. Lowest CoV was achieved using a non-triggered LL sequence with 5 beat readout and a 45o flip angle (mean T1 1733 ms ± 89 ms, CoV 1.3% ± 0.58%). Conclusion T1-measurements in the hepatic portal vein can be performed with high precision using either MOLLI or LL sequences provided that LL sampling duration is sufficiently long and flip angle sufficiently high. The advantage of constant timing outweighed the advantage of ECG-triggering. A phase-cycled temperature-sensitive fast spin echo sequence with conductivity bias correction for monitoring of mild RF hyperthermia with PRFS Abstract Objective Mild hyperthermia (HT) treatments are generally monitored by phase-referenced proton resonance frequency shift calculations. A novel phase and thus temperature-sensitive fast spin echo (TFSE) sequence is introduced and compared to the double echo gradient echo (DEGRE) sequence. Theory and methods For a proton resonance frequency shift (PRFS)-sensitive TFSE sequence, a phase cycling method is applied to separate even from odd echoes. This method compensates for conductivity change-induced bias in temperature mapping as does the DEGRE sequence. Both sequences were alternately applied during a phantom heating experiment using the clinical setup for deep radio frequency HT (RF-HT). The B0 drift-corrected temperature values in a region of interest around temperature probes are compared to the temperature probe data and further evaluated in Bland–Altman plots. The stability of both methods was also tested within the thighs of three volunteers at a constant temperature using the subcutaneous fat layer for B0-drift correction. Results During the phantom heating experiment, on average TFSE temperature maps achieved double temperature-to-noise ratio (TNR) efficiency in comparison with DEGRE temperature maps. In-vivo images of the thighs exhibit stable temperature readings of ± 1 °C over 25 min of scanning in three volunteers for both methods. On average, the TNR efficiency improved by around 25% for in vivo data. Conclusion A novel TFSE method has been adapted to monitor temperature during mild HT. A study of within-subject reliability of the brain's default-mode network Abstract Objective Resting-state functional magnetic resonance imaging (fMRI) is promising for Alzheimer's disease (AD). This study aimed to examine short-term reliability of the default-mode network (DMN), one of the main haemodynamic patterns of the brain. Materials and methods Using a 1.5 T Philips Achieva scanner, two consecutive resting-state fMRI runs were acquired on 69 healthy adults, 62 patients with mild cognitive impairment (MCI) due to AD, and 28 patients with AD dementia. The anterior and posterior DMN and, as control, the visual-processing network (VPN) were computed using two different methodologies: connectivity of predetermined seeds (theory-driven) and dual regression (data-driven). Divergence and convergence in network strength and topography were calculated with paired t tests, global correlation coefficients, voxel-based correlation maps, and indices of reliability. Results No topographical differences were found in any of the networks. High correlations and reliability were found in the posterior DMN of healthy adults and MCI patients. Lower reliability was found in the anterior DMN and in the VPN, and in the posterior DMN of dementia patients. Discussion Strength and topography of the posterior DMN appear relatively stable and reliable over a short-term period of acquisition but with some degree of variability across clinical samples. The feasibility of a novel limited field of view spiral cine DENSE sequence to assess myocardial strain in dilated cardiomyopathy Abstract Objective Develop an accelerated cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) sequence to enable clinically feasible myocardial strain evaluation in patients with dilated cardiomyopathy (DCM). Materials and methods A spiral cine DENSE sequence was modified by limiting the field of view in two dimensions using in-plane slice-selective pulses in the stimulated echo. This reduced breath hold duration from 20RR to 14RR intervals. Following phantom and pilot studies, the feasibility of the sequence to assess peak radial, circumferential, and longitudinal strain was tested in control subjects (n = 18) and then applied in DCM patients (n = 29). Results DENSE acquisition was possible in all participants. Elements of the data were not analysable in 1 control (6%) and 4 DCM r(14%) subjects due to off-resonance or susceptibility artefacts and low signal-to-noise ratio. Peak radial, circumferential, short-axis contour strain and longitudinal strain was reduced in DCM patients (p < 0.001 vs. controls) and strain measurements correlated with left ventricular ejection fraction (with circumferential strain r = − 0.79, p < 0.0001; with vertical long-axis strain r = − 0.76, p < 0.0001). All strain measurements had good inter-observer agreement (ICC > 0.80), except peak radial strain. Discussion We demonstrate the feasibility of CMR strain assessment in healthy controls and DCM patients using an accelerated cine DENSE technique. This may facilitate integration of strain assessment into routine CMR studies. Accelerated multi-contrast high isotropic resolution 3D intracranial vessel wall MRI using a tailored k-space undersampling and partially parallel reconstruction strategy Abstract Objective To develop a 3D multi-contrast IVW protocol with 0.5-mm isotropic resolution and a scan time of 5 min per sequence. Materials and methods Pre-contrast T1w VISTA, DANTE prepared PDw VISTA, SNAP, and post-contrast T1w VISTA were accelerated using cartesian undersampling with target ordering method (CUSTOM) and self-supporting tailored k-space estimation for parallel imaging reconstruction (STEP). CUSTOM + STEP IVW was compared to full-sample IVW, SENSE-accelerated IVW, and CUSTOM + zero-filled Fourier reconstruction in normal volunteers and subjects with intracranial atherosclerotic disease (ICAD). Image quality, vessel delineation, CSF suppression, and blood suppression were compared. Results CUSTOM + STEP vessel wall delineation was comparable to full-sample IVW and better than SENSE IVW for vessel wall delineation on T1w VISTA and luminal contrast on SNAP. Average image quality and wall depiction were significantly improved using STEP reconstruction compared with zero-filled Fourier reconstruction, with no significant difference in CSF or blood suppression. Conclusions CUSTOM + STEP allowed multi-contrast 3D 0.5-mm isotropic IVW within 30 min. Although some quantitative and qualitative scores for CUSTOM − STEP were lower than fully sampled IVW, CUSTOM + STEP provided comparable vessel wall delineation as full-sample IVW and was superior to SENSE. CUSTOM + STEP IVW was well tolerated by patients and showed good delineation of ICAD plaque. Feasibility of diffusion-weighted imaging with DWIBS in staging Hodgkin lymphoma in pediatric patients: comparison with PET/CT Abstract Objective The aim of the study was to evaluate feasibility of diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) method in diagnosing Hodgkin lymphoma in pediatric patients and to compare it with 18F-FDG PET/CT as a gold standard. Materials and methods Eleven patients (median age 14) with newly diagnosed Hodgkin lymphoma were examined with 18F-FDG PET/CT and MRI including whole-body DWIBS sequence (b = 0, 800 s/mm2), before the oncologic treatment. About 26 locations of lymphatic tissues were evaluated visually and quantitatively using ADCmean (DWIBS) and SUVmax (18F-FDG PET/CT), respectively. Results All affected lymph node regions (n = 134) diagnosed in 18F-FDG PET/CT were found with DWIBS, presenting decreased diffusion. Significant correlation was found between ADC and SUV values (R2 = − 0.37; p = 0.0001). Nevertheless, additional 33 regions were recognized only by DWIBS. They were significantly smaller than regions diagnosed by both methods. Discussion Agreement between DWIBS and 18F-FDG PET/CT for detection and staging of malignant lymphoma is high. DWIBS can be used for the evaluation of pediatric Hodgkin lymphoma. Challenges for labeling and longitudinal tracking of adoptively transferred autoreactive T lymphocytes in an experimental type-1 diabetes model Abstract Objective Tracking the autoreactive T-cell migration in the pancreatic region after labeling with fluorinated nanoparticles (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[3-(2-pyridyldithio)propionate]-perfluoro-15-crown-5-ether nanoparticles, PDP-PFCE NPs) in a diabetic murine model using 19F MRI. Materials and methods Synthesis of novel PDP-PFCE fluorine tracer was performed for in vitro labeling of T cells. Labeling conditions were optimized using different PDP-PFCE NPs concentrations. For in vivo 19F MRI, mice were longitudinally followed after adoptive transfer of activated, autoreactive, labeled T cells in NOD.SCID mice. Results Established MR protocols were used for challenging T cell labeling to track inflammation in a model of diabetes after successful labeling of CD4+ and CD8+ T cells with PDP-PFCE NPs. However, T cells were difficult to be detected in vivo after their engraftment in animals. Discussion We showed successful in vitro labeling of T cells using novel fluorinated liposomal nanoparticles. However, insufficient and slow accumulation of labeled T cells and subsequent T cell proliferation in the pancreatic region remains as limitations of in vivo cell imaging by 19F MRI. In-bore biopsies of the prostate assisted by a remote-controlled manipulator at 1.5 T Abstract Purpose To evaluate the technical and clinical utility of a fully MRI-compatible, pneumatically driven remote-controlled manipulator (RCM) for targeted biopsies of the prostate at 1.5 T. Materials and methods The data of the first 22 patients that were biopsied under robotic assistance were analyzed. Interventional planning relied on T2-weighted (T2w) turbo spin-echo (TSE) images (axial and sagittal) with a high-b-value diffusion-weighted acquisition added in selected cases. Alignment of the needle guide was controlled with a short balanced SSFP sequence in two oblique planes along the MR-visible sheath. Signals were acquired with a combination of elements from a 30-channel body and a 32-channel spine coil. Biopsy samples were taken with a fully automatic 18-G biopsy gun with a length of 150 or 175 mm. Results Mean age was 66.6 years and average PSA level was 11.5 ng/ml. Fourteen out of 22 patients (63%) had received prior biopsies under transrectal ultrasound guidance. Diagnostic MRI reports (before biopsy) involved 17 cases with a single suspicious finding (four PI-RADS 3, one PI-RADS 3–4, eight PI-RADS 4 and nine PI-RADS 5 cases). The median effective procedure time was 33.9 (range 25.0–55.9) min for 16 cases with one CSR and 63.4 (52.7–81.8) min for 5 cases with two CSRs. The biopsy with three CSRs took 74.0 min. Histopathologic examination revealed prostate cancer in 14 of 22 cases. Conclusion MR-targeted, transrectal biopsy of the prostate could be reliably performed with a robotic manipulator at a field strength of 1.5 T. Balanced SSFP imaging is considered a viable option for fast procedural control. Follow-up work needs to evaluate to what extent in-bore adjustments and workflow enhancements will contribute to shorter procedure times or higher patient comfort.

Oncology,Oecology,Radiology,Pediatric Drugs,Pediatric Surgery,Patients Clinical Oncology RFA experiences, indications and clinical outcomes Abstract Backgound Early-stage breast cancer is increasingly detected by screening mammography, and we aim to establish radiofrequency ablation therapy (RFA) as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. Although there were many studies on resection after RFA, none of them provided sufficient evidence to support RFA as a standard therapy for breast cancer. Results In our Phase I study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically. Our phase II multicenter study of RFA without resection for early breast cancer will evaluate the long-term safety and efficacy of RFA as well as its cosmetic results, which are a perceived advantage of this technique. We started a phase III multicenter study to demonstrate the non-inferiority of RFA compared with standard treatment (breast-conserving surgery) in terms of ipsilateral breast tumor recurrence (IBTR) rate, which is the best index of local control. Conclucion To standardize RFA for breast cancer, the results of our multicenter study, Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (the RAFAELO study) that began in 2013, are eagerly awaited. Control of intracranial disease is associated with improved survival in patients with brain metastasis from hepatocellular carcinoma Abstract Background Brain metastasis is a rare event in patients with hepatocellular carcinoma (HCC). This retrospective study aimed to identify the prognostic factors and determine the outcomes of patients with brain metastases from HCC. Methods About 86 patients with brain metastases (0.6%) from HCC were identified from two institutions; of them, 32 underwent tumor-removing surgery or stereotactic radiosurgery (SRS) with or without adjuvant whole brain radiotherapy (WBRT) (group 1), 30 had WBRT alone (group 2), and 24 received conservative treatment (group 3). Estimates for overall survival (OS) after brain metastases were determined, and clinical prognostic factors were identified. Results The median OS after development of brain metastases was 50 days. About 75 (87.2%) patients had lung metastases at the time of brain metastasis diagnosis. Group 1 showed better OS, followed by group 2 and group 3, sequentially (p < 0.001). Univariate analyses showed that treatment with curative intent (surgery or SRS), Child–Pugh class A, alpha-fetoprotein level < 400 ng/ml, and recursive partitioning analysis classification I or II were associated with improved survival (p < 0.001, 0.002, 0.029, and 0.012, respectively). Multivariate analysis showed that treatment with curative intent and Child–Pugh class A was associated with improved OS (p < 0.001 and 0.009, respectively). Conclusion Although the overall prognosis of patients with brain metastases from HCC is extremely poor, patients actively treated with surgery or radiosurgery have prolonged survival, suggesting that interventions to control intracranial disease are important in these patients. Adjuvant therapy in renal cell carcinoma: the perspective of urologists Abstract Background Until recently, there was no approved adjuvant therapy (AT) for renal cell carcinoma (RCC) unless sunitinib was approved in the US. We evaluated clinical opinion and estimated use regarding different treatment options and patient selection of AT in RCC patients based on current scientific data and individual experience in Germany. Methods We conducted an anonymous survey during a national urology conference in 01/2017. Answers of 157 urologists treating RCC patients could be included. Questions were related to practice setting, treatment of RCC, follow-up strategy, physicians' personal opinion and individually different important parameters regarding S-TRAC and ASSURE-trial. Results 82% were office based. 67% were located in larger cities. 83% reported that nephron-sparing surgery (NSS) was performed in tumors with diameter < 4 cm. Follow-up was done mainly in concordance with guideline recommendations. 68% treated an average of 2.9 patients/year with systemic therapy. Therapy was predominantly advocated using sunitinib (94%). Urologists were informed about S-TRAC and ASSURE-trial. For 47%, reported hazard ratio is the most important parameter to understand trial results followed by overall survival (OS) in 46%, disease-free survival in 38%, and results of other trials in 34%. The most convincing parameter to decide on AT is OS (69%). 62% placed their confidence in ASSURE over STRAC-trial. 44% would use AT for 12 months. Nodal involvement was the most common denominator for use of AT. 82% favor sunitinib as AT. Conclusions A minority of urologists would use AT and are more confident in ASSURE-trial. Reluctance of prescribing AT mainly is based on lack of OS data and conflicting trial results. Optimal treatment strategy for rectal cancer based on the risk factors for recurrence patterns Abstract Background For rectal cancer, multimodality therapeutic approach is necessary to prevent local recurrence and distant metastasis. However, the efficacy of additional treatments, such as neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy (NAC), and lateral pelvic lymph node dissection (LPLND), has not been scrutinized. Methods Recurrence patterns were categorized into local recurrence and distant metastasis. Local recurrence was classified into two types: (1) pelvic cavity recurrence and (2) LPLN recurrence. First, we analyzed the risk factors for each recurrence pattern. Second, based on the status of clinically suspected involvement of circumferential resection margin (cCRM), the efficacy of additional treatments was investigated. Results A total of 240 patients was enrolled. nCRT was performed for 25 (10%), NAC was for 46 (19%), and LPLND was for 35 patients (15%). As the recurrence patterns, pelvic cavity recurrence occurred in 15 (6%), LPLN recurrence in 8 (3%), and distant metastasis in 42 patients (18%). Five-year overall survival and relapse-free survival were 87% and 70%, respectively. Multivariate analysis indicated that pelvic cavity recurrence was associated with cCRM status and tumor histology, that LPLN recurrence was with serum carcinoembryonic antigen level and LPLN swelling, and that distant metastasis was with clinical N category. In the cCRM-positive subgroup (n = 66), cumulative rate of pelvic cavity recurrence was lower in the nCRT group than in the NAC or non-NAC/nCRT group (P = 0.02 and 0.09, respectively). Conclusion cCRM status was associated with pelvic cavity recurrence, and LPLN swelling was with LPLN recurrence. nCRT could reduce pelvic cavity recurrence in cCRM-positive subgroup. Cryosurgery for primary breast cancers, its biological impact, and clinical outcomes Abstract Recently, a number of new minimally invasive image-guided percutaneous ablation treatments, including cryoablation, radiofrequency ablation, microwave ablation, high-intensity focused ultrasound, laser ablation, and irreversible electroporation have been developed. Several studies have shown the feasibility and safety of these cryoablation therapies for the treatment of benign breast tumors and small invasive breast cancer. Although the complete response rate of cryoablation for breast cancer is reported to be relatively good, most studies enrolled a small number of patients, and so reliable conclusions could not be drawn. In this review, we introduce the mechanisms of action of cryoablation, and summarize the current literature on the efficacy and safety of cryoablation for breast cancer. Cryoablation also induces an immunomodulatory effect, which is an interesting topic of research in the era of immune checkpoint inhibitors. Cryoablation for primary tumor may enhance the treatment effect of immune checkpoint inhibitors in patients with breast cancer. Further investigations of this new therapeutic strategy are needed. CT and clinical characteristics that predict risk of EGFR mutation in non-small cell lung cancer: a systematic review and meta-analysis Abstract Introduction To systematically analyze CT and clinical characteristics to find out the risk factors of epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC). Then the significant characteristics were used to set up a mathematic model to predict EGFR mutation in NSCLC. Materials and methods PubMed, Web of Knowledge and EMBASE up to August 17, 2018 were systematically searched for relevant studies that investigated the evidence of association between CT and clinical characteristics and EGFR mutation in NSCLC. After study selection, data extraction, and quality assessment, the pooled odds ratios (ORs) were calculated. Then from May 2017 to August 2018, all NSCLC received EGFR mutation examination and CT examination in our hospital were chosen to test the prediction model by receiver operating characteristic (ROC) curves. Results Seventeen original studies met the inclusion criteria. The results showed that the ORs of ground-glass opacity (GGO), air bronchogram, pleural retraction, vascular convergence, smoking history, female gender were, respectively, 1.93 (P = 0.003), 2.09 (P = 0.03), 1.59 (P < 0.01), 1.61 (P = 0.001), 0.28 (P < 0.01), 0.35 (P < 0.01). The result of speculation, cavitation/bubble-like lucency, lesion shape, margin, pathological stage were, respectively, 1.19 (P = 0.32), 0.99 (P = 0.97), 0.82 (P = 0.42), 1.02 (P = 0.90), 0.77 (P = 0.30). 121 NSCLC received EGFR mutation test were included to test the prediction model. The mathematical model based on the results of meta-analysis was: 0.74 × air bronchogram + 0.46 × pleural retraction + 0.48 × vascular convergence − 1.27 × non-smoking history − 1.05 × female. The area under the ROC curve was 0.68. Conclusion Based on the current evidence, GGO presence, air bronchogram, pleural retraction, vascular convergence were significant risk factors of EGFR mutation in NSCLC. And the prediction model can help to predict EGFR mutation status. Lymph node ratio has impact on relapse and outcome in patients with stage III melanoma Abstract Background Even though both the involvement of regional lymph nodes and the number of metastatic lymph nodes are regarded as major determinants of survival in cutaneous melanoma, the extent of node dissection has been analyzed as an independent prognostic indicator in only a few studies. This study aims to determine how the lymph node ratio (NR) (ratio of positive nodes to total nodes removed) might predict the disease relapse and survival in node-positive melanoma. Materials and methods A total of 317 patients with stage III primary melanoma were included in the study and reviewed retrospectively. All patients had nodal staging (N) by radical lymph node dissection. Patients were divided into three groups based on NR1 ≤ 10%, NR2 10–25%, and NR3 > 25%. Results The median age was 50 years (range 16–86) and men were predominant (59.3%). The majority of the patients had thicker Breslow depth (> 2 mm) (83.3%), higher mitotic rate (> 2/mm2) (64.1%) and ulcerated lesions (69.4%). The median number of positive nodes was 1 (range 1–32). The largest group was N1 (52.4%), which was followed by N2 (29.6%) and N3 (18%). The ratios of patients were 37.5%, 35.3%, and 27.1% in NR1, NR2, and NR3, respectively. The median number of excised lymph nodes was 13 (range 1–73). For all patients the estimated 5-and 10-year relapse-free survival (RFS) rates were 41% and 39%, respectively; and the estimated 5-and 10-year overall survival (OS) rates were 51% and 42%, respectively. Nodular histopathology, ulcerated lesions, higher mitotic rates, and higher node substages were the independent variables that were inversely correlated with survival for all patients; and NR was one of the significant prognostic factors and strongest predictors of relapse and survival (p = 0.03 and p = 0.01, respectively). Conclusion Our results suggest that, apart from the conventional nodal status, NR is an independent prognostic factor-regarding both RFS and OS in stage III cutaneous melanoma. Radiotherapy alone as a possible de-intensified treatment for human papillomavirus-related locally advanced oropharyngeal squamous cell carcinoma Abstract Background Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown. Methods We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model. Results Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. Conclusions Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC. Resection of pancreatic metastatic renal cell carcinoma: experience and long-term survival outcome from a large center in China Abstract Purpose This study aimed to determine the outcome of pancreatic metastatic renal cell carcinoma (PmRCC) after treatment and share the relevent results. Methods In total, 13 patients with PmRCC were diagnosed and treated in our institution from December 2013 to October 2017. We retrospectively reviewed the records and analyzed the patient demographics, perioperative outcomes, and overall survival. Simultaneously, our experience including treatment and misdiagnosis was shared. Results The median time between nephrectomy and reoperation for pancreatic recurrence was 11 years (range 1–20 years). Four patients had multiple tumors and nine patients had solitary tumor. Five patients accepted distal pancreatectomy, and five patients underwent pancreaticoduodenectomy. One patient underwent total pancreatectomy, one patient underwent duodenum-preserving pancreatic head resection plus distal pancreatectomy, and one patient underwent exploratory laparotomy and gastrointestinal bypass due to widespread metastasis with clear obstructive symptoms. The misdiagnosis rate of preoperative diagnosis at our center was 69.2% (9/13). The median follow-up duration was 26 months (range 7–53 months, until June 2018). By the end of follow-up, 12 patients were alive and one patient died of gastrointestinal bleeding within 1 month after surgery. Conclusions PmRCCs are uncommon, but pancreatic metastasectomy has a relatively good prognosis and may, therefore, be a good therapeutic choice for patients with PmRCCs. Because PmRCC occurs long after the primary tumor resection, long-term follow-up is necessary. Besides, detailed medical history and specific manifestation in imaging features could contribute to avoiding misdiagnosis. Saddle pulmonary embolism and in-hospital mortality in patients with cancer Abstract Purpose Saddle pulmonary embolism (PE) has been associated with an increased risk of 1 year mortality when compared to non-saddle PE among patients with cancer. We sought to evaluate the association between saddle PE and in-hospital outcomes among patients with comorbid cancer. Methods The 2013 and 2014 United States National Inpatient Sample was used to identify adult patients hospitalized for acute PE. Only patients with an International Classification Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code indicating comorbid cancer were included. Identified admissions were stratified into the following 2 cohorts: saddle (defined as ICD-9-CM code = 415.13) and non-saddle PE. Multivariable logistic regression was performed to determine the association between saddle PE and the odds of in-hospital mortality after adjustment for age ≥ 80 years and sex. Results A total of 10,660 admissions for acute PE in patients with comorbid cancer were identified. Of which, 4.5% (n = 475) had a saddle PE. Median age was 67 years (interquartile range = 58–76) and 48.9% were male. In-hospital mortality occurred in 6.1% of patients. Upon multivariable adjustment, the odds of in-hospital mortality were higher in saddle versus non-saddle PE (odds ratio = 1.51; 95% confidence interval 1.08–2.10). Conclusion In this retrospective study of admissions for acute PE in patients with comorbid cancer, saddle PE was associated with a higher odds of in-hospital mortality. Acta Oecologica Earthworms contribute to ecosystem process in no-till systems with high crop rotation intensity in Argentina Publication date: July 2019 Source: Acta Oecologica, Volume 98 Author(s): J.C. Bedano, F. Vaquero, A. Domínguez, M.P. Rodríguez, L. Wall, P. Lavelle Abstract In the Pampas region of Argentina agriculture is dominated by intensive no-till (NT) soybean cropping which produce negative consequences on soil quality. A group of farmers started to use the Good Agricultural Practices (GAP) which include a higher crop rotation, use of winter cover crops and nutrient restoration. In this NT system earthworms have a significant role in soil functioning, particularly in organic matter cycling and soil structure formation. The aim of this paper was to examine the contribution of earthworm activity to the process of C incorporation and soil structure maintenance in soils with different NT variants of: NT with GAP for 30 years (NT + r30); NT with some of the GAP for 12 years (NT-r12) and NT with soybean monoculture (NTm). Also a natural grassland (NA) was sampled as a reference. Earthworm aggregates were obtained by gently separating them from surrounding soil. Fine (HOC) and coarse (POC) organic matter fractions, water-stable aggregates (WSA) and mean weight diameter (MWD) were calculated for earthworm aggregates and bulk soil. In all sites only one species (Aporrectodea caliginosa) was found, with higher density in the NA, followed by NT + r30, that had about 9 times more earthworms than NTm. The number of earthworm aggregates was higher in the NT + r30 followed by the NA, both showing differences with the other NT systems. The earthworm aggregates in NA and NT + r30 had significantly more POC than the surrounding soil (230% increase in NA and 100% NT + r30). Earthworm casts had higher values of MWD and WSA than physical soil aggregates in both NA and NT + r30 management treatments. Our results show the existence of a positive feedback loop we called earthworm-driven virtuous cycle. The increase in earthworm abundance promotes higher production of earthworm aggregates which are richer in organic matter and more water stable than the surrounding soil. This has favourable results in terms of soil quality but also increase crop yields (57% in maize and 18% in soybean), by means of biologically mediated soil processes, which is a highly desirable way to sustainability of agricultural production. Farmers, politicians and the whole society should pay more attention to soil as a key component supporting agricultural production by means of internal biological soil functioning. Heterogeneity in millipede communities (Diplopoda) within a forest–forest edge–meadow habitat complex Publication date: July 2019 Source: Acta Oecologica, Volume 98 Author(s): Slavomír Stašiov, Vladimír Kubovčík, Marek Čiliak, Andrea Diviaková, Ivan Lukáčik, Vladimír Pätoprstý, Martin Dovciak Abstract The positive influence of heterogeneity in vegetation and land-use on animal diversity is generally well established, but it has not been conclusively confirmed yet in millipede communities inhabiting karst canyons where biodiversity is to large extent determined by variation in topography (e.g., elevation). We studied how millipede assemblages (Diplopoda) vary between forest, forest edge, and meadow habitats in this specific karst environment. We sampled millipedes by pitfall trapping during two vegetation seasons (from March to October in 2001 and 2002) in approximately monthly intervals across nine sites in Central Slovakia (Veľká Fatra Mts). In total, 951 individuals belonging to 12 species from 6 families and 10 orders were collected. The dominant species was Unciger foetidus, which was also one of the two most frequent species along with Polydesmus complanatus. Although the total number of captured millipedes was greatest on forest edges (395 individuals), intermediate in meadows, and lowest in forests (214 individuals), millipede abundance and species composition varied considerably within each habitat type among the sites. Total millipede species richness in meadow and forest edge habitats was the same (11 species) and it was lower in forest habitats (7 species), while species diversity (Shannon's H′) and equitability (E) were greatest in meadows. Millipede diversity measures (species richness or equitability) were correlated positively with species richness of herb layer and negatively with shrub layer equitability, soil conductivity, and soil phosphorus. Thus, we found complex patterns of heterogeneity in millipede community composition and richness across studied habitats and elevations that were driven by habitat type and plant community and soil characteristics. While millipede abundance patterns varied, open habitats supported most species-rich millipede communities at lower elevations, while forest edges were most species-rich at the high elevation. Fear alone reduces energy processing by resident 'keystone' prey threatened by an invader; a non-consumptive effect of 'killer shrimp' invasion of freshwater ecosystems is revealed Publication date: July 2019 Source: Acta Oecologica, Volume 98 Author(s): Calum MacNeil, Mark Briffa Abstract Non-consumptive effects (NCEs) of predators – so called 'fear' responses – encompass costly antipredator behaviours, such as reduced feeding efficiency. NCEs can influence prey population dynamics and community structure, if prey are 'keystone' species such as Gammarus spp. amphipod 'shrimps'. These freshwater macroinvertebrates have the ecosystem functional role of shredding fallen leaf litter, making it accessible to other taxa. Across Europe, the invasive predatory 'killer shrimp' Dikerogammarus villosus is replacing resident Gammarus spp., potentially threatening this vital ecosystem function. While predation (consumptive effects (CEs)) of this invader has been well studied, for the first time we test whether NCEs can be evident in prey only exposed to D. villosus presence and whether this could potentially impact on the prey's functional role. In mesocosms, exposure to constrained D. villosus did not result in mortalities of any of three Gammarus prey species but the leaf shredding efficiencies of all prey were significantly reduced compared to a control treatment. This clear NCE has the potential to propagate through the ecological community via decreased energy processing. This study demonstrates the potential for fear of invasive predator presence alone to impact on ecosystem function. Determinants of spatial patterns of plant diversity depend on the biogeographical affinities of the taxa − a case study in Northwest Yunnan, Southwest China Publication date: May 2019 Source: Acta Oecologica, Volume 97 Author(s): Jianmeng Feng Abstract The influence of the biogeographical affinities of taxa on the spatial determinants of plant diversity remains largely unknown. I explored the spatial patterns of tropical and temperate plant diversity in Northwest Yunnan and their primary determinants. Generalized linear models (GLMs) and variance partitioning were used to investigate the influences of predictors. Temperate genus diversity significantly increased with latitude, whereas tropical genus diversity did not show any obvious latitudinal trends. Proportions of tropical genera decreased with latitude, whereas those of temperate genera were on the contrary. Environment heterogeneity explained higher percentage of the spatial variation of temperate genus diversity than for that of tropical genus diversity. It may imply that the influence of environment heterogeneity on plant diversity may depend on the taxa's biogeographic affinities, which might modify the exploitation of environment heterogeneity, though the flora diversification induced by the uplifting of the Tibet Plateau may also play important roles. Climate predictors explained higher percentages of variation in the proportions of tropical genera than for the variations in tropical genus diversity. It may suggest that compared with the associations between genus diversity with tropical affinities and climatic conditions, the associations between the proportions of tropical plants and climatic conditions might more accurately reflect niche conservatism of tropical plants in the study area. Microclimatic effects on the incubation success, hatchling morphology and locomotor performance of marine turtles Publication date: May 2019 Source: Acta Oecologica, Volume 97 Author(s): Melissa N. Staines, David T. Booth, Colin J. Limpus Abstract Global atmospheric temperatures are predicted to rapidly increase within the next hundred years, consequently altering the microclimates of the sand dune environment where marine turtles lay their eggs. High nest temperatures can increase embryonic mortality, decrease hatchling vigour and size (i.e. quality), and also feminises the sex-ratio of clutches. Sand composition, vegetation cover, rainfall and sun exposure affect the temperature of sand surrounding a nest, however the effect of this variability in the beach environment on the incubation success of a sea turtle clutch is still relatively unknown. We conducted a manipulative study on loggerhead turtle nests at Mon Repos, Queensland, Australia, to investigate the effect of ground-cover vegetation vs bare sand and tree-shade vs no shade on incubation success, hatchling morphology and hatchling locomotor performance. Twenty-four nests were used in a two-factor experimental design, with tree-shade/sun and, ground-cover vegetated/cleared as fixed factors. Sun-exposed nests experienced higher nest temperatures (∼2 °C warmer), shorter incubation periods and poorer incubation success than those in tree-shade. Ground-cover-vegetated nests in tree-shade had lower hatching and emergence success (73%, 66% respectively) than sun-exposed nests placed in sites cleared of ground-cover vegetation (79%, 83% respectively). Hatchlings that emerged from cooler, tree-shaded nests were also larger and crawled faster than hatchlings from sun-exposed nests. We suggest for conservation projects on naturally 'hot' beaches, active management strategies such as selective groundcover vegetation removal and increased shading could be implemented to increase high quality hatchling production. Graphical abstract Linking local people's perception of wildlife and conservation to livelihood and poaching alleviation: A case study of the Dja biosphere reserve, Cameroon Publication date: May 2019 Source: Acta Oecologica, Volume 97 Author(s): Manfred Aimé Epanda, André Junior Mukam Fotsing, Thomas Bacha, Daniel Frynta, Luc Lens, Isaac Roger Tchouamo, Dupain Jef Abstract This Paper examines how people's livelihoods and perceptions of wildlife are related to self-reported poaching (here defined as commercial bushmeat hunting) in 25 villages at the northern buffer zone of the Dja Biosphere Reserve, East Cameroon. Using a six-point Likert scale questionnaire among 263 households interviewed form March to June 2017, the following hypothesis were tested: (1) Households with positive perceptions of wildlife are less involved in poaching; (2) Positive perceptions of wildlife are linked to sustainable livelihood improvement of households; and (3) Sustainable livelihood improvement of households leads to poaching alleviation. The study area has been the site since 2010 for a community-centered conservation Program that aims to improve local people's livelihoods (through the creation of income sources based on cocoa-based agroforestry and Non Timber Forest Products (NTFPs) Valorization) and their perceptions of wildlife (mainly through awareness raising and wildlife education) and therefore divert them from poaching. The main findings of the study indicates that positive perceptions of wildlife are linked to lower levels of poaching. Similarly, positive perception of wildlife was positively related to Livelihood improvement of the respondents. However, livelihood improvement alone did not predict poaching alleviation though we reported a significant difference in poaching frequencies of cocoa and non-cocoa producers with the firsts less involved in poaching. The findings of this study recommend more holistic approaches of biodiversity conservation that integrate simultaneously perception and livelihood improvement. Snake diversity in floodplains of central South America: Is flood pulse the principal driver? Publication date: May 2019 Source: Acta Oecologica, Volume 97 Author(s): Liliana Piatti, Dan F. Rosauer, Cristiano de C. Nogueira, Christine Strussmann, Vanda Lúcia Ferreira, Marcio Martins Abstract Seasonal flood pulses drive important seasonal ecosystem changes, trigger ecological processes that control spatial and temporal distribution of organisms and their life-history strategies, and are considered a key ecological process shaping diversity in floodplains. We used generalized dissimilarity modelling (GDM) to analyse the relative importance of flooding as a driver of snake community composition in the Paraguay River Basin (PRB), which encompasses discontinuous seasonal flooded areas, including the Pantanal floodplain, one of the largest Neotropical wetland systems. We modelled the beta diversity of pairs of PRB snake communities (based on species occurrence and phylogenetic relationships) as a function of biogeographical and environmental dissimilarities between areas, considering predictors that represent distinct limitations of species' ability to use an area. Annual flooding directly drives snake diversity, mainly when ancient evolutionary relationships between species were considered to calculate the phylogenetic diversity of the communities. Floods recurrently produce major changes in the environment and probably limit the persistency of species extremely specialized in habitat use. Despite the confirmation of the effect of flooding, the most important predictor of beta diversity between snake communities in the PRB was forest cover where communities were placed. Forest cover seems to constrain the occurrence of some species in both gradient extremities through the absence of suitable conditions for either specialized habitat use or thermoregulatory behaviours. Geographical distance was also an important predictor of beta diversity, highlighting the importance of neutral process in the assembly of local communities in systems such as seasonally flooded areas, where annual disturbances of varying intensities continually disassemble and reassemble biological communities. For the first time, we quantified the relative importance of flooding affecting patterns of biological communities in the Pantanal floodplain, compared to multiple factors also acting on species turnover in the area. Prey abundance drives habitat occupancy by jaguars in Amazonian floodplain river islands Publication date: May 2019 Source: Acta Oecologica, Volume 97 Author(s): Rafael M. Rabelo, Susan Aragón, Júlio César Bicca-Marques Abstract The jaguar (Panthera onca) is widely distributed across a broad range of habitat types, where its feeding habits and habitat use patterns vary significantly. The jaguar and its main arboreal prey – the brown-throated sloth (Bradypus variegatus) and the red howler monkey (Alouatta juara) – are widespread in the Amazonian floodplain forests of the Mamirauá Reserve. These forest-dwelling species are the most common mammal species both in the continuous forest and the forest patches surrounded by a river matrix – the fluvial islands – of the Solimões and Japurá rivers. We used sign surveys along line-transects to assess the pattern of habitat occupancy by jaguars in Amazonian floodplain forests. Specifically, we (i) tested whether habitat occupancy by jaguars differs between river islands and continuous forest; and (ii) evaluated whether and how the local abundance of sloths and howler monkeys influence the probability of site occupancy by jaguars. We built an occupancy model and used Bayesian inference to reach these goals. The proportion of sites estimated to be used by jaguars was ψ = 0.75 (HPD95: 0.36–1.00), and it did not differ between islands and continuous forest. The abundance of both prey species had a direct influence on jaguar's habitat use, whereas the aquatic matrix seems to have a negligible effect on the use of islands by jaguars. We conclude that the isolation of the river islands within the aquatic matrix does not hamper jaguars to use them. We also conclude that prey search modulates jaguars' habitat occupancy patterns with both prey species having a similar effect. This finding is compatible with the previously reported importance of sloths to the diet of jaguars in the study region despite its lower abundance than howlers. Finally, we suggest that sign surveys are an alternative method to assess the pattern of jaguar habitat occupancy in floodplain forests. Environmental adaptation and ecological distribution of streamside annual plants in northern Japan Publication date: May 2019 Source: Acta Oecologica, Volume 97 Author(s): Mayuko Suzuki, Takashi Nakamura, Takeshi Shindo, Masahito T. Kimura Abstract Environmental adaptation and distribution of three annual plants, Impatiens noli-tangere, I. textori and Persicaria thunbergii, occurring in streamside environments were studied in Sapporo, northern Japan. Impatiens noli-tangere was found along steep streams as well as gentle streams, whereas I. textori and P. thunbergii were less frequent along steep streams than along gentle streams. Impatiens noli-tangere was the least tolerant or resistant to environmental disturbances such as submergence, rapid water current, herbivory and possibly shading. P. thunbergii was the most tolerant or resistant, and I. textori showed an intermediate response. On the other hand, I. noli-tangere started reproduction earliest, followed by I. textori and P. thunbergii. Earlier start of reproduction of I. noli-tangere is assumed to serve as a means to reduce risks to encounter catastrophic events before reproduction. In addition, I. noli-tangere was the tallest per stem dry-weight unit. Growing taller would be an adaptation to reduce risk of shading. It is assumed that earlier reproduction enables I. noli-tangere to leave offspring along steep streams where water current after heavy rain is more rapid and catastrophic. Quad bike impacts on vegetation and soil physicochemical properties in an arid ecosystem Publication date: May 2019 Source: Acta Oecologica, Volume 97 Author(s): Ana L. Navas Romero, Mario A. Herrera Moratta, Antonio D. Dalmasso, Agustina Barros Abstract The increase use of Off-Road Vehicles (ORVs) coupled with the absence of control strategies have led to extensive use of natural areas for the creation of recreational trails. We assessed the effects of quad bikes on vegetation and soils in an arid ecosystem subjected to intensive quad bike use. We selected randomly eight traffic sites (disturbed sites) and eight adjacent control sites (undisturbed sites). Plant cover and composition were assessed with the point-intercept method and phytosociological census. In each site, we collected soil samples to assess soil physicochemical properties, including apparent specific weight (ASG), actual specific weight (RSG), porosity, texture, electric conductivity (EC) and pH. Soil compaction was measured at 30 spaces points per site. Plant cover and richness was significant lower in disturbed sites, with only four species present in areas subjected to disturbance. There were also changes in species dominance, with native perennial shrubs and grasses characterizing the undisturbed sites while the disturbed sites were mainly dominated by the invasive exotic herb Salsola kali. ORVs traffic also affected soil physicochemical properties including soil compaction, ASG, EC and soil pH. Soil compaction was more than double in disturbed sites and ASG tended to be higher under this condition. The EC was significantly higher and soil pH was significantly lower in the disturbed sites. Reduced vegetation cover and changes to soils physicochemical properties on quadbike trails highlights the impacts of ORVs in the landscape and the need to develop management strategies to minimize disturbance from ORVs on vegetation and soils. Radiology Global Outreach for U.S. Radiology Training Programs Abstract Purpose of Review Utilization of medical imaging is increasing in the developing world, creating new opportunities for U.S. radiology training programs to establish international electives for interested faculty and residents. Though the nature of each initiative will vary, the process of creating a global outreach elective involves core elements. Recent Findings Development of a sustainable and impactful global elective requires forethought and planning, including abiding by regulations from governing bodies and preparation for practicing in a culturally different and often resource-limited environment. Summary This article will provide a summary of requirements for creating and sustaining a global outreach elective and provide ideas and resources for overcoming common roadblocks. Imaging in Lung Cancer Abstract Purpose of Review To describe the current role of imaging in the detection, staging, therapy planning and response assessment in lung cancer. Recent Findings Lung cancer screening using low-dose CT has been shown to reduce mortality in risk groups of active or former smokers and has, thus, been recommended by several societies and organisations worldwide. There remain, however, questions regarding optimum definition of risk factors and screening intervals. Staging criteria for lung cancer have been updated in the 8th edition of the TNM staging to better reflect prognosis. Preliminary research in radiomics in lung cancer has provided data that may add to identification of early lung cancer, prediction of prognosis and therapy response. Targeted systemic therapy has recently had a significant impact in advanced lung cancer both in terms of efficacy and toxicity, but radiologists need to be aware that response assessment criteria differ from those used for classic chemotherapy, and new side effects that may occur. Summary Modern imaging, particulary exploiting radiomics will improve early detection, classification, staging, therapy planning and ultimately, hopefully, prognosis in lung cancer. PET Imaging of Hepatocellular Carcinoma Abstract Purpose of Review Positron emission tomography has not traditionally played a major role in the evaluation of hepatocellular carcinoma (HCC). Owing to high background liver uptake and molecular mechanisms within HCC lesions, uptake of 18F-fluorodeoxyglucose (FDG) is variable and prior studies have shown only modest overall detection of intrahepatic disease. Recent Findings Tracers such as 18F- and 11C-choline as well as 11C-acetate have been explored either in isolation or together with 18F-FDG have shown greater promise in detection of intrahepatic lesions, but yet are not in widespread clinical use. 68 Ga-Prostate specific membrane antigen is a tracer developed for use in prostate cancer but a pilot study and several case reports have indicated that there may be the potential for use in the evaluation of HCC. Summary Increased rates of lesion detection using 18F-FDG may be seen in poorly differentiated tumors and in the setting of metastatic disease or within recurrent tumor following loco-regional therapies and FDG uptake may indicate a greater risk of recurrence following transplantation. Further work will be required to elucidate the precise role of other non FDG tracers in the evaluation of patients at risk for or with HCC. Humanitarian Teleradiology Abstract Purpose of Review To outline the current state of humanitarian teleradiology: scope of projects, technical and organization challenges, and to outline how recent technological developments will change the face of humanitarian teleradiology and global health. Recent Findings Technical and information technology improvements in recent years have enabled small- and large-scale teleradiology projects in many regions, some quite remote, of low- and middle-income countries (LMICs). These are aimed at alleviating the severe shortage of radiologists in LMICs. Teleradiology offers an opportunity for radiologists in high-income countries (HICs) to volunteer and contribute on an ongoing basis without the commitment of time and effort required by volunteers in other forms of global health. Recent and anticipated improvements in internet availability, as well as the emergence of artificial intelligence (AI), will continue to change the face of teleradiology and radiology in LMICs. Summary Humanitarian teleradiology provides valuable benefits to patient care in LMICs, and the combination of AI and widespread access to high-speed internet will revolutionize the field within the next decade. Emerging Role of Fluciclovine and Other Next Generation PET Imaging Agents in Prostate Cancer Management Abstract Purpose of Review Prostate cancer recurrence after definitive therapy is not uncommon. Recurrent disease is first detected by the elevation of prostate specific antigen (PSA) and may often be radiographically occult. The use of molecular imaging for the localization and staging of recurrent prostate cancer is promising. 