The genomic and epigenomic landscape in thymic carcinoma

Abstract

Thymic carcinoma (TC) is a rare cancer whose genomic features have been examined in only a limited number of patients of European descent. Here, we characterized both genomic and epigenomic aberrations by whole exome sequencing, RNA sequencing, methylation array and copy number analyses in TCs from Asian patients and compared them with those in TCs from USA/European patients. Samples analyzed were 10 pairs of snap-frozen surgical specimens of cancerous and non-cancerous thymic tissue. All 10 cases were Japanese patients treated at the National Cancer Center Hospital, Japan, between 1994 and 2010. Mutational signature analysis indicated that the accumulation of age-related mutations drive TC development. We identified recurrent somatic mutations in TET2, CYLD, SETD2, TP53, FBXW7, HRAS and RB1, and no mutations in GTF2I, supporting the hypothesis that TC and thymoma are distinguishable by their genetic profiles. TCs with TET2 mutations had more hypermethylated genes than those without, and hyper-methylation was associated with downregulation of gene expression. Focal genome copy number gains, associated with elevated gene expression, were observed at the KIT (which is known to drive thymic carcinogenesis) and AHNAK2 gene loci. Taken together, the results suggest that the molecular processes leading to TC depend on the accumulation of genetic and epigenetic aberrations. In addition, epigenetic dysregulation as a result of the TET2 mutation was observed in a subset of TCs.

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Deletions at SLC18A1 increased the risk of CRC and lower SLC18A1 expression associated with poor CRC outcome

Abstract

Copy number variations (CNVs) contribute to the development of colorectal cancer (CRC). We conducted a two-stage association study to identify CNV risk loci for CRC. We performed a gene-based rare CNV study on 694 sporadic CRC and 1641 controls using Illumina Human-OmniExpress-12v1.0 BeadChips, and further replicated in 934 CRC cases and 2680 controls for risk CNVs by using TaqMan Copy Number Assay. Tumor buddings, cancer cells in the center of primary tumor and normal intestinal epithelial cells were captured using laser capture microdissection (LCM) and were assayed using AffymetrixGeneChip® Human Genome U133 Plus 2.0 Array. In addition, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus data were assessed for the effects of risk CNVs. We found that germline deletions affecting the last six exons of SLC18A1 significantly associated with CRC with a combined P value of 6.4 × 10^–5 by a two-stage analysis. Both in TCGA CRC RNA seq dataset and GDS4382, SLC18A1 was significantly down regulated in CRC tissues than in paired normal tissues (N = 32 and 17 pairs, P = 0.004 and 0.009, respectively). In LCM samples, similar observations were obtained that the expression levels of SLC18A1 in the tumor buddings, cancer cells in the center of primary tumor, and stroma of both tumor budding and cancer cells were lower than normal intestinal epithelial and stromal cells (fold change = 0.17–0.62, 0.12–0.57 and 0.37–0.68, respectively). In summary, the germline deletions at SLC18A1 contributed to the development of CRC. The role of SLC18A1 required further exploration.

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Metabolome-wide association study identified the association between a circulating polyunsaturated fatty acids variant rs174548 and lung cancer

Abstract

Quantitative trait loci (QTLs) are widely used as instruments to infer causal risk factors of diseases based on the idea of mendelian randomization. Plasma metabolites can serve as risk factors of cancer, and the heritability of many circulating metabolites was high. We conducted a metabolome-wide association study (MWAS) to systematically investigate the effects of genetic variants on metabolites and lung cancer based on published genome-wide association study (GWASs) and metabolic-QTL (mQTL) study. Then we confirmed the results by subsequent genetic and metabolic validations and inferred the causal relationship between identified metabolites and lung cancer through genetic variant(s). We firstly identified six polyunsaturated fatty acids (PUFAs) represented by rs174548-linked haplotype were significantly associated with lung cancer risk in a Chinese GWAS (2311 cases and 3077 controls). Rs174548 was further confirmed to be associated with lung cancer in 13 821 Europeans and 18 471 Asians (OR_meta = 0.87, P_meta = 1.76 × 10^–15) and the effect was much stronger in females (P_interaction = 6.00 × 10^–4). We next validated rs174548-plasma PUFA association in 253 Chinese subjects (β = −0.57, P = 1.68 × 10^–3). Rs174548 was also found associated with FADS1 (the major fatty acid desaturase of identified PUFAs) expression in liver tissues. Taken together, we found that rs174548 was associated with both PUFAs and lung cancer. Because rs174548 was the only mQTL variant of PUFAs reported by previous GWASs and explained a large proportion of heritability, we proposed that plasma PUFAs could be causally associated with lung cancer based on the idea of mendelian randomization. These findings provide a diet-related risk factor and may have important implications for prevention on lung cancer.

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Spectrum of germline mutations in smokers and non-smokers in Brazilian non-small-cell lung cancer (NSCLC) patients

Abstract

Lung cancer (LC) is a leading cause of cancer-related mortality. Although smoking is the major risk factor, ~15% of all cases occur in never-smokers, suggesting that genetic factors play a role in LC predisposition. Indeed, germline mutations in the TP53 gene predispose to multiple cancer types, including LC. To date, few studies compared the somatic and germline mutational profiles of LC cases by smoking status, and none was reported in Brazilians. Whole-exome sequencing (WES) was performed on two pools (seven smokers and six non-smokers) of tumor-derived DNA using the Illumina HiSeq2000 platform. Files from pools were analyzed separately using Ingenuity^®Variant Analysis^TM and Mendel,MD. Validation of all candidate variants was performed by Sanger sequencing. Subsequently, validated mutations were analyzed in germline DNA from the same patients and in ethnically matched controls. In addition, a single recurring Brazilian TP53 germline mutation (R337H) was genotyped in 45 non-small-cell lung cancer patients.Four novel germline variants in the ATAD2, AURKA, PTPRD and THBS1 genes were identified exclusively in smoker patients, and four germline missense variants in PLCD1, RAD52, CP and CDC6 genes were identified solely in non-smokers. There were 4/45 (8.9%) germline carriers of the R337H TP53 mutation. In conclusion, the recurring Brazilian TP53 mutation should be genotyped in all non-small-cell lung cancer in Brazil, regardless of smoking status. Distinct pathogenic mutations and novel sequence variants are detected in Brazilian non-small-cell lung cancer patients, by smoking status. The contribution of these sequence variants to LC pathogenesis remains to be further explored.

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Resistance mediated by alternative receptor tyrosine kinases in FGFR1-amplified lung cancer

Abstract

Fibroblast growth factor receptor 1 (FGFR1) amplification has been identified in 10–20% of patients with squamous non-small-cell lung cancer. Preclinical models showed promising activity of specific FGFR inhibitors, but early clinical trials showed that only a small fraction of patients with FGFR1-amplified lung cancer responded to FGFR inhibitors. These unsatisfactory results were partly explained by heterogeneous amplicons around the 8p11 genomic region, leading to false-positive amplification results. Furthermore, discrepancies in the gene amplification and protein expression of FGFR1 were also reported. In this study, we identified the roles of alternative receptor tyrosine kinases (RTKs) in FGFR1-amplified lung cancer. These alternative RTKs dominantly activate phosphoinositide 3-kinase-AKT signaling and also mitigate sustained inhibition of mitogen-activated protein kinase signaling by FGFR inhibitors. The rebound activation of extracellular signal-regulated kinase phosphorylation was associated with sensitivity to the drugs. Combinatorial inhibition of alternative RTKs and FGFR1 was required to suppress both AKT and extracellular signal-regulated kinase phosphorylation and to induce key pro-apoptotic proteins BIM and p53 upregulated modulator of apoptosis (PUMA). Furthermore, even in FGFR inhibitor-sensitive NCI-H1581 lung cancer cells, MET-expressing clones were already detectable at a very low frequency before resistance induction. Selection of these pre-existing subclones resulted in FGFR inhibitor resistance because of the activation of AKT and extracellular signal-regulated kinase by MET signaling that was mediated by GRB2 associated binding protein 1 (GAB1). These results suggest that incomplete suppression of key survival signals led to intrinsic and acquired resistance to FGFR inhibitors. Our results may help explain the low clinical response rates to FGFR inhibitors in FGFR1-amplified lung cancer.

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Glycemic index, glycemic load and carbohydrate intake in association with risk of renal cell carcinoma

Abstract

Carbohydrate intake affects postprandial glucose levels and insulin response, which plays a role in carcinogenesis. The relationship between carbohydrate intake, dietary glycemic index (GI) and glycemic load (GL), and risk of renal cell carcinoma (RCC) remains unclear. We conducted a case–control study including 854 patients with newly diagnosed RCC (cases) and 1255 healthy participants (controls) recruited since 2002. GI, GL and carbohydrate intake were obtained via a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, adjusting for potential confounders. We found that higher GI was significantly associated with RCC risk with an OR of 1.32 (95% CI, 0.99–1.74; P_trend = 0.026) (the highest versus the lowest quartiles). We also observed an inverse association between fiber intake and RCC risk with OR of 0.70 (95% CI = 0.50–0.99) as well as between starch intake and risk of RCC with OR of 0.65 (95% CI = 0.49–0.87). Individuals with a high-GI diet and hypertension or high body mass index (BMI) had a 2.7 times (OR = 2.67, 95% CI = 1.96–3.64) and two times (OR = 1.95, 95% CI = 1.29–2.92) higher RCC risk, respectively, than those without these factors. Our findings suggest that a high-GI diet is associated with an increased risk of RCC, whereas increased fiber and starch intakes appear to be associated with a decreased risk of RCC. We found that reducing GI levels and increasing fiber intake could be a dietary strategy to decrease RCC risk, especially for individuals with hypertension or high BMI.

