Semantic context and visual feature effects in object naming: an fMRI study using arterial spin labeling

Previous behavioral studies reported a robust effect of increased naming latencies when objects to be named were blocked within semantic category, compared to items blocked between category. This semantic context effect has been attributed to various mechanisms including inhibition or excitation of lexico-semantic representations and incremental learning of associations between semantic features and names, and is hypothesized to increase demands on verbal self-monitoring during speech production. Objects within categories also share many visual structural features, introducing a potential confound when interpreting the level at which the context effect might occur. Consistent with previous findings, we report a significant increase in response latencies when naming categorically related objects within blocks, an effect associated with increased perfusion fMRI signal bilaterally in the hippocampus and in the left middle to posterior superior temporal cortex. No perfusion changes were observed in the middle section of the left middle temporal cortex, a region associated with retrieval of lexical–semantic information in previous object naming studies. Although a manipulation of visual feature similarity did not influence naming latencies, we observed perfusion increases in the perirhinal cortex for naming objects with similar visual features that interacted with the semantic context in which objects were named. These results provide support for the view that the semantic context effect in object naming occurs due to an incremental learning mechanism, and involves increased demands on verbal self-monitoring

Developing and testing a community-based nursing intervention to improve engagement of HIV Patients in care and treatment (Conect) (Abstract only)

The health outcomes now achievable for people living with HIV require long-term engagement with treatment and care. This is problematic for a significant minority. Disengagement from HIV services is strongly associated with poor health outcomes and reduced life expectancy. It accounts for a large proportion of avoidable hospital admissions and has considerable public health implications associated with onward transmission. Preventing disengagement is a major challenge for HIV services. Those who disengage from care commonly have complex needs and a range of psychosocial problems. This indicates the need for reengagement interventions that take an individualised approach. The aim of this project is to develop and test a community-delivered nursing intervention designed to prevent individuals disengaging from HIV treatment and care. The project involves development of a reengagement intervention and delivery of the intervention through a pilot community HIV nursing service. The intervention is structured around a strengths-based approach and theoretically based on the Behaviour Change Wheel. A process and outcome evaluation will establish effectiveness and acceptability of the intervention. A structured and theoretically informed intervention has the potential to make a significant contribution to reducing disengagement rates in this population. Establishing a pilot service to deliver this intervention and conducting a comprehensive evaluation will enable us to assess its effectiveness and identify the key determinants of success to inform transferability of this approach

Better care moves for older people: co-production of practice guidance

Moves between care settings in later life are challenging for older people but are also sometimes unavoidable. Social care practitioners have a significant role in supporting older people moving into and between social care settings, but may lack understanding of the needs of older people and their carers and the confidence, guidance or knowledge of resources. This co-designed ‘Better Care Moves’ project seeks to provide practitioners and other stakeholders with coherent evidence and a practical toolbox that will be used to inform and support older people’s moves into and between social care settings or services (e.g. home care, care homes or extra care housing). Through our networks and partnerships in Kent and East Sussex, we have established a co-production group, including four older people and/or family carers, four social care practitioners/managers working in different adult social care organisations and four social care researchers. Working together, we: 1) conducted a literature review to identify and synthesise what is already known about key unmet move-related needs of older people and the approaches used by social care practitioners in supporting moves; 2) interviewed 6 older people, 11 family carers and 10 social care practitioners who have lived experience of moves (or supporting moves) between social care settings/services or from hospital into social care settings; and 3) are co-producing move-related practice guidance for social care practitioners, grounded in real-life experience and evidence from the literature review and interviews. This guidance would include a move-related practical toolbox, accessible and creative learning briefings, key lessons from good practice examples, and case scenarios with identified needs, challenges and potential solutions/resources. We are preparing the outputs in both written and video formats. Ultimately, we aim to provide practitioners, older people, family carers and local decision makers with coherent evidence and practice guidance for supporting older people’s moves into and between different social care settings

Phosphoprotein enriched in astrocytes (PEA)-15 is a novel regulator of adipose tissue expansion

Acknowledgements P.J.V. was funded by a British Heart Foundation Ph.D. scholarship (FS/16/25/32136). This work was also sup- ported by the Medical Research Council (MR/L002620/1 to J.J.R.), the Biotechnology and Biological Sciences Research Council (BB/K017772/1 to J.J.R.), Diabetes UK (18/0005884 to J.J.R.) and the British Heart Foundation (PG/14/43/30889 to M.D.). The authors gratefully acknowledge the Microscopy and Histology core facility and the Medical Research Facility, University of Aberdeen for their support and assistance in this work.Peer reviewedPublisher PD

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia (ARREST): study protocol for a randomised controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common and serious infection, with an associated mortality of ~25%. Once in the blood, S. aureus can disseminate to infect almost any organ, but bones, joints and heart valves are most frequently affected. Despite the infection's severity, the evidence guiding optimal antibiotic therapy is weak: fewer than 1,500 patients have been included in 16 randomised controlled trials investigating S. aureus bacteraemia treatment. It is uncertain which antibiotics are most effective, their route of administration and duration, and whether antibiotic combinations are better than single agents. We hypothesise that adjunctive rifampicin, given in combination with a standard first-line antibiotic, will enhance killing of S. aureus early in the treatment course, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. Our aim is to determine whether adjunctive rifampicin reduces all-cause mortality within 14 days and bacteriological failure or death within 12 weeks from randomisation. METHODS: We will perform a parallel group, randomised (1:1), blinded, placebo-controlled trial in NHS hospitals across the UK. Adults (≥ 18 years) with S. aureus (meticillin-susceptible or resistant) grown from at least one blood culture who have received ≤ 96 h of active antibiotic therapy for the current infection and do not have contraindications to the use of rifampicin will be eligible for inclusion. Participants will be randomised to adjunctive rifampicin (600-900 mg/day; orally or intravenously) or placebo for the first 14 days of therapy in combination with standard single-agent antibiotic therapy. The co-primary outcome measures will be all-cause mortality up to 14 days from randomisation and bacteriological failure/death (all-cause) up to 12 weeks from randomisation. 940 patients will be recruited, providing >80% power to detect 45% and 30% reductions in the two co-primary endpoints of death by 14 days and bacteriological failure/death by 12 weeks respectively. DISCUSSION: This pragmatic trial addresses the long-standing hypothesis that adjunctive rifampicin improves outcome from S. aureus bacteraemia through enhanced early bacterial killing. If proven correct, it will provide a paradigm through which further improvements in outcome from S. aureus bacteraemia can be explored.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia: the ARREST RCT.

BACKGROUND: Staphylococcus aureus bacteraemia is a common and frequently fatal infection. Adjunctive rifampicin may enhance early S. aureus killing, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. OBJECTIVES: To determine whether or not adjunctive rifampicin reduces bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. Secondary objectives included evaluating the impact of rifampicin on all-cause mortality, clinically defined failure/recurrence or death, toxicity, resistance emergence, and duration of bacteraemia; and assessing the cost-effectiveness of rifampicin. DESIGN: Parallel-group, randomised (1 : 1), blinded, placebo-controlled multicentre trial. SETTING: UK NHS trust hospitals. PARTICIPANTS: Adult inpatients (≥ 18 years) with meticillin-resistant or susceptible S. aureus grown from one or more blood cultures, who had received < 96 hours of antibiotic therapy for the current infection, and without contraindications to rifampicin. INTERVENTIONS: Adjunctive rifampicin (600-900 mg/day, oral or intravenous) or placebo for 14 days in addition to standard antibiotic therapy. Investigators and patients were blinded to trial treatment. Follow-up was for 12 weeks (assessments at 3, 7, 10 and 14 days, weekly until discharge and final assessment at 12 weeks post randomisation). MAIN OUTCOME MEASURES: The primary outcome was all-cause bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. RESULTS: Between December 2012 and October 2016, 758 eligible participants from 29 UK hospitals were randomised: 370 to rifampicin and 388 to placebo. The median age was 65 years [interquartile range (IQR) 50-76 years]. A total of 485 (64.0%) infections were community acquired and 132 (17.4%) were nosocomial; 47 (6.2%) were caused by meticillin-resistant S. aureus. A total of 301 (39.7%) participants had an initial deep infection focus. Standard antibiotics were given for a median of 29 days (IQR 18-45 days) and 619 (81.7%) participants received flucloxacillin. By 12 weeks, 62 out of 370 (16.8%) patients taking rifampicin versus 71 out of 388 (18.3%) participants taking the placebo experienced bacteriological (microbiologically confirmed) failure/recurrence or died [absolute risk difference -1.4%, 95% confidence interval (CI) -7.0% to 4.3%; hazard ratio 0.96, 95% CI 0.68 to 1.35; p = 0.81]. There were 4 (1.1%) and 5 (1.3%) bacteriological failures (p = 0.82) in the rifampicin and placebo groups, respectively. There were 3 (0.8%) versus 16 (4.1%) bacteriological recurrences (p = 0.01), and 55 (14.9%) versus 50 (12.9%) deaths without bacteriological failure/recurrence (p = 0.30) in the rifampicin and placebo groups, respectively. Over 12 weeks, there was no evidence of differences in clinically defined failure/recurrence/death (p = 0.84), all-cause mortality (p = 0.60), serious (p = 0.17) or grade 3/4 (p = 0.36) adverse events (AEs). However, 63 (17.0%) participants in the rifampicin group versus 39 (10.1%) participants in the placebo group experienced antibiotic or trial drug-modifying AEs (p = 0.004), and 24 (6.5%) participants in the rifampicin group versus 6 (1.5%) participants in the placebo group experienced drug-interactions (p = 0.0005). Evaluation of the costs and health-related quality-of-life impacts revealed that an episode of S. aureus bacteraemia costs an average of £12,197 over 12 weeks. Rifampicin was estimated to save 10% of episode costs (p = 0.14). After adjustment, the effect of rifampicin on total quality-adjusted life-years (QALYs) was positive (0.004 QALYs), but not statistically significant (standard error 0.004 QALYs). CONCLUSIONS: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S. aureus bacteraemia. FUTURE WORK: Given the substantial mortality, other antibiotic combinations or improved source management should be investigated. TRIAL REGISTRATIONS: Current Controlled Trials ISRCTN37666216, EudraCT 2012-000344-10 and Clinical Trials Authorisation 00316/0243/001. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 59. See the NIHR Journals Library website for further project information.NIHR HTA Programm

Voltage- and temperature-dependent activation of TRPV3 channels is potentiated by receptor-mediated PI(4,5)P2 hydrolysis

TRPV3 is a thermosensitive channel that is robustly expressed in skin keratinocytes and activated by innocuous thermal heating, membrane depolarization, and chemical agonists such as 2-aminoethyoxy diphenylborinate, carvacrol, and camphor. TRPV3 modulates sensory thermotransduction, hair growth, and susceptibility to dermatitis in rodents, but the molecular mechanisms responsible for controlling TRPV3 channel activity in keratinocytes remain elusive. We show here that receptor-mediated breakdown of the membrane lipid phosphatidylinositol (4,5) bisphosphate (PI(4,5)P2) regulates the activity of both native TRPV3 channels in primary human skin keratinocytes and expressed TRPV3 in a HEK-293–derived cell line stably expressing muscarinic M1-type acetylcholine receptors. Stimulation of PI(4,5)P2 hydrolysis or pharmacological inhibition of PI 4 kinase to block PI(4,5)P2 synthesis potentiates TRPV3 currents by causing a negative shift in the voltage dependence of channel opening, increasing the proportion of voltage-independent current and causing thermal activation to occur at cooler temperatures. The activity of single TRPV3 channels in excised patches is potentiated by PI(4,5)P2 depletion and selectively decreased by PI(4,5)P2 compared with related phosphatidylinositol phosphates. Neutralizing mutations of basic residues in the TRP domain abrogate the effect of PI(4,5)P2 on channel function, suggesting that PI(4,5)P2 directly interacts with a specific protein motif to reduce TRPV3 channel open probability. PI(4,5)P2-dependent modulation of TRPV3 activity represents an attractive mechanism for acute regulation of keratinocyte signaling cascades that control cell proliferation and the release of autocrine and paracrine factors

Optimizing Sparse RFI Prediction using Deep Learning

Radio Frequency Interference (RFI) is an ever-present limiting factor among radio telescopes even in the most remote observing locations. When looking to retain the maximum amount of sensitivity and reduce contamination for Epoch of Reionization studies, the identification and removal of RFI is especially important. In addition to improved RFI identification, we must also take into account computational efficiency of the RFI-Identification algorithm as radio interferometer arrays such as the Hydrogen Epoch of Reionization Array grow larger in number of receivers. To address this, we present a Deep Fully Convolutional Neural Network (DFCN) that is comprehensive in its use of interferometric data, where both amplitude and phase information are used jointly for identifying RFI. We train the network using simulated HERA visibilities containing mock RFI, yielding a known "ground truth" dataset for evaluating the accuracy of various RFI algorithms. Evaluation of the DFCN model is performed on observations from the 67 dish build-out, HERA-67, and achieves a data throughput of 1.6$\times 10^{5}$ HERA time-ordered 1024 channeled visibilities per hour per GPU. We determine that relative to an amplitude only network including visibility phase adds important adjacent time-frequency context which increases discrimination between RFI and Non-RFI. The inclusion of phase when predicting achieves a Recall of 0.81, Precision of 0.58, and $F_{2}$ score of 0.75 as applied to our HERA-67 observations.Comment: 11 pages, 7 figure