A new life for sterile neutrino dark matter after the pandemic

We propose a novel mechanism to generate sterile neutrinos $\nu_s$ in theearly Universe, by converting ordinary neutrinos $\nu_\alpha$ in scatteringprocesses $\nu_s\nu_\alpha\to\nu_s\nu_s$. After initial production byoscillations, this leads to an exponential growth in the $\nu_s$ abundance. Weshow that such a production regime naturally occurs for self-interacting$\nu_s$, and that this opens up significant new parameter space where $\nu_s$make up all of the observed dark matter. Our results provide strong motivationto further push the sensitivity of X-ray line searches, and to improve onconstraints from structure formation.<br

A new life for sterile neutrino dark matter after the pandemic

We propose a novel mechanism to generate sterile neutrinos $\nu_s$ in the early Universe, by converting ordinary neutrinos $\nu_\alpha$ in scattering processes $\nu_s\nu_\alpha\to\nu_s\nu_s$. After initial production by oscillations, this leads to an exponential growth in the $\nu_s$ abundance. We show that such a production regime naturally occurs for self-interacting $\nu_s$, and that this opens up significant new parameter space where $\nu_s$ make up all of the observed dark matter. Our results provide strong motivation to further push the sensitivity of X-ray line searches, and to improve on constraints from structure formation

A new life for sterile neutrino dark matter after the pandemic

We propose a novel mechanism to generate sterile neutrinos $\nu_s$ in theearly Universe, by converting ordinary neutrinos $\nu_\alpha$ in scatteringprocesses $\nu_s\nu_\alpha\to\nu_s\nu_s$. After initial production byoscillations, this leads to an exponential growth in the $\nu_s$ abundance. Weshow that such a production regime naturally occurs for self-interacting$\nu_s$, and that this opens up significant new parameter space where $\nu_s$make up all of the observed dark matter. Our results provide strong motivationto further push the sensitivity of X-ray line searches, and to improve onconstraints from structure formation.<br

Объемная капнография как способ оценки эффективности альвеолярной вентиляции в клинической практике

The purpose of the study was to compare the relationship between the dead space volume and tidal volume (VD/VT) using volumetric capnography (VCap) during pressure controlled (PCV) and pressure supported (PSV) ventilation mode in the postoperative period.Materials and methods. 30 randomly assigned cardiac surgical patients undergoing CABG (coronary artery bypass grafting) using ECC (extracorporeal circuit) were included in an observational, prospective study. Patients were connected to the ventilator immediately after ICU admission. After that, monitoring VD/VT, CO2 production (VECO2) as well as ventilation parameters was carried out. The parameters during PCV and PSV mode were statistically evaluated using t-test.Results. Expiratory CO2 (ETCO2) concentration were not significantly different in both PCV or PSV (p=NS), although both VECO2 and minute ventilation (MV) increased during PSV mode (p&lt;0.01). VD/VT in PSV mode was lower than in PCV. Gas exchange represented by alveolar ventilation (VA) was better during PSV (p&lt;0.01). VA was also higher during PSV (p&lt;0.05). The calculated VD/VT ratio differed between PCV and PSV mode (p&lt;0.01).Conclusion. VCap represents a tool for monitoring of CO2 exchange effectivness. We registered a decrease in VD/VT with improved alveolar ventilation (VA) in PSV mode. VCap seems to be a suitable instrument for adjustment of protective lung ventilation.Цель исследования — сравнить взаимосвязь между объемом мертвого пространства и дыхательным объемом (VD/VT) методом объемной капнографии (VCap) в режимах искусственной вентиляции легких с управляемым давлением (PCV) и поддержкой давлением (PSV) в послеоперационном периоде.Материалы и методы. В обсервационное, проспективное исследование методом случайного выбора включили 30 пациентов из отделения сердечно-сосудистой хирургии, перенесших операцию аортокоронарного шунтирования (АКШ) с экстракорпоральным кровообращением. Пациентов подключали к системе вентиляции легких сразу при поступлении в отделение интенсивной терапии. Затем проводили мониторинг VD/VT, продукции CO2 (VECO2), а также параметров вентиляции. Параметры вентиляции в режимах с управляемым давлением (PCV) и поддержкой давлением (PSV) статистически оценивалиРезультаты. Не выявили достоверных различий концентрации CO2 во выдыхаемом воздухе (ETCO2) между режимами PCV и PSV (p=NS), хотя как VECO2, так и минутная вентиляция (MV) возрастали в режиме PSV (p&lt;0,01). Отношение VD/VT в режиме PSV было ниже, чем в режиме PCV. Газообмен, представленный альвеолярной вентиляцией (VA), был лучше в режиме PSV (p&lt;0,01). Показатель VA был также выше в режиме PSV (p&lt;0,05). Расчетное отношение VD/VT различалось между режимами PCV и PSV (p&lt;0,01).Заключение. Объемная капнография (VCap) является средством мониторинга эффективности обмена CO2. Отмечали снижение VD/VT с улучшением альвеолярной вентиляции (VA) в режиме PSV. VCap представляется подходящим методом регулирования протективной вентиляции легких

T cell-mediated hypersensitivity to quinolones: mechanisms and cross-reactivity

BACKGROUND: Quinolones are widely used, broad spectrum antibiotics that can induce immediate- and delayed-type hypersensitivity reactions, presumably either IgE or T cell mediated, in about 2-3% of treated patients. OBJECTIVE: To better understand how T cells interact with quinolones, we analysed six patients with delayed hypersensitivity reactions to ciprofloxacin (CPFX), norfloxacin (NRFX) or moxifloxacin (MXFX). METHODS: We confirmed the involvement of T cells in vivo by patch test and in vitro by means of the lymphocyte proliferation test (LTT). The nature of the drug-T cell interaction as well as the cross-reactivity with other quinolones were investigated through the generation and analysis (flow cytometry and proliferation assays) of quinolone-specific T cell clones (TCC). RESULTS: The LTT confirmed the involvement of T cells because peripheral blood mononuclear cells (PBMC) mounted an enhanced in vitro proliferative response to CPFX and/or NRFX or MXFX in all patients. Patch tests were positive after 24 and 48 h in three out of the six patients. From two patients, CPFX- and MXFX-specific CD4(+)/CD8(+) T cell receptor (TCR) alphabeta(+) TCC were generated to investigate the nature of the drug-T cell interaction as well as the cross-reactivity with other quinolones. The use of eight different quinolones as antigens (Ag) revealed three patterns of cross-reactivity: clones exclusively reacting with the eliciting drug, clones with a limited cross-reactivity and clones showing a broad cross-reactivity. The TCC recognized quinolones directly without need of processing and without covalent association with the major histocompatability complex (MHC)-peptide complex, as glutaraldehyde-fixed Ag-presenting cells (APC) could present the drug and washing quinolone-pulsed APC removed the drug, abrogating the reactivity of quinolone-specific TCC. CONCLUSION: Our data show that T cells are involved in delayed immune reactions to quinolones and that cross-reactivity among the different quinolones is frequent

Transcaval Versus Transaxillary TAVR in Contemporary Practice: A Propensity-Weighted Analysis

Objectives: The aim of this study was to compare transcaval and transaxillary artery access for transcatheter aortic valve replacement (TAVR) at experienced medical centers in contemporary practice. Background: There are no systematic comparisons of transcaval and transaxillary TAVR access routes. Methods: Eight experienced centers contributed local data collected for the STS/ACC TVT Registry (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry) between 2017 and 2020. Outcomes after transcaval and axillary/subclavian (transaxillary) access were adjusted for baseline imbalances using doubly robust (inverse propensity weighting plus regression) estimation and compared. Results: Transcaval access was used in 238 procedures and transaxillary access in 106; for comparison, transfemoral access was used in 7,132 procedures. Risk profiles were higher among patients selected for nonfemoral access but similar among patients requiring transcaval and transaxillary access. Stroke and transient ischemic attack were 5-fold less common after transcaval than transaxillary access (2.5% vs 13.2%; OR: 0.20; 95% CI: 0.06-0.72; P = 0.014) compared with transfemoral access (1.7%). Major and life-threatening bleeding (Valve Academic Research Consortium 3 ≥ type 2) were comparable (10.0% vs 13.2%; OR: 0.66; 95% CI: 0.26-1.66; P = 0.38) compared with transfemoral access (3.5%), as was blood transfusion (19.3% vs 21.7%; OR: 1.07; 95% CI: 0.49-2.33; P = 0.87) compared with transfemoral access (7.1%). Vascular complications, intensive care unit and hospital length of stay, and survival were similar between transcaval and transaxillary access. More patients were discharged directly home and without stroke or transient ischemic attack after transcaval than transaxillary access (87.8% vs 62.3%; OR: 5.19; 95% CI: 2.45-11.0; P \u3c 0.001) compared with transfemoral access (90.3%). Conclusions: Patients undergoing transcaval TAVR had lower rates of stroke and similar bleeding compared with transaxillary access in a contemporary experience from 8 US centers. Both approaches had more complications than transfemoral access. Transcaval TAVR access may offer an attractive option

Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction

We examined clinical outcomes with proton pump inhibitors (PPI) use within CYP2C19 genotype groups during clopidogrel treatment following acute myocardial infarction (AMI). 2062 patients were genotyped for CYP2C19*2 and *17 variants in TRIUMPH. 12 month clinical outcomes were analyzed among patients discharged on clopidogrel within CYP2C19*2 carrier, CYP2C19*17 carrier, and CYP2C19*1 homozygote genotype groups. PPI use was not associated with a difference in mortality. Among clopidogrel-treated Caucasians following AMI, PPI use was associated with a significantly higher rate of cardiac rehospitalization (HR 1.62, 95% CI 1.19-2.19; P=0.002) compared with no PPI use. PPI users who were carriers of the CYP2C19*17 variant experienced significantly higher rates of cardiac rehospitalization (HR 2.05, 95% CI 1.26-3.33; P=0.003), carriers of the CYP2C19*2 variant had a trend toward increased 1-year cardiac rehospitalization (HR 1.69, 95% CI 0.95-2.99; P=0.07), while no significant differences were observed among CYP2C19*1 homozygotes. These results indicate that the risks associated with PPI use among clopidogrel-treated Caucasian post-MI patients are impacted by CYP2C19 genotype, and suggest knowledge of genotype may be useful for personalizing PPI use among patients following AMI to reduce rehospitalization