The Bells of St. Mary\u27s

https://digitalcommons.library.umaine.edu/mmb-vp/1094/thumbnail.jp

The Bells of St. Mary\u27s

https://digitalcommons.library.umaine.edu/mmb-vp/1093/thumbnail.jp

Levosimendan for the prevention of acute organ dysfunction in sepsis

BACKGROUND Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. METHODS We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events. RESULTS The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04). CONCLUSIONS The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials number, ISRCTN12776039.

(Cock-a-Doodle I\u27m Off My Noodle) My Baby\u27s Back

With Ukulele arrangement. Contains advertisements and/or short musical examples of pieces being sold by publisher.https://digitalcommons.library.umaine.edu/mmb-vp/7102/thumbnail.jp

Epistasis not needed to explain low dN/dS

An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a phenomenon known as epistasis. In a recent letter to Nature, Breen et al. (2012) argued that epistasis must be "pervasive throughout protein evolution" because the observed ratio between the per-site rates of non-synonymous and synonymous substitutions (dN/dS) is much lower than would be expected in the absence of epistasis. However, when calculating the expected dN/dS ratio in the absence of epistasis, Breen et al. assumed that all amino acids observed in a protein alignment at any particular position have equal fitness. Here, we relax this unrealistic assumption and show that any dN/dS value can in principle be achieved at a site, without epistasis. Furthermore, for all nuclear and chloroplast genes in the Breen et al. dataset, we show that the observed dN/dS values and the observed patterns of amino acid diversity at each site are jointly consistent with a non-epistatic model of protein evolution.Comment: This manuscript is in response to "Epistasis as the primary factor in molecular evolution" by Breen et al. Nature 490, 535-538 (2012

The North Atlantic Fish Revolution (ca. AD 1500)

UID/HIS/04666/2013We propose the concept of the “Fish Revolution” to demarcate the dramatic increase in North Atlantic fisheries after AD 1500, which led to a 15-fold increase of cod (Gadus morhua) catch volumes and likely a tripling of fish protein to the European market.We consider three key questions: (1) What were the environmental parameters of the Fish Revolution? (2) What were the globalising effects of the Fish Revolution? (3) What were the consequences of the Fish Revolution for fishing communities? While these questions would have been considered unknowable a decade or two ago, methodological developments in marine environmental history and historical ecology have moved information about both supply and demand into the realm of the discernible. Although much research remains to be done, we conclude that this was a major event in the history of resource extraction from the sea, mediated by forces of climate change and globalisation, and is likely to provide a fruitful agenda for future multidisciplinary research.publishersversionpublishe

Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa

OBJECTIVE: The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. METHOD: Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes. RESULTS: Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h2SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. CONCLUSIONS: Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology

UK-Wide Surveillance of Neurological and Neuropsychiatric Complications of COVID-19: The First 153 Patients

Background: Increasingly neurological complications of COVID-19 are identified, mostly in small series. Larger studies have been limited by both geography and specialty. Consequently, the breadth of complications is not represented. Comprehensive characterization of clinical syndromes is critical to rationally select and evaluate potential therapies. / Methods: During the exponential pandemic phase, we developed coordinated online portals for rapid notification across the spectrum of major UK neuroscience bodies, representing neurology, stroke, psychiatry, and intensive care. Evidence of infection and clinical case definitions were applied prospectively. Cases were compared to overall Government Public Health COVID-19 reporting. / Findings: Within three weeks, 153 cases were notified, both geographically and temporally representative of overall COVID-19 Public Health reports. Median (range) age was 71 (23-94) years. 77 (62%) had a cerebrovascular event: 57 (74%) ischemic strokes, nine (12%) intracerebral hemorrhages, and one CNS vasculitis. The second most common group were 39 (31%) who had altered mental status, including 16 (41%) with encephalopathy of whom seven (44%) had encephalitis. The remaining 23 (59%) had a psychiatric diagnosis of whom 21 (92%) were new diagnoses; including ten (43%) with psychosis, six (26%) neurocognitive (dementia-like) syndrome, and 4 (17%) an affective disorder. Cerebrovascular events predominated in older patients. Conversely, altered mental status, whilst present in all ages, had disproportionate representation in the young. / Interpretation: This is the first nationwide, cross-specialty surveillance study of acute complications of COVID-19 in the nervous system. Alteration in mental status was common, reflecting encephalopathy/encephalitis and primary psychiatric diagnoses, often in young patients. These data provide valuable and timely information urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy throughout the areas of neurology and neuropsychiatry

Autoimmune hemolytic anemia occurred prior to evident nephropathy in a patient with chronic hepatitis C virus infection: case report

BACKGROUND: Renal involvement in patients with chronic hepatitis C virus infection has been suggested to be due to a variety of immunological processes. However, the precise mechanism by which the kidneys are damaged in these patients is still unclear. CASE PRESENTATION: A 66 year old man presented with the sudden onset of autoimmune hemolytic anemia. Concomitant with a worsening of hemolysis, his initially mild proteinuria and hemoglobinuria progressed. On admission, laboratory tests revealed that he was positive for hepatitis C virus in his blood, though his liver function tests were all normal. The patient displayed cryoglobulinemia and hypocomplementemia with cold activation, and exhibited a biological false positive of syphilic test. Renal biopsy specimens showed signs of immune complex type nephropathy with hemosiderin deposition in the tubular epithelial cells. CONCLUSIONS: The renal histological findings in this case are consistent with the deposition of immune complexes and hemolytic products, which might have occurred as a result of the patient's underlying autoimmune imbalance, autoimmune hemolytic anemia, and chronic hepatitis C virus infection