Uranium nitride-silicide advanced nuclear fuel: Higher efficiency and greater safety

The development of new nuclear fuel compositions is being driven by an interest in improving efficiency/lowering cost and increasing safety margins. Nuclear fuel efficiency is in large measure a function of the atomic density of the uranium, that is, the more fissionable uranium available per unit volume the less fuel volume that is required. Proliferation concerns limit the concentration of fissile 235U, and thus attention is directed to higher overall uranium content fuel. Among the options are the high temperature phases U3Si2 and composite UN- U3Si2 where the design would have the more water-stable U3Si2 surround the more soluble, but higher uranium density UN grains. (Uranium metal of course has the highest atomic density, however its low melting point, high degree of swelling under irradiation, and chemical reactivity eliminate it from consideration.) Another advantage of the nitride and silicide phases are their high thermal conductivity, greatly exceeding the current standard UO2 fuel, with the high conductivity potentially allowing the fuel to operate at a higher power density. Please click Additional Files below to see the full abstract

Simultaneous prenatal ethanol and nicotine exposure affect ethanol consumption, ethanol preference and oxytocin receptor binding in adolescent and adult rats

Ethanol consumption and smoking during pregnancy are common, despite the known adverse effects on the fetus. The teratogenicity of each drug independently is well established; however, the effects of concurrent exposure to ethanol and nicotine in preclinical models remain unclear. This study examined the impact of simultaneous prenatal exposure to both ethanol and nicotine on offspring ethanol preference behaviors and oxytocin system dynamics. Rat dams were given liquid diet (17% ethanol derived calories(EDC)) on gestational day (GD) 5 and 35% EDC fromGD 6-20 and concurrently an osmotic minipump delivered nicotine (3-6 mg/kg/day) from GD 4 - postpartum day 10. Offspring were tested for ethanol preference during adolescence (postnatal day (PND) 30-43) and again at adulthood (PND 60-73), followed by assays for oxytocin mRNA expression and receptor binding in relevant brain regions. Prenatal exposure decreased ethanol preference in males during adolescence, and decreased consumption and preference in females during adulthood compared to controls. Oxytocin receptor binding in the nucleus accumbens and hippocampus was increased in adult prenatally exposed males only. Prenatal exposure to these drugs sex-specifically decreased ethanol preference behavior in offspring unlike reports for either drug separately. The possible role of oxytocin in reduction of ethanol consumption behavior is highlighted

Studying Trail Enhancement Plans - Health Impact Assessment

This report reflects work on the Studying Trail Enhancement Plans - Health Impact Assessment (STEP-HIA) for the proposed new Cuba Continental Divide National Scenic Trail segment as of April 30, 2015. It is provided to the Santa Fe National Forest and Bureau of Land Management New Mexico for use in preparing an Environmental Impact Assessment and subsequent planning for the proposed project. It was prepared by the University of New Mexico Prevention Research Center and Step Into Cuba Alliance, a partnership of individuals and organizations dedicated to the promotion of walking and hiking for better health in Cuba, NM. In this report, we present information by way of a sequential series of questions that support and lead to predictions and recommendations for the new trail segment

Health Related Quality of Life in Adult Low and High-Grade Glioma Patients Using the National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS) and Neuro-QOL Assessments

Health related quality of life (HRQOL) measures have become increasingly important in the management of glioma patients in both research and clinical practice settings. Functional impairment is common in low-grade and high-grade glioma patients as the disease has both oncological and neurological manifestations. Natural disease history as well as medical or surgical treatment can negatively influence HRQOL. There are no universal standards for HRQOL assessment in glioma patients. In this study, we examine patient perspectives on functional outcome domains and report the prevalence of impairments rates using the National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS) and Neuro-QOL item banks as measures of HRQOL. Retrospective analysis of a prospectively collected dataset involving 79 glioma patients reveals that quality of life concerns are the most important consideration behind making decisions about treatment in 80.7% of patients. The prevalence of functional impairment by PROMIS and NEURO-QOL assessment is high, ranging from 28.6% in the physical function domain to 43.9% in the cognitive function domain. Pain and anxiety related to physical decline is higher in LGG patients compared to HGG patients. Aphasia severity also impacts HRQOL. The results of this study suggest that the PROMIS and NEURO-QOL assessments may be important HRQOL metrics for future use in larger clinical research and clinical trial settings

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant