bluuebunny/crossref_metadata_2025 huggingface dataset:
Bronchodilator responsiveness as a predictor of success for bronchial thermoplasty
Authors: Langton David , Ing Alvin , Fielding David , Wang Wei , Plummer Virginia , Thien Francis
Published: July 2018

Background and objective

A characteristic feature of asthma is hypertrophied airway smooth muscle, responsible for bronchoconstriction. This is the target of bronchial thermoplasty (BT). It is known that with increasing time and severity some patients develop remodelled airways with fixed airflow obstruction. The question arises whether these patients will still respond to BT.

Methods

Forty‐nine consecutive severe asthmatic patients were prospectively evaluated at baseline and then 6 months after BT. The characteristics recorded included medication usage, exacerbation history, spirometry and the Asthma Control Questionnaire 5‐Item Version score (ACQ‐5). Seven patients were excluded as they did not demonstrate airflow obstruction at baseline (forced expiratory ratio (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)) < 70%). The remaining 42 patients were divided into two cohorts based on their response to bronchodilator. Eighteen patients in whom the FEV1 improved by at least 12% and 200 mL following bronchodilator were allocated to Group 1 (reversible). The remaining patients were allocated to Group 2 (fixed). The outcomes following BT in these two groups were then compared.

Results

The patient age was 57.2 ± 12.4 years, the ACQ‐5 was 3.2 ± 1.0 and the FEV1 56.0 ± 16.4% predicted. At baseline, the patient cohorts were very similar, save for the response to bronchodilator, which was 28.1 ± 12.5% in Group 1 and 4.1 ± 5.3% in Group 2. Both groups responded to BT equally well, with significant improvements in ACQ‐5, salbutamol usage, exacerbation frequency and the weaning of oral corticosteroids.

Conclusion

In patients with severe asthma, the presence or absence of variable airflow obstruction as measured by spirometry does not appear to influence outcomes from BT.
White Ethnic Diversity in Small Town Iowa: A Multilevel Analysis of Community Attachment
Authors: Flagg Chloe , Painter Matthew A.
Published: July 2018

Community attachment is the feeling of being connected to community life. Within the community attachment literature, two classic approaches frame scholars’ understanding of this important dimension of community life: the linear development and systemic models. Our empirical models emphasize different factors for community attachment, including population size, density, and heterogeneity for the linear development model and age, length of residence, and social status for the systemic model. Surprisingly, heterogeneity has been omitted from analyses of the linear development model throughout the literature since its introduction, a shortcoming our study addresses. Though heterogeneity can be conceptualized in a number of ways, a large—and growing—body of literature focuses on the effects of race and ethnicity for communities. Here, we focus on a particular type of ethnic heterogeneity—European ancestry—and reincorporate this essential dimension of communities back into the linear development model of community attachment. Using data from the 2004 wave of the Iowa Community Survey and multilevel modeling techniques, we explore how white ethnic diversity matters for community life. We conclude with a discussion of the implications of our study, including potential avenues for future research focusing on other ethnicities that are often subsumed under broader racial and panethnic labels.
The transition from arable lands to rubber tree plantations in northern Thailand impacts weed assemblages and soil physical properties
Authors: Neyret M. , Robain H. , de Rouw A. , Soulileuth B. , Trisophon K. , Jumpa K. , Valentin C.
Published: July 2018

In South‐East Asia, rapid land use changes in recent decades have raised concerns for biodiversity and soil conservation. Weeds provide many ecosystemic services for soil protection and support biodiversity, and could mitigate the negative effects of intensification. We investigated the changes in weed assemblages and weed–soil interactions on a chronosequence from annual crops to mature rubber tree plantations. We sampled five fields for each of four land uses in mountainous northern Thailand (rainfed upland rice, maize, young rubber tree (RT) intercropped with maize, and mature RT). We characterized weed assemblages (abundance, richness) and soil properties (bulk density, water, carbon and nitrogen content). Rice had the most diverse and abundant weed assemblages. Weed assemblages differed between (i) rice, (ii) maize and young RT with maize and (iii) mature RT. Soil water content was the highest in mature RT. Other soil properties varied strongly within and among fields, and did not vary significantly among land uses. Water and nitrogen content increased overall with living soil cover but decreased with weed species richness in mature RT. Such interactions could provide a basis for sustainable weeding practices favourable to soil and biodiversity conservation.
The multiple ontologies of freshness in theUKand Portuguese agri‐food sectors
Authors: Jackson Peter , Evans David M. , Truninger Mónica , Meah Angela , Baptista João Afonso
Published: July 2018

This paper adopts a material‐semiotic approach to explore the multiple ontologies of “freshness” as a quality of food. The analysis is based on fieldwork in theUKand Portugal, with particular emphasis on fish, poultry, and fruit and vegetables. Using evidence from archival research, ethnographic observation and interviews with food businesses (including major retailers and their suppliers) plus qualitative household‐level research with consumers, the paper unsettles the conventional view of freshness as a single, stable quality of food. Rather than approaching the multiplicity of freshness as a series of social constructions (different perspectives on essentially the same thing), we identify its multiple ontologies. The analysis explores their enactment as uniform and consistent, local and seasonal, natural and authentic, and sentient and lively. The paper traces the effects of these enactments across the food system, drawing out the significance of our approach for current and future geographical studies of food.
Skylar, Inc.: Traditional Cost System vs. Activity-Based Cost System – A Managerial Accounting Case Study
Authors: Huang Qianyun
Published: July 2018

This case is about a fictitious office workstation manufacturing company “Skylar Inc.” and their implementation of the traditional cost system and the activity-based cost system (ABC, hereafter) when allocating product costs. The case focuses on the application of activity-based costing in assigning costs to activity cost pools, calculating activity rates, and assigning activity costs to cost objects. It also highlights the difference between the traditional cost system and ABC in regards to allocating manufacturing and non-manufacturing overhead costs and assigning direct costs to products. This case is designed to provide students with both number crunching exercises and theoretical discussions of the topics.
Estimating the Impact of Structural Reforms to Increase the Female Participation Rate in Malta
Authors: Micallef Brian
Published: July 2018

Malta registered the largest increase in the female participation rate among European countries since 2008. This increase was driven by various policy initiatives aimed to attract more females to the labour market but also by the changing role of women in society. Furthermore, at 53.8% in 2015, the female participation rate in Malta still remains relatively low by European standards, suggesting further catching-up potential. The trend increase in participation, driven mostly by females, is estimated to have contributed, on average, to 0.8 percentage points per annum to Malta’s potential GDP between 2008 and 2015. The impact of reforms is calculated by adjusting the post-2008 participation rate to long run trends in Maltese society, as well as using a cohort model that accounts for the changing demographics and education attainment of the workforce. The median impact of the estimates presented in this paper suggests that around half of the increase in the female participation rate is attributable to reforms. These reforms are estimated to have raised potential GDP growth in Malta by around 0.3 percentage point per annum between 2008 and 2015.
Reviewer Acknowledgements
Authors: Young James
Published: July 2018

International Journal of Social Science Studies (IJSSS) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether IJSSS publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue. Reviewers for Volume 6, Number 8Abdul Azim Akhtar, Independent Academic & Researcher, Delhi, IndiaAgboola O. Paul", Universiti Teknologi Malaysia, MalaysiaAmir Hossain, IBAIS University, BangladeshAslan,Yasin, Sinop University, TurkeyEmanuele Achino, C. D. T. O., ItalyFroilan Mobo, Philippine Merchant Marine Academy, PhilippinesLaura Diaconu Maxim, "Alexandru Ioan Cuza University" of Iasi, RomaniaMałgorzata Haładewicz, Opole University of Technology, PolandMichael Brooks, North Carolina A&T State University, USASerkan Cicek, Mugla Sitki Kocman University, Turkey
Preconditioning contractions prevent the delayed onset of myofibrillar dysfunction after damaging eccentric contractions
Authors: Yamada Ryotaro , Himori Koichi , Tatebayashi Daisuke , Ashida Yuki , Ikezaki Kazumi , Miyata Hirohumi , Kanzaki Keita , Wada Masanobu , Westerblad Håkan , Yamada Takashi
Published: July 2018

Key points

We examined the mechanisms underlying the positive effect of preconditioning contractions (PCs) on the recovery of muscle force after damaging eccentric contractions (ECCs).

The mechanisms underlying the immediate force decrease after damaging ECCs differ from those causing depressed force with a few days’ delay, where reactive oxygen species (ROS) produced by invading immune cells play an important causative role.

PCs counteracted the delayed onset force depression and this could be explained by prevention of immune cell invasion, which resulted in decreased myeloperoxidase‐mediated ROS production, hence avoiding cell membrane disruption, calpain activation and degenerative changes in myosin and actin molecules.

Preconditioning contractions (PCs) have been shown to result in markedly improved contractile function during the recovery periods after muscle damage from eccentric contractions (ECCs). Here, we examined the mechanisms underlying the beneficial effect of PCs with a special focus on the myofibrillar function. Rat medial gastrocnemius muscles were exposed to 100 repeated damaging ECCs in situ and excised immediately (recovery 0, REC0) or after 4 days (REC4). PCs with 10 repeated non‐damaging ECCs were applied 2 days before the damaging ECCs. PCs improved in situ maximal isometric torque at REC4. Skinned muscle fibres were used to directly assess changes in myofibrillar function. PCs prevented the damaging ECC‐induced depression in maximum Ca2+‐activated force at REC4. PCs also prevented the following damaging ECC‐induced effects at REC4: (i) the reduction in myosin heavy chain and actin content; (ii) calpain activation; (iii) changes in redox homeostasis manifested as increased expression levels of malondialdehyde‐protein adducts, NADPH oxidase 2, superoxide dismutase 2 and catalase, and activation of myeloperoxidase (MPO); (iv) infiltration of immune cells and loss of cell membrane integrity. Additionally, at REC0, PCs enhanced the expression levels of heat shock protein (HSP) 70, HSP25, and αB‐crystallin in the myofibrils and prevented the increased mRNA levels of granulocyte‐macrophage colony‐stimulating factor and interleukin‐6. In conclusion, PCs prevent the delayed force depression after damaging ECCs by an HSP‐dependent inhibition of degenerative changes in myosin and actin molecules caused by myeloperoxidase‐induced membrane lysis and subsequent calpain activation, which were triggered by an inflammatory reaction with immune cells invading damaged muscles.
Hepatic mitochondrial adaptations to physical activity: impact of sexual dimorphism, PGC1α and BNIP3‐mediated mitophagy
Authors: Von Schulze Alex , McCoin Colin S. , Onyekere Chiemela , Allen Julie , Geiger Paige , Dorn Gerald W. , Morris E. Matthew , Thyfault John P.
Published: July 2018

Key points

Hepatic mitochondrial adaptations to physical activity may be regulated by mitochondrial biogenesis (PGC1α) and mitophagy (BNIP3). Additionally, these adaptations may be sex‐dependent.

Chronic increase in physical activity lowers basal mitochondrial respiratory capacity in mice.

Female mice have higher hepatic electron transport system protein content, elevated respiratory capacity, lowered mitophagic flux, and emit less mitochondrial H2O2 independent of physical activity.

Males require chronic daily physical activity to attain a similar mitochondrial phenotype compared to females. In contrast, females have limited hepatic adaptations to chronic physical activity.

Livers deficient in PGC1α and BNIP3 display similar mitochondrial adaptations to physical activity to those found in wild‐type mice.

Hepatic mitochondrial adaptations to physical activity may be regulated by biogenesis‐ and mitophagy‐associated pathways in a sex‐dependent manner. Here, we tested if mice with targeted deficiencies in liver‐specific peroxisome proliferator‐activated receptor γ coactivator 1α (PGC1α; LPGC1α+/−) and BCL2/adenovirus E1B 19 kDa protein‐interacting protein 3 (BNIP3)‐mediated mitophagy (BNIP3−/−) would have reduced physical activity‐induced adaptations in respiratory capacity, H2O2 emission and mitophagy compared to wild‐type (WT) controls and if these effects were impacted by sex. Male and female WT, LPGC1α+/− and BNIP3−/− C57BL6/J mice were divided into groups that remained sedentary or had access to daily physical activity via voluntary wheel running (VWR) (n = 6–10/group) for 4 weeks. Mice had ad libitum access to low‐fat diet and water. VWR reduced basal mitochondrial respiration, increased mitochondrial coupling and altered ubiquitin‐mediated mitophagy in a sex‐specific manner in WT mice. Female mice of all genotypes displayed higher electron transport system content, displayed increased ADP‐stimulated respiration, produced less mitochondrially derived reactive oxygen species, exhibited reduced mitophagic flux, and were less responsive to VWR compared to males. Males responded more robustly to VWR‐induced changes in hepatic mitochondrial function resulting in a match to adaptations found in females. Deficiencies in PGC1α and BNIP3 alone did not largely alter mitochondrial adaptations to VWR. However, VWR restored sex‐dependent abnormalities in mitophagic flux in LPGC1α+/−. Finally, BNIP3−/− mice had elevated mitochondrial content and increased mitochondrial respiration putatively through repressed mitophagic flux. In conclusion, hepatic mitochondrial adaptations to physical activity are more dependent on sex than PGC1α and BNIP3.
Reflection of an ultrasonic wave on the bone-implant interface: A numerical study of the effect of the multiscale roughness
Authors: Hériveaux Yoann , Nguyen Vu-Hieu , Haïat Guillaume
Published: July 2018

Quantitative ultrasound is used to characterize and stimulate osseointegration processes at the bone-implant interface (BII). However, the interaction between an ultrasonic wave and the implant remains poorly understood. This study aims at investigating the sensitivity of the ultrasonic response to the microscopic and macroscopic properties of the BII and to osseointegration processes. The reflection coefficient R of the BII was modeled for different frequencies using a two-dimensional finite element model. The implant surface roughness was modeled by a sinusoidal function with varying amplitude h and spatial frequency L. A soft tissue layer of thickness W was considered between bone tissue and the implant in order to model non-mineralized fibrous tissue. For microscopic roughness, R is shown to increase from around 0.55 until 0.9 when kW increases from 0 to 1 and to be constant for kW > 1, where k is the wavenumber in the implant. These results allow us to show that R depends on the properties of bone tissue located at a distance comprised between 1 and 25 μm from the implant surface. For macroscopic roughness, R is highly dependent on h and this dependence may be explained by phase cancellation and multiple scattering effects for high roughness parameters.
CDK12-mediated transcriptional regulation of noncanonical NF-κB components is essential for signaling
Authors: Henry Kate L. , Kellner Debra , Bajrami Bekim , Anderson John E. , Beyna Mercedes , Bhisetti Govinda , Cameron Tom , Capacci Andrew G. , Bertolotti-Ciarlet Andrea , Feng Jun , Gao Benbo , Hopkins Brian , Jenkins Tracy , Li Kejie , May-Dracka Tricia , Murugan Paramasivam , Wei Ru , Zeng Weike , Allaire Norm , Buckler Alan , Loh Christine , Juhasz Peter , Lucas Brian , Ennis Katelin A. , Vollman Elisabeth , Cahir-McFarland Ellen , Hett Erik C. , Ols Michelle L.
Published: July 2018

Combining a phenotypic screen with chemoproteomics reveals CDK12 as a potential therapeutic target to inhibit noncanonical NF-κB in inflammation and cancer.
Supplementing leukemia therapy
Authors: Foley John F.
Published: July 2018

Increasing the amount of dietary histidine enhances the sensitivity of leukemia xenografts in mice to methotrexate.
Sulfide Protects Staphylococcus aureus from Aminoglycoside Antibiotics but Cannot Be Regarded as a General Defense Mechanism against Antibiotics
Authors: Weikum Julia , Ritzmann Niklas , Jelden Nils , Klöckner Anna , Herkersdorf Sebastian , Josten Michaele , Sahl Hans-Georg , Grein Fabian
Published: July 2018

