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Sign language is an interactive language through which deaf-mute people can communicate with ordinary people. There are two ways to translate sign language: contact-based recognition and vision-based recognition. The contact-based method depends on external electrical devices, such as sensors, to identify the movements made by the person and translate them into text. The real-time motion of a person is caught via a web camera in the case of the vision-based technique and is subsequently converted to text using image processing and deep learning algorithms. In this paper, we try to compare and contrast various techniques for Sign Language Recognition and Translation. From our review, we came to a conclusion that the models that were trained on custom datasets were more accurate than the one's which were trained on datasets accumulated by researchers like WLASL. And most of the literature used CNN or a form of RNN, like GRU, LSTM and Transformers. From our study, we found that LSTM outperformed all the models with an average accuracy of 85.4% when data augmentation is utilized. [ABSTRACT FROM AUTHOR]

Research drives development of sustainable electrocatalytic technologies, but efforts are hindered by inconsistent reporting of advances in catalytic performance. Iridium-based oxide catalysts are widely studied for electrocatalytic technologies, particularly for the oxygen evolution reaction (OER) for proton exchange membrane water electrolysis, but insufficient techniques for quantifying electrochemically accessible iridium active sites impede accurate assessment of intrinsic activity improvements. We develop mercury underpotential deposition and stripping as a reversible electrochemical adsorption process to robustly quantify iridium sites and consistently normalize OER performance of benchmark IrO x electrodes to a single intrinsic activity curve, where other commonly used normalization methods cannot. Through rigorous deconvolution of mercury redox and reproportionation reactions, we extract net monolayer deposition and stripping of mercury on iridium sites throughout testing using a rotating ring disk electrode. This technique is a transformative method to standardize OER performance across a wide range of iridium-based materials and quantify electrochemical iridium active sites.