18F-Fluciclovine is a synthetic amino acid analog positron emission tomography (PET) tracer which has demonstrated great utility in the evaluation of patients with suspected recurrence disease. Other newer PET tracers such 68Ga/18F-PSMA-ligands are being investigated for prostate imaging with promising results. The purpose of this article is to review the emerging role of fluciclovine in clinical practice for patients with prostate cancer. Recent Findings Since the approval of fluciclovine by the Food and Drug Administration, the modality is widely used in the USA for patients with suspect disease recurrence. With the coming approval of newer generation of PET tracers, it is important to understand the unique mechanism of action and the diagnostic performance of fluciclovine PET/CT in prostate cancer imaging to allow better allocation of the radiotracers. Summary This review article provides a broad literature review of the current and the future potential role of fluciclovine PET/CT in prostate cancer imaging. Somatostatin Receptor Positron Emission Tomography: Beyond Gastroenteropancreatic Neuroendocrine Tumors Abstract Purpose of Review Similar to various gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), somatostatin receptors (SSTRs) are overexpressed in a wide array of malignant and benign conditions. Using somatostatin positron emission tomography (PET) analogs ([68Ga]DOTA-peptides) this overexpression of SSTRs can be exploited for clinical management in terms of diagnosis, therapy, and for peptide receptor radionuclide therapy (PRRT). Recent Findings Recent reports suggest that [68Ga]DOTA-peptide PET tracers have an emerging role in the management of wide array of non-GEP-NETs due to overexpression of SSTRs. The potential role of SSTR-PET imaging in the management of medullary thyroid cancer, paraganglioma, Merkel cell carcinoma, phosphaturic mesenchymal tumors, and inflammation will be discussed. The emerging role of theranostic and personalized medicine with PRRT using peptides labeled with yttrium-90 (90Y) or lutetium-177 (177Lu) beta emitters will also be discussed. Summary SSTR-PET imaging with [68Ga]DOTA-peptides has utility in malignant and benign conditions other than GEP-NETs. Combining SSTR-PET with other anatomic and functional imaging modalities has demonstrated superior diagnostic accuracy. The presence of SSTRs in these conditions opens up new possibilities in the management of these conditions in terms of imaging and therapeutics. Technology-Mediated Education in Global Radiology: Opportunities and Challenges Abstract Purpose of review This review explores opportunities and challenges in utilizing technology-mediated educational strategies for radiology education in parts of the world where attending radiologist support is limited. In efforts to increase the number of radiologists globally, radiology residencies have been established in regions where radiologists are scarce, several of which have partnerships with programs in other parts of the world. Technology-mediated educational strategies could leverage these partnerships to provide critical infrastructure to these recently established residencies. Recent findings The efficacies of strategies such as teleradiology and teleconferencing in global radiology have been evaluated, as have the effectiveness of technology-mediated educational tools in radiology. The topic of technology-mediated instruction for the newly established radiology residencies in other parts of the world has not yet been described or assessed, however. Summary Technology-mediated education has potential in the expanding realm of global radiology resident education, but there are some important constraints in the execution of these programs. Amino Acid PET Imaging of Glioma Abstract Purpose of Review Gliomas are among the most lethal malignancies in the world with dismal outcomes for high-grade tumors. These lesions are difficult to completely characterize with conventional magnetic resonance imaging and amino acid positron emission tomography is a rapidly progressing area of research with widespread clinical use. Recent Findings Amino acid positron emission tomography allows for more accurate glioma characterization compared to traditional imaging techniques including grading of disease, delineation of tumor spread, identification of recurrent disease, and prognosis. While the summarized radiotracers share some diagnostic properties, each also has its own weaknesses and strengths. Summary This article summarizes recent developments and clinical applications of the most widely used amino acid radiotracers. While none of these agents are FDA approved in the United States, they are considered standard of care in Europe and other parts of the world with > 10,000 studies being performed in some centers (Langen et al. in J Neurooncol 120(3):665–666, 2014). Molecular Imaging of Renal Malignancy: A Review Abstract Purpose of Review Renal cell carcinoma (RCC) is a common malignancy that is often detected incidentally in patients undergoing cross-sectional imaging of the abdomen for workup of pain or other symptoms. Due to overlap in imaging findings of RCC and benign tumors, biopsy may be necessary to confirm the diagnosis. Biopsies are occasionally non-diagnostic, however, and in small lesions or patients with comorbidities may not be technically feasible. Molecular imaging techniques can characterize tumors as being more likely malignant or benign and obviate the need for invasive testing, as well as providing accurate whole-body staging in patients with known RCC. Recent Findings PET/CT with 18F-FDG and other radionuclides can identify primary renal masses with higher malignant potential and also allows for sensitive detection of metastatic RCC. SPECT/CT imaging with 99mTc-sestamibi can provide useful information to support the diagnosis of benign oncocytic neoplasms over more aggressive RCC subtypes. Investigational molecular imaging techniques such as immunoPET and hyperpolarized 13C MRI have also shown promise in renal mass characterization. Summary This review article aims to outline the various molecular imaging modalities available in the evaluation of primary renal tumors and in whole-body staging of metastatic RCC. Thyroid Sonography: Nuclear Medicine Point of View Abstract Purpose of Review The American Cancer Society estimated that cancer of the thyroid causes 53,990 new cases and about 2060 deaths in 2018. The chance of being diagnosed with thyroid cancer has risen and this increment seems to be the result of increased use of ultrasound, CT and MR imaging examinations for reasons unrelated to the thyroid. Up to 50% of adults in central Europe have one or multiple thyroid nodules. However, the prevalence of latent carcinoma in an unselected autopsy study was 8.6%. The main diagnostic task is to differentiate between benign and malignant lesions, preferably based upon on ultrasound parameters or scoring systems like TI-RADS. Recent Findings Although there are no pathognomonic features for malignant thyroid nodules at ultrasonography or any other imaging modality, sonography of the thyroid gland has beyond doubt become the imaging method of choice for the last three decades, combined with FNA in suspicious cases. Summary Several technological improvements like ultrasound elastography, and a proliferating literature of different scoring systems allow the conclusion that ultrasound is an important gatekeeper for further diagnostic steps but not capable, so far, to identify autonomy or malignancy with a sufficiently high accuracy. Pediatric Drugs Current and Emerging Therapeutic Options for the Management of Rare Skeletal Diseases Abstract Increasing knowledge in the field of rare diseases has led to new therapeutic approaches in the last decade. Treatment strategies have been developed after elucidation of the underlying genetic alterations and pathophysiology of certain diseases (e.g., in osteogenesis imperfecta, achondroplasia, hypophosphatemic rickets, hypophosphatasia and fibrodysplasia ossificans progressiva). Most of the drugs developed are specifically designed agents interacting with the disease-specific cascade of enzymes and proteins involved. While some are approved (asfotase alfa, burosumab), others are currently being investigated in phase III trials (denosumab, vosoritide, palovarotene). To offer a multi-disciplinary therapeutic approach, it is recommended that patients with rare skeletal disorders are treated and monitored in highly specialized centers. This guarantees the greatest safety for the individual patient and offers the possibility of collecting data to further improve treatment strategies for these rare conditions. Additionally, new therapeutic options could be achieved through increased awareness, not only in the field of pediatrics but also in prenatal and obstetric specialties. Presenting new therapeutic options might influence families in their decision of whether or not to terminate a pregnancy with a child with a skeletal disease. Vancomycin Prescribing and Therapeutic Drug Monitoring in Children With and Without Acute Kidney Injury After Cardiac Arrest Abstract Background Acute kidney injury (AKI) commonly occurs after cardiac arrest. Those subsequently treated with vancomycin are at additional risk for drug-induced kidney injury. Objective We aimed to determine whether opportunities exist for improved drug monitoring after cardiac arrest. Methods This was a retrospective cohort study of children aged 30 days–17 years treated after cardiac arrest in an intensive care unit from January 2010 to September 2014 who received vancomycin within 24 h of arrest. Vancomycin dosing and monitoring were compared between those with and without AKI, with AKI defined as pRIFLE (pediatric risk, injury, failure, loss, end-stage renal disease) stage 2–3 AKI at day 5 using Schwartz formula-calculated estimated glomerular filtration rate (eGFR). Results Of 43 children, 16 (37%) had AKI at day 5. Age, arrest duration, median time to first vancomycin dose, and the number of doses before and time to first vancomycin concentration measurement were similar between groups. Children with AKI had higher initial vancomycin concentrations than those without AKI (median 16 vs. 7 mg/L; p = 0.003). A concentration was not measured before the second dose in 44% of children with AKI. Initial eGFR predicted day 5 AKI. In children with AKI, the initial eGFR was lower in those with than those without a concentration measurement before the second dose (29 mL/min/1.73 m2 [interquartile range (IQR) 23–47] vs. 52 [IQR 50–57]; p = 0.03) but well below normal in both. Conclusions In children with AKI after cardiac arrest, decreased vancomycin clearance was evident early, and early monitoring was not performed universally in those with low initial eGFR. Earlier vancomycin therapeutic drug monitoring is indicated in this high-risk population. Medical Options for the Adjuvant Treatment and Management of Pediatric Melanoma Abstract Although melanoma is a rare diagnosis in the pediatric population, advances in the management of adults with melanoma offer the prospect of promising therapeutic options for children. At this time, medical management is not considered curative but may reduce the risk of recurrence or prolong survival. Surgical management remains the mainstay of treatment. Medical therapy of pediatric melanoma is not thought to have a role for in situ, early-stage, or localized disease, but adjuvant therapy may have a role in improving the prognosis of patients with positive sentinel lymph node biopsy (SLNB), spread beyond the regional lymph node basin, metastatic disease, or recurrent disease. Medical treatment options include immunotherapies, particularly checkpoint inhibitors, and targeted therapies, which have provided improved toxicity profiles compared with traditional chemotherapy regimens in the setting of advanced disease. There is a growing body of pediatric-specific data relevant to the use of adjuvant therapies for advanced melanoma in children. Efficacy and Safety of Oral Paracetamol vs. Oral Ibuprofen in the Treatment of Symptomatic Patent Ductus Arteriosus in Premature Infants Abstract Background The ductus arteriosus (DA) is situated between the aortic arch and the pulmonary artery in fetal circulation, and its closure is one of the most important changes required for the transition to extrauterine life. Prolonged duration of patent DA (PDA) impairs hemodynamics and contributes both to morbidity associated with prematurity and to mortality. Therefore, when best to initiate treatment and what drug to use as first-line treatment to close the ductus is important. Objective The aim of this study was to compare the efficacy and side effects of the oral forms of ibuprofen and paracetamol and to contribute to the literature investigating the first drug to be selected in the medical treatment of PDA. Methods This observational, retrospective cohort study was conducted in infants born at ≤ 28 weeks' gestation and admitted to our Neonatal Intensive Care Unit (Manisa Merkezefendi State Hospital, Manisa, Turkey) between February 2015 and April 2018. Included infants were born at ≤ 28 weeks' gestation, had PDA-related clinical findings and hemodynamically significant PDA on echocardiography, and received oral ibuprofen or oral paracetamol therapy as the closure treatment. Results The most common clinical findings for the diagnosis of PDA were hyperdynamic circulation, tachycardia, and increased oxygen requirement. In total, 43 of the 51 (84.3%) premature infants in the ibuprofen group and 32 of the 36 (88.8%) in the paracetamol group achieved PDA closure after the first treatment cycle. There was no statistically significant difference between the two groups in terms of respiratory morbidity, renal and liver function, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, length of hospital stay, and mortality. Conclusions Our results indicate that oral paracetamol was as effective as oral ibuprofen in the medical treatment of PDA. In addition, both drugs were considered well-tolerated in terms of effects on kidney, liver, and intestinal functions. Our results demonstrate that oral paracetamol can be used effectively and safely as the first-line treatment of PDA. Neuropathic Pain in Pediatric Oncology: A Clinical Decision Algorithm Abstract Neuropathic pain in pediatric oncology can be caused by distinct lesions or disease processes affecting the somatosensory system, including chemotherapy-related neuronal injury, solid tumor-related involvement of neural structures, post-surgical neuropathic pain—including phantom limb pain and pain after limb-sparing surgery—and the complex circumstances of neuropathic pain at the end of life. Treatment algorithms reflect the general treatment principles applied for adult neuropathic pain, but the dose regimens applied in children are modest and rarely escalated to the maximum doses to optimize analgesic efficacy. Pharmacological management of neuropathic pain should be based on a stepwise intervention strategy, as combinations of medications are the most effective approach. Gabapentinoids and tricyclic antidepressants are recommended as first-line therapy. Methadone, ketamine, and lidocaine may be useful adjuvants in selected patients. Prospective studies extended over a substantial length of time are recommended because of the nature of neuropathic pain as persistent, chronic pain and based on the need for sufficient time to escalate medication dose regimens to full analgesic efficacy. Childhood-Onset Takayasu Arteritis (c-TA): Current and Future Drug Therapy Abstract Childhood-onset Takayasu arteritis (c-TA) is the third most common systemic vasculitic disorder in children. Vascular stenosis is the main complication, and aneurysms are reported in 19–65% of cases, often in combination with stenotic lesions. Management of patients with c-TA is largely based on studies involving predominantly patients with adult-onset TA (a-TA). More widely used criteria for patients with c-TA have been devised by the joint European League Against Rheumatism, Pediatric Rheumatology International Trials Organization, and Pediatric Rheumatology European Society. Of the available imaging modalities, those that do not use radiation (color Doppler ultrasound and magnetic resonance angiogram) are preferred over 18F-labeled fluoro-2-deoxyglucose (18F-FDG) positron-emission tomography, computed tomography (CT), and CT angiogram in children. Remission rates have been reported to be lower in c-TA than in a-TA, and published mortality rates in c-TA range from 16 to 40%, which is much higher than reported in patients with a-TA. The usual drug therapy options include steroids plus steroid-sparing second-line immunosuppressants, such as mycophenolate, azathioprine, methotrexate, cyclophosphamide, and cyclosporine, along with antiplatelet agents. Interleukin-6 inhibitors such as tocilizumab, as well as the tumor necrosis factor inhibitors, are other aggressive therapeutic options. As yet, no randomized controlled trials have been conducted in c-TA. Pharmacotherapeutic Management of Wilms Tumor: An Update Abstract Although differences exist in treatment and risk-stratification strategies for children with Wilms tumor (WT) between the European [International Society of Paediatric Oncology (SIOP)] and American [Children's Oncology Group (COG)] study groups, outcomes are very similar, with an overall survival of > 85%. Future strategies aim to de-intensify treatment and reduce toxicity for children with a low risk of relapse and intensify treatment for children with high-risk disease. For metastatic WT, response of lung nodules to chemotherapy is used as a marker to modify treatment intensity. For recurrent WT, a unified approach based on the use of agents that were not used for primary therapy is being introduced. Irinotecan is being explored as a new strategy in both metastatic and relapsed WT. Introduction of biology-driven approaches to risk stratification and new drug treatments has been slower in WT than in some other childhood cancers. While several new biological pathways have been identified recently in WT, their individual rarity has hampered their translation into clinical utility. Identification of robust prognostic factors requires extensive international collaborative studies because of the low proportion who relapse or die. Molecular profiling studies are in progress that should ultimately improve both risk classification and signposting to more targeted therapies for the small group for whom current therapies fail. Accrual of patients with WT to early-phase trials has been low, and the efficacy of these new agents has so far been very disappointing. Better in vitro model systems to test mechanistic dependence are needed so available new agents can be more rationally prioritized for recruitment of children with WT to early-phase trials. Pancreatic Enzyme Supplementation in Patients with Atopic Dermatitis and Food Allergies: An Open-Label Pilot Study Abstract Background Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects both patients and their families. Current therapies often alleviate symptoms but do not prevent or eradicate the disease. Objectives Our objective was to determine whether pancreatic enzyme supplementation is an effective and safe treatment in refractory pediatric AD associated with food allergies. Methods We conducted an open-label pilot study using a case–control design. Patients with severe AD and known food allergies refractory to conventional therapies and exclusion diets were recruited and treated for 6 weeks with oral supplementation of pancreatic enzymes. The primary endpoint was the severity of AD, using the Scoring Atopic Dermatitis (SCORAD) index. Secondary measures included markers of intestinal permeability (urinary sucrose and lactulose/mannitol excretion). Results A total of 11 patients met all eligibility criteria and completed the trial. Significant improvement in AD was observed after 6 weeks of pancreatic enzyme supplementation (SCORAD index 52.3 ± 5.5 vs. 34.6 ± 7.6; p = 0.0008). Beneficial effect was observed in 9 of 11 patients, without adverse events. Fractional urinary sucrose excretion improved to a level comparable to that of age-matched controls (p < 0.05). However, urinary lactulose:mannitol ratios remained abnormally high compared with those of controls (p = 0.01). Conclusions Pancreatic enzyme supplementation was associated with improved AD and gastroduodenal permeability. Additional randomized placebo-controlled studies are required before this treatment can be recommended in this clinical setting. Serious Adverse Events Associated with Off-Label Use of Azithromycin or Fentanyl in Children in Intensive Care Units: A Retrospective Chart Review Abstract Objectives Half of prescription drugs commonly given to children lack product labeling on pediatric safety, efficacy, and dosing. Two drugs most widely used off-label in pediatrics are azithromycin and fentanyl. We sought to determine the risk of serious adverse events (SAEs) when oral azithromycin or intravenous/intramuscular fentanyl are used off-label compared to on-label in pediatric intensive care units (ICUs). Study Design Six pediatric hospitals participated in a retrospective chart review of patients administered oral azithromycin (n = 241) or intravenous/intramuscular fentanyl (n = 367) between January 5, 2013 and December 26, 2014. Outcomes were SAEs by drug and labeling status: off-label compared to on-label by Food and Drug Administration (FDA)-approved age and/or indication. Statistical analysis was performed using logistic regression to estimate odds ratios (ORs) and Cox regression to estimate hazard ratios (HRs). Results Twenty-one (9%) children receiving azithromycin experienced SAEs. Off-label use of azithromycin was not associated with a higher risk of SAE (OR 0.87, 95% CI 0.27–2.71, p = 0.81). Ninety-five (26%) children receiving fentanyl experienced SAEs. Fentanyl off-label use by both age and indication was not associated with a higher risk of overall SAEs compared to on-label use (OR 1.99, 95% CI 0.94–4.19, p = 0.07). However, the risk of the SAE respiratory depression was significantly greater when fentanyl was used off-label by both age and indication (OR 5.05, 95% CI 1.08–23.56, p = 0.044). Results based on HRs were similar. Conclusions Azithromycin off-label use in pediatric ICUs does not appear to be associated with an increased risk of SAEs. Off-label use of fentanyl appears to be more frequently associated with respiratory depression when used off-label by both age and indication in pediatric ICUs. Prospective studies should be undertaken to assess the safety and efficacy of fentanyl in the pediatric population so that data can be added to the FDA labeling. Clinical Features and Treatment of Down Syndrome Arthropathy: Experience from Two US Tertiary Hospitals Abstract Background Arthropathy of Down syndrome (DA) is largely under-recognized, with an average 2-year delay in diagnosis. Most patients present with polyarthritis, and treatment has historically been challenging. Objectives Our objective was to investigate the clinical features and treatment of DA in the largest cohort reported to date. Methods In a retrospective chart review at two tertiary care hospitals, International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) codes for Down syndrome (DS) and juvenile idiopathic arthritis (JIA), between 1 January 1995 and 31 December 2015, were identified and charts reviewed. Results In total, 43 patients were identified, with an average (± standard deviation [SD]) follow-up period of 6 ± 4.4 years. The average age of symptom onset was 7.4 ± 3.9 years, with a mean delay of 19 ± 17 months from symptom onset to diagnosis. At diagnosis, 77% of patients had morning stiffness and 72% had abnormal laboratory values; there was an average of 15 ± 13 active joints (range 1–56). Treatment approaches varied, and there was a significant decrease in joints with active arthritis (p < 0.001), with 25% and 39% having at least one change in disease-modifying antirheumatic drug (DMARD) and biologic therapy, respectively. DMARD therapy was discontinued in 60% because of side effects, and 39% had inadequate response to first-line biologic therapy. Conclusions DA remains under-recognized, with delays in diagnosis and extensive musculoskeletal symptoms at presentation. While DA can improve with current therapy for JIA (corticosteroids, DMARDs, biologics), barriers include medication toxicity, intolerance, and ineffectiveness. Earlier diagnosis through improved screening and more targeted treatment may allow for earlier disease control and better outcomes. The Patient - Patient-Centered Outcomes Research Patient Perspectives on the Value of Patient Preference Information in Regulatory Decision Making: A Qualitative Study in Swedish Patients with Rheumatoid Arthritis Abstract Background There is increasing interest in involving patient preferences for benefits and risks in regulatory decision making. Therefore, it is essential to identify patient perspectives regarding the value of patient preference information (PPI). Objectives The aim of this study was to explore how patients with rheumatoid arthritis (RA) value the use of PPI in regulatory decision making regarding medical products. Methods Regulators and patients with RA were interviewed to gather initial insights into opinions on the use of PPI in regulatory decisions regarding medical products. The interviews were used to draft and validate the interview guide for focus groups with patients with RA. Participants were purposively sampled in collaboration with the Swedish Rheumatism Association in Stockholm and Uppsala. Each focus group consisted of three to six patients (18 in total). All interviews were audio-recorded, transcribed verbatim, and analysed using content analysis. Results According to the participants, PPI could lead to regulators considering patients' needs, lifestyles and well-being when making decisions. PPI was important in all stages of the medical product lifecycle. Participants reported that, when participating in a preference study, it is important to be well-informed about the use of the study and the development, components, administration, and risks related to the medical products. Conclusions Patients thought PPI could be valuable to consider in regulatory decisions. It is essential for patients to be well-informed when asked for their preferences. Research on information materials to inform patients in preference studies is needed to increase the value of PPI in regulatory decision making. High Proportion of Subjective Component to the Disease Activity Score is Associated with Favorable Response to Abatacept in Rheumatoid Arthritis Abstract Background Response prediction of certain biologic agents for the treatment of rheumatoid arthritis (RA) remains an unmet need in real-world clinical practice. The contribution of patient-reported components to the 28-joint Disease Activity Score (DAS28) was termed DAS28-P and investigated as a predictor of response to biologic agents, mostly tumor necrosis factor inhibitors. We aimed to evaluate DAS28-P as a predictor of the European League Against Rheumatism (EULAR) response to abatacept in patients with RA. Methods The study population was a prospective, observational, multicenter cohort of Korean patients with RA, who were followed up for a nationwide post-marketing surveillance study of abatacept. Correlation of DAS28-P with DAS28, change of DAS28, and EULAR response groups were evaluated. Logistic regression analysis was used to predict good-to-moderate EULAR response to abatacept in the study population. Results A total of 341 patients were involved in the analysis stratified on the EULAR response criteria. Presence of comorbidities, previous exposure to biologic agents, baseline DAS28, three of its components (tender joint counts, global health visual analog scale, erythrocyte sedimentation rate), and baseline DAS28-P were significantly associated with EULAR response to abatacept at 6 months. Stratified upon EULAR response, a group with good-to-moderate response had a higher baseline value and lower interval change for DAS28-P. Logistic regression analysis showed that a DAS28-P cut-off of > 0.44 was more positively associated with good-to-moderate EULAR response with abatacept treatment than naivety to biologic agents. Conclusions The DAS28-P could be predictive of response to abatacept. A higher baseline DAS28-P is associated with a favorable therapeutic response to abatacept. Trial registration Trial name, Korean Post-marketing Surveillance for Orencia®. Trial registration number, NCT01583244. Registered on April 20, 2012. Healthcare Experience and their Relationship with Demographic, Disease and Healthcare-Related Variables: A Cross-Sectional Survey of Patients with Chronic Diseases Using the IEXPAC Scale Abstract Background Patient experience is acknowledged as a principal aspect of quality healthcare delivery, and it has implications with regard to outcomes. Objectives Our objective was to evaluate the healthcare experience of patients with chronic diseases to identify patient-perceived healthcare gaps and to assess the influence of demographic and healthcare-related variables on patient experiences. Methods A cross-sectional survey was delivered to adult patients with chronic diseases: diabetes mellitus (DM), human immunodeficiency virus (HIV) infection, inflammatory bowel disease (IBD) or rheumatic diseases. Patient experiences were assessed with the Instrument for Evaluation of the Experience of Chronic Patients (IEXPAC) questionnaire, with possible scores ranging from 0 (worst) to 10 (best experience). Results Of the 2474 patients handed the survey, 1618 returned it (response rate 65.4%). Patients identified gaps in healthcare related mainly to access to reliable information and services, interaction with other patients and continuity of healthcare after hospital discharge. The mean ± standard deviation (SD) IEXPAC score was 6.0 ± 1.9 and was higher for patients with HIV (6.6 ± 1.7) than for those with rheumatic disease (5.5 ± 2.0), IBD (5.9 ± 2.0) or DM (5.9 ± 1.9) (p < 0.001). In multivariate models, better overall IEXPAC experience was associated with follow-up by the same physician, follow-up by a nurse, receiving healthcare support from others and treatment with subcutaneous or intravenous drugs. The multivariate model that confirmed patients with HIV or DM had better experience than did those with rheumatic diseases. Conclusions Through IEXPAC, patients identified aspects for healthcare quality improvements and circumstances associated with better experience, which may permit greater redirection of healthcare toward patient-centered goals while facilitating improvements in social care and long-term healthcare quality. Elicitation of Health-Related Utility in Perianal Fistula in Crohn's Disease Abstract Background and Objective Perianal fistulae are a common complication of Crohn's disease (CD) and pose a substantial burden on quality of life. Data capturing health-related utility associated with perianal fistulae in CD are scarce. The current study aims to value health states related to different stages of the disease to quantitatively evaluate the impact of complex perianal fistulae on CD patients' quality of life. Methods Eight health state descriptions associated with complex perianal fistulae in CD were developed following qualitative research with patients and validation by clinicians. Following pre-testing, a survey was administered online in two samples of UK respondents: the general population and patients with CD. A choice-based valuation technique, the time trade-off (TTO), was used for direct utility measurement. CD patients also valued their current health state using the TTO. Exclusion criteria for respondents displaying logical inconsistencies were applied. Results Usable responses were received from 835 respondents, reflective of the UK population in age and sex, in the general population survey and 162 CD patients in the patient survey. Non-remission states were valued much lower than the remission state by both samples, ranging from 0.20 for proctectomy with a negative outcome to 0.66 for chronic symptomatic fistulae with mild symptoms. Patients currently experiencing fistulae reported lower values for current health than those without fistulae. Conclusion Low utility values were assigned to the non-remission health states for perianal fistulae in CD by the general public and patients with CD. This demonstrates the high humanistic burden of inadequately managed perianal fistula in CD. Creation of a Decision Support Tool for Expectant Parents Facing Threatened Periviable Delivery: Application of a User-Centered Design Approach Abstract Background Shared decision-making (SDM) is optimal in the context of periviable delivery, where the decision to pursue life-support measures or palliation is both preference sensitive and value laden. We sought to develop a decision support tool (DST) prototype to facilitate SDM by utilizing a user-centered design research approach. Methods We convened four patient and provider advisory boards with women and their partners who had experienced a surviving or non-surviving periviable delivery, pregnant women who had not experienced a prior preterm birth, and obstetric providers. Each 2-h session involved design research activities to generate ideas and facilitate sharing of values, goals, and attitudes. Participant feedback shaped the design of three prototypes (a tablet application, family story videos, and a virtual reality experience) to be tested in a final session. Results Ninety-five individuals (48 mothers/partners; 47 providers) from two hospitals participated. Most participants agreed that the prototypes should include factual, unbiased outcomes and probabilities. Mothers and support partners also desired comprehensive explanations of delivery and care options, while providers wanted a tool to ease communication, help elicit values, and share patient experiences. Participants ultimately favored the tablet application and suggested that it include family testimonial videos. Conclusion Our results suggest that a DST that combines unbiased information and understandable outcomes with family testimonials would be meaningful for periviable SDM. User-centered design was found to be a useful method for creating a DST prototype that may lead to improved effectiveness, usability, uptake, and dissemination in the future, by leveraging the expertise of a wide range of stakeholders. A Guide to Measuring and Interpreting Attribute Importance Abstract Stated-preference (SP) methods, such as discrete-choice experiments (DCE) and best–worst scaling (BWS), have increasingly been used to measure preferences for attributes of medical interventions. Preference information is commonly characterized using attribute importance. However, attribute importance measures  can vary in value and interpretation depending on the method used to elicit preferences, the specific context of the questions, and the approach used to normalize attribute effects. This variation complicates the interpretation of preference results and the comparability of results across subgroups in a sample. This article highlights the potential consequences of ignoring variations in attribute importance measures, and makes the case for reporting more clearly how these measures are obtained and calculated. Transparency in the calculations can clarify what conclusions are supported by the results, and help make more accurate and meaningful comparisons across subsamples. Issues in the Design of Discrete Choice Experiments The Value of Treatment Processes in Germany: A Discrete Choice Experiment on Patient Preferences in Complementary and Conventional Medicine Abstract Background The effects of health interventions are often complex, and it is argued that they comprise more than pure changes in clinical parameters. Aspects of the treatment process, so-called 'benefits beyond health', are often overlooked in the evaluation of health interventions but can be of value to the patients. Objectives The aim of this study was to assess patients' preferences and willingness to pay regarding the treatment process and its attributes in patients using acupuncture, homeopathy or general medicine (GM). Methods A systematic literature search, six semi-structured interviews and a stakeholder involvement were conducted to determine the attributes of the treatment process. Five process attributes and one cost attribute were used to construct the experimental design of the discrete choice experiment (DCE) (6 × 3), a cross sectional survey method. Patients were recruited by outpatient physicians practicing in Berlin and Munich, Germany. Process attributes were effects-coded. Data were analyzed in a conditional logit regression. Results Data from 263 patients were analyzed. DCE results showed that the treatment process attributes 'active listening' and 'time' were most relevant to all patients. Preferences for the attributes 'holistic treatment' (more relevant to the acupuncture and homeopathy groups) and 'information' (more relevant to the GM group) seemed to differ slightly between the groups. Willingness-to-pay values were higher in the acupuncture and homeopathy groups. Conclusions The time physicians take and the extent to which they listen attentively are most important and are equally important to all patients. These results may contribute to the debate about more patient-centered healthcare. They support a strengthening of medical consultations in the German healthcare system. We suggest giving physicians the opportunity to spend more time with their patients, which may be achieved by changing the general conditions of remuneration (e.g., improved reimbursement of medical consultations). German Clinical Trial Register DRKS00013160. Systematic Review of Public Preferences for the Allocation of Donor Organs for Transplantation: Principles of Distributive Justice Abstract Background Solid organ transplantation is the treatment of choice for organ failure, but donor organs are a scarce resource because of a large mismatch between supply and demand. This scarcity leads to an ethical dilemma, forcing priority setting in organ allocation to individual patients. Little is known about public preferences regarding priority setting in organ allocation. A systematic review was performed to review the existing evidence and provide an overview of the criteria and criterion levels in regard to ethical aspects of distributive justice. Methods The PubMed, Web of Science, EBSCO and PsycINFO databases were searched for literature published between January 2000 and December 2018. Only original studies were selected. The criteria were identified, extracted and grouped into a self-developed matrix according to the principles of distributive justice to ascertain public preferences. Results Overall, 9645 references were identified, and 15 studies were included. In total, 27 criteria clustered in seven theory-guided groups could be identified: "equality", "effectiveness/benefit", "medical urgency", "own fault", "value for society", "medical background" and "sociodemographic status". It was shown that not only a single principle but rather a combination of principles are relevant for the allocation. Therefore, a public propensity towards a rational utilitarian ethical model of allocation could be recognised. Conclusions The general public not only wanted to allocate organs mainly to those with a good probability of having a successful transplantation but also wanted to consider those who need an organ most urgently to prevent fatal consequences, resulting in unclear trade-offs between effectiveness/benefit and medical urgency. Public preferences for organ allocation are therefore complex, and data regarding clear trade-offs are still lacking. Multi-Method Patient-Engagement Approach: A Case Example from a PCORI-Funded Training Project Pediatric Surgery Immature gastric teratoma in a newborn Publication date: August 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 47 Author(s): Sandheeah Ramdeny, Katherine Broad, Prabhu Sekaran, Sara Harrison, Philip Connor, Mallinath Chakraborty Abstract We present a full-term male infant with a palpable abdominal mass who presented with severe haematemesis associated with cardiovascular compromise. Although an initial ultrasound imaging identified a left supra-renal calcified mass suggesting a neuroblastoma, further imaging suggested an atypical mass which was separate from the spleen and left kidney. An upper gastro-intestinal contrast study localised the mass to the stomach and a computed tomograph suggested the possibility of a gastric teratoma likely in combination with a raised serum Alpha-fetoprotein. The mass was completely surgically resected, and histology confirmed an immature gastric teratoma.We would like to draw the attention of clinicians of the possibility of a gastric teratoma in an infant who presents with an abdominal mass and haematemesis. Splenic abscess with salmonella enteritidis following marsupialization of a splenic cyst Publication date: August 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 47 Author(s): Yolla Youssef, Lena Naffaa, Sarah Chamseddine, Ahmad Zaghal, Mohammad Khalife, Nadine Yazbeck, Ghassan Dbaibo, Rima Hanna-Wakim Abstract Splenic abscess in the setting of salmonella infection is a rare entity, which has been reported during the course of typhoid fever. We describe the presentation of a healthy 11 year-old boy who had abdominal pain, incidental finding of splenic cyst and who developed Salmonella enteritidis gastroenteritis and splenic abscess shortly following laparoscopic removal of the splenic cyst. We review 11 additional cases of nontyphoidal salmonellae splenic abscesses in pediatric patients. Small intestinal obstruction by sunflower seed bezoar Publication date: July 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 46 Author(s): Tatiana de Warren, Melanie B. LaPlant, Daniel A. Saltzman, Donavon J. Hess Abstract Bezoars are rare mass formations in the gastrointestinal tract caused by consumption of indigestible materials such as plant fibers (Phytobezoars) or hair (Trichobezoars). We report a case of a 12-year-old boy who presented with abdominal pain, nausea and vomiting without any other clinical findings. Radiographic findings showed an area of obstruction in the small bowel, which we confirmed by performing an exploratory laparotomy. The treatment consisted of surgical removal of the obstructing bezoar from the distant ileum as well as excision of an incidentally identified Meckel's diverticulum. Postoperative discussions revealed, that the patient had ingested a large amount of unshelled sunflower seeds, which had caused a mass formation and obstruction of his small bowel. The patient did not suffer any complications during or after surgery and experienced a rapid recovery. Bezoars should be considered among adolescents presenting with intestinal obstruction, especially among baseball players. Spontaneous perinatal gallbladder perforation Publication date: July 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 46 Author(s): Iran Tavakoli, David Bigam, Consolato Sergi, Bryan Dicken Using silver poly (acrylate) matrix (Haemoblock) in children with lymphatic malformations Publication date: July 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 46 Author(s): D.A. Safin, D.V. Romanov Abstract Lymphatic malformations (LM) are a congenital malformation of lymphatic vessels. There exist large, small and mixed cystic LMs. Up to the present day, the causes of LM remain the subject of scientific research. Special sclerosing agents such as Doxycycline, Bleocyne, Picibanil (OK-432) and other drugs are used for sclerosing of LM. Due to the special characteristics of the impact of each drug on the endothelium, during the early post-surgical period there occur various undesirable effects (swelling, pain conditions, toxic effects, allergies, etc.), moreover, the effectiveness of the used sclerosing agents is not always sufficient to obtain a good clinical effect. The goal of our work is to evaluate the use of the Haemoblock™ sclerotherapy in children with various forms of lymphatic malformations. We carried out a retrospective analysis of the use of the silver poly (acrylate) matrix (Haemoblock™) for sclerotherapy (off-label protocol) of various forms of LM in children who underwent treatment at the Center for Vascular Pathology (Moscow) during the period from 2016 to 2018. After the conducted surgery - sclerotherapy with the Haemoblock™ in children with various LMs, we obtained the following results: excellent and good - in 6 cases, satisfactory - in 2 cases, no negative result was obtained. In the Center for Vascular Pathology (Moscow) in 2016–2018, there was conducted a treatment of 8 children with LM of various types and localization. During the early post-surgical stages (1–3 h after surgery), 4 children showed severe pain syndrome, which stopped on its own without prescription of drug-induced pain killers. 12–24 h after sclerotherapy, 6 children also showed an increase in swelling in the area of the surgery. The swelling persisted for 3–6 days, and stopped on its own. Considering the positive results of treatment, further multi center study of the use of the Haemoblock™ is needed for the purpose of the LM sclerotherapy in children. Malignant sacro-coccygeal teratoma with growing teratoma syndrome Publication date: July 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 46 Author(s): Tamador Al-Shamaileh, Fatena Ajlouni, Rasha Deebajah, Iyad Sultan, Mohammad M. Saleem, Khalil Ghandour Abstract A 13-month-old female with sacro-coccygeal tumor type II by Altman, was proven by biopsy to be a malignant germ cell tumor. Serum tumor markers were normal. During neo-adjuvant chemotherapy visible tumor progression was confirmed radiologically and progressed despite changing chemotherapy. The external growing mass forced its way out of the skin. More importantly, CT showed resolution of the pelvic component. Complete tumor resection with coccygectomy was performed. Histopathology showed mature teratoma, immature cells in the coccyx and no malignant germ cells. Three months after ending her therapy she remains in remission. We report the first case of growing teratoma syndrome (GTS) in the coccygeal region. Hybrid open and endovascular repair of a blunt traumatic thoracic aortic injury in a 7 year old boy Publication date: July 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 46 Author(s): Jennifer M. Brewer, Sarah Grout, Mohiuddin Cheema, Thomas Divinagracia, Carissa Webster-Lake, Douglas Moote, Nahum I. Kryzman, Edward Cortland, Brendan T. Campbell Abstract We describe a 7-year-old boy who sustained a blunt thoracic aortic injury following a rollover motor vehicle crash where the vehicle fell 200 feet down an embankment. The chest x-ray on arrival showed widening of the superior mediastinum, a left-sided hemothorax, and first rib fracture. The screening CTA of the chest revealed bilateral pulmonary contusions, a large left hemothorax, and evidence of aortic injury with active contrast extravasation. The patient was intubated due to respiratory distress and had a left chest tube placed. The patient became hypotensive with greater than 1.5 L of blood from the chest tube, so a resuscitative thoracotomy was performed. Bleeding was controlled with a sponge stick initially and definitively with a Satinsky vascular clamp. Next the patient was transported to the hybrid OR at the adjacent adult hospital with an open chest for endovascular graft placement. The patient was admitted to the PICU post-operatively, transferred to the floor on POD 4, and discharged home on POD 9. Aortic injury after blunt trauma in pre-adolescent children is uncommon and often fatal. Endovascular repair of traumatic thoracic aortic injury in adults is currently the standard of care, but there is a paucity of clinical data to guide management of these types of injuries in pediatric patients. Melanotic neuroectodermal tumor of infancy Publication date: July 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 46 Author(s): Hao Tran Kiem, Kim Hoa Nguyen Thi, Phu Tran Xuan, Loi Nguyen Hong, Son Nguyen Huu, Duy Phan Canh, Carlos Rodriguez Galindo, McKay McKinnon Abstract Introduction Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, rapidly growing pigmented neoplasm of neural crest origin generally arising in infants during the first year of life. Case We report a 15-month old male who presented with a 2-month history of a rapidly growing mass in the anterior. A biopsy showed melanotic neuroectodermal tumor, and complete resection with negative margins was subsequently achieved. The patient is in remission at 11 months from surgery. Conclusion Due to its rapid growth potential and locally destructive behaviour, early diagnosis is extremely important to limit local expansion. The treatment of choice for melanotic neuroectodermal tumor of infancy (MNTI) is surgical excision. Ureteral injury following vertebral body tethering for adolescent idiopathic scoliosis Publication date: July 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 46 Author(s): JuliAnne R. Rathbun, Daniel S. Hoernschemeyer, Mark R. Wakefield, Elizabeth A. Malm-Buatsi, Katie S. Murray, Venkataraman Ramachandran Abstract Adolescent idiopathic scoliosis (AIS) is a deformity of the spine of unknown etiology and no definitive cure. A novel technique for correction during growth known as vertebral body tethering (VBT) was introduced in 2005 in animal models, and then quickly adapted for human implementation [Courvoisier, 2015]. This method is in the early stages of growth and adaptation as well as evaluating risks to improve safety and feasibility. Some of the most common complications reported are atelectasis [Newton, 2018], proximal junctional kyphosis and reoperation for device breakage or addition [Hardesty, 2017]. There are no case reports describing ureteral injury following VBT. We present a case of primary ureteral injury following VBT with subsequent erosion and stricture formation requiring definitive ureteral reconstruction. We discuss the possible causes of this complication, its management, follow up, and short-term outcome. Re-do Kasai procedure in a preterm infant Publication date: July 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 46 Author(s): Hiromu Tanaka, Hideyuki Sasaki, Masatoshi Hashimoto, Masaki Nio Abstract We report the case of a 10-day old boy with biliary atresia (BA) who was delivered by caesarean section at 33 weeks 4 days of gestation (birth weight, 2135 g). At birth, his direct bilirubin level was high, and stools were light yellow. Abdominal ultrasonography showed no triangular cord sign, and duodenal fluid examination showed no bile. We performed a Kasai procedure (KP) 27 days after birth. His liver biopsy showed intrahepatic bile duct reduction. No bile excretion occurred postoperatively. We performed a redo KP 83 days after birth. Postoperative bile excretion was good, and his jaundice promptly resolved. The patient's liver biopsy showed bile duct development. Jaundice recurred at 8 months of age, and brain-dead-donor liver transplantation was required. The patient died of liver failure at 23 months of age. Surgery for BA during the neonatal period is usually effective, and the results of re-operation in cases with poor postoperative biliary excretion are poor. Here, we present a novel case that illustrates the progression and timing of the pathological hepatic changes in BA and consider the indications for and timing of re-operation in preterm infants. Magnetic Resonance Materials in Physics, Biology and Medicine Projection-based respiratory-resolved left ventricular volume measurements in patients using free-breathing double golden-angle 3D radial acquisition Abstract Objective To refine a new technique to measure respiratory-resolved left ventricular end-diastolic volume (LVEDV) in mid-inspiration and mid-expiration using a respiratory self-gating technique and demonstrate clinical feasibility in patients. Materials and methods Ten consecutive patients were imaged at 1.5 T during 10 min of free breathing using a 3D golden-angle radial trajectory. Two respiratory self-gating signals were extracted and compared: from the k-space center of all acquired spokes, and from a superior–inferior projection spoke repeated every 64 ms. Data were binned into end-diastole and two respiratory phases of 15% respiratory cycle duration in mid-inspiration and mid-expiration. LVED volume and septal–lateral diameter were measured from manual segmentation of the endocardial border. Results Respiratory-induced variation in LVED size expressed as mid-inspiration relative to mid-expiration was, for volume, 1 ± 8% with k-space-based self-gating and 8 ± 2% with projection-based self-gating (P = 0.04), and for septal–lateral diameter, 2 ± 2% with k-space-based self-gating and 10 ± 1% with projection-based self-gating (P = 0.002). Discussion Measuring respiratory variation in LVED size was possible in clinical patients with projection-based respiratory self-gating, and the measured respiratory variation was consistent with previous studies on healthy volunteers. Projection-based self-gating detected a higher variation in LVED volume and diameter during respiration, compared to k-space-based self-gating. Realization of 19 F MRI oximetry method using perfluorodecalin Abstract Objective To identify the technical aspects of the potential use of clinically approved perfluorodecalin (PFD, C10F18) for 19F magnetic resonance imaging (MRI) oximetry method at high magnetic field 7.05 T. Materials and methods 19F T1 measurements were made on a set of PFD samples with different oxygen contents (0%, 21%, and 100%) at room (21 °C) and body temperature (37 °C). In vivo MRI studies were carried out on one healthy rat and two rats with C6 brain glioma. Results The selective excitation of the magnetically equivalent 19F nuclei of CF2 groups of trans-isomer of PFD, which give a doublet at a frequency of about − 140 ppm (in relation the chemical shift of trifluoroacetic acid, which is − 76.55 ppm) should be done for correct implementation of 19F MRI oximetry method. The amount of PFD equal to 30 μl is the optimal for obtaining reliable data on the measured T1 values. In this case, the standard deviation of T1 does not exceed 5%. In vivo MRI studies showed that the values of the partial pressure of oxygen (pO2) decrease from normal values of about 38 mmHg (healthy brain) to almost 0 mmHg at the last stage of tumor growth. Conclusion The study showed the feasibility of the successful application of PFD for 19F MRI oximetry method. Precision of T1-relaxation time measurements in the hepatic portal vein: influence of measurement technique and sequence parameters Abstract Objective To investigate the effects of a range of parameter settings on T1 measurement stability in the portal vein using the T1-mapping sequences Look-Locker (LL) and Modified Look-Locker inversion recovery (MOLLI). Materials and methods Ten different versions of LL and MOLLI sequences were tested and compared to a reference sequence provided by the MR manufacturer. Ten healthy volunteers were imaged multiple times on two separate scan days at 3T. The mean T1 values and coefficient of variation (CoV) were calculated for each of the ten sequences and compared to the reference sequence. Results Six of the tested sequences had T1 values close to the reference sequence; among those, three sequences achieved lower CoV than the reference sequence. Lowest CoV was achieved using a non-triggered LL sequence with 5 beat readout and a 45o flip angle (mean T1 1733 ms ± 89 ms, CoV 1.3% ± 0.58%). Conclusion T1-measurements in the hepatic portal vein can be performed with high precision using either MOLLI or LL sequences provided that LL sampling duration is sufficiently long and flip angle sufficiently high. The advantage of constant timing outweighed the advantage of ECG-triggering. A phase-cycled temperature-sensitive fast spin echo sequence with conductivity bias correction for monitoring of mild RF hyperthermia with PRFS Abstract Objective Mild hyperthermia (HT) treatments are generally monitored by phase-referenced proton resonance frequency shift calculations. A novel phase and thus temperature-sensitive fast spin echo (TFSE) sequence is introduced and compared to the double echo gradient echo (DEGRE) sequence. Theory and methods For a proton resonance frequency shift (PRFS)-sensitive TFSE sequence, a phase cycling method is applied to separate even from odd echoes. This method compensates for conductivity change-induced bias in temperature mapping as does the DEGRE sequence. Both sequences were alternately applied during a phantom heating experiment using the clinical setup for deep radio frequency HT (RF-HT). The B0 drift-corrected temperature values in a region of interest around temperature probes are compared to the temperature probe data and further evaluated in Bland–Altman plots. The stability of both methods was also tested within the thighs of three volunteers at a constant temperature using the subcutaneous fat layer for B0-drift correction. Results During the phantom heating experiment, on average TFSE temperature maps achieved double temperature-to-noise ratio (TNR) efficiency in comparison with DEGRE temperature maps. In-vivo images of the thighs exhibit stable temperature readings of ± 1 °C over 25 min of scanning in three volunteers for both methods. On average, the TNR efficiency improved by around 25% for in vivo data. Conclusion A novel TFSE method has been adapted to monitor temperature during mild HT. A study of within-subject reliability of the brain's default-mode network Abstract Objective Resting-state functional magnetic resonance imaging (fMRI) is promising for Alzheimer's disease (AD). This study aimed to examine short-term reliability of the default-mode network (DMN), one of the main haemodynamic patterns of the brain. Materials and methods Using a 1.5 T Philips Achieva scanner, two consecutive resting-state fMRI runs were acquired on 69 healthy adults, 62 patients with mild cognitive impairment (MCI) due to AD, and 28 patients with AD dementia. The anterior and posterior DMN and, as control, the visual-processing network (VPN) were computed using two different methodologies: connectivity of predetermined seeds (theory-driven) and dual regression (data-driven). Divergence and convergence in network strength and topography were calculated with paired t tests, global correlation coefficients, voxel-based correlation maps, and indices of reliability. Results No topographical differences were found in any of the networks. High correlations and reliability were found in the posterior DMN of healthy adults and MCI patients. Lower reliability was found in the anterior DMN and in the VPN, and in the posterior DMN of dementia patients. Discussion Strength and topography of the posterior DMN appear relatively stable and reliable over a short-term period of acquisition but with some degree of variability across clinical samples. The feasibility of a novel limited field of view spiral cine DENSE sequence to assess myocardial strain in dilated cardiomyopathy Abstract Objective Develop an accelerated cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) sequence to enable clinically feasible myocardial strain evaluation in patients with dilated cardiomyopathy (DCM). Materials and methods A spiral cine DENSE sequence was modified by limiting the field of view in two dimensions using in-plane slice-selective pulses in the stimulated echo. This reduced breath hold duration from 20RR to 14RR intervals. Following phantom and pilot studies, the feasibility of the sequence to assess peak radial, circumferential, and longitudinal strain was tested in control subjects (n = 18) and then applied in DCM patients (n = 29). Results DENSE acquisition was possible in all participants. Elements of the data were not analysable in 1 control (6%) and 4 DCM r(14%) subjects due to off-resonance or susceptibility artefacts and low signal-to-noise ratio. Peak radial, circumferential, short-axis contour strain and longitudinal strain was reduced in DCM patients (p < 0.001 vs. controls) and strain measurements correlated with left ventricular ejection fraction (with circumferential strain r = − 0.79, p < 0.0001; with vertical long-axis strain r = − 0.76, p < 0.0001). All strain measurements had good inter-observer agreement (ICC > 0.80), except peak radial strain. Discussion We demonstrate the feasibility of CMR strain assessment in healthy controls and DCM patients using an accelerated cine DENSE technique. This may facilitate integration of strain assessment into routine CMR studies. Accelerated multi-contrast high isotropic resolution 3D intracranial vessel wall MRI using a tailored k-space undersampling and partially parallel reconstruction strategy Abstract Objective To develop a 3D multi-contrast IVW protocol with 0.5-mm isotropic resolution and a scan time of 5 min per sequence. Materials and methods Pre-contrast T1w VISTA, DANTE prepared PDw VISTA, SNAP, and post-contrast T1w VISTA were accelerated using cartesian undersampling with target ordering method (CUSTOM) and self-supporting tailored k-space estimation for parallel imaging reconstruction (STEP). CUSTOM + STEP IVW was compared to full-sample IVW, SENSE-accelerated IVW, and CUSTOM + zero-filled Fourier reconstruction in normal volunteers and subjects with intracranial atherosclerotic disease (ICAD). Image quality, vessel delineation, CSF suppression, and blood suppression were compared. Results CUSTOM + STEP vessel wall delineation was comparable to full-sample IVW and better than SENSE IVW for vessel wall delineation on T1w VISTA and luminal contrast on SNAP. Average image quality and wall depiction were significantly improved using STEP reconstruction compared with zero-filled Fourier reconstruction, with no significant difference in CSF or blood suppression. Conclusions CUSTOM + STEP allowed multi-contrast 3D 0.5-mm isotropic IVW within 30 min. Although some quantitative and qualitative scores for CUSTOM − STEP were lower than fully sampled IVW, CUSTOM + STEP provided comparable vessel wall delineation as full-sample IVW and was superior to SENSE. CUSTOM + STEP IVW was well tolerated by patients and showed good delineation of ICAD plaque. Feasibility of diffusion-weighted imaging with DWIBS in staging Hodgkin lymphoma in pediatric patients: comparison with PET/CT Abstract Objective The aim of the study was to evaluate feasibility of diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) method in diagnosing Hodgkin lymphoma in pediatric patients and to compare it with 18F-FDG PET/CT as a gold standard. Materials and methods Eleven patients (median age 14) with newly diagnosed Hodgkin lymphoma were examined with 18F-FDG PET/CT and MRI including whole-body DWIBS sequence (b = 0, 800 s/mm2), before the oncologic treatment. About 26 locations of lymphatic tissues were evaluated visually and quantitatively using ADCmean (DWIBS) and SUVmax (18F-FDG PET/CT), respectively. Results All affected lymph node regions (n = 134) diagnosed in 18F-FDG PET/CT were found with DWIBS, presenting decreased diffusion. Significant correlation was found between ADC and SUV values (R2 = − 0.37; p = 0.0001). Nevertheless, additional 33 regions were recognized only by DWIBS. They were significantly smaller than regions diagnosed by both methods. Discussion Agreement between DWIBS and 18F-FDG PET/CT for detection and staging of malignant lymphoma is high. DWIBS can be used for the evaluation of pediatric Hodgkin lymphoma. Challenges for labeling and longitudinal tracking of adoptively transferred autoreactive T lymphocytes in an experimental type-1 diabetes model Abstract Objective Tracking the autoreactive T-cell migration in the pancreatic region after labeling with fluorinated nanoparticles (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[3-(2-pyridyldithio)propionate]-perfluoro-15-crown-5-ether nanoparticles, PDP-PFCE NPs) in a diabetic murine model using 19F MRI. Materials and methods Synthesis of novel PDP-PFCE fluorine tracer was performed for in vitro labeling of T cells. Labeling conditions were optimized using different PDP-PFCE NPs concentrations. For in vivo 19F MRI, mice were longitudinally followed after adoptive transfer of activated, autoreactive, labeled T cells in NOD.SCID mice. Results Established MR protocols were used for challenging T cell labeling to track inflammation in a model of diabetes after successful labeling of CD4+ and CD8+ T cells with PDP-PFCE NPs. However, T cells were difficult to be detected in vivo after their engraftment in animals. Discussion We showed successful in vitro labeling of T cells using novel fluorinated liposomal nanoparticles. However, insufficient and slow accumulation of labeled T cells and subsequent T cell proliferation in the pancreatic region remains as limitations of in vivo cell imaging by 19F MRI. In-bore biopsies of the prostate assisted by a remote-controlled manipulator at 1.5 T Abstract Purpose To evaluate the technical and clinical utility of a fully MRI-compatible, pneumatically driven remote-controlled manipulator (RCM) for targeted biopsies of the prostate at 1.5 T. Materials and methods The data of the first 22 patients that were biopsied under robotic assistance were analyzed. Interventional planning relied on T2-weighted (T2w) turbo spin-echo (TSE) images (axial and sagittal) with a high-b-value diffusion-weighted acquisition added in selected cases. Alignment of the needle guide was controlled with a short balanced SSFP sequence in two oblique planes along the MR-visible sheath. Signals were acquired with a combination of elements from a 30-channel body and a 32-channel spine coil. Biopsy samples were taken with a fully automatic 18-G biopsy gun with a length of 150 or 175 mm. Results Mean age was 66.6 years and average PSA level was 11.5 ng/ml. Fourteen out of 22 patients (63%) had received prior biopsies under transrectal ultrasound guidance. Diagnostic MRI reports (before biopsy) involved 17 cases with a single suspicious finding (four PI-RADS 3, one PI-RADS 3–4, eight PI-RADS 4 and nine PI-RADS 5 cases). The median effective procedure time was 33.9 (range 25.0–55.9) min for 16 cases with one CSR and 63.4 (52.7–81.8) min for 5 cases with two CSRs. The biopsy with three CSRs took 74.0 min. Histopathologic examination revealed prostate cancer in 14 of 22 cases. Conclusion MR-targeted, transrectal biopsy of the prostate could be reliably performed with a robotic manipulator at a field strength of 1.5 T. Balanced SSFP imaging is considered a viable option for fast procedural control. Follow-up work needs to evaluate to what extent in-bore adjustments and workflow enhancements will contribute to shorter procedure times or higher patient comfort. Alchemy, Medicine, and Commercial Book Production: A Codicological and Linguistic Study of the Voigts-Sloane Manuscript Group by Alpo Honkapohja (review) Alchemy, Medicine, and Commercial Book Production: A Codicological and Linguistic Study of the Voigts-Sloane Manuscript Group by Alpo Honkapohja W Black - Manuscript Studies: A Journal of the Schoenberg …, 2019 Winston Black Manuscript Studies: A Journal of the Schoenberg Institute for Manuscript Studies University of Pennsylvania Press Volume 4, Number 1, Spring 2019 pp. 176-181 10.1353/mns.2019.0009 REVIEW View Citation Additional Information In lieu of an abstract, here is a brief excerpt of the content: Reviewed by: Winston Black KEY WORDS Manuscript studies, England, Alchemy, Medicine, Codicology, Linguistics, astrology, book production, book trade, Medieval Latin, Middle English, London, code-switching, multilingualism, scriptoria Alpo Honkapohja. Alchemy, Medicine, and Commercial Book Production: A Codicological and Linguistic Study of the Voigts-Sloane Manuscript Group. Turnhout: Brepols, 2017. Xv + 250 pp., 57 black and white illustrations + 3 color illustrations, 20 black and white tables. €80. ISBN: 978-2-503-56647-4 IN A SERIES OF articles from 1989 to 2003, Linda Ehrsam Voigts identified a group of eleven manuscripts produced in England during the later fifteenth century that are relatively uniform in layout, contents, or both. These professionally made, but utilitarian, paper manuscripts contain similar medical, alchemical, astrological, and magical texts written mostly in self-contained booklets. Because six of the eleven manuscripts are found in the Sloane manuscript collection of the British Library (the other five are in different libraries), Voigts called them the "Sloane Group." She tentatively argued that the Sloane Group was an example of speculative publishing, aimed at a growing market for technical literature, before the advent of printing in England. Her theories about the Sloane Group have had a great influence on the study of book production at the dawn of print, but they have also been accepted uncritically at times. Alpo Honkapohja's Alchemy, Medicine, and Commercial Book Production is the first book-length study of the Sloane Group, in which he modifies or challenges the ideas of Voigts and other scholars about the production of [End Page 176] these manuscripts and their supposedly sophisticated multilingualism. This is an important book and should provoke historians and linguists to rethink some received ideas about later medieval book production, especially in technical fields like alchemy and medicine. Honkapohja rechristens the Sloane Group as the "Voigts-Sloane Group" (hereafter VSG) both in recognition of Voigts's scholarly contributions and to avoid confusion with the entire Sloane collection of the British Library. He remains respectful of Voigts and her work while frequently calling into question details of her arguments about the VSG. Honkapohja's approach to the study of the VSG is framed as a response to a call made by Claire Jones in a 2004 essay for more detailed analyses of the codicology and languages of this and similar manuscript groups to test Jones's arguments about the "discourse communities" reflected in medical manuscripts. Honkapohja carefully applies both types of analysis (codico-logical and linguistic) to the VSG "to see whether they contain signs of a publisher, co-ordination, speculative sale, or even 'veritable mass production'" (21) and to determine whether some or all of the texts were written in London or Westminster, as Voigts originally proposed. This is a highly technical study, intended for scholars already versed in codicology and Middle English linguistics. After a detailed introduction on the definition and historiography of the VSG and a disconcertingly short Chapter 1 on "The Book Trade in London Before Printing," Honkapohja dedicates three chapters to the codicology of the VSG and two to a linguistic analysis of the Middle English texts. The arguments in both sections of the book (that is, Chapters 2–4 and 5–6) are supported by a profuse number of collation diagrams, tables, dialect maps, and grayscale and color images of the manuscript texts. An appendix is dedicated to the full collation of British Library, MS Sloane 1118, which Honkapohja uses as representative of the entire VSG. Voigts divided the VSG into a Core Group of manuscripts sharing a typical mise-en-page of compressed Secretary script and dramatically large margins, and a Sibling Group unified not by appearance but by a common anthology of twelve short medical and astrological treatises, which Honkapohja calls the Sibling Set Texts. Each group contains six manuscripts, with [End Page 177] Sloane 2320 shared between the two subgroups, for a total of eleven. Honkapohja further divides the Sibling Group into three subgroups: Sloane 2320, a group of three "half-sisters, or at least cousins," and two manuscripts of the Second Generation, dating from the 1480s... Alexandros Sfakianakis Anapafseos 5 . Agios Nikolaos Crete.Greece.72100 2841026182 6948891480 alsfakia@gmail.com Intraoperative balloon pulmonary annulus dilation: A new alchemy or polishing a meatball? D Bichell - 2019 Intraoperative balloon pulmonary annulus dilation: A new alchemy or polishing a meatball? Author links open overlay panelDavidBichellM.D. Department of Cardiac Surgery, Monroe Carell, Jr. Children's Hospital, Vanderbilt University Medical Center, Nashville, Tennessee Available online 15 May 2019. Show less https://doi.org/10.1053/j.semtcvs.2019.05.008Get rights and content Refers to María Lozano-Balseiro, Maria Garcia-Vieites, Isaac Martínez-Bendayán, Irene García-Hernández, Jose J. Cuenca-Castillo, Fernando Rueda-Núñez, Victor Bautista-Hernandez Valve-Sparing Tetralogy of Fallot Repair With Intraoperative Dilation of the Pulmonary Valve. Mid-Term Results Seminars in Thoracic and Cardiovascular Surgery, Available online 18 April 2019, Pages Purchase PDF Brief summary Late right heart performance obligates attention to pulmonary valve preservation at TOF repair. Intraoperative balloon dilation of the annulus has enjoyed some enthusiasm, yet mid-term results show a discouraging reintervention rate and valve incompetence. Refined patient selection and modifications of the technique may improve results, but further study is needed. Conflicts of interest: The author has no disclosures © 2019 Published by Elsevier Inc. Alexandros Sfakianakis Anapafseos 5 . Agios Nikolaos Crete.Greece.72100 2841026182 6948891480 alsfakia@gmail.com ALCHEMY: AQuantum CHEMISTRY DATASET FOR BENCHMARKING AI MODELS [PDF] ALCHEMY: AQuantum CHEMISTRY DATASET FOR BENCHMARKING AI MODELS G Chen, CYK Hsieh, CK Lee, BB Liao, J Qiu, Q Sun…   Published as a conference paper at ICLR 2019 ALCHEMY: A QUANTUM CHEMISTRY DATASET FOR BENCHMARKING AI MODELS Guangyong Chen1∗ , Chang-Yu (Kim) Hsieh1 , Chee-Kong Lee1 , Ben Ben Liao1 , Jiezhong Qiu1,2 , Qiming Sun1 , Jie Tang2 , Shengyu Zhang1,3 1Quantum Lab, Tencent Co. Ltd., 2Department of Computer Science and Technology, Tsinghua University, 3Department of Computer Science and Engineering, CUHK. {gycchen,kimhsieh,cheekonglee,bliao,qssun,shengyzhang}@tencent.com qiujz16@mails.tsinghua.edu.cn,jietang@tsinghua.edu.cn ABSTRACT We introduce a new molecular dataset, named AlChemy, for developing machine learning models useful in chemistry and materials science. The dataset, as of the workshop submission date, comprises of 12 quantum mechanical properties of 67,000 organic molecules up to 12 heavy atoms, sampled from the GDB database. The Alchemy dataset expands the volume and diversity of existing molecular datasets. Our preliminary benchmark of the state-of-the-art machine learning models on AlChemy clearly manifests the usefulness of new data in validating and developing machine learning models. Recent advances in machine learning (ML) techniques have proven immensely useful for a broad range of applications including natural language processing (Shen et al., 2017), computer vision (He et al.) and strategic plannings (Silver et al., 2016; 2017) etc. These remarkably successful demonstrations have drawn high interests from the physical and biological science communities. For instance, ML-enhanced abilities to predict molecular properties with high precision (Gilmer et al., 2017; Liao et al., 2019), efficient generations of novel molecular structures (Jin et al., 2018), and better strategies in synthesis planning (Segler et al., 2018) and rectrosynthesis (Segler et al., 2017) will significantly accelerate drug design and novel material discovery (Sanchez-Lengeling & AspuruGuzik, 2018; Gomez-Bombarelli et al., 2018). However, the scarcity of high-quality datasets and ´ the lack of transferability of ML techniques impede the wide-scale adoption of molecular ML techniques in practice. The importance of supervised information for ML development cannot be understated. The ImageNet (Deng et al., 2009), a collection of more than 1.5 million labelled images distributed over 1, 000 classes, facilitates the development of new model such as ResNet (He et al.) that surpasses human performance in image recognition. In another instance, the Stanford Question Answering Dataset (SQuAD) (Rajpurkar et al., 2016), a reading comprehension dataset consisting of 150, 000 questions and answers, is critical to the development of a powerful language representation model BERT (Devlin et al., 2019). Recognizing the importance of abundance of datasets, the chemistry community has recently compiled a comprehensive collection of benchmarking datasets, the MoleculeNet (Wu et al., 2018), for supervised learning tasks. Despite this effort by the Pande group at Stanford, the amount of data in the MoleculeNet is often inadequate in comparison to the typical size of ML training datasets. For instance, there are less than 150K molecular entries for training models to predict the quantum mechanical properties of small organic molecules. The biggest dataset QM9 within MoleculeNet is further restricted to curating molecules composed of Hydrogen (H), Carbon (C), Nitrogen (N), Oxygen (O) and Florine (F). A better data variety, such as presence of more atom types, can help to more thoroughly investigate and improve some aspects of ML models such as transferability and generalibility. Herein we report a dataset that contains the quantum mechanical properties of around 67,000 organic molecules with up to 12 heavy atoms (C, N, O, S, and halogens including F) from the GDB17 MedChem database (Ruddigkeit et al., 2012). We name our collection the AlChemy dataset. ∗Authors are ordered alphabetically 1 Published as a conference paper at ICLR 2019 Table 1: Dataset Details: number of molecules and tasks Dataset Data Type #Tasks #Molecules Rec-Split Maximum #Heavy Atoms QM7 SMILES, 3D coordinates 1 7,160 Stratified 7 QM7b 3D coordinates 14 7,210 Random 7 QM8 SMILES, 3D coordinates 12 21,786 Random 8 QM9 SMILES, 3D coordinates 12 133,885 Random 9 AlChemy SMILES, 3D coordinates 12 67,000 Random 12 The quantum mechanical properties are calculated with the Python-based Simulations of Chemistry Framework (PySCF) (Sun et al., 2018). As compared to the full GDB-17 database, the MedChem subset contains molecules that are more suitable for medicinal chemistry, based on functional group and complexity considerations. Therefore, the AlChemy dataset is significantly more comprehensive than existing quantum chemistry datasets, and the molecules are considered more drug-like. AlChemy dataset could serve for evaluation, benchmarking and development of ML methods for applications in chemistry and materials science. 1 RELATED WORK There are only a few molecular datasets specifically built for benchmarking ML models for chemistry and material applications. Recently, a collection of various datasets have been compiled and collectively branded as the MoleculeNet. These datasets are furthered divided into different categories: quantum mechanics, physical chemistry, biophysics and physiology. In this work, we report our contributions of new datasets for multi-task learning of quantum mechanical properties of organic molecules. Hence, only the subset of quantum mechanical databsets within the MoleculeNet is summarized below. QM7/QM7b The QM7 dataset contains 7,165 molecules, a subset of GDB-13, with at most 7 C,N,O,S atoms. The learning task is to predict a single electronic property, the atomization energy given the input feature in Table 1. All the physical properties listed in the dataset were calculated with the ab-initio density function theory at the level of PEB0/tier2 basis set. QM7b is an extension. 13 additional properties are computed at different levels of accuracy (ZINDO, SCS, PBE0, GW). The data is further expanded to 7,211 molecules. QM8 This dataset provides electronic properties of 21,800 molecules comprising up to 8 C,N,O,F atoms, a subset of GDB-17. Not only ground-state electronic properties but also four excited-state properties at different levels of accuracy (TDDFT using PBE0 and CAM-B3LYP and CC2) are computed for multi-task learning. QM9 This dataset contains geometric, energetic, electronic and thermodynamics (totalling 13) properties for 134,000 organic molecule comprising up to 9 non-hydrogen atom within the GDB-17 database. All physical properties are computed at the accuracy of B3LYP/6-31G(2df,p) based DFT. 2 THE ALCHEMY DATASET 2.1 MOLECULAR REPRESENTATIONS: SMILES AND 3D GEOMETRY Intuitively, a molecule is a stable 3D configurations of atoms connected by chemical bonds. The essential features of a molecule can be encoded into a molecular graph with each vertex representing an atom and each edge representing a bond. Simplified Molecular-Input Line-Entry System (SMILES) is a text-based data structure to store molecular graphs on computers. While SMILES and graphs give a minimalist approach to describing molecules, one needs the 3D coordinates of all atoms in a stable configuration for quantum chemistry calculations. This process of recovering 3D geometry from the SMILE string is called the geometry optimization. 2 Published as a conference paper at ICLR 2019 Table 2: Calculated properties. Last two entries are not present in the QM9 dataset Property Unit Mean Relative Error Meam Absolute Error Rotational constants GHz - - Dipole moment (mu) Debye 0.1928 0.6401 Polarizability (alpha) a 3 0 0.0104 0.7610 HOMO Eh 0.0244 0.0060 LUMO Eh 0.2114 0.0061 gap Eh 0.0275 0.0073 hR 2 i (R2) a 2 0 0.0404 52.3778 Zero point energy (zpve) Eh 0.0021 0.0003 Internal energy (U0) Eh 0.0006 0.2486 Internal energy at 298.15 K (U) Eh 0.0006 0.2486 Enthalpy at 298.15 K (H) Eh 0.0006 0.2486 Free energy at 298.15 K (G) Eh 0.0006 0.2486 Heat capacity at 298.15 K (Cv) EhK −1 0.0038 3.8×10−7 Dipole moment vector - - - 3×3 Polarizability tensor - - - 2.2 DETAIL FOR THE DATA GENERATION The molecular properties were calculated using PySCF's implementation of the DFT Kohn-Sham method at the B3LYP level with the basis set 6-31G(2df,p). The quantum chemistry model B3LYP/6-31G(2df,p) was validated in an early work (Ramakrishnan et al., 2014) for small organic molecules. Building a complementary dataset along the line of QM-series introduced in Sec. 1, we computed the following categories of molecular properties: ground state equilibrium geometry, ground state electronic properties, and ground state thermochemical properties. The detail is summarized in Table 2. In the remaining sections, we clarify a few technical aspects of our workflow for interested experts in quantum chemistry. The equilibrium geometry was optimized in three passes. We first used OpenBabel (O'Boyle et al., 2011) to parse SMILES string and built the Cartesian coordinates with MMFF94 force field optimization. The second pass employed the HF/STO-3G theory (incorporate quantum mechanical effects) to generate a preliminary geometry. In the final pass of geometry relaxation, we used the B3LYP/6-31G(2df,p) model with the density fitting approximation for electron repulsion integrals. The auxiliary basis cc-pVDZ-jkfit (Weigend, 2002) is employed in density fitting to build the Coulomb matrix and the HF exchange matrix. When computing the ground state electronic properties and ground state thermochemical properties, the density fitting technique was disabled in our dataset generation program. In addition to the molecular properties proposed by the original QM9 dataset, we also report the dipole moment vector, the 3×3 polarizability tensor and the atomic charges obtained by the meta-Lowdin population analysis (Sun & Chan, 2014). The advantage of meta-lowdin population analysis, like other advanced population analysis prescriptions (Knizia, 2013), is that the obtained atomic charges possess good transferability in different molecular environments. 2.3 COMPARISON TO THE QM9 DATASET In AlChemy dataset, we reproduced results for a random selection of 28,732 molecules from QM9 and calculated properties for another selection of 38,268 molecules up to 12 heavy atoms in the GDB-17 MedChem. The running time statistics and an example of geometry optimization can be found in Appendix. The reproduction of selected QM9 data helps to validate the accuracy of our computations. We draw attention to the third and fourth columns of Table 2. The mean relative error and mean absolute error refers to the disagreement between our results and the original QM9. Our calculations agree well with the original QM9 given the fact that different definitions of B3LYP functionals were used in these calculations. Nevertheless, we notice a few disparities. The relative error on LUMO energy is less a concern as we get a good agreement on the HOMO-LUMO energy gap. It is well-known that the two definitions of B3LYP functionals tend to systematically shift orbital energies in these calculations, and the energy gap should be a more appropriate comparison criterion. However, inconsistency on mu and R2 constitutes more serious indications of disagree3 Published as a conference paper at ICLR 2019 Table 3: Performance Comparison (MAE) QM9 AlChemy MPNN2 (Gilmer et al., 2017) MPNN (Wu et al., 2018) MPNN (our impl.) MPNN (our impl.) mu 0.03 - 0.5316 2.7448 alpha 0.092 - 0.4171 17.9973 HOMO 0.04257 - 0.0033 0.0173 LUMO 0.03741 - 0.0034 0.0261 gap 0.0688 - 0.0048 0.0262 R2 0.18 - 25.4747 362.8817 ZPVE 0.001524 - 0.0003 0.0186 U0 0.01935 - 0.1200 98.3374 U 0.01935 - 0.1201 98.5954 H 0.01677 - 0.0800 92.4926 G 0.01892 - 0.2802 98.2963 Cv 0.04 - 0.1422 33.6612 Average 0.0472245 ∼2.73 2.2648 67.0912 ments. We unambiguously trace this inconsistency back to the complexity of searching the optimal molecular conformation among enormous molecular geometry local minimum. The geometry optimization could be stuck at the sub-optimal molecular conformation in either our dataset or QM9. The large deviation between our dataset and QM9's indicates that R2, as a direct output of molecular geometry, is less predictable. This is also observed in our model training practice (Table 3). 3 THE BENCHMARKING RESULTS We setup baselines using the Message Passing Neural Network (MPNN) model (Gilmer et al., 2017). Our MPNN implementation is based on the authors' prefer model trained individually on each target. As for hyper-parameters not declared in MPNN paper (Gilmer et al., 2017), we refer to their git repository1 for default parameter setting. For detailed hyper-parameter setting, we list them in Appendix (Table 4). The code of our implementation will be publicly available after the double-blind review period ends. In the preliminary part of our experiment, we first reproduce the QM9 experiments for 12 targets listed in (Gilmer et al., 2017) with the MPNN model. It is the state-of-the-art model for all regression tasks of the QM9 dataset. QM9 contains 133,885 molecules. We use 10,000 for validation, 10,000 for testing, and the rest for training. The primary part of our experiment focuses on testing the transferability of existing ML models in quantum chemistry tasks. Models shall be first trained on QM9, and then tested against a subset of our AlChemy dataset with the same atom types (C, N, H, O, F). This fraction contains 37,178 molecules with exactly 10 heavy atoms. The task of generalization to molecular graphs with more heavy atoms is marked as a difficult problem in (Gilmer et al., 2017). As for comparison metric, Mean absolute error (MAE) is used as evaluation metric in both experiments. Results are reported in Table 3. For reader's convenience, we list the corresponding results reported in (Gilmer et al., 2017; Wu et al., 2018) as well. We first focus on the comparison among our MPNN implementation and MPNN in (Gilmer et al., 2017) and (Wu et al., 2018). Our MPNN implementation achieves similar performance to (Wu et al., 2018), but differs from (Gilmer et al., 2017)'s results by two orders of magnitude. We also investigate the generalizability of MPNN to larger molecules (see fifth column in Table. 3). Interestingly, we observe large deviations among all targets — the test MAEs on AlChemy dataset differs from those on QM9 dataset by up to orders of magnitude, which again reveals the difficulty in transferring 1https://github.com/brain-research/mpnn 2The MAEs of Gilmer et al. (2017)'s MPNN can be calculated as (Error Ratio (from their Table. 2)) × (Chemical Accuracy (from their Table. 5)). Interestd readers can refer to a detailed discussion in Appendix. 3Refer to Figure 14 in Wu et al. (2018) 4 Published as a conference paper at ICLR 2019 knowledge learned from small molecules to larger molecules, although we only increase the number of heavy atoms by one. 4 CONCLUSIONS AND FUTURE WORK The process of building the AlChemy dataset has been a rewarding experience. Along this journey, we face the difficulty to optimize molecular geometries efficiently and accurately. We eventually use a combination of two geometry optimization tools to overcome this problem. All the discrepancies between our data and QM9's can be precisely attributed to the disagreements on the optimized geometries. Our preliminary benchmark results clearly manifest the usefulness of the AlChemy dataset. The public availability of this dataset shall inspire further improvement of existing ML models as well as the proposals of entirely new ones. REFERENCES J. Deng, W. Dong, R. Socher, L.-J. Li, K. 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Chemical Science, 9(2):513–530, 2018. 5 APPENDIX 5.1 HYPER-PARAMETERS We list detailed hyper-parameter settings of our MPNN implementation in Tabel. 4. 5.2 MORE DETAILS ON ALCHEMY DATA GENERATION Figure. 1 shows AlChemy's running time statistics; Figure. 2 shows an example of geometry optimization process from AlChemy dataset. 5.3 CONVERSION OF UNITS As clearly specified in Table 2, we adopt the atomic units for all numerics in the AlChemy dataset. This choice is consistent with the QM9 dataset. However, we caution that the MAEs in the second column of Table 3, quoted from Gilmer's work (Gilmer et al., 2017), are given in a different set of units. For instance, one has to divides all energy-related MAEs except the one for the zero-point vibrational energy by 27 to convert the numbers into the atomic units. After appropriate conversions, the disagreements between the actual numbers of Gilmer's original work and our MPNN results will be more pronounced. 6 Published as a conference paper at ICLR 2019 Table 4: Hyper-parameters. Category Hyper-parameter Value Preprocessing edge features bond type + raw distance node features Table 1 in Gilmer et al. (2017) use Mulliken partial charges No Message Passing Function (Edge Network) message passing steps T 6 edge network layers 4 edge network hidden dim 50 use multiple towers No Update Function (GRU, as in GG-NN (Li et al., 2016)) node hidden units d 50 GRU layer 1 Readout Function (set2set (Vinyals et al., 2015)) set2set computations M 12 output NN hidden layer 1 output NN hidden units 200 Training initial learning rate 0.00013 learning rate decay factor 0.5 optimizer Adam batch size 20 traing epochs 540 0.0 0.2 0.4 0.6 HF/STO-3G (hours) 0 2 4 6 8 10 12 Histogram 0 5 10 15 DFT (hours) 0.0 0.1 0.2 0.3 0.4 0.5 10 20 30 40 Property (hours) 0.00 0.02 0.04 0.06 0.08 0.10 0 10 20 30 40 50 Total (hours) 0.00 0.02 0.04 0.06 0.08 Figure 1: AlChemy's running time statistics for molecules (with 10 heavy atoms) from GDB-17 MedChem. Each step takes 0.1/1.9/14.4 hours on average, respectively. The average total running time is 16.4 hours. (a) OpenBabel geometry (b) HF/STO-3G geometry (c) DFT geometry Figure 2: An example for molecule CC(O)C(C)C(=O)NC=O, a random sample from AlChemy dataset. 7   Alexandros Sfakianakis Anapafseos 5 . Agios Nikolaos Crete.Greece.72100 2841026182 6948891480 alsfakia@gmail.com ALEXANDROS SFAKIANAKIS ANAPAFSEOS 5 AGIOS NIKOLAOS CRETE 72100 GREECE +306932607174 +302841026182

ALEXANDROS SFAKIANAKIS ANAPAFSEOS 5 AGIOS NIKOLAOS CRETE 72100 GREECE +306932607174 +302841026182