The Antiviral Mechanism of Action of Molnupiravir in Humans with COVID-19 (preprint)

Meaningful metrics of antiviral activity are essential for determining the efficacy of therapeutics in human clinical trials. Molnupiravir (MOV) is a broadly acting antiviral nucleoside analog prodrug that acts as a competitive alternative substrate for the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). We developed an assay, Culture-PCR, to better understand the impact of MOV therapy on infectious SARS-CoV-2. Culture-PCR revealed MOV eliminated infectious virus within 48 hours in the nasopharyngeal compartment, the upper airway location with the greatest levels of infectious virus. MOV therapy was associated with increases in mutations across the viral genome but select regions were completely unaffected, thus identifying regions where mutation likely abrogates infectivity. MOV therapy did not alter the magnitude or neutralization capacity of the humoral immune response, a documented correlate of protection. Thus, we provide holistic insights into the function of MOV in adults with COVID-19.

Risk of 12-month mortality following a severe inpatient hypoglycaemic event: A single centre retrospective study from the North-West of England

Aims: At our Trust, all severe inpatient hypoglycaemic episodes in individuals with diabetes (defined as a hypoglycaemic episode requiring injectable treatment) are reported to NaDIA-Harms (National Diabetes Inpatient Audit). We conducted a detailed review of the care of all these events to improve patient safety. In this study, we assessed the risk of 12-month mortality following an episode of severe inpatient hypoglycaemia. Method(s): Reportable NaDIA harms of patients admitted during the period 2018-2022 were recorded into a dataset. Applicable patient records were reviewed at 12 months following the event to see how many patients were deceased and details of comorbidities at the time of the severe hypoglycaemic episode were collected. Result(s): To date, of 107 inpatients who experienced a severe hypoglycaemic episode 55% were deceased within 12 months. In patients admitted during the peak of the Covid-19 pandemic recorded as year April 2020/March 2021, 80% of patients who had a NaDIA hypoglycaemic event died within 12 months. Conclusion(s): Mortality rate following an episode of inpatient hypoglycaemia appears to be several-fold higher than previous reported rates of 4.45%-22.1% for community-dwelling individuals who experience a severe hypoglycaemic event. This maybe partially explained by the increased frailty, polypharmacy and multimorbidity among this cohort, but there is evidence linking hypoglycaemia with cardiovascular mortality. Although no causality between severe inpatient hypoglycaemia and death can be inferred from this study because of the observational nature, it does highlight the importance preventing inpatient episodes of hypoglycaemia through effective monitoring and proactive treatment modification.

Effects of the Good Behavior Game on Students' Academic Engagement in Remote Classrooms During the COVID-19 Pandemic

This multiple-baseline design study examined the effects of the Good Behavior Game (GBG) on class-wide academic engagement in online general education classrooms. Teachers in three third- through fifth-grade classrooms implemented the GBG remotely during the COVID-19 pandemic. Treatment integrity was supported using aspects of implementation planning and by providing emailed performance feedback. Teachers' perceived usability and students' perceived acceptability of the GBG were assessed. Visual analysis results indicated two clear demonstrations of an effect, but experimental control was limited by smaller and delayed effects in one classroom. Statistical analyses of the data suggest that implementing the GBG was associated with moderate to strong, statistically significant improvements in students' academic engagement in all three classrooms. Teachers reported that the GBG was usable in their online classrooms, and students reported finding the intervention acceptable to participate in remotely. These results provide initial support for further examining the effectiveness and social validity of using the GBG to improve elementary students' academic engagement during remote instruction.

Low Barrier Tele-Buprenorphine in the Time of COVID-19: A Case Report

Background: To reduce the spread of coronavirus disease 2019 (COVID-19), many substance use disorder treatment programs have transitioned to telemedicine. Emergency regulatory changes allow buprenorphine initiation without an in-person visit. We describe the use of videoconferencing for buprenorphine initiation combined with street outreach to engage 2 patients experiencing homelessness with severe opioid use disorder (OUD). Case Presentation: Patient 1 was a 30-year-old man with severe OUD who had relapsed to injection heroin/fentanyl after incarceration. A community drop-in center outreach harm reduction specialist facilitated a videoconference with an addiction specialist at an OUD bridge clinic. The patient completed a community buprenorphine/naloxone initiation and self-titrated to his prior dose, 8/2 mg twice daily. One week later, he reconnected with the outreach team for a follow-up videoconference visit. Patient 2, a 36-year-old man with severe OUD, connected to the addiction specialist via a syringe service program harm reduction specialist. He had been trying to connect to a community buprenorphine/naloxone provider, but access was limited due to COVID-19, so he was using diverted buprenorphine/naloxone to reduce opioid use. He was restarted on his previous dose of 12/3 mg daily which was continued via phone follow-up 16 days later. Conclusion(s): COVID-19-related regulatory changes allow buprenorphine initiation via telemedicine. We describe 2 cases where telemedicine was combined with street outreach to connect patients experiencing homelessness with OUD to treatment. These cases highlight an important opportunity to provide access to life-saving OUD treatment for vulnerable patients in the setting of a pandemic that mandates reduced face-to-face clinical interactions.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.

Development of a Questionnaire on Access to Sickle Cell Disease Care in the Indigenous Tharu Population of Nepal

Purpose of Study Sickle cell disease (SCD) disproportionately affects the Tharu population of Nepal, a marginalized indigenous group concentrated in the Dang district. SCD is a structural hemoglobinopathy resulting in abnormal red blood cells with a tendency to occlude microvasculature. Since 2015, University of British Columbia medical students and a local community partner, Creating Possibilities, have improved access to SCD screening and diagnosis for the Tharu population. However, interviews conducted in 2016- 2017 found that SCD-afflicted community members encounter a number of challenges to obtain treatment once diagnosed. The purpose of this study was to develop a questionnaire on barriers to accessing SCD care in this community. Methods Used The Barriers to Accessing SCD Care Questionnaire was developed from items in existing scales, deductive and inductive item generation, and feedback from expert local partners. Reviewing literature on barriers to accessing healthcare in the Western region of Nepal informed region-specific questionnaire items, while literature on accessing SCD treatment in resource-limited settings informed SCD-specific questionnaire items. We also reviewed the literature on barriers to treatment for various stigmatized chronic health conditions in low-resource settings. Summary of Results Qualitative interviews with SCD-afflicted Tharu individuals in 2016-2017 identified inadequate local medical resources, transportation, financial strain, and limited awareness as barriers to care. Based on the literature review, we organized all survey items under the themes transportation, medical infrastructure, finances, community attitudes, and personal attitudes. The questionnaire includes closed-ended questions using a Likert scale, as well as open-ended interview prompts. It was made in collaboration with local community members to ensure it is culturally appropriate, needs-specific, and easily understandable. The questionnaire received ethics board approval, and interviews will begin once local health authorities lift COVID-19 restrictions. Conclusions Results from the Barriers to Accessing SCD Care questionnaire will guide future community-based interventions.

University of British Columbia Nepal Sickle Cell Project Status Report 2015-2020

Purpose of Study In 2015 the University of British Columbia partnered with Creating Possibilities (CP), a charitable organization located in Dang, Nepal. Each year, a team of medical students is sent to assist CP in the long term management of sickle cell disease (SCD) in rural Western Nepal. Due to COVID-19 limitations, we were unable to travel to Nepal this year for the field component of our project. Instead, we took this opportunity to reflect on the project as a whole and create a project status report, outlining the past five years of work. The purpose of this report included: summarizing overall project progress, identifying future project directions, and improving communication amongst project stakeholders. Methods Used To create the project status report, our team reviewed all project documents since 2015. We also conducted virtual interviews with previous team leads to clarify questions and fill in gaps. Project progress was assessed by comparing activities completed to date to the project's initial three main objectives. Summary of Results The first objective of characterizing the prevalence of SCD among the Tharu population is currently ongoing. Since 2015, we have conducted large-scale screening of the Tharu population, with 4483 individuals having been screened by our team. Thus far, a hemoglobin S prevalence of 9.3% has been estimated. Our second objective of identifying barriers to SCD management is also ongoing. Since 2016, yearly focus groups and needs assessments have been conducted with community members and health workers. Common themes of barriers included accessibility, financial limitations, and education. Finally, our third objective of implementing sustainable solutions for long term detection and management of SCD still needs to be addressed. Conclusions Screening and needs assessments will continue as we progress toward addressing our first two objectives. Following consultation with experts and a literature review, we have identified a pilot newborn screening program for SCD as the first step in addressing our third objective.

Use of a device-based remote management heart failure care pathway is associated with reduced hospitalization and improved patient outcomes: TriageHF Plus real-world evaluation

Background: Heart failure (HF) is a leading cause of hospital admission. However, prompt identification of worsening HF using implantable device data and proactive intervention may reduce hospitalizations. The validated TriageHF algorithm in enabled ICD/CRT devices uses sensor data to risk stratify patients for HF hospitalization in the next 30 days. TriageHF Plus is a novel device-based HF care pathway (DHFP) that uses high risk status as the trigger for remote intervention (see Figure 1 for pathway overview). Outcomes after DHFP implementation in a clinical setting have not been examined. Purpose(s): To evaluate the impact of TriageHF Plus clinical pathway on hospitalisation rates. Method(s): A prospective, multi-center evaluation comparing monthly hospitalization rates for patients enrolled in a DHFP with a concurrent standard of care (SoC) cohort and characterizing staffing resources necessary to implement the DHFP. The DHFP cohort received telephonic assessment and guideline-directed clinical care upon transition to high-risk status. Propensity scores (PS) were applied to DHFP and SoC cohorts to allow unbiased comparison. A negative binomial model was fitted to the monthly number of all-cause hospitalizations with treatment group (DHFP vs. SoC) as a covariate, using PS as weights. Result(s): Between 09/11/2019 and 06/24/2021, 758 patients were included in the study (443 DHFP, 315 SoC). Proportion CRT 76%/ 89% and LVEF <50% 78%/ 66% for DHFP/ SoC, respectively. 196 high risk transmissions prompted telephone assessment, with successful contact in 182;of which, 79 (43%) identified an explanatory acute medical issue. A secondary intervention was undertaken in 44/79 (56%). High risk transmissions took on average 19 minutes per clinical assessment (initial telephone triage and 30 day follow up). The rate of hospitalizations was 58% lower in the DHFP group, compared with SoC, after PS adjustment (IRR 0.42, 95% CI: 0.23, 0.76, p=0.004), see Figure 2. Sensitivity analyses showed Covid-19 had little effect on results. Conclusion(s): This is the first prospective, real-world evaluation of a device-based HF care pathway to report a reduction in hospitalizations and does so with minimal staffing time. Integrated into existing HF services, device-based remote monitoring of HF patients can improve outcomes. (Figure Presented) .

Economic impact of nature-based tourism.

Protected areas (PAs) can help address biodiversity loss by promoting conservation while fostering economic development through sustainable tourism. Nature-based tourism can generate economic benefits for communities in and around PAs; however, its impacts do not lend themselves to conventional impact evaluation tools. We utilize a Monte Carlo simulation approach with econometric estimations using microdata to estimate the full economic impact of nature-based tourism on the economies surrounding three terrestrial and two marine PAs. Simulations suggest that nature-based tourism creates significant economic benefits for communities around PAs, including the poorest households, and many of these benefits are indirect, via income and production spillovers. An additional tourist increases annual real income in communities near the PAs by US$169-$2,400, significantly more than the average tourist's expenditure. Conversely, lost tourism due to the COVID-19 pandemic and economic costs of human-wildlife conflict have disproportionately large negative impacts on local incomes.

Preserved T cell but attenuated antibody response in MS patients on fingolimod and ocrelizumab following 2nd and 3rd SARS-CoV-2 mRNA vaccine.

Background: There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. Objectives: Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination. Methods: We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab. Results: After 2-vax, 8/33 (24.2%) patients in ocrelizumab group, 5/7 (71.4%) in fingolimod group, and 29/29 (100%) in HC group (P = 5.7 × 10-11) seroconverted. After 3-vax, 9/22 (40.9%) patients in ocrelizumab group, 19/21 (90.5%) in fingolimod group, and 7/7 (100%) in HC group seroconverted (P = 0.0003). The percentage of SARS-CoV-2 peptide reactive total CD4+ T cells increased in HC and ocrelizumab group but not in fingolimod group after 2-vax and 3-vax (P < 0.0001). The percentage of IFNγ and TNFα producing total CD4+ and CD8+ T cells increased in fingolimod group as compared to HC and ocrelizumab group after 2-vax and 3-vax (P < 0.0001). Conclusions: MS patients on ocrelizumab and fingolimod had attenuated humoral responses, but preserved cytokine producing T cell responses compared to HCs after SARS-CoV-2 mRNA vaccination. Clinical Trials Registration: NCT05060354.

Retention strategies among those on community supervision in the South: Lessons learned during the COVID-19 pandemic.

OBJECTIVES: Cohort studies must implement effective retention strategies to produce internally valid and generalizable results. Ensuring all study participants are retained, particularly those involved in the criminal legal system, ensures study findings and future interventions will be relevant to this group, who are often lost to follow-up: critical to achieving health equity. Our objective was to characterize retention strategies and describe overall retention among an 18-month longitudinal cohort study of persons on community supervision prior to and during the COVID-19 pandemic. METHODS: We implemented various retention strategy best-practices (e.g., multiple forms of locator information, training study staff on rapport building, study-branded items). During the COVID-19 pandemic, we developed and describe new retention strategies. We calculated overall retention and analyzed differences between those retained and lost to follow-up by demographic characteristics. RESULTS: Prior to the start of the COVID-19 pandemic, 227 participants enrolled across three sites (N = 46 North Carolina; N = 99 Kentucky; N = 82 Florida). Of these, 180 completed the final 18-month visit, 15 were lost to follow-up, and 32 were ineligible. This resulted in an overall retention of 92.3% (180/195). While most participant characteristics did not differ by retention status, a greater proportion of those experiencing unstable housing were lost to follow-up. CONCLUSION: Our findings highlight that when retention strategies are flexible, particularly during a pandemic, high retention is still achievable. In addition to retention best-practices (e.g., frequent requests for updated locator information) we suggest other studies consider retention strategies beyond the study participant (e.g., paying participant contacts) and incentivize on-time study visit completion (e.g., providing a bonus when completed the study visit on time).

Anxiety, stress, and depression in Australian pregnant women during the COVID-19 pandemic: A cross sectional study.

BACKGROUND: The COVID-19 pandemic necessitated rapid responses by health services to suppress transmission of the virus. AIM: This study aimed to investigate predictors of anxiety, stress and depression in Australian pregnant women during the COVID-19 pandemic including continuity of carer and the role of social support. METHODS: Women aged 18 years and over in their third trimester of pregnancy were invited to complete an online survey between July 2020 and January 2021. The survey included validated tools for anxiety, stress, and depression. Regression modelling was used to identify associations between a range of factors including continuity of carer, and mental health measures. FINDINGS: 1668 women completed the survey. One quarter screened positive for depression, 19% for moderate or higher range anxiety, and 15.5% for stress. The most significant contribution to higher anxiety, stress, and depression scores was a pre-existing mental health condition, followed by financial strain and a current complex pregnancy. Protective factors included age, social support, and parity. DISCUSSION: Maternity care strategies to reduce COVID-19 transmission restricted women's access to their customary pregnancy supports and increased their psychological morbidity. CONCLUSION: Factors associated with anxiety, stress and depression scores during the COVID-19 pandemic were identified. Maternity care during the pandemic compromised pregnant women's support systems.

Advances in RT-LAMP for COVID-19 testing and diagnosis.

INTRODUCTION: The SARS-CoV-2 pandemic, and the subsequent limitations on standard diagnostics, has vastly expanded the user base of Reverse Transcription Loop-mediated isothermal Amplification (RT-LAMP) in fundamental research and development. RT-LAMP has also penetrated commercial markets, with emergency use authorizations for clinical diagnosis. AREAS COVERED: This review discusses the role of RT-LAMP within the context of other technologies like RT-qPCR and rapid antigen tests, progress in sample preparation strategies to enable simplified workflow for RT-LAMP directly from clinical specimens, new challenges with primer and assay design for the evolving pandemic, prominent detection modalities including colorimetric and CRISPR-mediated methods, and translational research and commercial development of RT-LAMP for clinical applications. EXPERT OPINION: RT-LAMP occupies a middle ground between RT-qPCR and rapid antigen tests. The simplicity approaches that of rapid antigen tests, making it suitable for point-of-care use, but the sensitivity nears that of RT-qPCR. RT-LAMP still lags RT-qPCR in fundamental understanding of the mechanism, and the interplay between sample preparation and assay performance. Industry is now beginning to address issues around scalability and usability, which could finally enable LAMP and RT-LAMP to find future widespread application as a diagnostic for other conditions, including other pathogens with pandemic potential.

Use of a device-based remote management heart failure care pathway is associated with reduced hospitalization and improved patient outcomes: TriageHF Plus real-world evaluation

Background: Heart failure (HF) is a leading cause of hospital admission. However, prompt identification of worsening HF using implantable device data and proactive intervention may reduce hospitalizations.The validated TriageHF algorithm in enabled ICD/CRT devices uses sensor data to risk stratify patients for HF hospitalization in the next 30 days. TriageHF Plus is a novel device-based HF care pathway (DHFP) that uses "high” risk status as the trigger for remote intervention (see Figure 1 for pathway overview). Outcomes after DHFP implementation in a clinical setting have not been examined. Purpose: To evaluate the impact of TriageHF Plus clinical pathway on hospitalisation rates. Methods: A prospective, multi-center evaluation comparing monthly hospitalization rates for patients enrolled in a DHFP with a concurrent standard of care (SoC) cohort and characterizing staffing resources necessary to implement the DHFP. The DHFP cohort received telephonic assessment and guideline-directed clinical care upon transition to high-risk status. Propensity scores (PS) were applied to DHFP and SoC cohorts to allow unbiased comparison. A negative binomial model was fitted to the monthly number of all-cause hospitalizations with treatment group (DHFP vs. SoC) as a covariate, using PS as weights. Results: Between 09/11/2019 and 06/24/2021, 758 patients were included in the study (443 DHFP, 315 SoC). Proportion CRT 76%/ 89% and LVEF <50% 78%/ 66% for DHFP/ SoC, respectively.196 high risk transmissions prompted telephone assessment, with successful contact in 182;of which, 79 (43%) identified an explanatory acute medical issue. A secondary intervention was undertaken in 44/79 (56%). High risk transmissions took on average 19 minutes per clinical assessment (initial telephone triage and 30 day follow up). The rate of hospitalizations was 58% lower in the DHFP group, compared with SoC, after PS adjustment (IRR 0.42, 95% CI: 0.23, 0.76, p=0.004), see Figure 2. Sensitivity analyses showed Covid-19 had little effect on results. Conclusions: This is the first prospective, real-world evaluation of a device-based HF care pathway to report a reduction in hospitalizations and does so with minimal staffing time. Integrated into existing HF services, device-based remote monitoring of HF patients can improve outcomes. Funding Acknowledgement: Type of funding sources: Private company. Main funding source(s): MedtronicFigure 1. Pathway OverviewFigure 2. Outcomes

Barriers and facilitators in the implementation of ASP in Mexico and the impact of COVID-19

Background. Hospital antimicrobial stewardship programs (ASP) involve a continuous effort by health institutions to monitor and optimize the use of antimicrobials. In this study, we aimed to explore barriers and opportunities in the implementation of ASP perceived by personnel of Mexican hospitals, as well as their views on the impact of COVID-19 in ASP activities. Methods. An online survey was applied to a purposive sample of 40 hospitals that perform regular antimicrobial stewardship activities in Mexico, during the last trimester of 2021. Results. A total of 40 hospitals (62.5% public and 37.5% private) in 13 states in Mexico responded to the survey. Regarding the perception of barriers, they identified the overload of activities (73%), hospital reconversion due to COVID-19 (65%), the scarcity of human resources, and resistance of personnel to new procedures (63% each). The main perceived facilitators were the support by hospital authorities (60%) and the commitment by the ASP team and health professionals in the implementation of ASP (48%). Only 15% of hospitals reported that support by health authorities or other hospitals were factors favoring implementation. The main reported changes due to COVID-19 were: temporary suspension of ASP activities (60%);greater workload due to increased prescription of antimicrobials (33%);involvement in interventions (such as education and guidelines) directed to improve antimicrobial use in COVID-19 patients (18%), as well as implementation of new protocols in pharmacy (44%) and microbiology laboratory (51%). 18% reported no changes in ASP. Conclusion. Implementation of ASP in Mexican Hospitals could be strengthened by the inclusion of sufficient human resources with protected time for ASP activities, the active involvement of hospital authorities, as well as encouraging the training and leadership of ASP teams. The impact of COVID-19 was two-way: the stagnation of the program in some hospitals, as well as the active participation in the response to the emergency, in other hospitals.

WHEN AND WHERE: LESSONS LEARNED ABOUT TECHNOLOGY FROM AN INTERVENTION FOR CAREGIVERS OF PERSONS WITH HEART FAILURE

Use of technology in older adult populations is growing, therefore it is important to understand opportunities for healthcare initiatives that support older adults using technology. The aim of the pilot study was to test Caregiver Support, a self-care and social support intervention, for caregivers of persons living with heart failure (N=24). Originally, the protocol was designed with in-person visits. We expected this option to reduce participant burden: the caregiver would not have to travel, and the interventionist would gain more insight about the home context to aid with intervention delivery. However, due to the COVID-19 pandemic, it became necessary to conduct the visits virtually. All participants completed the 5-component intervention via virtual meeting and there were no dropouts related to technology use. When asked about the virtual modality, participants emphasized the flexibility of virtual meetings. In summary, the intervention visits conducted virtually were perceived as a caregiver-centered approach.

Evaluating Student Learning Gain: A Study to Consider How Teaching Online During the Covid-19 Pandemic Affected Student Learning

Due to the Covid-19 pandemic and the resulting enforced national lockdowns, universities have had to replace in-person teaching with online alternatives. With the ongoing marketization of Higher Education, it is important to understand how this change in delivery may have impacted upon student learning. To assess student learning, this paper used a model for evaluating learning gain, which considered student learning in the form of explicit knowledge gained (distance travelled), which relates to codifiable models and theories, and tacit understanding (journey travelled), which relates to practical skills and know-how. Self-reflective surveys were used to collect learning gain data from final year students studying an organisational leadership module as part of an undergraduate business studies degree course at a UK university. The research collected data in 2019 (before the Covid-19 pandemic) for a cohort of students, and again in 2021 (during the Covid-19 pandemic) for the subsequent cohort of students. Through an analysis of both sets of data, a comparison has been possible between how students perceived their learning to have changed due to the alternative online educational delivery method being offered. Whereas a decrease in reported learning was expected from the online teaching, this was not always the case, and predominantly females appear to have particularly valued the educational experience offered by the online learning delivery. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

A comparison of methods for forecasting value at risk and expected shortfall of cryptocurrencies

Several procedures to forecast daily risk measures in cryptocurrency markets have been recently implemented in the literature. Among them, long-memory processes, procedures taking into account the presence of extreme observations, procedures that include more than a single regime, and quantile regression-based models have performed substantially better than standard methods in terms of forecasting risk measures. Those procedures are revisited in this paper, and their value at risk and expected shortfall forecasting performance are evaluated using recent Bitcoin and Ethereum data that include periods of turbulence due to the COVID-19 pandemic, the third halving of Bitcoin, and the Lexia class action. Additionally, in order to mitigate the influence of model misspecification and enhance the forecasting performance obtained by individual models, we evaluate the use of several forecast combining strategies. Our results, based on a comprehensive backtesting exercise, reveal that, for Bitcoin, there is no single procedure outperforming all other models, but for Ethereum, there is evidence showing that the GAS model is a suitable alternative for forecasting both risk measures. We found that the combining methods were not able to outperform the better of the individual models. © 2022 John Wiley & Sons Ltd.

ViralVar: A Web Tool for Multilevel Visualization of SARS-CoV-2 Genomes.

The unprecedented growth of publicly available SARS-CoV-2 genome sequence data has increased the demand for effective and accessible SARS-CoV-2 data analysis and visualization tools. The majority of the currently available tools either require computational expertise to deploy them or limit user input to preselected subsets of SARS-CoV-2 genomes. To address these limitations, we developed ViralVar, a publicly available, point-and-click webtool that gives users the freedom to investigate and visualize user-selected subsets of SARS-CoV-2 genomes obtained from the GISAID public database. ViralVar has two primary features that enable: (1) the visualization of the spatiotemporal dynamics of SARS-CoV-2 lineages and (2) a structural/functional analysis of genomic mutations. As proof-of-principle, ViralVar was used to explore the evolution of the SARS-CoV-2 pandemic in the USA in pediatric, adult, and elderly populations (n > 1.7 million genomes). Whereas the spatiotemporal dynamics of the variants did not differ between these age groups, several USA-specific sublineages arose relative to the rest of the world. Our development and utilization of ViralVar to provide insights on the evolution of SARS-CoV-2 in the USA demonstrates the importance of developing accessible tools to facilitate and accelerate the large-scale surveillance of circulating pathogens.

The whole grain manifesto: From Green Revolution to Grain Evolution

Grains have historically represented a major component of human diets and were predominantly consumed in whole form until the first half of the 19th century, when a combination of technological innovations and market dynamics made refined grains, hitherto a premium product, affordable and available to the masses. Grains still account for more than half of the total caloric intake among vulnerable populations worldwide, and their dominant consumption in refined form turns a nutrient-dense, protective food into a nutrient-poor one contributing to growing rates of obesity and noncommunicable disease. Shifting a substantial portion of global grain consumption to whole grains is potentially one of the most significant and achievable improvements to diets and food systems worldwide. In countries with significant micronutrient deficiencies, a switch from refined to fortified whole grain foods can enable institutional channels such as school feeding programs to measurably improve diet quality in a budget-neutral way.