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Occupational exposure to diesel engine exhaust and alterations in immune/inflammatory markers: a cross-sectional molecular epidemiology study in China

Abstract

The relationship between diesel engine exhaust (DEE), a known lung carcinogen, and immune/inflammatory markers that have been prospectively associated with lung cancer risk is not well understood. To provide insight into these associations, we conducted a cross-sectional molecular epidemiology study of 54 males highly occupationally exposed to DEE and 55 unexposed male controls from representative workplaces in China. We measured plasma levels of 64 immune/inflammatory markers in all subjects using Luminex bead-based assays, and compared our findings to those from a nested case–control study of these markers and lung cancer risk, which had been conducted among never-smoking women in Shanghai using the same multiplex panels. Levels of nine markers that were associated with lung cancer risk in the Shanghai study were altered in DEE-exposed workers in the same direction as the lung cancer associations. Among these, associations with the levels of CRP (β= −0.53; P = 0.01) and CCL15/MIP-1D (β = 0.20; P = 0.02) were observed in workers exposed to DEE and with increasing elemental carbon exposure levels (P_trends <0.05) in multivariable linear regression models. Levels of a third marker positively associated with an increased lung cancer risk, CCL2/MCP-1, were higher among DEE-exposed workers compared with controls in never and former smokers, but not in current smokers (P_interaction = 0.01). The immunological differences in these markers in DEE-exposed workers are consistent with associations observed for lung cancer risk in a prospective study of Chinese women and may provide some insight into the mechanistic processes by which DEE causes lung cancer.

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Blackface in America and Africa: Popular Arts and Diaspora Consciousness in Cape Town and the Gold Coast

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Revisoren müssen unabhängig sein

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Mehr Transparenz wünschenswert

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SOX8 regulates cancer stem-like properties and cisplatin-induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β-catenin pathway

Abstract

A sub-population of chemoresistant cells exhibits biological properties similar to cancer stem cells (CSCs), and these cells are believed to be a main cause for tumour relapse and metastasis. In this study, we explored the role of SOX8 and its molecular mechanism in the regulation of the stemness properties and the epithelial mesenchymal transition (EMT) of cisplatin-resistant tongue squamous cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin-resistant TSCC cells, which displayed CSC-like properties and exhibited EMT. SOX8 was also overexpressed in chemoresistant patients with TSCC and was associated with higher lymph node metastasis, advanced tumour stage and shorter overall survival. Stable knockdown of SOX8 in cisplatin-resistant TSCC cells inhibited chemoresistance, tumoursphere formation and EMT. The Wnt/β-catenin pathway mediated the cancer stem-like properties in cisplatin-resistant TSCC cells. Further studies showed that the transfection of active β-catenin in SOX8 stable-knockdown cells partly rescued the SOX8 silencing-induced repression of stem-like features and chemoresistance. Through chromatin immunoprecipitation and luciferase assays, we observed that SOX8 bound to the promoter region of Frizzled-7 (FZD7) and induced the FZD7-mediated activation of the Wnt/β-catenin pathway. In summary, SOX8 confers chemoresistance and stemness properties and mediates EMT processes in chemoresistant TSCC via the FZD7-mediated Wnt/β-catenin pathway. This article is protected by copyright. All rights reserved.

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Erythrocyte membrane fatty acids and breast cancer risk: A prospective analysis in the Nurses' Health Study II

Abstract

The roles of specific fatty acids in breast cancer etiology are unclear, particularly among premenopausal women. We examined 34 individual fatty acids, measured in blood erythrocytes collected between 1996-1999, and breast cancer risk in a nested case-control study of primarily premenopausal women in the Nurses' Health Study II. Breast cancer cases diagnosed after blood collection and before June 2010 (n=794) were matched to controls and conditional logistic regression was used to estimate OR's (95% CI's) for associations of fatty acids with breast cancer; unconditional logistic regression was used for stratified analyses. Fatty acids were not significantly associated with breast cancer risk overall; however, heterogeneity by body mass index (BMI) was observed. Among overweight/obese women (BMI≥25), several odd-chain saturated (SFA, e.g. 17:0, OR_Q4vsQ1(95%CI) =1.85 (1.18-2.88), p_trend=0.006 p_int<0.001), trans (TFA, e.g. 18:1, OR_Q4vsQ1(95%CI) =2.33 (1.45-3.77), p_trend<0.001, p_int=0.007) and dairy-derived fatty acids (SFA 15:0 + 17:0 + TFA 16:1n-7t; OR_Q4vsQ1(95%CI) =1.83(1.16-2.89), p_trend=0.005, p_int<0.001) were positively associated, and n-3 polyunsaturated fatty acids (n-3 PUFA, e.g. alpha-linolenic acid; OR_Q4vsQ1(95%CI) =0.57 (0.36-0.89), p_trend=0.017, p_int=0.03) were inversely associated with breast cancer. Total SFA were inversely associated with breast cancer among women with BMI<25 (OR_Q4vsQ1(95%CI) =0.68 (0.46-0.98), p_trend=0.05, p_int=0.01). Thus, while specific fatty acids were not associated with breast cancer overall, our findings suggest positive associations of several SFA, TFA and dairy-derived fatty acids and inverse associations of n-3 PUFA with breast cancer among overweight/obese women. Given these fatty acids are influenced by diet, and therefore are potentially modifiable, further investigation of these associations among overweight/obese women is warranted. This article is protected by copyright. All rights reserved.

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Genomic Characterization of Chromosomal Insertions: Insights into the Mechanisms Underlying Chromothripsis

Chromosomal insertions are rare structural rearrangements, and the molecular mechanisms underlying their origin are unknown. In this study, we used whole genome sequencing to analyze breakpoints and junction sequences in 4 patients with chromosomal insertions. Our analysis revealed that none of the 4 cases involved a simple insertion mediated by a 3-chromosomal breakage and rejoining events. The inserted fragments consisted of multiple pieces derived from a localized genomic region, which were shuffled and rejoined in a disorderly fashion with variable copy number alterations. The junctions were blunt ended or with short microhomologies or short microinsertions, suggesting the involvement of nonhomologous end-joining. In one case, analysis of the parental origin of the chromosomes using nucleotide variations within the insertion revealed that maternal chromosomal segments were inserted into the paternal chromosome. This patient also carried both maternal alleles, suggesting the presence of zygotic trisomy. These data indicate that chromosomal shattering may occur in association with trisomy rescue in the early postzygotic stage.
Cytogenet Genome Res

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IJMS, Vol. 18, Pages 2244: Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A-Double Mutant

IJMS, Vol. 18, Pages 2244: Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A-Double Mutant

International Journal of Molecular Sciences doi: 10.3390/ijms18112244

Authors: Edson Ramírez-Nava Daniel Ortega-Cuellar Hugo Serrano-Posada Abigail González-Valdez America Vanoye-Carlo Beatriz Hernández-Ochoa Edgar Sierra-Palacios Jessica Hernández-Pineda Eduardo Rodríguez-Bustamante Roberto Arreguin-Espinosa Jesús Oria-Hernández Horacio Reyes-Vivas Jaime Marcial-Quino Saúl Gómez-Manzo

Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme that plays a crucial role in the regulation of cellular energy and redox balance. Mutations in the gene encoding G6PD cause the most common enzymopathy that drives hereditary nonspherocytic hemolytic anemia. To gain insights into the effects of mutations in G6PD enzyme efficiency, we have investigated the biochemical, kinetic, and structural changes of three clinical G6PD variants, the single mutations G6PD A+ (Asn126AspD) and G6PD Nefza (Leu323Pro), and the double mutant G6PD A− (Asn126Asp + Leu323Pro). The mutants showed lower residual activity (≤50% of WT G6PD) and displayed important kinetic changes. Although all Class III mutants were located in different regions of the three-dimensional structure of the enzyme and were not close to the active site, these mutants had a deleterious effect over catalytic activity and structural stability. The results indicated that the G6PD Nefza mutation was mainly responsible for the functional and structural alterations observed in the double mutant G6PD A−. Moreover, our study suggests that the G6PD Nefza and G6PD A− mutations affect enzyme functions in a similar fashion to those reported for Class I mutations.

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Clinical Decision Support System for Diabetes Based on Ontology Reasoning and TOPSIS Analysis

Introduction. Although a number of researchers have considered the positive potential of Clinical Decision Support System (CDSS), they did not consider that patients' attitude which leads to active treatment strategies or HbA1c targets. Materials and Methods. We adopted the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) published to propose an HbA1c target and antidiabetic medication recommendation system for patients. Based on the antidiabetic medication profiles, which were presented by the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE), we use TOPSIS to calculate the ranking of antidiabetic medications. Results. The endocrinologist set up ten virtual patients' medical data to evaluate a decision support system. The system indicates that the CDSS performs well and is useful to 87%, and the recommendation system is suitable for outpatients. The evaluation results of the antidiabetic medications show that the system has 85% satisfaction degree which can assist clinicians to manage T2DM while selecting antidiabetic medications. Conclusions. In addition to aiding doctors' clinical diagnosis, the system not only can serve as a guide for specialty physicians but also can help nonspecialty doctors and young doctors with their drug prescriptions.

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A Data-Driven Customer Quality of Experience System for a Cellular Network

Improving customer-perceived service quality is a critical mission of telecommunication service providers. Using 35 billion call records, we develop a call quality score model to predict customer complaint calls. The score model consists of two components: service quality score and connectivity score models. It also incorporates human psychological impacts such as the peak and end effects. We implement a large-sized data processing system that manages real-time service logs to generate quality scores at the customer level using big data processing technology and analysis techniques. The experimental results confirm the validity of the developed model in distinguishing probable complaint callers. With the adoption of the system, the first call resolution rate of the call center increased from 45% to 73%, and the field engineer dispatch rate from 46% to 25%.

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Mechanical Property and Analysis of Asphalt Components Based on Molecular Dynamics Simulation

The asphalt-aggregate interface interaction plays a significant role in the overall performances of asphalt mixture. In order to analyze the chemical constitution of asphalt effects on the asphalt-aggregate interaction, the average structure C64H52S2 is selected to represent the asphalt, and the colloid, saturated phenol, and asphaltene are selected to represent the major constitutions in asphalt. The molecular models are established for the three compositions, respectively, and the Molecular Dynamics (MD) simulation was conducted for the three kinds of asphaltene-aggregate system at different presses. Comparing the value of Young modulus of these three polymers, the maximum modulus value of asphaltene was 2.80 GPa, the modulus value of colloid was secondary, and the minimum modulus of saturated phenol was 0.52 GPa. This result corresponds to conventional understanding.

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Semantics-Powered Healthcare Engineering and Data Analytics

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Automatic Supervision of Temperature, Humidity, and Luminance with an Assistant Personal Robot

Smart environments and Ambient Intelligence (AmI) technologies are defining the future society where energy optimization and intelligent management are essential for a sustainable advance. Mobile robotics is also making an important contribution to this advance with the integration of sensors and intelligent processing algorithms. This paper presents the application of an Assistant Personal Robot (APR) as an autonomous agent for temperature, humidity, and luminance supervision in human-frequented areas. The robot multiagent capabilities allow gathering sensor information while exploring or performing specific tasks and then verifying human comfortability levels. The proposed methodology creates information maps with the distribution of temperature, humidity, and luminance and interprets such information in terms of comfort and warns about corrective actuations if required.

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Investigation and Assessment of the CFD for Horizontal Flow in the VHTR Core

A nuclear power station using gas as a cooling medium has attracted so much attention because it offers high efficiency and greater safety. For a nuclear station that operates at a very high temperature, a gas-cooled reactor is fueled by uranium, moderated by graphite, and customarily cooled by helium. Nevertheless, throughout the operation, the bypass flow might be a result of a change in graphite shape that is caused by neutron damage. Core bypass and cross flows are significant elements to consider since the cross gap set hurdles to the flow field that are capable of diverting sufficient amount of coolant from reactor core location and initiating a possible fuel overheating. However, there is a great need to sufficiently validate this method by carrying out a thorough evaluation based on working environment analysis. Comparing the computed results with the existing data from Groehn's NHDA PMR-200 study was the only way to validate data. A model simulation was performed on a two-prismatic fuel block with a cross gap to examine the gaping size effect. Finally, the prediction methods for horizontal flow phenomena using a CFD technique and the field investigation results from the VHTR core were verified, and the identification of the horizontal flow behavior played a vital role in investigating the coolant velocity and pressure distribution in the horizontal gap.

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Systemic Treatment of Metastatic Conjunctival Melanoma

Conjunctival melanoma (CM) is an exceptionally rare tumor, with a propensity for local and distant recurrence, with the lungs, skin, liver, and brain being the most common sites of metastasis. Recent progress in systemic treatments, with checkpoint inhibitors and targeted therapies blocking BRAF and MEK, has redefined the standard of care of advanced unresectable and metastatic melanoma. Although most trials did not include patients with conjunctival melanoma, its close molecular and genetic relationship to cutaneous melanoma might suggest a similar response to these novel agents. The authors describe two uncommon cases of metastatic conjunctival melanomas with distinct genetic profiles and, as such, submitted to different systemic treatments.

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Theory of Nonlinear Guided Electromagnetic Waves in a Plane Two-Layered Dielectric Waveguide

Propagation of transverse electric electromagnetic waves in a homogeneous plane two-layered dielectric waveguide filled with a nonlinear medium is considered. The original wave propagation problem is reduced to a nonlinear eigenvalue problem for an equation with discontinuous coefficients. The eigenvalues are propagation constants (PCs) of the guided waves that the waveguide supports. The existence of PCs that do not have linear counterparts and therefore cannot be found with any perturbation method is proven. PCs without linear counterparts correspond to a novel propagation regime that arises due to the nonlinearity. Numerical results are also presented; the comparison between linear and nonlinear cases is made.

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Targeted Resequencing of Putative Growth-Related Genes Using Whole Exome Sequencing in Patients with Severe Primary IGF-I Deficiency

Background/Aims: To elucidate the genetic causes of severe primary insulin-like growth factor-I deficiency (SPIGFD) by systematic, targeted, next-generation sequencing (NGS)-based resequencing of growth-related genes. Methods: Clinical phenotyping followed by NGS in 17 families including 6 affected sib pairs. Results: We identified disease-causing, heterozygous, de novo variants in HRAS (p.Gly13Cys) and FAM111A (p.Arg569His) in 2 male patients with syndromic SPIGFD. A previously described homozygous GHR nonsense variant was detected in 2 siblings of a consanguineous family (p.Glu198*). Furthermore, we identified an inherited novel variant in the IGF2 gene (p.Arg156Cys) of a maternally imprinted gene in a less severely affected father and his affected daughter. We detected 2 other novel missense variants in SH2B1 and SOCS2, both were inherited from an unaffected parent. Conclusions: Screening of growth-related genes using NGS-based, large-scale, targeted resequencing identified disease-causing variants in HRAS, FAM111A, and GHR. Considering the increased risk of subjects with HRAS mutations for neoplasms, close clinical monitoring and a thorough discussion of the risk/benefit ratio of the treatment with recombinant IGF-I is mandatory. Segregation analysis proved to be critical in the interpretation of potential SPIGFD-associated gene variations.
Horm Res Paediatr

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Sodium Chloride Supplementation Is Not Routinely Performed in the Majority of German and Austrian Infants with Classic Salt-Wasting Congenital Adrenal Hyperplasia and Has No Effect on Linear Growth and Hydrocortisone or Fludrocortisone Dose

Introduction: Sodium chloride supplementation in salt-wasting congenital adrenal hyperplasia (CAH) is generally recommended in infants, but its implementation in routine care is very heterogeneous. Objective: To evaluate oral sodium chloride supplementation, growth, and hydrocortisone and fludrocortisone dose in infants with salt-wasting CAH due to 21-hydroxylase in 311 infants from the AQUAPE CAH database. Results: Of 358 patients with classic CAH born between 1999 and 2015, 311 patients had salt-wasting CAH (133 females, 178 males). Of these, 86 patients (27.7%) received oral sodium chloride supplementation in a mean dose of 0.9 ± 1.4 mmol/kg/day (excluding nutritional sodium content) during the first year of life. 225 patients (72.3%) were not treated with sodium chloride. The percentage of sodium chloride-supplemented patients rose from 15.2% in children born 1999–2004 to 37.5% in children born 2011–2015. Sodium chloride-supplemented and -unsupplemented infants did not significantly differ in hydrocortisone and fludrocortisone dose, target height-corrected height-SDS, and BMI-SDS during the first 2 years of life. Conclusion: In the AQUAPE CAH database, approximately one-third of infants with salt-wasting CAH receive sodium chloride supplementation. Sodium chloride supplementation is performed more frequently in recent years. However, salt supplementation had no influence on growth, daily fludrocortisone and hydrocortisone dose, and frequency of adrenal crisis.
Horm Res Paediatr

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Insights from a rare genetic disease may help treat multiple myeloma

A new class of drugs for blood cancers such as leukaemia and multiple myeloma is showing promise. But it is hobbled by a problem that also plagues other cancer drugs: targeted cells can develop resistance. Now scientists, reporting in ACS Central...

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Researchers engineer complex TCR immunotherapy that may target relapsing leukaemia

Researchers at Fred Hutchinson Cancer Research Center and the University of Washington have developed a novel way to genetically engineer T cells that may be effective for treating and preventing leukaemia relapse. The findings, published online in the...

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A Blueprint to Advance Colorectal Cancer Immunotherapies

Fight Colorectal Cancer (Fight CRC) and the Cancer Research Institute (CRI), have announced "A Blueprint to Advance Colorectal Cancer Immunotherapies" is published in the journal Cancer Immunology Research. The article is the culmination of an over...

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The Bright Side of Jesus, oder Einführung in die Brianologie. Wirkungsgeschichtliche und theologische Annäherungen an “Monty Python's Life of Brian”

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Stromkonzerne auf dem Prüfstand

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Editorial: Telling Stories about Self in Digital Contexts: Same, Same, but Different?

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Larval honey bees infected with Nosema ceranae have increased vitellogenin titers as young adults

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Exceptional appendage and soft-tissue preservation in a Middle Triassic horseshoe crab from SW China

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Removal of cationic and anionic heavy metals from water by 1D and 2D-carbon structures decorated with magnetic nanoparticles

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Bisphenol A in eggs causes development-specific liver molecular reprogramming in two generations of rainbow trout

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In situ TEM observation of alpha-particle induced annealing of radiation damage in Durango apatite

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Psychotropic in the environment: risperidone residues affect the behavior of fish larvae

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Evaluating anthropogenic threats to endangered killer whales to inform effective recovery plans

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Evaluating different approaches to non-destructive nitrogen status diagnosis of rice using portable RapidSCAN active canopy sensor

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Field evidence for transfer of plastic debris along a terrestrial food chain

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Self-cleaning liner for halogenated hydrocarbon control in landfill leachate

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What Is New? Recent Knowledge on Fungal Extracellular Vesicles

Abstract

Purpose of Review

Fungal extracellular vesicles (EVs) were first characterized a decade ago. Knowledge in this field expanded rapidly and although several questions remain unanswered, it is now clear that EVs play fundamental biological roles in fungi. In this manuscript, we update the reader with the most recent information on the participation of EVs in fungal physiology and pathogenesis.

Recent Findings

Fungal EVs were initially associated with the transport of macromolecules across the cell wall and extracellular delivery of virulence factors. However, recent findings indicate that they might also participate in prion transmission, response to nutrient availability, RNA export, morphological transition, and stimulation of different phagocytes.

Summary

The recent literature on fungal EVs reinforces the perception that these compartments are involved in intercellular communication and may represent interesting targets for antifungal development and tools for the generation of fungal vaccines.

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Candida auris : Antifungal Multi-Resistant Emerging Yeast

Abstract

Purpose of Review

The purpose of this review is to contribute to the knowledge about the existence of Candida auris as an emerging pathogenic fungus, multi-resistant to antifungal, and causing health care-associated infections (HCAI).

Recent Findings

C. auris emerges as yeast with clonal transmission resistance to three families of commonly used antifungals, mainly azoles (fluconazole and voriconazole), diminishing therapeutic options for the treatment of fungal infections. In 2009, C. auris was isolated for the first time in Japan and by the time of this review, it has been reported in different countries in Africa, America, Asia, and Europe.

Summary

It is important to identify yeasts of the Candida genus up to species, to perform susceptibility tests and to implement surveillance, prevention, and control measures, to minimize the global spread of this fungus, due to its impact on public health.

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A Comprehensive Analysis of MALDI-TOF MS and Ribosomal DNA Sequencing for Identification of Clinical Yeasts

Abstract

Purpose of Review

The purpose of this study is to analyze the current knowledge about matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) identification of clinical yeasts comparing with the ribosomal DNA sequencing identification. We also review the lasts taxonomical and nomenclature changes of clinical yeasts.

Recent Findings

In most studies, the two main commercially available, MALDI Biotyper and VITEK MS, correctly identified more than 90% of yeasts isolates. Most drawbacks are due to low discrimination between closely related species or due to a lack of the reference main spectra (MSP) in the database. The addition of MSPs in the databases improves the performance.

Summary

MALDI-TOF MS has proven to be good for the identification of clinical yeasts and to differentiate some closely related species or species undifferentiated by conventional techniques. However, some species remain difficult to differentiate by this technique and should be identified by ribosomal DNA sequencing. Accurate and rapid yeasts identification could improve the management of patients with yeasts infections.

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Ultrasound detects muscle changes in ICU patients

Using ultrasound to evaluate changes to the skeletal muscles after trauma may...

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Related Reading:

How ultrasound can trigger pain relief

U.K. issues new ultrasound guidelines

3D ultrasound quantifies subclinical atherosclerosis

Munich team develops handheld scanner

Ultrasound-induced drug uptake requires caution

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Reuters: Siemens IPO moves ahead

German industrial giant Siemens AG continues to make progress in planning for...

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Related Reading:

Siemens debuts new PET/CT system at EANM 2017

Siemens to place new SPECT/CT scanner in U.K.

Siemens exec: AI will have massive effect on radiology

Siemens 7T MRI gets CE Mark for clinical use

Siemens health posts revenues, profit gain in Q3, plans IPO

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Introduzione

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Standard Symptom Inventories for Asylum Seekers in a Psychiatric Hospital: Limited Utility Due to Poor Symptom Validity

Abstract

We examined symptom validity in two samples (Ns = 27 and 35) of asylum seekers who had been admitted to a psychiatric facility. Considerable proportions over-endorsed atypical symptoms (63 and 83%, respectively) and underperformed on a simple forced-choice task requiring the identification of basic emotions (41 and 71%, respectively). Over-endorsement and underperformance were unrelated to Dutch language proficiency but were related to raised scores on standard symptom inventories commonly used to assess psychiatric symptoms of asylum seekers. This pattern of findings casts doubts on attempts to monitor symptom severity and treatment progress in psychiatric asylum seekers without taking symptom validity into account.

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Treatment of Glioblastoma in Older Adults

Abstract

Glioblastoma is the most common primary malignant brain tumor diagnosed in the USA and is associated with a poor prognosis. The outcomes in elderly patients (more than 65 years of age) are worse when compared to those younger than age 65 at the time of diagnosis. Older patients are not always offered treatments that would otherwise be considered standard of care due to comorbidities and concerns about toxicity and tolerability. The initial European Organization for Research and Treatment of Cancer study that led to approval of temozolomide in glioblastoma excluded patients more than 70 years of age. This review outlines challenges that arise in the treatment of glioblastoma in the elderly population and discusses results of recent studies that established the role of adjuvant chemotherapy in addition to radiation and surgery. There is evidence that these patients can benefit from a more aggressive and safe resection, from hypofractionated radiation treatments, and from adjuvant temozolomide.

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Plans to sell off NHS land—ludicrous financial idiocy

Naylor and Chand debate plans to sell off NHS land.1 Three concepts underpin the Naylor report: freeing up public land to build housing to solve the housing crisis; new models of care have different...

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Treating pain on skin graft donor sites: Review and clinical recommendations

ABSTRACT: Split-thickness skin grafting is the most common reconstructive procedure in managing burn injuries. Harvesting split-thickness skin creates a new partial thickness wound referred to as the donor site. Pain at the donor site is reported to be one of the most distressing symptoms during the early postoperative period. Here, we (a) identify strategies for managing donor site pain, (b) assess the quality of individual studies, and (c) formulate evidence-based recommendations based on the amount and consistency of evidence. Our analysis revealed five distinct approaches to minimize donor site pain. These include: continuous subcutaneous local anesthetic infusion (three studies), subcutaneous anesthetic injection (five studies), topical agents (six studies), nonpharmacological interventions (three studies), and wound dressings (18 studies). Available randomized control trials typically evaluated pain on standardized scales (i.e. Visual Analog Scale, Numerical Rating Scale), and compared the experimental group with standard care. Recommended treatments include: (a) subcutaneous anesthetic injection of adrenaline-lidocaine; (b) ice application; (c) topical agents, such as lidocaine and bupivacaine; and (d) hydrocolloid- and polyurethane-based wound dressings accompanied with fibrin sealant. Methodologically sound randomized control trials examining the efficacy of modified tumescent solution, ropivacaine, plasma therapy, noncontact ultrasound, and morphine gels are lacking and should be a priority for future research.

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Basil A. Pruitt, Jr., MD, and the US Army Institute for Surgical Research: Five decades of science, clinical care, mentorship, and leadership

Over the past half century, Dr. Basil A. Pruitt, Jr., a great citizen, surgeon, innovator, mentor, and leader, transformed our world through his dogged commitment to science and service to humanity. Dr. Pruitt's contribution lives on in the work of the US Army Institute of Surgical Research and the surgeons, physicians and scientists he shaped and inspired. (C) 2017 Lippincott Williams & Wilkins, Inc.

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Thoracoscopic purse-string suture technique for managing superior vena caval impalement from central venous catheterization

No abstract available

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The renaissance man of burn surgery: Basil A. Pruitt, Jr.

Dr. Basil A. Pruitt Jr., a consummate clinical and translational surgeon-scientist, has spent over half a century at the forefront of an advancing standard of burn care. Commanding the US Army Institute for Surgical Research in San Antonio, he trained generations of leading burn clinicians and allied scientists. At his direction, there were forged discoveries in resuscitation from shock, treatment of inhalation injury, control of burn-related infections, prevention of iatrogenic complications, and understanding the sympathetic, endocrine, and immune responses to burn injury. Most consequentially, this team was among the first to recognize and define alterations in the basal metabolic rate and thermoregulation consequent to burn injury. These investigations prompted groundbreaking insights into the coordinated nervous, autonomic, endocrine, immune, and metabolic outflows that a severely burned patient uses to remain alive and restore homeostasis. Marking his scientific consequence, many of his reports continue to bear fruit when viewed through a contemporary lens. This article summarizes some of the major findings of his career thus far and is intended to complement a Festschrift recently held in his honor. (C) 2017 Lippincott Williams & Wilkins, Inc.

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Buddy-aid battlefield pain management

No abstract available

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Building on the legacy of Dr. Basil A. Pruitt, Jr., at the US Army Institute of Surgical Research during the wars in Iraq and Afghanistan

No abstract available

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Quality, reliability, repeatability—What about excellence?

