Reviews

Review of Low pay and the minimum wage, Labour relations in the public service: developing countries, Public employment law: the role of the contract of employment in Australia and Britain, The system of industrial relations in New Zealan

New-Onset Atrial Fibrillation After PCI or CABG for Left Main Disease: The EXCEL Trial

Background: There is limited information on the incidence and prognostic impact of new-onset atrial fibrillation (NOAF) following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD). Objectives: This study sought to determine the incidence of NOAF following PCI and CABG for LMCAD and its effect on 3-year cardiovascular outcomes. Methods: In the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, 1,905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. Outcomes were analyzed according to the development of NOAF during the initial hospitalization following revascularization. Results: Among 1,812 patients without atrial fibrillation on presentation, NOAF developed at a mean of 2.7 ± 2.5 days after revascularization in 162 patients (8.9%), including 161 of 893 (18.0%) CABG-treated patients and 1 of 919 (0.1%) PCI-treated patients (p < 0.0001). Older age, greater body mass index, and reduced left ventricular ejection fraction were independent predictors of NOAF in patients undergoing CABG. Patients with versus without NOAF had a significantly longer duration of hospitalization, were more likely to be discharged on anticoagulant therapy, and had an increased 30-day rate of Thrombolysis In Myocardial Infarction major or minor bleeding (14.2% vs. 5.5%; p < 0.0001). By multivariable analysis, NOAF after CABG was an independent predictor of 3-year stroke (6.6% vs. 2.4%; adjusted hazard ratio [HR]: 4.19; 95% confidence interval [CI]: 1.74 to 10.11; p = 0.001), death (11.4% vs. 4.3%; adjusted HR: 3.02; 95% CI: 1.60 to 5.70; p = 0.0006), and the primary composite endpoint of death, MI, or stroke (22.6% vs. 12.8%; adjusted HR: 2.13; 95% CI: 1.39 to 3.25; p = 0.0004). Conclusions: In patients with LMCAD undergoing revascularization in the EXCEL trial, NOAF was common after CABG but extremely rare after PCI. The development of NOAF was strongly associated with subsequent death and stroke in CABG-treated patients. Further studies are warranted to determine whether prophylactic strategies to prevent or treat atrial fibrillation may improve prognosis in patients with LMCAD who are undergoing CABG. (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularizatio

Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial

Importance Hypothermia for 72 hours at 33.5°C for neonatal hypoxic-ischemic encephalopathy reduces death or disability, but rates continue to be high. Objective To determine if cooling for 120 hours or to a temperature of 32.0°C reduces death or disability at age 18 months in infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants Randomized 2 × 2 factorial clinical trial in neonates (≥36 weeks’ gestation) with hypoxic-ischemic encephalopathy at 18 US centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network between October 2010 and January 2016. Interventions A total of 364 neonates were randomly assigned to 4 hypothermia groups: 33.5°C for 72 hours (n = 95), 32.0°C for 72 hours (n = 90), 33.5°C for 120 hours (n = 96), or 32.0°C for 120 hours (n = 83). Main Outcomes and Measures The primary outcome was death or moderate or severe disability at 18 to 22 months of age adjusted for center and level of encephalopathy. Severe disability included any of Bayley Scales of Infant Development III cognitive score less than 70, Gross Motor Function Classification System (GMFCS) level of 3 to 5, or blindness or hearing loss despite amplification. Moderate disability was defined as a cognitive score of 70 to 84 and either GMFCS level 2, active seizures, or hearing with amplification. Results The trial was stopped for safety and futility in November 2013 after 364 of the planned 726 infants were enrolled. Among 347 infants (95%) with primary outcome data (mean age at follow-up, 20.7 [SD, 3.5] months; 42% female), death or disability occurred in 56 of 176 (31.8%) cooled for 72 hours and 54 of 171 (31.6%) cooled for 120 hours (adjusted risk ratio, 0.92 [95% CI, 0.68-1.25]; adjusted absolute risk difference, −1.0% [95% CI, −10.2% to 8.1%]) and in 59 of 185 (31.9%) cooled to 33.5°C and 51 of 162 (31.5%) cooled to 32.0°C (adjusted risk ratio, 0.92 [95% CI, 0.68-1.26]; adjusted absolute risk difference, −3.1% [95% CI, −12.3% to 6.1%]). A significant interaction between longer and deeper cooling was observed (P = .048), with primary outcome rates of 29.3% at 33.5°C for 72 hours, 34.5% at 32.0°C for 72 hours, 34.4% at 33.5°C for 120 hours, and 28.2% at 32.0°C for 120 hours. Conclusions and Relevance Among term neonates with moderate or severe hypoxic-ischemic encephalopathy, cooling for longer than 72 hours, cooling to lower than 33.5°C, or both did not reduce death or moderate or severe disability at 18 months of age. However, the trial may be underpowered, and an interaction was found between longer and deeper cooling. These results support the current regimen of cooling for 72 hours at 33.5°C

Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects

Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species

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

Effects of nutrient enrichment on surface microbial community gene expression in the oligotrophic North Pacific Subtropical Gyre

Marine microbial communities are critical for biogeochemical cycles and the productivity of ocean ecosystems. Primary productivity in the surface ocean is constrained by nutrients which in part are supplied by mixing with deeper water. Little is known about the time scales, frequency, or impact of mixing on microbial communities. We combined in situ sampling using the Environmental Sample Processor and a small-scale mixing experiment with lower euphotic zone water to determine how individual populations respond to mixing. Transcriptional responses were measured using the MicroTOOLs (Microbiological Targets for Ocean Observing Laboratories) microarray, which targets all three domains of life and viruses. The experiment showed that mixing substantially affects photosynthetic taxa as expected, but surprisingly also showed that populations respond differently to unfiltered deep water which contains particles (organisms and detritus) compared to filtered deep water that only contains nutrients and viruses, pointing to the impact of biological interactions associated with these events. Comparison between experimental and in situ population transcription patterns indicated that manipulated populations can serve as analogs for natural populations, and that natural populations may be frequently or continuously responding to nutrients from deeper waters. Finally, this study also shows that the microarray approach, which is complementary to metatranscriptomic sequencing, is useful for determining the physiological status of in situ microbial communities

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome