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Oral administration of a pharmacologically active agent is the common and most preferred route among patients suffering from different types of illness. In the market, different type of oral dosage form is available among them tablet is the most favorite and demanded formulation. Further, the tablets, which are easy to use and swallow, are the ideal dosage form like orally disintegrating tablets (ODT’s). The main advantage of this type of formulation is that they can give easily to old aged and under-aged patients. In this research work, ODT’s formulation was manufactured, which get easily disintegrates and gives no bitter taste in the buccal cavity during administration. To achieve this task, moxifloxacin was complexed with suitable ion exchange resins (IER) like Kyron T314. In this course of action, multiple trials were performed using variable percentages or ratio of moxifloxacin and Kyron T 314. The resulting complex powder was characterized by different parameters like IR spectroscopy and differential scanning calorimetry (DSC). Along with the other excipients, drug resin complex (DRC) was used to manufacture the tablets. In this process, two super disintegrants viz. cross povidone and Ac di sol were used, and tablets were prepared by direct compression methodology. The finished product parameters of the tablet were estimated using the different available analytical methodologies. In this research work, it was concluded that the minimum time (19 seconds) for the wetting of tablets was observed when the quantity of crospovidone used was around 10% (MIT05). Additionally, this formulation gives maximum drug release (84.48%) after 120 minutes. Therefore, by using a suitable IER, taste-masked ODT’s of moxifloxacin can be prepared. This method is more efficient and effective in the development of such type of formulations.

Gokshura tablet is an ayurvedic formulation with gokhru (Tribulus terrestris) as best fixing recommended for building vitality levels. It enhances life, sexual want and drive. Pushyanug churna is an ayurvedic polyherbal formulation, hence this seems essential to explain the material institutionalization, various bioactive markers, blends exhibit in the polyherbal ayurveda compositions such as pushyanug churna. Point of the exhibit effort has been to create what’s more, approve a high-performance thin layer chromatography (HPTLC) strategy for assurance of diosgenin present in gokshura tablet. Mangiferin and chlorogenic acid are present in pushyanug churna. Diosgenin, a biomarker chemical found in gokshura tablets, and mangiferin, a biomarker compound found in pushyanug churna, were standardized using recently developed easy and accurate HPTLC procedures. Pre-coated silica gel 60-F254 was employed at the stationary phase and a mixture of toluene, ethyl acetate, and formic acid (in the proportions 5:4:1) was employed for the mobile phase in the development methodology for diosgenin. In the mobile phase, mangiferin, ethyl acetate and methanol were added in a ratio of 40:60 v/v were utilized. In the chlorogenic acid mobile phase, ethyl acetate:formic acid:acetic acid:water (10:1.1:1.1:2.6 v/v). It was determined that the Rf value of the marker chemical was 0.77 (diosgenin) in gokhsura tablet and 0.23 mangiferin, 0.75 chlorogenic acid in pushyanug churna. For bioactive marker chemicals found in in-house and commercially available formulations, the developed HPTLC approach has shown to be straightforward, sensitive, specific, and dependable.

There are two important parameters for a control release formulation. Primarily, it should be available in the form of a single-dose formulation. It should be given to the patient per day or few days a week during the treatment of patients suffering from diseases like arthritis, angina and diabetes. The second important characteristic of such formulation is that they release the active molecule at the site of action. This will reduce the chances and the level of the side effects of the drug. Among the available such type of dosage form, sustained-release formulations (SR) give the most promising and desirable results. In the SR dosage form, the drug release profile is controlled by the pharmaceutical engineering in the core matrix of tablet. In this study, SR oral tablet of divalproex sodium was manufactured by varying the quantity of drug release-controlling polymers like metolose 65 SH and metolose 90 SH. In the formulations, these polymers were used in different proportions and evaluated their impact on the physical and chemical characteristics of the finished drug product. The results of all formulations were as per the requirement of standard pharmacopoeial monograph. However, drug dissolution results of two formulations viz. DF9 and DF16 were observed to be optimum and excellent among all batches.

Peripheral neuropathy though a common neurological illness has complex aetiology and several different presentations. The term peripheral neuropathy includes symmetric polyneuropathy, single and multiple mononeuropathy, and radiculopathy. Further classication depends on a mixture of phenomenological, pathological, and genetic or other aetiological features. It is heterogeneous in aetiology, diverse in pathology, and varied in severity. Managing a case of perpipheral neuropathy brings along numerous challenges include identifying a case of peripheral neurophy and differentiating it from mimicks, working up for etiology and treatment based on aetiology. Patients can present with either positive or negative symptoms (or both) linked to motor and sensory systems or with autonomic disturbances in some neuropathies. A detailed history and physical examination provides information regarding onset, course and progression of the disease and the type of involvement like generalized, distal or proximal, symmetric or asymmetric, also the type of bre involvement like large myelinated or small unmyelinated and may give clues to neuro anatomic localization of the disease. The diagnosis can be conrmed through a appropriate investigation for the neuropathic pattern like blood tests, Cerebrospinal uid (CSF) analysis, MRI Brain, Ultrasound (USg). These test along with Electro diagnostic investigations like Nerve Conduction Studies (NCS), needle electromyography (EMG) can narrow down differentials and possible aetiologies, However in signicant cases etiology remain undiagnosed. Genetic testing is most diagnostic in carefully selected cases. Sometimes nerve biopsy and skin biopsy may be needed to conrm the etiologies.

Coronary heart disease (CHD) is a worldwide health epidemic. It has been defined as “impairment of heart function due to inadequate blood flow to heart compared to its needs caused by obstructive changes in the coronary circulation to the heart”(1). It is the cause of 25-30% of deaths in most of the industrialized countries. In India also it is a major public health problem. It is aptly called by WHO as the 'modern epidemic'. The increasing incidence of coronary heart disease may be a reflection of increased longevity, adoption of high fat diet based on meats decreased exercise, modern lifestyle, made possible by increasing affluence.The present study is to ascertain the factors influencing outcome of thrombolysis in acute MI and concludes that Gender and Pre infarction not influence the success rate of thrombolysis, Better success rate has been seen in those consuming alcohol and smokers had a lesser success rate than non smokers but statistically not significant. Hypertensives did not show any difference with non hypertensives in the success rate. Diabetics did not differ much from non diabetics with respect to the success rate of thrombolysis. Inferior wall myocardial infarction had a better success rate than anterior wall myocardial infarctions. Those who are having short window period had a better success rate after thrombolysis. Shorter the window period higher the success rate.

Congestive heart failure is a type of disease which is mainly observed due to the improper supply of blood to the heart. In this disease patient feels severe pain in the chest and may cause serious illness. Sudden treatment is needed in this disease to prevent any fatality. Nitroglycerin is the choice of drug for this disease. This study prepares a dosage form that can deliver the drug at a fast rate like a sublingual tablet of nitroglycerin. Sublingual dosage form was manufactured by direct compression method. For the formulation, multiple excipients like super disintegrants, sweeteners and lubricants were used. The finished dosage form was evaluated for different quality parameters. Optimum formulation was compared with the marketed product and kept on the accelerated stability study. Results were observed as satisfactory and comparable with the marketed product.

We present a multiproxy record of grain size and stable carbon isotope from the Lilaur lake, Ganga Basin, India to understand the history of lake formation linked to changes in Indian monsoon precipitation during ~13714 to 3073 calibrated year before Present (cal yr BP). A comparison is made between Lilaur lake proxy record with those from other parts of South Asia as well as North Atlantic to understand extent and causes of monsoon variability and its influence on the fauna and flora of the region. Chronology of lake core was constrained using AMS 14C and optically stimulated luminescence (OSL) dates. This study suggests a transition from river to lake during ~5800 to 5189 cal yr BP which is supported by reduced precipitation with weakening of the Indian summer monsoon (ISM). This river to lake transition culminated in a severe arid phase during 4250 to 4050 cal yr BP (4.2 ka event), corresponding to enhanced El Nino activity, southward shift of the Inter-Tropical Convergence Zone, and aridification of India when the ISM was weak.

Background: Resident or junior doctors and nursing staff make up the backbone of any public health care facility more so in cases of centers affiliated to teaching hospitals. Resident physicians have the most prolonged contact with patients as they represent the first communication interface between the attending physician and the patient. Similarly, the nursing staff has a critical role in patient care. Therefore, to minimize the morbidity and mortality due to Covid-19, it is important to be fully informed and compliant with measures to contain Covid-19. Objectives: To assess the perception of the junior doctors and nurses regarding the various aspects of Covid-19 disease. Methods: A preformed structured questionnaire with closed end questions was sent to the study subjects using the electronic media. In this study, questionnaire was sent to the convenient sample of 250 persons (100 junior doctors or residents and 150 nurses) working in the clinical departments of the hospital, from July 20 to 27th, 2020. This questionnaire was prepared after literature reviews based on information collected from CDC Atlanta, and Ministry of Health and Family Welfare (MOHFW), New Delhi and consisted of three sections: the demographic data, the knowledge and practices sections. The data were collected through anonymous, self-rated questionnaire that was distributed to all participants over the internet (WhatsApp and email). Results- The questionnaire was sent to 250 persons (100 junior doctors and 150 nurses) working in the clinical departments of the hospital, out of which,139 responded comprising 58 (41.73%) junior doctors and 81 (58.27%) nurses. Overall, 79.14% (n= 110) had sufficient knowledge regarding the disease and majority (94.96%) was practicing safe measures. In univariate logistic regression analysis of various variables with knowledge, the qualification was only variable which was found to be more significantly associated as far as knowledge and practices were concerned (junior doctors as compared to nursing staff). Conclusion- Adequate knowledge apart from defining day to day behavior of health care workers, also prepares them for coping strategies in cases of crisis in critical situation like the our world is experiencing now.

Background There is a continued need for therapeutics for the treatment of COVID-19, including intramuscular (IM) agents, which will enable broader use across a variety of healthcare delivery settings. Methods COMET-PEAK (NCT04779879) is a 3-part study evaluating the safety, tolerability, pharmacokinetics (Part A), and viral pharmacodynamics (PD) of sotrovimab as treatment in adults ≥ 18 years with early mild/moderate COVID-19. In Parts B and C, the safety, tolerability and viral PD of sotrovimab administered as a 500 mg intravenous (IV) infusion or as a 500 mg or 250 mg IM injection, respectively, was evaluated. The primary objective for Parts B and C was to compare the virologic response of sotrovimab IM to IV, with an endpoint of mean area under the curve (AUC) of SARS-CoV-2 viral load as measured by qRT-PCR from Day 1 to Day 8 (AUCD1-8) in nasopharyngeal swabs and predefined 90% confidence interval (CI) limits of 0.5-2.0 indicating equivalence. Results A total of 167 and 157 participants were enrolled in Part B and C, respectively, from February-July 2021. The median age of participants was 47 and 42 years in Part B and C, respectively, and ∼50% had ≥ 1 risk factor for progression to severe disease. The viral load at baseline and through Day 29 of follow-up for each arm is shown in Table 1 and Figure 1. The primary objective was met for both study parts: the ratio of the least square geometric mean viral load AUC(D1-8) of sotrovimab IM vs IV was 1.04 (90% CI, 0.98, 1.09) and 1.02 (90% CI, 0.94, 1.11), for Part B and C, respectively. Through Day 29 of follow-up, the most common adverse event was injection site reactions (ISRs) in the IM arms. A total of 10 (12%) participants in the 500 mg IM group and 4 (5%) participants in the 250 mg IM group experienced an ISR, all Grade 1. Serious adverse events were uncommon, and related to COVID-19 progression, including one death in the 250 mg IM arm (Table 2). ISRs aside, there were few treatment-related AEs (2/84 IV, 1/82 IM) in Part B, none serious. Conclusion IM administration of sotrovimab 500 mg and 250 mg each demonstrated equivalence to 500 mg sotrovimab IV in viral load assessments. Overall, there were no treatment-related serious AEs and sotrovimab was well tolerated. An 500 mg IM formulation will allow for expanded treatment potential with sotrovimab. Funding Vir/GSK (NCT04779879). Disclosures Anil K. Gupta, MD, Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support|Vir Biotechnology: Speaker Moti Ramgopal, MD, FACP, FIDSA, AbbVie: Grant/Research Support|Gilead Sciences Inc.: Advisor/Consultant|Gilead Sciences Inc.: Grant/Research Support|Gilead Sciences Inc.: Honoraria|Gilead Sciences Inc.: Stocks/Bonds|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: Honoraria|GlaxoSmithKline: Stocks/Bonds|Janssen Research & Development LLC: Advisor/Consultant|Janssen Research & Development LLC: Grant/Research Support|Janssen Research & Development LLC: Honoraria|Janssen Research & Development LLC: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Merck: Stocks/Bonds|Shionogi: Grant/Research Support|ViiV: Advisor/Consultant|ViiV: Grant/Research Support Jennifer Han, MD, GlaxoSmithKline: Employee Jennifer Moore, MD, GlaxoSmithKline: Employee Rudrani Banerjee, PhD, GSK: Employee|GSK: Stocks/Bonds Phillip Yates, PhD, GSK: Employee during conduct of this research|GSK: Stocks/Bonds Jill Walker, PhD, GlaxoSmithKline: Employee Gretja Schnell, PhD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Mary Beth Connolly, PharmD, GSK: Employee|GSK: Stocks/Bonds Andrea L. Cathcart, PhD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Varsha Imber, MSc, GSK: Employee|GSK: Stocks/Bonds Rabia Anselm, n/a, GSK: Employee|GSK: Stocks/Bonds Lindsay Winograd, MSc, GSK: Employee|GSK: Stocks/Bonds Nancy Haeusser, n/a, GSK: Employee|GSK: Stocks/Bonds Scott Segal, MD, GSK: Employee|GSK: Stocks/Bonds Andrew Skingsley, MD, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds Melissa Aldinger, PharmD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Amanda Peppercorn, MD, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds.

Background: High-risk pregnancy (HRP) puts current pregnancy at an increased risk of complications. In the absence of pre-existing HRP implementation model of the country, in collaboration with the Government of Himachal Pradesh, a new digital HRP model called the 'SEWA—A System E-approach for Women at risk' was developed. The current article demonstrates a model for the early identification and line listing of high-risk pregnant women (PW) with appropriate referrals and increased engagement with the healthcare workers using a digital tool in the form of the Android App. Methods: SEWA was implemented as a pilot intervention in two community development blocks of the Chamba district. The key implementation steps included finalizing protocols for the identification of HRPs, defining processes and roles, mapping health facilities, setting up the communication loop, and developing of digital solutions. The digital app, used by the auxiliary nurse midwife (ANM) and program officers, tracked PW for a year from October 19 to October 20 and recorded the ANC visits, referrals, and birth outcomes. A qualitative assessment was conducted among the health workers to find out their level of acceptance. Results: A total of 1,340 high-risk PW were identified. The intervention year saw a rise in the identification of HRP to 27.9% from 3.5% in the previous year. A total of 2,559 conditions were tagged to the identified 1,340 women categorized into current pregnancy (81%), previous pregnancy (16%), and any existing chronic illness (3%). A majority of the women who required urgent referrals were provided referrals. The application recorded 53% of the delivered HRP with a digital birth preparedness plan, prepared and shared with the PW and Accredited Social Health Activists (ASHA), by text message for compliance. Conclusion: The SEWA application is a feasible and sustainable solution to complement the competency of the care providers for early identification of the high-risk conditions and reduce the burden of preventable unprecedented deaths around the time of birth.

Heinrich Stadial 4 during the last glacial period was marked by severe cooling at northern high latitudes along with the attendant changes in Asian Monsoon (Chinese Stadial 4) and South American Monsoon (South American Stadial 4). Here we present improved constraints on timings of Heinrich/Chinese/South American Stadial 4 onset and termination at sub-centennial precision based on speleothem records. We show that their initial onsets were essentially synchronous (40.20 ± 0.08 thousand years ago) and led the Antarctic warming by ~300 years. The Heinrich/Chinese Stadial 4 termination commenced at 38.34 ± 0.07 thousand years ago following a centennial-scale reduction in the Amazon River runoff and a poleward shift of the Southern Westerly wind belt. These two precursor events may have contributed to a reduced Amazon Plume Region and an enhanced Agulhas salt/heat leakage that led to an abrupt resumption of the Atlantic Meridional Ocean Circulation eventually triggering the Heinrich/Chinese Stadial 4 termination. Severe cooling at high northern latitudes, which marked the onset of Heinrich Stadial 4, was synchronous with changes in tropical monsoon systems and preceded Antarctic warming by around 300 years, according to a compilation of speleothem and ice core records.

