Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis.

The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy

Biomass burning emission inventory with daily resolution: Application to aircraft observations of Asian outflow

Asian outflo

Burden of Rare Sarcomere Gene Variants in the Framingham and Jackson Heart Study Cohorts

Rare sarcomere protein variants cause dominant hypertrophic and dilated cardiomyopathies. To evaluate whether allelic variants in eight sarcomere genes are associated with cardiac morphology and function in the community, we sequenced 3,600 individuals from the Framingham Heart Study (FHS) and Jackson Heart Study (JHS) cohorts. Out of the total, 11.2% of individuals had one or more rare nonsynonymous sarcomere variants. The prevalence of likely pathogenic sarcomere variants was 0.6%, twice the previous estimates; however, only four of the 22 individuals had clinical manifestations of hypertrophic cardiomyopathy. Rare sarcomere variants were associated with an increased risk for adverse cardiovascular events (hazard ratio: 2.3) in the FHS cohort, suggesting that cardiovascular risk assessment in the general population can benefit from rare variant analysis

Impact of Scotland’s comprehensive, smoke-free legislation on stroke

<p>Background: Previous studies have reported a reduction in acute coronary events following smoke-free legislation. Evidence is lacking on whether stroke is also reduced. The aim was to determine whether the incidence of stroke, overalland by sub-type, fell following introduction of smoke-free legislation across Scotland on 26 March 2006.</p> <p>Methods and Findings: A negative binomial regression model was used to determine whether the introduction of smokefree legislation resulted in a step and/or slope change in stroke incidence. The model was adjusted for age-group, sex, socioeconomic deprivation quintile, urban/rural residence and month. Interaction tests were also performed. Routine hospital administrative data and death certificates were used to identify all hospital admissions and pre-hospital deaths due to stroke (ICD10 codes I61, I63 and I64) in Scotland between 2000 and 2010 inclusive. Prior to the legislation, rates of all stroke, intracerebral haemorrhage and unspecified stroke were decreasing, whilst cerebral infarction was increasing at 0.97% per annum. Following the legislation, there was a dramatic fall in cerebral infarctions that persisted for around 20 months. No visible effect was observed for other types of stroke. The model confirmed an 8.90% (95% CI 4.85, 12.77, p,0.001) stepwise reduction in cerebral infarction at the time the legislation was implemented, after adjustment for potential cofounders.</p> <p>Conclusions: Following introduction of national, comprehensive smoke-free legislation there was a selective reduction in cerebral infarction that was not apparent in other types of stroke.</p&gt

Radioactive Demonstration Of Mineralized Waste Forms Made From Hanford Low Activity Waste (Tank SX-105 And AN-103) By Fluidized Bed Steam Reformation

One of the immobilization technologies under consideration as a Supplemental Treatment for Hanford’s Low Activity Waste (LAW) is Fluidized Bed Steam Reforming (FBSR). The FBSR technology forms a mineral waste form at moderate processing temperatures thus retaining and atomically bonding the halides, sulfates, and technetium in the mineral phases (nepheline, sodalite, nosean, carnegieite). Additions of kaolin clay are used instead of glass formers and the minerals formed by the FBSR technology offers (1) atomic bonding of the radionuclides and constituents of concern (COC) comparable to glass, (2) short and long term durability comparable to glass, (3) disposal volumes comparable to glass, and (4) higher Na2O and SO{sub 4} waste loadings than glass. The higher FBSR Na{sub 2}O and SO{sub 4} waste loadings contribute to the low disposal volumes but also provide for more rapid processing of the LAW. Recent FBSR processing and testing of Hanford radioactive LAW (Tank SX-105 and AN-103) waste is reported and compared to previous radioactive and non-radioactive LAW processing and testing

Intelligence within BAOR and NATO's Northern Army Group

During the Cold War the UK's principal military role was its commitment to the North Atlantic Treaty Organisation (NATO) through the British Army of the Rhine (BAOR), together with wartime command of NATO's Northern Army Group. The possibility of a surprise attack by the numerically superior Warsaw Pact forces ensured that great importance was attached to intelligence, warning and rapid mobilisation. As yet we know very little about the intelligence dimension of BAOR and its interface with NATO allies. This article attempts to address these neglected issues, ending with the impact of the 1973 Yom Kippur War upon NATO thinking about warning and surprise in the mid-1970s. It concludes that the arrangements made by Whitehall for support to BAOR from national assets during crisis or transition to war were - at best - improbable. Accordingly, over the years, BAOR developed its own unique assets in the realm of both intelligence collection and special operations in order to prepare for the possible outbreak of conflict

A multi‐institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99090/1/cncr28117.pd

The Unknown and Awakening Europe

Program for the fourth annual RISD Cabaret held in the Cellar at the top of the Waterman Building. Design by Daniel Kraft.https://digitalcommons.risd.edu/liberalarts_cabaret_programs/1003/thumbnail.jp

The experiences of patients ill with COVID-19-like symptoms and the role of testing for SARS-CoV-2 in supporting them: a qualitative study in eight European countries during the first wave of the pandemic

Background Access to testing during the first wave of the COVID-19 pandemic was limited, impacting patients with COVID-19-like symptoms. Current qualitative studies have been limited to one country or were conducted outside Europe. Objectives To explore - in eight European countries - the experiences of patients consulting in primary care with COVID-19-like symptoms during the first wave of the pandemic. Methods Sixty-six semi-structured interviews, informed by a topic guide, were conducted by telephone or in person between April and July 2020. Patients with COVID-19-like symptoms were purposively recruited in primary care sites in eight countries and sampled based on age, gender, and symptom presentation. Deductive and inductive thematic analysis techniques were used to develop a framework representing data across settings. Data adequacy was attained by collecting rich data. Results Seven themes were identified, which described the experiences of patients consulting. Two themes are reported in this manuscript describing the role of COVID-19 testing in this experience. Patients described significant distress due to their symptoms, especially those at higher risk of complications from COVID-19, and those with severe symptoms. Patients wanted access to testing to identify the cause of their illness and minimise the burden of managing uncertainty. Some patients testing positive for COVID-19 assumed they would be immune from future infection. Conclusion Patients experiencing novel and severe symptoms, particularly those with comorbidities, experienced a significant emotional and psychological burden due to concerns about COVID-19. Testing provided reassurance over health status and helped patients identify which guidance to follow. Testing positive for SARS-CoV-2 led to some patients thinking they were immune from future infection, thus influencing subsequent behaviour

Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma

SummaryWe have profiled promoter DNA methylation alterations in 272 glioblastoma tumors in the context of The Cancer Genome Atlas (TCGA). We found that a distinct subset of samples displays concerted hypermethylation at a large number of loci, indicating the existence of a glioma-CpG island methylator phenotype (G-CIMP). We validated G-CIMP in a set of non-TCGA glioblastomas and low-grade gliomas. G-CIMP tumors belong to the proneural subgroup, are more prevalent among lower-grade gliomas, display distinct copy-number alterations, and are tightly associated with IDH1 somatic mutations. Patients with G-CIMP tumors are younger at the time of diagnosis and experience significantly improved outcome. These findings identify G-CIMP as a distinct subset of human gliomas on molecular and clinical grounds