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.

BACKGROUND: The Women's Health Needs Study (WHNS) collected information on the health characteristics, needs, and experiences, including female genital mutilation (FGM) experiences, attitudes, and beliefs, of women aged 18 to 49 years who were born, or whose mothers were born, in a country where FGM is prevalent living in the US. The purpose of this paper is to describe the WHNS design, methods, strengths and limitations, as well as select demographic and health-related characteristics of participants. METHODS: We conducted a cross-sectional survey from November 2020 -June 2021 in four US metropolitan areas, using a hybrid venue-based sampling (VBS) and respondent-driven sampling (RDS) approach to identify women for recruitment. RESULTS: Of 1,132 participants, 395 were recruited via VBS and 737 RDS. Most were born, or their mothers were born, in either a West African country (Burkina Faso, Guinea, Mali, Mauritania, Sierra Leone, The Gambia) (39.0%) or Ethiopia (30.7%). More than a third were aged 30-39 years (37.5%) with a majority who immigrated at ages ≥13 years (86.6%) and had lived in the United States for ≥5 years (68.9%). Medicaid was the top health insurer (52.5%), followed by private health insurance (30.5%); 17% of participants had no insurance. Nearly half of women reported 1-2 healthcare visits within the past 12 months (47.7%). One in seven did not get needed health care due to cost (14.8%). Over half have ever used contraception (52.1%) to delay or avoid pregnancy and 76.9% had their last pelvic and/or Papanicolaou (pap) exam within the past 3 years. More than half experienced FGM (55.0%). Nearly all women believed that FGM should be stopped (92.0%). CONCLUSION: The VBS/RDS approach enabled recruitment of a diverse study population. WHNS advances research related to the health characteristics, needs, and experiences of women living in the US from countries where FGM is prevalent.

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.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.

A clear understanding of the genetic basis of antibiotic resistance in Mycobacterium tuberculosis is required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype-phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6-90.9%), while for isoniazid it was 78.2% (77.4-79.0%) and their specificities were 96.3% (95.7-96.8%) and 94.4% (93.1-95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1-70.6%) for capreomycin to 88.2% (85.1-90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1-92.5%) for moxifloxacin to 99.5% (99.0-99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors of M. tuberculosis drug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis.

Syphilis is a bacterial infection that is of particular concern during pregnancy because of the risk for transplacental fetal infection. Pregnancies complicated by untreated syphilis are at increased risk for adverse outcomes, including stillbirth and long-term physical and cognitive sequelae in the affected infant. After implementation of enhanced efforts (1) by the Chicago Department of Public Health (CDPH) to eliminate congenital syphilis, including improvements to the surveillance and case management system, the number of Chicago congenital syphilis cases steadily decreased during 2015–2019, despite national increases in congenital syphilis and local increases in syphilis among females of reproductive age.* In 2020, with the emergence of the COVID-19 pandemic, the trend in Chicago abruptly shifted, and cases of congenital syphilis increased during the next 3 years.

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).

Histoplasmosis is one of the most under-diagnosed and under-reported endemic mycoses in the United States. Histoplasma capsulatum is the causative agent of this disease. To date, molecular epidemiologic studies detailing the phylogeographic structure of H. capsulatum in the United States have been limited. We conducted genomic sequencing using isolates from histoplasmosis cases reported in the United States. We identified North American Clade 2 (NAm2) as the most prevalent clade in the country. Despite high intra-clade diversity, isolates from Minnesota and Michigan cases were predominately clustered by state. Future work incorporating environmental sampling and veterinary surveillance may further elucidate the molecular epidemiology of H. capsulatum in the United States and how genomic sequencing can be applied to the surveillance and outbreak investigation of histoplasmosis.

INTRODUCTION: Event-based surveillance (EBS) is a critical component of Early Warning, Alert and Response (EWAR) capacity needed for outbreak prevention and control. To better understand existing EBS and monitor the progress of capacity-building efforts over time, Africa CDC developed an EBS scorecard as part of a revision to the EBS Framework. METHODS: We distributed the scorecard to African Union (AU) Member States (MSs). Survey responses from the MSs' human health sector were aggregated, cleaned, and analysed. MS, regional, and continental EBS capacity was assessed. RESULTS: Between 21 July 2022 and 4 April 2023, a total of 63 respondents representing 49 (89%) of 55 MSs completed the survey. Given Africa CDC's public health mandate, we acknowledged the importance of One Health collaboration in MSs but focused on and analysed only the human health sector responses. Thirty-four (71%) MSs stated having EBS in place; hotline was the most common type of EBS implemented (76%). Seventeen (50%) MSs reported multisectoral, One Health collaboration as part of EBS implementation. Scorecard outcomes showed a minimal (score of <60%) to average (score between 60-80%) level of EBS capacity in 29 and five (5) MSs respectively. DISCUSSION: Current EBS capacity levels need to be strengthened in Africa to ensure the continent remains prepared for future public health threats. The Africa CDC EBS scorecard provides a useful way to measure and track this capacity over time. Results can be used to advocate for and target resources for capacity building to foster public health emergency preparedness efforts.

In July 2022, the Pennsylvania Department of Health received two reports of laboratory-confirmed Legionnaires disease in patients who had recently received lung transplants from the same donor at a single Pennsylvania hospital. The donor's cause of death was freshwater drowning in a river, raising suspicion of potential donor-derived transmission, because Legionella bacteria naturally live in fresh water. Further investigation of patients receiving other organs from the same donor did not identify additional legionellosis cases. Health care-associated infection caused by water exposure at the hospital was also evaluated as a potential source of infection and was found to be unlikely. Hospital water quality parameter measurements collected during May-June 2022 were within expected ranges and no water disruptions were noted, although no testing for Legionella was performed during this period. Notifiable disease data did not identify any other Legionnaires disease cases with exposure to this hospital within the 6 months before or after the two cases. Although laboratory testing did not confirm the source of recipient infections, available data suggest that the most likely source was the donor lungs. This cluster highlights the need for increased clinical awareness of possible infection with Legionella in recipients of lungs from donors who drowned in fresh water before organ recovery.

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs). DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to identify factors associated with HOB preventability. RESULTS: Among 6,733 blood cultures obtained from 3,558 hospitalized patients, there were 409 and 59 unique HOB and NHSN-reportable CLABSI events, respectively. CLABSIs accounted for 59 (14%) of 409 HOB events. There was a moderate but non-significant correlation (r = 0.51; P = .070) between HOB and CLABSI rates. Among 300 reviewed HOB cases, CLABSIs were identified as source in only 38 (13%). Although 157 (52%) of all 300 HOB cases were potentially preventable, CLABSIs accounted for only 22 (14%) of these 157 preventable HOB events. In multivariable analysis, neutropenia, and sepsis as an indication for blood culture were associated with decreased odds of HOB preventability, whereas hospital stay ≥7 days and presence of a urinary catheter were associated with increased likelihood of preventability. CONCLUSIONS: HOB may have utility as a healthcare-associated infection metric in LMIC settings because it captures preventable bloodstream infections beyond NHSN-reportable CLABSIs.

We performed whole-genome sequencing of 174 Salmonella Typhi and 54 Salmonella Paratyphi A isolates collected through prospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patterns of emergence and spread of antimicrobial resistance. We evaluated the relationship between the spatial distance between households and genetic clustering of isolates. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing ≥3 quinolone resistance-determining region mutations. Two H58 isolates carried an IncX3 plasmid containing bla(SHV-12), associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant isolates from India independently evolved on multiple occasions. Among S. Typhi, we identified two main clades circulating (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (odds ratio [OR] = 0.72 per km; 95% credible interval [CrI]: 0.66-0.79). This effect was seen for distances up to 5 km (OR = 0.65 per km; 95% CrI: 0.59-0.73) but not seen for distances beyond 5 km (OR = 1.02 per km; 95% CrI: 0.83-1.26). There was a non-significant reduction in odds of clustering for pairs of isolates in vaccination communities compared with non-vaccination communities or mixed pairs compared with non-vaccination communities. Our findings indicate that S. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission. IMPORTANCE Enteric fever remains a major public health concern in many low- and middle-income countries, as antimicrobial resistance (AMR) continues to emerge. Geographical patterns of typhoidal Salmonella spread, critical to monitoring AMR and planning interventions, are poorly understood. We performed whole-genome sequencing of S. Typhi and S. Paratyphi A isolates collected in Navi Mumbai, India before and after a typhoid conjugate vaccine introduction. From timed phylogenies, we found two dominant circulating lineages of S. Typhi in Navi Mumbai-lineage 2.2, which expanded following a single introduction a decade prior, and 4.3.1 (H58), which had been introduced repeatedly from other parts of India, frequently containing "triple mutations" conferring high-level ciprofloxacin resistance. Using Bayesian hierarchical statistical models, we found that spatial distance between cases was strongly associated with genetic clustering at a fine scale (<5 km). Together, these findings suggest that antimicrobial-resistant S. Typhi frequently flows between cities and then spreads highly locally, which may inform surveillance and prevention strategies.

BackgroundSeveral reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size, and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies.MethodsDNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample.FindingsIn this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p &lt; 1.12×10−7. Seven CpGs showed differences at p &lt; 1×10−5 and 48 at 1×10−4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpGs hits, which was consistent across EWAS and meQTL discovery p-value thresholds.ConclusionsWe report the largest case-control EWAS study of ASD to date. No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the 7 sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD.

Close contact between people is the primary route for transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). We sought to quantify interpersonal contact at the population-level by using anonymized mobile device geolocation data. We computed the frequency of contact (within six feet) between people in Connecticut during February 2020 - January 2021. Then we aggregated counts of contact events by area of residence to obtain an estimate of the total intensity of interpersonal contact experienced by residents of each town for each day. When incorporated into a susceptible-exposed-infective-removed (SEIR) model of COVID-19 transmission, the contact rate accurately predicted COVID-19 cases in Connecticut towns during the timespan. The pattern of contact rate in Connecticut explains the large initial wave of infections during March-April, the subsequent drop in cases during June-August, local outbreaks during August-September, broad statewide resurgence during September-December, and decline in January 2021. Contact rate data can help guide public health messaging campaigns to encourage social distancing and in the allocation of testing resources to detect or prevent emerging local outbreaks more quickly than traditional case investigation. ONE SENTENCE SUMMARY: Close interpersonal contact measured using mobile device location data explains dynamics of COVID-19 transmission in Connecticut during the first year of the pandemic.

We performed whole genome sequencing of 174 Salmonella Typhi and 54 Salmonella Paratyphi A isolates collected through prospective and retrospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patters of emergence and spread of antimicrobial resistance. Additionally, we evaluated the relationship between the spatial distance between households and genetic clustering of isolates using hierarchical Bayesian models. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing >=3 mutations in the quinolone resistance determining region, conferring high-level resistance. Two H58 isolates carried an IncX3 resistance plasmid containing bla<inf>SHV-12</inf>, associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant S. Typhi isolates from India have evolved independently on multiple occasions. Among S. Typhi isolates, we identified two main clades circulating in Navi Mumbai (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (OR 0.72 per km; 95% CrI: 0.66-0.79). This effect was seen for distances up to 5 km (OR 0.65 per km; 95% CrI: 0.59-0.73) but was not seen for distances beyond 5 km (OR 1.02 per km; 95% CrI: 0.83-1.26). Our findings indicate that S. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial-genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Awkward kneeling in sloped shingle installation operations exposes roofers to knee musculoskeletal disorder (MSD) risks. To address the varying levels of risk associated with different phases of shingle installation, this research investigated utilizing machine learning to automatically classify seven distinct phases in a typical shingle installation task. The classification process relied on analyzing knee kinematics data and roof slope information. Nine participants were recruited and performed simulated shingle installation tasks while kneeling on a sloped wooden platform. The knee kinematics data were collected using an optical motion capture system. Three supervised machine learning classification methods (i.e., k-nearest neighbors (KNNs), decision tree (DT), and random forest (RF)) were selected for evaluation. The KNN classifier provided the best performance for overall accuracy. The results substantiated the feasibility of applying machine learning in classifying shingle installation phases from workers’ knee joint rotation and roof slope angles, which may help facilitate method and tool development for automated knee MSD risk surveillance and assessment among roofers. © 2023 by the authors.

The application of statistical analysis software programs has proven useful for the investigation of rockfall runout distance along a designed slope. Rockfall modeling programs are continually being upgraded with more sophisticated analysis tools, such as the use of the rigid body versus lump mass models. Engineers at mine sites utilizing the software may have varied experience related to these models, their associated input parameters, and how to interpret the generated results. To address this concern, researchers at the Spokane Mining Research Division (SMRD) of the US National Institute for Occupational Safety and Health (NIOSH) investigated the influence of slope height, slope angle, slope material, and rock size for both rigid body and lump mass models in a 2-D statistical analysis program. Based on a literature search and industry input, specific ranges common to that of an open pit mining environment were chosen for each of the input parameters to determine 90% rock runout distance as well as their sensitivity to change. Data collected from this numerical analysis and simulation will be compared to empirical rockfall data gathered through the duration of the Highwall Safety project conducted by NIOSH from 2022–2026. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2020. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years. In 2020, there were 11 ADDM Network sites across the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. A child met the case definition if their record documented 1) an ASD diagnostic statement in an evaluation, 2) a classification of ASD in special education, or 3) an ASD International Classification of Diseases (ICD) code. RESULTS: For 2020, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 23.1 in Maryland to 44.9 in California. The overall ASD prevalence was 27.6 per 1,000 (one in 36) children aged 8 years and was 3.8 times as prevalent among boys as among girls (43.0 versus 11.4). Overall, ASD prevalence was lower among non-Hispanic White children (24.3) and children of two or more races (22.9) than among non-Hispanic Black or African American (Black), Hispanic, and non-Hispanic Asian or Pacific Islander (A/PI) children (29.3, 31.6, and 33.4 respectively). ASD prevalence among non-Hispanic American Indian or Alaska Native (AI/AN) children (26.5) was similar to that of other racial and ethnic groups. ASD prevalence was associated with lower household income at three sites, with no association at the other sites.Across sites, the ASD prevalence per 1,000 children aged 8 years based exclusively on documented ASD diagnostic statements was 20.6 (range = 17.1 in Wisconsin to 35.4 in California). Of the 6,245 children who met the ASD case definition, 74.7% had a documented diagnostic statement of ASD, 65.2% had a documented ASD special education classification, 71.6% had a documented ASD ICD code, and 37.4% had all three types of ASD indicators. The median age of earliest known ASD diagnosis was 49 months and ranged from 36 months in California to 59 months in Minnesota.Among the 4,165 (66.7%) children with ASD with information on cognitive ability, 37.9% were classified as having an intellectual disability. Intellectual disability was present among 50.8% of Black, 41.5% of A/PI, 37.8% of two or more races, 34.9% of Hispanic, 34.8% of AI/AN, and 31.8% of White children with ASD. Overall, children with intellectual disability had earlier median ages of ASD diagnosis (43 months) than those without intellectual disability (53 months). INTERPRETATION: For 2020, one in 36 children aged 8 years (approximately 4% of boys and 1% of girls) was estimated to have ASD. These estimates are higher than previous ADDM Network estimates during 2000-2018. For the first time among children aged 8 years, the prevalence of ASD was lower among White children than among other racial and ethnic groups, reversing the direction of racial and ethnic differences in ASD prevalence observed in the past. Black children with ASD were still more likely than White children with ASD to have a co-occurring intellectual disability. PUBLIC HEALTH ACTION: The continued increase among children identified with ASD, particularly among non-White children and girls, highlights the need for enhanced infrastructure to provide equitable diagnostic, treatment, and support services for all children with ASD. Similar to previous reporting periods, findings varied considerably across network sites, indicating the need for additional research to understand the nature of such differences and potentially apply successful identification strategies across states.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2020. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates prevalence and characteristics of ASD and monitors timing of ASD identification among children aged 4 and 8 years. In 2020, a total of 11 sites (located in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin) conducted surveillance of ASD among children aged 4 and 8 years and suspected ASD among children aged 4 years. Surveillance included children who lived in the surveillance area at any time during 2020. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement in an evaluation, 2) a special education classification of autism (eligibility), or 3) an ASD International Classification of Diseases (ICD) code (revisions 9 or 10). Children aged 4 years were classified as having suspected ASD if they did not meet the case definition for ASD but had a documented qualified professional's statement indicating a suspicion of ASD. This report focuses on children aged 4 years in 2020 compared with children aged 8 years in 2020. RESULTS: For 2020, ASD prevalence among children aged 4 years varied across sites, from 12.7 per 1,000 children in Utah to 46.4 in California. The overall prevalence was 21.5 and was higher among boys than girls at every site. Compared with non-Hispanic White children, ASD prevalence was 1.8 times as high among Hispanic, 1.6 times as high among non-Hispanic Black, 1.4 times as high among Asian or Pacific Islander, and 1.2 times as high among multiracial children. Among the 58.3% of children aged 4 years with ASD and information on intellectual ability, 48.5% had an IQ score of ≤70 on their most recent IQ test or an examiner's statement of intellectual disability. Among children with a documented developmental evaluation, 78.0% were evaluated by age 36 months. Children aged 4 years had a higher cumulative incidence of ASD diagnosis or eligibility by age 48 months compared with children aged 8 years at all sites; risk ratios ranged from 1.3 in New Jersey and Utah to 2.0 in Tennessee. In the 6 months before the March 2020 COVID-19 pandemic declaration by the World Health Organization, there were 1,593 more evaluations and 1.89 more ASD identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. After the COVID-19 pandemic declaration, this pattern reversed: in the 6 months after pandemic onset, there were 217 fewer evaluations and 0.26 fewer identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. Patterns of evaluation and identification varied among sites, but there was not recovery to pre-COVID-19 pandemic levels by the end of 2020 at most sites or overall. For 2020, prevalence of suspected ASD ranged from 0.5 (California) to 10.4 (Arkansas) per 1,000 children aged 4 years, with an increase from 2018 at five sites (Arizona, Arkansas, Maryland, New Jersey, and Utah). Demographic and cognitive characteristics of children aged 4 years with suspected ASD were similar to children aged 4 years with ASD. INTERPRETATION: A wide range of prevalence of ASD by age 4 years was observed, suggesting differences in early ASD identification practices among communities. At all sites, cumulative incidence of ASD by age 48 months among children aged 4 years was higher compared with children aged 8 years in 2020, indicating improvements in early identification of ASD. Higher numbers of evaluations and rates of identification were evident among children aged 4 years until the COVID-19 pandemic onset in 2020. Sustained lower levels of ASD evaluations and identification seen at a majority of sites after the pandemic onset could indicate disruptions in typical practices in evaluations and identification for health service providers and schools through the end of 2020. Sites with more recovery could indicate successful strategies to mitigate service interruption, such as pivoting to telehealth approaches for evaluation. PUBLIC HEALTH ACTION: From 2016 through February of 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing ASD evaluation and identification 4 years earlier (from 2012 until March 2016) among the cohort of children aged 8 years in 2020 . From 2016 to March 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing that among children aged 8 years in 2020 from 2012 until March 2016. The disruptions in evaluation that coincided with the start of the COVID-19 pandemic and the increase in prevalence of suspected ASD in 2020 could have led to delays in ASD identification and interventions. Communities could evaluate the impact of these disruptions as children in affected cohorts age and consider strategies to mitigate service disruptions caused by future public health emergencies.

