Kinematic Mechanism of Plasma Electron Hole Transverse Instability

It is shown through multidimensional particle-in-cell simulations that at least in Maxwellian background plasmas the long-wavelength transverse instability of plasma electron holes is caused not by the previously proposed focusing of trapped particles but instead by kinematic jetting of marginally passing electrons. The mechanism is explained and heuristic analytic estimates obtained which agree with the growth rates and transverse wave numbers observed in the simulations.United States. National Aeronautics and Space Administration (Grant NNX16AG82G

Plasma electron hole oscillatory velocity instability

In this paper, we report a new type of instability of electron holes (EHs) interacting with passing ions. The nonlinear interaction of EHs and ions is investigated using a new theory of hole kinematics. It is shown that the oscillation in the velocity of the EH parallel to the magnetic field direction becomes unstable when the hole velocity in the ion frame is slower than a few times the cold ion sound speed. This instability leads to the emission of ion-acoustic waves from the solitary hole and decay in its magnitude. The instability mechanism can drive significant perturbations in the ion density. The instability threshold, oscillation frequency and instability growth rate derived from the theory yield quantitative agreement with the observations from a novel high-fidelity hole-tracking particle-in-cell code

Effect of N2, Ne and Ar seeding on Alcator C-Mod H-mode confinement

The mitigation of divertor heat fluxes is an active topic of investigation on existing tokamaks. One approach uses radiation, both inside and outside the last closed flux surface (LCFS), to convert plasma thermal energy, usually directed towards dedicated plasma facing components, to soft X-ray and ultraviolet radiation, spread over a much larger surface area. Recent enhanced D-α H-mode experiments on Alcator C-Mod varied the ICRF input power and radiative power losses via impurity seeding to demonstrate that normalized energy confinement depends strongly on the difference between input power and the radiated power inside the LCFS. These investigations also show that when seeded with either Ne or N2, a factor of two and higher reduction in outer divertor heat flux is achieved while maintaining H[subscript 98,y2] ∼ 1.0. Conversely, when seeding with Ar, confinement is limited to H[subscript 98,y2] ∼ 0.8 for a similar level of exhaust power.United States. Dept. of Energy (DOE Contract Number DEFC0299ER54512

Poloidal asymmetries in edge transport barriers

Measurements of impurities in Alcator C-Mod indicate that in the pedestal region, significant poloidal asymmetries can exist in the impurity density, ion temperature, and main ion density. In light of the observation that ion temperature and electrostatic potential are not constant on a flux surface [Theiler et al., Nucl. Fusion 54, 083017 (2014)], a technique based on total pressure conservation to align profiles measured at separate poloidal locations is presented and applied. Gyrokinetic neoclassical simulations with XGCa support the observed large poloidal variations in ion temperature and density, and that the total pressure is approximately constant on a flux surface. With the updated alignment technique, the observed in-out asymmetry in impurity density is reduced from previous publishing [Churchill et al., Nucl. Fusion 53, 122002 (2013)], but remains substantial (nz,H/nz,L∼6). Candidate asymmetry drivers are explored, showing that neither non-uniform impurity sources nor localized fluctuation-driven transport are able to explain satisfactorily the impurity density asymmetry. Since impurity density asymmetries are only present in plasmas with strong electron density gradients, and radial transport timescales become comparable to parallel transport timescales in the pedestal region, it is suggested that global transport effects relating to the strong electron density gradients in the pedestal are the main driver for the pedestal in-out impurity density asymmetry.United States. Department of Energy (DE-FC02-99ER54512)United States. Department of Energy (DE-FG02-06ER54845)United States. Department of Energy (DE-FG02-86ER53223)United States. Department of Energy (DE-AC02-09CH11466

Alcator C-Mod: research in support of ITER and steps beyond

This paper presents an overview of recent highlights from research on Alcator C-Mod. Significant progress has been made across all research areas over the last two years, with particular emphasis on divertor physics and power handling, plasma–material interaction studies, edge localized mode-suppressed pedestal dynamics, core transport and turbulence, and RF heating and current drive utilizing ion cyclotron and lower hybrid tools. Specific results of particular relevance to ITER include: inner wall SOL transport studies that have led, together with results from other experiments, to the change of the detailed shape of the inner wall in ITER; runaway electron studies showing that the critical electric field required for runaway generation is much higher than predicted from collisional theory; core tungsten impurity transport studies reveal that tungsten accumulation is naturally avoided in typical C-Mod conditions.United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-AC02-09CH11466)United States. Department of Energy (DE-FG02-96ER-54373)United States. Department of Energy (DE-FG02-94ER54235

Virology under the microscope—a call for rational discourse

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns – conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we – a broad group of working virologists – seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570