Sulfide production has been proposed to be a universal defense mechanism against antibiotics in bacteria (K. Shatalin, E.
Impact of InducibleblaDHA-1on Susceptibility of Klebsiella pneumoniae Clinical Isolates to LYS228 and Identification of ChromosomalmplandampDMutations Mediating Upregulation of Plasmid-BorneblaDHA-1Expression
Authors: Jones Adriana K. , Ranjitkar Srijan , Lopez Sara , Li Cindy , Blais Johanne , Reck Folkert , Dean Charles R.
Published: July 2018

Twenty-threeKlebsiella pneumoniae(blaDHA-1) clinical isolates exhibited a range of susceptibilities to LYS228, with MICs of ≥8 μg/ml for 9 of these. Mutants with decreased susceptibility to LYS228 and upregulated expression ofblaDHA-1were selected from representative isolates.
Genetic Determinants of Penicillin Tolerance in Vibrio cholerae
Authors: Weaver Anna I. , Murphy Shannon G. , Umans Benjamin D. , Tallavajhala Srikar , Onyekwere Ikenna , Wittels Stephen , Shin Jung-Ho , VanNieuwenhze Michael , Waldor Matthew K. , Dörr Tobias
Published: July 2018

Many bacteria are resistant to killing (tolerant) by typically bactericidal antibiotics due to their ability to counteract drug-induced cell damage.
Vibrio cholerae
, the cholera agent, displays an unusually high tolerance to diverse inhibitors of cell wall synthesis.
Mobile Genetic Elements Associated with Antimicrobial Resistance
Authors: Partridge Sally R. , Kwong Stephen M. , Firth Neville , Jensen Slade O.
Published: July 2018

Strains of bacteria resistant to antibiotics, particularly those that are multiresistant, are an increasing major health care problem around the world. It is now abundantly clear that both Gram-negative and Gram-positive bacteria are able to meet the evolutionary challenge of combating antimicrobial chemotherapy, often by acquiring preexisting resistance determinants from the bacterial gene pool.
Multicenter Evaluation of Two Next-Generation HIV-1 Quantitation Assays, Aptima Quant Dx and Cobas 6800, in Comparison to the RealTi
m
e HIV-1 Reference Assay
Authors: Wiesmann Frank , Ehret Robert , Naeth Gudrun , Däumer Martin , Fuhrmann Jörg , Kaiser Rolf , Noah Christian , Obermeier Martin , Schalasta Gunnar , Tiemann Carsten , Wolf Eva , Knechten Heribert , Braun Patrick
Published: July 2018

High accuracy and precision at the lower end of quantification are crucial requirements of a modern HIV viral load (VL) assay, since some clinically relevant thresholds are located at 50 and 200 copies/ml. In this study, we compared the performance of two new fully automated HIV-1 VL assays, Aptima HIV-1 Quant Dx and Cobas HIV-1 (Cobas 6800), with the established RealTi
m
e
m
2000 assay.
Surfactin Inhibits Membrane Fusion during Invasion of Epithelial Cells by Enveloped Viruses
Authors: Yuan Lvfeng , Zhang Shuai , Wang Yongheng , Li Yuchen , Wang Xiaoqing , Yang Qian
Published: July 2018

Membrane fusion inhibitors are a rapidly emerging class of antiviral drugs that inhibit the infection process of enveloped viruses. They can be classified, on the basis of the viral components targeted, as fusion protein targeting or membrane lipid targeting. Lipid-targeting membrane fusion inhibitors have a broader antiviral spectrum and are less likely to select for drug-resistant mutations. Here we show that surfactin is a membrane fusion inhibitor and has a strong antiviral effect. The insertion of surfactin into the viral envelope lipids reduces the probability of viral fusion. We also demonstrate that oral administration of surfactin protects piglets from PEDV infection. Surfactin is the first naturally occurring wedge lipid membrane fusion inhibitor that has been identified and may be effective against many viruses beyond the scope of this study. Understanding its mechanism of action provides a foundation for the development of novel antiviral agents.
Protein Mismatches Caused by Reassortment Influence Functions of the Reovirus Capsid
Authors: Thete Deepti , Danthi Pranav
Published: July 2018

Cells coinfected with viruses that possess a multipartite or segmented genome reassort to produce progeny viruses that contain a combination of gene segments from each parent. Reassortment places new pairs of genes together, generating viruses in which mismatched proteins must function together. To test if such forced pairing of proteins that form the virus shell or capsid alters the function of the particle, we investigated properties of reovirus variants in which the σ1 attachment protein and the λ2 protein that anchors σ1 on the particle are mismatched. Our studies demonstrate that a σ1-λ2 mismatch produces particles with lower levels of encapsidated σ1, consequently decreasing virus attachment and infectivity. The mismatch between σ1 and λ2 also altered the capacity of the viral capsid to undergo conformational changes required for cell entry. These studies reveal new functions of reovirus capsid proteins and illuminate both predictable and novel implications of reassortment.
Nonsteroidal Anti-inflammatory Drugs Potently Inhibit the Replication of Zika Viruses by Inducing the Degradation of AXL
Authors: Pan Ting , Peng Zhilin , Tan Likai , Zou Fan , Zhou Nan , Liu Bingfeng , Liang Liting , Chen Cancan , Liu Jun , Wu Liyang , Liu Guangyan , Peng Zhiqin , Liu Weiwei , Ma Xiancai , Zhang Junsong , Zhu Xun , Liu Ting , Li Mengfeng , Huang Xi , Tao Liang , Zhang Yiwen , Zhang Hui
Published: July 2018

Zika virus (ZIKV) infection, which causes congenital malformations, including microcephaly and other neurological disorders, has attracted global attention. We observed that several NSAIDs significantly inhibited ZIKV infection. Based on our observations, we propose a novel mechanism of action of antiviral compounds which involves the blockade of virus entry via degradation of the entry cofactor. Furthermore, NSAIDs can be practically used for preventing ZIKV infection in pregnant women, as certain NSAIDs, including ibuprofen and acetaminophen, are considered clinically safe.
First International Precision Vaccines Conference: Multidisciplinary Approaches to Next-Generation Vaccines
Authors: Borriello Francesco , van Haren Simon D. , Levy Ofer
Published: July 2018

Vaccines represent a remarkable success in the history of medicine since they have prevented and, in some instances, eradicated a range of infectious diseases. However, for many existing vaccines, immunogenicity is limited, requiring multiple booster doses, and we are still unable to target many pathogens due to intrinsic features of the microorganism, such as genetic/antigenic variability between strains, and our limited understanding of the variables that regulate vaccine responsiveness, including age- and sex-specific differences.
Discovery of Human-Specific Immunodominant
Chlamydia trachomatis
B Cell Epitopes
Authors: Rahman K. Shamsur , Darville Toni , Russell Ali N. , O’Connell Catherine M. , Wiesenfeld Harold C. , Hillier Sharon L. , Chowdhury Erfan U. , Juan Yen-Chen , Kaltenboeck Bernhard
Published: July 2018

Current serological assays for species-specific detection of anti-
Chlamydia
species antibodies suffer from well-known shortcomings in specificity and ease of use. Due to the high prevalences of both anti-
C. trachomatis
and anti-
C. pneumoniae
antibodies in human populations, species-specific serology is unreliable. Therefore, novel specific and simple assays for chlamydial serology are urgently needed. Conventional antigens are problematic due to extensive cross-reactivity within
Chlamydia
spp. Using accurate B cell epitope prediction and a robust peptide ELISA methodology developed in our laboratory, we identified immunodominant
C. trachomatis
B cell epitopes by screening performed with sera from
C. trachomatis
-infected women. We discovered 38 novel human host-dependent antigens from 20 immunodominant
C. trachomatis
proteins, in addition to confirming 10 host-independent mouse serum peptide antigens that had been identified previously. This extended set of highly specific
C. trachomatis
peptide antigens can be used in simple ELISA or multiplexed microarray formats and will provide high specificity and sensitivity to human
C. trachomatis
serodiagnosis.
Comprehensive Molecular Serology of HumanChlamydia trachomatisInfections by Peptide Enzyme-Linked Immunosorbent Assays
Authors: Rahman K. Shamsur , Darville Toni , Russell Ali N. , O'Connell Catherine M. , Wiesenfeld Harold C. , Hillier Sharon L. , Lee De’Ashia E. , Kaltenboeck Bernhard
Published: July 2018

For detection of anti-Chlamydia trachomatisantibodies by serological assays, use of classical whole-organism chlamydial antigens results in high cross-reactivity. These antigens bind mainly antibodies against the major outer membrane protein (OmpA) and bind antibodies against other immunodominant non-OmpA proteins to a lesser extent, resulting in poor assay sensitivity. The specificity ofC. trachomatisserology is also compromised by the high prevalence of cross-reactive anti-C. pneumoniaeantibodies in human populations. We previously identified 48 highly specificC. trachomatisB cell epitope peptide antigens of 21 immunodominant proteins. This study validated peptide antigen-based novel ELISAs that provide highly specific and sensitive detection of anti-C. trachomatisantibodies. Compared to four commercial ELISAs that achieved only poor sensitivities (51.5% to 64.8%), the combined signals of 5 to 11 peptides provided high sensitivity (86.5% to 91.8%) at the same 98% specificity. Thus, by using multiple peptide antigens of immunodominant proteins, we created simple ELISAs with specificity and sensitivity superior to standardC. trachomatisserodiagnosis.
Prevalence, incidence and predictors of volunteer community health worker attrition in Kwale County, Kenya
Authors: Ngugi Anthony K , Nyaga Lucy W , Lakhani Amyn , Agoi Felix , Hanselman Margrette , Lugogo George , Mehta Kala M
Published: July 2018

Introduction

In underserved populations, the contribution of community health workers (CHWs) is vital to the healthcare systems. Attrition of these workers causes critical breakdowns in the delivery of essential services to these populations. Literature on reasons for attrition is limited, although some have been identified in studies on sustainability of CHW programmes. These factors are, however, likely to be influenced by context. We measured CHW attrition and its predictors in a rural area in Kenya.

Methods

We conducted a nested case–control study and focus group discussions among CHWs involved in a maternal and child health project. A training register of 1005 CHWs was used to sample and follow CHWs for attrition. Incidence of CHW attrition was calculated using a Poisson model. Separately, we used logistic regression to determine predictors of CHW attrition.

Results

Of the 1005 CHWs, 498 (49.6%) had left the project by the time of the study. The incidence of attrition was 46.8/1000 person-years (95% CI 38.7 to 56.5). In the case–control study, lack of interest in peer organisation membership (OR 5.3; 95% CI 1.3 to 20.6) was associated with attrition. Absence of refresher training (OR 4.0; 95% CI 2.2 to 7.1) and receiving no feedback from supervisors (OR 2.0; 95% CI 1.0 to 3.9) were also associated with attrition. Discordance in expectations and perceived heavy workload were also identified as key reasons for attrition in the qualitative study.

Conclusion

This study estimates high prevalence and incidence of CHW attrition in Kwale County, Kenya. Ongoing training, feedback and peer support are also important in enhancing retention of CHWs. Additionally, expectations regarding the roles and benefits of involvement in CHW work should be communicated clearly, and workload should be kept reasonable or negotiated with the CHWs.
Research barriers in children and young people with life-limiting conditions: a survey
Authors: Peake Jordana Natalie , Beecham Emma , Oostendorp Linda J M , Hudson Briony F , Stone Patrick , Jones Louise , Lakhanpaul Monica , Bluebond-Langner Myra
Published: July 2018

Studies indicate research ethics committee (REC) approval and clinician gatekeeping are two key barriers in recruiting children and young people (CYP) with life-limiting conditions (LLCs) and life-threatening illnesses (LTIs) and their families to research.

Objectives

To explore the reported experiences, difficulties and proposed solutions of chief investigators (CIs) recruiting CYP with LLCs/LTIs and families in the UK.

Methods

61 CIs conducting studies with CYP with LLCs/LTIs and their families, identified from the UK National Institute of Health Research portfolio, completed an anonymous, web-based questionnaire, including both closed and open-ended questions. Descriptive statistics and inductive and deductive coding were used to analyse responses.

Results

UK CIs cited limitations on funding, governance procedures including Research and Development, Site-Specific and REC approval processes, and clinician gatekeeping as challenges to research. CIs offered some solutions to overcome identified barriers such as working with CYP and their families to ensure their needs are adequately considered in study design and communicated to ethics committees; and designing studies with broad inclusion criteria and developing effective relationships with clinicians in order to overcome clinician gatekeeping.

Conclusions

Many of the challenges and solutions reported by UK CIs have applicability beyond the UK setting. The involvement of clinicians, patients and their families at the inception of and throughout paediatric palliative care research studies is essential. Other important strategies include having clinician research champions and increasing the visibility of research. Further research on the perspectives of all stakeholders, leading to mutually agreed guidance, is required if care and treatment are to improve.
Understanding the management of patients with head injury taking warfarin: who should we scan and when? Lessons from the AHEAD study
Authors: Mason Suzanne M , Evans Rachel , Kuczawski Maxine
Published: July 2018

Anticoagulated patients represent an important and increasing proportion of the patients with head trauma attending the ED, but there is no international consensus for their appropriate investigation and management. International guidelines vary and are largely based on a small number of studies, which provide poor-quality evidence for the management of patients taking warfarin. This article provides an overview of the clinical research evidence for CT scanning head-injured patients taking warfarin and a discussion of interpretation of risk and acceptable risk. We aim to provide shop floor clinicians with an understanding of the limitations of the evidence in this field and the limitations of applying ‘one-size-fits-all’ guidelines to individual patients. There is good evidence for a more selective scanning approach to patients with head injuries taking warfarin than is currently recommended by most guidelines. Specifically, patients without any head injury–related symptoms and GCS score 15 have a reduced risk of adverse outcome and may not need to be scanned. We argue that there is evidence to support an individualised approach to decision to CT scan in mild head injuries on warfarin and that clinicians should feel able to discuss risks with patients and sometimes decide not to scan.
Use of zebrafish models to investigate rare human disease
Authors: Adamson Kathryn Isabel , Sheridan Eamonn , Grierson Andrew James
Published: July 2018

Rare diseases are collectively common and often extremely debilitating. Following the emergence of next-generation sequencing (NGS) technologies, the variants underpinning rare genetic disorders are being unearthed at an accelerating rate. However, many rare conditions lack effective treatments due to their poorly understood pathophysiology. There is therefore a growing demand for the development of novel experimental models of rare genetic diseases, so that potentially causative variants can be validated, pathogenic mechanisms can be investigated and therapeutic targets can be identified. Animal models of rare diseases need to be genetically and physiologically similar to humans, and well-suited to large-scale experimental manipulation, considering the vast number of novel variants that are being identified through NGS. The zebrafish has emerged as a popular model system for investigating these variants, combining conserved vertebrate characteristics with a capacity for large-scale phenotypic and therapeutic screening. In this review, we aim to highlight the unique advantages of the zebrafish over other in vivo model systems for the large-scale study of rare genetic variants. We will also consider the generation of zebrafish disease models from a practical standpoint, by discussing how genome editing technologies, particularly the recently developed clustered regularly interspaced repeat (CRISPR)/CRISPR-associated protein 9 system, can be used to model rare pathogenic variants in zebrafish. Finally, we will review examples in the literature where zebrafish models have played a pivotal role in confirming variant causality and revealing the underlying mechanisms of rare diseases, often with wider implications for our understanding of human biology.
The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) protocol: novel method for evaluating human stroke
Authors: Fraser Justin F , Collier Lisa A , Gorman Amy A , Martha Sarah R , Salmeron Kathleen E , Trout Amanda L , Edwards Danielle N , Davis Stephanie M , Lukins Douglas E , Alhajeri Abdulnasser , Grupke Stephen , Roberts Jill M , Bix Gregory J , Pennypacker Keith R
Published: July 2018

Background

Ischemic stroke research faces difficulties in translating pathology between animal models and human patients to develop treatments. Mechanical thrombectomy, for the first time, offers a momentary window into the changes occurring in ischemia. We developed a tissue banking protocol to capture intracranial thrombi and the blood immediately proximal and distal to it.

Objective

To develop and share a reproducible protocol to bank these specimens for future analysis.

Methods

We established a protocol approved by the institutional review board for tissue processing during thrombectomy (www.clinicaltrials.govNCT03153683). The protocol was a joint clinical/basic science effort among multiple laboratories and the NeuroInterventional Radiology service line. We constructed a workspace in the angiography suite, and developed a step-by-step process for specimen retrieval and processing.

Results

Our protocol successfully yielded samples for analysis in all but one case. In our preliminary dataset, the process produced adequate amounts of tissue from distal blood, proximal blood, and thrombi for gene expression and proteomics analyses. We describe the tissue banking protocol, and highlight training protocols and mechanics of on-call research staffing. In addition, preliminary integrity analyses demonstrated high-quality yields for RNA and protein.

Conclusions

We have developed a novel tissue banking protocol using mechanical thrombectomy to capture thrombus along with arterial blood proximal and distal to it. The protocol provides high-quality specimens, facilitating analysis of the initial molecular response to ischemic stroke in the human condition for the first time. This approach will permit reverse translation to animal models for treatment development.
Management of obstructive sleep apnoea in a primary care vs sleep unit setting: a randomised controlled trial
Authors: Tarraubella Nuria , Sánchez-de-la-Torre Manuel , Nadal Nuria , De Batlle Jordi , Benítez Iván , Cortijo Anunciación , Urgelés Maria Cruz , Sanchez Virginia , Lorente Iñigo , Lavega M Mercé , Fuentes Araceli , Clotet Joan , Llort Laia , Vilo Lidia , Juni M Carmen , Juarez Aurelia , Gracia Maribel , Castro-Grattoni Anabel L , Pascual Lydia , Minguez Olga , Masa Juan F , Barbé Ferran
Published: July 2018

Objective

To assess the effectiveness and cost-effectiveness of primary care (PC) and sleep unit (SU) models for the management of subjects with suspected obstructive sleep apnoea (OSA).

Methods

Multicentre, open-label, two-arm, parallel-group, non-inferiority randomised controlled trial. A total of 302 subjects with suspected OSA and/or resistant hypertension were consecutively enrolled, 149 were treated at 11 PC units and 153 patients at a SU. The primary outcomes were a 6-month change in the Epworth Sleepiness Scale (ESS) score and Health Utilities Index (HUI). The non-inferiority margin for the ESS score was −2.0.

Results

A total of 80.2% and 70.6% of the PC and SU patients were diagnosed with OSA, respectively, and 59.3% and 60.4% of those were treated with CPAP in PC and SU units, respectively. The Apnoea–Hypopnoea Index was similar between the groups (PC vs SU (median (IQR); 23.1 (26.8) events/h vs 21.8 (35.2) events/h), and the baseline ESS score was higher in the PC than in the SU group (10.3 (6.6) vs 9 (7.2)). After 6 months, the ESS score of the PC group decreased from a mean of 10.1 to 7.6 (−2.49; 95% CI −3.3 to −1.69), and that of the SU group decreased from 8.85 to 5.73 (−3.11; 95% CI −3.94 to 2.28). The adjusted difference between groups for the mean change in the ESS score was −1.25 (one-sided 95% CI −1.88; p=0.025), supporting the non-inferiority of PC management. We did not observe differences in the HUI between groups. The cost analysis showed a median savings of €558.14/patient for the PC setting compared with the SU setting.

Conclusions

Among patients with suspected OSA, the PC model did not result in a worse ESS score or HUI than the specialist model and generated savings in terms of management cost. Therefore, the PC model was more cost-efficient than the SU model.

Trial registration

Results; >>NCT02234765, Clinical Trials.gov.
Impact of the WHO FCTC on non-cigarette tobacco products
Authors: Zaatari Ghazi S , Bazzi Asma
Published: July 2018

Introduction

This paper investigates to what extent Framework Convention on Tobacco Control (FCTC) parties have successfully implemented regulatory measures against non-cigarette tobacco product (NCTP) use, considers the challenges and peculiarities in applying such regulations and proposes effective means.

Data and methods

This review was based on many sources mainly: International Legal Consortium, International Tobacco Control, Campaign for Tobacco-Free Kids, FCTC, expert group visits and published literature.

Findings and conclusion

The FCTC provided a framework that applies to all forms of tobacco and this encouraged some parties to adopt control measures against NCTP and to incorporate them into their national tobacco control plans. Although a number of countries have adopted measures specifically targeted towards smokeless and waterpipe tobacco, greater global progress is needed. The strongest achievements have been in protection from exposure to tobacco smoke; controlling advertising, promotion and sponsorship; controlling sales to and by minors; education, communication and public awareness; and packaging and labelling of NCTP. Countries which adopted broad definitions of tobacco products have demonstrated encouraging trends in curbing their use. Future work should address the deep-rooted social acceptance of NCTP, the laxity in their control, their exclusion from regulations in some countries and the failure to subject them to increased taxation. Control measures should also specifically target the initiation risk to youth and adolescents and all factors that contribute to that such as banning flavourings and promotions through social media. Stronger global surveillance of NCTP use, tracking of policy implementation and evaluation of policy impact will provide important evidence to assist parties in fully implementing the FCTC to control their use.
Gap thinning improves soil water content, changes the vertical water distribution, and decreases the fluctuation
Authors: Wang Zhe , He Qihua , Hu Bin , Pang Xueyong , Bao Weikai
Published: July 2018

Although it is clear that gap thinning significantly increases the soil water content (SWC) of the topsoil, less is known about whether and how this treatment affects deeper layers. From December 2008 to April 2012, we monitored the SWC at depths of 10, 20, 30, 45, 60, and 90 cm in gap creation treatments (small gap size of 30 m2, intermediate gap size of 80 m2, and unthinned plots) in a typical pine plantation in the eastern Tibetan Plateau. Among gap treatments, differences in SWC and its coefficient of variation (CV) at each depth and the soil water content proportion (SWCP) of the whole soil profile at specific depths were compared. Gap thinning improved SWC and decreased the CV at each depth. The SWCPs in thinned plots were lower at depths from 10 to 30 cm compared with unthinned plots but higher at depths of 45 and 60 cm. Also, in each season, the patterns were similar to the general results. In conclusion, gap thinning improves the SWC, changes the vertical soil water distribution, and decreases the SWC heterogeneity. The soil water conditions in intermediate gaps are more appropriate for local forest restoration.
Geographical description and molecular characterization of genetic structure and diversity using a 6K SNP array in Turkish oat germplasm
Authors: Cömertpay Gönül , Habyarimana Ephrem , Baloch Faheem Shehzad , Güngör Hüseyin , Dokuyucu Tevrican , Akkaya Aydın , Dumlupinar Ziya
Published: July 2018

Cultivated oat (Avena sativa L. and Avena byzantina Koch) is native to Turkey, a secondary center of oat diversity. Oat breeding has received less attention relative to other cereals. In this work, the diversity of oat landraces collected from different regions of Turkey as well as obtained from different gene banks was investigated using 3293 high quality SNP markers. Expected heterozygosity (Hs), observed heterozygosity (Ho), inbreeding coefficient (Fis), and overall genetic diversity (Ht) of the oat gene pool were 0.22, 0.01, 0.96, and 0.38, respectively. The value of the genetic differentiation (Fst) metric for genetic structure was 0.41 and indicated that kinship was more of a determinant for population structure than the geographical provenance. The populations from different geographical regions shared a great proportion of genetic diversity. Clustering using model-based STRUCTURE, principal coordinates (PCoA), and neighbour-joining (NJ) algorithms were mostly comparable except for five discrepantly clustered accessions in NJ and PCoA relative to STRUCTURE, which can be attributed to the relatively reduced resolution power in the NJ and PCoA approaches. SNP markers partitioned all oat accessions into four main groups (A, B, C, and D) with 10 unclassified accessions. Some landraces were identical based on genetic distance and can represent duplications in gene banks. The data presented in this work represent the initial results on genetic diversity as investigated in Turkish oat, and are an important resource for systematicians, geneticists, and breeders interested in Turkish oat germplasm. These results are expected to open new opportunities for further studies in oat genomics and cultivar development.
Metabolomics: a tool to characterize the effect of phthalates and bisphenol A
Authors: Gómez Cristina , Gallart-Ayala Hector
Published: July 2018

The study of physiological disruptions induced upon exposure to a given chemical substance has emerged as a research field. The assessment of the effects of chemical substances at low concentration levels is not always doable using classical toxicological studies. The use of metabolomics approaches integrated with conventional toxicological studies is expected to provide valuable information for risk assessment. This review recapitulates some of the recent publications related to the use of metabolomics to study the effect of bisphenol A (BPA) and phthalates exposure. Mass spectrometry and nuclear magnetic resonance metabolomics approaches revealed the principal metabolic pathways such as amino acids, energy storage compounds, or organic osmolytes were altered. To investigate phthalates and BPA effects is relevant to assist in potential correlations between exposure and adverse human effects and to provide data and evidence for effective regulatory policies and risk exposure assessment.
A Neuronal Network Model of the Primate Visual System: Color Mechanisms in the Retina, LGN and V1
Authors: Martínez-Cañada Pablo , Morillas Christian , Pelayo Francisco
Published: July 2018

Color plays a key role in human vision but the neural machinery that underlies the transformation from stimulus to perception is not well understood. Here, we implemented a two-dimensional network model of the first stages in the primate parvocellular pathway (retina, lateral geniculate nucleus and layer 4C[Formula: see text] in V1) consisting of conductance-based point neurons. Model parameters were tuned based on physiological and anatomical data from the primate foveal and parafoveal vision, the most relevant visual field areas for color vision. We exhaustively benchmarked the model against well-established chromatic and achromatic visual stimuli, showing spatial and temporal responses of the model to disk- and ring-shaped light flashes, spatially uniform squares and sine-wave gratings of varying spatial frequency. The spatiotemporal patterns of parvocellular cells and cortical cells are consistent with their classification into chromatically single-opponent and double-opponent groups, and nonopponent cells selective for luminance stimuli. The model was implemented in the widely used neural simulation tool NEST and released as open source software. The aim of our modeling is to provide a biologically realistic framework within which a broad range of neuronal interactions can be examined at several different levels, with a focus on understanding how color information is processed.