From nanoliter to large-scale bioreactors: How integrated technologies bring antibody treatments to patients faster

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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

Raman and Mössbauer spectroscopic studies of tungsten doped Ni–Zn nano ferrite

In this study, tungsten substituted Ni-Zn nano ferrites of the composition Ni0.5Zn0.5WxFe2−xO4 with x = 0.0, 0.2, 0.4 have been synthesized by a co-precipitation method. The prepared samples were pre-sintered at 850 °C and then annealed at 1000 °C for 3 h each. The structural, morphological, optical and magnetic properties of these samples were studied by using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy (RS) and Mössbauer spectroscopy (MS). XRD revealed the formation of spinel single-phase structure with an average crystallite size of 53–60 nm. Fourier transform infrared spectroscopy show two prominent peaks primarily due to the tetrahedral and octahedral stretching vibrations in the range of 400–600 cm−1. Raman spectra indicate first order three Raman active modes; (A1 g + Eg + T2 g) at around 688, 475 and 326 cm−1. Mössbauer spectroscopy reveals that substitution of W3+ for Fe3+ cation results in reduction of total magnetic moment and consequently the net magnetization

Midterm outcomes of open repair versus endovascular descending thoracic aortic aneurysm repairCentral MessagePerspective

Objective: The study objective was to evaluate the midterm outcome of thoracic endovascular aortic repair compared with open repair in patients with descending thoracic aortic aneurysm. Methods: From August 1993 to February 2023, 499 patients with descending thoracic aortic aneurysms underwent open repair (n = 221) or thoracic endovascular aortic repair (n = 278). Of these, 120 matched pairs were identified using propensity score matching based on age, sex, chronic lung disease, stroke, coronary artery disease, diabetes, ejection fraction, dialysis, peripheral vascular disease, prior cardiac surgery, connective tissue disease, and chronic dissection. Primary outcomes were postoperative paralysis, operative mortality, reoperation, and midterm survival. Results: After matching, the preoperative demographics and comorbidities were balanced in both groups. Intraoperatively, open repair had a lower temperature (18 °C vs 36 °C) and more patients required blood products (66% vs 8%), P < .001. Postoperatively, patients undergoing thoracic endovascular aortic repair had fewer strokes (2.5% vs 9.2%; P = .03), less dialysis (0% vs 3.3%; P = .04), and shorter length of stay (5 days vs 12 days, P < .001), but similar lower-extremity paralysis (2.5% vs 2.5%, P = 1.00) compared with open repair. Furthermore, thoracic endovascular aortic repair had higher 7-year incidence of first reoperation (16.1% vs 3.6%, P < .001) but similar operative mortality (0.8% vs 4.2%; P = .10) and 10-year survival outcome (56%; 95% CI, 43-72 vs 58%; 95% CI, 49-68; P = .55) compared with open aortic repair. The hazard ratio was 0.93 (P = .78) for thoracic endovascular aortic repair for midterm mortality and 6.87 (P < .001) for reoperation. Conclusions: Open repair could be the first option for patients with descending thoracic aortic aneurysms who were surgical candidates

Original research by young twinkle students (ORBYTS): Ephemeris refinement of transiting exoplanets

We report follow-up observations of transiting exoplanets that have either large uncertainties (>10 min) in their transit times or have not been observed for over 3 yr. A fully robotic ground-based telescope network, observations from citizen astronomers, and data from TESS have been used to study eight planets, refining their ephemerides and orbital data. Such follow-up observations are key for ensuring accurate transit times for upcoming ground- and space-based telescopes, which may seek to characterize the atmospheres of these planets. We find deviations from the expected transit time for all planets, with transits occurring outside the 1σ uncertainties for seven planets. Using the newly acquired observations, we subsequently refine their periods and reduce the current predicted ephemeris uncertainties to 0.28-4.01 min. A significant portion of this work has been completed by students at two high schools in London as part of the Original Research By Young Twinkle Students (ORBYTS) programme.Fil: Edwards, Billy. Colegio Universitario de Londres; Reino UnidoFil: Changeat, Quentin. Colegio Universitario de Londres; Reino UnidoFil: Yip, Kai Hou. Colegio Universitario de Londres; Reino UnidoFil: Tsiaras, Angelos. Colegio Universitario de Londres; Reino UnidoFil: Taylor, Jake. University of Oxford; Reino UnidoFil: Akhtar, Bilal. Preston Manor High School; Reino UnidoFil: Aldaghir, Josef. Preston Manor High School; Reino UnidoFil: Bhattarai, Pranup. Preston Manor High School; Reino UnidoFil: Bhudia, Tushar. Beal High School; Reino UnidoFil: Chapagai, Aashish. Preston Manor High School; Reino UnidoFil: Huang, Michael. Preston Manor High School; Reino UnidoFil: Kabir, Danyaal. Beal High School; Reino UnidoFil: Khag, Vieran. Beal High School; Reino UnidoFil: Khaliq, Summyyah. Beal High School; Reino UnidoFil: Khatri, Kush. Preston Manor High School; Reino UnidoFil: Kneth, Jaidev. Beal High School; Reino UnidoFil: Kothari, Manisha. Beal High School; Reino UnidoFil: Najmudin, Ibrahim. Preston Manor High School; Reino UnidoFil: Panchalingam, Lobanaa. Beal High School; Reino UnidoFil: Patel, Manthan. Preston Manor High School; Reino UnidoFil: Premachandran, Luxshan. Beal High School; Reino UnidoFil: Qayyum, Adam. Beal High School; Reino UnidoFil: Rana, Prasen. Preston Manor High School; Reino UnidoFil: Shaikh, Zain. Preston Manor High School; Reino UnidoFil: Syed, Sheryar. Beal High School; Reino UnidoFil: Theti, Harnam. Beal High School; Reino UnidoFil: Zaidani, Mahmoud. Preston Manor High School; Reino UnidoFil: Saraf, Manasvee. Colegio Universitario de Londres; Reino UnidoFil: Di Sisto, Romina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Fernandez Lajus, Eduardo Eusebio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; Argentin

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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