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    Vitamin D, muscle strength and function in South Asian women aged ≥ 60 years living in the North of England: a cross-sectional observational study

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    Purpose The importance of vitamin D is well established for bone health and there is some evidence that inadequate/deficient vitamin D status is associated with reduced skeletal muscle strength and physical function in older adults. Most of this evidence for the muscular effect has come from white population groups and the evidence base is sparse for other ethnic groups. This study investigates the relationship between vitamin D status, muscle strength and function in UK South Asian women aged ≥ 60 years. Methods This cross-sectional study included 120 community-dwelling Indian and Pakistani women, aged ≥ 60 years living in the North of England. Circulating blood 25(OH)D concentration was assessed by HPLC–MS using finger prick blood samples; functional capacity was assessed using handgrip strength, single and repeated chair stands, timed up and go, and balance test. Regression analysis was used to analyse the relationships between vitamin D status and muscle strength and function. Results The median (IQR) age of the women was 66 (64–73) years. Forty-seven percent of the women were vitamin D inadequate/deficient. Around forty-one percent of the women reported taking a daily vitamin D supplement, 86% of whom were vitamin D sufficient (≥ 50 nmol/L). In non-vitamin D supplement users 32% were vitamin D sufficient. Women with vitamin D sufficiency had significantly better single chair stand (p = 0.045), repeated chair stand (p = 0.01), and balance (p = 0.040) test than those with deficiency/inadequacy. No difference was observed in handgrip strength and timed up and go. Conclusion In this group of South Asian women aged ≥ 60 years, vitamin D deficiency/inadequacy was common in those not taking vitamin D supplements. Inadequate/deficient vitamin D status was associated with poor performance of lower limb muscle function, but no association was found with handgrip strength and timed up and go. The associations between supplementation, vitamin D status and lower limb strength helps support a rationale for targeted supplementation in this population of older UK South Asian women

    Enhancing wave-particle duality

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    To enhance the consistency between the quantum descriptions of waves and particles, we quantise mechanical point particles in this paper in the same physically-motivated way as we previously quantised light in quantum electrodynamics [Bennett et al., Eur. J. Phys. 37, 014001 (2016)]. To identify the relevant Hilbert space, we notice that mechanical particles can occupy any position x while moving at any velocity v. Afterwards, we promote the classical states (x,v) to pairwise orthogonal quantum states |x,v> and demand that these evolve according to Newton's equations of motion. The resulting quantum theory is mass-independent, when Newton's equations of motion are mass-independent, as one would expect. The basic formulation of quantum mechanics emerges from quantum mechanics in configuration space as a semi-classical approximation when a fixed mass is imposed and several other adjustments are made

    Epidemiology of Meal‐Related Abdominal Discomfort or Pain in Irritable Bowel Syndrome

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    Background Patients with IBS often report meal-related symptoms, which may negatively affect IBS-related quality of life, psychological health, and lead to food-avoidant behaviors. However, the understanding of the epidemiology of these symptoms is limited. Methods We compared characteristics of adult patients with Rome IV-defined IBS with and without meal-related abdominal discomfort or pain ≥ 50% of the time. Participants were recruited from the ContactME-IBS research register. We collected data concerning demographics, IBS symptoms, psychological health, quality of life, and impact on work and daily activities using validated questionnaires. We used logistic regression to explore independent predictors of meal-related discomfort or pain ≥ 50% of the time in IBS. Key Results Of 752 respondents with Rome IV IBS, 561 (74.6%) reported meal-related abdominal discomfort or pain ≥ 50% of the time. 89.3% of individuals with meal-related discomfort or pain ≥ 50% of the time were female vs. 80.6% of those without (p = 0.002). Those with meal-related discomfort or pain ≥ 50% of the time were younger (43.7 years vs. 50.1 years, p < 0.001), had a higher prevalence of symptoms meeting criteria for functional dyspepsia (FD), especially postprandial distress syndrome (49.1% vs. 30.2%, p < 0.001), and reported higher gastrointestinal symptom-specific anxiety scores, lower IBS-related quality of life scores, and higher levels of activity impairment (p < 0.001 for all analyses). After logistic regression analysis, females, those meeting criteria for FD, younger individuals, and those reporting higher gastrointestinal symptom-specific anxiety scores were more likely to report meal-related discomfort or pain ≥ 50% of the time. Conclusions Meal-related abdominal discomfort or pain ≥ 50% of the time was associated with female sex, younger age, and comorbid FD. Better characterization and recognition of patients affected by meal-related discomfort or pain may allow more personalized dietary and psychological interventions

    Gaseous ozone assisted Maillard reaction of chickpea protein isolate- arabinose: Improving structural and functional properties and enhancing emulsion stability

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    To break through the limitation of technological functionalities of chickpea protein isolate (CPI) in food processing conditions (e. g. high temperature and pH variations) and broaden CPI application, glycosylation modification was used to improve the structural and functional properties of CPI. Herein, ozone treatment was utilized to unfold CPI structure for promoting the Maillard reaction between CPI and arabinose (Ara). Then the influence of glycosylation modification on the structural and functional properties of CPI was investigated, and the stability of oil-in-water (O/W) emulsions loaded with β-carotene prepared with glycosylated products was evaluated. Compared to CPI, CPI pretreatment with ozone (CPI/O3) conjugated with Ara efficiently, with a (CPI/O3)/Ara mass ratio of 1:2, the degree of graft reached 25.3 %, suggesting the successful covalent binding of Ara to the protein. Fourier transform infrared spectroscopy (FTIR), intrinsic fluorescence spectroscopy and surface hydrophobicity analyses demonstrated that glycosylation could alter secondary and tertiary structure of CPI. Notably, the glycosylation significantly improved solubility, oil holding capacity, emulsifying properties and interfacial characteristics. Moreover, emulsions prepared with CPI/O3-Ara conjugates, especially CPI/O3-Ara 1:2 conjugate, showed a higher encapsulation efficiency for β-carotene, smaller droplet size, stronger ζ-potential and lower turbiscan stability index compared to emulsions made with CPI, displaying excellent stability under heating treatment and pH variation. Collectively, the results revealed that the ozone-assisted glycosylation is an efficient approach for the improvement of the functional and interfacial properties of CPI

    ‘Will there be money? Yes, but you’ll pay more for it’: variegated financialization in social housing

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    Research on the financialization of social housing has focused on its construction as an asset class. Less studied are the transformations occurring where financialization is relatively mature. This paper uses the English housing association (HA) sector to advance a conceptualization of financialization as variegated and subject to political and economic risks. Empirically it provides a mixed method, longitudinal framework to demonstrate that the path dependency of HA business models influences the form and extent of institutional investment. Furthermore, it explores the transformation of social housing as the preconditions for the extension of finance – low interest rates and expenditure, increased commercial revenue – are disrupted. In a more challenging environment, risk is distributed unevenly across the HA sector. HAs experiencing constraints upon their borrowing capacity face acute trade-offs between financial viability and investment in new and existing homes. The paper illustrates how the variegated financialization of housing systems continues to reproduce itself, albeit at greater cost for affected social landlords

    Characterisation of an allosteric site in PLCγ enzymes and implications for development of their specific inhibitors

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    PLCγ enzymes are key components of intracellular signal transduction processes and are involved in disease development, including immune dysregulation, specific cancer types, and neurodegeneration. Although recognised as important targets for intervention, validated pharmacological tools are lacking. Here, we demonstrate that inhibitory nucleotides bind directly to an allosteric site at the interface between the PLC-core and regulatory-array unique for PLCγ, underlying their specificity for the PLCγ family. This binding site overlaps with the PLCγ autoinhibitory interface, suggesting that the inhibitory impact of nucleotides involves stabilization of autoinhibition. We have also analysed disease-linked variants of PLCγ1 and PLCγ2 to show that multiple mechanisms could underpin their gain-of-function phenotype. While sensitivity of these variants to physiological nucleotide inhibition is reduced, we identified artificial nucleotide compounds that can inhibit such variants not only in vitro but also in cell-based assays. Therefore, our findings suggest a route for development of isozyme specific PLCγ inhibitors allowing further studies of their roles in health and disease

    Physics-informed modeling of afterburn in explosive simulations with GPU-accelerated CFD

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    Quasi-static pressure (QSP) in confined detonations is dominated by the internal-energy rise of the enclosed gases and, for oxygen-deficient charges, by post-detonation “afterburn” of detonation products and binder with atmospheric oxygen. We present a new explicit afterburn model in Viper Blast and compare this to confined detonation experiments for PE10. The newly developed explicit afterburn model in Viper Blast is outlined, and it is shown how the model tracks both the detonation and combustion products through separate species, with the afterburn combustion process both limited by stoichiometry and temperature. This method is compared to the classic Miller-type afterburn process currently available in Viper Blast – and it is shown that it removes user input for both the amount of afterburn energy and time scales for combustion. Initial results using the new Viper Blast implementation reproduce the experimental PE10 trends in air and nitrogen. We outline the variable gamma methodology used inside the explicit solver without sacrificing GPU performance

