Workers regularly using vibrating hand tools may develop a disorder referred to as hand-arm vibration syndrome (HAVS). HAVS is characterized by cold-induced vasospasms in the hands and fingers that result in blanching of the skin, loss of sensory function, pain, and reductions in manual dexterity. Exposure to vibration induces some of these symptoms. However, the soft tissues of the hands and fingers of workers are compressed as a result of the force generated when a worker grips a tool. The compression of these soft tissues might also contribute to the development of HAVS. The goal of this study was to use an established rat tail model to determine the mechanisms by which compression of the tail tissues affects (1) the ventral tail artery (VTA) and ventral tail nerves (VTN), (2) nerves and sensory receptors in the skin, (3) dorsal root ganglia (DRG), and (4) spinal cord. Tissue compression resulted in the following changes (1) circulating pituitary and steroid hormone concentrations, (2) expression of factors that modulate vascular function in the skin and tail artery, and (3) factors associated with nerve damage, DRG, and spinal cord. Some of these observed effects differed from those previously noted with vibration exposure. Based upon these findings, the effects of applied force and vibration are different. Studies examining the combination of these factors might provide data that may potentially be used to improve risk assessment and support revision of standards.

Over-exposure of the hand-arm system to intense vibration and force over time may cause degeneration of the vascular, neurological, and musculoskeletal systems in the fingers. A novel animal model using rat tails has been developed to understand the health effects on human fingers exposed to vibration and force when operating powered hand tools or workpieces. The biodynamic responses, such as vibration stress, strain, and power absorption density, of the rat tails can be used to help evaluate the health effects related to vibration and force and to establish a dose-effect relationship. While the biodynamic responses of cadaver rat tails have been investigated, the objective of the current study was to determine whether the biodynamic responses of living rat tails are different from those of cadaver rat tails, and whether the biodynamic responses of both living and cadaver tails change with exposure duration. To make direct comparisons, the responses of both cadaver and living rat tails were examined on four different testing stations. The transfer function of each tail under a given contact force (2 N) was measured at each frequency in the one-third octave bands from 20 to 1000 Hz, and used to calculate the mechanical system parameters of the tails. The transfer functions were also measured at different exposure durations to determine the time dependency of the response. Differences were observed in the vibration biodynamic responses between living and cadaver tails, but the general trends were similar. The biodynamic responses of both cadaver and living rat tails varied with exposure duration. © 2024 by the authors.

Since 1994, the U.S. Vaccines for Children (VFC) program has covered the cost of vaccines for children whose families might not otherwise be able to afford vaccines. This report assessed and quantified the health benefits and economic impact of routine U.S. childhood immunizations among both VFC-eligible and non-VFC-eligible children born during 1994-2023. Diphtheria and tetanus toxoids and acellular pertussis vaccine; Haemophilus influenzae type b conjugate vaccine; oral and inactivated poliovirus vaccines; measles, mumps, and rubella vaccine; hepatitis B vaccine; varicella vaccine; pneumococcal conjugate vaccine; hepatitis A vaccine; and rotavirus vaccine were included. Averted illnesses and deaths and associated costs over the lifetimes of 30 annual cohorts of children born during 1994-2023 were estimated using established economic models. Net savings were calculated from the payer and societal perspectives. Among approximately 117 million children born during 1994-2023, routine childhood vaccinations will have prevented approximately 508 million lifetime cases of illness, 32 million hospitalizations, and 1,129,000 deaths, at a net savings of $540 billion in direct costs and $2.7 trillion in societal costs. From both payer and societal perspectives, routine childhood vaccinations among children born during 1994-2023 resulted in substantial cost savings. Childhood immunizations continue to provide substantial health and economic benefits, while promoting health equity.

BACKGROUND: Telehealth has emerged as an effective tool for managing common chronic conditions such as hypertension, especially during the COVID-19 pandemic. However, the impact of state telehealth payment and coverage parity laws on hypertension medication adherence remains uncertain. METHODS: Data from the 2016 to 2021 Merative MarketScan Commercial Claims and Encounters Database were used to construct the study cohort, which included nonpregnant individuals aged 25 to 64 years with hypertension. We coded telehealth parity laws related to hypertension management in all 50 US states and the District of Columbia, distinguishing between payment and coverage parity laws. The primary outcomes were measures of antihypertension medication adherence: the average medication possession ratio; medication adherence (medication possession ratio ≥80%); and average number of days of drug supply. We used a generalized difference-in-differences design to examine the impact of these laws. RESULTS: Among 353 220 individuals (mean [SD] age, 49.5 (7.1) years; female, 45.55%), states with payment parity laws were significantly linked to increased average medication possession ratio by 0.43 percentage point (95% CI, 0.07-0.79), and an increase of 0.46 percentage point (95% CI, 0.06-0.92) in the probability of medication adherence. Payment parity laws also led to an average increase of 2.14 days (95% CI, 0.11-4.17) in prescription supply, after controlling for state-fixed effects, year-fixed effects, individual sociodemographic characteristics and state time-varying covariates including unemployment rates, gross domestic product per capita, and poverty rates. In contrast, coverage parity laws were associated with a 2.13-day increase (95% CI, 0.19-4.07) in days of prescription supply but did not significantly increase the average medication possession ratio or probability of medication adherence. CONCLUSIONS: State telehealth payment parity laws were significantly associated with greater medication adherence, whereas coverage parity laws were not. With the increasing adoption of telehealth parity laws across states, these findings may support policymakers in understanding potential implications on management of hypertension.

OBJECTIVE(S): To examine associations between Index of Concentration at the Extremes (ICE) measures (proxy for structural racism) for economic and Hispanic/Latino-White racial segregation and HIV outcomes among adults in the U.S. METHODS: Census tract-level HIV diagnoses, linkage to HIV medical care within 1 month of diagnosis (linkage), and viral suppression within 6 months of diagnosis (viral suppression) data for 2021 from the National HIV Surveillance System were used. Three ICE measures were obtained from the American Community Survey: ICEincome (income segregation), ICErace (Hispanic/Latino-White racial segregation), and ICEincome + race (Hispanic/Latino-White racialized economic segregation). Rate ratios (RRs) for HIV diagnosis and prevalence ratios (PRs) for linkage and viral suppression were used to examine differences in HIV outcomes across ICE quintiles with Quintile5 (Q5: most privileged) as reference group and adjusted by selected characteristics. RESULTS: Among the 32,529 adults, diagnosis rates were highest in Quintile1 (Q1: most deprived) for ICEincome (28.7) and ICEincome + race (28.4) and Q2 for ICErace (27.0). We also observed higher RRs in HIV diagnosis and lower PRs in linkage and viral suppression (except for ICErace for linkage) in Q1 compared to Q5. Higher RRs and lower PRs in ICE measures were observed among males (diagnosis), adults aged 18‒34 (diagnosis and linkage) and aged ≥ 45 (viral suppression), and among adults in the South (all 3 HIV outcomes). CONCLUSIONS: Barriers in access to care/treatment in more Hispanic/Latino-White racialized economic segregated communities perpetuate the disproportionate impact of HIV on the population. Removing barriers to HIV care/treatment created by systemic racism/segregation may improve HIV outcomes and reduce disparities.

BACKGORUND: The development of vibration-induced finger disorders is likely associated with combined static and dynamic responses of the fingers to vibration exposure. To study the mechanism of the disorders, a new rat-tail model has been established to mimic the finger vibration and pressure exposures. However, the mechanical behavior of the tail during compression needs to be better understood to improve the model and its applications. OBJECTIVE: To investigate the static and time-dependent force responses of the rat tail during compression. METHODS: Compression tests were conducted on Sprague-Dawley cadaver rat tails using a micromechanical system at three deformation velocities and three deformation magnitudes. Contact-width and the time-histories of force and deformation were measured. Additionally, force-relaxation tests were conducted and a Prony series was used to model the force-relaxation behavior of the tail. RESULTS: The rat tails' force-deformation and stiffness-deformation relationships were strongly nonlinear and time-dependent. Force/stiffness increased with an increase in deformation and deformation velocity. The time-dependent force-relaxation characteristics of the tails can be well described using a Prony series. CONCULSIONS: We successfully quantified the static and time-dependent force responses of rat tails under compression. The identified mechanical behavior of the tail can help improve the rat-tail model and its applications.

Benzathine benzylpenicillin is a globally indispensable medicine. As a long-lasting injectable penicillin, it serves as the primary treatment for syphilis, group A streptococcal infections, rheumatic fever and rheumatic heart disease. A competitive market and low profit margins, compounded by limited visibility of demand, have resulted in a decreased number of active pharmaceutical ingredient (API) manufacturers. By 2016, only three Chinese API manufacturers remained, continuing to supply to the global market today. Recurring global shortages, a consequence of supply and demand imbalances, indicate underlying market risks. Therefore, the need for mitigation strategies is imperative.

IMPORTANCE: Economic policies have the potential to impact management and control of hypertension. OBJECTIVES: To review the evidence on the association between economic policies and hypertension management and control among adults with hypertension in the US. EVIDENCE REVIEW: A search was carried out of PubMed/MEDLINE, Cochrane Library, Embase, PsycINFO, CINAHL, EconLit, Sociological Abstracts, and Scopus from January 1, 2000, through November 1, 2023. Included were randomized clinical trials, difference-in-differences, and interrupted time series studies that evaluated the association of economic policies with hypertension management. Economic policies were grouped into 3 categories: insurance coverage expansion such as Medicaid expansion, cost sharing in health care such as increased drug copayments, and financial incentives for quality such as pay-for-performance. Antihypertensive treatment was measured as taking antihypertensive medications or medication adherence among those who have a hypertension diagnosis; and hypertension control, measured as blood pressure (BP) lower than  140/90 mm Hg or a reduction in BP. Evidence was extracted and synthesized through dual review of titles, abstracts, full-text articles, study quality, and policy effects. FINDINGS: In total, 31 articles were included. None of the studies examined economic policies outside of the health care system. Of these, 16 (52%) assessed policies for insurance coverage expansion, 8 (26%) evaluated policies related to patient cost sharing for prescription drugs, and 7 (22%) evaluated financial incentive programs for improving health care quality. Of the 16 studies that evaluated coverage expansion policies, all but 1 found that policies such as Medicare Part D and Medicaid expansion were associated with significant improvement in antihypertensive treatment and BP control. Among the 8 studies that examined patient cost sharing, 4 found that measures such as prior authorization and increased copayments were associated with decreased adherence to antihypertensive medication. Finally, all 7 studies evaluating financial incentives aimed at improving quality found that they were associated with improved antihypertensive treatment and BP control. Overall, most studies had a moderate or low risk of bias in their policy evaluation. CONCLUSIONS AND RELEVANCE: The findings of this systematic review suggest that economic policies aimed at expanding insurance coverage or improving health care quality successfully improved medication use and BP control among US adults with hypertension. Future research is needed to investigate the potential effects of non-health care economic policies on hypertension control.

To infer population genetics of Enterocytozoon bieneusi in nonhuman primates (NHPs), 126 positive specimens in 839 fecal specimens from 23 NHP species in China based on ITS locus were used, belonging to genotypes Type IV, D, Peru8, Henan V, Peru11, PigEBITS7 and 3 novel ones (CM1, CM2 and CM3). Multilocus sequence typing employing four micro and minisatellites (MS1, MS3, MS4 and MS7) and ITS were used to analyze population structure of 85 isolates successfully amplified at all five loci, which yielded 59 multilocus genotypes. Linkage disequilibrium (LD) was measured using both multilocus sequences and allelic profile data. The observation of strong and significant LD with limited recombination in multilocus sequence analysis indicated the presence of overall clonal population structure of E. bieneusi, which was supported by allelic profile data analysis. Fu's selective neutrality test demonstrated the absence of neutral mutations and molecular selection. The population structure of common ITS genotypes (CM1, Type IV and D) was compared. Strong LD in multilocus sequence analysis versus insignificant LD and/or LE in allelic profile data analysis implied epidemic population in common ITS genotypes. No significant genetic isolation was evidenced by either phylogenetic or substructural analyses. The population genetics was also compared among the sub-population 1 (contained mainly genotype Type IV), sub-population 2 (contained mainly genotypes CM1 and D), sub-population 3 (contained mixed genotypes) and sub-population 4 (contained genotype Henan V). The presence of strong LD in multilocus data analysis with insignificant LD and/or LE in allele profile data analysis suggested the epidemic population in sub-populations.

Mast climbing work platforms (MCWPs) have been increasingly used for construction projects, whereas their safety remains an important issue. As the mast in the Mast climbing work platform (MCWP) system is "slender" structurally, its anchorages must play an important role in maintaining its stability. Therefore, the anchorages and their attachments to a construction structure are likely among the most critical components for the MCWPs. This study developed finite element models of a representative MCWP and applied them to analyze the characteristics of the reaction forces at the anchorages when the work platform operates at different heights and under different loading conditions and to simulate the mast structure responses to the failure of one of the three anchorages. The results of this study indicate that the anchorage reaction forces are sensitive to the loading and operational conditions of the MCWP. The responses of the anchorage reaction forces may reflect the stability status or risk potential of the mast structure of the MCWP to collapse. The characteristics of the anchorage forces identified in this study can be used to help develop a structural safety monitoring system, to minimize the risk of catastrophic failures of MCWPs. The knowledge obtained in the study would help improve MCWP safety management at construction sites and help MCWP manufacturers to improve anchorage design and installation procedures to reduce the risk of the mast structure's instability or collapse.

OBJECTIVE: This study described the effects of applied force (grip) on vascular and sensorineural function in an animal model of hand-arm vibration syndrome (HAVS). METHODS: Rat tails were exposed to 0, 2 or 4 newtons (N) of applied force 4 hr/day for 10 days. Blood flow and sensitivity to transcutaneous electrical stimulation and pressure were measured. RESULTS: Applied force increased blood flow but reduced measures of arterial plasticity. Animals exposed to force tended to be more sensitive to 250 Hz electrical stimulation and pressure applied to the tail. CONCLUSIONS: Effects of applied force on blood flow and sensation are different than those of vibration. Studies examining co-exposures to force and vibration will provide data that can be used to determine how these factors affect risk of workers developing vascular and sensorineural dysfunction (i.e., HAVS).

