Mechanism of NSF: New evidence challenging the prevailing theory

Nephrogenic systemic fibrosis (NSF) has been associated with the administration of gadolinium-based contrast agents in patients with severely impaired renal function (SIRF), endstage renal disease (ESRD), or acute renal failure (ARF). Since the vast majority of these patients do not get NSF, it is highly likely that patient factors play a role in its development. Although free or dechelated gadolinium is thought by some to be the only trigger of NSF, recent evidence suggests that chelated gadolinium may be important. Chelated gadolinium such as Omniscan (gadodiamide) and Magnevist (gadopentetate) can directly stimulate macrophages and monocytes in vitro to release profibrotic cytokines and growth factors capable of initiating and supporting the tissue fibrosis that is characteristic of NSF. In addition, an effect of chelated gadolinium on fibroblasts has also been demonstrated. Chelated gadolinium in the form of Omniscan, Magnevist, MultiHance, and ProHance increased proliferation of human dermal fibroblasts. Indeed, increased numbers of macrophages, together with activated fibroblasts and fibrocytes, are essential cells in the fibrotic process and are present in NSF skin. Accordingly, it is important that chelated gadolinium, in combination with patient cofactors, is considered in the etiology of NSF associated with enhanced scans

Electronic structure of the neutral silicon-vacancy center in diamond

The neutrally-charged silicon vacancy in diamond is a promising system for quantum technologies that combines high-efficiency optical spin initialization with long spin lifetimes (T2 ≈ 1 ms at 4 K) and up to 90 % of optical emission into its 946 nm zero-phonon line. However, the electronic structure of SiV0 is poorly understood, making further exploitation difficult. Performing photoluminescence spectroscopy of SiV0 under uniaxial stress, we find the previous excited electronic structure of a single 3A1u state is incorrect, and identify instead a coupled 3Eu − 3A2u system, the lower state of which has forbidden optical emission at zero stress and efficiently decreases the total emission of the defect. We propose a solution employing finite strain to define a spin-photon interface scheme using SiV0

Planar selective Leidenfrost propulsion without physically structured substrates or walls

The Leidenfrost effect allows droplets to be transported on a virtually frictionless layer of vapor above a superheated substrate. The substrates are normally topographically structured using subtractive techniques to produce saw-tooth, herringbone, and other patterns and bulk heated, leading to significant challenges in energy consumption and controlled operation. Here, we propose a planar lithographic approach to levitate and propel droplets using temperature profiles, which can be spatially patterned and controlled in time. We show that micro-patterned electrodes can be heated and provide control of the pressure profile and the vapor flow. Using these almost featureless planar substrates, we achieve self-directed motion of droplets, with velocities of approximately 30 mms−1, without topographically structuring the substrate or introducing physical walls. Our approach has the potential to be integrated into applications, such as digital microfluidics, where frictionless and contactless droplet transport may be advantageous

Doubly charged silicon vacancy center, Si-N complexes, and photochromism in N and Si codoped diamond

Diamond samples containing silicon and nitrogen are shown to be heavily photochromic, with the dominant visible changes due to simultaneous change in total SiV0/− concentration. The photochromism treatment is not capable of creating or destroying SiV defects, and thus we infer the presence of the optically inactive SiV2− . We measure spectroscopic signatures we attribute to substitutional silicon in diamond, and identify a silicon-vacancy complex decorated with a nearest-neighbor nitrogen SiVN, supported by theoretical calculations

A synthesis is emerging between biodiversity–ecosystem function and ecological resilience research: reply to Mori

Letter

Improving the representativeness of UK’s national COVID-19 Infection Survey through spatio-temporal regression and post-stratification

Population-representative estimates of SARS-CoV-2 infection prevalence and antibody levels in specific geographic areas at different time points are needed to optimise policy responses. However, even population-wide surveys are potentially impacted by biases arising from differences in participation rates across key groups. Here, we used spatio-temporal regression and post-stratification models to UK’s national COVID-19 Infection Survey (CIS) to obtain representative estimates of PCR positivity (6,496,052 tests) and antibody prevalence (1,941,333 tests) for different regions, ages and ethnicities (7-December-2020 to 4-May-2022). Not accounting for vaccination status through post-stratification led to small underestimation of PCR positivity, but more substantial overestimations of antibody levels in the population (up to 21 percentage points), particularly in groups with low vaccine uptake in the general population. There was marked variation in the relative contribution of different areas and age-groups to each wave. Future analyses of infectious disease surveys should take into account major drivers of outcomes of interest that may also influence participation, with vaccination being an important factor to consider

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes