bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling determinants of quality in blended learning: are there gender-based differences?
Authors: Savara Vandana , Parahoo Sanjai
Published: August 2018

Purpose

The purpose of this paper is to model the factors influencing the quality of learning experiences (LE) of students in blended learning (BL) environments in higher education (HE) sector, and to assess whether these factors differ across gender.

Design/methodology/approach

A literature review combined with in-depth interviews of a broad range of stakeholders were used to develop a conceptual study model, which was then empirically tested using data collected from a global sample of 267 students from diverse BL environments. Factor analysis and binary logistic regression were used to test the study model.

Findings

A five factor solution emerged for both genders, therefore concluding that the identified factors did not play a statistically significant role in predicting the gender of students. Thus, the same factors may be used to enhance the quality of LE of both male and female students.

Research limitations/implications

Even though the sample represents respondents from different universities around the world, and the methodology used has authenticated the findings, the results need to be implemented carefully due to the non-probabilistic sampling. Therefore, similar studies can be repeated in future in other BL environments to validate the results in a broader context.

Practical implications

The findings suggest that managers of HE institutions may use similar factors to achieve quality LE for both male and female students.

Social implications

Effective design of courses suitable for both genders will support better LE potentially leading to higher retention and enrollment rates for students and supporting lifelong learning.

Originality/value

While universities worldwide are increasingly using BL environments as delivery mode, limited research has focused on the factors that affect the quality of LE in such settings. This paper addresses this gap and tests whether the same factors are relevant for both genders.
The contrasting roles of host species diversity and parasite population genetic diversity in the infection dynamics of a keystone parasitic plant
Authors: Rowntree Jennifer K. , Craig Hayley
Published: August 2018

Diversity among species and genetic diversity within species are both important components of ecological communities that can determine the outcome of species interactions, especially between hosts and parasites. We sought to understand the impact of species diversity on host community resistance to infection by a keystone parasitic plant (Rhinanthus minorL.) and genetic diversity of the parasite on its successful establishment in a grassland community.

We used an experimental approach where large pots were planted with mixtures of mesotrophic grassland species at high and low species diversity. The parasitic plant was sown in a proportion of these with high and low genetic diversity treatments. Establishment of the parasite was monitored over 2 years and the pots harvested at the end of each growing season to determine the impact of infection on plant community biomass.

We found a strong effect of host plant species diversity on the establishment of the parasitic plant, with successful establishment considerably lower in the high species diversity treatment. Genetic diversity appeared to promote establishment of the parasite in the high species diversity treatment, and also facilitated longer term fitness in the low species diversity treatment. Host community structure was influenced byR. minor, with grass relative biomass decreasing and legume relative biomass increasing when the parasite was present. There was no direct impact of the presence of the parasite on the relative biomass of nonleguminous forbs.

Synthesis. Our data demonstrate the importance of host community species diversity in deterring the establishment of a generalist parasite. They also highlight the role of genetic diversity in determining the outcome of host–parasite interactions in multispecies communities. These findings, therefore, have important implications for the establishment and management of species‐rich grasslands and provide insight into the community dynamics of parasitic plants and their hosts.
The Salisbury Poisoning Case and German–Russian Relations: Ambiguity and Ambivalence
Authors: Wood Steve , Henke Otto
Published: August 2018

Governments of Western democracies responded quickly to the poisoning—allegedly by agents of the Russian state—of former Soviet spy, Sergei Skripal, and his daughter in Salisbury, UK in March 2018. Germany's response was not as categorically reproachful and drew attention to its relationship with Vladimir Putin's Russia more generally. It expelled four Russian diplomats and has applied sanctions since Russia's annexation of Crimea, yet continues with other bilateral trade and investment, significantly in the energy sector, and it has been hesitant about unconditionally rebuking aggressive Russian behaviour. A complex mix of domestic politics and international relations, historical memory, economic incentives, and political psychology in the age of the internet and ‘fake news’ serve to influence German attitudes toward Russia. A contest between Putin critics and sympathisers sharpens in a polity in which the majority are ambivalent. In the aftermath of the Skripal affair, some rethinking of an ambiguous policy is occurring at high levels.
Anchoring to Purchase Price and Fundamentals: Application of Salience Theory to Housing Cycle Diagnosis
Authors: Clapp John M. , Lu‐Andrews Ran , Zhou Tingyu
Published: August 2018

We propose that, in addition to the first price of a repeat pair, sellers also anchor to local fundamentals at the date of the first sale. We redefine an important diagnostic tool for housing cycles by replacing the ratio of house prices to fundamentals with a salient gap: change in market value minus change in local fundamental value between any two sales. Connecticut data shows that the salient gap influences asking and market prices for sellers facing expected gains or losses and that the gap provides early, robust diagnosis of bubble conditions compared to ratios.
Application of 3D Imaging Technology to Latent Fingermark Aging Studies
Authors: De Alcaraz‐Fossoul Josep , Mancenido Michelle , Soignard Emmanuel , Silverman Nathaniel
Published: August 2018

In most latent fingermark aging studies, two‐dimensional (2D) features are obtained from photo images, scans, or inked impressions. However, some relevant information is possibly being missed because fingermarks are three‐dimensional (3D) objects that age in all three dimensions. A feature that has not been carefully examined is how the height of ridges changes over time. In this report, a 3D imaging technology—called optical profilometry—is introduced as a tool for the visual examination of the aging process. Optical profilometry is a nondestructive technology that allows the visualization and data acquisition of unprocessed latent fingermarks. Detailed ridge images and spatiotemporal data were successively obtained on the x‐, y‐ and z‐axis, delivering 3D topographical information. OP was able to detect the loss of ridge heights over time. The feasibility of employing this technology to collect data on the aging process of ridges has been proven.
A Reappraisal of Developing Deciduous Tooth Length as an Estimate of Age in Human Immature Skeletal Remains
Authors: Cardoso Hugo F.V. , Meyers Julia , Liversidge Helen M.
Published: August 2018

This study provides an update on a quantitative method for immature age estimation based on postnatal deciduous mandibular tooth length. Two known sex and age skeletal collections from Western Europe were sampled (n = 97). Linear regression models for age estimated were calculated for each individual tooth, each sex, and sex combined sample using classical calibration. Prediction errors, residuals, and percentage of individuals whose real age fell within the 95% prediction interval were calculated. The teeth which develop earlier in life, the incisors and the first molar, showed the greatest precision, while the canine showed the least. This method has greater applicability to archeological skeletons or to children in developing countries than for use in North American or European forensic contexts. The method can be applied to incomplete or poorly preserved remains of unknown sex, particularly when dental radiographs are not an option or when teeth have been removed from the alveolus or crypt.
Security interventions for workplace violence in the emergency department
Authors: Mitra Biswadev , Nikathil Shradha , Gocentas Robert , Symons Evan , O'Reilly Gerard , Olaussen Alexander
Published: August 2018

Objectives

Despite a policy of zero tolerance towards workplace violence (WPV) in Australian public hospital EDs, the incidence of WPV continues to increase. The aim of this study was to characterise security responses to WPV within an adult level 4 ED.

Methods

A retrospective single‐centre review of episodes of WPV perpetrated by adults occurring within the ED was conducted between 1 January 2013 and 31 December 2015. Cases were identified using a prospectively recorded security register that records all events of security personnel attendance. The presence of police officers on initial presentation was the primary exposure variable.

Results

There were 1853 violent episodes committed by 1224 patients requiring security intervention during the study period, with half the episodes (n = 916; 49%) involving perpetrators who had committed at least two or more violent acts during the study period. Most cases (n = 1057, 57%; 95% CI: 55–59) occurred in the absence of police presence. Only 144 (7.8%) cases were managed by the presence of security personnel without physical security interventions.

Conclusions

EDs should not rely on police response to prevent or handle violence. The finding of a high proportion of events being perpetrated by repeat offenders indicate that data sharing between EDs for identification of perpetrators of WPV can be useful for prevention of future episodes. ACEM policy for WPV in EDs should encompass further details on security credentialing and preventive strategies towards minimisation of WPV in the Australian EDs.
Alectinib treatment response in lung adenocarcinoma patient with novel EML4‐ALK variant
Authors: Song Peng , Zhang Jingcheng , Shang Congcong , Zhang Li
Published: August 2018

Common gene fusion of the ALK gene is fusion of the ALK tyrosine kinase area and the 5’end of EML4. Seventeen EML4‐ALK fusion variants have been reported. Herein, we report a novel EML4‐ALK variant detected by next‐generation sequencing in a 36‐year‐old female lung adenocarcinoma patient who experienced disease progression after six months of alectinib treatment. Second generation sequencing revealed an EML4‐ALK fusion variant in which intron 19 of EML4 was fused to exon 20 of ALK. This is the first case of EML4‐ALK (E19: A20) fusion to be reported. Alectinib may show unsatisfactory therapeutic effects for this kind of ALK fusion.
A transdiagnostic dimensional approach towards a neuropsychological assessment for addiction: an international Delphi consensus study
Authors: Yücel Murat , Oldenhof Erin , Ahmed Serge H. , Belin David , Billieux Joel , Bowden‐Jones Henrietta , Carter Adrian , Chamberlain Samuel R. , Clark Luke , Connor Jason , Daglish Mark , Dom Geert , Dannon Pinhas , Duka Theodora , Fernandez‐Serrano Maria Jose , Field Matt , Franken Ingmar , Goldstein Rita Z. , Gonzalez Raul , Goudriaan Anna E. , Grant Jon E. , Gullo Matthew J. , Hester Robert , Hodgins David C. , Le Foll Bernard , Lee Rico S. C. , Lingford‐Hughes Anne , Lorenzetti Valentina , Moeller Scott J. , Munafò Marcus R. , Odlaug Brian , Potenza Marc N. , Segrave Rebecca , Sjoerds Zsuzsika , Solowij Nadia , van den Brink Wim , van Holst Ruth J. , Voon Valerie , Wiers Reinout , Fontenelle Leonardo F. , Verdejo‐Garcia Antonio
Published: August 2018

Background

The US National Institutes of Mental Health Research Domain Criteria (RDoC) seek to stimulate research into biologically validated neuropsychological dimensions across mental illness symptoms and diagnoses. The RDoC framework comprises 39 functional constructs designed to be revised and refined, with the overall goal of improving diagnostic validity and treatments. This study aimed to reach a consensus among experts in the addiction field on the ‘primary’ RDoC constructs most relevant to substance and behavioural addictions.

Methods

Forty‐four addiction experts were recruited from Australia, Asia, Europe and the Americas. The Delphi technique was used to determine a consensus as to the degree of importance of each construct in understanding the essential dimensions underpinning addictive behaviours. Expert opinions were canvassed online over three rounds (97% completion rate), with each consecutive round offering feedback for experts to review their opinions.

Results

Seven constructs were endorsed by ≥ 80% of experts as ‘primary’ to the understanding of addictive behaviour: five from the Positive Valence System (reward valuation, expectancy, action selection, reward learning, habit); one from the Cognitive Control System (response selection/inhibition); and one expert‐initiated construct (compulsivity). These constructs were rated to be related differentially to stages of the addiction cycle, with some linked more closely to addiction onset and others more to chronicity. Experts agreed that these neuropsychological dimensions apply across a range of addictions.

Conclusions

The study offers a novel and neuropsychologically informed theoretical framework, as well as a cogent step forward to test transdiagnostic concepts in addiction research, with direct implications for assessment, diagnosis, staging of disorder, and treatment.
Farming out of place:
Authors: OFSTEHAGE ANDREW
Published: August 2018

North American soybean farmers have responded to farmland inaccessibility in the US Midwest by purchasing and operating large soybean farms in western Bahia, Brazil. They have turned to “flexible farming” and flexible crops, labor, and land that are commodified, replaceable, and alienated from social and physical relations. Nevertheless, temporalities of farming survive, redefined in terms of progress and backwardness, and new materialities and models of farming emerge. This emergent agrarianism is flexible in terms of fungible means of production and farmer subjectivities that push the boundaries of “family farming.” The detachment and mobility of things and people in global agricultural production disrupts rural life and generates values and practices as farmers engage with the land and make meaning out of transnational farming. [flexibility,work,land,crops,transnationalism,agriculture,Brazil,United States]
Refusal as political practice:
Authors: McGRANAHAN CAROLE
Published: August 2018

Is it possible to be both a refugee and a citizen? For six decades, Tibetan refugees have refused citizenship in South Asia as part of their claims to Tibetan state sovereignty. They have lived in India and Nepal as refugee noncitizens, either undocumented or underdocumented, for multiple generations. But as Tibetans migrate to the United States and Canada, they gain citizenship through political asylum while maintaining their belonging to the Dalai Lama's refugee community. This shift in political practice is as situated in specific histories as it is in geographies. Tibetan citizenship practices in exile are not claims for recognition or forms of resistance; they are, rather, a refusal of international norms through a present‐day insistence on past and future political sovereignty.
Risk of repeat cesarean delivery in women undergoing trial of labor: A population‐based cohort study
Authors: Lindblad Wollmann Charlotte , Ahlberg Mia , Saltvedt Sissel , Johansson Kari , Elvander Charlotte , Stephansson Olof
Published: August 2018

Introduction

The aim of this study was to consult women on best mode of delivery after a first cesarean section, more knowledge regarding risk for a repeat unplanned cesarean is needed. We investigated the association between indication of first cesarean and cervical dilation during labor preceding the first cesarean and risk of repeat cesarean in women undergoing trial of labor.

Material and methods

A population‐based cohort study using electronic medical records of all women delivering in the Stockholm‐Gotland region, Sweden, between 2008 and 2014. The population consisted of 3116 women with a first cesarean undergoing a trial of labor with a singleton infant in cephalic presentation at ≥37 weeks of gestation. Relative risks (RR) with 95% CI were estimated using Poisson regression analyses.

Results

Women with a first unplanned cesarean had higher risk of repeat cesarean compared with women with elective first cesarean (35.7% vs 20.7%, adjusted RR 1.64, 95% CI 1.43‐1.89). In women with a cesarean due to dystocia, increasing cervical dilation in first labor decreased the risk of repeat cesarean in second labor. The adjusted RR of repeat cesarean was 2.48 with dilation ≤5 cm, 1.98 with dilation 6‐10 cm, and 1.46 if fully dilated.

Conclusions

Almost 70% of all women eligible for trial of labor after cesarean had a vaginal birth, even women with a history of labor dystocia had a good chance of success. A greater cervical dilation in the first delivery ending with a cesarean was not in vain, since the chance of vaginal birth in the subsequent delivery increased with greater dilation.
Optimal introduction of laparoscopic liver resection for Child–Pugh B
Authors: Fuji Hiroaki , Seo Satoru , Toda Rei , Yoh Tomoaki , Ikeno Yoshinobu , Fukumitsu Ken , Ishii Takamichi , Taura Kojiro , Hatano Etsuro , Kaido Toshimi , Uemoto Shinji
Published: August 2018

Introduction

Surgery for Child–Pugh B liver function is considered risky because of its high morbidity rate and the acceptable indication criteria for laparoscopic liver resection (LLR) for Child–Pugh B patients have not been identified. We conducted a retrospective cohort study to determine the optimal introduction of LLR for Child–Pugh B patients based on our single‐institute experience.

Methods

A total of 17 Child–Pugh B patients underwent LLR between 2005 and 2017. Their clinical outcomes were compared to those of LLR for Child–Pugh A patients (103 cases), conventional open liver resection for Child–Pugh B patients (19 cases), and radiofrequency ablation (RFA) for Child–Pugh B patients (20 cases) during the same period.

Results

LLR for Child–Pugh B patients had a significantly higher conversion rate than LLR for Child–Pugh A patients (Child–Pugh A vs B: 3.9% vs 35.3%, P < 0.01). However, patients who successfully underwent laparoscopic resection (11 cases) had fewer postoperative ascites and shorter postoperative hospital stays compared to patients who underwent conventional open liver resection. In comparison to the RFA group, the LLR group more frequently had lesions in the left lateral segment (LLR vs RFA: 50.0% vs 10.0%, P = 0.02) and exophytic tumor (21.4% vs 0%, P = 0.02) than did the RFA group. Also, compared to the RFA group, the LLR group had a lower local recurrence rate (0% vs 15%, P = 0.25) and a longer recurrence‐free survival (P = 0.049), but the overall survival was similar between the two groups.

Conclusions

In the treatment of Child–Pugh B liver malignancy, the minimal invasiveness of LLR was revealed. Our results suggest that lesions in the left lateral segment and exophytic tumors are good indications for LLR for Child–Pugh B.
Examining the use of e‐assessment in higher education: teachers and students’ viewpoints
Authors: Rolim Catarina , Isaias Pedro
Published: August 2018

The combination of teaching and information technologies is at the origin of a more embracing, flexible and accessible approach to learning. Assessment is considered an integral part of the learning process, but it has always been considered challenging for teachers. Through the adoption of information technologies, it is possible to create new opportunities to improve assessment. Despite its numerous advantages, e‐assessment remains a topic of much discussion for many, due to doubts that arise about its efficiency and effectiveness. In order to understand this issue, this study aims to explore e‐assessment in higher education, from the viewpoint of teachers and students. Four online surveys were distributed among teachers and students in Portugal and other countries. While the results show that Portugal is slightly behind in terms of adoption, there is a strong awareness of the importance of e‐assessment. Internationally, e‐assessment has higher adoption rates, and both teachers and students believe that this method of assessment is advantageous.
Measuring the effects of α1‐antitrypsin polymerisation on the structure and biophysical properties of the endoplasmic reticulum
Authors: Chambers Joseph E. , Dickens Jennifer A. , Marciniak Stefan J.
Published: August 2018

An important function of the endoplasmic reticulum (ER) is to serve as a site of secretory protein folding. When the accumulation of misfolded proteins threatens to disturb luminal homoeostasis, the cell is said to experience ER stress. By contrast, the accumulation of well‐folded proteins inside the ER leads to a distinct form of strain called ER overload. The serpins comprise a large family of proteins whose folding has been studied in great detail. Some mutant serpins misfold to cause ER stress, whereas others fold but then polymerise to cause ER overload. We discuss recent advances in the use of dynamic fluorescence imaging to study these phenomena. We also discuss a new technique that we recently published, rotor‐based organelle viscosity imaging (ROVI), which promises to shed more light on the biophysical features of ER stress and ER overload.
The polyphenol resveratrol promotes skeletal growth in mice through a sirtuin 1‐bone morphogenic protein 2 longevity axis
Authors: Zhao Ming , Ko Seon‐Yle , Garrett I Ross , Mundy Gregory R , Gutierrez Gloria E , Edwards James R
Published: August 2018

Background and Purpose

The polyphenol resveratrol (RSV) exists in high quantities in certain foods (e.g. grapes and nuts). However, the capacity of RSV to confer physiological health benefits and a biological mechanism through which this might occur remains unclear.

Experimental Approach

Aged, RSV‐treated (300 mg·kg−1·day−1) and genetically modified [endothelial NOS (eNOS−/−)] female mice were assessed using histomorphometric and μCT analysis. Alongside in vivo analysis, molecular siRNA knockdown and pharmacological manipulation of eNOS, BMP2 and sirtuin 1 (SIRT1) and functional cellular assays in an osteoblast cell line panel, explored the mechanism through which RSV might impact overall bone volume.

Key Results

RSV promoted osteoblast activity and bone growth in vivo. RSV dose‐dependently and simultaneously increased alkaline phosphatase (ALP) and eNOS levels. Similarly, NO‐donor treatment increased ALP, runt homology transcription factor 2, BMP2 and stimulated bone formation, whilst eNOS‐deficient mice displayed a bone loss phenotype. Moreover, RSV‐induced increase in ALP and BMP2 expression was blocked in eNOS−/− osteoblasts and by BMP‐inhibitor noggin. The longevity‐linked SIRT1 enzyme was positively regulated by RSV and SIRT1 deletion reduced eNOS, BMP2 and ALP. Like eNOS deletion, loss of SIRT1 blocked RSV‐induced osteoblast activity; however, SIRT1 levels remained unchanged in eNOS−/− mice, indicating RSV activation of SIRT1 stimulates BMP2 release via eNOS. This signalling axis is supported by decreased SIRT1, eNOS and BMP2 confirmed in old versus young bone.

Conclusions and Implications

These findings suggest a new mechanism of action in bone remodelling and the ageing skeleton, where RSV positively impacts bone homeostasis via SIRT1 activation of BMP2.
Brain histamine modulates recognition memory: possible implications in major cognitive disorders
Authors: Provensi Gustavo , Costa Alessia , Izquierdo Ivan , Blandina Patrizio , Passani Maria Beatrice
Published: August 2018

Several behavioural tests have been developed to study and measure emotionally charged or emotionally neutral memories and how these may be affected by pharmacological, dietary or environmental manipulations. In this review, we describe the experimental paradigms used in preclinical studies to unravel the brain circuits involved in the recognition and memorization of environmentally salient stimuli devoid of strong emotional value. In particular, we focus on the modulatory role of the brain histaminergic system in the elaboration of recognition memory that is based on the judgement of the prior occurrence of an event, and it is believed to be a critical component of human declarative memory. The review also addresses questions that may help improve the treatment of impaired declarative memory described in several affective and neuropsychiatric disorders such as ADHD, Alzheimer's disease and major neurocognitive disorder.

Linked Articles

This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc
Cysteine residues in mitochondrial intermembrane space proteins: more than just import
Authors: Habich Markus , Salscheider Silja Lucia , Riemer Jan
Published: August 2018

The intermembrane space (IMS) is a very small mitochondrial sub‐compartment with critical relevance for many cellular processes. IMS proteins fulfil important functions in transport of proteins, lipids, metabolites and metal ions, in signalling, in metabolism and in defining the mitochondrial ultrastructure. Our understanding of the IMS proteome has become increasingly refined although we still lack information on the identity and function of many of its proteins. One characteristic of many IMS proteins are conserved cysteines. Different post‐translational modifications of these cysteine residues can have critical roles in protein function, localization and/or stability. The close localization to different ROS‐producing enzyme systems, a dedicated machinery for oxidative protein folding, and a unique equipment with antioxidative systems, render the careful balancing of the redox and modification states of the cysteine residues, a major challenge in the IMS. In this review, we discuss different functions of human IMS proteins, the involvement of cysteine residues in these functions, the consequences of cysteine modifications and the consequences of cysteine mutations or defects in the machinery for disulfide bond formation in terms of human health.

Linked Articles

This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc
The bidirectional interaction between the sympathetic nervous system and immune mechanisms in the pathogenesis of hypertension
Authors: Carnagarin Revathy , Matthews Vance , Zaldivia Maria T K , Peter Karlheinz , Schlaich Markus P
Published: August 2018

Over the last few years, evidence has accumulated to suggest that hypertension is, at least in part, an immune‐mediated inflammatory disorder. Many links between immunity and hypertension have been established and provide a complex framework of mechanistic interactions contributing to the rise in BP. These include immune‐mediated inflammatory processes affecting regulatory brain nuclei and interactions with other mediators of cardiovascular regulation such as the sympathetic nervous system. Sympathoexcitation differentially regulates T‐cells based upon activation status of the immune cell as well as the resident organ. Exogenous and endogenous triggers activate signalling pathways in innate and adaptive immune cells resulting in pro‐inflammatory cytokine production and activation of T‐lymphocytes in the cardiovascular and renal regions, now considered major factors in the development of essential hypertension. The inflammatory cascade is sustained and exacerbated by the immune flow via the brain–bone marrow–spleen–gastrointestinal axis and thereby further aggravating immune‐mediated pathways resulting in a vicious cycle of established hypertension and target organ damage. This review summarizes the evidence and recent advances in linking immune‐mediated inflammation, sympathetic activation and their bidirectional interactions with the development of hypertension.

Linked Articles

This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Contribution of the commensal microbiota to atherosclerosis and arterial thrombosis
Authors: Kiouptsi Klytaimnistra , Reinhardt Christoph
Published: August 2018

The commensal gut microbiota is an environmental factor that has been implicated in the development of cardiovascular disease. The development of atherosclerotic lesions is largely influenced not only by the microbial‐associated molecular patterns of the gut microbiota but also by the meta‐organismal trimethylamine N‐oxide pathway. Recent studies have described a role for the gut microbiota in platelet activation and arterial thrombosis. This review summarizes the results from gnotobiotic mouse models and clinical data that linked microbiota‐induced pattern recognition receptor signalling with atherogenesis. Based on recent insights, we here provide an overview of how the gut microbiota could affect endothelial cell function and platelet activation, to promote arterial thrombosis.

Linked Articles

This article is part of a themed section on When Pharmacology Meets the Microbiome: New Targets for Therapeutics? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.24/issuetoc
Setting a patient‐centered research agenda for cerebral palsy: a participatory action research initiative
Authors: Gross Paul H , Bailes Amy F , Horn Susan D , Hurvitz Edward A , Kean Jacob , Shusterman Michele ,   For the cerebral palsy research network
Published: August 2018

Aim

To establish a patient‐centered research agenda for cerebral palsy (CP).

Method

We engaged a large cross‐section of the extended community of people living with CP and those providing healthcare to people with CP (‘the community’) in an educational series and collaborative survey platform to establish an initial list of prioritized research ideas. After online workshops, a facilitated Delphi process was used to select the 20 highest priorities. Select participants attended an in‐person workshop to provide comment and work toward consensus of research priorities.

Results

A research agenda for CP was developed by the community, which included consumers, clinicians, and researchers interested in advancing the established research agenda. The results included the top 16 research concepts produced by the process to shape and steward the research agenda, and an engaged cross‐section of the community.

Interpretation

It has been shown that proactively engaging consumers with clinical researchers may provide more meaningful research for the community. This study suggests that future research should have more focus on interventions and outcomes across the lifespan with increased emphasis on the following outcome measures: function, quality of life, and participation.

What this paper adds

A patient‐centered research agenda for cerebral palsy was established.

Comparative effectiveness of interventions, physical activity, and understanding ageing were leading themes.

Longitudinal studies across the lifespan, clinical spectrum, and ages were highly ranked.

Participants reported high value for participation outcomes.

Participants reported great appreciation for the engagement between consumers and clinician researchers.
Genetic polymorphisms of the endocannabinoid system in obesity and diabetes
Authors: Doris Joseph M. , Millar Sophie A. , Idris Iskandar , O'Sullivan Saoirse E.
Published: August 2018

The endocannabinoid system (ECS) is involved in many physiological processes including fertility, pain and energy regulation. The aim of this systematic review was to examine the contribution of single nucleotide polymorphisms (SNPs) of the ECS to adiposity and glucose metabolism. Database searches identified 734 articles, of which 65 were included; these covered 70 SNPs in genes coding for cannabinoid receptors 1 and 2 (CB1, CB2), fatty acid amide hydrolase (FAAH) and N‐acyl phosphatidylethanolamine phospholipase D (NAPE‐PLD). No studies included SNPs relating to monoacylglycerol lipase or diacylglycerol lipase. The CB1 receptor SNP rs1049353 showed 17 associations with lower body mass index (BMI) and fat mass (five studies). It also showed three associations with lower insulin levels (one study). Conversely, the CB1 receptor SNP rs806368 was associated with increased BMI and waist circumference (two studies). The FAAH SNP rs324420 was associated with increased obesity (three studies). A haplotype of NAPE‐PLD was associated with decreased BMI (one study). A total of 60 SNPs showed no association with any measured outcome. This review suggests a complex but important role of ECS SNPs in energy and glucose metabolism.
Patient‐reported outcomes are worse for progressive‐onset multiple sclerosis than relapse‐onset multiple sclerosis, particularly early in the disease process
Authors: Zhang Y. , Taylor B. V. , Simpson S. , Blizzard L. , van der Mei I.
Published: August 2018

Background and purpose

Treatments for progressive‐onset multiple sclerosis (MS) are lacking. To improve the disease management for progressive‐onset MS, the differences between relapse‐onset MS and progressive‐onset MS in patient‐reported disability, progression and symptoms were examined.

Methods

A total of 1985 participants of the Australian Multiple Sclerosis Longitudinal Study were included. Associations between onset type and outcomes were assessed with negative binomial regression.

Results

The severity of 17 of the 19 outcomes was significantly higher for progressive‐onset MS patients than relapse‐onset MS patients, including perspectives from disability, progression over the last year, fatigue, sensory, walking difficulties, pain, balance, spasticity, sexual dysfunction, bladder, bowel, anxiety, depression and the European quality of life (EQ‐5D) (P < 0.05; adjusted mean ratio ranged from 1.11 to 1.52). The differences between the two onset types were most pronounced early in the disease process and reduced with increasing MS duration, and the interaction was significant for disability, progression over the last year, walking difficulties, bladder problems, bowel problems and spasticity.

Conclusion

Participants with progressive‐onset MS were significantly worse off on nearly all patient‐reported outcomes than relapse‐onset MS participants, and the differences were most pronounced early in the disease course, highlighting the importance of early intervention for those with progressive‐onset MS.
Where mitoxantrone for multiple sclerosis is still valuable in 2018
Authors: Buttmann M.
Published: August 2018

Click here to view the accompanying paper in this volume.
SLC6A1variants identified in epilepsy patients reduce γ‐aminobutyric acid transport
Authors: Mattison Kari A. , Butler Kameryn M. , Inglis George Andrew S. , Dayan Oshrat , Boussidan Hanna , Bhambhani Vikas , Philbrook Bryan , da Silva Cristina , Alexander John J. , Kanner Baruch I. , Escayg Andrew
Published: August 2018