    Quantitative faecal immunochemical tests to guide colorectal cancer pathway referral in primary care. A systematic review, meta-analysis and cost-effectiveness analysis

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    Background Faecal immunochemical tests may be better than symptoms alone at identifying which patients who present to primary care with symptoms are at high risk of colorectal cancer and should have a colonoscopy. This could reduce waiting lists and patient anxiety/discomfort and enable earlier treatment of colorectal cancer. The threshold used will affect how well faecal immunochemical tests work, with a higher threshold resulting in fewer referrals but a greater chance of missing disease. Objective What is the most clinically effective and cost-effective way to use faecal immunochemical tests to reduce the number of people without significant bowel pathology who are referred to the suspected cancer pathway for colorectal cancer, taking into consideration potential colonoscopy capacity constraints for urgent and non-urgent referrals? Tests were HM-JACKarc, OC-Sensor, FOB Gold, NS-Prime, QuikRead go, IDK TurbiFIT, IDK Hb, IDK Hb/Hp complex and IDKHb+Hb/Hp ELISAs. Design Systematic review, meta-analysis and cost-effectiveness analyses were conducted. Review methods Searches across four databases and six registries were conducted (December 2022). Diagnostic accuracy studies conducted in patients presenting to or referred from primary care with symptoms suggestive of colorectal cancer using any reference standard were included. Risk of bias was assessed with quality assessment of diagnostic test accuracy studies version 2. For each test, sensitivity and specificity were pooled at all reported thresholds and summary estimates were provided at all possible thresholds within the observed range. Comparative accuracy between tests was considered. Other outcomes, for example test uptake, failure and patient acceptability, were also extracted. Cost-effectiveness analysis methods A mathematical model was developed to compare three different diagnostic strategies that used quantitative faecal immunochemical tests in primary care patients with symptoms of colorectal cancer to determine subsequent management pathways. The model assessed the health outcomes and costs associated with each strategy over a lifetime horizon from the perspective of the United Kingdom National Health Service and Personal Social Services, using evidence from published literature and other sources. Results Syntheses of sensitivity and specificity were conducted for HM-JACKarc (n = 16 studies), OC-Sensor (n = 11 studies) and FOB Gold (n = 3 studies). No synthesis was conducted for QuikRead go, NS-Prime IDK Hb or IDK Hb/Hp as there was only one study for each. No eligible studies were found for IDK Hb+Hb/Hp or for IDK TurbiFIT. Other outcomes (e.g. patient acceptability) were also synthesised. Model results suggest that faecal immunochemical tests generate a positive incremental net monetary benefit compared with current care, typically in the range of £200–350 per patient, regardless of the threshold used, for the majority of faecal immunochemical tests strategies assessed. These conclusions were robust to the sensitivity analyses undertaken. Conclusions For all faecal immunochemical test brands, there are strategies at which the incremental net monetary benefit is positive compared with current care. The exact brand and threshold(s) that generate the greatest incremental net monetary benefit could not be robustly determined due to the similarity of incremental net monetary benefit values, parameter uncertainty and the possibility of omissions from the model structure. Future work More data are needed on comparative diagnostic test accuracy and whether different thresholds should be used in some patients (e.g. anaemic, male/female, younger/older). Study registration This study is registered as PROSPERO CRD42022383580. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135637) and is published in full in Health Technology Assessment; Vol. 29, No. 46. See the NIHR Funding and Awards website for further award information

    Hybrid BAG-seq: DNA and RNA from the same single nucleus reveals interactions between genomic and transcriptomic landscapes in human tumor samples

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    We introduce hybrid BAG-seq: a high-throughput, multi-omic method that simultaneously captures DNA and RNA from single nuclei. We apply this protocol to 65,499 single nuclei from samples of five uterine cancer patients and validate the clustering using RNA-only and DNA-only protocols from the same tissues. Multiple tumor genome or expression clusters are often present within a patient, with different tumor clones projecting into distinct or shared expression states, demonstrating nearly all possible genome-transcriptome correlations. We also identify mutant stroma with significant X chromosome loss in various cell types and patient-specific stromal subtypes exhibiting aberrant expression patterns

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