Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Potential role of Vitamin D in immune response in patients with viral hepatitis.

BACKGROUND: To study the relationship of Vitamin D with innate and adaptive immune response parameters in chronic hepatitis B and C patients. METHODS: The laboratory data between January 1, 2013 and February 1, 2023, for patients with chronic hepatitis B (CHB), and chronic hepatitis C (CHC) were extracted. Serum 25-hydroxyl vitamin D, hepatitis B virus serological markers, complements, and subsets of T lymphocytes were determined. Study cohorts were divided into groups based on serum 25-hydroxyl vitamin D levels with further evaluation of laboratory data. RESULTS: In CHB and CHC patients the percentage of CD4+ T lymphocytes and the CD4+/CD8+ ratio significantly decreased (P < 0.05), but the percentage of CD8+ increased (P < 0.05) compared to the control group. In CHB patients Vitamin D decrease was significant (P < 0.001) but not in CHC patients. Vitamin D showed a moderate negative influence on the CD8 cell count in CHB patients. The positive ratio of HBV DNA and HBsAg decreased with increasing serum vitamin D levels. The vitamin D deficient group showed significantly lower antibody production compared to the normal group, and exhibited significantly decreased CD4 numbers and increased CD8 numbers (P < 0.05 and P < 0.001, respectively), while the CD4/CD8 ratio was also significantly decreased in the insufficiency group (P < 0.001). Complement C3 levels were not associated with CD4 and CD8, but had an inverse relation with Vitamin D. Vitamin D levels were significantly associated with complement C3, CD8+, CD4+, CD19+ cells, and HBV DNA levels. CONCLUSIONS: Vitamin D may be a modulator of immune function not only via CD8+ and CD4+ cells but also via CD19+ cells in the course of chronic HBV infection. The negative relationship between vitamin D and complement C3 needs elucidation. Moreover, the increased proportion of B cells and decreased CD4+ cells in Vitamin D deficiency disrupt the immune response against HBV since the expected antibody response was not obtained despite the increase in B cell ratio. This indicates an influence of CD4+ cells for B cell functionality. In summary, sufficient levels of Vitamin D may lead to a sustained virological response that is debatable by artificially correcting the deficiency.

Investigating the effect of a school-based WASH intervention on soil-transmitted helminth and schistosome infections and nutritional status of school children in Ethiopia: a quasi-experimental study.

BACKGROUND: The impact of access to improved water, sanitation and hygiene (WASH) and health education on large-scale deworming programs aimed at controlling soil-transmitted helminth (STH) and schistosome (SCH) infections has not been well studied. We assessed the additional impact of improved WASH infrastructure and health education at schools on STH and SCH infections in Ethiopia. METHODS: The study used a quasi-experimental design under which 30 schools were assigned to either an intervention (15 schools) or control (15 schools) arm. Both arms received a standard deworming treatment and lunch. In the intervention arm, improved WASH and health education were provided. At three consecutive time points (baseline in 2013, 2014 and 2015), the prevalence and intensity of STH and SCH infections and the nutritional status [hemoglobin concentrations and physical growth (height and weight)] were determined. To verify whether interventions were successfully implemented, the WASH status at school and the student knowledge, attitudes and practices related to WASH (WASH-KAP) were recorded. Differences in metrics between arms at baseline (2013) and follow-up (2015) were assessed both within and between the arms. RESULTS: A significant increase in scores for both the school WASH and student KAP was found in the intervention arm, indicating successful implementation of the intervention. The prevalence of any STH infection was significantly reduced in the intervention arm but not in the control arm (F = 4.486, p = 0.034). There was a significantly greater reduction in the intensity of infection of hookworm and Ascaris lumbricoides compared to baseline in both arms. The intervention did not affect school children's height-for-age z-score (intervention arm * time coef = 0.12, p = 0.400) and body mass index-for-age z-scores (intervention * time coef = - 0.06, p = 0.526). Hemoglobin concentrations increased significantly more in the control than the intervention arm (coef = - 0.16, p = 0.006). CONCLUSIONS: Although the intervention did increase school WASH and student WASH-KAP, our study found poor evidence of the additional benefit of improved WASH and health education to deworming and school food programs on parasite re-infection and the health outcomes of children.

Hit-and-run or hit-and-stay? Unintended effects of a stricter BAC limit.