Today, I will be giving a general overview of the quality question. I will divide quality into four topics: first essential element-data, second essential element-process, third essential element-culture, and hidden dangers. We were fairly "high on the hog" in the House of Surgery in the late 20th century but then came the Institute of Medicine (IOM) reports. Partly in response to the IOM reports, we have discussed incessantly airplanes and aircrews. However, this is not the only challenge for in addition to this quality problem, we have a cost problem. These intersecting challenges appear insurmountable, but there is hope. We need better data, better process, and an evolution of our culture. The easiest type of data to collect is process measure data. We should all be aware of Surgical Care Improvement Project (SCIP), Physician Reporting Quality System (PRQS), and Merit-Based Incentive Payment System (MIPS). On the performance measures side of the house, the National Surgical Quality Incentive Program and the University Health-System Collaborative are major initiatives. There is an abundance of data, but if we are to improve care, we also need a good process. There is increased attention into process such as checklists, bundles, and standard operating procedures. Data and process is important, but we also need to be strategic. For a process to be effective, it needs to be part of a coherent strategy. And once we have data, process, and strategic thinking, we come to the third essential element, which is culture. Are there some dangers in embracing these new approaches? In a word, yes. We cannot abandon the traditional role of surgeons as leaders. We need to think about training the next generation of surgeons and the risk that this over-systemization of care begets. Surgeons have always led change, so though these new challenges seem profoundly disruptive, I am sure that we will again rise to the task. (C) 2017 Lippincott Williams & Wilkins, Inc.

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The role of splenic angioembolization as an adjunct to nonoperative management of blunt splenic injuries: A systematic review and meta-analysis

BACKGROUND: Nonoperative management (NOM) of hemodynamically normal patients with blunt splenic injury (BSI) is the standard of care. Guidelines recommend additional splenic angioembolization (SAE) in patients with American Association for the Surgery of Trauma (AAST) Grade IV and Grade V BSI, but the role of SAE in Grade III injuries is unclear and controversial. The aim of this systematic review was to compare the safety and effectiveness of SAE as an adjunct to NOM versus NOM alone in adults with BSI. METHODS: A systematic literature search (Medline, Embase, and CINAHL) was performed to identify original studies that compared outcomes in adult BSI patients treated with SAE or NOM alone. Primary outcome was failure of NOM. Secondary outcomes included morbidity, mortality, hospital length of stay, and transfusion requirements. Bayesian meta-analyses were used to calculate an absolute (risk difference) and relative (risk ratio [RR]) measure of treatment effect for each outcome. RESULTS: Twenty-three studies (6,684 patients) were included. For Grades I to V combined, there was no difference in NOM failure rate (SAE, 8.6% vs NOM, 7.7%; RR, 1.09 [0.80–1.51]; p = 0.28), mortality (SAE, 4.8% vs NOM, 5.8%; RR, 0.82 [0.45–1.31]; p = 0.81), hospital length of stay (11.3 vs 9.5 days; p = 0.06), or blood transfusion requirements (1.8 vs 1.7 units; p = 0.47) between patients treated with SAE and those treated with NOM alone. However, morbidity was significantly higher in patients treated with SAE (SAE, 38.1% vs NOM, 18.6%; RR, 1.83 [1.20–2.66]; p

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Defining the gastroesophageal junction in trauma: Epidemiology and management of a challenging injury

BACKGROUND: Injuries to the gastroesophageal (GE) junction are infrequently encountered because of the high mortality of associated injuries. Consequently, there is a paucity of literature on the patient demographics and treatment options. The aim of this study was to examine the epidemiology, surgical management, and outcomes of these rare injuries. METHODS: Patients presenting to LAC + USC Medical Center (January 2008 to August 2016) with traumatic esophageal or gastric injury (DRG International Classification of Diseases—9th Rev.—Clinical Modification and 10th Rev. codes) were extracted from the trauma registry. Patient charts were reviewed, and all patients who sustained an injury to the GE junction were enrolled. Patient demographics, injury characteristics, procedures, and outcomes were analyzed. RESULTS: Of the 238 patients who sustained an injury to the esophagus or stomach during the study period, 28 (12%) were found to have a GE junction injury. Mean age was 26 years (range, 14–57 years), 89% male. Mechanism of injury was penetrating in 96% (n = 27), the majority of which were gunshot wounds (n = 22, 81%). Most patients (n = 18, 64%) were taken directly to the operating room. Ten (36%) underwent computed tomography scan before going to the operating room, all demonstrating a GE junction injury. All patients underwent repair via laparotomy. One (4%) also required thoracotomy to facilitate delayed reconstruction. GE junction injuries were typically managed with primary repair (n = 22, 79%). Associated injuries were frequent (n = 26, 93%), and injury severity was high (mean Injury Severity Score, 25 [9–75]). Mortality was 25% (n = 7), and all patients required intensive care unit admission. Most did not require total parenteral nutrition (n = 25, 89%) or a surgically placed feeding tube (n = 26, 93%). Of the 13 patients who presented for clinical follow-up, all but one (n = 12, 92%) were eating independently by the first clinic visit. CONCLUSION: GE junction injuries are uncommon and occur almost exclusively after penetrating trauma. Patients are severely injured with a high mortality rate and frequently have associated intracavitary injuries. Most can be fixed through the abdomen alone and do not require thoracotomy for repair. Despite the severity of injuries, the majority of survivors are eating independently by the first clinic visit. LEVEL OF EVIDENCE: Epidemiological, level V.

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Peripheral rapid infusion via the corpus cavernosum: An investigation of penile vascular access flow rates

No abstract available

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Development of the emergency preservation and resuscitation for cardiac arrest from trauma clinical trial

BACKGROUND: Patients who suffer a cardiac arrest from trauma rarely survive, even with aggressive resuscitation attempts, including an emergency department thoracotomy. Emergency Preservation and Resuscitation (EPR) was developed to utilize hypothermia to buy time to obtain hemostasis before irreversible organ damage occurs. Large animal studies have demonstrated that cooling to tympanic membrane temperature 10°C during exsanguination cardiac arrest can allow up to 2 hours of circulatory arrest and repair of simulated injuries with normal neurologic recovery. STUDY DESIGN: The Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma trial has been developed to test the feasibility and safety of initiating EPR. Select surgeons will be trained in the EPR technique. If a trained surgeon is available, the subject will undergo EPR. If not, the subject will be followed as a control subject. For this feasibility study, 10 EPR and 10 control subjects will be enrolled. STUDY PARTICIPANTS: Study participants will be those with penetrating trauma who remain pulseless despite an emergency department thoracotomy. INTERVENTIONS: Emergency Preservation and Resuscitation will be initiated via an intra-aortic flush of a large volume of ice-cold saline solution. Following surgical hemostasis, delayed resuscitation will be accomplished with cardiopulmonary bypass. OUTCOME MEASURES: The primary outcome will be survival to hospital discharge without significant neurologic deficits. Secondary outcomes include long-term survival and functional outcome. IMPLICATIONS: Once data from these 20 subjects are reviewed, revisions to the inclusion criteria and/or the EPR technique may then be tested in a second set of EPR and control subjects.

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Penetrating injuries to the duodenum: An analysis of 879 patients from the National Trauma Data Bank, 2010 to 2014

BACKGROUND: Despite wide belief that the duodenal Organ Injury Scale has been validated, this has not been reported in the published literature. Based on clinical experience, we hypothesize that the American Association for Surgery of Trauma Organ Injury Scale (AAST-OIS) for duodenal injuries can independently predict mortality. Our objectives were threefold: (1) describe the national profile of penetrating duodenal injuries, (2) identify predictors of morbidity and mortality, and (3) validate the duodenum AAST-OIS as a statistically significant predictor of mortality. METHODS: Using the Abbreviated Injury Scale 2005 and International Classification of Diseases—9th Rev.—Clinical Modification (ICD-9-CM) E-codes, we identified 879 penetrating duodenal trauma patients from the National Trauma Data Bank between 2010 and 2014. We controlled patient-level covariates of age, biological sex, systolic blood pressure (SBP), Glasgow Coma Scale (GCS) score, pulse, Injury Severity Score (ISS), and Organ Injury Scale (OIS) grade. We estimated multivariable generalized linear mixed models to account for the nesting of patients within trauma centers. RESULTS: Our results indicated an overall mortality rate of 14.4%. Approximately 10% of patients died within 24 hours of admission, of whom 76% died in the first 6 hours. Patients averaged approximately five associated injuries, 45% of which involved the liver and colon. Statistically significant independent predictors of mortality were firearm mechanism, SBP, GCS, pulse, ISS, and AAST-OIS grade. Specifically, odds of death were decreased with 10 mm Hg higher admission SBP (13% decreased odds), one point higher GCS (14.4%), 10-beat lower pulse (8.2%), and 10-point lower ISS (51.0%). CONCLUSION: This study is the first to report the national profile of penetrating duodenal injuries. Using the National Trauma Data Bank, we identified patterns of injury, predictors of outcome, and validated the AAST-OIS for duodenal injuries as a statistically significant predictor of morbidity and mortality. LEVEL OF EVIDENCE: Epidemiologic/Prognostic, level IV.

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Risk Evaluation of Debris Flow Hazard Based on Asymmetric Connection Cloud Model

Risk assessment of debris flow is a complex problem involving various uncertainty factors. Herein, a novel asymmetric cloud model coupled with connection number was described here to take into account the fuzziness and conversion situation of classification boundary and interval nature of evaluation indicators for risk assessment of debris flow hazard. In the model, according to the classification standard, the interval lengths of each indicator were first specified to determine the digital characteristic of connection cloud at different levels. Then the asymmetric connection clouds in finite intervals were simulated to analyze the certainty degree of measured indicator to each evaluation standard. Next, the integrated certainty degree to each grade was calculated with corresponding indicator weight, and the risk grade of debris flow was determined by the maximum integrated certainty degree. Finally, a case study and comparison with other methods were conducted to confirm the reliability and validity of the proposed model. The result shows that this model overcomes the defect of the conventional cloud model and also converts the infinite interval of indicators distribution into finite interval, which makes the evaluation result more reasonable.

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Echinacoside Alleviates UVB Irradiation-Mediated Skin Damage via Inhibition of Oxidative Stress, DNA Damage, and Apoptosis

Ultraviolet B (UVB) irradiation has been known to cause skin damage, which is associated with oxidative stress, DNA damage, and apoptosis. Echinacoside is a phenylethanoid glycoside isolated from Herba Cistanches, which exhibits strong antioxidant activity. In this study, we evaluate the photoprotective effect of echinacoside on UVB-induced skin damage and explore the potential molecular mechanism. BALB/c mice and HaCaT cells were treated with echinacoside before UVB exposure. Histopathological examination was used to evaluate the skin damage. Cell viability, lactate dehydrogenase (LDH) levels, antioxidant enzyme activities, reactive oxygen species (ROS) generation, DNA damage, and apoptosis were measured as well. Western blot was used to measure the expression of related proteins. The results revealed that pretreatment of echinacoside ameliorated the skin injury; attenuated oxidative stress, DNA damage, and apoptosis caused by UVB exposure; and normalized the protein levels of ATR, p53, PIAS3, hnRNP K, PARP, and XPA. To summarize, echinacoside is beneficial in the prevention of UVB-induced DNA damage and apoptosis of the skin in vivo and in vitro.

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Interactive -Means Clustering Method Based on User Behavior for Different Analysis Target in Medicine

Clustering algorithm as a basis of data analysis is widely used in analysis systems. However, as for the high dimensions of the data, the clustering algorithm may overlook the business relation between these dimensions especially in the medical fields. As a result, usually the clustering result may not meet the business goals of the users. Then, in the clustering process, if it can combine the knowledge of the users, that is, the doctor's knowledge or the analysis intent, the clustering result can be more satisfied. In this paper, we propose an interactive -means clustering method to improve the user's satisfactions towards the result. The core of this method is to get the user's feedback of the clustering result, to optimize the clustering result. Then, a particle swarm optimization algorithm is used in the method to optimize the parameters, especially the weight settings in the clustering algorithm to make it reflect the user's business preference as possible. After that, based on the parameter optimization and adjustment, the clustering result can be closer to the user's requirement. Finally, we take an example in the breast cancer, to testify our method. The experiments show the better performance of our algorithm.

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Aptamers as the Agent in Decontamination Assays (Apta-Decontamination Assays): From the Environment to the Potential Application In Vivo

The binding specificity and affinity of aptamers have long been harnessed as the key elements in the development of aptamer-based assays, particularly aptasensing application. One promising avenue that is currently explored based on the specificity and affinity of aptamers is the application of aptamers in the decontamination assays. Aptamers have been successfully harnessed as the decontamination agents to remove contaminants from the environment and to decontaminate infectious elements. The reversible denaturation property inherent in aptamers enables the repeated usage of aptamers, which can immensely save the cost of decontamination. Analogous to the point-of-care diagnostics, there is no doubt that aptamers can also be deployed in the point-of-care aptamer-based decontamination assay, whereby decontamination can be performed anywhere and anytime for instantaneous decision-making. It is also prophesied that aptamers can also serve more than as a decontaminant, probably as a tool to capture and kill hazardous elements, particularly pathogenic agents.

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End-to-End Data Rate Performance of Decode-and-Forward Relaying with Different Resource Allocation Schemes

This paper studies the end-to-end (e2e) data rate of dual-hop Decode-and-Forward (DF) infrastructure relaying under different resource allocation schemes. In this context, we first provide a comparative analysis of the optimal resource allocation scheme with respect to several other approaches in order to provide insights into the system behavior and show the benefits of each alternative. Then, assuming the optimal resource allocation, a closed form expression for the distribution of the mean and outage data rates is derived. It turns out that the corresponding mean e2e data rate formula attains an expression in terms of an integral that does not admit a closed form solution. Therefore, a tight lower bound formula for the mean e2e data rate is presented. Results can be used to select the most convenient resource allocation scheme and perform link dimensioning in the network planning phase, showing the explicit relationships that exist between component link bandwidths, SNR values, and mean data rate.

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Rotating Arm-Based Experimental Study on Droplet Behavior in the Shoulder Region of an Aircraft Aerodynamic Surface

An experimental study has been performed on water droplet deformation in the shoulder region of an airfoil. The experiments have been carried out in a rotating arm facility 2.2 m long and able to rotate up to 400 rpm (90 m/s). A blunt airfoil model (chord length equal to 0.468 m) was placed at the end of the arm. A droplet generator was used to generate a stream of water droplets with an initial diameter of 1000 μm. An imaging system was set up to record the trajectories and deformations of the droplets in three different regions close to the airfoil shoulder. The base flow field was characterized using a particle image velocimetry system. The experiments show that droplet deformation results in the shoulder region of the airfoil are different from those pertaining to the leading edge region. In particular, droplets in the shoulder region tend to rotate to the direction of the incoming airfoil which generates an interference effect between the droplets that make up the stream. These differences have been quantified applying an existing theoretical model specifically developed for the leading edge region to the results obtained in the present study.

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Solvability of Some Two-Point Fractional Boundary Value Problems under Barrier Strip Conditions

Topological techniques are used to establish existence results for a class of fractional differential equations , with one of the following boundary value conditions: and or and where is a real number, is the conformable fractional derivative, and is continuous. The main conditions on the nonlinear term are sign conditions (i.e., the barrier strip conditions). The topological arguments are based on the topological transversality theorem.

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Review: Citizenship and the Pursuit of a Worthy Life

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'She was sensational:' New Brunswick dentist killed at conference in Alberta

New Brunswick dentist Cindy McCormick was a fearless, vibrant woman, known as much for belting out karaoke tunes as for constantly changing her colourful hairstyles. "She had it all: She was the jock, she was the brainiac, she was gorgeous.

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Risk factors and clinical outcomes of pediatric liver transplant recipients with post-transplant lymphoproliferative disease in a multi-ethnic Asian cohort

Abstract

Background

We aimed to evaluate clinical characteristics, risk factors, and disease outcomes for liver transplant recipients (LTR) with post-transplant lymphoproliferative disease (PTLD) at our center.

Methods

Retrospective review of data of all pediatric LTR (1991-2015) was conducted.

Results

The overall incidence of PTLD was 16.4% (18/110), the majority (13/18) were early lesions, while 3/18 were polymorphic/monomorphic PTLD. The risk factors significant on univariate analysis were as follows: mean age (years) at transplant (1.66 vs 4.76, P = .006); age < 2 years at transplant (odds ratio [OR] 3.53 [95% confidence interval [CI]: 1.16-10.73], P = .026); cytomegalovirus (CMV) primary infection (OR 11.39 [95%CI: 3.44-37.7], P <.001); recipient CMV seronegativity (OR 7.50 [95%CI: 2.02-27.78], P = .003); presence of CMV end-organ disease (OR 4.00 [95%CI: 1.22-13.16], P = .022); Chinese ethnicity; and higher mean duration of intravenous ganciclovir prophylaxis. In multivariate analysis, CMV primary infection (OR 5.22 [95%CI: 1.25-21.87], P = .024), CMV seronegativity (OR 5.91 [95%CI: 1.13-30.90, P = .035]), and having acute cellular rejections (ACR) prior to PTLD (OR 5.53 [95%CI: 1.43-21.48, P = .013]) were significant risk factors for PTLD, with the latter two factors having a synergistic effect in increasing PTLD risk in a stratified analysis. The final multivariate model in predicting the risk of PTLD, utilizing CMV primary infection, recipient CMV seronegativity, and ACR before PTLD as predictive variables, was statistically significant (likelihood ratio chi square statistic = 25.18, P < .0001 with df = 3).

Conclusions

We report a unique clinicopathologic and risk factor profile in our cohort –early lesion PTLD accounts for the majority and the incidence of monomorphic PTLD remains low. In addition, we show a synergism between CMV naivety and ACR on PTLD risk, a higher prevalence of gastrointestinal manifestations, and a lack of significant association with Epstein-Barr virus seronegativity.

This article is protected by copyright. All rights reserved.

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Adult T-Cell Leukemia/Lymphoma With Primary Lacrimal Gland Involvement.

A 69-year-old Japanese male presented with a 3-month history of bilateral ptosis with lacrimal gland bulge. He came from western Japan, an area endemic for human T-lymphotropic virus Type 1 infection. Physical examination and imaging revealed bilaterally enlarged lacrimal glands. Hematologic testing, biopsy with histopathology, and immunohistochemistry were all consistent with adult T-cell leukemia/lymphoma. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Single-Stage Repair of Palatal Fistula and Velopharyngeal Incompetence by the New L Flap.

Objective: To describe and assess the results of use of the new L-shaped posterior pharyngeal flap for repair of both palatal fistula and velopharyngeal incompetence. Methods: This study included 10 patients who were diagnosed to have soft palate fistula and persistent velopharyngeal insufficiency (VPI). L-shaped superiorly based pharyngeal flap was harvested from oropharynx and inserted into the soft palate closing the fistula after fistula trimming. The palatal part of the flap (transverse limb) was spread 1 cm horizontally and 1 cm in the anteroposterior direction in soft palate at fistula site closing it without tension. Prior to and after surgery, patients were assessed by examination, video-nasoendoscopy, and speech assessment. Results: Closure of the palatal fistula could be achieved in all patients. Postoperative speech assessment showed significant improvement in the nasal emission, resonance, intraoral pressure, and articulation defects. Grade 4 velopharyngeal valve closure (complete closure) could be achieved in all patients. No patients showed dehiscence (partial or total) of the flap and no obstructive sleep apnea reported. Conclusion: The new used L-shaped pharyngeal flap could properly close palatal fistula and correct velopharyngeal functions (closure and speech) in patients with persistent VPI with no reported significant complication and without the need for palatal dissection or flaps. (C) 2017 by Mutaz B. Habal, MD.

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Surgical Hypercorrection of Trigonocephaly: Evaluation of Surgical Outcomes.

Background: A lasting correction of trigonocephaly is difficult to achieve, as a durable correction requires significant expansion to overcome galeal restriction and soft tissue recoil of the scalp. High rates of relapse have been reported throughout the literature. The specific aim of this study was to determine if the senior author's method of "hypercorrection" decreases relapse and the need for subsequent revisional surgery. Methods: Patients who underwent operative correction of metopic craniosynostosis between 1988 and 2011 were reviewed. All patients underwent the "hypercorrection" technique performed by the senior author. Hypercorrection consisted of a fronto-orbital advancement of 2.5 to 3.5 cm and a concomitant hyperexpansion of bitemporal projection. Split cranial bone grafting ensured adequate coverage of the significantly expanded cranial vault. Only patients who had at least 5 years of follow-up were included for review of outcomes. Relapse was defined as recurrence of bitemporal constriction or lateral orbital retrusion, requiring surgical correction. Results: Fifty-eight patients met criteria. Mean age at the time of surgery was 11 months. Mean follow-up was 9.0 years. During this time, 2 patients exhibited relapse requiring camouflage procedures. Cranial bone defects were found in 4 patients (7%), 3 of whom underwent cranial bone grafting, while 1 underwent methylmethacrylate placement at an outside institution. One patient underwent fat grafting for areas of soft tissue irregularity. No patients exhibited persistent sequelae of hypercorrection significant enough to require repeat fronto-orbital advancement. Conclusion: Surgical hypercorrection of trigonocephaly seems to minimize relapse and the need for revision in long-term follow-up and is therefore an important technique to consider. (C) 2017 by Mutaz B. Habal, MD.

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Isolated Intraorbital Frontosphenoidal Synostosis.

Unilateral anterior plagiocephaly is most commonly the result of deformational plagiocephaly or unilateral coronal synostosis, a premature fusion of the frontoparietal suture. However, other sutures within the coronal ring have been implicated in producing anterior cranial asymmetries. These fusions can occur in isolation or in concert with adjacent sutures. The frontosphenoidal suture is one such suture within the coronal ring that has been involved both concomitantly with and independently of frontoparietal suture fusion. Although isolated frontosphenoidal synostosis has been presented previously in the literature, these reports include patients with fusion of the extraorbital portion of the frontosphenoidal suture. This clinical report presents the first clearly documented patient of isolated frontosphenoidal synostosis that occurs entirely within the intraorbital region. The patient presented to Plastic Surgery Clinic at 3 months of age with left frontal flattening, supraorbital rim retrusion, and temporal bulging that was noted soon after birth. Computed tomography analysis revealed an isolated fusion of the greater and lesser wings of the sphenoid bone to the frontal bone on the left side. The patient had no family history of cranial anomalies and genetic testing was negative for mutations. The infant was treated with a cranial orthotic for 3 months, underwent open fronto-orbital advancement and cranial vault remodeling at 6 months, and continued wearing a cranial orthotic for another 4.5 months. Following surgical and orthotic treatment, the patient achieved a satisfactory result. (C) 2017 by Mutaz B. Habal, MD.

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Positive Effect of Incubated Adipose-Derived Mesenchymal Stem Cells on Microfat Graft Survival.

Autologous fat grafting is commonly used for soft tissue augmentation, but its unpredictably high resorption rate remains a major limitation. Although adipose-derived mesenchymal stem cells (ASCs) are an attractive candidate for enhancing graft retention, their poor posttransplantation viability limits their application. The authors aimed to evaluate the effect of incubated ASCs on microfat graft survival in an immunocompromised mouse model. Lipoaspirates for microfat injection were collected from the wasted lower abdominal adipose tissues of 5 patients who had undergone breast reconstructive surgery with an abdominal flap. Adipose-derived mesenchymal stem cells were also isolated and proliferated from these fat tissues. Sixty athymic mice were randomly allocated to a control group (microfat grafting alone; n = 30) or ASCs group (microfat grafting plus simultaneous human ASCs injection; n = 30). The volume and weight of survived fat were measured at 8 and 16 weeks, and histopathological and immunologic staining was performed at 16 weeks. The survived fat volume of the ASCs group was significantly greater than that of the control group at 8 and 16 weeks, whereas the weight of survived fat tissues did not significantly differ. Histologic evaluation of the harvested fat indicated significantly higher levels of adipocytes, and fewer cysts and fibrosis in the tissues in the ASCs group than in the control group. The ASCs group also exhibited a significantly higher number of capillary vessels than the control group on CD31 and alpha-smooth muscle actin staining. In conclusion, transplanted fat survival is markedly higher when simultaneous microfat graft and ASCs injection were performed, as compared with that in the classical microfat graft alone method in mice; this improvement was primarily attributed to the increased ability to produce blood vessels. (C) 2017 by Mutaz B. Habal, MD.

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More Than Meets the Eye: The Effect of Intercanthal Distance on Perception of Beauty and Personality.

In judging normalcy, surgeons rely on established facial anthropometric measures and proportions. However, there exists a range of "normal," and a degree of disproportion may be considered more attractive. The authors set out to determine how changes in only intercanthal distance affect the layperson's perception of beauty and personality traits of a face. The authors used Amazon.com's Mechanical Turk (MTurk), a crowdsourcing tool, to determine how changes in intercanthal distance affect overall perception of beauty and personality. MTurk respondents provided demographic information and were asked to survey 16 female subjects, each digitally edited to be hypoteloric or hyperteloric. Data were collected from 490 MTurk crowd raters. Paired t test analysis found that respondents perceived subjects to be more submissive, friendly, and attractive with increased intercanthal distance (P 46 years of age were less likely to perceive a change in any of the 7 traits upon intercanthal widening, compared with respondents between 18 and 25 years of age (P

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An Algorithm for Managing Intraosseous Vascular Anomalies of the Craniofacial Skeleton.

Background: Intraosseous vascular anomalies (IOVA) are rare in the craniofacial skeleton and present a diagnostic and therapeutic challenge. This study aims to describe the clinical management based on a large case series. Methods: A retrospective chart review was performed and 9 IOVA were identified over a 15-year period. Data on demographics, diagnostic features, clinical management, and outcomes were reviewed. Results: Five frontal bone IOVA and 4 orbital IOVA were identified. The postoperative follow-up ranged from 4 months to 4 years. All 9 lesions were diagnosed with computed tomography (CT) imaging. Magnetic resonance imaging (MRI) was used to delineate soft tissue involvement in 2 patients presenting with oculo-orbital dystopia and ophthalmoplegia. En bloc excision was performed in all patients. Preoperative interventional embolization was critical in the successful resection of an orbital IOVA following 2 previously failed attempts that were aborted secondary to hemorrhage. Intraoperative 3-dimensional stereotactic navigation was used for the accurate en bloc excision of a frontal IOVA to prevent injury to the frontal sinus. Reconstruction of esthetic and functional deformities was successfully accomplished. Conclusion: The diagnosis of IOVA relies primarily on clinical assessment and CT imaging. Further interpretation of the involvement of periorbital, facial, and intracranial soft tissue is best defined by MRI. Multidisciplinary care with interventional radiology and neurosurgery must be considered for ensuring the safe and adequate en bloc excision of craniofacial IOVA. (C) 2017 by Mutaz B. Habal, MD.

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Alterations in Nasal Sensibility Following Calcium Hydroxyapatite Dorsal Augmentation.

Background: There are a many types of filler products that surgeons used for soft tissue augmentation. Soft Tissue Fillers, also known as injectable grafts, is a medical device implants. One of the materials used in soft tissue fillers is calcium hydroxylapatite (CaHA) that is commonly used for treating nasal deformities and nasal reshaping too. Calcium hydroxylapatite is a kind of mineral that can be found in human teeth and bones. It is considered long-lasting but nonpermanent filler and is biocompatible with human tissue. Aim: The aim of this study is to measure the alterations in sensibility and patient satisfaction following CaHA filler injection. Patient/Methods: In a prospective study, 30 patients who underwent CaHA filler injections from January to December 2016 at a Private Tertiary Care Hospital in Riyadh, Saudi Arabia were included. Results: Means and standard deviations were measured for pressure threshold values at each test area preprocedure 2 weeks after procedure (Table 1). Alterations between pre and postprocedure values were verified using the match-paired Student t test preprocedures. None of the patients had any subjective sensory symptoms. Majority of patients were extremely satisfied with the results. Conclusion: With correct anatomic knowledge and precise technique in doing the CaHA gel injection procedure, nasal sensibility will not be altered. In addition, injection of CaHA gel can be valuable tool for plastic surgeons to consider for nasal reshaping. (C) 2017 by Mutaz B. Habal, MD.

