Human cardiac mesenchymal stem cell like cells, a novel cell population with therapeutic potential.

Cardiac stem/progenitors are being used in the clinic to treat patients with a range of cardiac pathologies. However, improvements in heart function following treatment have been reported to be variable, with some showing no response. This discrepancy in response remains unresolved. MSCs have been highlighted as a regenerative tool as these cells display both immunomodulatory and pro-regenerative activity. The purpose of this study was to derive a cardiac MSC population to provide an alternative/support to current therapies. We derived human cardiac-mesenchymal-stem-cell-like-cells (CMSCLC) so named as they share some MSC characteristics. However, CMSCLC lack the MSC tri-lineage differentiation capacity, being capable of only rare adipogenic differentiation and demonstrating low/no osteogenic or chondrogenic potential, a phenotype that may have advantages following transplantation. Further, CMSCLC expressed low levels of p16, high levels of MHCI and low levels of MHCII. A lack of senescent cells would also be advantageous for cells to be used therapeutically, as would the ability to modulate the immune response. Crucially, CMSCLC display a transcriptional profile which includes genes associated with cardio-protective/cardio-beneficial effects. CMSCLC are also secretory and multipotent, giving rise to cardiomyocytes and endothelial cells. Our findings support CMSCLC as a novel cell population suitable for use for transplantation

Photographing the wave function of the Universe

We show that density fluctuations in standard inflationary scenarios may take the most general non-Gaussian distribution if the wave function of the Universe is not in the ground state. We adopt the Schr\"odinger picture to find a remarkable similarity between the most general inflaton wavefunction and the Edgeworth expansion used in probability theory. Hence we arrive at an explicit relation between the cumulants of the density fluctuations and the amplitudes or occupation numbers of the various energy eigenstates. For incoherent superpositions only even cumulants may be non-zero, but coherent superpositions may generate non-zero odd cumulants as well. Within this framework measurements of cumulants in Galaxy surveys directly map the wavefunction of the Universe.Comment: Replaced with revised version Latex, 10 pages., accepted for publication in Phys. Lett.

Implementation of the National Early Warning Score in UK care homes:a qualitative evaluation

BACKGROUND: The National Early Warning Score (NEWS) is a tool for identifying and responding to acute illness. When used in care homes, staff measure residents' vital signs and record them on a tablet computer, which calculates a NEWS to share with health services. This article outlines an evaluation of NEWS implementation in care homes across one clinical commissioning group area in northern England. AIM: To identify challenges to implementation of NEWS in care homes. DESIGN AND SETTING: Qualitative analysis of interviews conducted with 15 staff members from six care homes, five health professionals, and one clinical commissioning group employee. METHOD: Interviews were intended to capture people's attitudes and experiences of using the intervention. Following an inductive thematic analysis, data were considered deductively against normalisation process theory constructs to identify the challenges and successes of implementing NEWS in care homes. RESULTS: Care home staff and other stakeholders acknowledged that NEWS could enhance the response to acute illness, improve communication with the NHS, and increase the confidence of care home staff. However, the implementation did not account for the complexity of either the intervention or the care home setting. Challenges to engagement included competing priorities, insufficient training, and shortcomings in communication. CONCLUSION: This evaluation highlights the need to involve care home staff and the primary care services that support them when developing and implementing interventions in care homes. The appropriateness and value of NEWS in non-acute settings requires ongoing monitoring

Experiences of a National Early Warning Score (NEWS) intervention in care homes during the COVID-19 pandemic: a qualitative interview study

Background: The COVID-19 pandemic has taken a heavy toll on the care home sector, with residents accounting for up to half of all deaths in Europe. The response to acute illness in care homes plays a particularly important role in the care of residents during a pandemic. Digital recording of a National Early Warning Score (NEWS), which involves the measurement of physical observations, started in care homes in one area of England in 2016. Implementation of a NEWS intervention (including equipment, training and support) was accelerated early in the pandemic, despite limited evidence for its use in the care home setting. Objectives: To understand how a NEWS intervention has been used in care homes in one area of North-East England during the COVID-19 pandemic, and how it has influenced resident care, from the perspective of stakeholders involved in care delivery and commissioning. Methods: A qualitative interview study with care home (n=10) and National Health Service (n=7) staff. Data were analysed using thematic analysis. Results: Use of the NEWS intervention in care homes in this area accelerated during the COVID-19 pandemic. Stakeholders felt that NEWS, and its associated education and support package, improved the response of care homes and healthcare professionals to deterioration in residents’ health during the pandemic. Healthcare professionals valued the ability to remotely monitor resident observations, which facilitated triage and treatment decisions. Care home staff felt empowered by NEWS, providing a common clinical language to communicate concerns with external services, acting as an adjunct to staff intuition of resident deterioration. Conclusions: The NEWS intervention formed an important part of the care home response to COVID-19 in the study area. Positive staff perceptions now need to be supplemented with data on the impact on resident health and well-being, workload, and service utilisation, during the pandemic and beyond

Measurement of brain glutathione with magnetic resonance spectroscopy in Schizophrenia-Spectrum disorders — A systematic review and Meta-Analysis

Oxidative stress may contribute to declining course and poor outcomes in psychosis. However, in vivo Magnetic Resonance Spectroscopy studies yield disparate results due to clinical stage, sample demographics, neuroanatomical focus, sample size, and acquisition method variations. We investigated glutathione in brain regions from participants with psychosis, and the relation of glutathione to clinical features and spectroscopy protocols. Meta-analysis comprised 21 studies. Glutathione levels did not differ between total psychosis patients (N = 639) and controls (N = 704) in the Medial Prefrontal region (k = 21, d = -0.09, CI = -0.28 to 0.10, p = 0.37). Patients with stable schizophrenia exhibited a small but significant glutathione reduction compared to controls (k = 14, d = -0.20, CI = -0.40 to -0.00, p = 0.05). Meta-regression showed older studies had greater glutathione reductions, possibly reflecting greater accuracy related to spectroscopy advancements in more recent studies. No significant effects of methodological variables, such as voxel size or echo time were found. Reduced glutathione in patients with stable established schizophrenia may provide novel targets for precision medicine. Standardizing MRS acquisition methods in future studies may help address discrepancies in glutathione levels. [Abstract copyright: Copyright © 2023 The Author(s)

A Supersymmetric SO(10) Model with Inflation and Cosmic Strings

We have built a supersymmetric SO(10) model consistent with cosmological observations. The model gives rise to a false vacuum hybrid inflationary scenario which solves the monopole problem. We argue that this type of inflationary scenario is generic in supersymmetric SO(10) model, and arises naturally from the theory. Neither any external field nor any external symmetry has to be added. It can just be a consequence of the theory. In our specific model, at the end of inflation, cosmic strings form. The properties of the strings are presented. The cosmic background radiation anisotropies induced by the inflationary perturbations and the cosmic strings are estimated. The model produces a stable lightest superparticle and a very light left-handed neutrino which may serve as the cold and hot dark matter. The properties of a mixed cosmic string-inflationary large scale structure formation scenario are discussed.Comment: 32 pages, uses RevTex. Misprint in a referenc

CMBPol Mission Concept Study: Probing Inflation with CMB Polarization

We summarize the utility of precise cosmic microwave background (CMB) polarization measurements as probes of the physics of inflation. We focus on the prospects for using CMB measurements to differentiate various inflationary mechanisms. In particular, a detection of primordial B-mode polarization would demonstrate that inflation occurred at a very high energy scale, and that the inflaton traversed a super-Planckian distance in field space. We explain how such a detection or constraint would illuminate aspects of physics at the Planck scale. Moreover, CMB measurements can constrain the scale-dependence and non-Gaussianity of the primordial fluctuations and limit the possibility of a significant isocurvature contribution. Each such limit provides crucial information on the underlying inflationary dynamics. Finally, we quantify these considerations by presenting forecasts for the sensitivities of a future satellite experiment to the inflationary parameters.Comment: 107 pages, 14 figures, 17 tables; Inflation Working Group contribution to the CMBPol Mission Concept Study; v2: typos fixed and references adde

Development and validation of a non-remission risk prediction model in first episode psychosis:An Analysis of 2 Longitudinal Studies

Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom nonremission in first-episode psychosis. Our development cohort consisted of 1027 patients with first-episode psychosis recruited between 2005 and 2010 from 14 early intervention services across the National Health Service in England. Our validation cohort consisted of 399 patients with first-episode psychosis recruited between 2006 and 2009 from a further 11 English early intervention services. The one-year nonremission rate was 52% and 54% in the development and validation cohorts, respectively. Multivariable logistic regression was used to develop a risk prediction model for nonremission, which was externally validated. The prediction model showed good discrimination C-statistic of 0.73 (0.71, 0.75) and adequate calibration with intercept alpha of 0.12 (0.02, 0.22) and slope beta of 0.98 (0.85, 1.11). Our model improved the net-benefit by 15% at a risk threshold of 50% compared to the strategy of treating all, equivalent to 15 more detected nonremitted first-episode psychosis individuals per 100 without incorrectly classifying remitted cases. Once prospectively validated, our first episode psychosis prediction model could help identify patients at increased risk of nonremission at initial clinical contact.</p

Slip-resistant footwear reduces slips among National Health Service workers in England : a randomised controlled trial

Objectives Assess the effectiveness of 5* GRIP-rated slip-resistant footwear in preventing slips in the workplace compared to usual footwear (control group). Methods A multicentre, randomised controlled trial; 4553 National Health Service (NHS) staff were randomised 1:1 to the intervention group (provided with 5* GRIP-rated slip-resistant footwear) or the control group. The primary outcome of incidence rate of self-reported slips in the workplace over 14 weeks was analysed using a mixed-effects negative binomial model. Secondary outcome measures included incidence rate of falls from a slip, falls not from a slip, proportion of participants reporting a slip, fall or fracture and time to first slip and fall. Results 6743 slips were reported: 2633 in the intervention group (mean 1.16 per participant, range 0 to 36) and 4110 in the control group (mean 1.80 per participant, range 0 to 83). There was a statistically significant reduction in slip rate in the intervention group relative to the control group (incidence rate ratio (IRR) 0.63, 95% CI 0.57 to 0.70, p<0.001). Statistically significant differences, in favour of the intervention group, were observed in falls from a slip (IRR 0.51, 95% CI 0.28 to 0.92, p=0.03), the proportion of participants who reported a slip (OR 0.58, 95% CI 0.50 to 0.66, p<0.001) or fall (OR 0.73, 95% CI 0.54 to 0.99, p=0.04) and time to first slip (HR 0.73, 95% CI 0.67 to 0.80, p<0.001). Conclusions The offer and provision of 5* GRIP-rated footwear reduced slips in NHS staff in the workplace. Trial registration number ISRCTN33051393