Although they comprise a relatively small subset of all traffic deaths, hit-and-run (HR) fatalities are both contemptible and preventable. We analyze longitudinal data from 1982 to 2008 to examine the effects of blood alcohol concentration (BAC) laws on HR traffic fatalities. Our results suggest that lower BAC limits may have an unintended consequence of increasing HR fatalities, whereas a similar effect is absent for non-HR fatalities. Specifically, we find that the adoption of a 0.08 BAC limit is associated to an 8.3% increase in HR fatalities. This unintended effect is more pronounced in urban areas and during weekends, which are typical settings for HR incidents.

Assembly and disassembly of branched ubiquitin chains.

Protein ubiquitylation is an essential post-translational modification that regulates nearly all aspects of eukaryotic cell biology. A diverse collection of ubiquitylation signals, including an extensive repertoire of polymeric ubiquitin chains, leads to a range of different functional outcomes for the target protein. Recent studies have shown that ubiquitin chains can be branched and that branched chains have a direct impact on the stability or the activity of the target proteins they are attached to. In this mini review, we discuss the mechanisms that control the assembly and disassembly of branched chains by the enzymes of the ubiquitylation and deubiquitylation machinery. Existing knowledge regarding the activities of chain branching ubiquitin ligases and the deubiquitylases responsible for cleaving branched chains is summarized. We also highlight new findings concerning the formation of branched chains in response to small molecules that induce the degradation of otherwise stable proteins and examine the selective debranching of heterotypic chains by the proteasome-bound deubiquitylase UCH37.

A general framework to support cost-efficient fecal egg count methods and study design choices for large-scale STH deworming programs-monitoring of therapeutic drug efficacy as a case study.

BACKGROUND: Soil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in stool. METHODS: We performed an in-depth analysis of the operational costs to process one stool sample for three diagnostic methods (Kato-Katz, Mini-FLOTAC and FECPAKG2). Next, we performed simulations to determine the probability of detecting a truly reduced therapeutic efficacy for different scenarios of STH species (Ascaris lumbricoides, Trichuris trichiura and hookworms), pre-treatment infection levels, survey design (screen and select (SS); screen, select and retest (SSR) and no selection (NS)) and number of subjects enrolled (100-5,000). Finally, we integrated the outcome of the cost assessment into the simulation study to estimate the total survey costs and determined the most cost-efficient survey design. PRINCIPAL FINDINGS: Kato-Katz allowed for both the highest sample throughput and the lowest cost per test, while FECPAKG2 required both the most laboratory time and was the most expensive. Counting of eggs accounted for 23% (FECPAKG2) or ≥80% (Kato-Katz and Mini-FLOTAC) of the total time-to-result. NS survey designs in combination with Kato-Katz were the most cost-efficient to assess therapeutic drug efficacy in all scenarios of STH species and endemicity. CONCLUSIONS/SIGNIFICANCE: We confirm that Kato-Katz is the fecal egg counting method of choice for monitoring therapeutic drug efficacy, but that the survey design currently recommended by WHO (SS) should be updated. Our generic framework, which captures laboratory time and material costs, can be used to further support cost-efficient choices for other important surveys informing STH control programs. In addition, it can be used to explore the value of alternative diagnostic techniques, like automated egg counting, which may further reduce operational costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.

Interpreting Suicide Notes: A Tripartite Method.

This paper will present a new method of interpreting suicide notes. It will begin with a discussion of the limitations of interpreting suicide notes. The paper will then clarify the purpose of interpretation as attempt at communication and how to understand the suicide note as an object of interpretation. This is followed by introduction of three traditional methods of interpretation: the pluralist, intentionalist, and psychoanalytic methods. Each suicide note is then interpreted using the appropriate method. The paper culminates in presenting a method to interpret suicide notes as a form of self-narration. This interpretation is done by using a tripartite method which combines the three previous methods as a way of focusing on the author's self-narration. The paper culminates in demonstrating the tripartite method and shows its effectiveness in elucidating the role of self-narrative in the suicide note.

Defining elimination as a public health problem for schistosomiasis control programmes: beyond prevalence of heavy-intensity infections.

