Immunotherapeutic Approaches to Biliary Cancer

Opinion statement

Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.

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Assessment of weight gain following adenotonsillectomy in children with Down syndrome

Adenotonsillectomy (T&A) has been associated with postoperative weight gain in children. The purpose of this study is to determine whether a similar association exists in children with Down syndrome (DS).

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Pathophysiology of esophageal impairment due to button battery ingestion

The increased use of button batteries with high energy densities in devices of daily life presents a high risk of injury, especially for toddlers and young children. If an accidental ingestion of a button battery occurs, this foreign body can become caught in the constrictions of the esophagus and cause serious damage to the adjacent tissue layers. The consequences can be ulcerations, perforations with fistula formation and damage to the surrounding anatomical structures. In order to gain a better understanding of the pathophysiology after ingestion, we carried out systematic studies on fresh preparations of porcine esophagi.

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Sleep quality and communication aspects in children

To correlate quality of life of children in terms of sleep, with their oral language skills, auditory processing and orofacial myofunctional aspects.

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Assessment of complete unilateral cleft lip and palate treatment outcome using EUROCRAN index and associated factors

Assessment of treatment outcome is the only non-invasive approach to identify the effects of cleft lip and palate repair and modify management accordingly. Here the aim is to assess the outcome of complete unilateral cleft lip and palate (CUCLP) patients using EUROCRAN index and to check whether there are any factors associated with the treatment outcome.

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Health, Wealth, and the U.S. Senate

New England Journal of Medicine, Ahead of Print.


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Immunotherapeutic Approaches to Biliary Cancer

Opinion statement

Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tjHA4b


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Recent Developments in Azaborinine Chemistry

Recent years have witnessed rapid advances in the field of BN/CC isosterism, in particular, in the case of azaborinines. Examples of each isomer have now been synthesized and characterized. This review provides a survey of the latest methods for the synthesis of new monocyclic B,N heterocycles, their reactivities and potential applications in biomedical and materials science.

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Immunotherapeutic Approaches to Biliary Cancer

Opinion statement

Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tjHA4b


from ! Medicine by Alexandros G. Sfakianakis via Αλέξανδρος Σφακιανάκης on Inoreader http://ift.tt/2sl7waQ
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Immunotherapeutic Approaches to Biliary Cancer

Opinion statement

Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tjHA4b


from ! Medicine by Alexandros G. Sfakianakis via alwin on Inoreader http://ift.tt/2sl7waQ
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Immunotherapeutic Approaches to Biliary Cancer

Opinion statement

Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.

from ! Medicine by Alexandros G. Sfakianakis via als.fakia on Inoreader http://ift.tt/2tjHA4b
via IFTTT

Immunotherapeutic Approaches to Biliary Cancer

Opinion statement

Biliary tract cancers (BTCs) are rare aggressive neoplasms with a poor prognosis and a median survival of less than 1 year in the locally advanced or metastatic setting. Among the few patients who undergo curative resection the recurrence rates are high. About 90% of patients are detected at advanced stages, and systemic chemotherapy is the mainstay of their treatment. The treatment options for these patients are limited and multiple modalities of therapy from targeted therapy to immunotherapy and combination therapies (immunotherapy, targeted therapy, and chemotherapy) have been tested in this disease. Targeted therapies have failed to show a survival benefit. The deregulation of the immune system plays a significant role in the pathogenesis of BTCs. Therefore, immunotherapy, especially, immune checkpoint inhibitors hold great promise for this group of cancers. Numerous trials of immunotherapy in BTC are currently ongoing. In this review, we will discuss the available data and evidence for immunotherapy in BTC.

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Therapeutic Strategies Targeting Inherited Cardiomyopathies

Abstract

Purpose of Review

Cardiomyopathies due to genetic mutations are a heterogeneous group of disorders that comprise diseases of contractility, myocardial relaxation, and arrhythmias. Our goal here is to discuss a limited list of genetically inherited cardiomyopathies and the specific therapeutic strategies used to treat them.

Recent Findings

Research into the molecular pathophysiology of the development of these cardiomyopathies is leading to the development of novel treatment approaches. Therapies targeting these specific mutations with gene therapy vectors are on the horizon, while other therapies which indirectly affect the physiologic derangements of the mutations are currently being studied and used clinically. Many of these therapies are older medications being given new roles such as mexiletine for Brugada syndrome and diflunisal for transthyretin amyloid cardiomyopathy. A newer targeted therapy, the inhibitor of myosin ATPase MYK-461, has been shown to suppress the development of ventricular hypertrophy, fibrosis, and myocyte disarray and is being studied as a potential therapy in patients with hypertrophic cardiomyopathy.

Summary

While this field is too large to be completely contained in a single review, we present a large cross section of recent developments in the field of therapeutics for inherited cardiomyopathies. New therapies are on the horizon, and their development will likely result in improved outcomes for patients inflicted by these conditions.

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Real-time parameterized expectations and the effects of government spending

In this paper, we explore the effects of government spending in the real business cycle model where agents use a learning mechanism to form expectations. In contrast to most of the learning literature, we study learning behaviour in the original non-linear model. Following the learning interpretation of the parameterized expectations method, agents' forecast rules are approximations of the conditional expectations appearing in the Euler equation. We show that variation in agents' beliefs about the coefficients of these rules, generates time variation in the transmission of government spending shocks to the economy. Hence, our modelling approach provides an endogenous mechanism for time-varying government spending multipliers in the standard real business cycle model.

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Spatial perspectives on knowledge brokers : evidence from Brussels

from ! Medicine by Alexandros G. Sfakianakis via als.fakia on Inoreader http://ift.tt/2tn03Nv
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Therapeutic Strategies Targeting Inherited Cardiomyopathies

Abstract

Purpose of Review

Cardiomyopathies due to genetic mutations are a heterogeneous group of disorders that comprise diseases of contractility, myocardial relaxation, and arrhythmias. Our goal here is to discuss a limited list of genetically inherited cardiomyopathies and the specific therapeutic strategies used to treat them.

Recent Findings

Research into the molecular pathophysiology of the development of these cardiomyopathies is leading to the development of novel treatment approaches. Therapies targeting these specific mutations with gene therapy vectors are on the horizon, while other therapies which indirectly affect the physiologic derangements of the mutations are currently being studied and used clinically. Many of these therapies are older medications being given new roles such as mexiletine for Brugada syndrome and diflunisal for transthyretin amyloid cardiomyopathy. A newer targeted therapy, the inhibitor of myosin ATPase MYK-461, has been shown to suppress the development of ventricular hypertrophy, fibrosis, and myocyte disarray and is being studied as a potential therapy in patients with hypertrophic cardiomyopathy.

Summary

While this field is too large to be completely contained in a single review, we present a large cross section of recent developments in the field of therapeutics for inherited cardiomyopathies. New therapies are on the horizon, and their development will likely result in improved outcomes for patients inflicted by these conditions.

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Economic drivers and specialization patterns in the spatial distribution of Framework Programme's participation

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Europese gerechtelijke taalbescherming

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Inter organizational trust and technology complexity : evidence for new technology-based firms

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Spatial perspectives on knowledge brokers : evidence from Brussels

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Politique européenne de voisinage

1. - La politique européenne de voisinage (PEV) est le fruit d'une genèse particulièrement longue. Elle est fondée sur l'article 8 du traité UE, est progressivement entrée en vigueur entre 2004 et 2007 et a été réorientée une première fois en 2011. Les propositions pour la révision à mi-parcours de 2017 ont été publiées en novembre 2015 (V. n° 1 à 33). 2. - La méthodologie et les principes de la PEV (conditionnalité positive, co-appropriation et différenciation) s'inspirent du modèle de la stratégie de préadhésion mais sans prévoir la perspective d'une adhésion des partenaires à l'Union européenne (V. n° 34 à 43). 3. - Les instruments de la PEV sont multiples et variés quant à leur nature juridique et leur portée. Il s'agit d'abord des accords de base qui se déclinent en trois types : les accords de partenariat et de coopération, les accords euro-méditerranéens d'association et une nouvelle génération d'accords d'association intégrant des accords de libre-échange complet et approfondi (V. n° 44 à 117). 4. - Des accords multilatéraux et sectoriels, de plus en plus nombreux, complètent les accords de base (V. n° 118 à 130). 5. - Les instruments relatifs à la coopération sont également très nombreux et parfois spécifiques à la politique européenne de voisinage. Il s'agit des règlements financiers d'application que sont l'Instrument européen de voisinage et de partenariat (2007-2013) et l'Instrument européen de voisinage ainsi que le règlement cadre horizontal (2014-2020). Ces instruments gouvernent les modalités de la coopération (V. n° 131 à 152). 6. - L'essentiel de la coopération est mis en œuvre dans le cadre d'une approche bilatérale pour laquelle de nombreux instruments de coopération spécifiques à la PEV, tels que les Plans d'action, sont utilisés (V. n° 153 à 166). 7. - Des instruments de coopération de nature multilatérale couvrent également les questions (inter-) régionales et transfrontalières et sont encadrés par le Partenariat oriental pour les pays européens et, dans une moindre mesure, par l'Union pour la Méditerranée pour les pays méditerranéens (V. n° 167 à 205).

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Economic drivers and specialization patterns in the spatial distribution of Framework Programme's participation

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Authentic Leadership and Job Satisfaction in Turbulent Times

from ! Medicine by Alexandros G. Sfakianakis via a.lsfakia on Inoreader http://ift.tt/2tnjqWB
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Diatomeeëngemeenschappen uit de pelagische en litorale zone van het Tanganyikameer

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Reconciliation ecology in practice : legal and policy considerations when implementing temporary nature on undeveloped lands in the European Union

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Sustainable agricultural development, land use change and food security in China

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Reorganising child health services: new evidence for the new millennium?

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Hoe is het gesteld met de tropische wouden?

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Aquaculture in the Third World

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Aquaculture in the Third World

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Paradoxen in het wereldvoedsel- en landbouwbeleid

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Reconciliation ecology in practice : legal and policy considerations when implementing temporary nature on undeveloped lands in the European Union

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Development potential for Bhutanese agriculture

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Europese gerechtelijke taalbescherming

from ! Medicine by Alexandros G. Sfakianakis via a.lsfakia on Inoreader http://ift.tt/2tWkePx
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Hoe is het gesteld met de tropische wouden?

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Sustainable agricultural development, land use change and food security in China

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Inter organizational trust and technology complexity : evidence for new technology-based firms

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Authentic Leadership and Job Satisfaction in Turbulent Times

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Authenticity at work: the role of leaders’ attachment style

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Authenticity at work: the role of leaders’ attachment style

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De internationale arbeiderssportbeweging tijdens het interbellum: CSIT 100

Uitgave naar aanleiding van 100 jaar Confédération Sportive Internationale Travailliste et Amateur (CSIT)

from ! Medicine by Alexandros G. Sfakianakis via als.fakia on Inoreader http://ift.tt/2tWAfVA
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Sustainable harvest methods for medicinal bark from trees (a research and development case study from Benin)

from ! Medicine by Alexandros G. Sfakianakis via a.lsfakia on Inoreader http://ift.tt/2tnxcc3
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Real-time parameterized expectations and the effects of government spending

In this paper, we explore the effects of government spending in the real business cycle model where agents use a learning mechanism to form expectations. In contrast to most of the learning literature, we study learning behaviour in the original non-linear model. Following the learning interpretation of the parameterized expectations method, agents' forecast rules are approximations of the conditional expectations appearing in the Euler equation. We show that variation in agents' beliefs about the coefficients of these rules, generates time variation in the transmission of government spending shocks to the economy. Hence, our modelling approach provides an endogenous mechanism for time-varying government spending multipliers in the standard real business cycle model.

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Pindanoten voor de ontluikende industriële revolutie: een alternatieve kijk op de Belgische commerciële expansie in West-Afrika (1844-1861)

from ! Medicine by Alexandros G. Sfakianakis via als.fakia on Inoreader http://ift.tt/2tn6eRL
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Politique européenne de voisinage

1. - La politique européenne de voisinage (PEV) est le fruit d'une genèse particulièrement longue. Elle est fondée sur l'article 8 du traité UE, est progressivement entrée en vigueur entre 2004 et 2007 et a été réorientée une première fois en 2011. Les propositions pour la révision à mi-parcours de 2017 ont été publiées en novembre 2015 (V. n° 1 à 33). 2. - La méthodologie et les principes de la PEV (conditionnalité positive, co-appropriation et différenciation) s'inspirent du modèle de la stratégie de préadhésion mais sans prévoir la perspective d'une adhésion des partenaires à l'Union européenne (V. n° 34 à 43). 3. - Les instruments de la PEV sont multiples et variés quant à leur nature juridique et leur portée. Il s'agit d'abord des accords de base qui se déclinent en trois types : les accords de partenariat et de coopération, les accords euro-méditerranéens d'association et une nouvelle génération d'accords d'association intégrant des accords de libre-échange complet et approfondi (V. n° 44 à 117). 4. - Des accords multilatéraux et sectoriels, de plus en plus nombreux, complètent les accords de base (V. n° 118 à 130). 5. - Les instruments relatifs à la coopération sont également très nombreux et parfois spécifiques à la politique européenne de voisinage. Il s'agit des règlements financiers d'application que sont l'Instrument européen de voisinage et de partenariat (2007-2013) et l'Instrument européen de voisinage ainsi que le règlement cadre horizontal (2014-2020). Ces instruments gouvernent les modalités de la coopération (V. n° 131 à 152). 6. - L'essentiel de la coopération est mis en œuvre dans le cadre d'une approche bilatérale pour laquelle de nombreux instruments de coopération spécifiques à la PEV, tels que les Plans d'action, sont utilisés (V. n° 153 à 166). 7. - Des instruments de coopération de nature multilatérale couvrent également les questions (inter-) régionales et transfrontalières et sont encadrés par le Partenariat oriental pour les pays européens et, dans une moindre mesure, par l'Union pour la Méditerranée pour les pays méditerranéens (V. n° 167 à 205).

from ! Medicine by Alexandros G. Sfakianakis via a.lsfakia on Inoreader http://ift.tt/2tnlwFV
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Sustainable harvest methods for medicinal bark from trees (a research and development case study from Benin)

from ! Medicine by Alexandros G. Sfakianakis via als.fakia on Inoreader http://ift.tt/2tnxcc3
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Development potential for Bhutanese agriculture

from ! Medicine by Alexandros G. Sfakianakis via als.fakia on Inoreader http://ift.tt/2tWPyh4
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De internationale arbeiderssportbeweging tijdens het interbellum: CSIT 100

Uitgave naar aanleiding van 100 jaar Confédération Sportive Internationale Travailliste et Amateur (CSIT)

from ! Medicine by Alexandros G. Sfakianakis via a.lsfakia on Inoreader http://ift.tt/2tWAfVA
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Diatomeeëngemeenschappen uit de pelagische en litorale zone van het Tanganyikameer

from ! Medicine by Alexandros G. Sfakianakis via a.lsfakia on Inoreader http://ift.tt/2tWxG5W
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Reorganising child health services: new evidence for the new millennium?

from ! Medicine by Alexandros G. Sfakianakis via a.lsfakia on Inoreader http://ift.tt/2tn6ksB
via IFTTT

Paradoxen in het wereldvoedsel- en landbouwbeleid

from ! Medicine by Alexandros G. Sfakianakis via a.lsfakia on Inoreader http://ift.tt/2tWNmpx
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Pindanoten voor de ontluikende industriële revolutie: een alternatieve kijk op de Belgische commerciële expansie in West-Afrika (1844-1861)

from ! Medicine by Alexandros G. Sfakianakis via a.lsfakia on Inoreader http://ift.tt/2tn6eRL
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Mammalian raw materials used to produce allergen extracts

To provide information about the complexity of skin-derived mammalian allergen extracts and recent advances made in their characterization and production.

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Genetic variants and risk of asthma in an American Indian population

Asthma is recognized as a complex, multifactorial disease with a genetic component that is well recognized. Certain genetic variants are associated with asthma in a number of populations.

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Point-of-care blood eosinophil count in a severe asthma clinic setting

One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers.

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Drug eruption caused by memantine

The treatment of Alzheimer disease has continued to develop during the past decade. Although an acetylcholine esterase (AchE) inhibitor has been widely used for the treatment of cognitive function in patients with Alzheimer disease through an enhancement of cholinergic function, an open-channel blockade agent targeted for N-methyl-d-aspartate (NMDA) has recently been established as a novel treatment of Alzheimer disease, namely, memantine. Memantine reduced clinical deterioration in moderate-to-severe Alzheimer disease.

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Editorial Board

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Association of altered gut microbiota composition with chronic urticaria

An altered gut microbiota composition has recently been linked to some types of allergies.

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Instructions for Authors

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Editorial Board

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Vitamin D and asthma

Several studies have associated low levels of 25-hydroxyvitamin D (25[OH]D) with higher risk of asthma.1,2 However, these studies could have residual confounding or reverse causation, making it difficult to draw conclusions on whether 25(OH)D is causally associated with asthma. Instrumental variable analysis was developed for assessing causality using genetic variants in epidemiologic research known as Mendelian randomization (MR). The rationale of MR is to find genetic variants associated with the exposure (eg, 25[OH]D) but not with other risk factors (eg, obesity) that affect the outcome (eg, asthma).

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Influence of antibiotic use in early childhood on asthma and allergic diseases at age 5

In the past few decades, the prevalence of allergic diseases has increased rapidly worldwide. At the same time, the overuse of antibiotics has been observed, especially in Japan.

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Table of Contents

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Effect of misoprostol on patients with aspirin-exacerbated respiratory disease undergoing aspirin challenge and desensitization

Prostaglandin E2 (PGE2) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE2 stabilizes inflammatory mediator release.

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Information for Readers

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Prolonged effect of allergen sublingual immunotherapy for house dust mites in elderly patients

The prolonged effect of allergen immunotherapy is unknown, especially in older patients.

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Grasshopper anaphylaxis in patients allergic to dust mite, cockroach, and crustaceans

Within the last year, 2 patients presented to our Southern California allergy clinic with a history of severe anaphylactic reactions (one with loss of consciousness and the other with urticaria, laryngeal edema, and near syncope) after the initial consumption of chapulines (roasted grasshopper from Oaxaca, Mexico) despite no previous occupational or natural exposure to chapulines and no history of having ever eaten chapulines before. This is the first documented report of anaphylaxis to chapuline in the medical literature.

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Cockroach allergen exposure and plasma cytokines among children in a tropical environment

Little is known about the effects of socioeconomic status or cockroach allergen on immune responses in school-age children, particularly in tropical environments.

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Patient satisfaction and experience with intravenously administered C1-inhibitor concentrates in the United States

Hereditary angioedema (HAE) is a rare genetic disorder with substantial morbidity and mortality. Despite expanded choices for effective acute treatment, prophylactic options are more limited. Intravenous C1 esterase inhibitor (C1-INH[IV]) is licensed and used to prevent HAE symptoms.

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Modern challenges of allergic bronchopulmonary aspergillosis diagnosis and management

Allergic bronchopulmonary aspergillosis (ABPA) is an exaggerated reaction to Aspergillus fumigatus antigens with a complex pathogenesis that is not fully clarified. The diagnosis sometimes can be a challenge because there is no universal consensus on the diagnostic criteria originally proposed by Rosenberg et al1 and later modified.2 ABPA is established by a combination of clinical, immunologic, and radiologic findings, but in clinical practice some patients do not fulfil all criteria at a given time.

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Erratum

In the article entitled "A case of atypical, complete DiGeorge syndrome without 22q11 mutation" (Ann Allergy Asthma Immunol 2017;118:629-647), the following sentence is incorrect: "Tetanus and pneumococcal immunoglobulin G titers were non-protective; the patient was not yet unvaccinated." The sentence should read, "Tetanus and pneumococcal immunoglobulin G titers were non-protective; the patient was not yet vaccinated."

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Desensitization to protein kinase inhibitors

Cancer is responsible for more than half a million American deaths every year and an estimated 39% of men and women will be diagnosed with at least 1 type of cancer during their lifetime.1 Cytotoxic agents were previously the mainstay of therapy and continue to be used frequently in oncology practice, but their nonspecific mechanism of action is associated with extensive adverse effect profiles. The development of "targeted" therapies in the form of biologic agents and protein kinase inhibitors (PKIs) revolutionized cancer treatment and dominate the oncology drug pipeline.

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Influence of antibiotic use in early childhood on asthma and allergic diseases at age 5

In the past few decades, the prevalence of allergic diseases has increased rapidly worldwide. At the same time, the overuse of antibiotics has been observed, especially in Japan.

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Vitamin D and asthma

Several studies have associated low levels of 25-hydroxyvitamin D (25[OH]D) with higher risk of asthma.1,2 However, these studies could have residual confounding or reverse causation, making it difficult to draw conclusions on whether 25(OH)D is causally associated with asthma. Instrumental variable analysis was developed for assessing causality using genetic variants in epidemiologic research known as Mendelian randomization (MR). The rationale of MR is to find genetic variants associated with the exposure (eg, 25[OH]D) but not with other risk factors (eg, obesity) that affect the outcome (eg, asthma).

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Association of altered gut microbiota composition with chronic urticaria

An altered gut microbiota composition has recently been linked to some types of allergies.

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Drug eruption caused by memantine

The treatment of Alzheimer disease has continued to develop during the past decade. Although an acetylcholine esterase (AchE) inhibitor has been widely used for the treatment of cognitive function in patients with Alzheimer disease through an enhancement of cholinergic function, an open-channel blockade agent targeted for N-methyl-d-aspartate (NMDA) has recently been established as a novel treatment of Alzheimer disease, namely, memantine. Memantine reduced clinical deterioration in moderate-to-severe Alzheimer disease.

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Mammalian raw materials used to produce allergen extracts

To provide information about the complexity of skin-derived mammalian allergen extracts and recent advances made in their characterization and production.

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Table of Contents

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Effect of misoprostol on patients with aspirin-exacerbated respiratory disease undergoing aspirin challenge and desensitization

Prostaglandin E2 (PGE2) is an anti-inflammatory compound that inhibits 5-lipoxygenase activity. Diminished PGE2 regulation in aspirin-exacerbated respiratory disease (AERD) leads to respiratory reactions on cyclooxygenase 1 inhibition. In vitro studies have found that exogenous PGE2 stabilizes inflammatory mediator release.

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Point-of-care blood eosinophil count in a severe asthma clinic setting

One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers.

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Information for Readers

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Prolonged effect of allergen sublingual immunotherapy for house dust mites in elderly patients

The prolonged effect of allergen immunotherapy is unknown, especially in older patients.

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Grasshopper anaphylaxis in patients allergic to dust mite, cockroach, and crustaceans

Within the last year, 2 patients presented to our Southern California allergy clinic with a history of severe anaphylactic reactions (one with loss of consciousness and the other with urticaria, laryngeal edema, and near syncope) after the initial consumption of chapulines (roasted grasshopper from Oaxaca, Mexico) despite no previous occupational or natural exposure to chapulines and no history of having ever eaten chapulines before. This is the first documented report of anaphylaxis to chapuline in the medical literature.

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Genetic variants and risk of asthma in an American Indian population

Asthma is recognized as a complex, multifactorial disease with a genetic component that is well recognized. Certain genetic variants are associated with asthma in a number of populations.

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Cockroach allergen exposure and plasma cytokines among children in a tropical environment

Little is known about the effects of socioeconomic status or cockroach allergen on immune responses in school-age children, particularly in tropical environments.

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Modern challenges of allergic bronchopulmonary aspergillosis diagnosis and management

Allergic bronchopulmonary aspergillosis (ABPA) is an exaggerated reaction to Aspergillus fumigatus antigens with a complex pathogenesis that is not fully clarified. The diagnosis sometimes can be a challenge because there is no universal consensus on the diagnostic criteria originally proposed by Rosenberg et al1 and later modified.2 ABPA is established by a combination of clinical, immunologic, and radiologic findings, but in clinical practice some patients do not fulfil all criteria at a given time.

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Erratum

In the article entitled "A case of atypical, complete DiGeorge syndrome without 22q11 mutation" (Ann Allergy Asthma Immunol 2017;118:629-647), the following sentence is incorrect: "Tetanus and pneumococcal immunoglobulin G titers were non-protective; the patient was not yet unvaccinated." The sentence should read, "Tetanus and pneumococcal immunoglobulin G titers were non-protective; the patient was not yet vaccinated."

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Patient satisfaction and experience with intravenously administered C1-inhibitor concentrates in the United States

Hereditary angioedema (HAE) is a rare genetic disorder with substantial morbidity and mortality. Despite expanded choices for effective acute treatment, prophylactic options are more limited. Intravenous C1 esterase inhibitor (C1-INH[IV]) is licensed and used to prevent HAE symptoms.

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Desensitization to protein kinase inhibitors

Cancer is responsible for more than half a million American deaths every year and an estimated 39% of men and women will be diagnosed with at least 1 type of cancer during their lifetime.1 Cytotoxic agents were previously the mainstay of therapy and continue to be used frequently in oncology practice, but their nonspecific mechanism of action is associated with extensive adverse effect profiles. The development of "targeted" therapies in the form of biologic agents and protein kinase inhibitors (PKIs) revolutionized cancer treatment and dominate the oncology drug pipeline.

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Instructions for Authors

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A Unique Case of Muscle-Invasive Metastatic Breast Cancer Mimicking Myositis

Breast cancer rarely metastasizes to the muscles, and it is even more unusual for this phenomenon to result in airway compromise. We present a unique case of an 84-year-old female who presented with neck swelling and upper airway obstruction due to metastatic breast cancer invading the sternocleidomastoid muscles. After establishing the diagnosis and discussing possible treatment options, the patient elected for antiestrogen therapy, palliative tracheostomy, radiation therapy, and hospice services.

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Photoregulation of Gold Nanoparticles Stabilized in a Diacetylenic Nanocapsule

The results of releasing a drug in a burst are unpredictable and one of the inherent drawbacks of using nanocarriers. Here, photoresponsive cationic gold nanoparticles to stabilize diacetylenic nanocapsules enabling photoregulated release of payloads are reported. The fabrication of these nanocapsules relied on an electrostatic interaction of a negatively charged diacetylenic core and a positively charged gold nanoparticle shell. Gold nanoparticles with photoresponsive ligands on their surfaces act as both hydrophobic core stabilizers and gatekeepers of the nanocapsules, while their polydiacetylene cores serve as hydrophobic drug carriers that can be tuned using UV irradiation. The morphology of nanocapsules was analyzed using TEM and dynamic light scattering. The resultant nanocapsules had a spherical shape with an average diameter of 152.9 ± 6.7 nm. Upon UV irradiation, the nanocapsules lost their integrity and an encapsulated model compound was released through diffusion. The release of a hydrophobic molecule was irradiation time dependent and thereby controllable. This light-triggered release provides an alternative strategy for controlled drug delivery.

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Cost Sharing in the Prevention of Supply Chain Disruption

We examine the influence of cost-sharing mechanism on the disruption prevention investment in a supply chain with unreliable suppliers. When a supply chain faces considerable loss following a disruption, supply chain members are motivated toward investing in manners that reduce their disruption probability. In improving supply chain reliability, the cost-sharing mechanism must be set appropriately to realize the efficiency of the disruption prevention investment. In a supply chain where the focal manufacturing company has its own subsidiary supplier and an outsourcing supplier, we analyze different forms of cost-sharing mechanisms when both suppliers confront disruption risks. Through the cost-sharing mechanisms presented in this study, supply chain members can improve their reliability via disruption prevention investments without considerably increasing the total supply chain cost. We present two concepts, the cost-sharing structure and the cost-sharing ratio, in this study. As the two key components of cost-sharing mechanism, these two elements constitute a practicable cost allocation mechanism to facilitate disruption prevention.

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Early Cleft Lip Repair Revisited: A Safe and Effective Approach Utilizing a Multidisciplinary Protocol.

Background: The optimal timing for cleft lip repair has yet to be established. Advances in neonatal anesthesia, along with a growing body of literature, suggesting benefits of earlier cleft lip and nasal repair, have set the stage for a reexamination of current practices. Methods: In this prospective study, cleft lip and nasal repair occurred on average at 34.8 days (13-69 days). Nasal correction was achieved primarily through molding the nasal cartilage without the placement of nasal sutures at the time of repair. A standardized anesthetic protocol aimed at limiting neurotoxicity was utilized in all cases. Anesthetic and postoperative complications were assessed. A 3-dimensional nasal analysis compared pre- and postoperative nasal symmetry for unilateral clefts. Surveys assessed familial response to repair. Results: Thirty-two patients were included (27 unilateral and 5 bilateral clefts). In this study, the overall complication rate was 3.1%. Anthropometric measurements taken from 3-dimensional-image models showed statistically significant improvement in ratios of nostril height (preoperative mean, 0.59; postoperative mean, 0.80), nasal base width (preoperative mean, 1.96; postoperative mean, 1.12), columella length (preoperative mean, 0.62; postoperative mean, 0.89; and columella angle (preoperative mean, 30.73; postoperative mean, 9.1). Survey data indicated that families uniformly preferred earlier repair. Conclusions: We present evidence that early cleft lip and nasal repair can be performed safely and is effective at improving nasal symmetry without the placement of any nasal sutures. Utilization of this protocol has the potential to be a paradigm shift in the treatment of cleft lip and nasal deformity. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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The Complexity of Simple – Bringing Order to Complex Systems by Chris Hicks

  The ability to simplify means to eliminate the unnecessary so that the necessary may speak –Hans Hofmann We live in complex times.  Resuscitation has gone endovascular, microvascular, mitochondrial.  EPR, ED-ECMO, REBOA–it's a fascinating time to be a Resuscitationist.  But the more we advance the resuscitation agenda, the more we learn how complex critical illness […]

EMCrit by Chris Hicks.

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A population level atlas of Mus musculus craniofacial skeleton and automated image-based shape analysis

Abstract

Laboratory mice are staples for evo/devo and genetics studies. Inbred strains provide a uniform genetic background to manipulate and understand gene–environment interactions, while their crosses have been instrumental in studies of genetic architecture, integration and modularity, and mapping of complex biological traits. Recently, there have been multiple large-scale studies of laboratory mice to further our understanding of the developmental basis, evolution, and genetic control of shape variation in the craniofacial skeleton (i.e. skull and mandible). These experiments typically use micro-computed tomography (micro-CT) to capture the craniofacial phenotype in 3D and rely on manually annotated anatomical landmarks to conduct statistical shape analysis. Although the common choice for imaging modality and phenotyping provides the potential for collaborative research for even larger studies with more statistical power, the investigator (or lab-specific) nature of the data collection hampers these efforts. Investigators are rightly concerned that subtle differences in how anatomical landmarks were recorded will create systematic bias between studies that will eventually influence scientific findings. Even if researchers are willing to repeat landmark annotation on a combined dataset, different lab practices and software choices may create obstacles for standardization beyond the underlying imaging data. Here, we propose a freely available analysis system that could assist in the standardization of micro-CT studies in the mouse. Our proposal uses best practices developed in biomedical imaging and takes advantage of existing open-source software and imaging formats. Our first contribution is the creation of a synthetic template for the adult mouse craniofacial skeleton from 25 inbred strains and five F1 crosses that are widely used in biological research. The template contains a fully segmented cranium, left and right hemi-mandibles, endocranial space, and the first few cervical vertebrae. We have been using this template in our lab to segment and isolate cranial structures in an automated fashion from a mixed population of mice, including craniofacial mutants, aged 4–12.5 weeks. As a secondary contribution, we demonstrate an application of nearly automated shape analysis, using symmetric diffeomorphic image registration. This approach, which we call diGPA, closely approximates the popular generalized Procrustes analysis (GPA) but negates the collection of anatomical landmarks. We achieve our goals by using the open-source advanced normalization tools (ANT) image quantification library, as well as its associated R library (ANTsR) for statistical image analysis. Finally, we make a plea to investigators to commit to using open imaging standards and software in their labs to the extent possible to increase the potential for data exchange and improve the reproducibility of findings. Future work will incorporate more anatomical detail (such as individual cranial bones, turbinals, dentition, middle ear ossicles) and more diversity into the template.

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Rheumatoid nodule on cytology

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Rheumatoid nodule on cytology

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Sculptors, Architects, and Painters Conceive of Depicted Spaces Differently

Abstract

Sculptors, architects, and painters are three professional groups that require a comprehensive understanding of how to manipulate spatial structures. While it has been speculated that they may differ in the way they conceive of space due to the different professional demands, this has not been empirically tested. To achieve this, we asked architects, painters, sculptors, and a control group questions about spatially complex pictures. Verbalizations elicited were examined using cognitive discourse analysis. We found significant differences between each group. Only painters shifted consistently between 2D and 3D concepts, architects were concerned with paths and spatial physical boundedness, and sculptors produced responses that fell between architects and painters. All three differed from controls, whose verbalizations were generally less elaborate and detailed. Thus, for the case of sculptors, architects, and painters, profession appears to relate to a different spatial conceptualization manifested through a systematically contrasting way of talking about space.

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Working night shifts reduces repair of DNA damage, study suggests

Working at night is associated with reduced repair of DNA damage, shows an observational study of healthcare shift workers that suggests that this effect was driven by suppression of melatonin.1The...

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