BACKGROUND: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. METHODS: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. FINDINGS: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. INTERPRETATION: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. FUNDING: WHO, US National Institutes of Health.

BACKGROUND: The National Hemophilia Foundation (NHF) conducted extensive all-stakeholder inherited bleeding disorder (BD) community consultations to inform a blueprint for future research. Sustaining and expanding the specialized and comprehensive Hemophilia Treatment Center care model, to better serve all people with inherited BDs (PWIBD), and increasing equitable access to optimal health emerged as top priorities. RESEARCH DESIGN AND METHODS: NHF, with the American Thrombosis and Hemostasis Network (ATHN), convened multidisciplinary expert working groups (WG) to distill priority research initiatives from consultation findings. WG5 was charged with prioritizing health services research (HSR); diversity, equity, and inclusion (DEI); and implementation science (IS) research initiatives to advance community-identified priorities. RESULTS: WG5 identified multiple priority research themes and initiatives essential to capitalizing on this potential. Formative studies using qualitative and mixed methods approaches should be conducted to characterize issues and meaningfully investigate interventions. Investment in HSR, DEI and IS education, training, and workforce development are vital. CONCLUSIONS: An enormous amount of work is required in the areas of HSR, DEI, and IS, which have received inadequate attention in inherited BDs. This research has great potential to evolve the experiences of PWIBD, deliver transformational community-based care, and advance health equity. | Research into how people get their health care, called health services research, is important to understand if care is being delivered equitably and efficiently. This research figures out how to provide the best care at the lowest cost and finds out if everyone gets equally good care. Diversity and inclusion research focuses on whether all marginalized and minoritized populations (such as a given social standing, race, ethnicity, sex, gender identity, sexuality, age, income, disability status, language, culture, faith, geographic location, or country of birth) receive equitable care. This includes checking whether different populations are all getting the care they need and looking for ways to improve the care. Implementation science studies how to make a potential improvement work in the real world. The improvement could be a new way to diagnose or treat a health condition, a better way to deliver health care or do research, or a strategy to remove barriers preventing specific populations from getting the best available care. The National Hemophilia Foundation focuses on improving the lives of all people with bleeding disorders (BD). They brought BDs doctors, nurses, physical therapists, social workers, professors, and government and industry partners together with people and families living with BDs to discuss research in the areas described above. The group came up with important future research questions to address racism and other biases, and other changes to policies, procedures, and practices to make BD care equitable, efficient, and effective. | eng

BACKGROUND: Viral respiratory infections (VRIs) are common and are occupational risks for healthcare personnel (HCP). VRIs can also be acquired at home and other settings among HCPs. We sought to determine if preschool-aged household contacts are a risk factor for VRIs among HCPs working in outpatient settings. METHODS: We conducted a secondary analysis of data from a cluster randomized trial at 7 medical centers in the United States over 4 influenza seasons from 2011-2012 to 2014-2015. Adult HCPs who routinely came within 6 feet of patients with respiratory infections were included. Participants were tested for respiratory viruses whenever symptomatic and at 2 random times each season when asymptomatic. The exposure of interest was the number of household contacts 0-5 years old (preschool-aged) at the beginning of each HCP-season. The primary outcome was the rate of polymerase chain reaction-detected VRIs, regardless of symptoms. The VRI incidence rate ratio (IRR) was calculated using a mixed-effects Poisson regression model that accounted for clustering at the clinic level. RESULTS: Among the 4476 HCP-seasons, most HCPs were female (85.4%) and between 30 and 49 years of age (54.6%). The overall VRI rate was 2.04 per 100 person-weeks. In the adjusted analysis, HCPs having 1 (IRR, 1.22 [95% confidence interval {CI}, 1.05-1.43]) and ≥2 (IRR, 1.35 [95% CI, 1.09-1.67]) preschool-aged household contacts had higher VRI rates than those with zero preschool-aged household contacts. CONCLUSIONS: Preschool-aged household contacts are a risk factor for developing VRIs among HCPs working in outpatient settings.

PURPOSE: Autism spectrum disorder (ASD) prevalence information is necessary for identifying community needs such as addressing disparities in identification and services. METHODS: Seven Autism and Developmental Disabilities Monitoring (ADDM) Network sites participated in a pilot project to link statewide health and education data to generate county-level prevalence estimates for a broader age range for their states for the first time. RESULTS: Statewide prevalence of ASD for ages 3-21 years in 2018 ranged from 1.5% in Tennessee and Wisconsin to 2.3% in Arizona. The median county-level prevalence of ASD was 1.4% of residents ages 3-21 years. More boys than girls had ASD at all sites, and prevalence was lower among non-Hispanic Black (Black), Hispanic, Asian/Pacific Islander (A/PI), and American Indian/Alaska Native (AI/AN) residents compared to non-Hispanic White (White) residents at most sites. ASD prevalence estimates for children aged 8 years were similar to 2018 ADDM Network estimates that used record review to provide more in-depth information, but showed greater variation for children aged 4 years. CONCLUSION: Linkage of statewide data sets provides less detailed but actionable local information when more resource-intensive methods are not possible.

BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa. METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year. FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs $150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114. INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing. FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Low-cost particulate matter (PM) sensors provide new methods for monitoring occupational exposure to hazardous substances, such as flour dust. These devices have many possible benefits, but much remains unknown about their performance for different exposure monitoring strategies in the workplace. We explored the performance of PM sensors for four different monitoring strategies (time-weighted average and high time resolution, each quantitative and semi-quantitative) for assessing occupational exposure using low-cost PM sensors in a field study in the industrial bakery sector. Measurements were collected using four types of sensor (PATS+, Isensit, Airbeam2, and Munisense) and two reference devices (respirable gravimetric samplers and an established time-resolved device) at two large-scale bakeries, spread over 11 participants and 6 measurement days. Average PM2.5 concentrations of the low-cost sensors were compared with gravimetric respirable concentrations for 8-h shift periods and 1-min PM2.5 concentrations of the low-cost sensors were compared with time-resolved PM2.5 data from the reference device (quantitative monitoring strategy). Low-cost sensors were also ranked in terms of exposure for 8-h shifts and for 15-min periods with a shift (semi-quantitative monitoring strategy). Environmental factors and methodological variables, which can affect sensor performance, were investigated. Semi-quantitative monitoring strategies only showed more accurate results compared with quantitative strategies when these were based on shift-average exposures. The main factors that influenced sensor performance were the type of placement (positioning the devices stationary versus personal) and the company or workstation where measurements were collected. Together, these findings provide an overview of common strengths and drawbacks of low-cost sensors and different ways these can be applied in the workplace. This can be used as a starting point for further investigations and the development of guidance documents and data analysis methods.

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.