Hominin evolution and dispersal: Insight from surface and subsurface dynamics of the western equatorial Indian Ocean

Prevention of infection and propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a high priority in the Coronavirus Disease 2019 (COVID-19) pandemic. Here we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin-converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 spike protein, thereby inhibiting viral entry, infectivity and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and, thus, the spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model and, thus, provide a novel avenue to pursue therapy.

Vicinal diamines are a common motif found in biologically active molecules. The hydroamination of allyl amine derivatives is a powerful approach for the synthesis of substituted 1,2-diamines. Herein, the rhodium-catalyzed hydroamination of primary and secondary allylic amines using diverse amine nucleophiles, including primary, secondary, acyclic, and cyclic aliphatic amines to access a wide range of unsymmetrical vicinal diamines, is presented. The utility of this methodology is further demonstrated through the rapid synthesis of several bioactive molecules and analogs.

Prevention of infection and propagation of SARS-CoV-2 is of high priority in the COVID-19 pandemic. Here, we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 Spike protein, thereby inhibiting viral entry, infectivity, and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and thus spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E-protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model, and thus provide a novel avenue for therapy.

In the recent scenario of global warming, the release of organic and inorganic carbon from the melting glaciers has been a subject of scientific research since it can have a pronounced effect on the riverine carbon cycle and primary productivity. Apart from being one of the largest Himalayan glaciers, Gangotri glacier provides water to the Bhagirathi River (Ganga River) which is the most important perennial river in India in terms of economy and livelihood. In the last decade, the melting and recession of Gangotri glacier have increased significantly leading to the formation of glacial lakes and debris-covered areas. As a result, primary productivity and microbial activity have increased in the subglacial areas which release a great amount of soil CO2 that has not been documented previously in the literature. In the present study, the Bhagirathi River, which is the proglacial melt-stream of the Gangotri glacier has been sampled during the Post-monsoon period. A total of 27 samples including river, groundwater, geothermal spring, and reservoir were collected and have been analyzed for pH, surface temperature, Electrical conductivity (EC), major ions, and stable isotopes of carbon. From the study of major ion abundance patterns and mixing ratios, it has been inferred that carbonate weathering is predominant in the basin, though the major rock type of the area are silicates. The (HCO3- ≈ Dissolved Inorganic Carbon, DIC) values of river water show no correlation with altitude (mean = 42.8 mg/L), while δ13C values show a decreasing trend with a decrease in altitude, with an overall range between -10 and - 5‰. As altitude decreases, organic matter activity increases, and thus more CO2 is washed out from the Soil Organic Matter (SOM), which makes the δ13C values of the river depleted. The δ13C of groundwater (mean = -11.8‰) and reservoir water (mean = -9.4‰) are depleted than river water due to mixing of soil carbon in them, and δ13C of geothermal spring water (mean = -3.6‰), shows enriched values since these are places of active CO2 degassing. The source of DIC in the river water is mainly carbonate weathering in the upstream part and soil CO2 in the downstream part of the study area. Quantifying pCO2 values of the river water and calculating carbon flux from the river would provide important information on whether the Bhagirathi River is acting as a carbon source or sink to the atmosphere.

