Studying the variability of fluorescence emission and the presence of clumpy wind in HMXB GX 301−-2 using XMM-Newton

We present the results from an analysis of data from an \textit{XMM-Newton} observation of the accreting high mass X-ray binary pulsar GX 301$-$2. Spectral analysis in the non-flaring segment of the observation revealed that the equivalent width of the iron fluorescence emission is correlated with the observed absorption column density and the ratio of the iron K$\beta$ and K$\alpha$ line strength varied with the flux of the source. Coherent pulsations were detected with the spin period of the pulsar of 687.9$\pm$0.1 s, and a secondary pulsation was also detected with a period of 671.8$\pm$0.2 s, most prominent in the energy band of the iron line. At the spin period of the neutron star, the pulsation of the iron line has a low amplitude and the profile is different from the continuum. Pulse phase-resolved spectroscopy also revealed pulsations of the iron emission line during the non-flaring segment of the light curve. At the secondary period, both the iron line and the continuum have nearly identical pulse fraction and pulse profile. The additional periodicity can be attributed to the beat frequency between the spin of the neutron star and the Keplerian frequency of a stellar wind clump in retrograde motion around the neutron star. Reprocessed X-ray emissions originating from the clump can produce the observed secondary pulsations both in the continuum and the iron fluorescence line. The clump rotating around the neutron star is estimated to be approximately five lt-s away from the neutron star.Comment: 11 pages, 15 figures, Accepted for publication in Monthly Notices of the Royal Astronomical Societ

Acute electrocardiographic changes during smoking: An observational study

Objective To study the temporal relationship of smoking with electrophysiological changes. Design Prospective observational study. Setting Tertiary cardiac center. Participants Male smokers with atypical chest pain were screened with a treadmill exercise test (TMT). A total of 31 such patients aged 49.8±10.5 years, in whom TMT was either negative or mildly positive were included. Heart rate variability (HRV) parameters of smokers were compared to those of 15 healthy non-smoking participants. Interventions All patients underwent a 24 h Holter monitoring to assess ECG changes during smoking periods. Results Heart rate increased acutely during smoking. Mean heart rate increased from 83.8±13.7 bpm 10 min before smoking, to 90.5±16.4 bpm during smoking, (p <0.0001) and returned to baseline after 30 min. Smoking was also associated with increased ectopic beats (mean of 5.3/h prior to smoking to 9.8/h during smoking to 11.3/h during the hour after smoking; p <0.001). Three patients (9.7%) had significant ST–T changes after smoking. HRV index significantly decreased in smokers (15.2±5.3) as compared to non-smoking controls participants (19.4±3.6; p=0.02), but the other spectral HRV parameters were comparable. Conclusions Heart rate and ectopic beats increase acutely following smoking. Ischaemic ST–T changes were also detected during smoking. Spectral parameters of HRV analysis of smokers remained in normal limits, but more importantly geometrical parameter—HRV index—showed significant abnormality

Science with the Daksha High Energy Transients Mission

We present the science case for the proposed Daksha high energy transients mission. Daksha will comprise of two satellites covering the entire sky from 1~keV to $>1$~MeV. The primary objectives of the mission are to discover and characterize electromagnetic counterparts to gravitational wave source; and to study Gamma Ray Bursts (GRBs). Daksha is a versatile all-sky monitor that can address a wide variety of science cases. With its broadband spectral response, high sensitivity, and continuous all-sky coverage, it will discover fainter and rarer sources than any other existing or proposed mission. Daksha can make key strides in GRB research with polarization studies, prompt soft spectroscopy, and fine time-resolved spectral studies. Daksha will provide continuous monitoring of X-ray pulsars. It will detect magnetar outbursts and high energy counterparts to Fast Radio Bursts. Using Earth occultation to measure source fluxes, the two satellites together will obtain daily flux measurements of bright hard X-ray sources including active galactic nuclei, X-ray binaries, and slow transients like Novae. Correlation studies between the two satellites can be used to probe primordial black holes through lensing. Daksha will have a set of detectors continuously pointing towards the Sun, providing excellent hard X-ray monitoring data. Closer to home, the high sensitivity and time resolution of Daksha can be leveraged for the characterization of Terrestrial Gamma-ray Flashes.Comment: 19 pages, 7 figures. Submitted to ApJ. More details about the mission at https://www.dakshasat.in

RNA Aptamers Rescue Mitochondrial Dysfunction in a Yeast Model of Huntington’s Disease

Huntington’s disease (HD) is associated with the misfolding and aggregation of mutant huntingtin harboring an elongated polyglutamine stretch at its N terminus. A distinguishing pathological hallmark of HD is mitochondrial dysfunction. Any strategy that can restore the integrity of the mitochondrial environment should have beneficial consequences for the disease. Specific RNA aptamers were selected that were able to inhibit aggregation of elongated polyglutamine stretch containing mutant huntingtin fragment (103Q-htt). They were successful in reducing the calcium overload, which leads to mitochondrial membrane depolarization in case of HD. In one case, the level of Ca2+ was restored to the level of cells not expressing 103Q-htt, suggesting complete recovery. The presence of aptamers was able to increase mitochondrial mass in cells expressing 103Q-htt, along with rescuing loss of mitochondrial genome. The oxidative damage to the proteome was prevented, which led to increased viability of cells, as monitored by flow cytometry. Thus, the presence of aptamers was able to inhibit aggregation of mutant huntingtin fragment and restore mitochondrial dysfunction in the HD cell model, confirming the advantage of the strategy in a disease-relevant parameter. Keywords: calcium homeostasis, intramers, membrane depolarization, mitochondrial mass, oxidative damage, reactive oxygen specie

Present Scenario of Childhood Deafness: A Tertiary Level Health Care Study

Abstract Introduction Hearing loss is the most common sensory deficit in humans today. Approximately 63 million people in India suffer from significant auditory impairment. Materials and Methods Fifty children of 0-7 years age group, presented to a tertiary level center in Kolkata were assessed by objective and behavioural audiological tests. Result Mean age of presentation was found to be 40.5 months. No risk factor could be identified in 72% of the cases. 47% fell into the profoundly deaf category. Discussion Numerous studies agree that half of the infants with sensorineural hearing loss have no risk factors at birth and thus would be missed by a targeted hearing screening.  Conclusion India certainly faces a worse situation regarding childhood deafness. Implementation of universal neonatal hearing screening along with pre-school hearing assessment can certainly change the scenario

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee