Radioactive isotopes reveal a non sluggish kinetics of grain boundary diffusion in high entropy alloys

High entropy alloys (HEAs) have emerged as a new class of multicomponent materials, which have potential for high temperature applications. Phase stability and creep deformation, two key selection criteria for high temperature materials, are predominantly influenced by the diffusion of constituent elements along the grain boundaries (GBs). For the first time, GB diffusion of Ni in chemically homogeneous CoCrFeNi and CoCrFeMnNi HEAs is measured by radiotracer analysis using the $^{63}$Ni isotope. Atom probe tomography confirmed the absence of elemental segregation at GBs that allowed reliable estimation of the GB width to be about 0.5 nm. Our GB diffusion measurements prove that a mere increase in number of constituent elements does not lower the diffusion rates in HEAs, but the nature of added constituents plays a more decisive role. The GB energies in both HEAs are estimated at about 0.8-0.9 J/m$^2$, they are found to increase significantly with temperature and the effect is more pronounced for the CoCrFeMnNi alloy.Comment: 11 pages, 9 figure

Effect of glycemic status on peripheral nerve conduction in lower limbs in type 2 diabetes mellitus patients

Background: Diabetes mellitus (DM) is one of the most common chronic diseases globally. Diabetic neuropathy is the most common & troublesome complication. But exact pathogenesis is not yet known. Comparatively there are few studies showing relation between glycemic status & diabetic neuropathy. Hence present study was conducted, which was aimed to assess the same in lower limbs in type 2 DM.  Methods: 60 type 2 diabetes mellitus male patients were selected from diabetic OPD. 30 were having glycated hemoglobin (HbA1c) 6%-9% (group B), 30 were having HbA1c > 9% (group C). They were compared with age and sex matched 30 normal healthy controls (group A). Conduction velocity and amplitude of bilateral sural sensory nerve action potential (SNAP) and peroneal compound muscle action potential (CMAP) were recorded. Glycated hemoglobin was measured using ion exchange resin method. Results: Group B and group C had significantly lesser means of conduction velocity and amplitude of sural SNAP (p<0.001) and peroneal CMAP (p<0.05) as compared to group A. Hb A1c had statistically significant negative correlation with conduction velocity and amplitude of sural SNAP (p<0.001) as well as peroneal CMAP (p<0.001). Conclusions: This study shows that diabetic patients with higher blood glucose levels are at increased risk of diabetic neuropathy. Diabetic neuropathy in lower limbs worsens with increasing blood glucose levels. Hence stringent action has to be taken at an early stage to control blood glucose levels. Also, patients should be encouraged for regular follow up and strict glycemic control.

Suppression of σ-phase in nanocrystalline CoCrFeMnNiV high entropy alloy by unsolicited contamination during mechanical alloying and spark plasma sintering

CoCrFeMnNiV high entropy alloy (HEA) exhibits a high content of σ-phase (70 vol%) when produced by casting route. In the present work, a combination of mechanical alloying (MA) and spark plasma sintering (SPS) has been used to synthesize nanocrystalline CoCrFeMnNiV HEA where the formation of σ-phase has been avoided. Electron microscopy and atom probe tomography analysis indicated the formation of FCC structured HEA matrix along with (Cr,V) carbide (15 vol%) precipitation, without the presence of σ-phase in SPS processed alloy. Gibbs energy vs composition (G-x) diagrams of binary subsystems and possible carbides and oxides substantiate the absence of σ-phase during SPS of CoCrFeMnNiV alloy. Thus, the unsolicited contamination during MA-SPS route proves beneficial in suppressing the complex phase formation. © 2020 Elsevier B.V

Grain boundary self- and Mn impurity diffusion in equiatomic CoCrFeNi multi-principal element alloy

Grain boundary self-diffusion of Co, Cr and Fe and impurity diffusion of Mn are measured in a coarse-grained equiatomic CoCrFeNi multi-principal alloy. The tracer diffusivities are determined in a wide temperature range of 643 K to 1273 K, which encompasses both the C- and B-type kinetic regimes of grain boundary diffusion in polycrystalline materials after Harrison’s classification. At higher temperatures $( T > 800 K)$, only one short-circuit (grain boundary) contribution is observed, while the existence of two distinct contributions is elucidated by thorough analysis of the penetration profiles corresponding to the C-type kinetic regime (643–703 K). The latter observations are explained in terms of a grain boundary phase decomposition after prolonged annealing below 700 K. The product of the segregation factor and the grain boundary width is found to be about 0.5 nm for all constituting elements. The grain boundary diffusion data indicate that Mn does not reveal a strong (if any) segregation in the equiatomic CoCrFeNi alloy

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

AbstractAutosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.Abstract Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids

Randomized factorial trial of esomeprazole and aspirin in Barrett’s oesophagus: the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT)

Background: Oesophageal adenocarcinoma (OA) is the sixth commonest cause of cancer death worldwide and Barrett’s oesophagus (BO) is the most significant risk factor. We evaluated the efficacy of high-dose esomeprazole proton pump inhibitor acid suppression (PPI) and aspirin in improving outcome for BO patients in the largest such randomized controlled trial. Methods: Patients with ≥1cm BO in UK and Canadian hospitals were randomized 1:1:1:1 using a computer-generated schedule held in a central trials unit in a 2X2 factorial design to high-dose (40mg twice-daily) or low-dose (20mg once-daily) PPI, alone or with aspirin (UK: 300mg/day, Canada: 325mg/day), unblinded (reporting pathologists blinded). The primary composite endpoint was time to all-cause mortality, OA, or high-grade dysplasia, analysed using accelerated failure time modelling adjusted for minimization factors (age, BO length, intestinal metaplasia). Findings: Recruited patients (N=2557) were followed for 8·9 years (median; interquartile range 8·2–9·8), collecting 20,095 follow-up years and 99·9% of planned data. There were 313 primary events. High-dose PPI was superior to low-dose PPI (p=0·037, N=1265 (low dose), N=1270 (high dose), time ratio (TR)=1·27, 95%CI=1·01–1·58). Aspirin was not significantly better than no aspirin (p=0·068, N=1142 (no aspirin), N = 1138 (aspirin), TR=1·24, 95%CI=0·98–1·57). If patients using NSAIDs were censored at time of first use,aspirin was significantly better than no Aspirin (p=0·043, N=2,236, TR=1·29 95%CI=1·01– 1·66). Combining high-dose PPI with aspirin had the strongest effect compared with low dose PPI without aspirin (p=0·0068, TR=1·59, 95%CI=1·14–2·23). NNT for PPI and aspirin benefit is 34 and 43, respectively. Only 1·0% (28) of participants reported study-treatment related serious adverse events. Interpretation: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improve outcome in BO patients

Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India.

BackgroundIn the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India.MethodsWe defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model.ResultsAmong hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM.ConclusionsHyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID

Multiethnic Exome-Wide Association Study of Subclinical AtherosclerosisCLINICAL PERSPECTIVE

The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease (CHD). We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent CHD