Previous reports have identifiedSLC6A1variants in patients with generalized epilepsies, such as myoclonic‐atonic epilepsy and childhood absence epilepsy. However, to date, none of the identifiedSLC6A1variants has been functionally tested for an effect onGAT‐1 transporter activity. The purpose of this study was to determine the incidence ofSLC6A1variants in 460 unselected epilepsy patients and to evaluate the impact of the identified variants on γ‐aminobutyric acid (GABA)transport. Targeted resequencing was used to screen 460 unselected epilepsy patients for variants inSLC6A1. Five missense variants, one in‐frame deletion, one nonsense variant, and one intronic splice‐site variant were identified, representing a 1.7% diagnostic yield. Using a [3H]‐GABAtransport assay, the seven identified exonic variants were found to reduceGABAtransport activity. A minigene splicing assay revealed that the splice‐site variant disrupted canonical splicing of exon 9 in themRNAtranscript, leading to premature protein truncation. These findings demonstrate thatSLC6A1is an important contributor to childhood epilepsy and that reducedGAT‐1 function is a common consequence of epilepsy‐causingSLC6A1variants.
Do children with Dravet syndrome continue to benefit from stiripentol for long through adulthood?
Authors: Chiron Catherine , Helias Marie , Kaminska Anna , Laroche Cecile , de Toffol Bertrand , Dulac Olivier , Nabbout Rima , An Isabelle
Published: August 2018

Objective

To evaluate continuing stiripentol treatment in adulthood in Dravet syndrome (DS).

Method

Longitudinal data were collected from the last visit prior to age 15 years (V15 y) to the last visit in adulthood (Vadult) in the 40 DS patients (32 typical, eight atypical) of a French historical cohort (Paris) of subjects who continued stiripentol from childhood or adolescence to adulthood.

Results

At Vadult (18‐40 years, median = 23 years), all the patients were still receiving stiripentol (exposure = 3‐24 years, median = 18 years), associated with clobazam (40/40), valproate (39/40), and topiramate (21/40). Between V15 y and Vadult, stiripentol was interrupted in five patients (two for adverse events) but reintroduced following seizure aggravation. Loss of appetite affected 15 of 40 patients but resolved after reducing the dose of stiripentol or valproate; no other new stiripentol‐related adverse events were reported. Mean stiripentol dose was progressively decreased from 39 to 25 mg/kg/d (P = 0.0002), whereas clobazam (0.27 mg/kg/d) and valproate (14 mg/kg/d) remained stable. At Vadult, 37 of 40 patients still had generalized tonic–clonic seizures, but none still had status epilepticus (vs three at V15 y) and only one had myoclonia. During adulthood, generalized tonic–clonic seizure frequency and duration continued to decrease (P = 0.02, P = 0.008) and 10 patients experienced seizure‐free periods ≥ 1 years (up to 5 years). All patients already had intellectual disability at V15 y, but retardation was more severe at Vadult (P = 0.03). Furthermore, neurological/gait condition had declined (two patients became bedridden) and behavior had worsened (P < 0.0002). Nevertheless, the 33 patients on stiripentol from infancy/childhood (<15 years) tended to have better seizure outcome in midadulthood than the seven treated from adolescence (>15 years) and the DS patients treated from adult age or stiripentol‐naive subjects reported in the literature.

Significance

The efficacy and safety of the stiripentol/valproate/clobazam combination started at pediatric age are maintained at very long term during adulthood. Such prolonged stiripentol therapy tends to positively impact the late prognosis of epilepsy, especially when initiated before adolescence.
Incidence of neonatal seizures, perinatal risk factors for epilepsy and mortality after neonatal seizures in the province of Parma, Italy
Authors: Pisani Francesco , Facini Carlotta , Bianchi Elisa , Giussani Giorgia , Piccolo Benedetta , Beghi Ettore
Published: August 2018

Objective

Information about the incidence of neonatal seizures (NS) is scarce. Previous studies relied primarily on a clinical diagnosis of seizures. This population‐based, retrospective study evaluated the incidence of electroencephalography (EEG)–confirmed seizures in neonates born in the province of Parma and the perinatal risk factors for mortality and epilepsy.

Methods

All neonates with suspected seizures or with medical conditions at high risk for seizures from the study area were recorded in the neonatal intensive care unit (NICU) of the Parma University Hospital. NS were EEG confirmed. Perinatal risk factors for mortality and epilepsy after NS were evaluated with Cox’s proportional hazards models.

Results

In a 13‐year period, 112 patients presented with NS: 102 newborns had electroclinical seizures (46 full‐term and 56 preterm), whereas 10 presented only electrical seizures. The incidence was 2.29/1000 live births (95% confidence interval [CI] 1.87‐2.72), with higher rates in preterm neonates (14.28/1000 in preterm vs 1.10/1000 in full‐term infants). The incidence increased with decreasing gestational age (31‐36 weeks of gestation: 5.01/1000, 28‐30: 54.9/1000, and <28: 85.6/1000) and with decreasing birth weight (≥2500 g: 1.19/1000, <1000 g: 127.57/1000). Twenty‐eight patients (25%) died, 16 (14.3%) had a diagnosis of epilepsy, 33 (29.5%) had cerebral palsy, and 39 (34.8%) had a developmental delay. Among the perinatal risk factors considered, the multivariate analysis showed an association between a 5‐minute Apgar score of 0‐7 and etiology with increased mortality and between female gender and status epilepticus with epilepsy.

