bluuebunny/crossref_metadata_2025 huggingface dataset:
Background selection and FST: Consequences for detecting local adaptation
Authors: Matthey‐Doret Remi , Whitlock Michael C.
Published: July 2019

Background selection is a process whereby recurrent deleterious mutations cause a decrease in the effective population size and genetic diversity at linked loci. Several authors have suggested that variation in the intensity of background selection could cause variation in FST across the genome, which could confound signals of local adaptation in genome scans. We performed realistic simulations of DNA sequences, using recombination maps from humans and sticklebacks, to investigate how variation in the intensity of background selection affects FST and other statistics of population differentiation in sexual, outcrossing species. We show that, in populations connected by gene flow, Weir and Cockerham's (1984; Evolution, 38, 1358) estimator of FST is largely insensitive to locus‐to‐locus variation in the intensity of background selection. Unlike FST, however, dXY is negatively correlated with background selection. Moreover, background selection does not greatly affect the false‐positive rate in FST outlier studies in populations connected by gene flow. Overall, our study indicates that background selection will not greatly interfere with finding the variants responsible for local adaptation.
Weighing Up Exercises on Phrasal Verbs: Retrieval Versus Trial‐and‐Error Practices
Authors: STRONG BRIAN , BOERS FRANK
Published: July 2019

English‐as‐a‐foreign‐language (EFL) textbooks and internet resources exhibit various formats and implementations of exercises on phrasal verbs. The experimental study reported here examines whether some of these might be more effective than others. EFL learners at a university in Japan were randomly assigned to 4 treatment groups. Two groups were presented first with phrasal verbs and their meaning before they were prompted to retrieve the particles from memory. The difference between these 2 retrieval groups was that 1 group studied and then retrieved items 1 at a time, while the other group studied and retrieved them in sets. The 2 other groups received the exercises as trial‐and‐error events, where participants were prompted to guess the particles and were subsequently provided with the correct response. One group was given immediate feedback on each item, while the other group tackled sets of 14 items before receiving feedback. The effectiveness of these exercise implementations was compared through an immediate and a 1‐week delayed posttest. The best test scores were obtained when the exercises had served the purpose of retrieval, although this advantage shrank in the delayed posttest (where scores were poor regardless of treatment condition). On average 70% of the posttest errors produced by the learners who had tackled the exercises by trial‐and‐error were duplicates of incorrect responses they had supplied at the exercise stage, which indicates that corrective feedback was often ineffective.
Smokeless tobacco use and oral neoplasia among urban Indian women
Authors: Mishra Gauravi A. , Pimple Sharmila A. , Gupta Subhadra D.
Published: July 2019

Objectives

Oral cavity cancers are fourth most common cancers among Indian women. The objectives were to create cancer awareness (CA) and screen tobacco‐using women for oral cavity cancers.

Materials and methods

A community‐based CA and screening programme was conducted among women in Mumbai, India. The tobacco‐using women participated in CA and oral cavity screening by oral visual inspection (OVI). All screen‐positive women were referred to nodal hospital and assisted for diagnostic confirmation and treatment completion.

Results

Twelve slum clusters comprising of 138,383 population and 13,492 tobacco‐using women have been covered. Among them, 11,895 (88.2%) participated in CA and 11,768 (87.2%) in OVI. A total of 377 (3.2%) women were screened positive, 275 (72.9%) complied with referral and 207 oral precancers [173 leukoplakia, 9 erythroplakia, 3 erythroleukoplakia and 41 sub‐mucus fibrosis (SMF) including 35 women with multiple precancers] and 7 oral cancers were diagnosed. The detection rate of oral precancerous lesions and oral cancers was 17.6 and 0.6 per 1,000 screened women. Thirty‐five women had multiple oral precancerous lesions. The results of multivariate analysis indicate dose–response relationship between tobacco use and risk of oral precancers.

Conclusion

Good participation rates (>85%) for cancer awareness and OVI were seen among urban slum women in India. Many oral precancer and cancer cases were detected and were managed at the nodal hospital.
Preparing for transition: The effects of a structured transition program on adolescent heart transplant patients’ adherence and transplant knowledge
Authors: Anton Corinne M. , Anton Kristin , Butts Ryan J.
Published: July 2019

Transition to adult health care has become a mainstream focus in pediatric health care as a higher percentage of patients are surviving into adulthood. This study investigated the success of a structured educational transition program in improving pediatric heart transplant patients’ overall medical knowledge, medication adherence, readiness to transition, as well as parental perceptions of their child's readiness to transition to aid in the successful transition to an adult heart transplant program. Patients underwent a structured transition program over 2 years that included a total of seven 2‐hour educational sessions hosted quarterly. This study comprised of a retrospective review of 12 heart transplant patients between the ages of 16‐22 years. Test results indicated a statistically significant increase in overall medical knowledge scores from presession assessment compared to post‐session assessment. Participants remained confident in their ability to transition throughout the program. Further, a statistically significant decrease in participant non‐adherence was observed, as percentage of calcineurin inhibitor levels determined to be out of range decreased over the course of the program. Results suggest that a structured transition program is effective in improving overall patient medical knowledge in relation to their heart transplant and enhancing patient medication adherence. To effectively facilitate transition, pediatric providers, caregivers, and patients must communicate to provide a purposeful planned transition experience from pediatric to adult health care.
Misclassification in defining and diagnosing microcephaly
Authors: Kalmin Mariah M. , Gower Emily W. , Stringer Elizabeth M. , Bowman Natalie M. , Rogawski McQuade Elizabeth T. , Westreich Daniel
Published: July 2019

