Despite annual vaccination, influenza B viruses (IBV) continue to cause significant morbidity and mortality in humans. We have found that IBV infection resulted in a weaker innate and adaptive immune response than influenza A viruses (IAV) in ferrets. To understand and overcome the weak immune responses to IBV in ferrets, we administered type-I or type-III interferon (IFN) to ferrets following infection or vaccination and evaluated their effects on the immune response. IFN signaling following viral infection plays an important role in the initial innate immune response and affects subsequent adaptive immune responses. In the respiratory tract, IFN lambda (IFNL) has regulatory effects on adaptive immunity indirectly through thymic stromal lymphopoietin (TSLP), which then acts on immune cells to stimulate the adaptive response. Following IBV infection or vaccination, IFN treatment (IFN-Tx) upregulated gene expression of early inflammatory responses in the upper respiratory tract and robust IFN, TSLP, and inflammatory responses in peripheral blood cells. These responses were sustained following challenge or vaccination in IFN-Tx animals. Serum IFNL and TSLP levels were enhanced in IFN-Tx animals following challenge/rechallenge over mock-Tx; however, this difference was not observed following vaccination. Antibody responses in serum of IFN-Tx animals following IBV infection or vaccination increased more quickly and to higher titers and were sustained longer than mock-Tx animals over 3 months. Following rechallenge of infected animals 3 months post treatment, antibody levels remained higher than mock-Tx. However, IFN-Tx did not have an effect on antibody responses following challenge of vaccinated animals. A strong direct correlation was found between TSLP levels and antibody responses following challenge-rechallenge and vaccination-challenge indicating it as a useful tool for predicting adaptive immune responses following IBV infection or vaccination. The effects of IFN on strengthening both innate and adaptive responses to IBV may aid in development of more effective treatments following infection and improved influenza vaccines.

Despite the development of the Model Aquatic Health Code (MAHC), U.S. public health departments and aquatics agencies face obstacles in incorporating this guidance into their pool codes. A cross comparison of five state pool codes with the MAHC was conducted to quantify MAHC incorporation into these state codes. The proportion of MAHC code agreement with state codes in this study had a range of 14%–86%. Only 2% of all the MAHC codes available were present in all five state codes, conversely, 12% of the MAHC codes were not found in any state. These differences in code agreement highlight the challenge of measuring MAHC effectiveness at the national level. To improve aquatic safety at a national level, a potential solution is development and use of common core elements in state and local pool codes. Once there is a basis for code comparisons across states, public health programs can investigate whether core MAHC codes result in reduced waterborne illness outbreaks, drowning incidents, injuries from pool chemicals, health outcomes from exposure to disinfection by-products, and swimming-related emergency department visits. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

BACKGROUND: Traumatic injury is a leading cause of death and disability among US workers. Severe injuries are less subject to systematic ascertainment bias related to factors such as reporting barriers, inpatient admission criteria, and workers' compensation coverage. A state-based occupational health indicator (OHI #22) was initiated in 2012 to track work-related severe traumatic injury hospitalizations. After 2015, OHI #22 was reformulated to account for the transition from the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to ICD-10-CM. This study describes rates and trends in OHI #22, alongside corresponding metrics for all work-related hospitalizations. METHODS: Seventeen states used hospital discharge data to calculate estimates for calendar years 2012-2019. State-panel fixed-effects regression was used to model linear trends in annual work-related hospitalization rates, OHI #22 rates, and the proportion of work-related hospitalizations resulting from severe injuries. Models included calendar year and pre- to post-ICD-10-CM transition. RESULTS: Work-related hospitalization rates showed a decreasing monotonic trend, with no significant change associated with the ICD-10-CM transition. In contrast, OHI #22 rates showed a monotonic increasing trend from 2012 to 2014, then a significant 50% drop, returning to a near-monotonic increasing trend from 2016 to 2019. On average, OHI #22 accounted for 12.9% of work-related hospitalizations before the ICD-10-CM transition, versus 9.1% post-transition. CONCLUSIONS: Although hospital discharge data suggest decreasing work-related hospitalizations over time, work-related severe traumatic injury hospitalizations are apparently increasing. OHI #22 contributes meaningfully to state occupational health surveillance efforts by reducing the impact of factors that differentially obscure minor injuries; however, OHI #22 trend estimates must account for the ICD-10-CM transition-associated structural break in 2015.