Significance

The incidence of NS is inversely associated with gestational age and birth weight. The etiology and a low Apgar score are strongly related to mortality; female gender and status epilepticus are risk factors for the development of epilepsy.
The role of trust and transparency in accountable outsourced prisoner transport
Authors: English L. M.
Published: August 2018

Explores the privatisation of prisoner transport in regional Western Australia. Focuses on the role collaboration plays in the development of transparency, trust and accountability in service delivery. Latent racism, the challenging physical environment, risks associated with unsuitable vehicles, uncaring contractors and ineffective departmental oversight contributed to transport failures. The complexity and scope of responsibilities, underfunding, poor departmental management, unresponsive contractors and the physical environment undermined the development of trust, transparency and accountability essential for building effective working relationships between government and contractors.
Balanced harvesting could reduce fisheries‐induced evolution
Authors: Law Richard , Plank Michael J.
Published: August 2018

Current fisheries management pays little attention to fisheries‐induced evolution. Methods of exploitation that have benefits in the short term while ameliorating selection in the longer term would therefore be advantageous. Balanced harvesting is a potential candidate. This tries to bring fishing more in line with natural production, and some short‐term benefits for conservation of aquatic ecosystems and for biomass yield have already been documented. It is also predicted to be relatively benign as a selective force on fish stocks, because it keeps the overall distribution of mortality relatively close to natural mortality. We test this prediction, coupling an ecological model of marine, size‐spectrum dynamics to an adaptive dynamics model of life history evolution. The evolutionary variable is the reproductive schedule, set by the maximum body mass and the mass at maturation. The prediction is supported by our numerical analysis: Directional selection under balanced harvesting is approximately an order of magnitude weaker than in a standard fishery in which fish experience a fixed rate of fishing mortality after recruitment. The benefit of balanced harvesting follows from relatively little fishing on large fish, due to the low somatic production rates the big fish have. These results therefore support the general argument for protecting big, old fish, both for ecological and for evolutionary reasons. Slot fisheries that protect large fish share some qualitative features with balanced harvesting and show similar evolutionary benefits.
Bioenergetic consequences of warming rivers to adult Atlantic salmon Salmo salar during their spawning migration
Authors: Lennox Robert J. , Eliason Erika J. , Havn Torgeir B. , Johansen Martin R. , Thorstad Eva B. , Cooke Steven J. , Diserud Ola H. , Whoriskey Frederick G. , Farrell Anthony P. , Uglem Ingebrigt
Published: August 2018

Climate change poses a challenge to wild fishes, yet little is known about the behavioural use and metabolic consequences of thermally heterogeneous water encountered by wild salmon during their energetically demanding upstream spawning migration.

Temperature, body size and activity levels were modelled to predict energy depletion of salmon during their spawning migration in rivers. Archival temperature loggers revealed the thermal habitat of adult migrating Atlantic salmon (Salmo salar Salmonidae), which we used to apply bioenergetics models that estimated size‐dependent temperature‐driven metabolic expenditures as part of the costs of the migration.

Between July 16 and August 19, the mean water temperature experienced by salmon (tFISH) ranged from 11.5 to 18.0°C (14.5 ± 1.2 SD °C) and closely followed the ambient surface water temperature (tRIVER) of the river (11.5–18.5°C; 14.8 ± 1.4°C) such that the regression equation tFISH = 3.24 + 0.76 (tRIVER) was highly correlated with observations (R2 = 0.94).

Although temperature increases were predicted and confirmed to increase energetic costs, rates of energy depletion were more sensitive to changes in swimming speed and body size than to temperature increases in the range explored for this system.

We conclude that warming could contribute to changing life history phenotypes of salmon in some rivers, for example, delayed river entry or reduced probability of iteroparity, with potentially more dire consequences for smaller individuals.
A 3,000‐year lag between the geological and ecological shutdown of Florida's coral reefs
Authors: Toth Lauren T. , Kuffner Ilsa B. , Stathakopoulos Anastasios , Shinn Eugene A.
Published: August 2018

The global‐scale degradation of coral reefs has reached a critical threshold wherein further declines threaten both ecological functionality and the persistence of reef structure. Geological records can provide valuable insights into the long‐term controls on reef development that may be key to solving the modern coral‐reef crisis. Our analyses of new and existing coral‐reef cores from throughout the Florida Keys reef tract (FKRT) revealed significant spatial and temporal variability in reef development during the Holocene. Whereas maximum Holocene reef thickness in the Dry Tortugas was comparable to elsewhere in the western Atlantic, most of Florida's reefs had relatively thin accumulations of Holocene reef framework. During periods of active reef development, average reef accretion rates were similar throughout the FKRT at ~3 m/ky. The spatial variability in reef thickness was instead driven by differences in the duration of reef development. Reef accretion declined significantly from ~6,000 years ago to present, and by ~3,000 years ago, the majority of the FKRT was geologically senescent. Although sea level influenced the development of Florida's reefs, it was not the ultimate driver of reef demise. Instead, we demonstrate that the timing of reef senescence was modulated by subregional hydrographic variability, and hypothesize that climatic cooling was the ultimate cause of reef shutdown. The senescence of the FKRT left the ecosystem balanced at a delicate tipping point at which a veneer of living coral was the only barrier to reef erosion. Modern climate change and other anthropogenic disturbances have now pushed many reefs past that critical threshold and into a novel ecosystem state, in which reef structures built over millennia could soon be lost. The dominant role of climate in the development of the FKRT over timescales of decades to millennia highlights the potential vulnerability of both geological and ecological reef processes to anthropogenic climate change.