bluuebunny/crossref_metadata_2025 huggingface dataset:
Profile fluctuation of peripheral blood in advanced melanoma patients treated with nivolumab
Authors: Saito Ryuichi , Sawada Yu , Saito‐Sasaki Natsuko , Yamamoto Kayo , Yoshioka Haruna , Ohmori Shun , Yoshioka Manabu , Okada Etsuko , Nakamura Motonobu
Published: September 2018

Melanoma is a malignant tumor of the melanocytes with an unfavorable clinical behavior. Nivolumab, a representative anti‐programmed death 1 (PD‐1) antibody, has recently been used for the treatment of metastatic malignant melanoma. However, there have been few appropriate biomarkers predicting the effect of nivolumab before the administration. Furthermore, the detailed characteristics of peripheral blood mononuclear cell (PBMC) profiles during nivolumab treatment remains unclear. In this study, we investigated fluctuations of PBMC profile during nivolumab treatment. PBMC analysis showed T‐helper (Th)2‐dominant conditions after a first course of nivolumab treatment. In a favorable case treated with nivolumab, a Th1/T‐cytotoxic 1 shift was observed after nivolumab was administrated. These results suggest that flow cytometric analysis of PBMC may be helpful for the treatment of nivolumab.
Productivity and diversity of annually harvested reconstructed prairie communities
Authors: Kordbacheh Farnaz , Jarchow Meghann , English Lydia , Liebman Matt
Published: September 2018

Biofuel production from cellulosic feedstocks may increase during the next century. To be sustainable, this production should protect environmental quality and biodiversity. Fertilized mixed‐species prairie can deliver substantial quantities of cellulosic ethanol per unit land area with minimal losses of NO3‐N in drainage water, but the long‐term maintenance of biodiversity in such systems has been uncertain.

We report how nitrogen, phosphorus, and potassium fertilizer application, precipitation, and time affected the species composition and productivity of reconstructed prairie communities harvested annually as biofuel feedstocks over a 9‐year period.

Results indicated that both precipitation and fertilizer application drove above‐ground biomass production, with the greatest response to fertilizer occurring in wetter than average years. Fertilization reduced species richness, but increased species evenness. Consequently, Simpson's diversity index did not differ between the fertilized and unfertilized communities, though it declined in both communities over time.

A total of 59 plant species was recorded, with eight of them explaining most of the differences in vegetation cover between the fertilized and unfertilized treatments. After 9 years, the high fertility community was dominated by the C4 grassAndropogon gerardii,the C3 grassElymus canadensis, and the non‐leguminous forbsHeliopsis helianthoides,Helianthus maximiliani, andMonarda fistulosa, whereas the low fertility community was dominated by the C4 grassesA. gerardiiandSorghastrum nutans, the C3 grassE. canadensis, and the non‐leguminous forbM. fistulosa. Fertilization increased the abundance of flowering forbs available to pollinators in the early, middle and late portions of the growing season.

Synthesis and applications. Results of our study suggest that maintenance of reasonably high levels of productivity and biodiversity are possible in fertilized prairie communities harvested annually for bioenergy, with plant cover more evenly distributed among different functional groups. In the future, if policy and markets favour biofuels and better delivery of ecosystem services from harvested land, prairie‐based feedstocks could become part of a renewable energy portfolio that fosters biodiversity and contributes to the provision of floral resources for pollinators.
Impact of Pharmacists on Access to Vaccine Providers: A Geospatial Analysis
Authors: SHAH PARTH D. , TROGDON JUSTIN G. , GOLDEN SHELLEY D. , GOLIN CAROL E. , MARCINIAK MACARY WECK , BREWER NOEL T.
Published: September 2018

Policy Points:

Policymakers in the United States should consider expanding pharmacy practice laws to allow pharmacists to vaccinate adolescents as a way to improve geographic access to adolescent vaccines, particularly for human papillomavirus (HPV) vaccine, which has low uptake.

Our state‐level analysis showed that pharmacists are more geographically dispersed than primary care physicians in the US state of Texas.

Including pharmacists among available adolescent vaccine providers would improve the geographic distribution of vaccine providers, especially in areas with an inadequate number of primary care physicians.

Context

The largest disparities in human papillomavirus (HPV) vaccination in the United States are due to geography. One potential way of addressing these disparities is by improving geographic access to HPV vaccination. Two federal panels have recommended including community pharmacists as HPV vaccine providers as a strategy to improve opportunities for HPV vaccination for adolescents. We sought to evaluate whether community pharmacists can improve the number of vaccine providers in areas with primary care physician shortages in the US state of Texas.

Methods

We gathered publicly available physician and pharmacist 2016 workforce data from the Texas Medical Board and Board of Pharmacy. We conducted geospatial analysis of census tracts to analyze the distribution of physicians and pharmacists and how pharmacists change vaccine provider coverage across the state.

Findings

Census tracts with high numbers of physicians per capita tended to be located near one another, in 5 of 5 analyses of Moran's I (median = .04). In contrast, pharmacist rates were not spatially dependent on census tract in any of our analyses. If pharmacists were added to primary care physicians as vaccine providers, 35% of urban census tracts that previously had inadequate coverage would be adequately covered, while 18% of inadequately covered rural census tracts would become adequately covered. Overall, when pharmacists were included with primary care physicians as vaccine providers, vaccine providers per capita increased in 2,413 of the 4,508 urban census tracts (54%), while the rate increased in 223 of 746 rural census tracts (30%).

Conclusions

Pharmacists are more geographically dispersed across census tracts than primary care physicians. As a result, adding pharmacists to the workforce would increase the availability of vaccine providers in areas with inadequate primary care provider coverage.
Diversity in Medical Device Clinical Trials: Do We Know What Works for Which Patients?
Authors: FOX‐RAWLINGS STEPHANIE R. , GOTTSCHALK LAURA B. , DOAMEKPOR LAURÉN A. , ZUCKERMAN DIANA M.
Published: September 2018

Policy Points:

A 1993 law required the National Institutes of Health to include women and racial and ethnic minorities in relevant research studies. Most federal health agencies adopted the same policy, but the US Food and Drug Administration (FDA) did not.

A 2012 law encouraged the FDA to ensure that new medical products be analyzed for safety and effectiveness for key demographic patient groups.

Our study of high‐risk medical devices reviewed by the FDA in 2014‐2017 found that due to lack of patient diversity and publicly available data, clinicians and patients often cannot determine which devices are safe and effective for specific demographic groups.

Context

Demographic differences can influence the safety and effectiveness of medical devices; however, clinical trials of devices for adults have historically underrepresented women, people of color, and patients over age 65. The US Food and Drug Administration (FDA) Safety and Innovation Act became law in 2012, encouraging greater diversity and subgroup analyses. In 2013, the FDA reported that there was diversity in clinical trials considered “pivotal” for approval decisions and that subgroup analyses were conducted for most applications for the highest‐risk medical devices. However, the FDA's report did not specify whether analyses included sufficient numbers to be meaningful, whether analyses were conducted for most major subgroups, or whether analyses included safety, effectiveness, or accuracy.

Methods

We examined publicly available documents for all 22 medical devices that the FDA designated “highest risk” or “novel,” were reviewed through the premarket approval pathway, and were scrutinized at FDA public meetings from 2014 to 2017. We evaluated patient demographics and subgroup analyses for all pivotal trials.

Findings

Only 3 (14%) of the devices provided subgroup analyses for both effectiveness and safety or both sensitivity and selectivity for gender, race, and age. However, 55% of the devices reported both of those subgroup analyses for at least 1 of the 3 subgroups. Whether analyses were reported or not, the number of patients in most subgroups was too small to draw meaningful conclusions. Subgroup analyses were more likely to be reported to the FDA's Advisory Committees than in the FDA's public reviews or labeling.

Conclusions

Despite a law encouraging more diversity and subgroup analyses in pivotal trials used as the basis for FDA approval, the results of our study indicate relatively few subgroup analyses are publicly available for the highest‐risk and novel medical devices. The lack of subgroup analyses makes it impossible to inform patients or physicians as to whether many newly approved medical devices are safe and effective for specific demographic subgroups defined by gender, race, and age.
Finding Nemo’s Genes: A chromosome‐scale reference assembly of the genome of the orange clownfishAmphiprion percula
Authors: Lehmann Robert , Lightfoot Damien J. , Schunter Celia , Michell Craig T. , Ohyanagi Hajime , Mineta Katsuhiko , Foret Sylvain , Berumen Michael L. , Miller David J. , Aranda Manuel , Gojobori Takashi , Munday Philip L. , Ravasi Timothy
Published: September 2018

The iconic orange clownfish,Amphiprion percula, is a model organism for studying the ecology and evolution of reef fishes, including patterns of population connectivity, sex change, social organization, habitat selection and adaptation to climate change. Notably, the orange clownfish is the only reef fish for which a complete larval dispersal kernel has been established and was the first fish species for which it was demonstrated that antipredator responses of reef fishes could be impaired by ocean acidification. Despite its importance, molecular resources for this species remain scarce and until now it lacked a reference genome assembly. Here, we present a de novo chromosome‐scale assembly of the genome of the orange clownfishAmphiprion percula. We utilized single‐molecule real‐time sequencing technology from Pacific Biosciences to produce an initial polished assembly comprised of 1,414 contigs, with a contig N50 length of 1.86 Mb. Using Hi‐C‐based chromatin contact maps, 98% of the genome assembly were placed into 24 chromosomes, resulting in a final assembly of 908.8 Mb in length with contig and scaffold N50s of 3.12 and 38.4 Mb, respectively. This makes it one of the most contiguous and complete fish genome assemblies currently available. The genome was annotated with 26,597 protein‐coding genes and contains 96% of the core set of conserved actinopterygian orthologs. The availability of this reference genome assembly as a community resource will further strengthen the role of the orange clownfish as a model species for research on the ecology and evolution of reef fishes.
Does Family History of Alcohol Use Disorder Relate to Differences in Regional Brain Volumes? A Descriptive Review with New Data
Authors: McPhee Matthew D. , Claus Eric D. , Boileau Isabelle , Lee Andy C. H. , Graff‐Guerrero Ariel , Hendershot Christian S.
Published: September 2018

Background

Differences in regional brain volumes as a function of family history (FH) of alcohol use disorder (AUD) have been reported, and it has been suggested that these differences might index genetic risk for AUD. However, results have been inconsistent. The aims of the current study were (i) to provide an updated descriptive review of the existing literature and (ii) to examine the association of FH with indices of subcortical volumes and cortical thickness in a sample of youth recruited based on FH status.

Methods

To address aim 1, a literature search located 15 published studies comprising 1,735 participants. Studies were characterized according to population, analytic methods, regions of interest, and primary findings. To address the second aim, we examined volumetric and cortical thickness in a sample of 69 youth (mean age = 19.71 years, SD = 0.79) recruited based on FH status and matched on drinking variables. Associations of sex and alcohol use with volumetric outcomes were also examined.

Results

Our descriptive review revealed an inconsistent pattern of results with respect to the presence, direction, and regional specificity of volumetric differences across FH groups. The most consistent finding, significantly smaller amygdala volumes in FH+ participants, was not replicated in all studies. In the current sample of youth, measures of subcortical volumes and cortical thickness did not significantly differ as a function of FH, sex, or their interaction.

Conclusions

Evidence for FH group differences in regional brain volumes is inconsistent, and the current study failed to detect any group differences. Further research is needed to confirm the reproducibility of FH group differences and implications for AUD risk.
Reduction in Nonabstinent WHO Drinking Risk Levels and Change in Risk for Liver Disease and Positive AUDIT‐C Scores: Prospective 3‐Year Follow‐Up Results in the U.S. General Population
Authors: Knox Justin , Wall Melanie , Witkiewitz Katie , Kranzler Henry R. , Falk Daniel , Litten Raye , Mann Karl , O'Malley Stephanie S. , Scodes Jennifer , Anton Raymond , Hasin Deborah S. ,   For the Alcohol Clinical Trials (ACTIVE) Workgroup
Published: September 2018

Background

Abstinence is often the treatment aim for alcohol use disorders (AUD), but this may deter individuals who prefer drinking reduction goals from entering treatment, and be an overly restrictive end point in alcohol clinical trials. Nonabstinent drinking reductions that predict improvement in how individuals feel or function may be useful clinical trial outcomes, for example, reductions in the 4‐category World Health Organization (WHO) drinking risk levels. To investigate the clinical relevance of these reductions, we examined their relationship with 2 outcomes of interest to medical providers: liver disease, and positive scores on an alcohol screening measure.

Methods

Current drinkers in a U.S. national survey (n = 21,925) were interviewed in 2001 to 2002 (Wave 1) and re‐interviewed 3 years later (Wave 2). WHO drinking risk levels, liver disease, and the Alcohol Use Disorders Identification Test‐Consumption (AUDIT‐C) were assessed at both waves. Adjusted odds ratios (aORs) were used to indicate the association of change in WHO drinking risk levels with Wave 2 liver disease and AUDIT‐C scores.

Results

Wave 1 very‐high‐risk drinkers who reduced 1, 2, or 3 WHO drinking risk levels had significantly lower odds of Wave 2 liver disease (aORs = 0.34, 0.23, 0.17) and positive AUDIT‐C scores (aORs = 0.27, 0.09, 0.03). Wave 1 high‐risk drinkers who reduced 1 or 2 WHO risk levels had significantly lower odds of positive AUDIT‐C scores (aORs = 0.61, 0.25). Adjusting for alcohol dependence or AUDIT‐C scoring variations did not affect results.

Conclusions

In the highest‐risk drinkers, reductions in WHO drinking risk levels predicted lower likelihood of liver disease and positive AUDIT‐C scores. Results add to findings that reductions in the 4‐category WHO drinking risk levels are a meaningful indicator of how individuals feel and function, and could serve as nonabstinent end points in clinical trials. Results also connect the WHO risk drinking levels to commonly used alcohol screening questions, which may be more familiar to healthcare providers.
Social media and its relationship with mood, self‐esteem and paranoia in psychosis
Authors: Berry N. , Emsley R. , Lobban F. , Bucci S.
Published: September 2018

Objective

An evidence‐base is emerging indicating detrimental and beneficial effects of social media. Little is known about the impact of social media use on people who experience psychosis.

Method

Forty‐four participants with and without psychosis completed 1084 assessments of social media use, perceived social rank, mood, self‐esteem and paranoia over a 6‐day period using an experience sampling method (ESM).

Results

Social media use predicted low mood, but did not predict self‐esteem and paranoia. Posting about feelings and venting on social media predicted low mood and self‐esteem and high paranoia, whilst posting about daily activities predicted increases in positive affect and self‐esteem and viewing social media newsfeeds predicted reductions in negative affect and paranoia. Perceptions of low social rank when using social media predicted low mood and self‐esteem and high paranoia. The impact of social media use did not differ between participants with and without psychosis; although, experiencing psychosis moderated the relationship between venting and negative affect. Social media use frequency was lower in people with psychosis.

Conclusion

Findings show the potential detrimental impact of social media use for people with and without psychosis. Despite few between‐group differences, overall negative psychological consequences highlight the need to consider use in clinical practice.
Correlation between handheld digital device use and asthenopia in Chinese college students: a Shanghai study
Authors: Xu Yupeng , Deng Guoying , Wang Weiheng , Xiong Shuyu , Xu Xun
Published: September 2018

Purpose

The purpose of this study was to investigate the use of handheld digital devices and the prevalence of self‐reported asthenopia among college students in China and their potential relationship.

Methods

Five thousand students were randomly assessed using a self‐reported asthenopia questionnaire. The students’ demographic characteristics and habits regarding digital device use were recorded. Univariate analysis was performed to select potential risk factors, and multivariate logistic regression was used to estimate the odds ratios for the selected risk factors of interest.

Results

Among the 4786 students who completed the survey, the prevalence of asthenopia was 53.3%. Multivariate analysis revealed significant relationships between asthenopia and each of the following: level of digital reliance (OR 1.350, 95%CI: 1.230–1.481), workload, time spent on computer per day, sex and time spent on handheld digital devices in bed and at desk. Aerobic exercise duration (OR 0.912, 95%CI: 0.839–0.990) was found to be strong predictor of less asthenopia complaints.

Conclusion

Asthenopia appears to be common among college students in China. Preventative measures against asthenopia include limiting the amount of time spent using digital devices in bed (<0.5 h), adopting a posture of lying on one's back while doing so and engaging in aerobic exercise for more than one hour per day. Furthermore, studies on this topic are needed.
Can the flipped classroom model improve students’ academic performance and training satisfaction in Higher Education instructional media design courses?
Authors: Kazanidis Ioannis , Pellas Nikolaos , Fotaris Panagiotis , Tsinakos Avgoustos
Published: September 2018

While “flipping” a classroom has gained attention in K‐12 and Secondary school programs, there has been relatively no explicit focus on its effectiveness as a teaching method for instructional media design courses in Higher Education. The purpose of this quasi‐experimental study was to determine the effectiveness of the flipped classroom approach to teaching instructional media design subjects by comparing students’ academic performance and training satisfaction in traditional lecture‐based instruction with those in a flipped classroom. A total of 128 undergraduate students participated voluntarily and were divided into a control (n = 62) and an experimental (n = 66) group, respectively. The study findings indicated substantial differences in both academic performance and training satisfaction between the two groups, with the students in the experimental group performing significantly better. Specifically, the results showed some determining factors associated with training satisfaction that explain why students in flipped classes achieved notably higher mastery in the learning objectives than their control group peers. This study adds to the literature by providing evidence on how a flipped classroom can potentially benefit students’ academic performance, leading to higher training satisfaction and deeper disciplinary understanding in instructional media design courses.
La rivière Romaine en chantier : Transformations contemporaines des territorialités des Innus d'Ekuanitshit
Authors: Desmeules Alexia , Guimond Laurie
Published: September 2018

Depuis 2009, les Innus de la communauté d'Ekuanitshit sur la Côte‐Nord au Québec sont confrontés à un mégaprojet hydroélectrique sur la rivière Romaine, partie intégrante du Nitassinan, leur territoire ancestral. Dans cet article, nous étudions les impacts du chantier sur le rapport tant matériel qu'idéel que les Innus entretiennent à la rivière. Nous explorons l'idée qu'il transforme le rapport traditionnel au territoire — marqué par un fort attachement identitaire et symbolique — en un rapport davantage utilitaire, dicté plutôt par des intérêts économiques et politiques. Notre analyse révèle que les territorialités des Innus, bien qu'elles se soient en partie transformées en s'ouvrant sur l'extérieur et l'altérité, demeurent ancrées dans un fort héritage culturel et une identification profonde au territoire. Nous avançons que ces conceptions différenciées en apparence, de traditions et de modernité, ne sont pas incompatibles. Elles composent des territorialités hybrides à la fois internes et externes, ancestrales et contemporaines, culturelles, sociales et politiques.
Can pain assessment tools accurately measure pain experience of disabled individuals?
Authors: Voepel‐Lewis Terri
Published: September 2018

This commentary is on the original article by Fox et al. on pages 69–74 of this issue.
Anticoagulation in the cardiac patient: A concise review
Authors: Larson Elise A. , German David M. , Shatzel Joseph , DeLoughery Thomas G.
Published: September 2018

Anticoagulation has multiple roles in the treatment of cardiovascular disease, including in management of acute myocardial infarction, during percutaneous coronary intervention, as stroke prophylaxis in patients with atrial arrhythmias, and in patients with mechanical heart valves. Clinical anticoagulation choices in the aforementioned diseases vary widely, due to conflicting data to support established agents and the rapid evolution of evidence‐based practice that parallels more widespread use of novel oral anticoagulants. This review concisely summarizes evidence‐based guidelines for anticoagulant use in cardiovascular disease, and highlights new data specific to direct oral anticoagulants.
Clinical implications of molecular markers in acute myeloid leukemia
Authors: Kayser Sabine , Levis Mark J.
Published: September 2018

The recently updated World Health Organization (WHO) Classification of myeloid neoplasms and leukemia reflects the fact that research in the underlying pathogenic mechanisms of acute myeloid leukemia (AML) has led to remarkable advances in our understanding of the disease. Gene mutations now allow us to explore the enormous diversity among cytogenetically defined subsets ofAML, particularly the large subset of cytogenetically normalAML. Despite the progress in unraveling the tumor genome, only a small number of recurrent mutations have been incorporated into risk‐stratification schemes and have been proven to be clinically relevant, targetable lesions. We here discuss the utility of molecular markers inAMLin prognostication and treatment decision making, specifically highlighting the aberrations included in the currentWHOclassification.
Insular‐limbic dissociation to intra‐epidermal electrical Aδ activation: A comparative study with thermo‐nociceptive laser stimulation
Authors: Hagiwara Koichi , Perchet Caroline , Frot Maud , Bastuji Hélène , Garcia‐Larrea Luis
Published: September 2018

Intra‐epidermal electrical stimulation (IEES) has been shown to activate selectively Aδ fibers subserving spinothalamic‐mediated sensations. Owing to electrically induced highly synchronous afferent volleys, IEES induces Aδ‐mediated evoked potentials at nonpainful intensities, contrasting with thermo‐nociceptive laser pulses which entail painful pricking sensations. Here, we recorded intracortical responses from sensory and limbic‐cognitive regions of human subjects in response to IEE and laser stimuli, in order to test the hypothesis that IEES could dissociate the sensory from nonsensory networks of nociceptive processing. Intracortical evoked potentials were obtained in 11 epileptic patients with stereotactically implanted electrodes in sensory regions receiving spinothalamic afferents (posterior insula), limbic regions receiving spino‐parabrachial input (amygdalar nucleus), and high‐order affective‐cognitive regions (anteromedial frontal cortex, including perigenual anterior cingulate and rostromedial prefrontal areas). Responses in the sensory posterior insula were of similar amplitude and latency to IEE and laser stimuli (after accounting for heat‐transduction time of laser), and consistent in both cases with spinothalamic activation. However, responses to IEES in the amygdala and the anteromedial frontal regions were inconsistent and significantly smaller compared to those evoked to the laser stimulation. Thus, IEES can effectively activate the spinothalamic‐sensory system with little recruitment of affective‐motivational networks, including those triggered by spino‐parabrachio‐amygdalar projections. The fact that identical sensory responses were associated to either painful or nonpainful percepts underscores that subjective pain perception is not solely dependent on the sensory recruitment, but rather on the combined activation of sensory, limbic and cognitive areas with precise spatiotemporal relations.
‘We were fighting for our place’: Resisting gender knowledge regimes through feminist knowledge network formation
Authors: Jones Sally , Martinez Dy Angela , Vershinina Natalia
Published: September 2018

The transformative potential of feminist knowledge in the disciplines of entrepreneurship, business and management has arguably been hindered by persistent gender knowledge regimes that marginalize feminist scholarship and channel widely applicable gender expertise into niche streams, conferences and publication outlets. Whilst offering valuable spaces for feminist knowledge production, removing gender expertise from mainstream fora reduces its centrality to broader debates, maintaining its marginality and limiting its impact. Taking a collaborative autoethnographic approach, we explore the formation and development of a UK‐based organization for feminist entrepreneurship scholars, the Gender and Enterprise Network, as a means of collective resistance to this perpetuation of enforced marginality. Our network challenges extant gender knowledge regimes and offers transformative opportunities within and outside of our respective organizations, providing insights for others wishing to form similar networks and contributing to ongoing debates on the value and valuing of feminist knowledge.
Helicobacter pylori and extragastric diseases
Authors: Ražuka‐Ebela Danute , Giupponi Bianca , Franceschi Francesco
Published: September 2018

Many studies have been performed in the last year concerning the potential role of Helicobacter pylori in different extragastric diseases, reinforcing the idea that specific microorganisms may cause diseases even far from the primary site of infection. While the role of H. pylori on idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency has been well established, there is a growing interest in other conditions, such as cardiovascular, neurologic, dermatologic, obstetric, immunologic, and metabolic diseases. Concerning neurologic diseases, there is a great interest in cognitive impairment and neurodegeneration. The aim of this review was to summarize the results of the most relevant studies published over the last year on this fascinating topic.
Gastric cancer: Basic aspects
Authors: Duarte Henrique O. , Gomes Joana , Machado José C. , Reis Celso A.
Published: September 2018

Despite major breakthroughs in the field of personalized medicine, gastric cancer (GC) remains a clinically challenging disease, characterized by scarce effective treatment options and the lack of reliable molecular tools for the prediction of patient outcome and response to therapy. The pronounced molecular heterogeneity that dictates the phenotypical aggressiveness of gastric neoplasms severely limits the antitumor efficacy of targeted agents brought to clinical trials, and constitutes a favorable setting for the emergence of refractory tumors exhibiting multidrug resistance. We will review the most recent advances in our understanding of GC biology, which are underlying the development and clinical testing of novel targeted therapeutic agents. We will also emphasize how their efficacy and acquired resistance relate to the aberrant molecular signatures that drive gastric malignancy.
Medium‐temperature sintering efficiency of ZrB2 ceramics using polymer‐derived SiBCN as a sintering aid
Authors: Feng Bo , Zhang Yue , Li Bingyang , Hu Shujuan
Published: September 2018

