Presphenoidal synchondrosis fusion in DBA/2J mice

Cranial base growth plates are important centers of longitudinal growth in the skull and are responsible for the proper anterior placement of the face and the stimulation of normal cranial vault development. We report that the presphenoidal synchondrosis (PSS), a midline growth plate of the cranial base, closes in the DBA/2J mouse strain but not in other common inbred strains. We investigated the genetics of PSS closure in DBA/2J mice by evaluating F1, F1 backcross, and/or F1 intercross offspring from matings with C57BL/6J and DBA/1J mice, whose PSS remain open. We observed that PSS closure is genetically determined, but not inherited as a simple Mendelian trait. Employing a genome-wide SNP array, we identified a region on chromosome 11 in the C57BL/6J strain that affected the frequency of PSS closure in F1 backcross and F1 intercross offspring. The equivalent region in the DBA/1J strain did not affect PSS closure in F1 intercross offspring. We conclude that PSS closure in the DBA/2J strain is complex and modified by different loci when outcrossed with C57BL/6J and DBA/1J mice. Electronic supplementary material The online version of this article (doi:10.1007/s00335-012-9437-8) contains supplementary material, which is available to authorized users

General practitioner workforce sustainability to maximise effective and equitable patient care: a realist review protocol

Introduction There are not enough general practitioners (GPs) in the UK National Health Service. This problem is worse in areas of the country where poverty and underinvestment in health and social care mean patients experience poorer health compared with wealthier regions. Encouraging more doctors to choose and continue in a GP career is a government priority. This review will examine which aspects of the healthcare system affect GP workforce sustainability, how, why and for whom. Methods and analysis A realist review is a theory-driven interpretive approach to evidence synthesis, that brings together qualitative, quantitative, mixed-methods research and grey literature. We will use a realist approach to synthesise data from the available published literature to refine an evidence-based programme theory that will identify the important contextual factors and underlying mechanisms that underpin observed outcomes relating to GP workforce sustainability. Our review will follow Pawson’s five iterative stages: (1) finding existing theories, (2) searching for evidence, (3) article selection, (4) data extraction and (5) synthesising evidence and drawing conclusions. We will work closely with key stakeholders and embed patient and public involvement throughout the review process to refine the focus of the review and enhance the impact and relevance of our research. Ethics and dissemination This review does not require formal ethical approval as it draws on secondary data from published articles and grey literature. Findings will be disseminated through multiple channels, including publication in peer-reviewed journals, at national and international conferences, and other digital scholarly communication tools such as video summaries, X and blog posts. PROSPERO registration number CRD42023395583

Give a little RESPECT: Patient and Public Involvement in Research

There are many reasons why patient and public involvement (PPI) is important for health research. This interactive workshop will discuss the value of PPI along with the hurdles and (more importantly) solutions. Examples will be drawn from our experiences of PPI involvement in the RESPECT study, which aims to improve the sexual health of people with serious mental illness

Public health surveillance in the UK revolutionises our understanding of the invasive Salmonella Typhimurium epidemic in Africa

Background:The ST313 sequence type ofSalmonellaTyphimurium causes invasive non-typhoidal salmonellosis and wasthought to be confined to sub-Saharan Africa. Two distinct phylogenetic lineages of African ST313 have been identified.Methods:We analysed the whole genome sequences ofS. Typhimurium isolates from UK patients that weregenerated following the introduction of routine whole-genome sequencing (WGS) ofSalmonella entericabyPublic Health England in 2014.Results:We found that 2.7% (84/3147) ofS. Typhimurium from patients in England and Wales were ST313 and wereassociated with gastrointestinal infection. Phylogenetic analysis revealed novel diversity of ST313 that distinguishedUK-linked gastrointestinal isolates from African-associated extra-intestinal isolates. The majority of genome degradationof African ST313 lineage 2 was conserved in the UK-ST313, but the African lineages carried a characteristic prophageand antibiotic resistance gene repertoire. These findings suggest that a strong selection pressure exists for certainhorizontally acquired genetic elements in the African setting. One UK-isolated lineage 2 strain that probably originatedin Kenya carried a chromosomally locatedblaCTX-M-15, demonstrating the continual evolution of this sequence type inAfrica in response to widespread antibiotic usage.Conclusions:The discovery of ST313 isolates responsible for gastroenteritis in the UK reveals new diversity in thisimportant sequence type. This study highlights thepower of routine WGS by public health agencies to makeepidemiologically significant deductions that would be missed by conventional microbiological methods. Wespeculate that the niche specialisation of sub-Saharan African ST313 lineages is driven in part by the acquisitionof accessory genome elements

Identifying schizophrenia patients who carry pathogenic genetic copy number variants using standard clinical assessment: retrospective cohort study

