Dynamic instability of the major urinary protein gene family revealed by genomic and phenotypic comparisons between C57 and 129 strain mice

Targeted sequencing, manual genome annotation, phylogenetic analysis and mass spectrometry were used to characterise major urinary proteins (MUPs) and the Mup clusters of two strains of inbred mice

Building primary care quality and performance via a clinical microsystems approach

APHCRI Conversations was a regular program of presentations held at the Department of Health to facilitate exchange between APHCRI Network researchers and Department policymakers. Topics are developed jointly with the Department of Health and involve a range of speakers from APHCRI, including CRE invited experts, CRE Chief Investigators and stream project Chief Investigator

HILT : High-Level Thesaurus Project M2M Feasibility Study : [Final Report]

The project was asked to investigate the feasibility of developing SOAP-based interfaces between JISC IE services and Wordmap APIs and non-Wordmap versions of the HILT pilot demonstrator created under HILT Phase II and to determine the scope and cost of the provision of an actual demonstrator based on each of these approaches. In doing so it was to take into account the possibility of a future Zthes1-based solution using Z39.50 or OAI-PMH and syntax and data-exchange protocol implications of eScience and semantic-web developments. It was agreed that the primary concerns of the study should be an assessment of the feasibility, scope, and cost of a follow-up M2M pilot that considered the best options in respect of: o Query protocols (SOAP, Z39.50, SRW, OAI) and associated data profiles (e.g. Zthes for Z39.50 and for SRW); o Standards for structuring thesauri and thesauri-type information (e.g. the Zthes XML DTD and SRW version of it and SKOS-Core2); The study was carried out within the allotted timescale, with this Final Report submitted to JISC on 31st March 2005 as scheduled. The detailed proposal for a follow-up project is currently under discussion and will be finalised – as agreed with JISC – by mid-April. It was concluded that an M2M pilot was feasible. A proposal for a follow-up M2M pilot project has been scoped, and is currently being costed

The Development of the Older Person's Nurse Fellowship: Education concept to delivery.

Background Preparing the nursing workforce to meet the challenges of an ageing population is a priority for many countries. The development of an Older Person's Nurse Fellowship (OPNF) programme for senior clinical nurses is an important innovation. Objectives This article describes the philosophical development, delivery and early evaluation of the OPNF. Design In 2014, Health Education England funded 24 senior clinical nurses to participate in the OPNF. The Fellowship was designed to build clinical leadership and innovation capability and develop a network of nurses to influence local and national strategy for older people's care. The Fellows selected were drawn from mental health (n = 4), community/primary care (n = 9) and acute care (n = 11). The twelve month programme consisted of two Masters-level modules, delivered through study days and e-learning. The first cohort (n = 12) commenced the course in November 2014 with a module designed to enhance clinical knowledge and skills. Methods Evaluation data were collected from the first cohort using anonymous surveys (n = 11) and focus group interviews (n = 9). Descriptive statistics are presented for the quantitative data and common themes are described in the qualitative data. Results The overall satisfaction with the clinical module was high with a median score of 18/20 (range 17–20). Topics such as comprehensive geriatric assessment, frailty, pharmacology and cognitive assessment were regarded as highly relevant and most likely to result in a change to clinical practice. In the focus group interviews students discussed their learning experience in terms of: module specificity, peer-to-peer learning and using the OPNF as leverage for change. Conclusions The OPNF is a timely innovation and a positive commitment to developing an academic pathway for senior nurses. It marks an important step in the future development of the older person's nursing workforce

