bluuebunny/crossref_metadata_2025 huggingface dataset:
Mild form of oculocutaneous albinism type 1: phenotypic analysis of compound heterozygous patients with the R402Q variant of the TYR gene
Authors: Monfermé Solene , Lasseaux Eulalie , Duncombe-Poulet Catherine , Hamel Christian , Defoort-Dhellemmes Sabine , Drumare Isabelle , Zanlonghi Xavier , Dollfus Hélène , Perdomo Yaurama , Bonneau Dominique , Korobelnik Jean-François , Plaisant Claudio , Michaud Vincent , Pennamen Perrine , Rooryck-Thambo Caroline , Morice-Picard Fanny , Paya Clement , Arveiler Benoit
Published: November 2018

Aim

Oculocutaneous albinism type 1 (OCA1) is due to TYR mutations. c.1205G>A/p.Arg402Gln (R402Q) is a thermosensitive variant of the TYR gene that has been reported to be responsible for mild forms of OCA1. The aim of our study was to define the phenotype associated with this variant.

Methods

In our retrospective series, among 268 patients diagnosed with OCA1, 122 (45.5%) harboured one pathogenic variant of TYR, and the R402Q variant ensured to be in trans by segregation analysis in 69 patients (25.7%), constituting the ‘R402Q-OCA1’ group. 146 patients harboured two pathogenic variants of the TYR gene other than R402Q. Clinical records were available for 119 of them, constituting the ‘Classical-OCA1’ group.

Results

Most R402Q-OCA1 patients presented with white or yellow-white hair at birth (71.43%), blond hair later (46.97%), a light phototype but with residual pigmentation (69.64%), and blue eyes (76.56%). Their pigmentation was significantly higher than in the classical-OCA1 group. All patients from the R402Q-OCA1 group presented with ocular features of albinism. However the prevalence of photophobia (78.13%) and iris transillumination (83.87%) and the severity scores of iris transillumination, retinal hypopigmentation and foveal hypoplasia were lower in the R402Q-OCA1 group. Visual acuity was higher in the R402Q-OCA1 group (0.38±0.21 logarithm of the minimum angle of resolution vs 0.76±0.24). Investigations concerning a possible additive effect of the c.575C>A/p.Ser192 (S192Y) variant of TYR in cis with R402Q, suggested by others, showed no significant impact on the phenotype.

Conclusion

The R402Q variant leads to variable but generally mild forms of albinism whose less typical presentation may lead to underdiagnosis.
Effects of managed care on the proportion of inappropriate elective diagnostic coronary angiographies in non-emergency patients in Switzerland: a retrospective cross-sectional analysis
Authors: Chmiel Corinne , Reich Oliver , Signorell Andri , Neuner-Jehle Stefan , Rosemann Thomas , Senn Oliver
Published: November 2018

Objective

Guidelines recommend non-invasive ischaemia testing (NIIT) for the majority of patients with suspected ischaemic heart disease in a non-emergency setting. A substantial number of these patients undergo diagnostic coronary angiography (CA) without therapeutic intervention inappropriately due to lacking preceding NIIT. The aim of this study was to evaluate the effect of voluntary healthcare models with limited access on the proportion of patients without NIIT prior to elective purely diagnostic CA.

Design

Retrospective cross-sectional analysis of insurance claims data from 2012 to 2015. Data included claims of basic and voluntary healthcare models from approximately 1.2 million patients enrolled with the Helsana Insurance Group. Voluntary healthcare models with limited health access are divided into gate keeping (GK) and managed care (MC) capitation models. Inclusion criteria: patients undergoing CA. Exclusion criteria: Patients<18 years, incomplete health insurance data coverage, acute cardiac ischaemia and emergency procedures, therapeutic CA (coronary angioplasty/stenting or coronary artery bypass grafting). The effect of voluntary healthcare models on the proportion of NIIT undertaken within 2 months before diagnostic CA was assessed by means of multiple logistic regression analysis, controlled for influencing factors.

Results

9173 patients matched inclusion criteria. 33.2% (3044) did not receive NIIT before CA. Compared with basic healthcare models, MC was independently associated with a higher proportion of NIIT (p<0.001, OR 1.17, CI 1.045 to 1.312), when additionally controlled for demographics, insurance coverage, inpatient treatment, cardiovascular medication, chronic comorbidities, high-risk status (patients with therapeutic cardiac intervention 1 month after or 18 months prior to diagnostic CA). GK models showed no significant association with the rate of NIIT (p=0.07, OR 1.11, CI 0.991 to 1.253).

Conclusions

In a non-GK healthcare system, voluntary MC healthcare models with capitation were associated with a reduced inappropriate use of diagnostic CA compared with GK or basic models.
Prevalence and associated factors of khat chewing among students in Ethiopia: a protocol for systematic review and meta-analysis
Authors: Alemu Wondale Getinet , Amare Zeleke Tadele , Takele Wubet Worku
Published: November 2018

Introduction

These days, in Ethiopia, khat chewing is one of the widely spreading public health problems affecting the most productive segment of the population. The health implications of khat chewing among students are strongly linked with poor mental, physical and social performances. However, the national magnitude of khat chewing and the associated factors among Ethiopian students are unknown. Therefore, this systematic review and meta-analysis will answer the national prevalence of khat chewing and the associated factors among students in Ethiopia.

Methods

Published primary relevant articles will be accessed using various databases, such as Medline, PubMed, EMBASE and Scopus. Other electronic search engines, for instance, Google Scholar and Google, will be used. Furthermore, additional studies will be collected by communicating with the author(s) and following the references of relevant articles. To select eligible studies, the Joanna Briggs Institute quality appraisal checklist will be used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist will be followed to keep the scientific rigour of the study. Heterogeneity between studies will be examined through forest plot and I2heterogeneity tests. To identify influential studies, sensitivity analysis will be done. For substantial heterogeneity (I2>50%), the DerSimonian and Laird random-effects model will be employed. Subgroup analyses will be conducted using the random-effect model. Moreover, small studies’ publication bias will be checked by funnel plots and objectively by Egger’s regression test. If in case Egger’s test was found to be statistically significant (p<0.05), trim and fill (Duval and Tweedie) analysis will be performed. The presence of association will be declared using p≤0.05 and OR with corresponding 95% CI.

Ethics and dissemination

Since the intention of the study is to describe earlier primary studies qualitatively and pool the results of those articles, ethical clearance will not be a concern. The results of the study will be published in a reputable peer-reviewed journal and presented at different scientific research conferences. It will also be disseminated to academic as well as other concerned institutions.

PROSPERO registration number

CRD-42,017,081,886.
Biomedical authors’ awareness of publication ethics: an international survey
Authors: Schroter Sara , Roberts Jason , Loder Elizabeth , Penzien Donald B , Mahadeo Sarah , Houle Timothy T
Published: November 2018

Objective

The extent to which biomedical authors have received training in publication ethics, and their attitudes and opinions about the ethical aspects of specific behaviours, have been understudied. We sought to characterise the knowledge and attitudes of biomedical authors about common issues in publication ethics.

Design

Cross-sectional online survey.

Setting and participants

Corresponding authors of research submissions to 20 journals.

Main outcome measure(s)

Perceived level of unethical behaviour (rated 0 to 10) presented in five vignettes containing key variables that were experimentally manipulated on entry to the survey and perceived level of knowledge of seven ethical topics related to publishing (prior publication, author omission, self-plagiarism, honorary authorship, conflicts of interest, image manipulation and plagiarism).

Results

4043/10 582 (38%) researchers responded. Respondents worked in 100 countries and reported varying levels of publishing experience. 67% (n=2700) had received some publication ethics training from a mentor, 41% (n=1677) a partial course, 28% (n=1130) a full course and 55% (n=2206) an online course; only a small proportion rated training received as excellent. There was a full range (0 to 10 points) in ratings of the extent of unethical behaviour within each vignette, illustrating a broad range of opinion about the ethical acceptability of the behaviours evaluated, but these opinions were little altered by the context in which it occurred. Participants reported substantial variability in their perceived knowledge of seven publication ethics topics; one-third perceived their knowledge to be less than ‘some knowledge’ for the sum of the seven ethical topics and only 9% perceived ‘substantial knowledge’ of all topics.

Conclusions

We found a large degree of variability in espoused training and perceived knowledge, and variability in views about how ethical or unethical scenarios were. Ethical standards need to be better articulated and taught to improve consistency of training across institutions and countries.
Surgical quality in organ procurement during day and night: an analysis of quality forms
Authors: de Boer Jacob , Van der Bogt Koen , Putter Hein , Ooms-de Vries Kirsten , Haase-Kromwijk Bernadette , Pol Robert , De Jonge Jeroen , Dejong Kees , Nijboer Mijntje , Van der Vliet Daan , Braat Dries
Published: November 2018

Objectives

To analyse a potential association between surgical quality and time of day.

Design

A retrospective analysis of complete sets of quality forms filled out by the procuring and accepting surgeon on organs from deceased donors.

Setting

Procurement procedures in the Netherlands are organised per region. All procedures are performed by an independent, dedicated procurement team that is associated with an academic medical centre in the region.

Participants

In 18 months’ time, 771 organs were accepted and procured in The Netherlands. Of these, 17 organs were declined before transport and therefore excluded. For the remaining 754 organs, 591 (78%) sets of forms were completed (procurement and transplantation). Baseline characteristics were comparable in both daytime and evening/night-time with the exception of height (p=0.003).

Primary outcome measure

All complete sets of quality forms were retrospectively analysed for the primary outcome, procurement-related surgical injury. Organs were categorised based on the starting time of the procurement in either daytime (8:00–17:00) or evening/night-time (17:00–8:00).

Results

Out of 591 procured organs, 129 organs (22%) were procured during daytime and 462 organs (78%) during evening/night-time. The incidence of surgical injury was significantly lower during daytime; 22 organs (17%) compared with 126 organs (27%) procured during evening/night-time (p=0.016). This association persists when adjusted for confounders.

Conclusions

This study shows an increased incidence of procurement-related surgical injury in evening/night-time procedures as compared with daytime. Time of day might (in)directly influence surgical performance and should be considered a potential risk factor for injury in organ procurement procedures.
Using the extended self-regulatory model to characterise diabetes medication adherence: a cross-sectional study
Authors: Shiyanbola Olayinka O , Unni Elizabeth , Huang Yen-Ming , Lanier Cameron
Published: November 2018

Objectives

To cluster the adherence behaviours of patients with type 2 diabetes based on their beliefs in medicines and illness perceptions and examine the psychosocial, clinical and sociodemographic characteristics of patient clusters.

