Formation of Plasmoid Chains in Fusion Relevant Plasmas

The formation of plasmoid chains is explored for the first time within the context of the Taylor problem, in which magnetic reconnection is driven by a small amplitude boundary perturbation in a tearing-stable slab plasma equilibrium. Numerical simulations of a magnetohydrodynamical model of the plasma show that for very small plasma resistivity and viscosity, the linear inertial phase is followed by a nonlinear Sweet-Parker evolution, which gives way to a faster reconnection regime characterized by a chain of plasmoids instead of a slower Rutherford phase

Extended theory of the Taylor problem in the plasmoid-unstable regime

A fundamental problem of forced magnetic reconnection has been solved taking into account the plasmoid instability of thin reconnecting current sheets. In this problem, the reconnection is driven by a small amplitude boundary perturbation in a tearing-stable slab plasma equilibrium. It is shown that the evolution of the magnetic reconnection process depends on the external source perturbation and the microscopic plasma parameters. Small perturbations lead to a slow nonlinear Rutherford evolution, whereas larger perturbations can lead to either a stable Sweet-Parker-like phase or a plasmoid phase. An expression for the threshold perturbation amplitude required to trigger the plasmoid phase is derived, as well as an analytical expression for the reconnection rate in the plasmoid-dominated regime. Visco-resistive magnetohydrodynamic simulations complement the analytical calculations. The plasmoid formation plays a crucial role in allowing fast reconnection in a magnetohydrodynamical plasma, and the presented results suggest that it may occur and have profound consequences even if the plasma is tearing-stable.Comment: Accepted for publication in Physics of Plasma

Gyro-induced acceleration of magnetic reconnection

The linear and nonlinear evolution of magnetic reconnection in collisionless high-temperature plasmas with a strong guide field is analyzed on the basis of a two-dimensional gyrofluid model. The linear growth rate of the reconnecting instability is compared to analytical calculations over the whole spectrum of linearly unstable wave numbers. In the strongly unstable regime (large \Delta '), the nonlinear evolution of the reconnecting instability is found to undergo two distinctive acceleration phases separated by a stall phase in which the instantaneous growth rate decreases. The first acceleration phase is caused by the formation of strong electric fields close to the X-point due to ion gyration, while the second acceleration phase is driven by the development of an open Petschek-like configuration due to both ion and electron temperature effects. Furthermore, the maximum instantaneous growth rate is found to increase dramatically over its linear value for decreasing diffusion layers. This is a consequence of the fact that the peak instantaneous growth rate becomes weakly dependent on the microscopic plasma parameters if the diffusion region thickness is sufficiently smaller than the equilibrium magnetic field scale length. When this condition is satisfied, the peak reconnection rate asymptotes to a constant value.Comment: Accepted for publication on Physics of Plasma

Solar and Interplanetary Turbulence: Lagrangian Coherent Structures

Talk delivered in 22nd EGU General Assembly, held online 4-8 May, 2020, id.4289, https://meetingorganizer.copernicus.org/EGU2020/EGU2020-4289.html.-- https://www.egu2020.eu/The dynamics of solar and interplanetary plasmas is governed by coherent structures such as current sheets and magnetic flux ropes which are responsible for the genesis of intermittent turbulence via magnetic reconnections in solar supergranular junctions, solar coronal loops, the shock-sheath region of an interplanetary coronal mass ejection, and the interface region of two interplanetary magnetic flux ropes. Lagrangian coherent structures provide a new powerful technique to detect time- or space-dependent transport barriers, and objective (i.e., frame invariant) kinematic and magnetic vortices in space plasma turbulence. We discuss the basic concepts of Lagrangian coherent structures in plasmas based on the computation of the finite-time Lyapunov exponent, the Lagrangian averaged vorticity deviation and the integrated averaged current deviation, as well as their applications to numerical simulations of MHD turbulence and space and ground observations.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation SEV-2017-070

Phase IIa trial of fingolimod for amyotrophic lateral sclerosis demonstrates acceptable acute safety and tolerability

ABSTRACT Introduction: Immune activation has been implicated in progression of amytrophic lateral sclerosis (ALS). Oral fingolimod reduces circulating lymphocytes. The objective of this phase IIa, randomized, controlled trial was to test the short‐term safety, tolerability, and target engagement of fingolimod in ALS. Methods: Randomization was 2:1 (fingolimod:placebo). Treatment duration was 4 weeks. Primary outcomes were safety and tolerability. Secondary outcomes included circulating lymphocytes and whole‐blood gene expression. Results: Thirty participants were randomized; 28 were administered a drug (fingolimod 18, placebo 10). No serious adverse events occurred. Adverse events were similar by treatment arm, as was study discontinuation (2 fingolimod vs. 0 placebo, with no statistical difference). Forced expiratory volume in 1 second (FEV1) and FEV1/slow vital capacity changes were similar in the fingolimod and placebo arms. Circulating lymphocytes decreased significantly in the fingolimod arm (P < 0.001). Nine immune‐related genes were significantly downregulated in the fingolimod arm, including forkhead box P3 (P < 0.001) and CD40 ligand (P = 0.003). Discussion Fingolimod is safe and well‐tolerated and can reduce circulating lymphocytes in ALS patients. Muscle Nerve 56: 1077–1084, 201

A High-Density Genome-Wide Association Screen of Sporadic ALS in US Veterans

Following reports of an increased incidence of amyotrophic lateral sclerosis (ALS) in U.S. veterans, we have conducted a high-density genome-wide association study (GWAS) of ALS outcome and survival time in a sample of U.S. veterans. We tested ∼1.3 million single nucleotide polymorphisms (SNPs) for association with ALS outcome in 442 incident Caucasian veteran cases diagnosed with definite or probable ALS and 348 Caucasian veteran controls. To increase power, we also included genotypes from 5909 publicly-available non-veteran controls in the analysis. In the survival analysis, we tested for association between SNPs and post-diagnosis survival time in 639 Caucasian veteran cases with definite or probable ALS. After this discovery phase, we performed follow-up genotyping of 299 SNPs in an independent replication sample of Caucasian veterans and non-veterans (ALS outcome: 183 cases and 961 controls; survival: 118 cases). Although no SNPs reached genome-wide significance in the discovery phase for either phenotype, three SNPs were statistically significant in the replication analysis of ALS outcome: rs6080539 (177 kb from PCSK2), rs7000234 (4 kb from ZNF704), and rs3113494 (13 kb from LOC100506746). Two SNPs located in genes that were implicated by previous GWA studies of ALS were marginally significant in the pooled analysis of discovery and replication samples: rs17174381 in DPP6 (p = 4.4×10−4) and rs6985069 near ELP3 (p = 4.8×10−4). Our results underscore the difficulty of identifying and convincingly replicating genetic associations with a rare and genetically heterogeneous disorder such as ALS, and suggest that common SNPs are unlikely to account for a substantial proportion of patients affected by this devastating disorder

Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020