Lung eQTLs to Help Reveal the Molecular Underpinnings of Asthma

Genome-wide association studies (GWAS) have identified loci reproducibly associated with pulmonary diseases; however, the molecular mechanism underlying these associations are largely unknown. The objectives of this study were to discover genetic variants affecting gene expression in human lung tissue, to refine susceptibility loci for asthma identified in GWAS studies, and to use the genetics of gene expression and network analyses to find key molecular drivers of asthma. We performed a genome-wide search for expression quantitative trait loci (eQTL) in 1,111 human lung samples. The lung eQTL dataset was then used to inform asthma genetic studies reported in the literature. The top ranked lung eQTLs were integrated with the GWAS on asthma reported by the GABRIEL consortium to generate a Bayesian gene expression network for discovery of novel molecular pathways underpinning asthma. We detected 17,178 cis- and 593 trans- lung eQTLs, which can be used to explore the functional consequences of loci associated with lung diseases and traits. Some strong eQTLs are also asthma susceptibility loci. For example, rs3859192 on chr17q21 is robustly associated with the mRNA levels of GSDMA (P = 3.55 × 10(-151)). The genetic-gene expression network identified the SOCS3 pathway as one of the key drivers of asthma. The eQTLs and gene networks identified in this study are powerful tools for elucidating the causal mechanisms underlying pulmonary disease. This data resource offers much-needed support to pinpoint the causal genes and characterize the molecular function of gene variants associated with lung diseases

A simulated “Night-onCall” to assess and address the readiness-for-internship of transitioning medical students

Transitioning medical students are anxious about their readiness-for-internship, as are their residency program directors and teaching hospital leadership responsible for care quality and patient safety. A readiness-for-internship assessment program could contribute to ensuring optimal quality and safety and be a key element in implementing competency-based, time-variable medical education. In this paper, we describe the development of the Night-onCall program (NOC), a 4-h readiness-for-internship multi-instructional method simulation event. NOC was designed and implemented over the course of 3 years to provide an authentic “night on call” experience for near graduating students and build measurements of students’ readiness for this transition framed by the Association of American Medical College’s Core Entrustable Professional Activities for Entering Residency. The NOC is a product of a program of research focused on questions related to enabling individualized pathways through medical training. The lessons learned and modifications made to create a feasible, acceptable, flexible, and educationally rich NOC are shared to inform the discussion about transition to residency curriculum and best practices regarding educational handoffs from undergraduate to graduate education

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

Compartir los datos de investigación en ciencia: introducción al data sharing

The emergence in the scientific community of an initiative known as data sharing, consisting of sharing research data among researchers and aiming to maximize efforts and resources, is analysed. First, the concept of research data and the related technical difficulties depending on the discipline are reviewed. We also examine the motivations, origins and growth of this movement, which has had an important impact on the scientific community’s behaviour through the creation of reposi- tories and data banks, raising both technical and social challenges. Then we discuss leading funding agencies’ initiatives and scientific journals’ editorial policies promoting these practices. Finally, we examine the impact these major changes in researchers’ habits have for librarians, including the emergence of new professional profiles

Hypoinsulinemia Regulates Amphetamine-Induced Reverse Transport of Dopamine

The behavioral effects of psychomotor stimulants such as amphetamine (AMPH) arise from their ability to elicit increases in extracellular dopamine (DA). These AMPH-induced increases are achieved by DA transporter (DAT)-mediated transmitter efflux. Recently, we have shown that AMPH self-administration is reduced in rats that have been depleted of insulin with the diabetogenic agent streptozotocin (STZ). In vitro studies suggest that hypoinsulinemia may regulate the actions of AMPH by inhibiting the insulin downstream effectors phosphotidylinositol 3-kinase (PI3K) and protein kinase B (PKB, or Akt), which we have previously shown are able to fine-tune DAT cell-surface expression. Here, we demonstrate that striatal Akt function, as well as DAT cell-surface expression, are significantly reduced by STZ. In addition, our data show that the release of DA, determined by high-speed chronoamperometry (HSCA) in the striatum, in response to AMPH, is severely impaired in these insulin-deficient rats. Importantly, selective inhibition of PI3K with LY294002 within the striatum results in a profound reduction in the subsequent potential for AMPH to evoke DA efflux. Consistent with our biochemical and in vivo electrochemical data, findings from functional magnetic resonance imaging experiments reveal that the ability of AMPH to elicit positive blood oxygen level–dependent signal changes in the striatum is significantly blunted in STZ-treated rats. Finally, local infusion of insulin into the striatum of STZ-treated animals significantly recovers the ability of AMPH to stimulate DA release as measured by high-speed chronoamperometry. The present studies establish that PI3K signaling regulates the neurochemical actions of AMPH-like psychomotor stimulants. These data suggest that insulin signaling pathways may represent a novel mechanism for regulating DA transmission, one which may be targeted for the treatment of AMPH abuse and potentially other dopaminergic disorders