Design

Cross-sectional study.

Setting

A face-to-face survey was administered to patients at two family medicine clinics in the Midwest, USA.

Participants

One hundred and seventy-four ≥20-year-old, English-speaking adult patients with type 2 diabetes who were prescribed at least one oral diabetes medicine daily were recruited using convenience sampling.

Primary and secondary outcome measures

Beliefs in medicines and illness perceptions were assessed using the Beliefs about Medicines Questionnaire and the Brief Illness Perception Questionnaire, respectively. Self-reported medication adherence was assessed using the Morisky Medication Adherence Scale. Psychosocial correlates of adherence, health literacy and self-efficacy were measured using the Newest Vital Sign and the Self-efficacy for Appropriate Medication Use, respectively. Two-step cluster analysis was used to classify patients.

Results

Participants’ mean age was 58.74 (SD=12.84). The majority were women (57.5%). Four clusters were formed (non-adherent clusters: ambivalent and sceptical; adherent clusters: indifferent and accepting). The ambivalent cluster (n=30, 17.2%) included low-adherent patients with high necessity beliefs, high concern beliefs and high illness perceptions. The sceptical cluster (n=53, 30.5%) included low adherent patients with low necessity beliefs but high concern beliefs and high illness perceptions. Both the accepting (n=40, 23.0%) and indifferent (n=51, 29.3%) clusters were composed of patients with high adherence. Significant differences between the ambivalent, sceptical, accepting and indifferent adherent clusters were based on self-efficacy, illness perception domains (treatment control and coherence) and haemoglobin A1c (p<0.01).

Conclusions

Patients with diabetes in specific non-adherent and adherent clusters still have distinct beliefs as well as psychosocial characteristics that may help providers target tailored medication adherence interventions.
From embracing to managing risks
Authors: Keen Justin , Nicklin Emma , Wickramasekera Nyantara , Long Andrew , Randell Rebecca , Ginn Claire , McGinnis Elizabeth , Willis Sean , Whittle Jackie
Published: November 2018

Objective

To assess developments over time in the capture, curation and use of quality and safety information in managing hospital services.

Setting

Four acute National Health Service hospitals in England.

Participants

111.5 hours of observation of hospital board and directorate meetings, and 72 hours of ward observations. 86 interviews with board level and middle managers and with ward managers and staff.

Results

There were substantial improvements in the quantity and quality of data produced for boards and middle managers between 2013 and 2016, starting from a low base. All four hospitals deployed data warehouses, repositories where datasets from otherwise disparate departmental systems could be managed. Three of them deployed real-time ward management systems, which were used extensively by nurses and other staff.

Conclusions

The findings, particularly relating to the deployment of real-time ward management systems, are a corrective to the many negative accounts of information technology implementations. The hospital information infrastructures were elements in a wider move, away from a reliance on individual professionals exercising judgements and towards team-based and data-driven approaches to the active management of risks. They were not, though, using their fine-grained data to develop ultrasafe working practices.
Associations of lifestyle and vascular risk factors with Alzheimer’s brain biomarker changes during middle age: a 3-year longitudinal study in the broader New York City area
Authors: Walters Michelle J , Sterling Joanna , Quinn Crystal , Ganzer Christine , Osorio Ricardo S , Andrews Randolph D , Matthews Dawn C , Vallabhajosula Shankar , de Leon Mony J , Isaacson Richard S , Mosconi Lisa
Published: November 2018

Objective

To investigate the associations between lifestyle and vascular risk factors and changes in Alzheimer’s disease (AD) biomarkers (beta-amyloid load via11C-PiB PET, glucose metabolism via18F-FDG PET and neurodegeneration via structural MRI) and global cognition in middle-aged asymptomatic participants at risk for AD.

Design

Prospective, longitudinal.

Setting

The study was conducted at New York University Langone/Weill Cornell Medical Centres in New York City.

Participants

Seventy cognitively normal participants from multiple community sources, aged 30–60 years with lifestyle measures (diet, intellectual activity and physical activity), vascular risk measures and two imaging biomarkers visits over at least 2 years, were included in the study.

Outcome measures

We examined MRI-based cortical thickness, fluoro-deoxy-glucose (FDG) glucose metabolism and PiB beta-amyloid in AD-vulnerable regions. A global cognitive z-score served as our summary cognition measure. We used regression change models to investigate the associations of clinical, lifestyle and vascular risk measures with changes in AD biomarkers and global cognition.

Results

Diet influenced changes in glucose metabolism, but not amyloid or cortical thickness changes. With and without accounting for demographic measures, vascular risk and baseline FDG measures, lower adherence to a Mediterranean-style diet was associated with faster rates of FDG decline in the posterior cingulate cortex (p≤0.05) and marginally in the frontal cortex (p=0.07).None of the other lifestyle variables or vascular measures showed associations with AD biomarker changes. Higher baseline plasma homocysteine was associated with faster rates of decline in global cognition, with and without accounting for lifestyle and biomarker measures (p=0.048). None of the lifestyle variables were associated with cognition.

Conclusions

Diet influenced brain glucose metabolism in middle-aged participants, while plasma homocysteine explained variability in cognitive performance. These findings suggest that these modifiable risk factors affect AD risk through different pathways and support further investigation of risk reduction strategies in midlife.
Improving household surveys and use of data to address health inequities in three Asian cities: protocol for the Surveys for Urban Equity (SUE) mixed methods and feasibility study
Authors: Elsey Helen , Poudel Ak Narayan , Ensor Tim , Mirzoev Tolib , Newell James Nicholas , Hicks Joseph Paul , Cartwright Christopher , Wong David , Tait Caroline , Baral Sushil , Bhattarai Radheshyam , Khanal Sudeepa , Dhungel Rajeev , Gajurel Subash , Manandhar Shraddha , Mashreky Saidur , Ferdoush Junnatul , Huque Rumana , Ferdous Tarana , Nasreen Shammi , Van Minh Hoang , Duc Duong Minh , Ngoc Bao , Thomson Dana , Wallace Hilary
Published: November 2018

Introduction

As rapid urbanisation transforms the sociodemographic structures within cities, standard survey methods, which have remained unchanged for many years, under-represent the urban poorest. This leads to an overly positive picture of urban health, distorting appropriate allocation of resources between rural and urban and within urban areas. Here, we present a protocol for our study which (i) tests novel methods to improve representation of urban populations in household surveys and measure mental health and injuries, (ii) explores urban poverty and compares measures of poverty and ‘slumness’ and (iii) works with city authorities to understand, and potentially improve, utilisation of data on urban health for planning more equitable services.

Methods and analysis

We will conduct household surveys in Kathmandu, Hanoi and Dhaka to test novel methods: (i) gridded population sampling; (ii) enumeration using open-access online maps and (iii) one-stage versus two-stage cluster sampling. We will test reliability of an observational tool to categorise neighbourhoods as slum areas. Within the survey, we will assess the appropriateness of a short set of questions to measure depression and injuries. Questionnaire data will also be used to compare asset-based, consumption-based and income-based measures of poverty. Participatory methods will identify perceptions of wealth in two communities in each city. The analysis will combine quantitative and qualitative findings to recommend appropriate measures of poverty in urban areas. We will conduct qualitative interviews and establish communities of practice with government staff in each city on use of data for planning. Framework approach will be used to analyse qualitative data allowing comparison across city settings.

Ethics and dissemination

Ethical approvals have been granted by ethics committees from the UK, Nepal, Bangladesh and Vietnam. Findings will be disseminated through conference papers, peer-reviewed open access articles and workshops with policy-makers and survey experts in Kathmandu, Hanoi and Dhaka.
Study of Concussion in Rugby Union through MicroRNAs (SCRUM): a study protocol of a prospective, observational cohort study
Authors: Yakoub Kamal M , O’Halloran Patrick , Davies David J , Bentley Conor , Watson Callum N , Forcione Mario , Scarpa Ugo , Bishop Jonathan R B , Toman Emma , Hammond Douglas , Cross Matthew J , Stokes Keith A , Kemp Simon P T , Menon David K , Di Pietro Valentina , Belli Antonio
Published: November 2018

Introduction

The diagnosis of mild traumatic brain injury or sports-related concussion is a challenge for all clinicians, players, coaches and parents involved in contact sports. Currently, there is no validated objective biomarker available to assess the presence or severity of concussion in sport, and so it is necessary to rely on subjective measures like self-reporting of symptoms which depend on the cooperation of the athlete. There is a significant health risk associated with repetitive injury if the diagnosis is missed, and so there is great value in an objective biomarker to assist diagnostic and prognostic decisions.

Objective

To establish a panel of non-invasive MicroRNA biomarkers in urine and saliva for the rapid diagnosis of sports-related concussion and investigate the kinetics and clinical utility of these biomarkers in assisting diagnostic, prognostic and return-to-play decisions.

Methods and analysis

Observational, prospective, multicentre cohort study recruiting between the 2017–2018 and 2018–2019 Rugby Union seasons. Professional rugby players in the two highest tiers of senior professional domestic rugby competition in England will be recruited prospectively to the study. During the season, three groups will be identified: athletes entering the World Rugby Head Injury Assessment (HIA) protocol, uninjured control athletes and control athletes with musculoskeletal injuries. Saliva and urine will be collected from these athletes at multiple timepoints, coinciding with key times in the HIA protocol and return-to-play process.

Ethics and dissemination

Ethics approval has been obtained. The compiled and analysed results will be presented at national and international conferences concerning the care of patients with traumatic brain injury. Results will also be submitted for peer review and publication in the subject journals/literature.
Patient-reported gout attack frequency and allopurinol use in general practice in the Netherlands: a prospective observational cohort study protocol
Authors: van Leeuwen Kevin D B , Bohnen Arthur M , Jacobs Marloes L , van Der Lei Johan , Janssens Hein J E M , Koffeman Aafke R , Bindels Patrick J E , Bierma-Zeinstra Sita M A
Published: November 2018

Introduction

Gout is the most common inflammatory arthritis in the Dutch general practice population and is often managed with long-term uric acid lowering treatment. The clinical relevance of this treatment in preventing gout attacks is unclear.

Primary research question

What is the frequency of self-reported gout attacks and what is the effect of allopurinol use in patients diagnosed with gout in general practice?

Methods and analysis

Adult patients with a diagnostic consultation code for gout in the year 2013, 2014 or 2015 will be invited to participate in this prospective observational cohort study. Patients with a limited life expectancy will be excluded. Baseline measurements will include blood pressure, body mass index and a blood sample (estimated glomerular filtration rate, serum uric acid, cholesterol (low-density lipoprotein (LDL) and high-density lipoprotein), glucose (fasting)). At the 2-year follow-up, patients will receive questionnaires every 3 months. The questionnaires at baseline, 12 months and 24 months assess the frequency of gout attacks, the presence of tophi, comorbidity, medication use, quality of life, diet and lifestyle. The questionnaires in between only assess the frequency of gout attacks and medication use for gout. Descriptive statistics will be used to calculate the mean frequency of self-reported gout attacks during the 2-year follow-up. The propensity score for each patient being offered allopurinol is estimated and used to match patients with and without allopurinol treatment. We will compare the frequency of gout attacks in these groups using multilevel Poisson regression analyses. With this type of analysis, we can calculate the corrected estimated effect of allopurinol on gout attack frequency.

Ethics and dissemination

The research protocol was approved by the Medical Ethical Committee of the Erasmus Medical Centre in Rotterdam. The knowledge generated by this study will be transferred to the Dutch College of General Practitioners, conferences and to (inter)national peer-reviewed journals.

Trial registration number

NTR6329; Pre-results.
How are risk ratios reported in orthopaedic surgery journals? A descriptive study of formats used to report absolute risks
Authors: Petrova Dafina , Joeris Alexander , Sánchez María-José , Salamanca-Fernández Elena , Garcia-Retamero Rocio
Published: November 2018

Purpose

The numerical format in which risks are communicated can affect risk comprehension and perceptions of medical professionals. We investigated what numerical formats are used to report absolute risks in empirical articles, estimated the frequency of biasing formats and rated the quality of figures used to display the risks.

Design

Descriptive study of reporting practices.

Method

We randomly sampled articles published in seven leading orthopaedic surgery journals during a period of 13 years. From these, we selected articles that reported group comparisons on a binary outcome (eg, revision rates in two groups) and recorded the numerical format used to communicate the absolute risks in the results section. The quality of figures was assessed according to published guidelines for transparent visual aids design.

Outcome measures

Prevalence of information formats and quality of figures.

Results

The final sample consisted of 507 articles, of which 14% reported level 1 evidence, 13% level 2 and 73% level 3 or lower. The majority of articles compared groups of different sizes (90%), reported both raw numbers and percentages (64%) and did not report the group sizes alongside (50%). Fifteen per cent of articles used two formats identified as biasing: only raw numbers (8%, ‘90 patients vs 100 patients’) or raw numbers reported alongside different group sizes (7%, ‘90 out of 340 patients vs 100 out of 490 patients’). The prevalence of these formats decreased in more recent publications. Figures (n=79) had on average two faults that could distort comprehension, and the majority were rated as biasing.

Conclusion

Authors use a variety of formats to report absolute risks in scientific articles and are likely not aware of how some formats and graph design features can distort comprehension. Biases can be reduced if journals adopt guidelines for transparent risk communication but more research is needed into the effects of different formats.
Case management in primary care for frequent users of healthcare services with chronic diseases and complex care needs: an implementation and realist evaluation protocol
Authors: Hudon Catherine , Chouinard Maud-Christine , Aubrey-Bassler Kris , Burge Frederick , Doucet Shelley , Ramsden Vivian R , Brodeur Magaly , Bush Paula L , Couturier Yves , Dubois Marie-France , Guénette Line , Légare France , Morin Paul , Poder Thomas G , Poitras Marie-Ève , Roberge Pasquale , Valaitis Ruta , Bighead Shirley , Campbell Cameron , Couture Martine , Davis Breanna , Deschenes Élaine , Edwards Lynn , Gander Sarah , Gauthier Gilles , Gauthier Patricia , Gibson Richard J , Godbout Julie , Landry Geneviève , Longjohn Christine , Rabbitskin Norma , Roy Denis A , Roy Judy , Sabourin Véronique , Sampalli Tara , Saulnier Amanda , Spence Claude , Splane Jennifer , Warren Mike , Young Joanne , Pluye Pierre
Published: November 2018

Introduction

Significant evidence in the literature supports case management (CM) as an effective intervention to improve care for patients with complex healthcare needs. However, there is still little evidence about the facilitators and barriers to CM implementation in primary care setting. The three specific objectives of this study are to: (1) identify the facilitators and barriers of CM implementation in primary care clinics across Canada; (2) explain and understand the relationships between the actors, contextual factors, mechanisms and outcomes of the CM intervention; (3) identify the next steps towards CM spread in primary care across Canada.

Methods and analysis

We will conduct a multiple-case embedded mixed methods study. CM will be implemented in 10 primary care clinics in five Canadian provinces. Three different units of analysis will be embedded to obtain an in-depth understanding of each case: the healthcare system (macro level), the CM intervention in the clinics (meso level) and the individual/patient (micro level). For each objective, the following strategy will be performed: (1) an implementation analysis, (2) a realist evaluation and (3) consensus building among stakeholders using the Technique for Research of Information by Animation of a Group of Experts method.

Ethics and dissemination

This study, which received ethics approval, will provide innovative knowledge about facilitators and barriers to implementation of CM in different primary care jurisdictions and will explain how and why different mechanisms operate in different contexts to generate different outcomes among frequent users. Consensual and prioritised statements about next steps for spread of CM in primary care from the perspectives of all stakeholders will be provided. Our results will offer context-sensitive explanations that can better inform local practices and policies and contribute to improve the health of patients with complex healthcare needs who frequently use healthcare services. Ultimately, this will increase the performance of healthcare systems and specifically mitigate ineffective use and costs.
Sampling design and methodology of the Violence Against Children and Youth Surveys
Authors: Nguyen Kimberly H , Kress Howard , Villaveces Andres , Massetti Greta M
Published: November 2018

Introduction

Globally 1 billion children are exposed to violence every year. The Violence Against Children Surveys (VACS) are nationally representative surveys of males and females ages 13–24 that are intended to measure the burden of sexual, physical and emotional violence experienced in childhood, adolescence and young adulthood. It is important to document the methodological approach and design of the VACS to better understand the national estimates that are produced in each country, which are used to drive violence prevention efforts.

Methods

This study describes the surveys’ target population, sampling design, statistical considerations, data collection process, priority violence indicators and data dissemination.

Results

Twenty-four national household surveys have been completed or are being planned in countries across Africa, Asia, the Caribbean, Central and South America, and Eastern Europe. The sample sizes range from 891 to 7912 among females (72%–98% response rate) and 803–2717 among males (66%–98% response rate). Two face-to-face interviews are conducted: a Household and an Individual Questionnaire. A standard set of core priority indicators are generated for each country that range from prevalence of different types of violence, contexts, risk and protective factors, and health consequences. Results are disseminated through various platforms to expand the reach and impact of the survey results.

Conclusion

Data obtained through VACS can inform development and implementation of effective prevention strategies and improve health service provision for all who experience violence. VACS serves as a standardised tool to inform and drive prevention through high-quality, comprehensive data.
Pipeline embolization device treatment of internal carotid artery terminus aneurysms
Authors: Pujari Amit , Howard Brian Matthew , Madaelil Thomas P , Skukalek Susana Libhaber , Roy Anil K , Dion Jacques E , Cawley C Michael , Grossberg Jonathan A
Published: November 2018

Background

The pipeline embolization device (PED) is approved for the treatment of large aneurysms of the proximal internal carotid artery (ICA). Its off-label application in treating aneurysms located specifically at the ICA terminus (ICA-T) has not been studied.

Methods

We conducted a retrospective chart review of patients from 2011 to 7 treated with PEDs. Out of 365 patients, 10 patients with ICA-T aneurysms were included. Patient demographics, procedural information, follow-up imaging, and clinical assessments were recorded.

Results

Mean age was 46.9 years (±8.8), and 6 (60%) patients were women. The mean maximum diameter of the aneurysms treated was 14.7 mm (±10.7) and the mean neck diameter was 9.3 mm (±6.6). Reasons for presentation included six incidental findings, one acute subarachnoid hemorrhage (SAH), and three patients with prior SAH. Kamran–Byrne Occlusion Scale scores for the treated aneurysms were as follows: three class IV (complete obliteration), four class III (<50% filling in both height and width for fusiform aneurysms or residual neck for saccular aneurysms), one class II fusiform aneurysm, 1 class 0 saccular aneurysm (residual aneurysm body), and one not classified due to pipeline thrombosis. Two clinically asymptomatic complications were noted: one patient who had a small distal cortical SAH post PED and one patient whose stent was found to be thrombosed on follow-up angiogram. All patients were seen in follow-up, and no patients were found to have worsening of their pre-procedure modified Rankin Scale score.

Conclusion

The PED has potential for treating ICA-T aneurysms not amenable to conventional treatment strategies. Further studies are warranted to confirm the long term outcomes.
Ginsenoside metabolite compound K induces apoptosis and autophagy in non-small cell lung cancer cells via AMPK–mTOR and JNK pathways
Authors: Li Chen , Dong Yuchao , Wang Libo , Xu Gongbin , Yang Qing , Tang Xiaofei , Qiao Yingying , Cong Zhonghuang
Published: November 2018

Compound K [C-K; 20-O-(β-d-glucopyranosyl)-20(S)-protopanaxadiol], as a metabolite of ginsenoside, has been verified to have antitumor effects in various cancers, including non-small cell lung cancer (NSCLC). However, the detailed mechanisms of C-K in NSCLC remain largely unknown. In this study, we aimed to evaluate the effect of C-K on apoptosis and autophagy in NSCLC cells as well as its related mechanisms. According to the results, C-K suppressed the proliferation, and led to G1 phase arrest and apoptosis in A549 and H1975 cells. Subsequently, C-K promoted autophagy, as confirmed by the enhanced rate of cells staining positive with acridine orange, increased levels of LC3II and Beclin-1, and with decreased levels of p62 in A549 and H1975 cells. Moreover, 3-methyladenine (3-MA; an inhibitor of autophagy) effectively suppressed the inhibition of proliferation and apoptosis that was induced with C-K. Finally, C-K treatment promoted the activation of the AMPK–mTOR and c-Jun N-terminal kinase (JNK) signaling pathways. Treatment with compound C (AMPK inhibitor) or SP600125 (JNK inhibitor) significantly restrained the inhibition of proliferation, apoptosis, and autophagy induced with C-K in A549 and H1975 cells. In conclusion, this study demonstrates that C-K promotes autophagy-mediated apoptosis in NSCLC via AMPK–mTOR and JNK signaling pathways.
A geostatistical approach to winter road surface condition estimation using mobile RWIS data
Authors: Gu Lian , Kwon Tae J. , Qiu Tony Z.
Published: November 2018

In winter, it is critical for cold regions to have a full understanding of the spatial variation of road surface conditions such that hot spots (e.g., black ice) can be identified for an effective mobilization of winter road maintenance operations. Acknowledging the limitations in present study, this paper proposes a systematic framework to estimate road surface temperature (RST) via the geographic information system (GIS). The proposed method uses a robust regression kriging method to take account for various geographical factors that may affect the variation of RST. A case study of highway segments in Alberta, Canada is used to demonstrate the feasibility and applicability of the method proposed herein. The findings of this study suggest that the geostatistical modelling framework proposed in this paper can accurately estimate RST with help of various covariates included in the model and further promote the possibility of continuous monitoring and visualization of road surface conditions.
Response of winter wheat to herbicide plus fungicide plus ammonium thiosulphate tank-mixes
Authors: Hooker David C. , Soltani Nader , Sikkema Peter H.
Published: November 2018

A study was conducted at six field sites near Exeter and Ridgetown, ON, over a 3 yr period (2014, 2015, and 2016) to determine the effect of ammonium thiosulphate (ATS), various fungicides (azoxystrobin/propiconazole, trifloxystrobin/prothioconazole, or pyraclostrobin/metconazole), and various herbicides (bromoxynil/MCPA, thifensulfuron/tribenuron + MCPA, pyrasulfotole/bromoxynil, or 2,4-D/dichlorprop) applied alone and in tank-mix combinations on winter wheat crop injury and grain yield. The treatments were applied using Hypro ULD120-02 flat-fan nozzles around Zadoks growth stage 30. The herbicides and fungicides caused <0.6% leaf injury when ATS was not added to the tank-mix. When averaged across fungicides in ATS tank-mixes, leaf injury 1 wk after treatment application was 3.5% to 3.7% with thifensulfuron/tribenuron and dichlorprop-P/2,4-D herbicides and 5.1% to 5.8% injury with bromoxynil/MCPA and thifensulfuron/tribenuron herbicides. On the three field sites with the highest leaf injury, a fungicide–ATS tank-mix increased injury to 4.5% averaged across fungicides and to 4.3% with a herbicide–ATS tank-mix averaged across herbicides. Three-way tank-mixes of herbicide–fungicide–ATS caused the highest injury (7.1%). Despite significant crop injury 1 WAA with some tank-mixes, there was no evidence that grain yields were adversely affected. This study shows that the co-application of a three-way tank-mix of ATS with fungicides (azoxystrobin/propiconazole, trifloxystrobin/prothioconazole, or pyraclostrobin/metconazole) and herbicides (bromoxynil/MCPA, thifensulfuron/tribenuron + MCPA, pyrasulfotole/bromoxynil, or dichlorprop-P/2,4-D) has the potential to cause considerable injury in winter wheat under some environmental conditions in Ontario, but the effect seems transient, with no grain yield reductions detected.
THE DARK SIDE OF GOSSIPS: HINTS FROM A SIMPLE OPINION DYNAMICS MODEL
Authors: DEFFUANT GUILLAUME , BERTAZZI ILARIA , HUET SYLVIE
Published: November 2018

We consider a simple model of agents modifying their opinion about themselves and about the others during random pair interactions. Two unexpected patterns emerge: (1) without gossips, starting from zero, agents’ opinions tend to grow and stabilize on average at a positive value; (2) when introducing gossips, this pattern is inverted; the opinions tend to decrease and stabilize on average at a negative value. We show that these patterns can be explained by the relative influence of a positive bias on self-opinions and of a negative bias on opinions about others. Without gossips, the positive bias on self-opinions dominates, leading to a positive average opinion. Gossips increase the negative bias about others, which can dominate the positive bias on self-opinions, leading to a negative average opinion.
Surjective H-Colouring over Reflexive Digraphs
Authors: Larose Benoît , Martin Barnaby , Paulusma Daniël
Published: November 2018

The S
urjective
H-C
olouring
problem is to test if a given graph allows a vertex-surjective homomorphism to a fixed graph H. The complexity of this problem has been well studied for undirected (partially) reflexive graphs. We introduce
endo-triviality
, the property of a structure that all of its endomorphisms that do not have range of size 1 are automorphisms, as a means to obtain complexity-theoretic classifications of S
urjective
H-C
olouring
in the case of reflexive
digraphs
. Chen (2014) proved, in the setting of constraint satisfaction problems, that S
urjective
H-C
olouring
is NP-complete if H has the property that all of its polymorphisms are essentially unary. We give the first concrete application of his result by showing that every endo-trivial reflexive digraph H has this property. We then use the concept of endo-triviality to prove, as our main result, a dichotomy for S
urjective
H-C
olouring
when H is a reflexive tournament: if H is transitive, then S
urjective
H-C
olouring
is in NL; otherwise, it is NP-complete. By combining this result with some known and new results, we obtain a complexity classification for S
urjective
H-C
olouring
when H is a partially reflexive digraph of size at most 3.
Prolonged intake of desloratadine: mesenteric lymphatic vessel dysfunction and development of obesity/metabolic syndrome
Authors: Gasheva Olga Y. , Tsoy Nizamutdinova Irina , Hargrove Laura , Gobbell Cassidy , Troyanova-Wood Maria , Alpini Sally F. , Pal Sarit , Du Christina , Hitt Angie R. , Yakovlev Vlad V. , Newell-Rogers M. Karen , Zawieja David C. , Meininger Cynthia J. , Alpini Gianfranco D. , Francis Heather , Gashev Anatoliy A.
Published: November 2018

This study aimed to establish mechanistic links between the prolonged intake of desloratadine, a common H1 receptor blocker (i.e., antihistamine), and development of obesity and metabolic syndrome. Male Sprague-Dawley rats were treated for 16 wk with desloratadine. We analyzed the dynamics of body weight gain, tissue fat accumulation/density, contractility of isolated mesenteric lymphatic vessels, and levels of blood lipids, glucose, and insulin, together with parameters of liver function. Prolonged intake of desloratadine induced development of an obesity-like phenotype and signs of metabolic syndrome. These alterations in the body included excessive weight gain, increased density of abdominal subcutaneous fat and intracapsular brown fat, high blood triglycerides with an indication of their rerouting toward portal blood, high HDL, high fasting blood glucose with normal fasting and nonfasting insulin levels (insulin resistance), high liver/body weight ratio, and liver steatosis (fatty liver). These changes were associated with dysfunction of mesenteric lymphatic vessels, specifically high lymphatic tone and resistance to flow together with diminished tonic and abolished phasic responses to increases in flow, (i.e., greatly diminished adaptive reserves to respond to postprandial increases in lymph flow). The role of nitric oxide in this flow-dependent adaptation was abolished, with remnants of these responses controlled by lymphatic vessel-derived histamine. Our current data, considered together with reports in the literature, support the notion that millions of the United States population are highly likely affected by underevaluated, lymphatic-related side effects of antihistamines and may develop obesity and metabolic syndrome due to the prolonged intake of this medication.

NEW & NOTEWORTHY Prolonged intake of desloratadine induced development of obesity and metabolic syndrome associated with dysfunction of mesenteric lymphatic vessels, high lymphatic tone, and resistance to flow together with greatly diminished adaptive reserves to respond to postprandial increases in lymph flow. Data support the notion that millions of the USA population are highly likely affected by underevaluated, lymphatic-related side effects of antihistamines and may develop obesity and metabolic syndrome due to the prolonged intake of this medication.
Measuring Occupants’ Behaviour for Buildings’ Dynamic Cosimulation
Authors: Naspi Federica , Arnesano Marco , Stazi Francesca , D’Orazio Marco , Revel Gian Marco
Published: November 2018

Measuring and identifying human behaviours are key aspects to support the simulation processes that have a significant role in buildings’ (and cities’) design and management. In fact, layout assessments and control strategies are deeply influenced by the prediction of building performance. However, the missing inclusion of the human component within the building-related processes leads to large discrepancies between actual and simulated outcomes. This paper presents a methodology for measuring specific human behaviours in buildings and developing human-in-the-loop design applied to retrofit and renovation interventions. The framework concerns the detailed building monitoring and the development of stochastic and data-driven behavioural models and their coupling within energy simulation software using a cosimulation approach. The methodology has been applied to a real case study to illustrate its applicability. A one-year monitoring has been carried out through a dedicated sensor network for the data recording and to identify the triggers of users’ actions. Then, two stochastic behavioural models (i.e., one for predicting light switching and one for window opening) have been developed (using the measured data) and coupled within the IESVE simulation software. A simplified energy model of the case study has been created to test the behavioural approach. The outcomes highlight that the behavioural approach provides more accurate results than a standard one when compared to real profiles. The adoption of behavioural profiles leads to a reduction of the discrepancy with respect to real profiles up to 58% and 26% when simulating light switching and ventilation, respectively, in comparison to standard profiles. Using data-driven techniques to include the human component in the simulation processes would lead to better predictions both in terms of energy use and occupants’ comfort sensations. These aspects can be also included in building control processes (e.g., building management systems) to enhance the environmental and system management.
Controversies and Misconceptions Related to Cerebrospinal Fluid Circulation: A Review of the Literature from the Historical Pioneers’ Theories to Current Models
Authors: Mantovani Giorgio , Menegatti Marta , Scerrati Alba , Cavallo Michele Alessandro , De Bonis Pasquale
Published: November 2018

Models of cerebrospinal fluid (CSF) circulation have been mainly proposed in the last century: CSF goes from the ventricles to the subarachnoidal space (SAS), passing through the aqueduct and the foramen of Luschka and Magendie. Indeed, new models, involving the Virchow-Robin space (VRS) and the perivascular space (PVS), have been proposed. We critically reviewed the literature, in order to clarify the “classical” errors and to discuss the “new” models that are evolving currently. Conclusions of past experiments are often not justified, due to lack of reproducibility and methodological issues. On the other hand, investigation on the microanatomy of Virchow-Robin spaces (VRS) and several new experiments showed a potential pathway for a more complex CSF “circulation,” with chaotic and unpredictable flows. It seems reasonable to elaborate a new model of CSF physiology, including new findings and questioning old certainties. However, proved data are still missing and it is hazardous to come to final conclusions. More studies are needed.