Discovery of CMX990: A Potent SARS-CoV-2 3CL Protease Inhibitor Bearing a Novel Warhead.

There remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by an increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (Mpro, 3CLpro) of SARS-CoV-2 is an attractive target due to its homology within the coronaviral family, and lack thereof toward human proteases. In this disclosure, we outline the advent of a novel SARS-CoV-2 3CLpro inhibitor, CMX990, bearing an unprecedented trifluoromethoxymethyl ketone warhead. Compared with the marketed drug nirmatrelvir (combination with ritonavir = Paxlovid), CMX990 has distinctly differentiated potency (∼5× more potent in primary cells) and human in vitro clearance (>4× better microsomal clearance and >10× better hepatocyte clearance), with good in vitro-to-in vivo correlation. Based on its compelling preclinical profile and projected once or twice a day dosing supporting unboosted oral therapy in humans, CMX990 advanced to a Phase 1 clinical trial as an oral drug candidate for SARS-CoV-2.

Alleviating summer heat stress in cowpea-baby corn intercropping with stress-reducing chemicals and fertility variations.

Over the past century, the average surface temperature and recurrent heatwaves have been steadily rising, especially during the summer season, which is affecting the yield potential of most food crops. Hence, diversification in cropping systems with suitable fertilizer management is an urgent need to ensure high yield potential during the summer season. Since intercropping has emerged as an important strategy to increase food production, the present study comprises five intercropping systems in the main plot (sole cowpea, sole baby corn, cowpea + baby corn in 2:1, 3:1, and 4:1 row ratio), three levels of fertilizer viz. 100 (N20 P40), 125 (N25 P50), and 150% (N30 P60) recommended dose of fertilizer (RDF) in the subplot, along with two stress-mitigating chemicals (0.5% CaCl2 and 1% KNO3) in the sub-sub plots. A split-split plot system with four replications was established to carry out the field experiment. The effect of intercropping, fertilizer levels, and stress-mitigating chemicals on crop growth rate (CGR), relative growth rate (RGR), plant temperature, relative water content (RWC) and chlorophyll content of cowpea and baby corn, as well as cowpea equivalent yield (CEY), was investigated during the summer seasons of 2019 and 2020. The experiment was conducted at Agriculture University, Kota (Rajasthan), India. Results showed that CGR, RGR, RWC and chlorophyll content of both crops and CEY were maximum under intercropping of cowpea and baby corn in a 2:1 row ratio compared to other intercropping systems. However, the plant temperature of both crops was significantly lower under this system. CEY, CGR, RGR, and chlorophyll content were considerably greater in the subplots with a fertilizer application of 150% RDF compared to lower levels of fertilizer (100 and 125% RDF). Our findings further show that foliar application of CaCl2 0.5% at the flowering and pod-developing stages of cowpea dramatically boosted CEY, CGR, RGR, RWC, and chlorophyll content of both crops and lowered the plant temperature.

A prospective study to assess and quantify the setup errors with cone-beam computed tomography in head-and-neck cancer image-guided radiotherapy treatment.

Introduction: This study was done to quantify the translational setup errors with cone-beam computed tomography (CBCT) in the image-guided radiation therapy (IGRT) treatment of head-and-neck cancer (HNC) patients. Aims: The objective was to quantify the setup errors by CBCT. Methodology: One hundred patients of HNC were enrolled from March 2020 to March 2021 for IGRT treatment. Pretreatment kV-CBCT images were obtained at the first 3 days of irradiations, and setup error corrections were done in the mediolateral (ML), superior-inferior (SI), and anterior-posterior (AP) directions. Subsequently, a weekly kV-CBCT was repeated for whole duration of radiotherapy for the next 6-7 weeks. Adequacy of planning target volume (PTV) margins was assessed by van Herk's formula. Results: Total 630 CBCT scans of 100 patients were analyzed. Setup errors greater than 3 mm and 5 mm were seen in 11.4% and 0.31% of the patients, respectively. Systematic errors and random errors before correction in ML, SI, and AP directions were 0.10 cm, 0.11 cm, and 0.12 cm and 0.24 cm, 0.20 cm, and 0.21 cm, respectively. Systematic errors and random errors after correction in ML, SI, and AP directions were 0.06 cm, 0.07 cm, and 0.07 cm and 0.13 cm, 0.10 cm, and 0.12 cm, respectively. Conclusion: CBCT at the first 3 fractions and then weekly during radiotherapy is effective to detect the setup errors. An isotropic PTV margin of 5 mm over clinical target volume is safe to account for setup errors, however, in the case of close organ at risk, or with IGRT, a PTV margin of 3 mm can be considered.

A comparison of the quality of images of chest X-ray between handheld portable digital X-ray & routinely used digital X-ray machine.

Background & objectives: Chest X-ray (CXR) is an important screening tool for pulmonary tuberculosis (TB). Accessibility to CXR facilities in difficult-to-reach and underserved populations is a challenge. This can potentially be overcome by deploying digital X-ray machines that are portable. However, these portable X-ray machines need to be validated before their deployment in the field. Here, we compare the image quality of CXR taken by a newly developed handheld X-ray machine with routinely used reference digital X-ray machine through the conduct of a feasibility study. Methods: A total of 100 participants with suspected pulmonary TB were recruited from the outpatient departments of a medical college and a community health centre in Agra. Each participant underwent CXR twice, once with each machine. Both sets of de-identified images were independently read by two radiologists, who were blinded to the type of X-ray machine used. The primary outcome was agreement between image qualities produced by these two machines. Results: The intra-observer (radiologist) agreements regarding the status of the 15 CXR parameters ranged between 74 per cent and 100 per cent, with an unweighted mean of 87.2 per cent (95% confidence interval: 71.5-100). The median Cohen's kappa values for intra-observer agreement were 0.62 and 0.67 for radiologists 1 and 2, respectively. In addition, on comparison of the overall median score of quality of the image, the handheld machine images had a higher score for image quality. Interpretation & conclusions: The current study shows that a handheld X-ray machine, which is easy to use and can potentially be carried to any area, produces X-ray images with quality that is comparable to digital X-ray machines routinely used in health facilities.

Psychological adjustments among lower limb amputees in North Indian population: A cross-sectional study.

Introduction: Limb amputation is an extremely stressful event for an individual, following which the amputee develops inferior body image, anxiety, and changes in self-concept and identity. For holistic rehabilitation, understanding the psychosocial status of the amputee and its' predictors is of utmost importance. Objective: The aim of the article is to assess the psychological adjustments in patients with lower limb amputation and determine its clinical and sociodemographic correlates. Material and Methods: A observational cross-sectional study was conducted from 2020 to 2022 among lower limb amputees of a tertiary care hospital in Lucknow which serves as the only rehabilitation and artificial limb center for the whole state of Uttar Pradesh. Baseline sociodemographic and clinical data were collected. The Hospital Anxiety and Depression Scale was used to determine underlying depression and anxiety, while the Trinity Amputation and Prosthesis Experience Scale was used for understanding the psychological adjustment. Results: The mean age of the amputee was 39.47 ± 16.99 years. The mean general, social adjustment, and adjustment to limitation score was 16.3 ± 3.34, 15.19 ± 3.59, and 12.76 ± 3.15, respectively. Male amputees, aged >40 years, and pensioners had significantly higher scores for general adjustment (P < 0.05). Those aged >40 years were pensioners and had no underlying depression and anxiety and had better social adjustment (P < 0.05). Those with transfemoral amputation had a significantly lesser adjustment to limitation (P = 0.003). Conclusion: Young age amputees had poor general and social adjustments and more activity restriction but high prosthesis satisfaction as compared to the elderly. Those with transfemoral amputation had a poor adjustment to limitation while those wearing above-knee prosthesis had more activity restriction.

Towards the development of phytoextract based healthy ageing cognitive booster formulation, explored through Caenorhabditis elegans model.

The positive effect of herbal supplements on aging and age-related disorders has led to the evolution of natural curatives for remedial neurodegenerative diseases in humans. The advancement in aging is exceedingly linked to oxidative stress. Enhanced oxidative stress interrupts health of humans in various ways, necessitating to find stress alleviating herbal resources. Currently, minimal scientifically validated health and cognitive booster resources are available. Therefore, we explored the impact of plant extracts in different combinations on oxidative stress, life span and cognition using the multicellular transgenic humanized C. elegans, and further validated the same in Mus musculus, besides testing their safety and toxicity. In our investigations, the final product-the HACBF (healthy ageing cognitive booster formulation) thus developed was found to reduce major aging biomarkers like lipofuscin, protein carbonyl, lipid levels and enhanced activity of antioxidant enzymes. Further confirmation was done using transgenic worms and RT-PCR. The cognitive boosting activities analyzed in C. elegans and M. musculus model system were found to be at par with donepezil and L-dopa, the two drugs which are commonly used to treat Parkinson's and Alzheimer's diseases. In the transgenic C. elegans model system, the HACBF exhibited reduced aggregation of misfolded disease proteins α-synuclein and increased the health of nicotinic acetylcholine receptor, levels of Acetylcholine and Dopamine contents respectively, the major neurotransmitters responsible for memory, language, learning behavior and movement. Molecular studies clearly indicate that HACBF upregulated major genes responsible for healthy aging and cognitive booster activities in C. elegans and as well as in M. musculus. As such, the present herbal product thus developed may be quite useful for healthy aging and cognitive boosting activities, and more so during this covid-19 pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s13237-022-00407-1.

Maximizing genetic gain through unlocking genetic variation in different ecotypes of kalmegh (Andrographis paniculata (Burm. f.) Nee).

Andrographis paniculata, commonly known as kalmegh is among the most popular medicinal herbs in Southeast Asia. It is widely cultivated for medicinal purposes. The bioactive molecule, Andrographolide accumulated in herb leaves has immense therapeutic and economic potential. However, comprehensive information regarding genetic diversity is very limited in this species. The present study assessed genetic diversity between and within the six populations (ecotypes) of twenty-four kalmegh accessions using multiple datasets (agro-morphological traits, phytochemical traits, and genic markers). This is the established report where EST-SSR (Expressed sequence tags-Simple Sequence Repeat) markers have been used to unlock genetic variation in kalmegh. Here, we identified and developed ninety-one metabolic pathway-specific EST-SSR markers. Finally, 32 random EST-SSR primer pairs were selected for genetic diversity assessment. Multivariate analysis to unveil the agro-morphological, phytochemical and genotypic variability was helpful in discriminating various germplasms studied in the present study. Among all the morphological discriptors used in present study, days to fifty percent flowering and dry herb yield were found as potential selection index for AP genetic improvement. Hierarchical cluster analysis built with agro-morphological data identified three major groups. However, corresponding analysis with phytochemical and molecular data generated two clear-cut groups among the studied individuals. Moreover, the grouping of individuals into different clusters using multiple datasets was geographically independent, and also showed inconsistency in grouping among agromorphological, phytochemical and molecular dataset based clusters. However, joint analysis using agro-morphological, phytochemical and genotypic information generated two genetic groups, which could be a valuable resource for identifying complementary crossing panels in the kalmegh breeding program. The accessions AP7, AP13, AP5, AP3 belong to cluster I and accessions AP17, AP18 belong to cluster II could be utilized as potential donors for high dry herb yield and andrographolide content, respectively in different selective breeding programs of AP. Thus, our results provided useful information about the overall genetic diversity and variation in economic traits useful for initiating selective breeding programs for contrasting traits of interest and maximizing genetic gain in kalmegh.

Measurement of Posterior Tibial Slope in Healthy Indian Population: A CT-Based Study.

Background: Recreation of near normal posterior tibial slope is required for proper knee biomechanics after unicondylar as well as total knee arthroplasties. It is also required for proper functioning of anterior cruciate ligament after high tibial osteotomies. Researchers have found differences in values of posterior tibial slopes in individuals of different ethnicities. So far there is no study measuring the posterior slopes of medial and lateral tibial plateau separately in knees of healthy Indian population via three dimensional imaging modalities like computed tomography. Aim: The aim of our study is to find out the slopes of medial and lateral tibial plateau separately through computed tomography (CT) scans. Materials and Methods: CT-based measurements of posterior tibial slopes were done in 62 healthy knees. There were 55 males and 7 females. Results: Age groups were in the range of 17-45 years. Mean values of Posterior tibial slope of medial and lateral tibial plateau for combined sample were 8.60° ± 3.51° and 7.94° ± 3.91°. Mean values of medial and lateral tibial plateau for males were 8.33° ± 3.51° and 7.71° ± 4.07° respectively; while for females were 10.69° ± 2.86° and 9.77° ± 1.32°, respectively.In our study, there was a large range of slopes, extending from + 0.6° to 15.6° for medial tibial slope, from 0° to 15° for lateral tibial slope. Conclusion: The minimum values of Medial tibial plateau slope are very low as compared to the previous study done in Asian population. Further CT based studies are required to measure values of posterior tibial slope for larger sample from Indian population. The implant design suitable and their implantation guidelines for western population may not be appropriate for Indian population.

Very rare incidence of ascending paralysis in a patient of traumatic spinal cord injury: a case report.

INTRODUCTION: After spinal cord injury, further neurological deterioration up to one to two neurological levels is not uncommon. Late neurological deterioration can occur after two months, mainly due to the syrinx formation. In a rare case like in sub-acute post-traumatic ascending myelopathy, the neurological level may ascend more than four levels from the initial level of injury and it usually starts within a few weeks after injury. CASE PRESENTATION: Our case was diagnosed as a case of traumatic spinal cord injury having a lower thoracic neurological level of injury initially, which rapidly progressed over a few weeks into a higher thoracic neurological level. He was operated with pedicle screw fixation of the spine before admission to rehabilitation unit. He was having progressive ascending neurological deterioration, starting a few days after surgery, which was evident by the progression of neurological level by more than four segments clinically. Cerebrospinal fluid(CSF) study showed no significant abnormality. Magnetic resonance imaging (MRI) study showed involvement of the spinal cord at the upper thoracic region. Patient was monitored to note any further worsening. Rehabilitation and supportive measures were provided according to standard protocol. DISCUSSION: Very few cases of ascending paralysis of more than four levels have been reported globally. It results in increased morbidity and mortality in spinal cord injury patients. In our case few possible reasons are ruled out but the actual underlying reason was not clear. Various hypotheses have been proposed as the cause in previous published literatures. Management is mostly supportive.

Cost of HSCT in a Tertiary Care Public Sector Hospital in India.

India harbours a significant burden of hematological diseases including cancers for which Hematopoietic Cell Transplant (HCT) is a definitive life-saving procedure. Very few studies in India have carried out the costing of the important procedure, hence we undertook a study to ascertain the cost of auto HCT in our tertiary care teaching hospital. We did a prospective study using Top-down and Bottom-up approach to arrive at the cost of autologous HCT which came out to be INR 699,200 ($10,282) out of which hospital bears 34% of the cost. The major share of the hospital cost is on account of expenditure on Human Resources. The rest 66% is Out of Pocket Expenditure (OOPE) for the patients. We also calculated the cost which is borne by patient attendants over & above the cost of procedure while caring for the patient, which on an average came to be INR 88,598. This is approximately 19% of the cost borne by the patient for the procedure itself. The cost is usually not factored in while contemplating the procedure and is not covered by any insurance scheme. The overall cost, OOPE & attendant cost can all lead to a substantial financial hardship. Hence, steps need to be taken to make HCT an affordable and accessible procedure.

Seasonal characterization of municipal solid waste for selecting feasible waste treatment technology for Guwahati city, India.

As quantities and composition of municipal solid waste (MSW) vary significantly with seasons, a seasonal characterization study is critical for developing an efficient MSW management system. MSW was characterized in three different seasons for selecting an appropriate waste treatment and management strategy for Guwahati city. Results of the study shows that the major components of the MSW were organics (42.2%) and plastic wastes (25.2%), which show high variations on a seasonal basis (22-49%). The chemical characterization of MSW revealed that on seasonal basis moisture content varies between 43.4% and 58.3%, pH between 5.5 and 6.5, volatile solid content from 32.9 to 58.9%, and the calorific value between 1203 and 3015 kcal/kg. Waste collected in the present study was a mixture of organics, recyclables, and inert material which is difficult and uneconomical for treatment in its present form. However, with proper waste segregation, bio-methanation, and composting could be sustainable waste treatment solutions due to the high moisture and volatile content of the MSW. Due to inadequate quantity, low calorific values, requirement of skilled supervision, and high capital investment, the thermochemical conversion of MSW may not be economically feasible for the present case.Implications: Present study is a novel attempt to analyze in-depth variation in the municipal solid waste (MSW) composition and properties in different seasons and how does it influence the selection and feasibility of the available waste treatment technologies. Search on Google scholar shows that only seven articles have been published till now which evaluated seasonal impact of MSW. Out to these published studies only one study have calculated energy potential of MSW on seasonal basis which is mainly restricted to incineration only. In-depth analysis of seasonal variation on anaerobic digestion, composting, refuse derived fuel (RDF), pyrolysis, and gasification is yet to determine. Furthermore, to best of our knowledge so far in India there was no such in-depth study has been published related to seasonal variation in MSW on large scale (city level). Present study provides in-depth valuable information regarding degree of variation in MSW composition and how does it affect resource recovery out of waste, which was not studied before in-depth before. Outcomes of the present study will definitely assist engineers and policymaker involved MSW management and planning for large urban areas to fulfil their sustainability goals.

A Randomized, Placebo-Controlled Study to Evaluate the Effect of Bio-Enhanced Turmeric Formulation on Radiation-Induced Oral Mucositis.

INTRODUCTION: Oral mucositis is the most common toxicity of chemoradiotherapy treatment of head and neck cancers. The present study was performed to evaluate the effect of a researched turmeric formulation on oral mucositis in patients receiving chemoradiotherapy for oral cancer. METHODS: This randomized double-blinded placebo-controlled trial included 60 patients with oral cancer who had undergone radical surgery. Patients were equally randomized into 3 arms. Bio-enhanced turmeric formulation (BTF) capsules (low dose [1 g/day] or high dose [1.5 g/day]) or placebo was administered daily for 6 weeks with concurrent chemoradiotherapy. Study endpoints included the impact of the treatment on chemoradiotherapy-induced oral mucositis along with dysphagia, oral pain, dermatitis, and weight loss. RESULTS: The incidence of grade 3 toxicity of oral mucositis, oral pain, dysphagia, and dermatitis was significantly lower in patients who received BTF than placebo. Twenty-five and 20% patients in BTF 1 g/day (p = 0.011) and 1.5 g/day (p = 0.004) arms, respectively, developed grade 3 oral mucositis compared to 65% patients in the placebo arm. Thirty-five and 30% patients in BTF 1 g/day (p = 0.027) and 1.5 g/day (p = 0.011) arms, respectively, developed grade 3 oral pain compared to 70% patients in the placebo arm. Twenty-five and 20% patients in BTF 1 g/day (p = 0.025) and 1.5 g/day (p = 0.010) arms, respectively, developed grade 3 dysphagia compared to 60% patients in the placebo arm. Ten and 5% patients in BTF 1 g/day (p = 0.114) and 1.5 g/day (p = 0.037) arms. respectively, developed grade 3 dermatitis compared to 30% patients in the placebo arm. Patients under BTF supplementation experienced significantly less weight loss and greater compliance with treatment than placebo. CONCLUSION: BTF (BCM-95®) can significantly reduce chemoradiotherapy-induced severe oral mucositis, dysphagia, oral pain, and dermatitis in oral cancer patients. TRIAL REGISTRATION: Clinical Trials Registry, India (Registration No. CTRI) (CTRI/2015/12/006413 dated December 4, 2015).

Civil servants' integrity in public sector: the case of Nepal.

Civil servants' integrity in delivering public service is the heart and soul of public sector governance worldwide, including in Nepal. Ensuring a higher level of integrity for civil servants is complex, as it is affected by several factors. With this consideration, this study aims to examine the factors affecting the integrity of civil servants in the delivery of public services in Nepal. Data on this subject were derived from the Nepal National Governance Survey 2017/18, and analyzed using a logistic regression model. The findings revealed that citizens perceived civil servants' integrity in public service was positively affected by civil servants' compliance with rules, their responsiveness in delivering service, their service on time, their hassle-free service, and their adequate salary, whereas negatively affected by civil servants' prior network/connection with citizens and their asking or receiving a bribe for public service. Therefore, the concerned authorities should focus on these factors to build and maintain civil servants' integrity in delivering public service. Our findings provide empirical evidence for concerned authorities who can contribute to adopting innovative governance approaches and appropriate policies to build and maintain civil servants' integrity in the coming days. The study contributes to the field of integrity and public service by highlighting the factors affecting the integrity of civil servants in the delivery of public services.

Therapeutic efficacy of probiotic Alkalihalobacillus clausii 088AE in antibiotic-associated diarrhea: A randomized controlled trial.

The use of probiotics in gastrointestinal ailments has shown therapeutic effects. The imbalance of the microbiota caused by antibiotic treatment or others has been shown to be restored to normal with probiotic treatment. In this study, a genomically and phenotypically safe probiotic Alkalihalobacillus clausii 088AE has been evaluated for ameliorating antibiotic-associated diarrhea (AAD) in pediatrics (PE, n = 60, 2-10 years), adolescent and adults (AA, n = 60, 11-65 years) through a randomized controlled clinical trial. A. clausii 088AE was administered for seven days (PE, 4 and AA, 6 billion/day) and primary and secondary endpoints were evaluated on different visits. Compared to the respective placebo arms, A. clausii 088AE improved the diarrheal (time to last unformed stool and diarrheal frequency) conditions in children, adolescents and adults. A. clausii 088AE treatment decreased AAD-severity score on visit 5 in both pediatric (0.12 ± 0.33, 12.39 folds), adult and adolescent (0.54 ± 0.36, 2.34 folds) groups compared to those respective placebo arm (p < 0.05). A. clausii 088AE was well tolerated, did not cause significant changes in vital and clinical safety parameters and subjects reported no adverse effects or serious adverse reactions. A. clausii 088AE is safe and therapeutically effective against AAD, reducing onset of diarrhea and related severity symptoms including abdominal discomfort and pain, bloating and flatulence. A. clausii 088AE may be recommended as a live bio-therapeutic agent for improving clinical pathophysiology of gastrointestinal ailments, in particular antibiotic-associated diarrhea and related symptoms.

Devastating impacts of COVID-19: An experience of abandoned child at a tertiary care hospital.

There were many challenges faced by both health-care workers and the common population during the COVID-19 pandemic. One such case was witnessed where a migrant worker abandoned his child in a tertiary care hospital, while he was undergoing treatment for acute liver disease and was reported COVID-19 positive. The child was treated for COVID-19 in the dedicated isolation facility of the hospital as per the guidelines. Later, when the child was declared COVID-19 negative and was ready to discharge, treating doctors found it difficult to hand over the child. The timely intervention and extraordinary efforts by the department of hospital administration and child welfare committee reunited the child with his family.

A simple monophasic LGPY medium for routine maintenance of Leishmania donovani promastigotes.

Here, we report a simple, economic and autoclavable monophasic LGPY medium supplemented with 10% fetal bovine serum (FBS), for routine maintenance of Leishmania donovani promastigotes for laboratory use. In comparison to commercially available M199 and RPMI-1640 media, LGPY has shown approximately seven fold more cell growth. The parasite has been observed to survive in the medium for at least 15 days post-inoculation. The medium also supports long-term sub-passaging of the promastigotes and can also be stored at 4 °C or room temperature for 14 months and 45 days, respectively.

Social distancing as risk reduction strategy during COVID-19 pandemic: A study of Delhi-NCT, India.

COVID-19 pandemic impacted countries all over the world calling as urgent need to enhance the capacity of individuals and communities to respond in such disease outbreaks. Public health interventions, such as social distancing could help to protect many vulnerable people and reduce secondary transmissions within the community. This research was undertaken as a longitudinal study to identify and comprehend the preferences given to different preventive measures adopted by individuals to ensure protection against the spread of coronavirus. An online survey was conducted with a representative sample of 176 stakeholders to identify practices and behaviour adopted by the key stakeholders working in the domains of water, health and disaster risk reduction to curb the spread of COVID-19 in Delhi-National Capital Territory of India (Delhi-NCT). Findings of this study shown preferred willingness to adopt sanitisation measures, often by cleaning their hands with soap and water, and restricting any movement inside and outside of the house. Three-fourth of the respondents considered washing their hands after returning from outside an important measure to limit the spread of the disease. Moreover, two-third of the people stopped ordering food from outside as a prevention strategy. Furthermore, only about 36% of the respondents showed interest in stocking up on grocery items as their most preferred choice, reflecting that this was considered to be the least important of all choices. Research outcomes of this study will help policymakers to better understand mitigation options that are used in the early and later stages of the lockdown to improve resilience from such viruses. Further, it will assist decision-makers to understand the range of individual-level practices adopted by stakeholders to mitigate disease transmission at the community level and inform the government's planning efforts in the future.

A randomized prospective study comparing acute toxicity, compliance and objective response rate between simultaneous integrated boost and sequential intensity-modulated radiotherapy for locally advanced head and neck cancer.

PURPOSE: Intensity-modulated radiotherapy (IMRT) provides higher dose to target volumes and limits the dose to normal tissues. IMRT may be applied using either simultaneous integrated boost (SIB-IMRT) or sequential boost (SEQ-IMRT) technique. The objectives of this study were to compare acute toxicity and objective response rates between SIB-IMRT and SEQ-IMRT in patients with locally advanced head and neck cancer. MATERIALS AND METHODS: Total 110 patients with locally advanced carcinoma of oropharynx, hypopharynx, and larynx were randomized equally into the two arms (SIB-IMRT vs. SEQ-IMRT). Patients in SIB-IMRT arm received dose of 66 Gy in 30 fractions, 5 days a week, over 6 weeks. SEQ-IMRT arm's patients received 70 Gy in 35 fractions over 7 weeks. Weekly concurrent cisplatin chemotherapy was given in both arms. Patients were assessed for acute toxicities during the treatment and for objective response at 3 months after the radiotherapy. RESULTS: Grade 3 dysphagia was significantly more with SIB-IMRT compared to SEQ-IMRT (72% vs. 41.2%; p = 0.006) but other toxicities including mucositis, dermatitis, xerostomia, weight-loss, incidence of nasogastric tube intubation and hospitalization for supportive management were similar in both the arms. Patients in SIB-IMRT arm showed better treatment-compliance and had significantly less treatment-interruption compared to SEQ-IMRT arm (p = 0.028). Objective response rates were similar in both the arms (p = 0.783). CONCLUSION: Concurrent chemoradiation with SIB-IMRT for locally advanced head and neck cancer is well-tolerated and results in better treatment-compliance, similar objective response rates, comparable incidence of mucositis and higher incidence of grade 3 dysphagia compared to SEQ-IMRT.

A novel analysis of COVID 19 risk in India incorporating climatic and socioeconomic Factors.

This study investigates the influence of climate variables (pressure, relative humidity, temperature and wind speed) in inducing risk due to COVID 19 at rural, urban and total (rural and urban) population scale in 623 pandemic affected districts of India incorporating the socioeconomic vulnerability factors. We employed nonstationary extreme value analysis to model the different quantiles of cumulative COVID 19 cases in the districts by using climatic factors as covariates. Wind speed was the most dominating climatic factor followed by relative humidity, pressure, and temperature in the evolution of the cases. The results reveal that stationarity, i.e., the COVID 19 cases which are independent of pressure, relative humidity, temperature and wind speed, existed only in 148 (23.7%) out of 623 districts. Whereas, strong nonstationarity, i.e., climate dependence, was detected in the cases of 474 (76.08%) districts. 334 (53.6%), 200 (32.1%) and 336 (53.9%) districts out of 623 districts were at high risk (or above) at rural, urban and total population scales respectively. 19 out of 35 states were observed to be under high (or above) Kerala, Maharashtra, Goa and Delhi being the most risked ones. The study provides high-risk maps of COVID 19 pandemic at the district level and is aimed at supporting the decision-makers to identify climatic and socioeconomic factors in augmenting the risks.