Lymph node macrophages restrict murine cytomegalovirus dissemination

Cytomegaloviruses (CMVs) establish chronic infections that spread from a primary entry site to secondary vascular sites, such as the spleen, and then to tertiary shedding sites, such as the salivary glands. Human CMV (HCMV) is difficult to analyze, because its spread precedes clinical presentation. Murine CMV (MCMV) offers a tractable model. It is hypothesized to spread from peripheral sites via vascular endothelial cells and associated monocytes. However, viral luciferase imaging showed footpad-inoculated MCMV first reaching the popliteal lymph nodes (PLN). PLN colonization was rapid and further spread was slow, implying that LN infection can be a significant bottleneck. Most acutely infected PLN cells were CD169(+) subcapsular sinus macrophages (SSM). Replication-deficient MCMV also reached them, indicating direct infection. Many SSM expressed viral reporter genes, but few expressed lytic genes. SSM expressed CD11c, and MCMV with a cre-sensitive fluorochrome switch showed switched infected cells in PLN of CD11c-cre mice but yielded little switched virus. SSM depletion with liposomal clodronate or via a CD169-diphtheria toxin receptor transgene shifted infection to ER-TR7(+) stromal cells, increased virus production, and accelerated its spread to the spleen. Therefore, MCMV disseminated via LN, and SSM slowed this spread by shielding permissive fibroblasts and poorly supporting viral lytic replication

A Global Portrait of Counselling Psychologists’ Characteristics, Perspectives, and Professional Behaviors

Counselling psychologists in eight countries (Australia, Canada, New Zealand, South Africa, South Korea, Taiwan, the United Kingdom, and the United States) responded to survey questions that focused on their demographics as well as their professional identities, roles, settings and activities. As well, they were asked about satisfaction with the specialty and the extent to which they endorsed 10 core counselling psychology values. This article reports those results, focusing both on areas in which there were between-country similarities as well as on those for which there were differences. These data provide is a snapshot of counselling psychology globally and establish a foundation for the other articles in this special issue of the journal

Pharmacists in general practice: a qualitative interview case study of stakeholders’ experiences in a West London GP Federation

Background Increased patient demand for healthcare services coupled with a shortage of general practitioners necessitates changes in professional roles and service delivery. In 2016, NHS England began a three year pilot study of pharmacists in general practice, however, this is not an entirely new initiative. There is limited, current, evidence-based, UK research to inform the pilot so studies of pre-existing services must suffice until findings from a formal national evaluation are available. Methods The aim of this exploratory, descriptive interview study was to explore the experiences of stakeholders in eight general practices in the Ealing GP Federation, West London, where pharmacy services have been provided for several years. Forty-seven participants, including pharmacy team members (pre-registration and clinical pharmacists, independent prescribers and pharmacy technicians), general practitioners, patients, practice managers, practice nurses and receptionists took part in semi-structured, audio-recorded qualitative interviews which were transcribed verbatim, coded and analysed thematically to extract the issues raised by participants and the practicalities of providing pharmacy services in general practice. Results Findings are reported under the themes of Complementarity (incorporating roles, skills, education and workloads); Integration (incorporating relationships, trust and communication) and Practicalities (incorporating location and space, access, and costs). Participants reported the need for time to develop and understand the various roles, develop communication processes and build inter-professional trust. Once these were established, however, experiences were positive and included decreased workloads, increased patient safety, improved job satisfaction, improved patient relationships, and enhanced cost savings. Areas for improvement included patients’ awareness of services; pharmacists’ training; and regular, onsite access for practice staff to the pharmacy team. Conclusions Recommendations are made for the development of clear role definitions, identification of training needs, dedication of time for team building, production of educational materials for practice staff members and patients, and provision of on-site, full-time pharmacy services. Future work should focus on evaluation of various models of employing pharmacy teams in general practice; integration of pharmacists and pharmacy technicians into multidisciplinary general practice teams; relationships between local community pharmacy and general practice personnel and patients’ service and information needs. A formal national evaluation of the pilot scheme is overdue

Case report: hypoglycemia due to a novel activating glucokinase variant in an adult – a molecular approach

We present a case of an obese 22-year-old man with activating GCK variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. We investigated him for asymptomatic hypoglycemia with a family history of hypoglycemia. Genetic testing yielded a novel GCK missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant. Glucokinase enables phosphorylation of glucose, the rate-limiting step of glycolysis in the liver and pancreatic β cells. It plays a crucial role in the regulation of insulin secretion. Inactivating variants in GCK cause hyperglycemia and activating variants cause hypoglycemia. Spleen-preserving distal pancreatectomy revealed diffuse hyperplastic islets, nuclear pleomorphism and periductular islets. Glucose stimulated insulin secretion revealed increased insulin secretion in response to glucose. Cytoplasmic calcium, which triggers exocytosis of insulin-containing granules, revealed normal basal but increased glucose-stimulated level. Unbiased gene expression analysis using 10X single cell sequencing revealed upregulated INS and CKB genes and downregulated DLK1 and NPY genes in β-cells. Further studies are required to see if alteration in expression of these genes plays a role in the metabolic and histological phenotype associated with glucokinase pathogenic variant. There were more large islets in the patient’s pancreas than in control subjects but there was no difference in the proportion of β cells in the islets. His hypoglycemia was persistent after pancreatectomy, was refractory to diazoxide and improved with pasireotide. This case highlights the variable phenotype of GCK mutations. In-depth molecular analyses in the islets have revealed possible mechanisms for hyperplastic islets and insulin hypersecretion

Understanding teaching assistant self-efficacy in role and in training: its susceptibility to influence

There has been a noted growth in the number of teaching assistants (TAs) in mainstream schools (DfE, 2013a). Research is inconclusive about their efficacy at changing outcomes for children (Alborz et al 2009; Blatchford et al, 2009) and has proposed more training for TAs (Russell et al, 2005). Generic training models have suggested that enhancing self-efficacy in turn improves performance. This exploratory study investigated factors that may influence TAs’ sense of self-efficacy and its susceptibility to influence in training. Following two modes of mode of school-based training by Educational Psychologists (EPs) data were collected from 14 mainstream secondary school TAs using focus groups. A thematic analysis noted themes regarding self-efficacy, aligned with Bandura’s (1977) sources of information, outcome expectations and whole school support and norms. Review of the data is likely to be able to guide potential trainers to coach consult strategies which are self-efficacy supportive and which address contextual factors including the perceived status of TAs in schools

A simple spreadsheet-based, MIAME-supportive format for microarray data: MAGE-TAB

BACKGROUND: Sharing of microarray data within the research community has been greatly facilitated by the development of the disclosure and communication standards MIAME and MAGE-ML by the MGED Society. However, the complexity of the MAGE-ML format has made its use impractical for laboratories lacking dedicated bioinformatics support. RESULTS: We propose a simple tab-delimited, spreadsheet-based format, MAGE-TAB, which will become a part of the MAGE microarray data standard and can be used for annotating and communicating microarray data in a MIAME compliant fashion. CONCLUSION: MAGE-TAB will enable laboratories without bioinformatics experience or support to manage, exchange and submit well-annotated microarray data in a standard format using a spreadsheet. The MAGE-TAB format is self-contained, and does not require an understanding of MAGE-ML or XML

The Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2): Science Requirements, Concept, and Implementation

The Ice, Cloud, and land Elevation Satellite (ICESat) mission used laser altimetry measurements to determine changes in elevations of glaciers and ice sheets, as well as sea ice thickness distribution. These measurements have provided important information on the response of the cryosphere (Earths frozen surfaces) to changes in atmosphere and ocean condition. ICESat operated from 2003-2009 and provided repeat altimetry measurements not only to the cryosphere scientific community but also to the ocean, terrestrial and atmospheric scientific communities. The conclusive assessment of significant ongoing rapid changes in the Earths ice cover, in part supported by ICESat observations, has strengthened the need for sustained, high accuracy, repeat observations similar to what was provided by the ICESat mission. Following recommendations from the National Research Council for an ICESat follow-on mission, the ICESat-2 mission is now under development for planned launch in 2018. The primary scientific aims of the ICESat-2 mission are to continue measurements of sea ice freeboard and ice sheet elevation to determine their changes at scales from outlet glaciers to the entire ice sheet, and from 10s of meters to the entire polar oceans for sea ice freeboard. ICESat carried a single beam profiling laser altimeter that produced approximately 70 m diameter footprints on the surface of the Earth at approximately 150 m along-track intervals. In contrast, ICESat-2 will operate with three pairs of beams, each pair separated by about 3 km across-track with a pair spacing of 90 m. Each of the beams will have a nominal 17 m diameter footprint with an along-track sampling interval of 0.7 m. The differences in the ICESat-2 measurement concept are a result of overcoming some limitations associated with the approach used in the ICESat mission. The beam pair configuration of ICESat-2 allows for the determination of local cross-track slope, a significant factor in measuring elevation change for the outlet glaciers surrounding the Greenland and Antarctica coasts. The multiple beam pairs also provide improved spatial coverage. The dense spatial sampling eliminates along-track measurement gaps, and the small footprint diameter is especially useful for sea surface height measurements in the often narrow leads needed for sea ice freeboard and ice thickness retrievals. The ICESat-2 instrumentation concept uses a low energy 532 nm (green) laser in conjunction with single-photon sensitive detectors to measure range. Combining ICESat-2 data with altimetry data collected since the start of the ICESat mission in 2003, such as Operation IceBridge and ESAs CryoSat-2, will yield a 15+ year record of changes in ice sheet elevation and sea ice thickness. ICESat-2 will also provide information of mountain glacier and ice cap elevations changes, land and vegetation heights, inland water elevations, sea surface heights, and cloud layering and optical thickness

Family day care educators : an exploration of their understanding and experiences promoting children\u27s social and emotional wellbeing

This study aimed to explore family day care (FDC) educators&rsquo; knowledge of child social and emotional wellbeing and mental health problems, the strategies used to promote children&rsquo;s wellbeing, and barriers and opportunities for promoting children&rsquo;s social and emotional wellbeing. Thirteen FDC educators participated in individual semi-structured interviews. FDC educators were more comfortable defining children&rsquo;s social and emotional wellbeing than they were in identifying causes and early signs of mental health problems. Strategies used to promote children&rsquo;s mental health were largely informal and dependent on educator skills and capacities rather than a systematic scheme-wide approach. Common barriers to mental health promotion were limited financial resources, a need for more training and hesitance raising child mental health issues with parents. There is a need to build FDC educators&rsquo; knowledge of child social and emotional wellbeing and for tailored mental health promotion strategies in FDC.<br /

Enhanced Extinction of Aversive Memories by High-Frequency Stimulation of the Rat Infralimbic Cortex

Electrical stimulation of the rodent medial prefrontal cortex (mPFC), including the infralimbic cortex (IL), immediately prior to or during fear extinction training facilitates extinction memory. Here we examined the effects of high-frequency stimulation (HFS) of the rat IL either prior to conditioning or following retrieval of the conditioned memory, on extinction of Pavlovian fear and conditioned taste aversion (CTA). IL-HFS applied immediately after fear memory retrieval, but not three hours after retrieval or prior to conditioning, subsequently reduced freezing during fear extinction. Similarly, IL-HFS given immediately, but not three hours after, retrieval of a CTA memory reduced aversion during extinction. These data indicate that HFS of the IL may be an effective method for reducing both learned fear and learned aversion