On the gravitational instability of a dissipative medium

This paper shows that the ordinary Jeans wave number can be obtained as a limiting case of a more general approach that includes dissipative effects. Corrections to the Jeans critical mass associated to viscosity are established. Some possible implications of the results are finally discussed.Comment: 5 pages, RevTe

Perovskite-Related Oxide Fluorides: The Use of Mössbauer Spectroscopy in the Investigation of Magnetic Properties

We review here some of our recent work on the synthesis and characterisation of new perovskite-related oxide fluorides. We demonstrate the use of low temperature fluorination methods for the preparation of new phases with high fluorine contents. We also show how fluorine can be accommodated in different sites according to the structural details of the initial oxide and the fluorine content. Importantly, we describe how Mössbauer spectroscopy is a powerful technique for monitoring changes in cation oxidation state as a result of fluorination and for examining the complex magnetic interactions which result from the accommodation of fluorine within the structures and how these can be related to structural properties and changes to the superexchange pathways

14-3-3 Proteins Interact with a Hybrid Prenyl-Phosphorylation Motif to Inhibit G Proteins

Signaling through G proteins normally involves conformational switching between GTP- and GDP-bound states. Several Rho GTPases are also regulated by RhoGDI binding and sequestering in the cytosol. Rnd proteins are atypical constitutively GTP-bound Rho proteins, whose regulation remains elusive. Here, we report a high-affinity 14-3-3-binding site at the C terminus of Rnd3 consisting of both the Cys241-farnesyl moiety and a Rho-associated coiled coil containing protein kinase (ROCK)-dependent Ser240 phosphorylation site. 14-3-3 binding to Rnd3 also involves phosphorylation of Ser218 by ROCK and/or Ser210 by protein kinase C (PKC). The crystal structure of a phosphorylated, farnesylated Rnd3 peptide with 14-3-3 reveals a hydrophobic groove in 14-3-3 proteins accommodating the farnesyl moiety. Functionally, 14-3-3 inhibits Rnd3-induced cell rounding by translocating it from the plasma membrane to the cytosol. Rnd1, Rnd2, and geranylgeranylated Rap1A interact similarly with 14-3-3. In contrast to the canonical GTP/GDP switch that regulates most Ras superfamily members, our results reveal an unprecedented mechanism for G protein inhibition by 14-3-3 proteins

Towards Upright Pedalling to drive recovery in people who cannot walk in the first weeks after stroke: movement patterns and measurement

Objectives: To examine whether people who are within 31 days of stroke onset are able to produce controlled lower limb movement, and phasic activity in antagonistic lower limb muscle groups, during Upright Pedalling (UP). Design: Observational study. Setting: Acute stroke unit within a University Hospital. Participants: Eight adults between 3 and 30 days from stroke onset, with unilateral lower limb paresis and unable to walk without assistance. Participants were considered fit to participate as assessed by a physician-led medical team and were able to take part in UP for one, one minute session. Intervention: Participants took part in one session of instrumented UP at their comfortable cadence, as part of a feasibility study investigating UP early after stroke. Outcome measures: Reciprocal activation of lower limb muscles derived from muscle activity recorded with surface EMG, quantified using Jaccards Coefficient (J); smoothness of pedalling determined from standard deviations of time spent in each of eight 45 degree wheel position bins (“S-Ped”). Motor behavioural measures: Motricity Index, Trunk Control Test, Functional Ambulatory Categories. Results: Participants were all unable to walk (FAC 0) with severe to moderate lower limb paresis (Motricity Index score/100 median 48.5, IQR 32-65.5). Smooth pedalling was observed; some participants pedalling similarly smoothly to healthy older adults, with a variety of muscle activation patterns in the affected and unaffected legs. Conclusion: These observational data indicate that people with substantial paresis early after stroke and who cannot walk, can produce smooth movement during UP using a variety of muscle activation strategies

Defining predictors of responsiveness to advanced therapies in Crohn’s disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine

Introduction: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient’s quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients. Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures. IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments. Methods and analysis: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures. Ethics and dissemination: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk. Trial registration number: ISRCTN96296121

Current experiences and educational preferences of general practitioners and staff caring for people with dementia living in residential facilities

<p>Abstract</p> <p>Background</p> <p>Residential care is important for older adults, particularly for those with advanced dementia and their families. Education interventions that achieve sustainable improvement in the care of older adults are critical to quality care. There are few systematic data available regarding the educational needs of Residential Care Facility (RCF) staff and General Practitioners (GPs) relating to dementia, or the sustainability of educational interventions. We sought to determine participation in dementia education, perceived levels of current knowledge regarding dementia, perceived unmet educational needs, current barriers, facilitators and preferences for dementia education.</p> <p>Methods</p> <p>A mixed methods study design was utilised. A survey was distributed to a convenience sample of general practitioners, and staff in 223 consecutive residential care facilities in Perth, Western Australia. Responses were received from 102 RCF staff working in 10 facilities (out of 33 facilities who agreed to distribute the survey) and 202 GPs (19% of metropolitan GPs). Quantitative survey data were summarised descriptively and chi squared statistics were used to analyse the distribution of categorical variables. Qualitative data were collected from general practitioners, staff in residential care facilities and family carers of people with dementia utilizing individual interviews, surveys and focus groups. Qualitative data were analysed thematically.</p> <p>Results</p> <p>Among RCF staff and GPs attending RCF, participation in dementia education was high, and knowledge levels generally perceived as good. The individual experiences and needs of people with dementia and their families were emphasised. Participants identified the need for a person centred philosophy to underpin educational interventions. Limited time was a frequently mentioned barrier, especially in relation to attending dementia care education. Perceived educational needs relating to behaviours of concern, communication, knowledge regarding dementia, aspects of person centred care, system factors and the multidisciplinary team were consistently and frequently cited. Small group education which is flexible, individualized, practical and case based was sought.</p> <p>Conclusion</p> <p>The effectiveness and sustainability of an educational intervention based on these findings needs to be tested. In addition, future interventions should focus on supporting cultural change to facilitate sustainable improvements in care.</p

Exclusive Photoproduction of the Cascade (Xi) Hyperons

We report on the first measurement of exclusive Xi-(1321) hyperon photoproduction in gamma p --> K+ K+ Xi- for 3.2 < E(gamma) < 3.9 GeV. The final state is identified by the missing mass in p(gamma,K+ K+)X measured with the CLAS detector at Jefferson Laboratory. We have detected a significant number of the ground-state Xi-(1321)1/2+, and have estimated the total cross section for its production. We have also observed the first excited state Xi-(1530)3/2+. Photoproduction provides a copious source of Xi's. We discuss the possibilities of a search for the recently proposed Xi5-- and Xi5+ pentaquarks.Comment: submitted to Phys. Rev.

Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial

BackgroundCardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.ObjectivesThe PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.MethodsThis prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m2 doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril.ResultsMyocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (&gt;26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of &gt;10% to &lt;50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.ConclusionsAdding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574

Real-time numerical forecast of global epidemic spreading: Case study of 2009 A/H1N1pdm

Background Mathematical and computational models for infectious diseases are increasingly used to support public-health decisions; however, their reliability is currently under debate. Real-time forecasts of epidemic spread using data-driven models have been hindered by the technical challenges posed by parameter estimation and validation. Data gathered for the 2009 H1N1 influenza crisis represent an unprecedented opportunity to validate real-time model predictions and define the main success criteria for different approaches. Methods We used the Global Epidemic and Mobility Model to generate stochastic simulations of epidemic spread worldwide, yielding (among other measures) the incidence and seeding events at a daily resolution for 3,362 subpopulations in 220 countries. Using a Monte Carlo Maximum Likelihood analysis, the model provided an estimate of the seasonal transmission potential during the early phase of the H1N1 pandemic and generated ensemble forecasts for the activity peaks in the northern hemisphere in the fall/winter wave. These results were validated against the real-life surveillance data collected in 48 countries, and their robustness assessed by focusing on 1) the peak timing of the pandemic; 2) the level of spatial resolution allowed by the model; and 3) the clinical attack rate and the effectiveness of the vaccine. In addition, we studied the effect of data incompleteness on the prediction reliability. Results Real-time predictions of the peak timing are found to be in good agreement with the empirical data, showing strong robustness to data that may not be accessible in real time (such as pre-exposure immunity and adherence to vaccination campaigns), but that affect the predictions for the attack rates. The timing and spatial unfolding of the pandemic are critically sensitive to the level of mobility data integrated into the model. Conclusions Our results show that large-scale models can be used to provide valuable real-time forecasts of influenza spreading, but they require high-performance computing. The quality of the forecast depends on the level of data integration, thus stressing the need for high-quality data in population-based models, and of progressive updates of validated available empirical knowledge to inform these models