322 research outputs found

    Structure of pair winds from compact objects with application to emission from bare strange stars

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    We present the results of numerical simulations of stationary, spherically outflowing, electron-positron pair winds, with total luminosities in the range 10^{34}- 10^{42} ergs/s. In the concrete example described here, the wind injection source is a hot, bare, strange star, predicted to be a powerful source of electron-positron pairs created by the Coulomb barrier at the quark surface. We find that photons dominate in the emerging emission, and the emerging photon spectrum is rather hard and differs substantially from the thermal spectrum expected from a neutron star with the same luminosity. This might help distinguish the putative bare strange stars from neutron stars.Comment: 4 pages, 6 figures, 1 table, added references, to appear in the proceedings of the conference "Isolated Neutron Stars: from the Surface to the Interior", London, UK, 24-28 April 200

    The cyclical cascade of HIV care: Temporal care engagement trends within a population-wide cohort

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    Background: The traditional HIV treatment cascade aims to visualise the journey of each person living with HIV from diagnosis, through initiation on antiretroviral therapy (ART) to treatment success, represented by virological suppression. This representation has been a pivotal tool in highlighting and quantifying sequential gaps along the care continuum. There is longstanding recognition, however, that this may oversimplify the complexity of real-world engagement with HIV services in settings with mature high-burden HIV epidemics. A complementary “cyclical” cascade has been proposed to represent the processes of disengagement at different points on the care continuum, with multiple pathways to re-engagement, although the feasibility of implementing this at scale has been uncertain. This study aimed to populate, refine, and explore the utility of a cyclical representation of the HIV cascade, using routine data from a high-burden HIV setting. Methods and findings: This observational cohort study leveraged person-level data on all people living with HIV in the Western Cape (WC), South Africa, who accessed public health services in the 2 years prior to 31 December 2023. Programme data from disease registers were complemented by data from pharmacy and laboratory systems. At study closure, 494 370 people were included, constituting 93% of those of those estimated to be living with HIV in the province, of whom 355 104 were on ART. Substantial disengagement from HIV care was evident at every point on the cascade. Early treatment emerged as a period of higher risk of disengagement, but it did not account for the majority of disengagement. Almost all those currently disengaged had prior experience of treatment. While re-engagement was also common, overall treatment coverage had increased slowly over 5 years. The transition to dolutegravir-based regimens was dramatic with good virological outcomes for those in care, notwithstanding a clearly discernible impact of the Coronavirus Disease 2019 (COVID-19) pandemic on viral load (VL) testing. People currently engaged and disengaged in care are similar with respect to age and gender. Those who died or disengaged recently were previously distributed across a range of cascade statuses, and a substantial proportion of those newly initiating and re-initiating treatment were no longer on treatment 6 months later. The main limitation of this study was incomplete evidence of HIV testing, linkage to HIV-specific services, and out-of-facility mortality. Conclusions: Using routine data, it was possible to populate and automate a cyclical cascade of HIV care that continuously captured the nonlinear care journeys of individuals living with HIV. In this generalised mature HIV epidemic, most people are treatment experienced. Disengagement is common and occurs at various points along the cascade, making it challenging to identify high-impact intervention opportunities. While historical HIV cascades remain valuable for target setting and service monitoring, they can be complemented with insights from more detailed cyclical cascades

    Durability of interior renderings in schools: optimization of envelope insulation for mitigation of mould growth risk

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    A high standard education is, nowadays, a clear objective for anymodern society. In Portugal, the retrofit of educational buildings has an enormousrelevance as demonstrated by the Program for Retrofit and Upgrade of HighSchools. Educational buildings specific characteristics such as high occupancyrates and high amount of time children spend in classrooms make them a specialcase compared to other buildings. Mould growth on envelope surfaces is frequentlyobserved in these buildings, reducing the expected durability of renderingsand coatings. The present work consisted of two main lines of research: one ofsimulation and other of optimization. The simulation part included modelling ofInterior Surfaces Temperature, Indoor Air Temperature and Relative Humidityvariation, before and after a hypothetical retrofit process. Optimization techniqueswere applied in the definition of insulation thickness to be numerically tested in theafter retrofit scenario. The objective was to minimise insulation thickness ineach building element of the envelope. The constraints were derived from thecontrol of surface temperature values that would result in mould growth risk

    Sex- and Ethnic-Specific Patterns in the Incidence of Hip Fracture Among Older US Asian and Non-Hispanic White Adults

