Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.

The United States Government (USG) public-private partnership “Accelerating COVID-19 Treatment Interventions and Vaccines” (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials. While only two ACTIV trials continue to enroll, the recommendations here reflect information from all the trials as of May 2023. We review clinical trial implementation challenges and corresponding lessons learned to inform future therapeutic clinical trials implemented in response to a public health emergency and the conduct of complex clinical trials during “peacetime,” as well.

For the first time, we report the identification of NUV bright red clump (RC) stars and the extension of RC stars over two magnitudes both in color and magnitude axis in NUV vs (NUV – optical) color magnitude diagram. We find that the extension of RC is not due to photometric uncertainties. We suggest that the extension could be an effect of field star contamination. We also suggest that if it is an intrinsic property of the cluster then age and/or metallicity spread within the cluster could be the possible reasons for extended RC.

High-intensity electron linacs have severe space-charge effects that lead to the production of beam halo which degrade the beam quality. For a given charge per bunch, hollow beams have a weaker nonlinear space-charge force. In this paper, we have investigated the possibility of using hollow beam to control halo growth in linacs. We simulate the dynamics of such a beam in a 17 MeV radio frequency linac using ASTRA beam dynamics code and show that it experiences a smaller emittance growth as well as reduced beam halo. The results suggest that using a hollow beam, high charge per bunch could be propagated and accelerated in a radio frequency linac.

ICAR-Directorate of Cashew Research is the nodal agency for conducting cashew research and manages the largest field gene bank in India. Cashew is a perennial tree and needs more land and other resources to maintain accessions. Conservation through seeds is not feasible because of cross-pollination. Tissue culture efforts to regenerate plants from mature explants are not successful. Therefore, efficient management of the filed gene bank particularly utilization requires designation of the core collection representing the spectrum of diversity present in the entire collection. In this study, a relatively new technique, the advanced M strategy with heuristic approach was deployed to develop the core collection. Sixty-eight morphometric characters of 478 accessions were subjected to analysis resulting in the core collection of 49 accessions. Further, another core collection of same number was constituted by K-Means clustering to compare the efficiency of two approaches. The validation parameters like mean difference, variance difference, coincidence rate, variable rate and class coverage among others were employed for comparative analysis. The results of these parameters revealed that the core collection designated by heuristic approach was better able to efficiently represent and retain the diversity of the entire collection compared with the core identified by clustering approach. Future conservation and breeding efforts will be focused on establishing a separate block in the field gene bank having 49 accessions of cashew core collection.

The solar active region (AR) 12192 was one of the most flare productive region of solar cycle 24, which produced many X-class flares; the most energetic being an X3.1 flare on October 24, 2014 at 21:10 UT. Customarily, such events are believed to be triggered by magnetic reconnection in coronal magnetic fields. Here we use the vector magnetograms from solar photosphere, obtained from Heliospheric Magnetic Imager (HMI) to investigate the magnetic field topology prior to the X3.1 event, and ascertain the conditions that might have caused the flare. To infer the coronal magnetic field, a novel non-force-free field (NFFF) extrapolation technique of the photospheric field is used, which suitably mimics the Lorentz forces present in the photospheric plasma. We also highlight the presence of magnetic null points and quasi-separatrix layers (QSLs) in the magnetic field topology, which are preferred sites for magnetic reconnections and discuss the probable reconnection scenarios.

Magnetic reconnections (MRs) for various magnetic field line (MFL) topologies are believed to be the initiators of solar eruptive events like flares and coronal mass ejections (CMEs). Consequently, important is a thorough understanding and quantification of the MFL topology and their evolution which leads to MRs. Contemporary standard is to extrapolate the coronal MFLs using equilibrium models where the Lorentz force on the coronal plasma is zero everywhere. In tandem, a non-force-free-field (NFFF) extrapolation scheme has evolved and allows for a Lorentz force which is non-zero only at the photosphere but asymptotically vanishes with height. The paper reports magnetohydrodynamic (MHD)- simulations initiated by NFFF extrapolation of the coronal MFLs for a flare producing active region NOAA 11158. Interestingly, quasi-separatrix layers (QSLs) which facilitate MRs are detected in the extrapolated MFLs and, here the paper makes an attempt to asses the role of QSLs in the flare onsets.

Low-temperature stress is an important factor affecting the growth and development of rice in temperate and high-elevation areas. In this study, 220 germplasm lines were used for screening of tolerant genotypes, validation of molecular markers and identification of robust markers for seedling-stage chilling stress tolerance to be used in marker-assisted breeding (MAS) programme. The temperature regimes imposed in the growth chamber simulated cold-stress injuries at the seedling stages of the germplasm lines. The genotypes were classified into six classes: those having susceptible genotypes were classified into moderately and highly susceptible types, while tolerant types into moderately tolerant, tolerant, highly tolerant and very highly tolerant classes. Genotypes namely Langma, Umleng-1 and Geetanjali showed survival up to 25 d, which were better than the positive check Kalinga-III surviving up to 20 d under chilling stress. Ten simple sequence repeat (SSR) markers were tested for differentiation of genotypes. Individual use of SSR markers like RM284, RM286, RM85, RM341 and RM5746 can be applied in MAS breeding including combination use of non-pair markers like RM284, RM239 and RM85, which was even better than the combined use of RM284 and RM85. However, combined use of all ten markers can most effectively be employed for cold tolerance through MAS breeding.

Antarctic and Southern Ocean science is vital to understanding natural variability, the processes that govern global change and the role of humans in the Earth and climate system. The potential for new knowledge to be gained from future Antarctic science is substantial. Therefore, the international Antarctic community came together to ‘scan the horizon’ to identify the highest priority scientific questions that researchers should aspire to answer in the next two decades and beyond. Wide consultation was a fundamental principle for the development of a collective, international view of the most important future directions in Antarctic science. From the many possibilities, the horizon scan identified 80 key scientific questions through structured debate, discussion, revision and voting. Questions were clustered into seven topics: i) Antarctic atmosphere and global connections, ii) Southern Ocean and sea ice in a warming world, iii) ice sheet and sea level, iv) the dynamic Earth, v) life on the precipice, vi) near-Earth space and beyond, and vii) human presence in Antarctica. Answering the questions identified by the horizon scan will require innovative experimental designs, novel applications of technology, invention of next-generation field and laboratory approaches, and expanded observing systems and networks. Unbiased, non-contaminating procedures will be required to retrieve the requisite air, biota, sediment, rock, ice and water samples. Sustained year-round access to Antarctica and the Southern Ocean will be essential to increase winter-time measurements. Improved models are needed that represent Antarctica and the Southern Ocean in the Earth System, and provide predictions at spatial and temporal resolutions useful for decision making. A co-ordinated portfolio of cross-disciplinary science, based on new models of international collaboration, will be essential as no scientist, programme or nation can realize these aspirations alone.

The affiliation listed for author Sergio Iannazzo for the article “Economic Evaluation of Intravenous Iodinated Contrast Media in Italy” was incorrect. The study and writeup were completed while Sergio Iannazzo was an IMS Health employee, and the author's correct affiliation for this paper is “IMS Health Italy.” The publisher regrets the error.

Resistance spot welding (RSW) of dual-phase (DP) steel subjected to various conditions of cooling rate (holding time) is studied in this work. Lap-shear tensile testing is used in order to evaluate the mechanical performance of the weldments. The microstructure is analyzed through optical and electron microscopy and the hardness is obtained through Vickers method. Results indicate an effective tempered region along the sub-critical heat affected zone in all the samples. A broken morphology accompanied with presence of small carbides within tempered martensite phase is consistently observed. Variations in the cooling rate (holding time) indicate minimal effect on the degree of softening and on the mechanical performance of the welds.

Faecal specimens of diarrhoea cases (n=2495, collected between November 2007 and October 2009) from Infectious Diseases and Beliaghata General (ID&BG) Hospital, Kolkata, India, were screened by RT–PCR using specific primers targeting region C of the capsid gene of noroviruses (NoVs) to determine the seasonal distribution and clinical characteristics of NoVs associated with diarrhoea. NoV infection was detected in 78 cases, mostly in children aged <2 years. In 22/78 positive cases, the virus was detected as the sole agent; others were as mixed infections with other enteric pathogens. Sequencing of NVGII strains showed clustering with GII.4 NoVs followed by GII.13 and GII.6 NoVs. Clinical characteristics of the diarrhoeic children and adults in Kolkata indicated that NoV infections were detected throughout the year and were associated with a mild degree of dehydration.

Extended abstract of a paper presented at Microscopy and Microanalysis 2010 in Portland, Oregon, USA, August 1 – August 5, 2010.