WHO's 2021-30 road map for neglected tropical diseases (NTDs) outlines disease-specific and cross-cutting targets for the control, elimination, and eradication of NTDs in affected countries. For schistosomiasis, the criterion for elimination as a public health problem (EPHP) is defined as less than 1% prevalence of heavy-intensity infections (ie, ≥50 Schistosoma haematobium eggs per 10 mL of urine or ≥400 Schistosoma mansoni eggs per g of stool). However, we believe the evidence supporting this definition of EPHP is inadequate and the shifting distribution of schistosomiasis morbidity towards more subtle, rather than severe, morbidity in the face of large-scale control programmes requires guidelines to be adapted. In this Viewpoint, we outline the need for more accurate measures to develop a robust evidence-based monitoring and evaluation framework for schistosomiasis. Such a framework is crucial for achieving the goal of widespread EPHP of schistosomiasis and to meet the WHO road map targets. We encourage use of overall prevalence of schistosome infection (instead of the prevalence of heavy-intensity infections), development of species-dependent and age-dependent morbidity markers, and construction of a standardised monitoring and evaluation protocol.

The Intraoperative Pelvic Radiograph During Total Hip Arthroplasty: Is It Reliable to Estimate Leg Length?

Background: Symptomatic leg length discrepancies (LLDs) are a significant complication after total hip arthroplasty. Many surgeons incorporate an intraoperative anteroposterior pelvis radiograph, to help prevent LLD; however, obtaining a high-quality radiograph is often difficult. The purpose of this study is to evaluate the accuracy and reliability of estimating LLD using different radiographic reference landmarks on suboptimal anteroposterior pelvis radiographs. Material and methods: We obtained 2 pelvis Sawbones models with attached femurs and created a true shortening of the left femur of the experimental model by 7 mm. We then obtained a series of radiographs manipulating each model in standardized increments for a total of 66 different permutations of suboptimal radiographs. Each radiograph was evaluated for LLD by 2 separate orthopedic surgeons using reference lines bisecting the following anatomic landmarks: ischial tuberosities, acetabular teardrops, obturator foramina, sacroiliac joints, and the femoral heads, to the lesser trochanters. The accuracy and reliability of each line were then analyzed. Results: The obturator foramina line yielded the most reliable LLD estimates with an intraclass correlation coefficient of 0.939. This reference line was also the most accurate, with an average difference of 1.5 mm from the true LLD (P < .001), with 95% confidence to be within 1.8 mm. Conclusion: The obturator foramen reference line on an intraoperative radiograph is an accurate and reliable tool that should be utilized by joint replacement surgeons to estimate LLD even if the radiograph is suboptimal. This estimate is reliably reproduced among multiple observers and puts the estimate within 1.8 mm of a true LLD.

National mapping of schistosomiasis, soil-transmitted helminthiasis and anaemia in Yemen: Towards better national control and elimination.

BACKGROUND: Schistosomiasis (SCH) and soil-transmitted helminthiasis (STH) are known to be endemic in Yemen. However, the distribution of both diseases had not previously been assessed by a well-structured national mapping study covering all governorates. The main aim of this study was, therefore, to map the prevalence of SCH and STH in Yemen in order to better inform implementation of effective national control and elimination interventions. The assessment of the distribution of anaemia was also included as a well-known consequence of infection with both SCH and STH. Secondarily, the study aimed to provide a broad indication of the impact of large-scale treatment on the distribution of infection. METHODOLOGY AND PRINCIPAL FINDINGS: To achive these aims, 80,432 children (10-14 years old) from 2,664 schools in 332 of Yemen's 333 districts were included, in 2014, into this national cross-sectional survey. Countrywide, 63.3% (210/332) and 75.6% (251/332) of districts were found to be endemic for SCH and STH respectively. More districts were affected by intestinal than urogenital SCH (54.2% and 31.6% respectively). SCH infection was mostly mild and moderate, with no districts reporting high infection. One quarter (24.4%) of Yemeni districts had high or moderate levels of Ascaris lumbricoides infection. Infection with Trichuris trichiura was the second most common STH (44.9% of districts infected) after A. lumbricoides (68.1%). Hookworm was the least prevalent STH (9.0%). Anaemia was prevalent in 96.4% of districts; it represented a severe public health problem (prevalence ≥ 40%) in 26.5% of districts, and a mild to moderate problem in two thirds of the districts (33.7% and 36.1% respectively). CONCLUSION: This study provided the first comprehensive mapping of SCH, STH, and anaemia across the country. This formed the basis for evaluating and continuing the national control and elimination programme for these neglected tropical diseases in Yemen.

Societal Costs and Outcomes of Medical and Recreational Marijuana Policies in the United States: A Systematic Review.

Significant support exists in the United States for legalization of marijuana/cannabis. As of 2021, 36 states and four territories approved the legalization of medical cannabis via medical marijuana laws (MMLs), and 15 states and District of Columbia (DC) have adopted recreational marijuana laws (RMLs). We performed structured and systematic searches of articles published from 2010 through September 2021. We assess the literature pertaining to adolescent marijuana use; opioid use and opioid-related outcomes; alcohol use; tobacco use; illicit and other drug use; marijuana growing and cultivation; employment, earnings, and other workplace outcomes; academic achievement and performance; criminal activity; perceived harmfulness; traffic and road safety; and suicide and sexual activity. Overall, 113 articles satisfied our inclusion criteria. Except for opioids, studies on use of other substances (illicit drugs, tobacco, and alcohol) were inconclusive. MMLs and RMLs do not generate negative outcomes in the labor market, lead to greater criminal activity, or reduce traffic and road safety.

Effect of preventive chemotherapy with praziquantel on schistosomiasis among school-aged children in sub-Saharan Africa: a spatiotemporal modelling study.

BACKGROUND: Over the past 20 years, schistosomiasis control has been scaled up. Preventive chemotherapy with praziquantel is the main intervention. We aimed to assess the effect of preventive chemotherapy on schistosomiasis prevalence in sub-Saharan Africa, comparing 2000-10 with 2011-14 and 2015-19. METHODS: In this spatiotemporal modelling study, we analysed survey data from school-aged children (aged 5-14 years) in 44 countries across sub-Saharan Africa. The data were extracted from the Global Neglected Tropical Diseases database and augmented by 2018 and 2019 survey data obtained from disease control programmes. Bayesian geostatistical models were fitted to Schistosoma haematobium and Schistosoma mansoni survey data. The models included data on climatic predictors obtained from satellites and other open-source environmental databases and socioeconomic predictors obtained from various household surveys. Temporal changes in Schistosoma species prevalence were estimated by a categorical variable with values corresponding to the three time periods (2000-10, 2011-14, and 2015-19) during which preventive chemotherapy interventions were scaled up. FINDINGS: We identified 781 references with relevant geolocated schistosomiasis survey data for 2000-19. There were 19 166 unique survey locations for S haematobium and 23 861 for S mansoni, of which 77% (14 757 locations for S haematobium and 18 372 locations for S mansoni) corresponded to 2011-19. Schistosomiasis prevalence among school-aged children in sub-Saharan Africa decreased from 23·0% (95% Bayesian credible interval 22·1-24·1) in 2000-10 to 9·6% (9·1-10·2) in 2015-19, an overall reduction of 58·3%. The reduction of S haematobium was 67·9% (64·6-71·1) and that of S mansoni 53·6% (45·2-58·3) when comparing 2000-10 with 2015-19. INTERPRETATION: Our model-based estimates suggest that schistosomiasis prevalence in sub-Saharan Africa has decreased considerably, most likely explained by the scale-up of preventive chemotherapy. There is a need to consolidate gains in the control of schistosomiasis by means of preventive chemotherapy, coupled with other interventions to interrupt disease transmission. FUNDING: European Research Council and WHO.

Control and Elimination of Schistosomiasis as a Public Health Problem: Thresholds Fail to Differentiate Schistosomiasis Morbidity Prevalence in Children.

BACKGROUND: Current World Health Organization guidelines utilize prevalence of heavy-intensity infections (PHIs), that is, ≥50 eggs per 10 mL of urine for Schistosoma haematobium and ≥400 eggs per gram of stool for S. mansoni, to determine whether a targeted area has controlled schistosomiasis morbidity or eliminated schistosomiasis as a public health problem. The relationship between these PHI categories and morbidity is not well understood. METHODS: School-age participants enrolled in schistosomiasis monitoring and evaluation cohorts from 2003 to 2008 in Burkina Faso, Mali, Niger, Tanzania, Uganda, and Zambia were surveyed for infection and morbidity at baseline and after 1 and 2 rounds of preventive chemotherapy. Logistic regression was used to compare morbidity prevalence among participants based on their school's PHI category. RESULTS: Microhematuria levels were associated with the S. haematobium PHI categories at all 3 time points. For any other S. haematobium or S. mansoni morbidity that was measured, PHI categories did not differentiate morbidity prevalence levels consistently. CONCLUSIONS: These analyses suggest that current PHI categorizations do not differentiate the prevalence of standard morbidity markers. A reevaluation of the criteria for schistosomiasis control is warranted.

The Application of a Hospital Medical Surge Preparedness Index to Assess National Pandemic and Other Mass Casualty Readiness.

EXECUTIVE SUMMARY: This article describes the use and findings of the Hospital Medical Surge Preparedness Index (HMSPI) tool to improve the understanding of hospitals' ability to respond to mass casualty events such as the COVID-19 pandemic. For this investigation, data from the U.S. Census Bureau, the Dartmouth Atlas Project, and the 2005 to 2014 annual surveys of the American Hospital Association (AHA) were analyzed. The HMSPI tool uses variables from the AHA survey and the other two sources to allow facility, county, and referral area index calculations. Using the three data sets, the HMSPI also allows for an index calculation for per capita ratios and by political (state or county) boundaries. In this use case, the results demonstrated increases in county and state HMSPI scores through the period of analysis; however, no statistically significant difference was found in HMSPI scores between 2013 and 2014. The HMSPI builds on the limited scientific foundation of medical surge preparedness and could serve as an objective and standardized measure to assess the nation's medical readiness for crises such as the COVID-19 pandemic and other large-scale emergencies such as mass shootings. Future studies are encouraged to refine the score, assess the validity of the HMSPI, and evaluate its relevance in response to future legislative and executive policies that affect preparedness measures.

Trends in Health Care Utilization and Expenditures in the United States Across 5 Decades: 1977-2017.

BACKGROUND: Health care expenditures in the United States are high and rising, with significant increases over the decades. The delivery, organization, and financing of the health care system has evolved over time due to technological innovation, policy changes, patient preferences, altering payment mechanisms, shifting demographics, and other factors. OBJECTIVE: The objective of this study was to examine trends over time in health care utilization and expenditures in the United States. RESEARCH DESIGN: This analysis employs descriptive statistics to examine 5 decades of health care utilization and expenditure data from the Agency for Healthcare Research and Quality (AHRQ) for 1977-2017. MEASURES: Measures include utilization and expenditures (not charges) for inpatient, emergency department, outpatient physician, outpatient nonphysician, office-based physician, dental, and out-of-pocket retail prescription drugs. RESULTS: We demonstrate that while health care expenditures have increased significantly overall and by type of care, utilization trends are less pronounced. The population of the United States grew 53% between 1977 and 2017, while annual total expenditures on health care increased by 208%. Amidst attention to out-of-pocket exposure for unexpected medical care bills, out-of-pocket payments for care have declined from 32% in 1977 to 12% in 2017 but increased in amount. CONCLUSIONS: This article provides the first extended snapshot of the dynamics of health care utilization and expenditures in the United States. Aspects of health care are much different today than in previous decades, yet the inpatient setting still dominates the expenditures.

Associations between infection intensity categories and morbidity prevalence in school-age children are much stronger for Schistosoma haematobium than for S. mansoni.

BACKGROUND: World Health Organization (WHO) guidelines for measuring global progress in schistosomiasis control classify individuals with Schistosoma spp. infections based on the concentration of excreted eggs. We assessed the associations between WHO infection intensity categories and morbidity prevalence for selected S. haematobium and S. mansoni morbidities in school-age children. METHODOLOGY: A total of 22,488 children aged 6-15 years from monitoring and evaluation cohorts in Burkina Faso, Mali, Niger, Uganda, Tanzania, and Zambia from 2003-2008 were analyzed using Bayesian logistic regression. Models were utilized to evaluate associations between intensity categories and the prevalence of any urinary bladder lesion, any upper urinary tract lesion, microhematuria, and pain while urinating (for S. haematobium) and irregular hepatic ultrasound image pattern (C-F), enlarged portal vein, laboratory-confirmed diarrhea, and self-reported diarrhea (for S. mansoni) across participants with infection and morbidity data. PRINCIPAL FINDINGS: S. haematobium infection intensity categories possessed consistent morbidity prevalence across surveys for multiple morbidities and participants with light infections had elevated morbidity levels, compared to negative participants. Conversely, S. mansoni infection intensity categories lacked association with prevalence of the morbidity measures assessed. CONCLUSIONS/SIGNIFICANCE: Current status infection intensity categories for S. haematobium were associated with morbidity levels in school-age children, suggesting urogenital schistosomiasis morbidity can be predicted by an individual's intensity category. Conversely, S. mansoni infection intensity categories were not consistently indicative of childhood morbidity at baseline or during the first two years of a preventive chemotherapy control program.

Death on the job: The Great Recession and work-related traffic fatalities.

In light of recent discussions about shifting employees from traditional workplaces to virtual employment, we are motivated by the question of whether this phenomenon will end up saving lives even in the absence of an infectious disease outbreak. Motor vehicle incidents are the leading cause of work-related fatalities in the US, killing more than 1200 workers each year, which make up about a quarter of all work-related deaths. Not only are motor vehicle crashes the top killer at work, but economic expansions can further increase occupational and traffic deaths as they both tend to be procyclical. In this paper, we examine the effects of business cycles on traffic fatalities in the US with a special focus on work-related deaths. Specifically, we implement a longitudinal design across all 50 states by compiling quarterly data for 2004-2012 and consider macroeconomic fluctuations around the Great Recession. Our findings show that traffic deaths during prosperous times are not solely due to an increase in risky behaviors such as drunk driving, but directly related to work. Given the highly preventable nature of traffic crashes, policy makers, public health advocates, and employers can develop effective strategies, including remote work arrangements, to improve both occupational and traffic safety.

Preventive chemotherapy for the control of strongyloidiasis in school-age children: Estimating the ivermectin need.

BACKGROUND: Strongyloides stercoralis is a soil-transmitted helminth (STH) that affects approximately 600 million people worldwide. Interventions targeting S. stercoralis have not been implemented yet. Specific treatment (ivermectin) could be included in already ongoing preventive chemotherapy (PC) campaigns targeting other STHs. The aim of this study was to estimate the quantity of ivermectin needed for an integrated STH/S. stercoralis control program. METHODODOLOGY/PRINCIPAL FINDINGS: Our study estimates the number of school- age children (SAC) (the main focus of STH deworming campaigns) in need of PC with ivermectin. The normal approximation of the binomial distribution was adopted to calculate the hypothetical prevalence distribution in each endemic country. Considering prevalence thresholds for PC equal to 10%, 15%, and 20%, we estimated the number of SAC in need of treatment. We adjusted the estimates accounting for ivermectin distributed in lymphatic filariasis and onchocerciasis elimination programs and excluded from our calculation areas where Loa loa is endemic. The global number of SAC that should be targeted in PC campaigns was estimated at 283.9 M (95% CI: 163.4-368.8), 207.2 M (95% CI: 160.9-380.7), and 160.7 M (95% CI: 86.6-225.7) when the threshold for intervention was set to 10%, 15%, and 20%, respectively. India, China, Indonesia, Bangladesh, and Nigeria accounted for about 50% of the global SAC would have to be covered by PC intervention. CONCLUSIONS/SIGNIFICANCE: Our analysis may support endemic countries to evaluate the ivermectin quantity needed for integrating strongyloidiasis in the existing STH programs. These estimates might also show to generic drug manufacturers the size of the potential market for ivermectin and encourage its production.

The relationships between marijuana use and exercise among young and middle-aged adults.

As decriminalization, increased access, and decreased perception of risk spurs the popularity of medical and recreational marijuana, more information is needed on possible links between marijuana use and social determinants of health. The goal of this study was to assess the relationships between marijuana use and exercise. Data sources included the two most recent waves of the National Longitudinal Study of Adolescent to Adult Health (Wave IV, 2008-2009; N = 14,784 and Wave V, 2016-2018; N = 12,043). The exercise variables included any form of exercise/sport during the past 7 days and the number of days participating in each of 7 types of exercise/sport. Marijuana-use variables comprised any current use and frequency of use during the past 30 days. Both fixed-effects and random-effects models were estimated with numerous control variables, along with binary and count measures of exercise. Results show that, particularly for fixed-effects models, marijuana use is not significantly related to exercise, counter to conventional wisdom that marijuana users are less likely to be active. Indeed, the only significant estimates suggest a positive relationship, even among heavier users during the past 30 days. These findings are at odds with much of the existing literature, which generally shows a negative relationship between marijuana use and exercise. As additional states legalize the medicinal and recreational use of marijuana, perhaps its impact on exercise, one of the leading social determinants of health, is not necessarily a primary concern.

Emerging functions of branched ubiquitin chains.

Ubiquitylation is a critical post-translational modification that controls a wide variety of processes in eukaryotes. Ubiquitin chains of different topologies are specialized for different cellular functions and control the stability, activity, interaction properties, and localization of many different proteins. Recent work has highlighted a role for branched ubiquitin chains in the regulation of cell signaling and protein degradation pathways. Similar to their unbranched counterparts, branched ubiquitin chains are remarkably diverse in terms of their chemical linkages, structures, and the biological information they transmit. In this review, we discuss emerging themes related to the architecture, synthesis, and functions of branched ubiquitin chains. We also describe methodologies that have recently been developed to identify and decode the functions of these branched polymers.