Use of cystatin C to inform metformin eligibility among adult veterans with diabetes.

AimsRecommendations for metformin use are dependent on eGFR category: eGFR >45 ml/min/1.73 m2 - "first-line agent"; eGFR 30-44 - "use with caution"; eGFR<30 - "do not use". Misclassification of metformin eligibility by creatinine-based MDRD GFR estimates (eGFRcr) may contribute to its misuse. We investigated the impact of cystatin c estimates of GFR (eGFRcys) on metformin eligibility.MethodsIn a consecutive cohort of 550 Veterans with diabetes, metformin use and eligibility were assessed by eGFR category, using eGFRcr and eGFRcys. Discrepancy in eligibility was defined as cases where eGFRcr and eGFRcys categories (<30, 30-44, 45-60, and >60 ml/min/1.73 m2) differed with an absolute difference in eGFR of >5 ml/min/1.73 m2. We modeled predictors of metformin use and eGFR category discrepancy with multivariable relative risk regression and multinomial logistic regression.ResultsSubjects were 95% male, median age 68, and racially diverse (45% White, 22% Black, 11% Asian, 22% unknown). Metformin use decreased with severity of eGFRcr category, from 63% in eGFRcr >60 to 3% in eGFRcr <30. eGFRcys reclassified 20% of Veterans into different eGFR categories. Factors associated with a more severe eGFRcys category compared to eGFRcr were older age (aOR = 2.21 per decade, 1.44-1.82), higher BMI (aOR = 1.04 per kg/m2, 1.01-1.08) and albuminuria >30 mg/g (aOR = 1.81, 1.20-2.73).ConclusionsMetformin use is low among Veterans with CKD. eGFRcys may serve as a confirmatory estimate of kidney function to allow safe use of metformin among patients with CKD, particularly among older individuals and those with albuminuria

Automatic detection of arcs and arclets formed by gravitational lensing

We present an algorithm developed particularly to detect gravitationally lensed arcs in clusters of galaxies. This algorithm is suited for automated surveys as well as individual arc detections. New methods are used for image smoothing and source detection. The smoothing is performed by so-called anisotropic diffusion, which maintains the shape of the arcs and does not disperse them. The algorithm is much more efficient in detecting arcs than other source finding algorithms and the detection by eye.Comment: A&A in press, 12 pages, 16 figure

Fast parallel algorithms for a broad class of nonlinear variational diffusion approaches

Variational segmentation and nonlinear diffusion approaches have been very active research areas in the fields of image processing and computer vision during the last years. In the present paper, we review recent advances in the development of efficient numerical algorithms for these approaches. The performance of parallel implement at ions of these algorithms on general-purpose hardware is assessed. A mathematically clear connection between variational models and nonlinear diffusion filters is presented that allows to interpret one approach as an approximation of the other, and vice versa. Numerical results confirm that, depending on the parametrization, this approximation can be made quite accurate. Our results provide a perspective for uniform implement at ions of both nonlinear variational models and diffusion filters on parallel architectures

Discretization of variational regularization in Banach spaces

Consider a nonlinear ill-posed operator equation $F(u)=y$ where $F$ is defined on a Banach space $X$. In general, for solving this equation numerically, a finite dimensional approximation of $X$ and an approximation of $F$ are required. Moreover, in general the given data \yd of $y$ are noisy. In this paper we analyze finite dimensional variational regularization, which takes into account operator approximations and noisy data: We show (semi-)convergence of the regularized solution of the finite dimensional problems and establish convergence rates in terms of Bregman distances under appropriate sourcewise representation of a solution of the equation. The more involved case of regularization in nonseparable Banach spaces is discussed in detail. In particular we consider the space of finite total variation functions, the space of functions of finite bounded deformation, and the $L^\infty$--space

Study protocol: the ILANA study - exploring optimal implementation strategies for long-acting antiretroviral therapy to ensure equity in clinical care and policy for women, racially minoritised people and older people living with HIV in the UK - a qualitative multiphase longitudinal study design.