INTRODUCTION: Quantifying disparities in social determinants of health between people with HIV and the total population could help address health inequities, and ensure health and well-being among people with HIV in the U.S., but estimates are lacking. METHODS: Several representative data sources were used to assess differences in social determinants of health between adults with diagnosed HIV (Centers for Disease Control and Prevention Medical Monitoring Project) and the total adult population (U.S. Census Bureau's decennial census, American Community Survey, Household Pulse Survey, the Current Population Survey Annual Social and Economic Supplements; the Department of Housing and Urban Development's point-in-time estimates of homelessness; and the Bureau of Justice Statistics). The differences were quantified using standardized prevalence differences and standardized prevalence ratios, adjusting for differences in age, race/ethnicity, and birth sex between people with HIV and the total U.S. population. RESULTS: Overall, 35.6% of people with HIV were living in a household with an income at or below the federal poverty level, and 8.1% recently experienced homelessness. Additionally, 42.9% had Medicaid and 27.6% had Medicare; 39.7% were living with a disability. Over half (52.3%) lived in large central metropolitan counties and 20.6% spoke English less than very well based on survey responses. After adjustment, poverty (standardized prevalence difference=25.1%, standardized prevalence ratio=3.5), homelessness (standardized prevalence difference=8.5%, standardized prevalence ratio=43.5), coverage through Medicaid (standardized prevalence difference=29.5%, standardized prevalence ratio=3.0) or Medicare (standardized prevalence difference=7.8%), and disability (standardized prevalence difference=30.3%, standardized prevalence ratio=3.0) were higher among people with HIV than the total U.S. population. The percentage of people with HIV living in large central metropolitan counties (standardized prevalence difference=13.4%) or who were recently incarcerated (standardized prevalence ratio=5.9) was higher than the total U.S. population. CONCLUSIONS: These findings provide a baseline for assessing national-level disparities in social determinants of health between people with HIV and the total U.S. population, and it can be used as a model to assess local disparities. Addressing social determinants of health is essential for achieving health equity, requiring a multipronged approach with interventions at the provider, facility, and policy levels.

Type I interferon receptor knockout (IFNAR-/-) mice are not able to generate a complete innate immune response, therefore, these mice are often considered to assess the pathogenicity of emerging viruses. We sought to assess the pathogenicity of emerging wildtype filovirus infections in IFNAR-/- mice since filovirus models using immunocompetent mice require a mouse-adapted viral strain. We infected IFNAR-/- mice with a low or high dose of Lloviu virus (LLOV) or Bombali virus (BOMV) by the intranasal (i.n.) or intraperitoneal (i.p.) route and compared virus loads at early and late timepoints after infection. No signs of disease and no viral RNA were detected after i.n. infection regardless of LLOV dose. In contrast, i.p. infections resulted in increased viral loads in the high-dose LLOV and BOMV groups at the early timepoint. The low-dose LLOV and BOMV groups achieved higher viral loads at the late timepoint. However, there was 100% survival in all groups and no signs of disease. In conclusion, our results indicate a limited value of the IFNAR-/- mouse model for investigation of the pathogenicity of LLOV and BOMV.

Commercially-available location-based services (LBS) data derived primarily from mobile devices may provide an alternative to surveys for monitoring physically-active transportation. Using Spearman correlation, we compared county-level metrics of walking and bicycling from StreetLight with metrics of physically-active commuting among U.S. workers from the American Community Survey. Our strongest pair of metrics ranked counties (n = 298) similarly for walking (rho = 0.53 [95% CI: 0.44-0.61]) and bicycling (rho = 0.61 [0.53-0.67]). Correlations were higher for denser and more urban counties. LBS data may offer public health and transportation professionals timely information on walking and bicycling behavior at finer geographic scales than some existing surveys.

Critical to identifying the risk of environmentally driven disease is an understanding of the cumulative impact of environmental conditions on human health. Here we describe the methodology used to develop an environmental burden index (EBI). The EBI is calculated at U.S. census tract level, a finer scale than many similar national-level tools. EBI scores are also stratified by tract land cover type as per the National Land Cover Database (NLCD), controlling for urbanicity. The EBI was developed over the course of four stages: 1) literature review to identify potential indicators, 2) data source acquisition and indicator variable construction, 3) index creation, and 4) stratification by land cover type. For each potential indicator, data sources were assessed for completeness, update frequency, and availability. These indicators were: (1) particulate matter (PM2.5), (2) ozone, (3) Superfund National Priority List (NPL) locations, (4) Toxics Release Inventory (TRI) facilities, (5) Treatment, Storage, and Disposal (TSD) facilities, (6) recreational parks, (7) railways, (8) highways, (9) airports, and (10) impaired water sources. Indicators were statistically normalized and checked for collinearity. For each indicator, we computed and summed percentile ranking scores to create an overall ranking for each tract. Tracts having the same plurality of land cover type form a 'peer' group. We re-ranked the tracts into percentiles within each peer group for each indicator. The percentile scores were combined for each tract to obtain a stratified EBI. A higher score reveals a tract with increased environmental burden relative to other tracts of the same peer group. We compared our results to those of related indices, finding good convergent validity between the overall EBI and CalEnviroScreen 4.0. The EBI has many potential applications for research and use as a tool to develop public health interventions at a granular scale.

On August 29, 2021, the United States government oversaw the emergent establishment of Operation Allies Welcome (OAW), led by the U.S. Department of Homeland Security (DHS) and implemented by the U.S. Department of Defense (DoD) and U.S. Department of State (DoS), to safely resettle U.S. citizens and Afghan nationals from Afghanistan to the United States. Evacuees were temporarily housed at several overseas locations in Europe and Asia* before being transported via military and charter flights through two U.S. international airports, and onward to eight U.S. military bases,(†) with hotel A used for isolation and quarantine of persons with or exposed to certain infectious diseases.(§) On August 30, CDC issued an Epi-X notice encouraging public health officials to maintain vigilance for measles among Afghan evacuees because of an ongoing measles outbreak in Afghanistan (25,988 clinical cases reported nationwide during January-November 2021) (1) and low routine measles vaccination coverage (66% and 43% for the first and second doses, respectively, in 2020) (2).

BACKGROUND: A four-month regimen containing rifapentine and moxifloxacin has non-inferior efficacy compared to the standard 6-month regimen for drug-sensitive tuberculosis. We evaluated the effect of regimens containing daily, high-dose rifapentine on efavirenz pharmacokinetics and viral suppression in patients with HIV-associated TB. METHODS: In the context of a Phase 3 randomized controlled trial, HIV-positive individuals already virally suppressed on efavirenz--containing ART (EFV1), or newly initiating efavirenz (EFV2) received TB treatment containing rifapentine (1200mg), isoniazid, pyrazinamide, and either ethambutol or moxifloxacin. Mid-interval efavirenz concentrations were measured (a) during ART and TB co-treatment (Weeks 4, 8, 12 and 17, different by EFV group) and (b) when ART was taken alone (pre- or post-TB treatment, Weeks 0 and 22). Apparent oral clearance (CL/F) was estimated and compared. Target mid-interval efavirenz concentrations were > 1 mg/L. Co-treatment was considered acceptable if >80% of participants had mid-interval efavirenz concentrations meeting this target. RESULTS: EFV1 and EFV2 included 70 and 41 evaluable participants, respectively. The geometric mean ratio comparing efavirenz CL/F with vs. without TB drugs was 0.79 [90% CI 0.72-0.85] in EFV1 and 0.84 [90% CI 0.69-0.97] in EFV2. The percent of participants with mid-interval efavirenz concentrations >1mg/L in EFV1 at Weeks 0, 4, 8, and 17 was 96%, 96%, 88%, and 89%, respectively. In EFV2, at approximately 4 and 8 weeks post efavirenz initiation, the value was 98%. CONCLUSIONS: TB treatment containing high-dose daily rifapentine modestly decreased (rather than increased) efavirenz clearance and therapeutic targets were met supporting the use of efavirenz with these regimens, without dose adjustment.

PURPOSE: Early COVID-19 mitigation relied on people staying home except for essential trips. The ability to stay home may differ by sociodemographic factors. We analyzed how factors related to social vulnerability impact a community's ability to stay home during a stay-at-home order. METHODS: Using generalized, linear mixed models stratified by stay-at-home order (mandatory or not mandatory), we analyzed county-level stay-at-home behavior (inferred from mobile devices) during a period when a majority of United States counties had stay-at-home orders (April 7 to April 20, 2020) with the Centers for Disease Control and Prevention Social Vulnerability Index. RESULTS: Counties with higher percentages of single-parent households, mobile homes, and persons with lower educational attainment were associated with lower stay-at-home behavior compared with counties with lower respective percentages. Counties with higher unemployment, higher percentages of limited-English-language speakers, and more multi-unit housing were associated with increases in stay-at-home behavior compared with counties with lower respective percentages. Stronger effects were found in counties with mandatory orders. CONCLUSIONS: Sociodemographic factors impact a community's ability to stay home during COVID-19 stay-at-home orders. Communities with higher social vulnerability may have more essential workers without work-from-home options or fewer resources to stay home for extended periods, which may increase risk for COVID-19. Results are useful for tailoring messaging, COVID-19 vaccine delivery, and responses to future outbreaks.

Documenting the importance of NK cell function as a biomarker for diseases and physiologic conditions including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), will require assays amenable to clinical implementation and standardization. Research studies typically perform NK functional assays on the day of sample collection. This pilot study was conducted to compare assay formats and specimen processing to identify those that are most tolerant of conditions required for shipping and amenable to standardization as shown by inter-assay and inter-laboratory correlation of results. We compared performance within and between assays that measure NK cell function using direct cytotoxicity [chromium-51 release (CRCA) or fluorescence (Flow Cytometry Cytotoxicity Assay, FCCA)] or an indirect surrogate marker (CD107a surface expression)]. Additional variables for within/between assay comparisons included time of testing (same day as specimen collection or next day within 24 h), specimen types [whole blood or isolated peripheral blood mononuclear cells (PBMCs)], and processing method (fresh or cryopreserved). Statistical measures included number of samples tested in assay conditions (n), medians (x͂), interquartile range (IQR), Pearson correlation coefficient (R(2)), and correlation p-value (p). Samples came from 3 clinics and included 31 participants. Same day testing was only available for the subset of participants enrolled from the site of the laboratory performing CRCA. Results from same day CRCA testing of whole blood were considered the gold standard [n = 10, x͂=10.0%, IQR = 7.2%], and correlated well with PBMCs isolated next day [n = 26, x͂= 15.6%, IQR = 13.1%] [R(2) = 0.59, p = 0.03]. Next day CRCA results were compromised using whole blood or frozen PBMCs. Next day FCCA cytotoxicity in PBMC [n = 30, x͂=34.1%, IQR = 15.5%] correlated with same day CRCA PMBC [R(2) = 0.8, p = 0.001] and next day CRCA PMBC [R(2) = 0.5, p < 0.0001]. CD107a expression after induction by PMA and ionomycin did not correlate with other cytotoxicity measures. NK function can be measured in PBMCs isolated after overnight shipping/storage at ambient temperature and CRCA and FCCA results on this sample type are well correlated.

BACKGROUND AND OBJECTIVE: Community mitigation strategies could help reduce COVID-19 incidence. In a national county-level analysis, we examined the probability of being identified as a county with rapidly increasing COVID-19 incidence (rapid riser identification) during the summer of 2020 by implementation of mitigation policies prior to the summer, overall and by urbanicity. METHODS: We analyzed county-level data on rapid riser identification during June 1-September 30, 2020 and statewide closures and statewide mask mandates starting March 19 (obtained from state government websites). Poisson regression models with robust standard error estimation were used to examine differences in the probability of rapid riser identification by implementation of mitigation policies (P-value<.05); associations were adjusted for county population size. RESULTS: Counties in states that closed for 0-59 days were more likely to become a rapid riser county than those that closed for >59 days, particularly in nonmetropolitan areas. The probability of becoming a rapid riser county was 43% lower among counties that had statewide mask mandates at reopening (adjusted prevalence ratio [aPR] = 0.57; 95% confidence intervals [CI] = 0.51-0.63); when stratified by urbanicity, associations were more pronounced in nonmetropolitan areas. CONCLUSIONS: These results underscore the potential value of community mitigation strategies in limiting the COVID-19 spread, especially in nonmetropolitan areas.

During early August 2020, county-level incidence of coronavirus disease 2019 (COVID-19) generally decreased across the United States, compared with incidence earlier in the summer (1); however, among young adults aged 18-22 years, incidence increased (2). Increases in incidence among adults aged ≥60 years, who might be more susceptible to severe COVID-19-related illness, have followed increases in younger adults (aged 20-39 years) by an average of 8.7 days (3). Institutions of higher education (colleges and universities) have been identified as settings where incidence among young adults increased during August (4,5). Understanding the extent to which these settings have affected county-level COVID-19 incidence can inform ongoing college and university operations and future planning. To evaluate the effect of large colleges or universities and school instructional format* (remote or in-person) on COVID-19 incidence, start dates and instructional formats for the fall 2020 semester were identified for all not-for-profit large U.S. colleges and universities (≥20,000 total enrolled students). Among counties with large colleges and universities (university counties) included in the analysis, remote-instruction university counties (22) experienced a 17.9% decline in mean COVID-19 incidence during the 21 days before through 21 days after the start of classes (from 17.9 to 14.7 cases per 100,000), and in-person instruction university counties (79) experienced a 56.2% increase in COVID-19 incidence, from 15.3 to 23.9 cases per 100,000. Counties without large colleges and universities (nonuniversity counties) (3,009) experienced a 5.9% decline in COVID-19 incidence, from 15.3 to 14.4 cases per 100,000. Similar findings were observed for percentage of positive test results and hotspot status (i.e., increasing among in-person-instruction university counties). In-person instruction at colleges and universities was associated with increased county-level COVID-19 incidence and percentage test positivity. Implementation of increased mitigation efforts at colleges and universities could minimize on-campus COVID-19 transmission.

Poverty, crowded housing, and other community attributes associated with social vulnerability increase a community's risk for adverse health outcomes during and following a public health event (1). CDC uses standard criteria to identify U.S. counties with rapidly increasing coronavirus disease 2019 (COVID-19) incidence (hotspot counties) to support health departments in coordinating public health responses (2). County-level data on COVID-19 cases during June 1-July 25, 2020 and from the 2018 CDC social vulnerability index (SVI) were analyzed to examine associations between social vulnerability and hotspot detection and to describe incidence after hotspot detection. Areas with greater social vulnerabilities, particularly those related to higher representation of racial and ethnic minority residents (risk ratio [RR] = 5.3; 95% confidence interval [CI] = 4.4-6.4), density of housing units per structure (RR = 3.1; 95% CI = 2.7-3.6), and crowded housing units (i.e., more persons than rooms) (RR = 2.0; 95% CI = 1.8-2.3), were more likely to become hotspots, especially in less urban areas. Among hotspot counties, those with greater social vulnerability had higher COVID-19 incidence during the 14 days after detection (212-234 cases per 100,000 persons for highest SVI quartile versus 35-131 cases per 100,000 persons for other quartiles). Focused public health action at the federal, state, and local levels is needed not only to prevent communities with greater social vulnerability from becoming hotspots but also to decrease persistently high incidence among hotspot counties that are socially vulnerable.

In recent years, phylogenetic analysis of HIV sequence data has been used in research studies to investigate transmission patterns between individuals and groups, including analysis of data from HIV prevention clinical trials; in molecular epidemiology; and in public health surveillance programs. Phylogenetic analysis can provide valuable information to inform HIV prevention efforts, but it also has risks, including stigma and marginalization of groups, or potential identification of HIV transmission between individuals. In response to these concerns, an interdisciplinary working group was assembled to address ethical challenges in United States-based HIV phylogenetic research. The working group developed recommendations regarding (1) study design; (2) data security, access, and sharing; (3) community engagement; (4) legal issues; and (5) communication and dissemination. The working group also identified areas for future research and scholarship to promote ethical conduct of HIV phylogenetic research.

Unintentional non-fire related (UNFR) carbon monoxide (CO) poisoning is a preventable cause of morbidity and mortality. Epidemiological data on UNFR CO poisoning can help monitor changes in the magnitude of this burden, particularly through comparisons of multiple countries, and to identify vulnerable sub-groups of the population which may be more at risk. Here, we collected data on age- and sex- specific number of hospital admissions with a primary diagnosis of UNFR CO poisoning in England (2002-2016), aggregated to small areas, alongside area-level characteristics (i.e. deprivation, rurality and ethnicity). We analysed temporal trends using piecewise log-linear models and compared them to analogous data obtained for Canada, France, Spain and the US. We estimated age-standardized rates per 100,000 inhabitants by area-level characteristics using the WHO standard population (2000-2025). We then fitted the Besag York Mollie (BYM) model, a Bayesian hierarchical spatial model, to assess the independent effect of each area-level characteristic on the standardized risk of hospitalization. Temporal trends showed significant decreases after 2010. Decreasing trends were also observed across all countries studied, yet France had a 5-fold higher risk. Based on 3399 UNFR CO poisoning hospitalizations, we found an increased risk in areas classified as rural (0.69, 95% CrI: 0.67; 0.80), highly deprived (1.77, 95% CrI: 1.66; 2.10) or with the largest proportion of Asian (1.15, 95% CrI: 1.03; 1.49) or Black population (1.35, 95% CrI: 1.20; 1.80). Our multivariate approach provides strong evidence for the identification of vulnerable populations which can inform prevention policies and targeted interventions.

Global environmental change has degraded ecosystems. Challenges such as climate change, resource depletion (with its huge implications for human health and wellbeing), and persistent social inequalities in health have been identified as global public health issues with implications for both communicable and noncommunicable diseases. This contributes to pressure on healthcare systems, as well as societal systems that affect health. A novel strategy to tackle these multiple, interacting and interdependent drivers of change is required to protect the population's health. Public health professionals have found that building strong, enduring interdisciplinary partnerships across disciplines can address environment and health complexities, and that developing Environmental and Public Health Tracking (EPHT) systems has been an effective tool. EPHT aims to merge, integrate, analyse and interpret environmental hazards, exposure and health data. In this article, we explain that public health decision-makers can use EPHT insights to drive public health actions, reduce exposure and prevent the occurrence of disease more precisely in efficient and cost-effective ways. An international network exists for practitioners and researchers to monitor and use environmental health intelligence, and to support countries and local areas toward sustainable and healthy development. A global network of EPHT programs and professionals has the potential to advance global health by implementing and sharing experience, to magnify the impact of local efforts and to pursue data knowledge improvement strategies, aiming to recognise and support best practices. EPHT can help increase the understanding of environmental public health and global health, improve comparability of risks between different areas of the world including Low and Middle-Income Countries (LMICs), enable transparency and trust among citizens, institutions and the private sector, and inform preventive decision making consistent with sustainable and healthy development. This shows how EPHT advances global health efforts by sharing recent global EPHT activities and resources with those working in this field. Experiences from the US, Europe, Asia and Australasia are outlined for operating successful tracking systems to advance global health.

Researchers from the National Institute for Occupational Safety and Health (NIOSH) developed a light-emitting diode (LED) area luminaire called the Saturn and conducted a laboratory study using a Fletcher High Dual-boom Mast Feed (HDDR) roof bolting machine. The Saturn luminaire was designed to (1) enhance floor illumination to enable better detection of trip hazards in the interior spaces of a roof bolter and (2) reduce glare that has typically been an issue of concern on roof bolters. This paper reports on the results of achieving the second objective. The existing roof bolter lighting was the baseline and was compared with three versions of the Saturn luminaire relative to light intensity (100%, 75%, and 50%). Discomfort and disability glare data were obtained from 30 participants that comprised three age groups. Discomfort glare perceptions were obtained using the De Boer rating scale, and disability glare was quantified by using Mars Letter Contrast Sensitivity tests. Discomfort glare was reduced at least 3 levels with all Saturn versions. Also, a predictive model was used to estimate discomfort glare, and the results were similar. Disability glare was the least for the Saturn’s 50% intensity, and all Saturn versions had significantly less disability glare than with the baseline lighting. Veiling luminance was calculated and used as another indicator of disability glare. Veiling luminance was 28 to 42 times greater with the baseline lighting as compared with that of the Saturn lighting. Lastly, visibility levels were calculated. The Saturn versions were 4 to 6.5 times better in terms of visibility level.

INTRODUCTION: Phase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen. METHODS/DESIGN: S31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients. Both of the four-month regimens contain high-dose rifapentine instead of rifampin, with ethambutol replaced by moxifloxacin in one regimen. All drugs are administered seven days per week, and under direct observation at least five days per week. The primary outcome is tuberculosis disease-free survival at twelve months after study treatment assignment. A total of 2500 participants will be randomized; this gives 90% power to show non-inferiority with a 6.6% margin of non-inferiority. DISCUSSION: This phase 3 trial formally tests the hypothesis that augmentation of rifamycin exposures can shorten tuberculosis treatment to four months. Trial design and standardized implementation optimize the likelihood of obtaining valid results. Results of this trial may have important implications for clinical management of tuberculosis at both individual and programmatic levels. TRIAL REGISTRATION: NCT02410772. Registered 8 April 2015,https://www.clinicaltrials.gov/ct2/show/NCT02410772?term=02410772&rank=1.

A 3rd generation roof bolter canopy air curtain (CAC) has been developed and constructed by J.H. Fletcher & Co., Inc. As with the previous generation of the CAC, this design uses the principle of providing uniform airflow across the canopy area as recommended by the National Institute for Occupational Safety and Health. The new modifications include a plenum that is constructed of a single flat aluminum plate, smaller-diameter airflow openings, and a single row of perimeter nozzles designed to prevent mine air contaminated by respirable dust from entering the CAC protection zone. Field testing was conducted on this new 3rd generation design showing reductions in coal mine respirable dust exposure for roof bolter operators. Dust control efficiencies for the CAC for the left bolter operator (intake side) ranged from approximately 26%-60%, while the efficiencies for the CAC for the right bolter operator (return side) ranged from 3% to 47%.

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.

Testing was completed on an earlier roof bolter CAC that used slots to provide a perimeter airflow. NIOSH tested it due to its unique design that differed from canopies that provided uniform airflow. Based upon NIOSH recommendations from the earlier testing, a 3rd generation roof bolter CAC has been developed by J.H. Fletcher & Co. The changes to this CAC involve design modifications to the plenum outlets, using a single row of outlets on the perimeter and a different material for the plenum. This laboratory testing was a continuation of the original perimeter slotted CAC design. Using gravimetric and instantaneous sampling of respirable dust concentrations underneath and outside of the CAC, the laboratory testing was completed using three different blower fans that delivered differing airflows. The maximum plenum airflow velocities ranged from 2.34 to 3.64 m/s (460–716 fpm). Results showed plenum respirable dust concentrations ranging from 34.6% to 49.3% lower than respirable dust concentrations outside the plenum protection zone, thus showing an improvement in protection for the roof bolter operators.

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures: A panel of several established cardiovascular risk factors. Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results: Of the 731728 participants from the ERFC, 403396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

Gulf War Illness (GWI) is a chronic multi-symptom disorder experienced by as many as a third of the veterans of the 1991 Gulf War; the constellation of "sickness behavior" symptoms observed in ill veterans is suggestive of a neuroimmune involvement. Various chemical exposures and conditions in theater have been implicated in the etiology of the illness. Previously, we found that GW-related organophosphates (OPs), such as the sarin surrogate, DFP, and chlorpyrifos, cause neuroinflammation. The combination of these exposures with exogenous corticosterone (CORT), mimicking high physiological stress, exacerbates the observed neuroinflammation. The potential relationship between the effects of OPs and CORT on the brain versus inflammation in the periphery has not been explored. Here, using our established GWI mouse model, we investigated the effects of CORT and DFP exposure, with or without a chronic application of pyridostigmine bromide (PB) and N,N-diethyl-meta-toluamide (DEET), on cytokines in the liver and serum. While CORT primed DFP-induced neuroinflammation, this effect was largely absent in the periphery. Moreover, the changes found in the peripheral tissues do not correlate with the previously reported neuroinflammation. These results not only support GWI as a neuroimmune disorder, but also highlight the separation between central and peripheral effects of these exposures.

Canopy air curtain (CAC) technology has been developed by the National Institute for Occupational Safety and Health (NIOSH) for use on continuous miners and subsequently roof bolting machines in underground coal mines to protect operators of these machines from overexposure to respirable coal mine dust. The next logical progression is to develop a CAC for shuttle cars to protect operators from the same overexposures. NIOSH awarded a contract to Marshall University and J.H. Fletcher to develop the shuttle car CAC. NIOSH conducted laboratory testing to determine the dust control efficiency of the shuttle car CAC. Testing was conducted on two different cab configurations: a center drive similar to that on a Joy 10SC32AA cab model and an end drive similar to that on a Joy 10SC32AB cab model. Three different ventilation velocities were tested-0.61, 2.0, 4.3 m/s (120, 400, and 850 fpm). The lowest, 0.61 m/s (120 fpm), represented the ventilation velocity encountered during loading by the continuous miner, while the 4.3 m/s (850 fpm) velocity represented ventilation velocity airflow over the shuttle car while tramming against ventilation airflow. Test results showed an average of the dust control efficiencies ranging from 74 to 83% for 0.61 m/s (120 fpm), 39%-43% for 2.0 m/s (400 fpm), and 6%-16% for 4.3 m/s (850 fpm). Incorporating an airflow spoiler to the shuttle car CAC design and placing the CAC so that it is located 22.86 cm (9 in.) forward of the operator improved the dust control efficiency to 51%-55% for 4.3 m/s (850 fpm) with minimal impact on dust control efficiencies for lower ventilation velocities. These laboratory tests demonstrate that the newly developed shuttle car CAC has the potential to successfully protect shuttle car operators from coal mine respirable dust overexposures.