Breast cancer treatment can be improved with biomarkers for early detection and individualized therapy. A set of 86 microRNAs (miRNAs) were identified to separate breast cancer tumors from normal breast tissues (n = 52) with an overall accuracy of 90.4%. Six miRNAs had concordant expression in both tumors and breast cancer patient blood samples compared with the normal control samples. Twelve miRNAs showed concordant expression in tumors vs. normal breast tissues and patient survival (n = 1093), with seven as potential tumor suppressors and five as potential oncomiRs. From experimentally validated target genes of these 86 miRNAs, pan-sensitive and pan-resistant genes with concordant mRNA and protein expression associated with in-vitro drug response to 19 NCCN-recommended breast cancer drugs were selected. Combined with in-vitro proliferation assays using CRISPR-Cas9/RNAi and patient survival analysis, MEK inhibitors PD19830 and BRD-K12244279, pilocarpine, and tremorine were discovered as potential new drug options for treating breast cancer. Multi-omics biomarkers of response to the discovered drugs were identified using human breast cancer cell lines. This study presented an artificial intelligence pipeline of miRNA-based discovery of biomarkers, therapeutic targets, and repositioning drugs that can be applied to many cancer types.

There is currently no gene expression assay that can assess if premalignant lesions will develop into invasive breast cancer. This study sought to identify biomarkers for selecting patients with a high potential for developing invasive carcinoma in the breast with normal histology, benign lesions, or premalignant lesions. A set of 26-gene mRNA expression profiles were used to identify invasive ductal carcinomas from histologically normal tissue and benign lesions and to select those with a higher potential for future cancer development (ADHC) in the breast associated with atypical ductal hyperplasia (ADH). The expression-defined model achieved an overall accuracy of 94.05% (AUC = 0.96) in classifying invasive ductal carcinomas from histologically normal tissue and benign lesions (n = 185). This gene signature classified cancer development in ADH tissues with an overall accuracy of 100% (n = 8). The mRNA expression patterns of these 26 genes were validated using RT-PCR analyses of independent tissue samples (n = 77) and blood samples (n = 48). The protein expression of PBX2 and RAD52 assessed with immunohistochemistry were prognostic of breast cancer survival outcomes. This signature provided significant prognostic stratification in The Cancer Genome Atlas breast cancer patients (n = 1100), as well as basal-like and luminal A subtypes, and was associated with distinct immune infiltration and activities. The mRNA and protein expression of the 26 genes was associated with sensitivity or resistance to 18 NCCN-recommended drugs for treating breast cancer. Eleven genes had significant proliferative potential in CRISPR-Cas9/RNAi screening. Based on this gene expression signature, the VEGFR inhibitor ZM-306416 was discovered as a new drug for treating breast cancer.

Sosuga virus (SOSV) is a recently discovered paramyxovirus with a single known human case of disease. There has been little laboratory research on SOSV pathogenesis or immunity, and no approved therapeutics or vaccines are available. Here, we report the discovery of human monoclonal antibodies (mAbs) from the circulating memory B cells of the only known human case and survivor of SOSV infection. We isolated six mAbs recognizing the functional attachment protein (HN) and 18 mAbs against the fusion (F) protein. The anti-HN mAbs all target the globular head of the HN protein and can be organized into 4 competition-binding groups that exhibit epitope diversity. The anti-F mAbs can be divided into pre- or post-fusion conformation-specific categories and further into 8 competition-binding groups. Generally, pre-fusion conformation-specific anti-F mAbs showed higher potency in neutralization assays than did mAbs only recognizing the post-fusion conformation of F protein. Most of the anti-HN mAbs were more potently neutralizing than the anti-F mAbs, with mAbs in one of the HN competition-binding groups possessing ultra-potent (<1 ng/mL) half maximal inhibitory (IC50) virus neutralization values. These findings provide insight into the molecular basis for human antibody recognition of paramyxovirus surface proteins and the mechanisms of SOSV neutralization. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

It has been hypothesized that the biodynamic responses of the human finger tissues to vibration are among the major stimuli that cause vibration health effects. Furthermore, the finger contact pressure can alter these effects. It is difficult to test these hypotheses using human subjects or existing animal models. The objective of this study was to develop a new rat-tail vibration model to investigate the combined effects of vibration and contact pressure and to identify their relationships with the biodynamic responses. Physically, the new exposure system was developed by adding a loading device to an existing rat-tail model. An analytical model of the rat-tail exposure system was proposed and used to formulate the methods for quantifying the biodynamic responses. A series of tests with six tails dissected from rat cadavers were conducted to test and evaluate the new model. The experimental and modeling results demonstrate that the new model behaves as predicted. Unlike the previous model, the vibration strain and stress of the rat tail does not depend primarily on the vibration response of the tail itself but on that of the loading device. This makes it possible to quantify and control the biodynamic responses conveniently and reliably by measuring the loading device response. This study also identified the basic characteristics of the tail biodynamic responses in the exposure system, which can be used to help design the experiments for studying vibration biological effects.

Sosuga virus (SOSV) is a recently discovered paramyxovirus with a single known human case of disease. There has been little laboratory research on SOSV pathogenesis or immunity, and no approved therapeutics or vaccines are available. Here, we report the discovery of human monoclonal antibodies (mAbs) from the circulating memory B cells of the only known human case and survivor of SOSV infection. We isolated six mAbs recognizing the functional attachment protein hemagglutinin-neuraminidase (HN) and 18 mAbs against the fusion (F) protein. The anti-HN mAbs all target the globular head of the HN protein and can be organized into 4 competition-binding groups that exhibit epitope diversity. The anti-F mAbs can be divided into pre- or postfusion conformation-specific categories and further into 8 competition-binding groups. The only antibody in the panel that did not display neutralization activity was the single, postfusion-specific anti-F mAb. Most of the anti-HN mAbs were more potently neutralizing than the anti-F mAbs, with mAbs in one of the HN competition-binding groups possessing ultra-potent (<1 ng/mL) half maximal inhibitory (IC50) virus neutralization values. These findings provide insight into the molecular basis for human antibody recognition of paramyxovirus surface proteins and the mechanisms of SOSV neutralization.

Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019–2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019–2020 WHO RSV EQA. Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. Conclusions: The WHO RSV EQA 2019–2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets. © 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.

As authorities braced for the arrival of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infrastructure investments and government directives prompted action in central Viet Nam to establish capacity for genomic surveillance sequencing. From 17 November 2021 to 7 January 2022, the Pasteur Institute in Nha Trang sequenced 162 specimens from 98 150 confirmed SARS-CoV-2 cases in the region collected from 8 November to 31 December 2021. Of these, all 127 domestic cases were identified as the B.1.617.2 (Delta) variant, whereas 92% (32/35) of imported cases were identified as the B.1.1.529 (Omicron) variant, all among international flight passengers. Patients were successfully isolated, enabling health-care workers to prepare for additional cases. Most (78%) of the 32 Omicron cases were fully vaccinated, suggesting continued importance of public health and social measures to control the spread of new variants.

Findings from epidemiological studies suggest that occupational exposure to whole-body vibration (WBV) may increase the risk of miscarriage and contribute to a reduction in fertility rates in both men and women. However, workers exposed to WBV may also be exposed to other risk factors that contribute to reproductive dysfunction. The goal of this experiment was to examine the effects of WBV on reproductive physiology in a rat model. Male and female rats were exposed to WBV at the resonant frequency of the torso (31.5 Hz, 0.3 g amplitude) for 4 hr/day for 10 days. WBV exposure resulted in a significant reduction in number of developing follicles, and decrease in circulating estradiol concentrations, ovarian luteinizing hormone receptor protein levels, and marked changes in transcript levels for several factors involved in follicular development, cell cycle, and steroidogenesis. In males, WBV resulted in a significant reduction in spermatids and circulating prolactin levels, elevation in number of males having higher circulating testosterone concentrations, and marked alterations in levels of transcripts associated with oxidative stress, inflammation, and factors involved in regulating the cell cycle. Based upon these findings data indicate that occupational exposure to WBV contributes to adverse alterations in reproductive physiology in both genders that may lead to reduction in fertility.

BACKGROUND: Black and Hispanic/Latino men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV). In the Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project, 7 community collaboratives were developed to provide comprehensive HIV prevention services for these populations. METHODS: We analyzed National HIV Surveillance System data to determine the number of HIV diagnoses for each year from 2014 to 2019 among Black, Hispanic/Latino, and White MSM in 7 THRIVE-eligible Metropolitan Statistical Areas (MSAs) that were awarded funding and 12 THRIVE-eligible MSAs that were not awarded funding. We used generalized linear Poisson regression models to estimate adjusted estimated annual percentage changes (EAPCs) with 95% confidence intervals for HIV diagnosis rates controlling for HIV prevalence, viral suppression, HIV testing rates, preexposure prophylaxis (PrEP) prescription rates, poverty, education, and insurance status. RESULTS: We found larger estimated decreases in HIV diagnosis rates in THRIVE jurisdictions compared with non-THRIVE jurisdictions. The adjusted EAPC among Black MSM was -8.2 (-11.7 to -4.6) in THRIVE MSAs compared with -4.2 (-7.8 to -0.4) in non-THRIVE MSAs. The adjusted EAPC among Hispanic/Latino MSM was -8.6 (-12.2 to -4.8) in THRIVE MSAs compared with -2.6 (-5.1 to -0.1)in non-THRIVE MSAs. The adjusted EAPC among White MSM was -7.6 (-12.0 to -3.1) in THRIVE MSAs compared with 5.9 (1.8-10.1) in non-THRIVE MSAs. CONCLUSIONS: The THRIVE community collaborative model was associated with a decrease in HIV diagnoses among Black and Hispanic/Latino MSM. To achieve the goals of the US Ending the HIV Epidemic initiative, effective interventions aimed to increase PrEP use need to be focused on Black and Hispanic/Latino MSM.

Black/African American (Black) versus White persons are unequally burdened by human immunodeficiency virus (HIV) in the United States. Structural factors can influence social determinants of health, key components in reducing HIV-related health inequality by race. This analysis examined HIV care outcomes among Black and White persons with diagnosed HIV (PWDH) in relation to three structural factors: racial redlining, Medicaid expansion, and Ryan White HIV/AIDS Program (RWHAP) use. Using National HIV Surveillance System, U.S. Census, and Home Mortgage Disclosure Act data, we examined linkage to HIV care and viral suppression (i.e., viral load < 200 copies/mL) in relation to the structural factors among 12,996 Black and White PWDH with HIV diagnosed in 2017/alive at year-end 2018, aged ≥ 18 years, and residing in 38 U.S. jurisdictions with complete laboratory data, geocoding, and census tract-level redlining indexes. Compared to White PWDH, a lower proportion of Black PWDH were linked to HIV care within 1 month after diagnosis and were virally suppressed in 2018. Redlining was not associated with the HIV care outcomes. A higher prevalence of PWDH residing (v. not residing) in states with Medicaid expansion were linked to HIV care ≤ 1 month after diagnosis. A higher prevalence of those residing (v. not residing) in states with > 50% of PWDH in RWHAP had viral suppression. Direct exposure to redlining was not associated with poor HIV care outcomes. Structural factors that reduce the financial burden of HIV care and improve care access like Medicaid expansion and RWHAP might improve HIV care outcomes of PWDH.

Studies on hand-transmitted vibration exposure, biodynamic responses, and biological effects were conducted by researchers at the Health Effects Laboratory Division (HELD) of the National Institute for Occupational Safety and Health (NIOSH) during the last 20 years. These studies are systematically reviewed in this report, along with the identification of areas where additional research is needed. The majority of the studies cover the following aspects: (i) the methods and techniques for measuring hand-transmitted vibration exposure; (ii) vibration biodynamics of the hand-arm system and the quantification of vibration exposure; (iii) biological effects of hand-transmitted vibration exposure; (iv) measurements of vibration-induced health effects; (iv) quantification of influencing biomechanical effects; and (v) intervention methods and technologies for controlling hand-transmitted vibration exposure. The major findings of the studies are summarized and discussed.

This study developed a novel methodology to correlate genome-scale microRNA (miRNA) expression profiles in a lung squamous cell carcinoma (LUSC) cohort (n = 57) with Surveillance, Epidemiology, and End Results (SEER)-Medicare LUSC patients (n = 33,897) as a function of composite tumor progression indicators of T, N, and M cancer stage and tumor grade. The selected prognostic and chemopredictive miRNAs were extensively validated with miRNA expression profiles of non-small-cell lung cancer (NSCLC) patient samples collected from US hospitals (n = 156) and public consortia including NCI-60, The Cancer Genome Atlas (TCGA; n = 1016), and Cancer Cell Line Encyclopedia (CCLE; n = 117). Hsa-miR-142-3p was associated with good prognosis and chemosensitivity in all the studied datasets. Hsa-miRNA-142-3p target genes (NUP205, RAN, CSE1L, SNRPD1, RPS11, SF3B1, COPA, ARCN1, and SNRNP200) had a significant impact on proliferation in 100% of the tested NSCLC cell lines in CRISPR-Cas9 (n = 78) and RNA interference (RNAi) screening (n = 92). Hsa-miR-142-3p-mediated pathways and functional networks in NSCLC short-term survivors were elucidated. Overall, the approach integrating SEER-Medicare data with comprehensive external validation can identify miRNAs with consistent expression patterns in tumor progression, with potential implications for prognosis and prediction of chemoresponse in large NSCLC patient populations.

Prolonged and intensive vibration exposures during the grinding of handheld workpieces may cause hand-arm vibration syndrome. The objectives of this study are to develop an on-the-hand method for evaluating vibration-reducing (VR) gloves, and to determine whether VR gloves can significantly reduce the vibration exposures. A worker holding and pressing a typical workpiece (golf club head) against a grinding wheel or belt in order to shape the workpiece was simulated, and the input vibration and those on the workpiece and hand-arm system were measured. Ten human subjects participated in the experiment. The results demonstrate that VR gloves significantly reduced the vibrations at the palm, hand dorsum, and wrist. The grinding interface condition and hand feed force did not substantially affect glove effectiveness. The use of gloves slightly increased the workpiece resonant response, but the resonant response did not significantly affect glove effectiveness. This study concluded that the use of VR gloves can help control vibration exposures of workers performing grinding of handheld workpieces.

Establishing accurate population size estimates (PSE) is important for prioritising and planning provision of services. Multiple source capture-recapture sampling method increases PSE accuracy and reliability. In August 2018, the three-source capture-recapture (3S-CRC) method was employed with a stringent assumption of sample independence to estimate the number of female sex workers (FSW) in Rwanda. Using Rwanda 2017 FSW hotspots mapping data, street and venue-based FSW were sampled at the sector level of each province and tagged with two unique gifts. Each capture was completed within one week to minimise FSW migration between provinces and recall bias. The three captures had 1042, 1204 and 1488 FSW. There were 111 FSW recaptured between captures 1 and 2; 237 between captures 2 and 3; 203 between captures 1 and 3 and 46 captured in all three. The PSE for street and venue-based FSW in Rwanda lies within 95% credible set: 8328-22 806 with corresponding median of 13 716 FSW. The 3S-CRC technique was low-cost and relatively easy to use for PSE in hard-to-reach populations. This estimate provides the basis for determining the denominators to assess HIV programme performance towards FSW and epidemic control and warrants further PSE for home- and cyber-based FSW in Rwanda.

Inflammation is a tissue response to a variety of harmful stimuli, such as pathogens, irritants, and injuries, and can eliminate insults and limit tissue damage. However, dysregulated inflammation is recognized as a cause of many human diseases, exemplified by organ fibrosis and cancer. In this regard, inflammation-promoted fibrosis is commonly observed in human lung diseases, such as idiopathic pulmonary fibrosis and pneumoconiosis. Carbon nanotubes (CNTs) are a type of nanomaterials with unique properties and various industrial and commercial applications. On the other hand, certain forms of CNTs are potent inducers of inflammation and fibrosis in animal lungs. Notably, acute inflammation is a remarkable phenotype elicited by CNTs in the lung during the early acute phase post-exposure; whereas a type 2 immune response is evidently activated and dominates during the late acute and chronic phases, leading to type 2 inflammation and lung fibrosis. Numerous studies demonstrate that these immune responses involve distinct immune cells, various pathologic factors, and specific functions and play crucial roles in the initiation and progression of inflammation and fibrosis in the lung exposed to CNTs. Thus, the mechanistic understanding of the immune responses activated by CNTs has drawn great attention in recent years. This article reviews the major findings on the cell signaling pathways that are activated in immune cells and exert functions in promoting immune responses in CNT-exposed lungs, which would provide new insights into the understanding of CNT-induced lung inflammation and inflammation-driven fibrosis, the application of CNT-induced lung inflammation and fibrosis as a new disease model, and the potential of targeting immune cells as a therapeutic strategy for relevant human lung diseases.

Slips and falls on sloped roof surfaces remain an important safety issue among construction workers. The slip potential has been conventionally analyzed and assessed primarily based on ground reaction forces, which cannot differentiate the specific roles of each of the force factors (e.g., workers’ motions-induced dynamic forces and slope-induced static forces) contributing to the slip potential. Their differentiation may enhance the understanding of the slip mechanisms on the sloped roof surfaces and help develop effective walking and working strategies/tactics to minimize the dangerous slips on the elevated roofs. Hence, the objective of this study is to develop a biodynamic method as an additional tool for analyzing the slip potential of a worker walking or working on sloped roof surfaces. A whole-body biodynamic model is proposed and used to develop the alternative method, in which the slip potential is expressed as an analytical function of its major controlling factors including coefficient of friction, slope angle, and biodynamic forces. Some experimental data available in the literature are used to demonstrate the application of the proposed method. The results suggest that the slope may not change the basic trends of the biodynamic forces, but the slope may affect their magnitudes, which can be explained using the system's energy equation also derived from the whole-body biodynamic model. The analytical results suggest that reducing the body acceleration in uphill direction or the deceleration in downhill direction can reduce the slip potential. ‘Zigging’ and ‘zagging’ walking on a sloped surface may also reduce the slip potential, as it reduces the effective slope angle. The proposed biodynamic theory can be used to enhance the safety guidelines not only for roofers but also for people walking on ramps, inclined walkways, and mountain terrains.

Human papilloma virus (HPV) causes a subset of head and neck squamous cell carcinomas (HNSCC) of the oropharynx. We combined targeted DNA- and genome-wide RNA-sequencing to identify genetic variants and gene expression signatures respectively from patients with HNSCC including oropharyngeal squamous cell carcinomas (OPSCC). DNA and RNA were purified from 35- formalin fixed and paraffin embedded (FFPE) HNSCC tumor samples. Immuno-histochemical evaluation of tumors was performed to determine the expression levels of p16INK4A and classified tumor samples either p16+ or p16-. Using ClearSeq Comprehensive Cancer panel, we examined the distribution of somatic mutations. Somatic single-nucleotide variants (SNV) were called using GATK-Mutect2 ("tumor-only" mode) approach. Using RNA-seq, we identified a catalog of 1,044 and 8 genes as significantly expressed between p16+ and p16-, respectively at FDR 0.05 (5%) and 0.1 (10%). The clinicopathological characteristics of the patients including anatomical site, smoking and survival were analyzed when comparing p16+ and p16- tumors. The majority of tumors (65%) were p16+. Population sequence variant databases, including gnomAD, ExAC, COSMIC and dbSNP, were used to identify the mutational landscape of somatic sequence variants within sequenced genes. Hierarchical clustering of The Cancer Genome Atlas (TCGA) samples based on HPV-status was observed using differentially expressed genes. Using RNA-seq in parallel with targeted DNA-seq, we identified mutational and gene expression signatures characteristic of p16+ and p16- HNSCC. Our gene signatures are consistent with previously published data including TCGA and support the need to further explore the biologic relevance of these alterations in HNSCC.

The highly pathogenic avian influenza virus (HPAIV) H5N1 A/goose/Guangdong/1996 lineage (Gs/GD) is endemic in poultry across several countries in the world, and has caused lethal, sporadic infections in humans. Vaccines are important in HPAI control for both poultry and in pre-pandemic preparedness in humans. This study assessed inactivated pre-pandemic vaccine strains in a One Health framework, focusing on the genetic and antigenic diversity of field H5N1 Gs/GD viruses from the agricultural sector and assessing cross protection in a chicken challenge model. Nearly half (47.92%) of the forty-eight combinations of vaccine/challenge viruses examined had bird protection of 80% or above. Most vaccinated groups had prolonged mean death time (MDT) and the virus shedding titers were significantly lower compared to the sham group (p≤ 0.05). The antibody titers in the pre-challenge sera were not predictive of protection. Although vaccinated birds had higher titers of hemagglutination inhibiting (HI) antibodies against homologous vaccine antigen, most of them also had lower or no antibody titer against the challenge antigen. The comparison of all parameters, homologous or closely related vaccine and challenge viruses, gave the best prediction protection. Through additional analysis, we identified a pattern of epitopes substitutions in the hemagglutinin (HA) of each challenge virus that impacted protection, regardless of the vaccine used. These changes were situated in the antigenic sites and/or reported epitopes associated with virus escape from antibody neutralization. As a result, this study highlights virus diversity, immune response complexity, and the importance of strain selection for vaccine development to control H5N1 HPAIV in the agricultural sector and for human pre-pandemic preparedness. We suggest that the engineering of specific antigenic sites can improve the immunogenicity of H5 vaccines.ImportanceThe sustained circulation of highly pathogenic avian influenza virus (HPAIV) H5N1 A/goose/Guangdong/1996 lineage (Gs/GD) in the agricultural sector and some wild birds has led to the evolution and selection of distinct viral lineages involved in the escape from vaccine protection. Our results using inactivated vaccine candidates from the human pandemic preparedness program in a chicken challenge model identified critical antigenic conformational epitopes on the H5 hemagglutinin (HA) from different clades that were associated with antibody recognition and escape. Even though other investigators have reported epitope mapping in the H5 HA, much of this information pertains to epitopes reactive towards mouse antibodies. Our findings validate changes in antigenic epitopes of HA associated with virus escape from antibody neutralization in chickens, which has direct relevance to field protection and virus evolution. Therefore, the knowledge of these immunodominant regions is essential to proactively develop diagnostic tests, improve surveillance platforms to monitor AIV outbreaks, and design more efficient and broad-spectrum agricultural and human prepandemic vaccines.

This study assessed within-trial cost-effectiveness of a shared care program (SC, n = 339) for pregnancy outcomes compared to usual care (UC, n = 361), as implemented in a randomized trial of Chinese women with gestational diabetes (GDM). SC consisted of an individualized dietary advice and physical activity counseling program. The UC was a one-time group education program. The effectiveness was measured by number needed to treat (NNT) to prevent one macrosomia/large for gestational age (LGA) infant. The cost-effectiveness was measured by incremental cost-effectiveness ratio in terms of cost (2012 Chinese Yuan/US dollar) per case of macrosomia and LGA prevented. The study took both a health care system and a societal perspective. This study found that the NNT was 16/14 for macrosomia/LGA. The incremental cost for treating a pregnant woman was ¥1,877 ($298) from a health care system perspective and ¥2,056 ($327) from a societal perspective. The cost of preventing a case of macrosomia/LGA from the two corresponding perspectives were ¥30,032/¥26,278 ($4,775/$4,178) and ¥32,896/¥28,784 ($5,230/$4,577), respectively. Considering the potential severe adverse health and economic consequences of a macrosomia/LGA infant, our findings suggest that implementing this lifestyle intervention for women with GDM is an efficient use of health care resources.