Background Copy number variants (CNVs) play a significant role in disease pathogenesis in a small subset of individuals with schizophrenia (~2.5%). Chromosomal microarray testing is a first-tier genetic test for many neurodevelopmental disorders. Similar testing could be useful in schizophrenia. Aims To determine whether clinically identifiable phenotypic features could be used to successfully model schizophrenia-associated (SCZ-associated) CNV carrier status in a large schizophrenia cohort. Method Logistic regression and receiver operating characteristic (ROC) curves tested the accuracy of readily identifiable phenotypic features in modelling SCZ-associated CNV status in a discovery data-set of 1215 individuals with psychosis. A replication analysis was undertaken in a second psychosis data-set (n = 479). Results In the discovery cohort, specific learning disorder (OR = 8.12; 95% CI 1.16–34.88, P = 0.012), developmental delay (OR = 5.19; 95% CI 1.58–14.76, P = 0.003) and comorbid neurodevelopmental disorder (OR = 5.87; 95% CI 1.28–19.69, P = 0.009) were significant independent variables in modelling positive carrier status for a SCZ-associated CNV, with an area under the ROC (AUROC) of 74.2% (95% CI 61.9–86.4%). A model constructed from the discovery cohort including developmental delay and comorbid neurodevelopmental disorder variables resulted in an AUROC of 83% (95% CI 52.0–100.0%) for the replication cohort. Conclusions These findings suggest that careful clinical history taking to document specific neurodevelopmental features may be informative in screening for individuals with schizophrenia who are at higher risk of carrying known SCZ-associated CNVs. Identification of genomic disorders in these individuals is likely to have clinical benefits similar to those demonstrated for other neurodevelopmental disorders

Longitudinal impact of changes in the residential built environment on physical activity: findings from the ENABLE London cohort study.

BACKGROUND: Previous research has reported associations between features of the residential built environment and physical activity but these studies have mainly been cross-sectional, limiting inference. This paper examines whether changes in a range of residential built environment features are associated with changes in measures of physical activity in adults. It also explores whether observed effects are moderated by socio-economic status. METHODS: Data from the Examining Neighbourhood Activity in Built Living Environments in London (ENABLE London) study were used. A cohort of 1278 adults seeking to move into social, intermediate, and market-rent East Village accommodation was recruited in 2013-2015, and followed up after 2 years. Accelerometer-derived steps (primary outcome), and GIS-derived measures of residential walkability, park proximity and public transport accessibility were obtained both at baseline and follow-up. Daily steps at follow-up were regressed on daily steps at baseline, change in built environment exposures and confounding variables using multilevel linear regression to assess if changes in neighbourhood walkability, park proximity and public transport accessibility were associated with changes in daily steps. We also explored whether observed effects were moderated by housing tenure as a marker of socio-economic status. RESULTS: Between baseline and follow-up, participants experienced a 1.4 unit (95%CI 1.2,1.6) increase in neighbourhood walkability; a 270 m (95%CI 232,307) decrease in distance to their nearest park; and a 0.7 point (95% CI 0.6,0.9) increase in accessibility to public transport. A 1 s.d. increase in neighbourhood walkability was associated with an increase of 302 (95%CI 110,494) daily steps. A 1 s.d. increase in accessibility to public transport was not associated with any change in steps overall, but was associated with a decrease in daily steps amongst social housing seekers (- 295 steps (95%CI - 595, 3), and an increase in daily steps for market-rent housing seekers (410 95%CI -191, 1010) (P-value for effect modification = 0.03). CONCLUSION: Targeted changes in the residential built environment may result in increases in physical activity levels. However, the effect of improved accessibility to public transport may not be equitable, showing greater benefit to the more advantaged

The feasibility and acceptability of a novel anxiety in bipolar disorder intervention compared to treatment as usual:a randomized controlled trial

1 Background Comorbid anxiety is common in bipolar disorder (BD) and associated with worse clinical outcomes including increased suicidality. Despite effective psychological treatments for anxiety, research into treating anxiety in BD is underdeveloped. This paper describes a novel psychological intervention to address anxiety in context of bipolar disorder (AIBD). 2 Methods Adults with BD and clinically significant anxiety symptoms were randomized to AIBD plus treatment as usual (TAU) or TAU alone. AIBD offered 10 sessions of psychological therapy using a formulation‐based approach. Feasibility and acceptability were evaluated through recruitment, retention, therapy attendance, alliance, fidelity, and qualitative feedback. Clinical outcomes were assessed at baseline, 16, 48, and 80 weeks: interim assessments of relapse at 32 and 64 weeks. 3 Results Seventy‐two participants were recruited with 88% retention to 16 weeks and 74% to 80 weeks (similar between arms). Therapy participants attended urn:x-wiley:10914269:media:da22781:da22781-math-00017.7 (SD 2.8) sessions. Therapeutic alliance and therapy fidelity were acceptable. Qualitative interviews indicated that participants valued integrated support for anxiety with BD and coping strategies. Some suggested a longer intervention period. Clinical outcomes were not significantly different between arms up to 80 weeks follow‐up. 4 Conclusions AIBD is feasible and acceptable but lack of impact on clinical outcomes indicates that adaptations are required. These are discussed in relation to qualitative feedback and recent literature published since the trial completed

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London