On December 8, 2017, the Utah Poison Control Center (UPCC) notified the Utah Department of Health (UDOH) of reports of emergency department visits associated with reported exposure to products labeled as CBD (cannabidiol), a nonpsychoactive compound derived from Cannabis sativa, the marijuana plant. Five patients experienced adverse reactions, including altered mental status, seizures, confusion, loss of consciousness, and hallucinations. These reactions were inconsistent with known CBD effects (1), which prompted concern for potential adulteration with a synthetic cannabinoid (2). CBD is being studied as a treatment for several health conditions* (3); however, the Food and Drug Administration has not approved any CBD product for the treatment of any condition, and the U.S. Department of Justice Drug Enforcement Administration considers CBD as a Schedule I drug.† Sale of CBD is currently illegal in Utah, although CBD is readily available online and in shops.

The 2013-16 Ebola virus disease outbreak in west Africa was associated with unprecedented challenges in the provision of care to patients with Ebola virus disease, including absence of pre-existing isolation and treatment facilities, patients' reluctance to present for medical care, and limitations in the provision of supportive medical care. Case fatality rates in west Africa were initially greater than 70%, but decreased with improvements in supportive care. To inform optimal care in a future outbreak of Ebola virus disease, we employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to develop evidence-based guidelines for the delivery of supportive care to patients admitted to Ebola treatment units. Key recommendations include administration of oral and, as necessary, intravenous hydration; systematic monitoring of vital signs and volume status; availability of key biochemical testing; adequate staffing ratios; and availability of analgesics, including opioids, for pain relief.

A well-designed physical education (PE) program is inclusive, active, enjoyable and supportive (SHAPE America – Society of Health and Physical Educators, 2015). Irrespective of location, programs are affected by a host of issues in the midst of various school and community climates. Trends toward urbanization in the United States (U.S. Census Bureau, 2012) and worldwide (World Health Organization, 2016) suggest that more and more PE teachers will be working in urban settings. | In October 2009, JOPERD published a special symposium about “Engaging Urban Youths in Physical Education and Physical Activity” (Murgia & McCullick, 2009). Seven years later, many of those considerations remain relevant, such as large class sizes (Dyson, Coviello, DiCesare, & Dyson, 2009; Schmidlein, Vickers, & Chepyator-Thomson, 2014) and limited access to equipment (Schmidlein et al., 2014), a dedicated gymnasium (Fernandes & Sturm, 2010), or outdoor space (Dyson et al., 2009; Hobin et al., 2013). These structural challenges matter. For example, some data suggest that larger class sizes and indoor lessons are associated with students spending significantly less time in moderate-to-vigorous physical activity and with teachers spending more time on classroom management (Skala et al., 2012). In addition, high rates of teacher turnover (Ingersoll, Merrill, & Stuckey, 2014), difficulties communicating with English language learners (ELLs; Kena et al., 2016), and low self-efficacy (Fletcher, Mandigo, & Kosnik, 2013) affect teachers’ ability to engage students in PE in urban settings.

PURPOSE: This paper describes an assessment of community readiness to implement a community-wide teen pregnancy prevention initiative, Youth First, and presents strategies used to enhance this readiness as informed by the assessment. METHODS: Twenty-five community stakeholder interviews were conducted to assess four domains of readiness: (1) attitudes, perception, and knowledge of teen pregnancy; (2) perceived level of readiness; (3) resources, existing and current efforts; and (4) leadership. Interview transcripts were coded and analyzed to identify key themes. RESULTS: Stakeholders acknowledged teen pregnancy as an issue but lacked contextual information. They also perceived the community as ready to address the issue and recognized some organizations already championing efforts. However, many key players were not involved, and ongoing data collection to assess teen pregnancy and prevention efforts was limited. Though many stakeholders were ready to engage in teen pregnancy prevention efforts, they required additional information and training to appropriately address the issue. CONCLUSIONS: In response to the assessment findings, several strategies were applied to address readiness and build Youth First partners' capacity to implement the community-wide initiative. Thus, to successfully implement community-wide prevention efforts, it is valuable to assess the level of community readiness to address health issues.

Testing of the roof bolter canopy air curtain (CAC) designed by the U.S. National Institute for Occupational Safety and Health (NIOSH) has gone through many iterations, demonstrating successful dust control performance under controlled laboratory conditions. J.H. Fletcher & Co., an original equipment manufacturer of mining equipment, further developed the concept by incorporating it into the design of its roof bolting machines. In the present work, laboratory testing was conducted, showing dust control efficiencies ranging from 17.2 to 24.5 percent. Subsequent computational fluid dynamics (CFD) analysis revealed limitations in the design, and a potential improvement was analyzed and recommended. As a result, a new CAC design is being developed, incorporating the results of the testing and CFD analysis.