Magnetic reconnection in current sheets is a magnetic-to-particle energy conversion process that is fundamental to many space and laboratory plasma systems. In the standard model of reconnection, ...this process occurs in a minuscule electron-scale diffusion region
. On larger scales, ions couple to the newly reconnected magnetic-field lines and are ejected away from the diffusion region in the form of bi-directional ion jets at the ion Alfvén speed
. Much of the energy conversion occurs in spatially extended ion exhausts downstream of the diffusion region
. In turbulent plasmas, which contain a large number of small-scale current sheets, reconnection has long been suggested to have a major role in the dissipation of turbulent energy at kinetic scales
. However, evidence for reconnection plasma jetting in small-scale turbulent plasmas has so far been lacking. Here we report observations made in Earth's turbulent magnetosheath region (downstream of the bow shock) of an electron-scale current sheet in which diverging bi-directional super-ion-Alfvénic electron jets, parallel electric fields and enhanced magnetic-to-particle energy conversion were detected. Contrary to the standard model of reconnection, the thin reconnecting current sheet was not embedded in a wider ion-scale current layer and no ion jets were detected. Observations of this and other similar, but unidirectional, electron jet events without signatures of ion reconnection reveal a form of reconnection that can drive turbulent energy transfer and dissipation in electron-scale current sheets without ion coupling.
The BNT162b2 mRNA (Pfizer–BioNTech) and ChAdOx1 nCoV-19 (Oxford–AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national ...vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19.
We did a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19—EAVE II—database comprising linked vaccination, primary care, real-time reverse transcription-PCR testing, and hospital admission patient records for 5·4 million people in Scotland (about 99% of the population) registered at 940 general practices. Individuals who had previously tested positive were excluded from the analysis. A time-dependent Cox model and Poisson regression models with inverse propensity weights were fitted to estimate effectiveness against COVID-19 hospital admission (defined as 1–adjusted rate ratio) following the first dose of vaccine.
Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated over the study period. The mean age of those vaccinated was 65·0 years (SD 16·2). The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85–94) for reduced COVID-19 hospital admission at 28–34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 88% (95% CI 75–94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72–89 at 28–34 days post-vaccination).
Mass roll-out of the first doses of the BNT162b2 mRNA and ChAdOx1 vaccines was associated with substantial reductions in the risk of hospital admission due to COVID-19 in Scotland. There remains the possibility that some of the observed effects might have been due to residual confounding.
UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK.
We report Magnetospheric Multiscale observations of macroscopic and electron-scale current layers in asymmetric reconnection. By intercomparing plasma, magnetic, and electric field data at multiple ...crossings of a reconnecting magnetopause on 22 October 2015, when the average interspacecraft separation was approximately 10 km, we demonstrate that the ion and electron moments are sufficiently accurate to provide reliable current density measurements at 30ms cadence. These measurements, which resolve current layers narrower than the interspacecraft separation, reveal electron-scale filamentary Hall currents and electron vorticity within the reconnection exhaust far downstream of the X line and even in the magnetosheath. Slightly downstream of the X line, intense (up to 3 μA/m2) electron currents, a super-Alfvenic outflowing electron jet, and nongyrotropic crescent shape electron distributions were observed deep inside the ion-scale magnetopause current sheet and embedded in the ion diffusion region. These characteristics are similar to those attributed to the electron dissipation/diffusion region around the X line.
Self-monitoring of physical activity (PA) and diet are key components of behavioral weight loss programs. The purpose of this study was to assess the relationship between diet (mobile app, website, ...or paper journal) and PA (mobile app vs no mobile app) self-monitoring and dietary and PA behaviors.
This study is a post hoc analysis of a 6-month randomized weight loss trial among 96 overweight men and women (body mass index (BMI) 25-45 kg/m(2)) conducted from 2010 to 2011. Participants in both randomized groups were collapsed and categorized by their chosen self-monitoring method for diet and PA. All participants received a behavioral weight loss intervention delivered via podcast and were encouraged to self-monitor dietary intake and PA.
Adjusting for randomized group and demographics, PA app users self-monitored exercise more frequently over the 6-month study (2.6±0.5 days/week) and reported greater intentional PA (196.4±45.9 kcal/day) than non-app users (1.2±0.5 days/week PA self-monitoring, p<0.01; 100.9±45.1 kcal/day intentional PA, p=0.02). PA app users also had a significantly lower BMI at 6 months (31.5±0.5 kg/m(2)) than non-users (32.5±0.5 kg/m(2); p=0.02). Frequency of self-monitoring did not differ by diet self-monitoring method (p=0.63); however, app users consumed less energy (1437±188 kcal/day) than paper journal users (2049±175 kcal/day; p=0.01) at 6 months. BMI did not differ among the three diet monitoring methods (p=0.20).
These findings point to potential benefits of mobile monitoring methods during behavioral weight loss trials. Future studies should examine ways to predict which self-monitoring method works best for an individual to increase adherence.
Asian buffaloes (Bubalus bubalis) have an important socio-economic role. The majority of the population is situated in developing countries. Due to the scarce resources in these countries, very few ...species-specific biotechnology tools exist and a lot of cattle-derived technologies are applied to buffaloes. However, the application of cattle genomic tools to buffaloes is not straightforward and, as results suggested, despite genome sequences similarity the genetic polymorphisms are different.
The first SNP chip genotyping platform designed specifically for buffaloes has recently become available. Herein, a genome-wide association study (GWAS) and gene network analysis carried out in buffaloes is presented. Target phenotypes were six milk production and four reproductive traits. GWAS identified SNP with significant associations and suggested candidate genes that were specific to each trait and also genes with pleiotropic effect, associated to multiple traits.
Network predictions of interactions between these candidate genes may guide further molecular analyses in search of disruptive mutations, help select genes for functional experiments and evidence metabolism differences in comparison to cattle. The cattle SNP chip does not offer an optimal coverage of buffalo genome, thereafter the development of new buffalo-specific genetic technologies is warranted. An annotated reference genome would greatly facilitate genetic research, with potential impact to buffalo-based dairy production.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non--small-cell ...lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization.
Two hundred two patients received VC (vinorelbine 25 mg/m(2)/wk and cisplatin 100 mg/m(2)/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m(2) over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months.
Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P =.002) and neutropenia (P =.008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P =.001, P =.007), and grade 3 peripheral neuropathy was higher on the PC arm (P <.001). More patients on the VC arm discontinued therapy because of toxicity (P =.001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs.
PC is equally efficacious as VC for the treatment of advanced non--small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.
Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the ...urothelium.
Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m2 days 1, 8 and 15; cisplatin 70 mg/m2 day 2) or standard MVAC every 28 days for a maximum of six cycles.
Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio HR, 1.04; 95% confidence interval CI, 0.82 to 1.32; P = .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively), and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alopecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue.
GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.
Autologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials ...of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS.
This study was a single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS). Patients underwent AHSCT using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin chemotherapeutic regimen.
The primary outcome was event-free survival (EFS); defined as no clinical or radiological relapses and no disability progression. Multiparameter flow cytometry was performed for evaluation of post-transplant IR in both MS and lymphoma patients receiving the same chemotherapy regimen.
Thirty-five patients (20 RRMS, 15 SPMS) completed AHSCT, with a median follow-up of 36 months (range 12-66). The median Expanded Disability Status Scores (EDSS) was 6 (2-7) and patients had failed a median of 4 (2-7) disease modifying therapies. 66% failed treatment with natalizumab. EFS at 3 years was 60%, (70% RRMS). Sustained improvement in EDSS was seen in 15 (44%) of patients. There was no treatment-related mortality. A sustained rise in CD39
T regulatory cells, immunosuppressive CD56
natural killer cells and ablation of proinflammatory mucosal-associated invariant T cells was seen for 12 months following AHSCT in patients with MS. These changes did not occur in patients with lymphoma receiving the same chemotherapy for AHSCT.
The EFS in our MS cohort is significantly greater than other high-efficacy immunosuppressive therapies and similar to other AHSCT studies despite a more heavily pretreated cohort.
ACTRN12613000339752.
Autologous haematopoietic stem cell transplantation shows increasing promise as a therapeutic option for patients with treatment-refractory autoimmune disease, particularly systemic sclerosis and ...multiple sclerosis. However, this intensive chemotherapy-based procedure is not always possible due to potential treatment toxicities and comorbidities. The biological mechanisms of how this procedure induces long-term remission in autoimmune disease are increasingly understood. The focus of this review is on recent research findings on the role of CD4+ T regulatory cells (Tregs) in resetting the immune system leading to the eradication of the autoimmune disease after transplantation. Discovery of the precise mechanisms of this process will allow development of novel Treg-based therapies and thus avoid the need for intensive chemotherapy-based treatment for these autoimmune diseases in the future.
The root morphology of ten temperate pasture species (four annual grasses, four perennial grasses and two annual dicots) was compared and their responses to P and N deficiency were characterised. ...Root morphologies differed markedly; some species had relatively fine and extensive root systems (Vulpia spp., Holcus lanatus L. and Lolium rigidum Gaudin), whilst others had relatively thick and small root systems (Trifolium subterraneum L. and Phalaris aquatica L.). Most species increased the proportion of dry matter allocated to the root system at low P and N, compared with that at optimal nutrient supply. Most species also decreased root diameter and increased specific root length in response to P deficiency. Only some of the species responded to N deficiency in this way. Root morphology was important for the acquisition of P, a nutrient for which supply to the plant depends on root exploration of soil and on diffusion to the root surface. Species with fine, extensive root systems had low external P requirements for maximum growth and those with thick, small root systems generally had high external P requirements. These intrinsic root characteristics were more important determinants of P requirement than changes in root morphology in response to P deficiency. Species with different N requirements could not be distinguished clearly by their root morphological attributes or their response to N deficiency, presumably because mass flow is relatively more important for N supply to roots in soil.
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