Background: A large body of evidence connects access to greenspace with substantial benefits to physical and mental health. In urban settings where access to greenspace can be limited, park access and use have been associated with higher levels of physical activity, improved physical health, and lower levels of markers of mental distress. Despite the potential health benefits of urban parks, little is known about how park usage varies across locations (between or within cities) or over time., Methods: We estimated park usage among urban residents (identified as residents of urban census tracts) in 498 US cities from 2019 to 2021 from aggregated and anonymised opted-in smartphone location history data. We used descriptive statistics to quantify differences in park usage over time, between cities, and across census tracts within cities, and used generalised linear models to estimate the associations between park usage and census tract level descriptors., Findings: In spring (March 1 to May 31) 2019, 18·9% of urban residents visited a park at least once per week, with average use higher in northwest and southwest USA, and lowest in the southeast. Park usage varied substantially both within and between cities; was unequally distributed across census tract-level markers of race, ethnicity, income, and social vulnerability; and was only moderately correlated with established markers of census tract greenspace. In spring 2019, a doubling of walking time to parks was associated with a 10·1% (95% CI 5·6-14·3) lower average weekly park usage, adjusting for city and social vulnerability index. The median decline in park usage from spring 2019 to spring 2020 was 38·0% (IQR 28·4-46·5), coincident with the onset of physical distancing policies across much of the country. We estimated that the COVID-19-related decline in park usage was more pronounced for those living further from a park and those living in areas of higher social vulnerability., Interpretation: These estimates provide novel insights into the patterns and correlates of park use and could enable new studies of the health benefits of urban greenspace. In addition, the availability of an empirical park usage metric that varies over time could be a useful tool for assessing the effectiveness of policies intended to increase such activities., Funding: Google., Competing Interests: Declaration of interests Google provided an unrestricted gift to the Boston University School of Public Health during the time the study was conducted. MTY, SSe, AKu, SSk, YS, SV, MB, Aka, SB, MK, TS, and EG are current or former employees of Google and may own stock or stock options from Google. GAW previously served as a visiting scientist to Google; currently serves as a consultant to the Health Effects Institute (Boston, MA, USA); reports consulting fees from Google and the Health Effects Institute; and his research at Boston University is supported in part by grants from the National Institutes of Health, the US Department of Defense, the Wellcome Trust, the Atlantic Council, and the Health Effects Institute. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Recruiting participants with cardiovascular disease into research during the COVID-19 pandemic was challenging, particularly those at risk of health disparities., Objective: During the pandemic, 12 cohorts of older women with cardiovascular disease were recruited from cardiology clinics into a lifestyle intervention trial to prevent cognitive decline. Objectives were to ( a ) describe the results of modified recruitment/screening strategies to overcome pandemic-related challenges and ( b ) evaluate differences in age, race, and ethnicity between patients recruited/randomized, recruited/not randomized (entered recruitment but not randomized because of being ineligible or not interested), and not recruited (clinic patients who met preliminary criteria but did not enter recruitment)., Methods: This was a cross-sectional descriptive analysis. In-person study strategies proposed before the COVID-19 pandemic were modified before study onset (September 2020). Women 65 years or older with cardiovascular disease were recruited from cardiology clinics by clinicians, posted flyers, and letters mailed to patients randomly selected from electronic health record data extractions. Patients were classified as recruited/randomized, recruited/not randomized, and not recruited., Results: Of 5719 patients potentially eligible, 1689 patients entered recruitment via referral (49.1%), posted flyers (0.5%), or mailed letters (50.3%), and 253 patients were successfully recruited/randomized. Recruited/randomized participants were, on average, 72.4 years old (range, 65-90 years old), non-Hispanic White (54.2%), non-Hispanic Black (38.3%), Hispanic/Latinx (1.6%), and other/not reported (5.1%). The recruited/randomized group was significantly younger with fewer patients of Hispanic/Latinx ethnicity compared with those not recruited., Conclusions: During the pandemic, all recruitment/screening goals were met using modified strategies. Differences in sociodemographic representation indicate a need for tailored strategies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Better accessibility for emergency obstetric care facilities can substantially reduce maternal and perinatal deaths. However, pregnant women and girls living in urban settings face additional complex challenges travelling to facilities. We aimed to assess the geographical accessibility of the three nearest functional public and private comprehensive emergency obstetric care facilities in the 15 largest Nigerian cities via a novel approach that uses closer-to-reality travel time estimates than traditional model-based approaches., Methods: In this population-based spatial analysis, we mapped city boundaries, verified and geocoded functional comprehensive emergency obstetric care facilities, and mapped the population distribution for girls and women aged 15-49 years (ie, of childbearing age). We used the Google Maps Platform's internal Directions Application Programming Interface to derive driving times to public and private facilities. Median travel time and the percentage of women aged 15-49 years able to reach care were summarised for eight traffic scenarios (peak and non-peak hours on weekdays and weekends) by city and within city under different travel time thresholds (≤15 min, ≤30 min, ≤60 min)., Findings: As of 2022, there were 11·5 million girls and women aged 15-49 years living in the 15 studied cities, and we identified the location and functionality of 2020 comprehensive emergency obstetric care facilities. City-level median travel time to the nearest comprehensive emergency obstetric care facility ranged from 18 min in Maiduguri to 46 min in Kaduna. Median travel time varied by location within a city. The between-ward IQR of median travel time to the nearest public comprehensive emergency obstetric care varied from the narrowest in Maiduguri (10 min) to the widest in Benin City (41 min). Informal settlements and peripheral areas tended to be worse off compared to the inner city. The percentages of girls and women aged 15-49 years within 60 min of their nearest public comprehensive emergency obstetric care ranged from 83% in Aba to 100% in Maiduguri, while the percentage within 30 min ranged from 33% in Aba to over 95% in Ilorin and Maiduguri. During peak traffic times, the median number of public comprehensive emergency obstetric care facilities reachable by women aged 15-49 years under 30 min was zero in eight (53%) of 15 cities., Interpretation: Better access to comprehensive emergency obstetric care is needed in Nigerian cities and solutions need to be tailored to context. The innovative approach used in this study provides more context-specific, finer, and policy-relevant evidence to support targeted efforts aimed at improving comprehensive emergency obstetric care geographical accessibility in urban Africa., Funding: Google., Competing Interests: Declaration of interests NS, YS, GP, MK, SV, TS, and CS are current or past employees of Google, which developed the Google Maps Platform. AB-T and BBA are funded by the Bill & Melinda Gates Foundation (investment identification INV-032911). PMM was supported by Newton International Fellowship (number NIF/R1/201418) of the Royal Society and acknowledges the support of the Wellcome Trust to the Kenya Major Overseas Programme (number 203077). UG-A is funded by a joint Clarendon, Balliol College, and Nuffield Department of Population Health DPhil scholarship. LB was funded in part by the Research Foundation–Flanders as part of her Senior Postdoctoral Fellowship. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Better geographical accessibility to comprehensive emergency obstetric care (CEmOC) facilities can significantly improve pregnancy outcomes. However, with other factors, such as affordability critical for care access, it is important to explore accessibility across groups. We assessed CEmOC geographical accessibility by wealth status in the 15 most-populated Nigerian cities., Methods: We mapped city boundaries, verified and geocoded functional CEmOC facilities, and assembled population distribution for women of childbearing age and Meta's Relative Wealth Index (RWI). We used the Google Maps Platform's internal Directions Application Programming Interface to obtain driving times to public and private facilities. City-level median travel time (MTT) and number of CEmOC facilities reachable within 60 min were summarised for peak and non-peak hours per wealth quintile. The correlation between RWI and MTT to the nearest public CEmOC was calculated., Results: We show that MTT to the nearest public CEmOC facility is lowest in the wealthiest 20% in all cities, with the largest difference in MTT between the wealthiest 20% and least wealthy 20% seen in Onitsha (26 vs 81 min) and the smallest in Warri (20 vs 30 min). Similarly, the average number of public CEmOC facilities reachable within 60 min varies (11 among the wealthiest 20% and six among the least wealthy in Kano). In five cities, zero facilities are reachable under 60 min for the least wealthy 20%. Those who live in the suburbs particularly have poor accessibility to CEmOC facilities., Conclusions: Our findings show that the least wealthy mostly have poor accessibility to care. Interventions addressing CEmOC geographical accessibility targeting poor people are needed to address inequities in urban settings., (© 2024. The Author(s).)

Background: Vascular diseases, including atherosclerotic cardiovascular disease (ASCVD) and stroke, increase the risk of Alzheimer's disease and cognitive impairment. Serum biomarkers, such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1), may be indicators of cognitive health., Objective: We examined whether vascular risk was associated with levels of cognition and serum biomarkers in older women with cardiovascular disease (CVD)., Methods: Baseline data from a lifestyle trial in older women (n = 253) with CVD (NCT04556305) were analyzed. Vascular risk scores were calculated for ASCVD (ASCVD risk estimator) and stroke (CHA2DS2-VASc) based on published criteria. Cognition-related serum biomarkers included BDNF, VEGF, and IGF-1. Cognition was based on a battery of neuropsychological tests that assessed episodic memory, semantic memory, working memory, and executive function. A series of separate linear regression models were used to evaluate associations of vascular risk scores with outcomes of cognition and serum biomarkers. All models were adjusted for age, education level, and racial and ethnic background., Results: In separate linear regression models, both ASCVD and CHA2DS2-VASc scores were inversely associated with semantic memory (β= -0.22, p = 0.007 and β= -0.15, p = 0.022, respectively), with no significant findings for the other cognitive domains. There were no significant associations between vascular risk scores and serum biomarkers., Conclusions: Future studies should prospectively examine associations between vascular risk and cognition in other populations and additionally consider other serum biomarkers that may be related to vascular risk and cognition.

Travel time estimation accounting for on-the-ground realities between the location where a need for emergency obstetric care (EmOC) arises and the health facility capable of providing EmOC is essential for improving pregnancy outcomes. Current understanding of travel time to care is inadequate in many urban areas of Africa, where short distances obscure long travel times and travel times can vary by time of day and road conditions. Here, we describe a database of travel times to comprehensive EmOC facilities in the 15 most populated extended urban areas of Nigeria. The travel times from cells of approximately 0.6 × 0.6 km to facilities were derived from Google Maps Platform's internal Directions Application Programming Interface, which incorporates traffic considerations to provide closer-to-reality travel time estimates. Computations were done to the first, second and third nearest public or private facilities. Travel time for eight traffic scenarios (including peak and non-peak periods) and number of facilities within specific time thresholds were estimated. The database offers a plethora of opportunities for research and planning towards improving EmOC accessibility., (© 2023. Springer Nature Limited.)

Background: The objectives of this study were to 1) evaluate the dietary diversity scores (DDS) and food variety scores (FVS) among Indian children and adolescents aged 9-18 y; 2) compare the DDS and FVS in association with demographic, socioeconomic, and health characteristics (growth and hemoglobin [Hb] concentrations); and 3) determine DDS and FVS cutoffs to identify dietary micronutrient adequacy., Methods: This study was performed in a subset (n = 1845) of children and adolescents enrolled in a multicenter study (2016-2017) from urban and rural areas of six Indian states. Height, weight, and Hb were measured, and anthropometric Z-scores were computed. Sociodemographic data were collected using a structured questionnaire. Dietary data collected by 24-h dietary recall were used to calculate the DDS and FVS. The mean adequacy ratio (MAR) for 10 micronutrients was computed. Receiver operating characteristic analysis was performed to define cutoffs of DDS and FVS., Results: In comparison with children and adolescents from rural areas, urban children and adolescents consumed more diverse diets (urban, 4.1 ± 1.1; rural, 3.5 ± 1; P < 0.01) and had a higher mean FVS (urban, 19.9 ± 5.7; rural, 15.9 ± 4.5; P < 0.01). Both the DDS and FVS were significantly correlated with each other (r = 0.860; P < 0.01) and were positively correlated with MAR, growth, and Hb (P < 0.001) and mother's educational level (P < 0.01). The cutoffs of ≥6.5 (DDS) and ≥17 (FVS) were determined to predict micronutrient adequacy., Conclusions: Both the DDS and FVS can be used interchangeably for assessing growth, health status, and nutritional adequacy. Single cutoff values of the DDS and FVS may aid in prompt identification of children and adolescents with micronutrient inadequacy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Ecoregion comprises all the environmental factors such as climate, vegetation, geomorphology, and soil taken together. The objectives of this study were to (1) assess differences in growth and body composition (BC) in 9-18-year-old children and adolescents (CA), across six ecoregions of India, (2) evaluate and compare the magnitude of the effect of ecoregional and lifestyle factors (LSF) on growth and BC in urban (U) and rural (R) children and adolescents, and (3) reassess the applicability of Bergmann's Rule and Allen's Rule to humans., Subjects and Methods: Data on 1845 CA (925 boys; 920 girls) were collected (2016-2017) from urban and rural areas of six ecoregions of India. Anthropometric and BC parameters were measured; Z-scores were computed. Lifestyle Index score (LIS) based on LSF-(socioeconomic status [SES], diet, physical activity) was computed (categorized as low, medium, high-indicates better LSF). Univariate analysis was performed to estimate effect size., Results: Significant differences were observed in growth and BC across urban and rural ecoregions. CA with high LIS were taller and heavier than those with low LIS (p < .05). Ecoregion had greater effect on growth (Partial eta square (η 2 ) for R = 0.136 vs. U = 0.057) and BC (η 2 for R = 0.094 vs. U = 0.058) of rural CA than urban (p < .01). LSF had more effect on the BC of urban CA (η 2  = 0.017) than rural (η 2  = 0.002, p < .01)., Conclusion: Disparities among the six ecoregions were not large enough to fully support Bergmann's Rule and Allen's Rule. Ecoregion had greater effect on growth and BC of rural CA than urban, while lifestyle factors had more effect on the BC of urban CA., (© 2022 Wiley Periodicals LLC.)

A private-academic partnership built the Vaccine Equity Planner (VEP) to help decision-makers improve geographic access to COVID-19 vaccinations across the United States by identifying vaccine deserts and facilities that could fill those deserts. The VEP presented complex, updated data in an intuitive form during a rapidly changing pandemic situation. The persistence of vaccine deserts in every state as COVID-19 booster recommendations develop suggests that vaccine delivery can be improved. Underresourced public health systems benefit from tools providing real-time, accurate, actionable data. ( Am J Public Health . 2023;113(4):363-367. https://doi.org/10.2105/AJPH.2022.307198).

Study Objectives: To determine efficacy and mechanisms of cognitive behavioral therapy for insomnia (CBT-I) and chronic obstructive pulmonary disease (COPD) education (COPD-ED) on clinical outcomes in adults with concurrent COPD and insomnia., Methods: We conducted a 2 × 2 factorial study to test the impact of CBT-I and COPD-ED delivered alone or in combination on severity of insomnia and fatigue, sleep, and dyspnea. Participants were randomized to 1 of 4 groups-group 1: CBT-I + attention control (AC; health videos, n = 27); group 2: COPD-ED + AC, n = 28; group 3: CBT-I + COPD-ED, n = 27; and group 4, AC only, n = 27. Participants received six 75-minute weekly sessions. Dependent variables included insomnia severity, sleep by actigraphy, fatigue, and dyspnea measured at baseline, immediately postintervention, and at 3 months postintervention. Presumed mediators of intervention effects included beliefs and attitudes about sleep, self-efficacy for sleep and COPD, and emotional function., Results: COPD patients (percent predicted forced expiratory volume in 1 second [FEV1pp] 67% ± 24% [mean ± standard deviation]), aged 65 ± 8 years, with insomnia participated in the study. Insomnia and sleep improved more in patients who received CBT-I than in those who did not, an effect that was sustained at 3 months postintervention and mediated by beliefs and attitudes about sleep. CBT-I was associated with clinically important improvements in fatigue and dyspnea. When CBT-I and COPD-ED were concurrently administered, effects on insomnia, fatigue, and dyspnea were attenuated., Conclusions: CBT-I produced significant and sustained decreases in insomnia improved sleep and clinically important improvement in fatigue, and dyspnea. The combination of CBT-I and COPD-ED reduced CBT-I's effectiveness. Further research is needed to understand the mechanisms associated with effects of insomnia therapy on multiple symptoms in COPD., Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: A Behavioral Therapy for Insomnia Co-existing with COPD; URL: https://clinicaltrials.gov/ct2/show/NCT01973647; Identifier: NCT01973647., Citation: Kapella M, Steffen A, Prasad B, et al. Therapy for insomnia with chronic obstructive pulmonary disease: a randomized trial of components. J Clin Sleep Med . 2022;18(12):2763-2774., (© 2022 American Academy of Sleep Medicine.)

Objectives: To assess grip strength and gender differences in grip strength in 9-18-y-old urban and rural Indian children, to study association of grip strength with body composition, and assess determinants of grip strength., Methods: This was part of a multicenter, cross-sectional, school-based study (n = 1978, mean age 13.3 ± 2.2 y) from three urban and rural states. Anthropometry, body composition, dietary intake, physical activity, sunlight exposure, and grip strength (in kg) were measured., Results: Mean grip strength increased with age but plateaued in girls after 12 y and was higher in boys (19.6 ± 9.2) than girls (14.3 ± 5.3) (p < 0.05). Mean grip strength was higher in urban (21.05 ± 9.7) than in rural boys (17.8 ± 8.2) (p < 0.05), and comparable in urban (14.9 ± 5.2) and rural girls (13.8 ± 5.5). Grip strength in girls remained lower than boys after adjusting for muscle mass. Difference between boys and girls reduced after body size [body mass index (BMI)] correction, but remained low in girls, plateauing after 15 y. Muscle mass and age were significant determinants of grip strength in all children. On addition of lifestyle factors to the model, grip strength was explained to varied degrees in the children., Conclusion: In boys, nutrition through body size and composition was largely responsible for the differences in grip strength, and in girls, additionally, sociocultural factors also possibly impacted grip strength., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Objectives: Among urban and rural Indian children ages 9 to 18 y, we aimed to assess the prevalence and determinants of primary hypertension (PH), and explore the relationship of fat indices and body composition with hypertension., Methods: Data from a multicenter study (2016-2017), representative of children (age 9-18 y) from six states were analyzed (n = 1818; urban n = 895). All anthropometric parameters (Z-scores), blood pressure (BP), body composition, and resting metabolic rate (RMR) were measured. Information from a 2-d 24-h diet recall was collected, nutrient and food group intakes were calculated, and physical activity (PA) was assessed. Children were categorized as normotensive or pre-/hypertensive (>90 th percentile), and a regression analysis was carried out for determinants., Results: Urban children were significantly taller, heavier, more overweight or obese (25% vs. 11%), pre-/hypertensive (18% vs. 10%), adipose, and had lower RMR/weight than rural children. All hypertensive children had higher fat indices, lower muscle mass, and RMR/weight than those who were normotensive (P < 0.05). Rural hypertensive children consumed more junk food, simple carbohydrate (CHO), fat, and sodium than those who were normotensive. RMR (R 2  = 33%) was found to be an important predictor of BP in rural children and body mass index (R 2  = 46%) in urban children, followed by central and peripheral obesity, PA, and diet., Conclusions: Our study highlights that rural children are also at risk of developing PH, especially those with a higher intake of junk food and carbohydrate. Another interesting finding was the negative association of PH with RMR/weight, increasing PA, as well as a micronutrient-rich diet with calcium and magnesium vital to prevent PH. Health care policies need to focus on the increasing prevalence of obesity and PH, not only in urban, but also rural children where different strategies may have to be applied., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The global pandemic of coronavirus disease 2019 (COVID-19) affected many aspects of randomized controlled trials, including recruiting and screening participants. The purpose of this paper is to (a) describe adjustments to recruitment and screening due to COVID-19, (b) compare the proportional recruitment outcomes (not completed, ineligible, and eligible) at three screening stages (telephone, health assessment, and physical activity assessment) pre- and post-COVID-19 onset, and (c) compare baseline demographic characteristics pre- and post-COVID-19 onset in the Working Women Walking program. The design is a cross-sectional descriptive analysis of recruitment and screening data from a 52-week sequential multiple assignment randomized trial (SMART). Participants were women 18-70 years employed at a large urban medical center. Recruitment strategies shifted from in-person and electronic to electronic only post-COVID-19 onset. In-person eligibility screening for health and physical activity assessments continued post-COVID-19 onset with Centers for Disease Control and Prevention precautions. Of those who expressed interest in the study pre- and post-COVID-19 onset (n = 485 & n = 269 respectively), 40% (n = 194) met all eligibility criteria pre-COVID-19 onset, and 45.7% (n = 123) post-COVID-19 onset. Although there were differences in the proportions of participants who completed or were eligible for some of the screening stages, the final eligibility rates did not differ significantly pre-COVID-19 versus post-COVID-19 onset. Examination of differences in participant demographics between pre- and post-COVID-19 onset revealed a significant decrease in the percentage of Black women recruited into the study from pre- to post-COVID-19 onset. Studies recruiting participants into physical activity studies should explore the impact of historical factors on recruitment., (© 2022 Wiley Periodicals LLC.)

COVID-19 is a potentially fatal infection caused by the SARS-CoV-2 virus. The SARS-CoV-2 3CL protease (Mpro) is a viral enzyme essential for replication and is the target for nirmatrelvir. Paxlovid (nirmatrelvir co-administered with the pharmacokinetic enhancer ritonavir) showed efficacy in COVID-19 patients at high risk of progressing to hospitalization and/or death. Nonclinical safety studies with nirmatrelvir are essential in informing benefit-risk of Paxlovid and were conducted to support clinical development. In vivo safety pharmacology assessments included a nervous system/pulmonary study in rats and a cardiovascular study in telemetered monkeys. Potential toxicities were assessed in repeat dose studies of up to 1 month in rats and monkeys. Nirmatrelvir administration (1,000 mg/kg, p.o.) to male rats produced transient increases in locomotor activity and respiratory rate but did not affect behavioral endpoints in the functional observational battery. Cardiovascular effects in monkeys were limited to transient increases in blood pressure and decreases in heart rate, observed only at the highest dose tested (75 mg/kg per dose b.i.d; p.o.). Nirmatrelvir did not prolong QTc-interval or induce arrhythmias. There were no adverse findings in repeat dose toxicity studies up to 1 month in rats (up to 1,000 mg/kg daily, p.o.) or monkeys (up to 600 mg/kg daily, p.o.). Nonadverse, reversible clinical pathology findings without clinical or microscopic correlates included prolonged coagulation times at ≥60 mg/kg in rats and increases in transaminases at 600 mg/kg in monkeys. The safety pharmacology and nonclinical toxicity profiles of nirmatrelvir support clinical development and use of Paxlovid for treatment of COVID-19.

This study focuses on the effects of fear factor due to COVID-19 on stress and well-being of college students in India. The authors conducted a cross-sectional survey among 625 Indian students across various Indian universities and structural equation modeling (SEM) has been performed for analyzing the data. The findings of the study show a positive effect of fear of COVID-19 on stress with β  = .27, p  < 0.05, and a negative effect on well-being ( β  = -.13, p  < 0.05). The results also depicted the mediating role of stress between fear of COVID-19 and well-being. Therefore, it is suggested that measures must be taken by individuals, society, and policy makers to include mental health maintenance in the pandemic response activities. Further longitudinal studies in different geographical regions and demographics can provide a more generalized understanding of the relationship between the pandemic and mental health. The limitations, policy implications, and suggestions are discussed., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Systemic toxicity assessments for oral or parenteral drugs often utilize the concentration of drug in plasma to enable safety margin calculations for human risk assessment. For topical drugs, there is no standard method for measuring drug concentrations in the stratum basale of the viable epidermis. This is particularly important since the superficial part of the epidermis, the stratum corneum (SC), is nonviable and where most of a topically applied drug remains, never penetrating deeper into the skin. We investigated the relative concentrations of a prototype kinase inhibitor using punch biopsy, laser capture microdissection, and imaging mass spectrometry methods in the SC, stratum basale, and dermis of minipig skin following topical application as a cream formulation. The results highlight the value of laser capture microdissection and mass spectrometry imaging in quantifying the large difference in drug concentration across the skin and even within the epidermis, and supports use of these methods for threshold-based toxicity risk assessments in specific anatomic locations of the skin, like of the stratum basale., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Social distancing have been widely used to mitigate community spread of SARS-CoV-2. We sought to quantify the impact of COVID-19 social distancing policies across 27 European counties in spring 2020 on population mobility and the subsequent trajectory of disease., Methods: We obtained data on national social distancing policies from the Oxford COVID-19 Government Response Tracker and aggregated and anonymized mobility data from Google. We used a pre-post comparison and two linear mixed-effects models to first assess the relationship between implementation of national policies and observed changes in mobility, and then to assess the relationship between changes in mobility and rates of COVID-19 infections in subsequent weeks., Results: Compared to a pre-COVID baseline, Spain saw the largest decrease in aggregate population mobility (~70%), as measured by the time spent away from residence, while Sweden saw the smallest decrease (~20%). The largest declines in mobility were associated with mandatory stay-at-home orders, followed by mandatory workplace closures, school closures, and non-mandatory workplace closures. While mandatory shelter-in-place orders were associated with 16.7% less mobility (95% CI: -23.7% to -9.7%), non-mandatory orders were only associated with an 8.4% decrease (95% CI: -14.9% to -1.8%). Large-gathering bans were associated with the smallest change in mobility compared with other policy types. Changes in mobility were in turn associated with changes in COVID-19 case growth. For example, a 10% decrease in time spent away from places of residence was associated with 11.8% (95% CI: 3.8%, 19.1%) fewer new COVID-19 cases., Discussion: This comprehensive evaluation across Europe suggests that mandatory stay-at-home orders and workplace closures had the largest impacts on population mobility and subsequent COVID-19 cases at the onset of the pandemic. With a better understanding of policies' relative performance, countries can more effectively invest in, and target, early nonpharmacological interventions., Competing Interests: The above stated commercial affiliations did not alter adherence to PLOS ONE policies on sharing data and materials.

Social distancing remains an important strategy to combat the COVID-19 pandemic in the United States. However, the impacts of specific state-level policies on mobility and subsequent COVID-19 case trajectories have not been completely quantified. Using anonymized and aggregated mobility data from opted-in Google users, we found that state-level emergency declarations resulted in a 9.9% reduction in time spent away from places of residence. Implementation of one or more social distancing policies resulted in an additional 24.5% reduction in mobility the following week, and subsequent shelter-in-place mandates yielded an additional 29.0% reduction. Decreases in mobility were associated with substantial reductions in case growth two to four weeks later. For example, a 10% reduction in mobility was associated with a 17.5% reduction in case growth two weeks later. Given the continued reliance on social distancing policies to limit the spread of COVID-19, these results may be helpful to public health officials trying to balance infection control with the economic and social consequences of these policies.

Risk management of in vitro aneugens for topically applied compounds is not clearly defined because there is no validated methodology to accurately measure compound concentration in proliferating stratum basale keratinocytes of the skin. Here, we experimentally tested several known aneugens in the EpiDerm reconstructed human skin in vitro micronucleus assay and compared the results to flow cytometric mechanistic biomarkers (phospho-H3; MPM2, DNA content). We then evaluated similar biomarkers (Ki-67, nuclear area) using immunohistochemistry in skin sections of minipigs following topical exposure the potent aneugens, colchicine, and hesperadin. Data from the EpiDerm model showed positive micronucleus responses for all aneugens tested following topical or direct media dosing with similar sensitivity when adjusted for applied dose. Quantitative benchmark dose-response analysis exhibited increases in the mitotic index biomarkers phospho-H3 and MPM2 for tubulin binders and polyploidy for aurora kinase inhibitors are at least as sensitive as the micronucleus endpoint. By comparison, the aneugens tested did not induce histopathological changes, increases in Ki-67 immunolabeling or nuclear area in skin sections from the in vivo minipig study at doses in significant excess of those eliciting a response in vitro. Results indicate the EpiDerm in vitro micronucleus assay is suitable for the hazard identification of aneugens. The lack of response in the minipig studies indicates that the barrier function of the minipig skin, which is comparable to human skin, protects from the effects of aneugens in vivo. These results provide a basis for conducting additional studies in the future to further refine this understanding., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Physical activity monitors, motivational text messages, personal calls, and group meetings, have proven to be efficacious physical activity interventions. However, individual participant response to these interventions varies drastically. A SMART design (sequential multiple assignment randomized trial) provides an effective way to test interventions that start with an initial treatment and then transition to an augmented treatment for non-responders. We describe a SMART to determine the most effective adaptive intervention to increase physical activity (steps, moderate-to-vigorous physical activity) and improve cardiovascular health among employed women who are not regularly physically active. The SMART uses combinations of four treatments: 1) enhanced physical activity monitor (Fitbit wearable activity monitor and mobile app with goal setting and physical activity prescription), 2) text messages, 3) personal calls, and 4) group meetings., Methods: Participants (N = 312) include women ages 18-70 employed at a large academic medical center. Women will be randomized to an initial intervention, either an enhanced physical activity monitor or enhanced physical activity monitor + text messaging. Non-responders to the initial intervention at 2 months will be randomized to either personal calls or groups meetings for the next 6 months. At 8 months, all participants will return to only an enhanced physical activity monitor until their final 12-month assessment., Discussion: Results of this study will add to the literature on improving physical activity in employed women. This study will identify effective interventions for women who respond to less intensive treatments, while maximizing benefits for those who need a more intensive approach., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sitting height (SH) and leg length (LL) help in assessing disproportionate growth. Anthropometric dissimilarity has been observed in different ethnicities. Aim: To (1) study sitting height and body proportions in children from different regions of India; and (2) compare sitting height and body proportions with data from other countries. Subjects and methods: This was a cross-sectional multicentric observational study, where 7961 (4328 boys) 3-18 year old children from five regions (north, south, east, west and central) were measured (height, weight and SH). Results: Boys from north India and girls from central India were taller and heavier (mean height 153.2 ± 18, 146.4 ± 11), while western boys and girls were the shortest (131.1 ± 20.7, 129.8 ± 19.5) ( p  < 0.05 for all). The highest SH was observed in the north (79.2 ± 8.5) and the lowest in the west (68.8 ± 9.1). Mean SH:LL ratio was highest in children from the northeast (1.13) followed by those from western, northern and central India (1.12, 1.10 and 1.07, respectively) and the ratio was the least in children from south India (1.05) ( p  < 0.0.5 for all except northeast and west). Children from the north and west were similar to the Dutch, children from the south were similar to South (black) Africans and the north-eastern children were similar to Chinese children. Conclusion: There were inter-regional differences in body proportions; similarities in body proportions with children from other ethnicities may throw light on the migration history of Indian people.

Objective and Aims: Overweight/obese children are at risk of developing type 2 diabetes mellitus. Random glucose elevations provide early warning signs of glycemic dysregulation. To assess random blood glucose (RBG) concentrations and risk factors associated with prediabetes in children aged 3-18 years from six Indian regions., Method: Multicenter, cross sectional, observational school-based study; multi-stage stratified random sampling was carried out. Height and weight measured; body mass index (BMI) was computed. RBG measured using a glucometer. National sample survey was used for dietary patterns. Data were analyzed using SPSS 25.0 for Windows., Setting: Study centers were from Maharashtra, Gujarat, Chhattisgarh, Assam, Tamil Nadu and Punjab from 40 selected schools., Participant: Children aged 3-18 years were measured., Results: Data on 14339 subjects (7413 boys) were analyzed. Prevalence of obesity was 5.8% and overweight-10.6%. Overall, 1% had low (<3 mmol/L), 93.7% in reference range (3.9-7.2 mmol/L) and 5.3% had elevated RBG (>7.2 mmol/L). With increasing mean BMI, there was increase in RBG concentrations. Children from Tamil Nadu were more likely to have RBG outside reference range compared to other regions ( P < 0.05). Assam and Punjab had highest prevalence of RBG and BMI within reference range. Energy intake partly explained regional variations. Multivariate analysis showed male gender, urban residency, age >10 yrs (girls) and 13 yrs (boys), and overweight or obesity were predictive of prediabetes., Conclusion: Increased prevalence of overweight, obesity and prediabetes in Indian children are a matter of concern. Regional differences suggest that strategies to prevent obesity and combat perturbations in blood sugar may have to be customized., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Endocrinology and Metabolism.)

Background: Sitting height (StH) percentiles are not described for the Indian paediatric population. Aim: To generate multicentre StH percentile values for Indian children. Subjects and methods: A total of 7961 apparently healthy children (3-17 years old, Boys: 4328) randomly selected from 10 schools from six states of India were measured for height (ht), StH and weight during July 2016-October 2017. Results: The StH:Ht ratio was 0.52 (0.02) and was similar between boys and girls ( p  > 0.1). The ratio decreased in boys until the age of 14 years and then slightly increased; the lowest ratio was observed during 13-15 years. In girls, however, the StH:Ht ratio decreased until the age of 9 years and then plateaued until 15 years of age with a slight increase at 16 years; the lowest ratio was observed at the age of 12-13 years. Sitting height percentiles (3rd, 10th, 25th, 50th, 75th, 90th and 97th) were computed using LMS chartmaker. Conclusions: The results indicate that, during the pubertal years, the lower limb growth is more predominant than trunk growth. Further, this study provides smoothened percentile curves for sitting height in Indian children for the first time.