Nitric oxide (NO), a small, gaseous, redox-active molecule, plays a diverse, key role in physiological functions like growth, development, environmental interactions, defense, stomatal regulation, and senescence. Transcriptional regulation of NO-dependent genes has also been reported under various abiotic stresses and pathogen/insect infestation. Following stress conditions, cellular reactive nitrogen species level increases which results in swift transcriptional reprogramming of nitric oxide signaling. The chapter has been divided into two sections for complete understanding of NO regulatory networks at transcriptional level: (1) in silico transcriptome (RNA-Seq) analysis of NO genes and (2) gene expression studies pertaining to NO signal transduction pathways under various biotic stresses. Transcriptome analysis will encompass transcriptional factors involved in NO signaling, functional annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of NO-dependent genes in plant disease resistance. Besides, gene expression studies include comprehensive knowledge of various NO-dependent genes expressing differentially under biotic stress. In addition, cross-talk of various transcriptional regulatory genes in plant disease resistance has been also discussed. Taken altogether, the chapter is well documented with both in silico transcriptome analysis and experimental recommendations of various NO signal transduction genes contributing to plant disease resistance.

Background: Smoking as a practice has been in existence since 5000 B.C. Smoking in public places was banned in India from 2nd October 2008. According to reports by WHO Tobacco kills more than 7 million people each year. Studies show that few people understand the specific health risks of tobacco use. The present study was done to analyze the impact of the Anti-smoking Campaign in the Institutes’ Campus and also to make people aware of the harmful effects of smoking and motivate them to quit this habit.Methodology: The campaign constituted of various interventions as screening & collection, monitoring through CCTV Surveillance, imposing penalty as per the Act, Destruction of collected material, Behavioral change communication through Anti-smoking March, Public Lectures, Display of Pamphlets/Signages at various places in the institute & No smoking Pledge and involvement of top management.Results: Total about 2613 Kgs of Tobacco and Tobacco products has been collected and destroyed from March 2014 till April 2020. On an average 40 Kilograms of Tobacco material is collected and destroyed per month. Till April 2020, 108 offenders who were caught smoking in the institute were penalized. ‘No smoking Pledge’ was taken by all the participants. Conclusion: The success achieved by the anti-smoking campaign in the Institute suggests that there is a dire need and challenge before us to launch such type of campaigns in all the institutes worldwide to curb this menace from our society.

Background COVID-19 disproportionately results in hospitalization and death in older patients and those with underlying comorbidities. Sotrovimab is a pan-sarbecovirus monoclonal antibody that binds a highly conserved epitope of the SARS-CoV-2 receptor binding domain and has an Fc modification that increases half-life. Sotrovimab retains activity against UK, S. Africa, Brazil, India, New York and California variants in vitro. Objectives To evaluate the efficacy and safety of treatment with sotrovimab in high-risk, non-hospitalized patients with mild/moderate COVID-19, as part of the COMET-ICE clinical trial. Methods Multicenter, double-blind, phase 3 trial in non-hospitalized patients with symptomatic COVID-19 and ≥1 risk factor for disease progression were randomized 1:1 to an IV infusion of sotrovimab 500 mg or placebo. The primary efficacy endpoint was the proportion of patients with COVID-19 progression, defined as hospitalization > 24 hours or death, due to any cause, ≤29 days of randomization. Results The study met the pre-defined primary efficacy endpoint in a preplanned interim analysis: the risk of COVID-19 progression was significantly reduced by 85% (97.24% CI, 44% to 96%; P = 0.002) in 583 patients. In the final intention-to-treat analysis (N = 1057), the adjusted relative risk reduction was 79% (95% CI, 50% to 91%; p< 0.001) through Day 29 in recipients of sotrovimab (n=528) vs. placebo (n=529). Treatment with sotrovimab (ITT) resulted in a numerical reduction in the need for ER visits for illness management, hospitalization for acute illness management (any duration) or death (any cause) compared to placebo. No participants on sotrovimab required ICU admission, compared to 9 participants on placebo, of whom 4 participants required mechanical ventilation. No participants who received sotrovimab died, compared to 4 participants on placebo. The incidence of adverse events was similar between treatment arms and SAEs were numerically more common in the placebo arm. Conclusion Treatment with sotrovimab 500 mg IV resulted in a clinically and statistically significant reduction in progression of COVID-19 to hospitalization or death in patients with mild/moderate disease and was well-tolerated. Study funding GSK & VIR; NCT04545060 Disclosures Jaynier Moya, MD, VIR Biotechnology (Other Financial or Material Support, Jaynier Moya received non-financial support for serving as a clinical trial investigator for Vir Biotechnology) Diego Rodrigues Falci, MD, MSc, PhD, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker's Bureau)GSK (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)MSD (Speaker's Bureau)Pfizer (Speaker's Bureau)United Medical (Speaker's Bureau, Other Financial or Material Support) Joel Solis, MD, VIR Biotechnology (Other Financial or Material Support, Joel Solis received non-financial support for serving as a clinical trial investigator for Vir Biotechnology) Hanzhe Zheng, PhD, VIR Biotechnology (Employee) Nicola Scott, MSc, GlaxoSmithKline (Employee, Shareholder) Andrea L. Cathcart, PhD, Gilead (Shareholder)VIR (Employee, Shareholder) Christy Hebner, PhD, Vir Biotechnology (Employee, Shareholder) Jennifer Sager, PhD, GSK (Other Financial or Material Support)Vir Biotechnology (Employee, Shareholder) Erik Mogalian, PharmD, PhD, Vir Biotechnology (Employee, Shareholder) Daren Austin, PhD, GlaxoSmithKline (Employee, Shareholder) Amanda Peppercorn, MD, GlaxoSmithKline (Employee) Elizabeth L. Alexander, MD, MSc, GlaxoSmithKline (Grant/Research Support, Other Financial or Material Support)VIR Biotechnology (Employee, Shareholder, GSK pharmaceuticals) Wendy W. Yeh, MD, Vir Biotechnology (Employee) Almena Free, MD, Amgen (Scientific Research Study Investigator)Astra Zeneca (Scientific Research Study Investigator)Cardurian (Scientific Research Study Investigator)Coherus (Scientific Research Study Investigator)Freenome (Scientific Research Study Investigator)GlaxoSmithKline/Vir (Scientific Research Study Investigator)Ionis (Scientific Research Study Investigator)Kowa (Scientific Research Study Investigator)New Amsterdam (Scientific Research Study Investigator)Regenacy (Scientific Research Study Investigator)Romark (Scientific Research Study Investigator)Scynexis (Scientific Research Study Investigator) Cynthia Brinson, MD, Abbvie (Scientific Research Study Investigator)BI (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau, Personal fees)GSK (Scientific Research Study Investigator)Novo Nordisk (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau) Melissa Aldinger, PharmD, VIR Biotechnology (Employee) Adrienne Shapiro, MD, PhD, Vir Biotechnology (Scientific Research Study Investigator)

The tropics experienced a unique monsoon climate that drove important changes in socio-economic conditions and shaped different phases of human history during the late Quaternary across the Indian subcontinent. This study presents a new high-resolution speleothem-record of Indian summer monsoon (ISM) variability ranging from ~45,000 to 34,000 yr BP combined with a published record up to 5500 yr BP from the Mawmluh cave, northeastern India. We document significant changes in solar insolation and precession harmonics, implicating solar activity as one of the major forcing factors for rapid monsoonal shifts. Our new δ18O time series shows high-amplitude shifts in the ISM during the marine isotope stage 3 (MIS 3), similar to Dansgaard-Oeschger (D-O) oscillations recorded at high northern latitudes, which mimic the Greenland ice sheet record. The sun driven Northern Hemisphere high latitude climate anomalies played an active role in driving ISM variability and changes in the regional hydrological cycle on centennial to millennial time scales across the Indian subcontinent.

These proceedings pertain to the JSPS-ICSSR seminar entitled ‘Understanding and Addressing Systemic Risks Behind the Socio-economic Impacts of Novel Coronavirus Disease (COVID-19) in Japan and India: Developing a Roadmap for a Resilient and Sustainable Future’. Led by the Institute for Global Environmental Strategies (IGES) and the Indian Institute of Technology, Tirupati (IIT-T) in collaboration with various Indian and Japanese research institutions, the seminar discussed an overview of the systemic risks of COVID-19 in Japan and India, and the impact of COVID-19 on the domestic economy in these countries. The seminar also discussed an overview of the role of governments and institutions in addressing systemic risks. The seminar delved into the nature of systemic risks, and how to manage and mitigate them in the future based on the experiences discussed in the seminar. These proceedings provide insights into the discussions and messages that came out of the seminar.