Background

Several health agencies define microcephaly for surveillance purposes using a single criterion, a percentile or Z‐score cut‐off for newborn head circumference. This definition, however, conflicts with the reported prevalence of microcephaly even in populations with endemic Zika virus.

Objective

We explored possible reasons for this conflict, hypothesising that the definition of microcephaly used in some studies may be incompletely described, lacking the additional clinical criteria that clinicians use to make a formal diagnosis. We also explored the potential for misclassification that can result from differences in these definitions, especially when applying a percentile cut‐off definition in the presence of the much lower observed prevalence estimates that we believe to be valid.

Methods

We conducted simulations under a theoretical bimodal distribution of head circumference. For different definitions of microcephaly, we calculated the sensitivity and specificity using varying cut‐offs of head circumference. We then calculated and plotted the positive predictive value for each of these definitions by prevalence of microcephaly.

Results

Simple simulations suggest that if the true prevalence of microcephaly is approximately what is reported in peer‐reviewed literature, then relying on cut‐off‐based definitions may lead to very poor positive predictive value under realistic conditions.

Conclusions

While a simple head circumference criterion may be used in practice as a screening or surveillance tool, the definition lacks clarification as to what constitutes true pathological microcephaly and may lead to confusion about the true prevalence of microcephaly in Zika‐endemic areas, as well as bias in aetiologic studies.
Socio‐economic inequalities in mortality in children with congenital heart disease: A systematic review and meta‐analysis
Authors: Best Kate E. , Vieira Rute , Glinianaia Svetlana V. , Rankin Judith
Published: July 2019

Background

The impact of socio‐economic status (SES) on congenital heart disease (CHD)‐related mortality in children is not well established.

Objectives

We aimed to systematically review and appraise the existing evidence on the association between SES (including poverty, parental education, health insurance, and income) and mortality among children with CHD.

Data sources

Seven electronic databases (Medline, Embase, Scopus, PsycINFO, CINAHL, ProQuest Natural, and Biological Science Collections), reference lists, citations, and key journals were searched.

Study selection and data extraction

We included articles reporting original research on the association between SES and mortality in children with CHD if they were full papers published in the English language and regardless of (a) timing of mortality; (b) individual or area‐based measures of SES; (c) CHD subtype; (d) age at ascertainment; (e) study period examined. Screening for eligibility, data extraction, and quality appraisal were performed in duplicate.

Synthesis

Meta‐analyses were performed to estimate pooled ORs for in‐hospital mortality according to health insurance status.

Results

Of 1388 identified articles, 28 met the inclusion criteria. Increased area‐based poverty was associated with increased odds/risk of postoperative (n = 1), neonatal (n = 1), post‐discharge (n = 1), infant (n = 1), and long‐term mortality (n = 2). Higher parental education was associated with decreased odds/risk of neonatal (n = 1) and infant mortality (n = 5), but not with long‐term mortality (n = 1). A meta‐analysis of four US articles showed increased unadjusted odds of in‐hospital mortality in those with government/public versus private health insurance (OR 1.40, 95% CI 1.24, 1.56). The association between area‐based income and CHD‐related mortality was conflicting, with three of eight articles reporting significant associations.

Conclusion

This systematic review provides evidence that children of lower SES are at increased risk of CHD‐related mortality. As these children are over‐represented in the CHD population, interventions targeting socio‐economic inequalities could have a large impact on improving CHD survival.
Insurance customer behavior: Lessons from behavioral economics
Authors: Richter Andreas , Ruß Jochen , Schelling Stefan
Published: July 2019

In economics it has traditionally been assumed that people make all their decisions like the so‐called homo oeconomicus – that is, maximizing (expected) utility of total wealth. In recent years, economics increasingly recognized that people often exhibit behavioral patterns which are incompatible with the idea of the homo oeconomicus. The field of behavioral economics incorporates insights from the field of psychology to explain discrepancies between predictions of traditional economic theory and actual observed behavior. In this paper, we summarize a selection of well‐established behavioral patterns observed in reality and discuss their relevance for the insurance industry when it comes to better understanding and predicting customer behavior. We also explain that people are not always risk‐averse and give a brief overview over Prospect Theory (probably the most popular behavioral economics alternative to Expected Utility Theory), its shortcomings for predicting behavior over a long time horizon, and its extensions. In total, we point out that, since dealing with risks and insurance products requires complex decision making processes, a deep understanding of the impacts of behavioral factors is essential to better assess and explain costumer behavior.
The facts of fake news: A research review
Authors: Tandoc Edson C.
Published: July 2019

This article offers a review of scholarly research on the phenomenon of fake news. Most studies have so far focused on three main themes: the definition and the scope of the problem; the potential causes; and the impact of proposed solutions. First, scholarly research has defined fake news as a form of falsehood intended to primarily deceive people by mimicking the look and feel of real news. While initial research has shown that only a small fraction of the online audience is exposed to fake news, for this small group of individuals, the impact of fake news can be quite substantial. Second, studies have identified cognitive processes that make individuals more prone to the influence of fake news, such as confirmation bias, selective exposure, and lack of analytical thinking. Fake news also derives its power from its appeal to partisanship, perceived novelty, and repeated exposure facilitated by both bots and human users that share them in the online sphere. Finally, while fact checking has also risen in response to fake news, studies have found that corrections to wrong information only work on some individuals.
Transcription of specific auxin efflux and influx carriers drives auxin homeostasis in tobacco cells
Authors: Müller Karel , Hošek Petr , Laňková Martina , Vosolsobě Stanislav , Malínská Kateřina , Čarná Mária , Fílová Markéta , Dobrev Petre I , Helusová Michaela , Hoyerová Klára , Petrášek Jan
Published: July 2019

Auxin concentration gradients are informative for the transduction of many developmental cues, triggering downstream gene expression and other responses. The generation of auxin gradients depends significantly on cell‐to‐cell auxin transport, which is supported by the activities of auxin efflux and influx carriers. However, at the level of individual plant cell, the co‐ordination of auxin efflux and influx largely remains uncharacterized. We addressed this issue by analyzing the contribution of canonical PIN‐FORMED (PIN) proteins to the carrier‐mediated auxin efflux in Nicotiana tabacum L., cv. Bright Yellow (BY‐2) tobacco cells. We show here that a majority of canonical NtPINs are transcribed in cultured cells and in planta. Cloning of NtPIN genes and their inducible overexpression in tobacco cells uncovered high auxin efflux activity of NtPIN11, accompanied by auxin starvation symptoms. Auxin transport parameters after NtPIN11 overexpression were further assessed using radiolabelled auxin accumulation and mathematical modelling. Unexpectedly, these experiments showed notable stimulation of auxin influx, which was accompanied by enhanced transcript levels of genes for a specific auxin influx carrier and by decreased transcript levels of other genes for auxin efflux carriers. A similar transcriptional response was observed upon removal of auxin from the culture medium, which resulted in decreased auxin efflux. Overall, our results revealed an auxin transport‐based homeostatic mechanism for the maintenance of endogenous auxin levels.

Open Research Badges

This article has earned an Open Data Badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The data is available at http://osf.io/ka97b/
Melatonin enhances cotton immunity to Verticillium wilt via manipulating lignin and gossypol biosynthesis
Authors: Li Cheng , He Qiuling , Zhang Fan , Yu Jingwen , Li Cong , Zhao Tianlun , Zhang Yi , Xie Qianwen , Su Bangrong , Mei Lei , Zhu Shuijin , Chen Jinhong
Published: July 2019

Plants endure challenging environments in which they are constantly threatened by diverse pathogens. The soil‐borne fungus Verticillium dahliae is a devastating pathogen affecting many plant species including cotton, in which it significantly reduces crop yield and fiber quality. Melatonin involvement in plant immunity to pathogens has been reported, but the mechanisms of melatonin‐induced plant resistance are unclear. In this study, the role of melatonin in enhancing cotton resistance to V. dahliae was investigated. At the transcriptome level, exogenous melatonin increased the expression of genes in phenylpropanoid, mevalonate (MVA), and gossypol pathways after V. dahliae inoculation. As a result, lignin and gossypol, the products of these metabolic pathways, significantly increased. Silencing the serotonin N‐acetyltransferase 1 (GhSNAT1) and caffeic acid O‐methyltransferase (GhCOMT) melatonin biosynthesis genes compromised cotton resistance, with reduced lignin and gossypol levels after V. dahliae inoculation. Exogenous melatonin pre‐treatment prior to V. dahliae inoculation restored the level of cotton resistance reduced by the above gene silencing effects. Melatonin levels were higher in resistant cotton cultivars than in susceptible cultivars after V. dahliae inoculation. The findings indicate that melatonin affects lignin and gossypol synthesis genes in phenylpropanoid, MVA, and gossypol pathways, thereby enhancing cotton resistance to V. dahliae.
Diaphragm fatigue and inspiratory muscle metaboreflex in men and women matched for absolute diaphragmatic work during pressure‐threshold loading
Authors: Geary Caitlin M. , Welch Joseph F. , McDonald Malcolm R. , Peters Carli M. , Leahy Michael G. , Reinhard Paige A. , Sheel A. William
Published: July 2019

Key points

The female diaphragm fatigues at a slower rate compared to that of males, with blunted cardiovascular consequences (i.e. inspiratory muscle metaboreflex). It is unclear if these findings are a function of relative or absolute diaphragmatic work.

We asked if sex differences in diaphragm fatigue and the inspiratory muscle metaboreflex persisted during inspiratory loading performed at equal absolute intensities.

We found that matching men and women for absolute diaphragmatic work resulted in an equal degree of diaphragm fatigue, despite women performing significantly greater work relative to body mass.

Metabolite‐induced reflex influences in sympathetic outflow originating from the diaphragm are attenuated in women, with potential implications for blood flow distribution during exercise.

In response to inspiratory pressure‐threshold loading (PTL), women have greater inspiratory muscle endurance time, slower rate of diaphragm fatigue development, and a blunted pressor response compared to men. It is unclear if these differences are due to discrepancies in absolute diaphragm force output. We tested the hypothesis that following inspirations performed at equal absolute intensities, females would develop a similar level of diaphragm fatigue and an attenuated cardiovascular response relative to men. Healthy young men (n = 8, age = 24 ± 3 years) and women (n = 8, age = 23 ± 3 years) performed PTL whilst targeting a transdiaphragmatic pressure (Pdi) of 92 cmH2O for 5 min. Diaphragm fatigue was assessed via twitch Pdi (Pdi,tw) using cervical magnetic stimulation. Heart rate (HR) and mean arterial blood pressure were monitored continuously. During PTL, the absolute amount of diaphragm work was not different between men (13,399 ± 2019 cmH2O s) and women (12,986 ± 1846 cmH2O s; P > 0.05); however, women performed the PTL task at a higher relative di/Pdi,max. Following inspiratory PTL, the magnitude of reduction in Pdi,tw was similar between men (−27.1 ± 7.2%) and women (−23.8 ± 13.8%; P > 0.05). There were significant increases in HR over time (P < 0.05), but this did not differ on the basis of sex (P > 0.05). Mean arterial blood pressure increased significantly over time in both men and women (P < 0.05); however, the rate of change was higher in men (6.24 ± 2.54 mmHg min−1) than in women (4.15 ± 2.52 mmHg min−1) (P < 0.05). We conclude that the female diaphragm is protected against severe fatigue when inspiratory work is excessive and as a result does not evoke overt sympathoexcitation.
Elastic Foundation Solution for the Energy Release Rate and Mode Partitioning of Face/Core Debonds in Sandwich Composites
Authors: Kardomateas George A. , Pichler Niels , Yuan Zhangxian
Published: July 2019

The goal of this paper is to derive closed form expressions for the energy release rate and mode partitioning of face/core debonds in sandwich composites, which include loading in shear. This is achieved by treating a finite length sandwich beam as having a “debonded” section where the debonded top face and the substrate (core and bottom face) are free and a “joined” section where a series of springs (elastic foundation) exists between the face and the substrate. The elastic foundation analysis is comprehensive and includes the deformation of the substrate part (unlike other elastic foundation studies in the literature) and is done for a general asymmetric sandwich construction. A J-integral approach is subsequently used to derive a closed form expression for the energy release rate. In the context of this elastic foundation model, a mode partitioning approach based on the transverse and axial displacements at the beginning of the elastic foundation (“debond tip”) is proposed. The results are compared with finite element results and show very good agreement.
Atomic deuteration of epitaxial many-layer graphene on 4H-SiC(0001¯)
Authors: Mazza Alessandro R. , Miettinen Anna , Conrad Matt , Charlton Timothy R. , He Xiaoqing , Guha Suchi , Bian Guang , Lin Jian , Conrad Edward H. , Miceli Paul F.
Published: July 2019

From studies of single-layer graphene, the authors find that atomic deuteration indeed does lead to reversible chemisorption. However, they find that atomic deuterium treatment of many-layer epitaxially grown graphene on C-face 4H-SiC only affects the surface graphene layer and the buried graphene/SiC interface. Raman and x-ray diffraction experiments reveal that only a small portion of the graphene is affected, showing no interlayer incorporation of deuterium. However, x-ray reflectivity and cross-sectional transmission electron microscopy demonstrate a change of the buried graphene/SiC interface, which resembles a delamination of graphene from the substrate. In some cases, multiple atomic treatments lead to complete delamination of the graphene film.
Nanostructured MoOx films deposited on c-plane sapphire
Authors: Novotný Petr , Lamb H. Henry
Published: July 2019

Molybdenum oxide films were deposited on α-Al2O3 (0001) at 580 °C using MoO3 from a conventional molecular beam epitaxy Knudsen cell. A relatively smooth film (RMS roughness 1.1 nm) was deposited in 1 min at 580 °C using a Knudsen cell temperature of 620 °C; however, after 15 min deposition under these conditions, isolated islands (30–50 nm wide × 10–20 nm tall) develop that are stable to annealing at 600 °C for 60 min. XPS evidenced that the films are oxygen deficient with an average formula of MoO2.7. The authors infer that this oxygen deficiency is responsible for their thermal stability and may have significant effects on their catalytic and electronic properties. In contrast, stoichiometric MoO3 films deposited at 400 °C sublime completely during annealing at 600 °C.
Stretchable batteries with gradient multilayer conductors
Authors: Gu Minsu , Song Woo-Jin , Hong Jaehyung , Kim Sung Youb , Shin Tae Joo , Kotov Nicholas A. , Park Soojin , Kim Byeong-Su
Published: July 2019

A new design for stretchable conductors is developed by stratified composite assembly for future stretchable devices.
Two-dimensional nuclear magnetic resonance spectroscopy with a microfluidic diamond quantum sensor
Authors: Smits Janis , Damron Joshua T. , Kehayias Pauli , McDowell Andrew F. , Mosavian Nazanin , Fescenko Ilja , Ristoff Nathaniel , Laraoui Abdelghani , Jarmola Andrey , Acosta Victor M.
Published: July 2019

We demonstrate a microfluidic platform for multidimensional NMR using prepolarization and detection with a diamond quantum sensor.
Model-Based Relationship between the Molecular Bacterial Load Assay and Time to Positivity in Liquid Culture
Authors: Svensson Robin J. , Sabiiti Wilber , Kibiki Gibson S. , Ntinginya Nyanda E. , Bhatt Nilesh , Davies Geraint , Gillespie Stephen H. , Simonsson Ulrika S. H.
Published: July 2019

The molecular bacterial load (MBL) assay is a new tuberculosis biomarker which provides results in ∼4 hours. The relationship between MBL and time-to-positivity (TTP) has not been thoroughly studied, and predictive models do not exist. We aimed to develop a model for MBL and identify the MBL-TTP relationship in patients.
A Specific Sugar Moiety in the Lactococcus lactis Cell Wall Pellicle Is Required for Infection by CHPC971, a Member of the Rare 1706 Phage Species
Authors: Marcelli Barbara , de Jong Anne , Karsens Harma , Janzen Thomas , Kok Jan , Kuipers Oscar P.
Published: July 2019

Gathering information on how lactococcal bacteriophages recognize their host and proliferate in the dairy environment is of vital importance for the establishment of proper starter culture rotation plans and to avoid fermentation failure and consequent great economic losses for dairy industries. We provide strong evidence on the type of receptor recognized by a newly isolated 1706-type lactococcal bacteriophage, increasing knowledge of phage-host interactions relevant to dairying. This information can help to prevent phage infection events that, so far, are hard to predict and avoid.
Molecular Basis of Unexpected Specificity of ABC Transporter-Associated Substrate-Binding Protein DppA from Helicobacter pylori
Authors: Rahman Mohammad M. , Machuca Mayra A. , Khan Mohammad F. , Barlow Christopher K. , Schittenhelm Ralf B. , Roujeinikova Anna
Published: July 2019

The World Health Organization listed
Helicobacter pylori
as a high-priority pathogen for antibiotic development. The potential of using peptide transporters in drug design is well recognized. We discovered that the substrate-binding protein of the ABC transporter for peptides, termed dipeptide permease, is an unusual member of its family in that it directly binds peptides of diverse amino acid sequences, ranging between two and eight residues in length. We also provided a structural rationale for the observed broad specificity. Since the ability to import peptides as a source of carbon is critical for
H. pylori
, our findings will inform drug design strategies based on inhibition or fusion of membrane-impermeant antimicrobials with peptides.
Timing Is Everything: Impact of Naturally Occurring
Staphylococcus aureus
AgrC Cytoplasmic Domain Adaptive Mutations on Autoinduction
Authors: Sloan Tim J. , Murray Ewan , Yokoyama Maho , Massey Ruth C. , Chan Weng C. , Bonev Boyan B. , Williams Paul
Published: July 2019

Virulence factor expression in
Staphylococcus aureus
is regulated via autoinducing peptide (AIP)-dependent activation of the sensor kinase AgrC, which forms an integral part of the
agr
quorum sensing system. In response to bound AIP, the cytoplasmic domain of AgrC (AgrC-cyt) undergoes conformational changes resulting in dimerization, autophosphorylation, and phosphotransfer to the response regulator AgrA. Naturally occurring mutations in AgrC-cyt are consistent with repositioning of key functional domains, impairing dimerization and restricting access to the ATP-binding pocket. Strains harboring specific AgrC-cyt mutations exhibit reduced AIP autoinduction efficiency and a timing-dependent attenuation of cytotoxicity which may confer a survival advantage during established infection by promoting colonization while restricting unnecessary overproduction of exotoxins.
A Virtual Tour of the Cell: Impact of Virtual Reality on Student Learning and Engagement in the STEM Classroom
Authors: Bennett Jennifer A. , Saunders Colin P.
Published: July 2019

This study assesses the educational impact of virtual reality (VR) on student learning and engagement in a sophomore-level cell biology course taught at Otterbein University. Using VR, students toured the cell and its environment within the human body. Next, students completed a team challenge where they worked as pairs to match images of cell components taken from the virtual reality application with the appropriate name. Finally, students were given a voluntary survey that presented questions about their perceptions of the VR experience and the associated cell sorting activity. Survey results revealed that a majority of students enjoyed the VR experience and felt that it had a positive impact on their education. These results indicate the potential supportive role that VR may have in a variety of undergraduate courses.
Using “Research Boxes” to Enhance Understanding of Primary Literature and the Process of Science
Authors: Carmichael Jeffrey S. , Allison Lizabeth A.
Published: July 2019

Helping undergraduate students engage with primary literature and understand the process of science are high-priority skills in most life science courses. Collaborative learning activities that enhance these skills will continue to be in high demand by instructors at all levels. Here we present a “Research Box” learning activity that helps students engage with primary research articles in a guided and collaborative fashion. Students summarize key components of an empirical study in a one-page figure. An assessment rubric is also included that can be easily modified by instructors to meet their specific needs. Assessment data from two institutions reveal that students value this activity and report that it increases their confidence at understanding primary research articles and experimental results. The Research Box activity is easy to implement, can be completed in a single class period, and provides instructors with a well-defined way to assess student comprehension of experimental design and data interpretation.
Revisiting Hepatitis B Virus: Challenges of Curative Therapies
Authors: Hu Jianming , Protzer Ulrike , Siddiqui Aleem
Published: July 2019

With a yearly death toll of 880,000, hepatitis B virus (HBV) remains a major health problem worldwide, despite an effective prophylactic vaccine and well-tolerated, effective antivirals. HBV causes chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The viral genome persists in infected hepatocytes even after long-term antiviral therapy, and its integration, though no longer able to support viral replication, destabilizes the host genome.
Скорости реакций, существенных для термоядерных мишеней
Authors: Белов Александр Александрович , Belov Aleksandr Aleksandrovich , Калиткин Николай Николаевич , Kalitkin Nikolai Nikolaevich , Топор Олег Игоревич , Topor Oleg Igorevich , Федоров И А , Fedorov I A
Published: July 2019

Для расчета задач управляемого термоядерного синтеза традиционно используют четыре ядерные реакции. В работе проведено сравнение сечений большого числа термоядерных реакций между легчайшими элементами. Показано, что помимо традиционных четырех реакций ощутимый вклад может внести реакция $\mathrm{T+T}\to2n+ ^4\mathrm{He}$. При низких температурах существенный вклад вносят реакции $\mathrm{D}+p\to \gamma+ ^3\mathrm{He}$ и $\mathrm{T}+p\to \gamma+ ^4\mathrm{He}$, остальными реакциями, по-видимому, можно пренебречь. Для указанных реакций проведена более тщательная обработка экспериментальных данных и построены аппроксимации высокой точности. У новых реакций точность нахождения $\mathrm{S}$-фактора составила $2$-$6%$, а точность скорости реакции - $3$-$5%$.
Гибридный фрактально-стохастический подход к моделированию кинетики переключения сегнетоэлектриков в режиме инжекции
Authors: Мороз Любовь Игоревна , Moroz Lyubov' Igorevna , Масловская Анна Геннадьевна , Maslovskaya A G
Published: July 2019

Работа посвящена разработке и реализации гибридного фрактально-стохастического подхода к математическому моделированию электронно-индуцированной кинетики переключения поляризации сегнетоэлектриков как самоподобных физических систем с памятью. Математическая модель фрактальной динамической системы включает начальную задачу для дифференциального уравнения дробного порядка. Вычислительные алгоритмы решения дробно-дифференциальной задачи построены с использованием предиктор-корректорных схем в концепции метода Адамса-Башфорта-Моултона. На основе метода Монте-Карло предложен стохастический алгоритм симуляции процесса зародышеобразования при перестройке доменной структуры сегнетоэлектрика. Описаны результаты вычислительных экспериментов по оценке тока переключения поляризации сегнетоэлектрика в сравнении с данными эксперимента в режиме инжекции.
Priority setting for new systematic reviews: processes and lessons learned in three regions in Africa
Authors: Effa Emmanuel E , Oduwole Olabisi , Schoonees Anel , Hohlfeld Ameer , Durao Solange , Kredo Tamara , Mbuagbaw Lawrence , Meremikwu Martin , Ongolo-Zogo Pierre , Wiysonge Charles , Young Taryn
Published: July 2019

Priority setting to identify topical and context relevant questions for systematic reviews involves an explicit, iterative and inclusive process. In resource-constrained settings of low-income and middle-income countries, priority setting for health related research activities ensures efficient use of resources. In this paper, we critically reflect on the approaches and specific processes adopted across three regions of Africa, present some of the outcomes and share the lessons learnt while carrying out these activities. Priority setting for new systematic reviews was conducted between 2016 and 2018 across three regions in Africa. Different approaches were used: Multimodal approach (Central Africa), Modified Delphi approach (West Africa) and Multilevel stakeholder discussion (Southern-Eastern Africa). Several questions that can feed into systematic reviews have emerged from these activities. We have learnt that collaborative subregional efforts using an integrative approach can effectively lead to the identification of region specific priorities. Systematic review workshops including discussion about the role and value of reviews to inform policy and research agendas were a useful part of the engagements. This may also enable relevant stakeholders to contribute towards the priority setting process in meaningful ways. However, certain shared challenges were identified, including that emerging priorities may be overlooked due to differences in burden of disease data and differences in language can hinder effective participation by stakeholders. We found that face-to-face contact is crucial for success and follow-up engagement with stakeholders is critical in driving acceptance of the findings and planning future progress.
Clinical benefit of two-times-per-day aclidinium bromide compared with once-a-day tiotropium bromide hydrate in COPD: a multicentre, open-label, randomised study
Authors: Kamei Tadashi , Nakamura Hiroyuki , Nanki Nobuki , Minakata Yoshiaki , Matsunaga Kazuto , Mori Yoshihiro
Published: July 2019

Objective

Chronic obstructive pulmonary disease (COPD) is mainly treated pharmaceutically with bronchodilators. The purpose of this study was to evaluate the clinical benefits of two-times-per-day aclidinium bromide (Acli-BID) compared with once-a-day tiotropium bromide hydrate (Tio-QD) in patients with COPD.

Design

This study was a multicentre, open-label, randomised study.

Setting

Fourcentres in Kagawa prefecture, Japan.

Participant

Patients who were diagnosed to have COPD Grade 2–3 according to the Global Initiative for Chronic Obstructive Lung Disease 2015 criteria were enrolled.

Interventions

Patients were randomly assigned to receive Acli-BID or Tio-QD at a 1:1 ratio, and followed for 8 weeks. Acli-BID was administered in the morning and night, and Tio-QD was administered in the night.

Primary and secondary outcome measures

Primary outcome was forced expiratory volume in one second area under the curve (FEV1AUC0-3), and secondary outcomes were pulmonary function, physical activity, St George’s Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC), the 8-item Short-Form Health Survey (SF-8) and COPD exacerbations. Adverse events were evaluated during the study.

Results

44 patients were included in this study. FEV1AUC0-3at week 8 was 4.62±1.43 L·hour in Acli-BID and 4.73±1.60 L·hour in Tio-QD (mean difference (MD) −0.11 L·hour; 95% CI), −1.04 to 0.83). Significant improvement was observed in activity-related subscales of SGRQ (MD −7.78; 95% CI −14.61 to −0.94) and SF-8 (MD 4.01; 95% CI 0.37 to 7.65), mMRC (MD −0.66; 95% CI −1.19 to −0.13) and rate ratio (0.52, 95% CI 0.27 to 0.99) of exacerbations in the Acli-BID compared with the Tio-QD. Acli-BID and Tio-QD significantly improved sedentary behaviour (MD −35.20 min; 95% CI −67.41 to −2.94 and MD −55.40 min; 95% CI −98.15 to −12.77) within each group, but there was no significant difference between the two groups.

Conclusion

Acli-BID as with Tio-QD could be one of the therapeutic options for patients with COPD to improve pulmonary function. Also, our results suggest that intervention with bronchodilators enhanced physical activity in patients with COPD.

Trial registration number

UMIN 000020020.
Effect of combined testing of ceramides with high-sensitive troponin T on the detection of acute coronary syndrome in patients with chest pain in China: a prospective observational study
Authors: Yao Kang , Wang Yanzhong , Xu Demin , Liu Xuebo , Shen Chengxing , Hu Wei , Wang Zhe , Wu Runda , Tang Xianglin , Sun Aijun , Zou Yunzeng , Qian Juying , Wu Guangyu , Guo Xin , Cheng Xiaoliang , Ge Junbo
Published: July 2019

Objective

Ceramides are associated with coronary plaque vulnerability. We aim to investigate the potential diagnostic value of ceramides for acute coronary syndrome (ACS) in Chinese patients with chest pain.

Design

Prospective observational survey.

Setting

Shanghai, China, 2016–2017.

Participants

A total of 2773 patients with chest pain from four hospitals in Shanghai, China, between August 2016 and October 2017.

Main outcome measures

Performance of metabolites model in detection of ACS cases including ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina.

Results

Plasma levels of 12 ceramide molecules and corresponding ratios were compared between patients diagnosed with ACS and those without. Cer(d18:1/24:1(15Z))/Cer(d18:1/24:0) ratio, Cer(d18:1/14:0) and Cer(d18:1/22:0) were independent predictors of ACS after adjustment of traditional risk factors and high-sensitivecardiac troponin T. Receiver operating characteristic curve analysis showed a significant improvement in detecting ACS in the multivariable model with ceramides compared with that without (0.865 (0.840 to 0.889) vs 0.808 (0.776 to 0.841), p<0.001).

Conclusion

Distinct plasma ceramides are independent diagnostic predictors of ACS among patients with chest pain. Ceramides together with high-sensitive troponin and traditional factors showed great potential in identifying ACS among patients with chest pain.
Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis
Authors: Bettiol Alessandra , Lombardi Niccolò , Crescioli Giada , Avagliano Laura , Mugelli Alessandro , Ravaldi Claudia , Vannacci Alfredo
Published: July 2019

Introduction

Fetal growth restriction (FGR) includes different conditions in which a fetus fails to reach the own full growth, and accounts for 28%–45% of non-anomalous stillbirths. The management of FGR is based on the prolongation of pregnancy long enough for fetal organs to mature while preventing starvation. As for pharmacological management, most guidelines recommend treatment with low-dose aspirin and/or with heparin, although this approach is still controversial and innovative promising therapies are under investigation. As no firm evidence exists to guide clinicians towards the most effective therapeutic intervention, this protocol describes methods for a systematic review and network meta-analysis (NetMA) of pharmacological treatments for FGR prevention.

Methods and analysis

We will search MEDLINE and Embase for clinical trials and observational studies performed on gestating women with clinically diagnosed risk of FGR. Experimental interventions will include heparin and low-molecular-weight heparin, acetylsalicylic acid, antiplatelet agents, phosphodiesterase type 3 and 5 inhibitors, maternal vascular endothelial growth factor gene therapy, nanoparticles, microRNA, statins, nitric oxide donors, hydrogen sulphide, proton pump inhibitors, melatonin, creatine and N-acetylcysteine, and insulin-like growth factors, compared between each other or to placebo or no treatment. Primary efficacy outcome is FGR. Secondary efficacy outcomes will be preterm birth, fetal or neonatal death and neonatal complications. For the safety outcome, all adverse events reported in included studies and experienced by either mothers, fetuses or newborns will be considered. Two review authors will independently screen title, abstract and full paper text, and will independently extract data from included studies. Where possible and appropriate, for primary and secondary efficacy outcomes, a NetMA will be performed using a random-effects model within a frequentist framework. Adverse events will be narratively described.

Ethics and dissemination

Results will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.

PROSPERO registration number

CRD42019122831.
Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies
Authors: Wildisen Lea , Moutzouri Elisavet , Beglinger Shanthi , Syrogiannouli Lamprini , Cappola Anne R , Åsvold Bjørn O , Bakker Stephan J L , Ceresini Graziano , Dullaart Robin , Ferrucci Luigi , Grabe Hans , Jukema J Wouter , Nauck Matthias , Trompet Stella , Völzke Henry , Westendorp Rudi G J , Gussekloo Jacobijn , Peeters Robin P , Klöppel Stefan , Aujesky Drahomir , Bauer Douglas C , Rodondi Nicolas , Del Giovane Cinzia , Feller Martin
Published: July 2019

Introduction

Prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association.

Methods and analysis

We will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model.

Ethics and dissemination

Formal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal.

PROSPERO registration number

CRD42018091627.
Financial conflicts of interest of clinicians making submissions to the pan-Canadian Oncology Drug Review: a descriptive study
Authors: Lexchin Joel
Published: July 2019

Objectives

This study examines financial conflict of interest (FCOI) of clinicians who made submissions to the pan-Canadian Oncology Drug Review (pCODR), the arm of the Canadian Agency for Drugs and Technology in Health that recommends whether oncology drug indications should be publicly funded. Final reports from pCODR published between October 2016 and February 2019 were examined.

Design

Descriptive study.

Data sources

Website of pCODR.

Interventions

None.

Primary and secondary outcomes

The primary outcome is the number of submissions declaring FCOI. Secondary outcomes are the number of times where clinicians agreed and disagreed with preliminary recommendation from pCODR and the association between the distribution of individual clinicians’ FCOI and pCODR’s funding recommendations.

Results

There were 46 drug indication reports from pCODR. Clinicians made 261 submissions. Clinicians declared they received payments from companies 323 times and named 38 different companies making those payments a total of 500 times. Financial conflicts with drug companies were declared in 176 (66.3%) of all submissions. In 21 (45.7%) of the 46 drug indications, 50% or more of the clinicians had a conflict with the company making the drug. Clinicians commented on 37 preliminary recommendations. In all 25 where pCODR recommended funding or conditional funding, the clinicians either agreed or agreed in part. pCODR recommended that the drug indication not be funded 12 times and 9 times clinicians disagreed with that recommendation. The distribution of clinician responses was statistically significantly different depending on whether pCODR recommended funding/conditional funding or do not fund p<0.0001 (Fisher exact test). The distribution of clinicians’ FCOI differed depending on whether the recommendation was fund/conditional fund or do not fund p=0.027 (Fisher exact test).

Conclusion

Financial conflicts with pharmaceutical companies are widespread among experts making submissions to the pCODR.