Polymer‐derived SiBCN, with superior thermal stability and amorphous activity, was introduced into ZrB2 powders. This sintering aid highly improved the sintering efficiency of ZrB2 ceramics at medium temperature (1000‐1600°C), which showed a different service temperature range from that of traditional crystal additives. The microstructure and densification behavior of ZrB2–SiBCN samples were mainly studied. The polymer structural evolution including construction, rearrangement, and crystallization of the amorphous SiBCN network, made a large contribution to the densification of ZrB2 ceramics. The carbothermal reduction of pyrolysis carbon with oxide impurities could not only decrease the oxygen content, but also develop the activity of chemical bonds in SiBCN network. Diffusions and reactions at the interface also benefited the microstructure and consolidation of ZrB2–SiBCN ceramics.
Essential role of ryanodine receptor 2 phosphorylation in the effect of azumolene on ventricular arrhythmia vulnerability in a rabbit heart model
Authors: Si Daoyuan , Azam Mohammed Ali , Lai Patrick F. H. , Zamiri Nima , Kichigina Galina , Asta John , Massé Stéphane , Bokhari Mahmoud M. , Porta‐Sánchez Andreu , Labos Christopher , Sun Huan , Yang Ping , Nanthakumar Kumaraswamy
Published: September 2018

Introduction

Following long‐duration ventricular fibrillation (LDVF), reinitiation of ventricular fibrillation (VF) poses a major challenge during resuscitation. Ryanodine receptor 2 (RyR2) becomes dysfunctional following VF. The relationship between LDVF, RyR2 modulation, and ventricular refibrillation, as well as the role of RyR2 phosphorylation, remains unknown.

Methods

Langendorff‐perfused rabbit hearts were subjected to global ischemia and treated with azumolene (or vehicle alone in controls) upon reperfusion. After electrical induction of an initial LDVF episode, each heart was further stimulated electrically to assess reinducibility of VF. Myocardial calcium dynamics were assessed by optical mapping. RyR2 phosphorylation in left ventricular tissue extracts was analyzed by Western blot analysis.

Results

Fewer episodes of refibrillation (lasting ≥ 10 seconds) were induced in azumolene‐treated hearts than in controls (P = 0.01); however, this reduction in refibrillation was abrogated in the presence of the protein kinase A inhibitor H89. Spontaneous calcium elevation was significantly lower in azumolene‐treated hearts than in control hearts (
P = 0.002) and in hearts pretreated with H89 before azumolene (
P = 0.01). RyR2 phosphorylation at Ser2808 was higher in hearts subjected to LDVF than in non‐VF hearts (
P = 0.029), while no significant difference was found at Ser2814. Pretreatment with H89 led to significantly less RyR2 phosphorylation at Ser2808 (
P = 0.04) after LDVF, while pretreatment with KN93 or azumolene alone showed no effects on RyR2 phosphorylation.

Conclusion

Ventricular refibrillation following LDVF was reduced by azumolene, which also improves calcium dynamics. RyR2 phosphorylation at Ser2808 is a prerequisite for the beneficial effects of azumolene.
Systematic re‐evaluation of SCN5A variants associated with Brugada syndrome
Authors: Denham Nathan C. , Pearman Charles M. , Ding Wern Yew , Waktare Johan , Gupta Dhiraj , Snowdon Richard , Hall Mark , Cooper Robert , Modi Simon , Todd Derick , Mahida Saagar
Published: September 2018

Background

A large number of SCN5A variants have been reported to underlie Brugada syndrome (BrS). However, the evidence supporting individual variants is highly heterogeneous.

Objective

We systematically re‐evaluated all SCN5A variants reported in BrS using the 2015 American college of medical genetics and genomics and the association for molecular pathology (ACMG‐AMP) guidelines.

Methods

A PubMed/Embase search was performed to identify all reported SCN5A variants in BrS. Standardized bioinformatic re‐analysis (SIFT, PolyPhen, Mutation Taster, Mutation assessor, FATHMM, GERP, PhyloP, and SiPhy) and re‐evaluation of frequency in the gnomAD database were performed. Fourteen ACMG‐AMP rules were deemed applicable for SCN5A variant analysis.

Results

Four hundred and eighty unique SCN5A variants were identified, the majority of which 425 (88%) were coding variants. One hundred and fifty‐six of 425 (37%) variants were classified as pathogenic/likely pathogenic. Two hundred and fifty‐eight (60%) were classified as variants of uncertain significance, while a further 11 (3%) were classified as benign/likely benign. When considering the subset of variants that were considered “null” variants separately, 95% fulfilled criteria for pathogenicity/likely pathogenicity. In contrast, only 17% of missense variants fulfilled criteria for pathogenicity/likely pathogenicity. Importantly, however, only 25% of missense variants had available functional data, which was a major score driver for pathogenic classification.

Conclusion

Based on contemporary ACMG‐AMP guidelines, only a minority of SCN5A variants implicated in BrS fulfill the criteria for pathogenicity or likely pathogenicity.
Kidney protective effects of baroreflex activation therapy in patients with resistant hypertension
Authors: Wallbach Manuel , Zürbig Petra , Dihazi Hassan , Müller Gerhard A. , Wachter Rolf , Beige Joachim , Koziolek Michael J. , Mischak Harald
Published: September 2018

Baroreflex activation therapy (BAT) is approved for the treatment of resistant hypertension. In addition to blood pressure (BP) reduction, pilot studies suggested several organoprotective effects of BAT. Thirty‐two patients with resistant hypertension were prospectively treated with BAT. Besides office BP and 24‐hour ambulatory BP (ABP) measurements, detection of a urinary proteome‐based classifier (CKD273), which has been shown to predict chronic kidney disease (CKD) progression, was carried out at baseline and after 6 months of BAT. Office BP significantly decreased from 170 ± 25/90 ± 18 to 149 ± 29/82 ± 18 mm Hg. Analysis of CKD273 score and eGFR with CKD‐EPI equation at baseline revealed strong correlation (r = 0.568, P < 0.001). After 6 months of BAT, there was no significant change in CKD273 score (−0.061 [95% CI: −0.262 to 0.140], P = 0.601). However, by stratification of the data regarding ABP response, there was a statistically significant (P = 0.0113) reduction in the CKD273 score from a mean of 0.161 [95% CI: −0.093 to 0.414] to −0.346 [95% CI: −0.632 to −0.060] after BAT in patients with systolic ABP decrease of ≥5 mm Hg. These data emphasized potential nephroprotective effects of BAT in patients with sufficient BP response.
Preventive parenting intervention during childhood and young black adults’ unhealthful behaviors: a randomized controlled trial
Authors: Brody Gene H. , Yu Tianyi , Miller Gregory E. , Ehrlich Katherine B. , Chen Edith
Published: September 2018

Objective

Lifestyle variables such as drug use and excessive weight gain contribute to adult morbidity and mortality. This study was designed to determine whether participation in a preventive intervention designed to enhance supportive parenting can reduce drug use and body mass index (BMI) in young Black adults from disadvantaged neighborhoods.

Method

This study was conducted in the rural southeastern United States. Black parents and their 11‐year‐old children (517 families) were assigned randomly to the Strong African American Families (SAAF) prevention trial or a control condition. Data assessing neighborhood socioeconomic status and supportive parenting were obtained when the youths were ages 11 and 16. When youths were ages 19–21 and 25, drug use and BMI were measured.

Results

As hypothesized, significant three‐way interactions were detected among neighborhood disadvantage, prevention condition, and gender for BMI (B = 3.341, p = .009, 95% CI [0.832, 5.849]) and substance use (B = −0.169, p = .049, 95% CI [−0.337, −0.001]). Living in a disadvantaged neighborhood during adolescence was associated with increased drug use among young men in the control group (simple‐slope = 0.215, p < .003) but not among those in the SAAF condition (simple‐slope = 0.030, p = .650). Neighborhood disadvantage was associated with elevated BMI among young women in the control group (simple‐slope = 3.343, p < .001), but not in the SAAF condition (simple‐slope = 0.204, p = .820).

Conclusions

The results suggest that participation during childhood in a preventive intervention to enhance supportive parenting can ameliorate the effects of life in a disadvantaged neighborhood on men's drug use and women's BMI across ages 19–25 years. These findings suggest a possible role for parenting enhancement programs in narrowing health disparities.
Prevalence of and risk factors for dermatoporosis: a prospective observational study of dermatology outpatients in a Finnish tertiary care hospital
Authors: Kluger N. , Impivaara S.
Published: September 2018

Background

Dermatoporosis describes the cutaneous signs and complications related to chronic cutaneous fragility related to ageing, chronic sun exposure and long‐term use of topical and systemic corticosteroids. Chronic renal failure may be an additional cofactor. The prevalence of dermatoporosis is estimated around 32–37% in France among the elderly.

Objective

We evaluated the prevalence of dermatoporosis and its risk factors in outpatients who attended a consultation in the department of dermatology of Helsinki University Central Hospital.

Methods

A prospective observational study of 176 consecutive outpatients aged 60 years and older, who attended a consultation in the department of dermatology of Helsinki University Central Hospital. Data collection included age, gender, reason for consultation, local or systemic corticosteroid therapy, antiplatelet drugs and anticoagulant therapy, diabetes and chronic kidney failure (glomerular filtration rate < 60 mL/min/m2). The presence of dermatoporosis, location on the body and staging were collected.

Results

30.7% presented dermatoporosis. Lesions were mainly located on the upper limbs (94%), and stage I was the most frequent (75.9% of the cases). Multivariate analysis revealed that dermatoporosis was significantly associated with ultrapotent topical corticosteroids (odds ratio (OR) 5.34, 95% CI 1.85–15.43, P = 0.002), oral corticosteroids (OR 3.22, 95% CI 1.18–8.80, P = 0.022), concomitant corticosteroid therapy, anticoagulant and chronic renal failure (OR 4.02, 95% CI 1.34–12.01, P = 0.013) and age (OR 1.05, 95% CI 1.01–1.10, P = 0.016). Patients with bullous pemphigoid were those with the highest prevalence of dermatoporosis in our cohort (64%).

Conclusion

Acknowledging the selection bias in our study, the prevalence of dermatoporosis in a dermatology consultation in Finland seems as frequent as in France. These results prompt us to weigh the indications of long‐term corticosteroids use in frail elderly patients.
Fin healing and regeneration in sturgeon
Authors: Allen Peter J. , Baumgartner Wes , Brinkman Erin , DeVries Robert J. , Stewart Heather A. , Aboagye Daniel L. , Ramee Shane W. , Ciaramella Michael A. , Culpepper Charlie M. , Petrie‐Hanson Lora
Published: September 2018

Pectoral fin healing in fin spines and rays were examined in juvenile Atlantic sturgeon Acipenser oxyrinchus oxyrinchus following three different sampling techniques (n = 8–9 fish per treatment): entire leading fin spine removed, a 1–2 cm portion removed near the point of articulation, or a 1–2 cm portion removed from a secondary fin ray. Also, to determine whether antibiotic treatment influences healing, an additional group of fish (n = 8) was not given an injection of an oxytetracycline (OTC)‐based antibiotic following removal of the entire leading fin spine. Following fin sampling, fish from different treatments were mixed equally between three large (4,000 I) recirculating systems and fin‐ray healing and mortality were monitored over a 12 month period. To assess healing, blood samples were collected at 4 months to measure immune system responses, radiographs were taken at 4, 8 and 12 months to assess the degree of calcification in regions of damaged fins and fins were analyzed histologically at 12 months. Fish grew from a mean weight of 1.8 to 3.2 kg during the experiment and survival was near 100% in all treatments, with only one fish dying of unknown causes. Leukocyte counts, an indication of health status and survival were similar among treatments and in groups with or without antibiotic injection. Radiographs revealed mineralization took longer in fish with the entire leading fin spine removed and was the slowest near the point of articulation, presumably due to the greater structural support for the pectoral fin at this location. Histological sampling indicated spines and rays had similar healing patterns. Following injury, an orderly matrix of collagen bundles and many evenly spaced scleroblasts were present, transitioning to Sharpey fibres, with concentric layers forming lamellar bone. Healing and mineralization were characterized as periosteal osteogenesis and included embedded osteocytes surrounded by an osteoid seam. Chondroid formation was apparent in a few fractures not associated with treatments. The duration of time for external wound healing and internal mineralization of spines and rays depended on the fin treatment, with the slowest healing observed in fish with the most tissue removed, the entire leading fin spine.
Quantifying damage contributions from convective and stratiform weather types: How well do precipitation and discharge data indicate the risk?
Authors: Schroeer Katharina , Tye Mari R.
Published: September 2018

Convective precipitation is intensifying in many regions, but potential implications of shifts in precipitation types on impacts have not been quantified. Furthermore, risk assessments often focus on rare extremes, but also more frequent hydro‐meteorological events burden private and public budgets. Here synoptic, hydrological, meteorological, and socio‐economic data are merged to analyse 25 years of damage claims in 480 Austrian municipalities. Exceedance probabilities of discharge and precipitation associated with damage reports are calculated and compared for convective and stratiform weather patterns. During April to November, 60% of claims are reported under convective conditions. Irrespective of the weather type, most of the accumulated cost links to minor hazard levels, not only indicating that frequent events are a highly relevant expense factor, but also pointing to deficiencies in observational data. High uncertainty in damage costs attributable to extreme events demonstrates the questionable reliability of calculating low‐frequency event return levels. Significant differences exist among weather types. Stratiform weather types are up to 10 times more often associated with damaging extreme discharge or precipitation, while convective weather shows the highest nuisance level contributions. The results show that changes in convective precipitation are pertinent to risk management as convective weather types have contributed significantly to damage in the past.
Propagation Mechanisms for Government Spending Shocks: A Bayesian Comparison
Authors: KORMILITSINA ANNA , ZUBAIRY SARAH
Published: September 2018

The inability of a simple real business cycle model to predict a rise in consumption in response to increased government expenditures, observed in many empirical studies, has stimulated the development of alternative theories of government spending shocks. Using the Bayesian approach, we evaluate the quantitative performance of five extant models, and find that neither of the considered transmission mechanisms for government spending helps improve the fit of the baseline model. Moreover, we find that consumption decreases in all estimated models in response to a rise in government spending.
A simultaneous oral and intramuscular prime/sublingual boost with a DNA/Modified Vaccinia Ankara viral vector‐based vaccine induces simian immunodeficiency virus‐specific systemic and mucosal immune responses in juvenile rhesus macaques
Authors: Curtis Alan D. , Jensen Kara , Van Rompay Koen K. A. , Amara Rama R. , Kozlowski Pamela A. , De Paris Kristina
Published: September 2018

Background

A pediatric vaccine to prevent breast milk transmission of human immunodeficiency virus (HIV) may generate greater immune responses at viral entry sites if given by an oral route.

Methods

We compared immune responses induced in juvenile macaques by prime/boosting with simian immunodeficiency virus (SIV)‐expressing DNA/modified vaccinia Ankara virus (MVA) by the intramuscular route (IM), the oral (O)/tonsillar routes (T), the O/sublingual (SL) routes, and O+IM/SL routes.

Results

O/T or O/SL immunization generated SIV‐specific T cells in mucosal tissues but failed to induce SIV‐specific IgA in saliva or stool or IgG in plasma. IM/IM or O+IM/SL generated humoral and cellular responses to SIV. IM/IM generated greater frequencies of TFH in spleen, but O+IM/SL animals had higher avidity plasma IgG and more often demonstrated mucosal IgA responses.

Conclusion

These results suggest that codelivery of HIV DNA/MVA vaccines by the oral and IM routes might be optimal for generating both systemic and mucosal antibodies.