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    BACKGROUND: Asian and Pacific Islander (Asian/PI) adults have lower hip fracture incidence than non-Hispanic White (NHW) adults, but data regarding Asian/PI subgroups are limited. We compared hip fracture incidence among older US Asian/PI and NHW populations, including ethnic subgroup differences. METHODS: Using observational data from a California healthcare system, we identified Asian/PI and NHW adults aged ≥50 years (2000-2019) and followed subjects to 2021 for hip fracture determined by principal/primary hospital diagnosis or by secondary hospital diagnosis with hip/femur procedure codes. Age-adjusted hip fracture incidence was calculated with 95% confidence intervals (CIs). Log-Poisson regression was used to determine fracture incidence rate ratios (IRRs, [CI]; NHW or Chinese as reference) adjusting for age and year. RESULTS: Among 215,359 Asian/PI and 776,839 NHW women, hip fracture incidence was 1.34 (1.28-1.40) and 2.97 (2.94-3.01) per 1000 person-years, respectively, with IRR 0.45 (0.43-0.47). Among 188,328 Asian/PI and 697,046 NHW men, hip fracture incidence was 0.62 (0.58-0.67) and 1.81 (1.78-1.84) per 1000 person-years, respectively, with IRR 0.34 (0.32-0.37). For the four largest Asian/PI subgroups, Filipina women (IRR 0.85 [0.75-0.96]) had lower, and Japanese (IRR 1.36 [1.20-1.54]) and South Asian (IRR 1.36 [1.07-1.72]) women had higher hip fracture incidence compared to Chinese women. Hip fracture incidence was only higher among South Asian (IRR 1.61 [1.21-2.14]) compared to Chinese men. CONCLUSION: Hip fracture incidence among US Asian/PI adults was 55% (women) and 66% (men) lower than NHW adults, but incidence varied by Asian/PI subgroup. The heterogeneity among Asian/PI adults highlights the importance of examining fracture risk by ethnic subgroup

    Early and accurate detection of cholangiocarcinoma in patients with primary sclerosing cholangitis by methylation markers in bile

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    Background and Aims Primary sclerosing cholangitis (PSC) is associated with increased risk of cholangiocarcinoma (CCA). Early and accurate CCA detection represents an unmet clinical need as the majority of patients with PSC are diagnosed at an advanced stage of malignancy. In the present study, we aimed at establishing robust DNA methylation biomarkers in bile for early and accurate diagnosis of CCA in PSC. Approach and Results Droplet digital PCR (ddPCR) was used to analyze 344 bile samples from 273 patients with sporadic and PSC-associated CCA, PSC, and other nonmalignant liver diseases for promoter methylation of cysteine dioxygenase type 1, cannabinoid receptor interacting protein 1, septin 9, and vimentin. Receiver operating characteristic (ROC) curve analyses revealed high AUCs for all four markers (0.77-0.87) for CCA detection among patients with PSC. Including only samples from patients with PSC diagnosed with CCA 36 months) as controls, and remained high (83%) when only including patients with PSC and dysplasia as controls (n = 23). Importantly, the bile samples from the CCA-PSCPeer reviewe

    Deglutarylation of glutaryl-CoA dehydrogenase by deacylating enzyme SIRT5 promotes lysine oxidation in mice

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    A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be nonenzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH) and show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal that glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We also demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a feedback loop model within the lysine/tryptophan oxidation pathway in which glutaryl-CoA is produced, in turn inhibiting GCDH function via glutaryl modification of GCDH lysine residues and can be relieved by SIRT5 deacylation activity

    Scaling Up ART Adherence Clubs in the Public Sector Health System in the Western Cape, South Africa: a Study of the Institutionalisation of a Pilot Innovation

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    In 2011, a decision was made to scale up a pilot innovation involving ‘adherence clubs’ as a form of differentiated care for HIV positive people in the public sector antiretroviral therapy programme in the Western Cape Province of South Africa. In 2016 we were involved in the qualitative aspect of an evaluation of the adherence club model, the overall objective of which was to assess the health outcomes for patients accessing clubs through epidemiological analysis, and to conduct a health systems analysis to evaluate how the model of care performed at scale. In this paper we adopt a complex adaptive systems lens to analyse planned organisational change through intervention in a state health system. We explore the challenges associated with taking to scale a pilot that began as a relatively simple innovation by a non-governmental organisation
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