Background: Actigraphy is commonly used to measure sleep outcomes so that sleep can be measured conveniently at home over multiple nights. Actigraphy has been validated in people with sleep disturbances; however, the validity of scoring settings in people with chronic medical illnesses such as chronic obstructive pulmonary disease remains unclear. The purpose of this secondary analysis was to compare actigraphy-customized scoring settings with polysomnography (PSG) for the measurement of sleep outcomes in people with chronic obstructive pulmonary disease who have insomnia., Methods: Participants underwent overnight sleep assessment simultaneously by PSG and actigraphy at the University of Illinois of Chicago Sleep Science Center. Fifty participants (35 men and 15 women) with mild-to-severe chronic obstructive pulmonary disease and co-existing insomnia were included in the analysis. Sleep onset latency, total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE) were calculated independently from data derived from PSG and actigraphy. Actigraphy sleep outcome scores obtained at the default setting and several customized actigraphy settings were compared to the scored PSG results., Results: Although no single setting was optimal for all sleep outcomes, the combination of 10 consecutive immobile minutes for sleep onset or end and an activity threshold of 10 worked well. Actigraphy overestimated TST and SE and underestimated WASO, but there was no difference in variance between PSG and actigraphy in TST and SE when the 10 × 10 combination was used. As the average TST and SE increased, the agreement between PSG and actigraphy appeared to increase, and as the average WASO decreased, the agreement between PSG and actigraphy appeared to increase., Conclusion: Results support the conclusion that the default actigraphy settings may not be optimal for people with chronic obstructive pulmonary disease and co-existing insomnia., (Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.)

Symptoms of narcolepsy tend to arise during adolescence or young adulthood, a formative time in human development during which people are usually completing their education and launching a career. Little is known about the impact of narcolepsy on the social aspects of health-related quality of life in young adults. The purpose of this study was to examine relationships between health-related stigma, mood (anxiety and depression) and daytime functioning in young adults with narcolepsy compared to those without narcolepsy. Young adults (age 18-35) with narcolepsy (N = 122) and without narcolepsy (N = 93) were mailed a packet that included questionnaires and a self-addressed postage paid envelope. The questionnaire included demographic information and a composite of instruments including the SF 36, Functional Outcomes of Sleep Questionnaire (FOSQ), Fife Stigma Scale (FSS), Epworth Sleepiness Scale (ESS) and Hospital Anxiety and Depression Scale (HADS). Variable associations were assessed using descriptive statistics, ANOVA, Mann-Whitney U Test, correlations, stepwise multiple regression and path analysis. Young adults with narcolepsy perceived significantly more stigma and lower mood and health-related quality of life than young adults without narcolepsy (p<0.01). Health-related stigma was directly and indirectly associated with lower functioning through depressed mood. Fifty-two percent of the variance in functioning was explained by the final model in the young adults with narcolepsy. Health-related stigma in young adults with narcolepsy is at a level consistent with other chronic medical illnesses. Health-related stigma may be an important determinant of functioning in young adults with narcolepsy. Future work is indicated toward further characterizing stigma and developing interventions that address various domains of stigma in people with narcolepsy.

Background: Hepatitis B virus (HBV) infection is an occupational health hazard among the healthcare workers. Vaccination against HBV has been established to be the most effective preventive strategy. The present study was designed to assess the efficacy of low dose intradermal HBV vaccine among the nursing staff in a tertiary care hospital setting., Patients and Methods: Staff nurses working in our hospital were included in the study as vaccine recipients. Each staff nurse was tested for HBsAg and anti-HBs (commercial ELISA). Those who tested negative for both the above markers were randomized to receive either three doses of intramuscular (i.m.) HBV vaccine (20 micrograms m each dose) at 0, 1 and 6 month interval or three doses of intradermal HBV vaccine (2 micrograms m each dose) at similar intervals. Each vaccine recipient was tested for the presence of anti HBs (commercial ELISA) at the end of 1 month and 1 year after the last dose of the vaccine. The anti-HBs titres were also estimated simultaneously in them., Results: Out of 153 staff nurses screened, 19 were either positive for HBsAg (n = 1) or anti HBs (n = 18). 96(72%) of the remaining 134 nurses agreed to receive HBV vaccine (i.m.--48, intradermal--48). At the end of 1 month after last dose of the vaccine, all vaccinees in both the group tested positive for anti-HBs. However the anti-HBs titres at 1 month were significantly higher among intramuscular vaccinees than the nurses receiving the vaccine through intra-dermal route (253 +/- 127.7 mIU/ml vs 151.3 +/- 92.8 mIU/ml, P < 0.001). Eighty four (85.5%) of these 96 vaccine recipient were available for evaluation of anti-HBs titre at the end of 1 year after the last dose of vaccine (1M group = 40, Intradermal group = 44). All the nurses continued to be positive for anti-HBs at the end of 1 year but the anti HBs-titre among i.m. vaccine recipient continued to remain at a significantly higher level than the similar titre among the intradermal vaccine recipients (256.4 +/- 124.7 mIU/ml vs 121.6 +/- 122.4 mIU/ml p < 0.001)., Conclusion: Intradermal route for HBV vaccine had similar immunogenic efficacy as the conventional intramuscular route, but the dose required in the former route is one tenth of the intramuscular route. Therefore intradermal route may reduce the cost of HBV vaccine markedly.