Nutritional Analysis of Whole Green Crab, Carcinus maenas, for Application as a Forage Fish Replacement in Agrifeeds

Nutritional composition of a composite sample of whole green crabs, Carcinus maenas (L.), was undertaken to evaluate efficacy as a forage fish replacement for seafood-meal manufacture. Whole green crabs sampled from New Hampshire waters were ground together and analyzed for proximate profile (moisture, lipid, protein, fiber, and ash), fatty acid profile, amino acid profile, mineral composition, and mercury content. Green crab mince contained 16.55 ± 0.29% ash, 12.27 ± 0.25% protein, and 0.21 ± 0.07% lipid, and comprised all amino acids essential for chickens and most species of fish. Fatty acid composition of ground green crab was 67.98% unsaturated, and 23.29% saturated, and was richer in eicosapentaenoic acid (EPA) than docosahexaenoic acid (DHA). Levels of mercury in green crab mince were below testable limits. The nutritional profile of green crab mince was evaluated relative to the nutritional profile of menhaden from the literature, and possible agrifeed applications for whole green crab were considered. Green crab showed great potential as a forage fish replacer in seafood-meal applications for chickens and ash tolerant species of fish

Divergent effects of DNMT3A and TET2 mutations on hematopoietic progenitor cell fitness

The DNA methylation regulators DNMT3A and TET2 are recurrently mutated in hematological disorders. Despite possessing antagonistic biochemical activities, loss-of-function murine models show overlapping phenotypes in terms of increased hematopoietic stem cell (HSC) fitness. Here, we directly compared the effects of these mutations on hematopoietic progenitor function and disease initiation. In contrast to Dnmt3a-null HSCs, which possess limitless self-renewal in vivo, Tet2-null HSCs unexpectedly exhaust at the same rate as control HSCs in serial transplantation assays despite an initial increase in self-renewal. Moreover, loss of Tet2 more acutely sensitizes hematopoietic cells to the addition of a common co-operating mutation (Flt

Pilot randomized trial of therapeutic hypothermia with serial cranial ultrasound and 18-22 month follow-up for neonatal encephalopathy in a low resource hospital setting in Uganda: study protocol

Background: There is now convincing evidence that in industrialized countries therapeutic hypothermia for perinatal asphyxial encephalopathy increases survival with normal neurological function. However, the greatest burden of perinatal asphyxia falls in low and mid-resource settings where it is unclear whether therapeutic hypothermia is safe and effective.Aims: Under the UCL Uganda Women's Health Initiative, a pilot randomized controlled trial in infants with perinatal asphyxia was set up in the special care baby unit in Mulago Hospital, a large public hospital with similar to 20,000 births in Kampala, Uganda to determine:(i) The feasibility of achieving consent, neurological assessment, randomization and whole body cooling to a core temperature 33-34 degrees C using water bottles(ii) The temperature profile of encephalopathic infants with standard care(iii) The pattern, severity and evolution of brain tissue injury as seen on cranial ultrasound and relation with outcome(iv) The feasibility of neurodevelopmental follow-up at 18-22 months of ageMethods/Design: Ethical approval was obtained from Makerere University and Mulago Hospital. All infants were in-born. Parental consent for entry into the trial was obtained. Thirty-six infants were randomized either to standard care plus cooling (target rectal temperature of 33-34 degrees C for 72 hrs, started within 3 h of birth) or standard care alone. All other aspects of management were the same. Cooling was performed using water bottles filled with tepid tap water (25 degrees C). Rectal, axillary, ambient and surface water bottle temperatures were monitored continuously for the first 80 h. Encephalopathy scoring was performed on days 1-4, a structured, scorable neurological examination and head circumference were performed on days 7 and 17. Cranial ultrasound was performed on days 1, 3 and 7 and scored. Griffiths developmental quotient, head circumference, neurological examination and assessment of gross motor function were obtained at 18-22 months.Discussion: We will highlight differences in neonatal care and infrastructure that need to be taken into account when considering a large safety and efficacy RCT of therapeutic hypothermia in low and mid resource settings in the future

Financial Characteristics of Companies Audited by Large Audit Firms

Purpose “ The purpose of this paper is to examine how financial characteristics associated with the choice of a big audit firm with further investigation on the agency costs of free cash flows.Design/methodology/approach “ The sample used for this work includes industrial listed companies from Germany and France. To test our hypothesis, we used a number of logit models, extending the standard model selection audit firm, to include the variables of interest. Following previous work, our dependent dummy variable is Big4 or non-Big4.Findings “ We observed that most independent variables in the German companies show similar results to previous work, but we did not have the same results for the French industry. Moreover, our findings suggest that the total debt and dividends can be an important reason for determining the choice of a large audit firm, reducing agency costs of free cash flows.Research limitations/implications “ This study has some limitations on the measurements of the cost of the audit fees and also generates opportunities for additional searching.Originality/value “ The paper provides only one aspect to explain the relationship between the problems of agency costs of free cash flow and influence in choosing a large auditing firm, which stems from investors\u27 demand for higher quality audits

Elevation in Body Temperature to Fever Range Enhances and Prolongs Subsequent Responsiveness of Macrophages to Endotoxin Challenge

Macrophages are often considered the sentries in innate immunity, sounding early immunological alarms, a function which speeds the response to infection. Compared to the large volume of studies on regulation of macrophage function by pathogens or cytokines, relatively little attention has been devoted to the role of physical parameters such as temperature. Given that temperature is elevated during fever, a long-recognized cardinal feature of inflammation, it is possible that macrophage function is responsive to thermal signals. To explore this idea, we used LPS to model an aseptic endotoxin-induced inflammatory response in BALB/c mice and found that raising mouse body temperature by mild external heat treatment significantly enhances subsequent LPS-induced release of TNF-α into the peritoneal fluid. It also reprograms macrophages, resulting in sustained subsequent responsiveness to LPS, i.e., this treatment reduces “endotoxin tolerance” in vitro and in vivo. At the molecular level, elevating body temperature of mice results in a increase in LPS-induced downstream signaling including enhanced phosphorylation of IKK and IκB, NF-κB nuclear translocation and binding to the TNF-α promoter in macrophages upon secondary stimulation. Mild heat treatment also induces expression of HSP70 and use of HSP70 inhibitors (KNK437 or Pifithrin-µ) largely abrogates the ability of the thermal treatment to enhance TNF-α, suggesting that the induction of HSP70 is important for mediation of thermal effects on macrophage function. Collectively, these results support the idea that there has been integration between the evolution of body temperature regulation and macrophage function that could help to explain the known survival benefits of fever in organisms following infection

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol

INTRODUCTION: Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months\u27 closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes. METHODS AND ANALYSIS: This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users. ETHICS AND DISSEMINATION: The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development