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Surgical Management of Migraine Headache.

Migraine surgery has been recently reported as an alternative to medical management to provide long-term relief in migraine sufferers. A prospective study was designed wherein patients diagnosed with migraine were screened for surgery by injecting botulinum toxin type A at the primary trigger site. Surgery consisted of corrugator supercilii muscle resection to decompress supra-trochlear and supra-orbital nerves with avulsion of zygomaticotemporal branch of trigeminal nerve. Using pre and postsurgery questionnaires, information regarding the degree of reduction of migraines with regard to severity and frequency; and surgical site problems was acquired. Thirty patients volunteered for migraine surgery. Mean migraine headaches reduced from 15.2 +/- 6.3 episodes per month to 1.9 +/- 2.4 episodes per month (P

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Rigid External Distractor-Aided Advancement After Simultaneously Performed LeFort-III Osteotomy and Fronto-Orbital Advancement.

Due to the complex development of the craniofacial skull, corrective surgery is a major challenge for patients with severe craniofaciostenosis. Although fronto-orbital advancement and simultaneous LeFort-III osteotomy in combination with distraction osteogenesis have been reported as a safe and successful method to obtain good esthetic and functional results, there is a lack of studies evaluating this method. Our retrospective study included 12 patients with syndromic craniofaciostenosis, who were primarily treated at our department in accordance with a standardized treatment protocol, consisting of a simultaneous fronto-orbital advancement with LeFort-III osteotomy in combination with a rigid external distractor (RED-II). Distraction distance, duration of operation, postoperative complications, perioperative hemoglobin concentration, esthetic outcome, and the subjective Whitaker Scale were used to evaluate the success of our surgical method. The esthetic outcome of all of our patients was assessed as good. Furthermore, the surgical outcome was assigned I for 11 patients and II for 1 patient, who suffered from wound healing disturbance at the left temporal site, which required revision 2 weeks postoperatively. The mean skeletal advancement of the midface was 16.4 mm, ranging from 12 to 20 mm. Our standardized treatment protocol, consisting of fronto-orbital advancement in combination with LeFort-III osteotomy and application of a rigid external distractor device (RED-III) for patients with severe syndromic craniofaciostenosis, goes along with low infection rates and more predictable and precise esthetic and functional outcomes than the conventional surgical technique without distraction osteogenesis. (C) 2017 by Mutaz B. Habal, MD.

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Targeted Intraoperative Radiotherapy Tumour Bed Boost during Breast-Conserving Surgery after Neoadjuvant Chemotherapy

Breast Care

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Chemical Composition and Pharmacological Effects of Geopropolis Produced by Melipona quadrifasciata anthidioides

Stingless bees produce geopropolis, which is popularly described for its medicinal properties, but for which few scientific studies have demonstrated pharmacological effects. The objective of this study was to investigate the chemical composition of the geopropolis of Melipona quadrifasciata anthidioides and to evaluate its antioxidant, antimutagenic, anti-inflammatory, and antimicrobial activities. The composition of the hydroethanolic extract of geopropolis (HEG) included di- and trigalloyl and phenylpropanyl heteroside derivatives, flavanones, diterpenes, and triterpenes. HEG showed antioxidant action via the direct capture of free radicals and by inhibiting the levels of oxidative hemolysis and malondialdehyde in human erythrocytes under oxidative stress. HEG also reduced the frequency of gene conversion and the number of mutant colonies of S. cerevisiae. The anti-inflammatory action of HEG was demonstrated by the inhibition of hyaluronidase enzyme activity. In addition, HEG induced cell death in all evaluated gram-positive bacteria, gram-negative bacteria, and yeasts, including clinical isolates with antimicrobial drug resistance. Collectively, these results demonstrate the potential of M. q. anthidioides geopropolis for the prevention and treatment of various diseases related to oxidative stress, mutagenesis, inflammatory processes, and microbial infections.

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Alternaria Mycotoxins in Food and Feed: An Overview

Alternaria is one of the major mycotoxigenic fungal genera with more than 70 reported metabolites. Alternaria mycotoxins showed notably toxicity, such as mutagenicity, carcinogenicity, induction of DNA strand break, sphingolipid metabolism disruption, or inhibition of enzymes activity and photophosphorylation. This review reports on the toxicity, stability, metabolism, current analytical methods, and prevalence of Alternaria mycotoxins in food and feed through the most recent published research. Half of the publications were focused on fruits, vegetables, and derived products—mainly tomato and apples—while cereals and cereal by-products represented 38%. The most studied compounds were alternariol, alternariol methyl ether, tentoxin, and tenuazonic acid, but altenuene, altertoxins (I, II, and III), and macrosporin have been gaining importance in recent years. Solid-liquid extraction (50%) with acetonitrile or ethyl acetate was the most common extraction methodology, followed by QuEChERS and dilution-direct injection (both 14%). High- and ultraperformance liquid chromatography coupled with tandem mass spectrometry was the predominant determination technique (80%). The highest levels of alternariol and alternariol methyl ether were found in lentils, oilseeds, tomatoes, carrots, juices, wines, and cereals. Tenuazonic acid highest levels were detected in cereals followed by beer, while alternariol, alternariol methyl ether, tenuazonic acid, and tentoxin were found in legumes, nuts, and oilseeds.

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Characterization and Analytical Separation of Fluorescent Carbon Nanodots

Carbon nanodots (C-dots) are recently discovered fluorescent carbon nanoparticles with typical sizes of

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New designs for new epidemiology.

No abstract available

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On the analysis of case-control studies in cluster-correlated data settings.

In resource-limited settings, long-term evaluation of national anti-retroviral treatment (ART) programs often relies on aggregated data, the analysis of which may be subject to ecological bias. As researchers and policy-makers consider evaluating individual-level outcomes such as treatment adherence or mortality, the well-known case-control design is appealing in that it provides efficiency gains over random sampling. In the context that motivates this paper, valid estimation and inference requires acknowledging any clustering although, to our knowledge, no statistical methods have been published for the analysis of case-control data for which the underlying population exhibits clustering. Furthermore, in the specific context of an ongoing collaboration in Malawi, rather than performing case-control sampling across all clinics, case-control sampling within clinics has been suggested as a more practical strategy. To our knowledge, while similar outcome-dependent sampling schemes have been described in the literature, a case-control design specific to correlated data settings is new. In this paper we describe this design, discuss balanced versus unbalanced sampling techniques, and provide a general approach to analyzing case-control studies in cluster-correlated settings based on inverse probability-weighted generalized estimating equations. Inference is based on a robust sandwich estimator with correlation parameters estimated to ensure appropriate accounting of the outcome-dependent sampling scheme. We conduct comprehensive simulations, based in part on real data on a sample of N=78,155 program registrants in Malawi between 2005-2007, to evaluate small-sample operating characteristics and potential trade-offs associated with standard case-control sampling or when case-control sampling is performed within clusters. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Outcome-related, auxiliary variable sampling designs for longitudinal binary data.

Background: Epidemiologists have long used case-control and related study designs to enhance variability of response and information available to estimate exposure-disease associations. Less has been done for longitudinal data. Methods: We discuss an epidemiological study design and analysis approach for longitudinal binary response data. We seek to gain statistical efficiency by over-sampling relatively informative subjects for inclusion into the sample. In this methodological demonstration, we develop this concept by sampling repeatedly from an existing cohort study to estimate the relationship of chronic obstructive pulmonary disease to past-year smoking in a panel of baseline smokers. To account for over-sampling, we describe a sequential offsetted regressions approach for valid inferences in this setting. Results: Targeted sampling can lead to increased statistical efficiency when combined with sequential offsetted regressions. Efficiency gains are degraded with increased prevalence of the disease response variable, with decreased association between the sampling variable and the response, and with other design and analysis parameters, providing guidance to those wishing to use these types of designs in the future. Conclusions: These designs hold promise for efficient use of resources in longitudinal cohort studies. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Extending the case-control design to longitudinal data: stratied sampling based on repeated binary outcomes.

We detail study design options that generalize case-control sampling when longitudinal outcome data are already collected as part of a primary cohort study, but new exposure data must be retrospectively processed for a secondary analysis. Furthermore, we assume that cost will limit the size of the subsample that can be evaluated. We describe a novel class of stratified outcome-dependent sampling designs for longitudinal binary response data where distinct strata are created for subjects who never, sometimes, and always experienced the event of interest during longitudinal follow-up. Individual designs within this class are differentiated by the stratum-specific sampling probabilities. We show for parameters associated with time-varying exposures, subjects who experience the event/outcome at some but not at all of the follow-up times (i.e., those who exhibit response variation) are highly informative. If the time-varying exposure varies exclusively within individuals (i.e., intraclass correlation coefficient is 0), then sampling all subjects with response variability can yield highly precise parameter estimates even when compared to an analysis of the original cohort. The flexibility of the designs and analysis procedures also permits estimation of parameters that correspond to time-fixed covariates, and we show that with an imputation-based estimation procedure, baseline covariate associations can be estimated with very high precision irrespective of the design. We demonstrate features of the designs and analysis procedures via a plasmode simulation using data from the Lung Health Study. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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