INTRODUCTION: Cabotegravir and rilpivirine (CAB+RPV long-acting (LA)) is recommended as a treatment for HIV-1 allowing people living with HIV to receive 2 monthly injectable treatment, rather than daily pills. Providing injectable therapy in a system designed to provide and manage study participants on oral treatments poses logistical challenges namely how resources are used to accommodate patient preference within constrained health economies with capacity limitations. In this pragmatic multicentre study, we aim to understand the implementation of CAB-RPV-LA administration in two settings via mixed methods to explore perspectives of participants and the clinical team delivering CAB+RPV LA. METHODS AND ANALYSIS: Women, racially minoritised people and older people are chronically under-represented in HIV clinical trials so the ILANA trial has set recruitment caps to ensure recruitment of 50% women, 50% ethnically diverse people and 30% over 50 years of age to include a more representative study population. Using a mixed-methods approach, the primary objective is to identify and evaluate the critical implementation strategies for CAB+RPV LA in both hospital and community settings. Secondary objectives include evaluating feasibility and acceptability of CAB+RPV LA administration at UK clinics and community settings from the perspective of HIV care providers, nurses and representatives at community sites, evaluating barriers to implementation, the utility of implementation strategies and adherence. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Health Research Authority Research Ethics Committee (REC reference: 22/PR/0318). The dissemination strategy has been formulated with the SHARE Collaborative Community Advisory Board to maximise the impact of this work on clinical care and policy. This strategy draws on and leverages existing resources within the participating organisations, such as their academic infrastructure, professional relationships and community networks. The strategy will leverage the Public Engagement Team and press office to support dissemination of findings. TRIAL REGISTRATION NUMBER: NCT05294159

Calcium sensor kinase activates potassium uptake systems in gland cells of Venus flytraps

The Darwin plant Dionaea muscipula is able to grow on mineral-poor soil, because it gains essential nutrients from captured animal prey. Given that no nutrients remain in the trap when it opens after the consumption of an animal meal, we here asked the question of how Dionaea sequesters prey-derived potassium. We show that prey capture triggers expression of a K+ uptake system in the Venus flytrap. In search of K+ transporters endowed with adequate properties for this role, we screened a Dionaea expressed sequence tag (EST) database and identified DmKT1 and DmHAK5 as candidates. On insect and touch hormone stimulation, the number of transcripts of these transporters increased in flytraps. After cRNA injection of K+-transporter genes into Xenopus oocytes, however, both putative K+ transporters remained silent. Assuming that calcium sensor kinases are regulating Arabidopsis K+ transporter 1 (AKT1), we coexpressed the putative K+ transporters with a large set of kinases and identified the CBL9-CIPK23 pair as the major activating complex for both transporters in Dionaea K+ uptake. DmKT1 was found to be a K+-selective channel of voltage-dependent high capacity and low affinity, whereas DmHAK5 was identified as the first, to our knowledge, proton-driven, high-affinity potassium transporter with weak selectivity. When the Venus flytrap is processing its prey, the gland cell membrane potential is maintained around -120 mV, and the apoplast is acidified to pH 3. These conditions in the green stomach formed by the closed flytrap allow DmKT1 and DmHAK5 to acquire prey-derived K+, reducing its concentration from millimolar levels down to trace levels

Necessary conditions for variational regularization schemes

We study variational regularization methods in a general framework, more precisely those methods that use a discrepancy and a regularization functional. While several sets of sufficient conditions are known to obtain a regularization method, we start with an investigation of the converse question: How could necessary conditions for a variational method to provide a regularization method look like? To this end, we formalize the notion of a variational scheme and start with comparison of three different instances of variational methods. Then we focus on the data space model and investigate the role and interplay of the topological structure, the convergence notion and the discrepancy functional. Especially, we deduce necessary conditions for the discrepancy functional to fulfill usual continuity assumptions. The results are applied to discrepancy functionals given by Bregman distances and especially to the Kullback-Leibler divergence.Comment: To appear in Inverse Problem

Water Futures and Solution - Fast Track Initiative (Final Report)

The Water Futures and Solutions Initiative (WFaS) is a cross-sector, collaborative global water project. Its objective is to apply systems analysis, develop scientific evidence and identify water-related policies and management practices, working together consistently across scales and sectors to improve human well-being through water security. The approach is a stakeholder-informed, scenario-based assessment of water resources and water demand that employs ensembles of state-of-the-art socio-economic and hydrological models, examines possible futures and tests the feasibility, sustainability and robustness of options that can be implemented today and can be sustainable and robust across a range of possible futures and associated uncertainties. This report aims at assessing the global current and future water situation

Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH