IMPORTANCE: Adults experiencing homelessness in the US face numerous challenges, including the management of chronic kidney disease (CKD). The extent of a potentially greater risk of adverse health outcomes in the population with CKD experiencing homelessness has not been adequately explored. OBJECTIVE: To evaluate the association between a history of homelessness and the risk of end-stage kidney disease (ESKD) and death among veterans with incident CKD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted between January 1, 2005, and December 31, 2017. Participants included veterans aged 18 years and older with incident stage 3 to 5 CKD utilizing the Veterans Health Administration health care network in the US. Patients were followed-up through December 31, 2018, for the occurrence of ESKD and death. Analyses were performed from September 2022 to October 2023. EXPOSURE: History of homelessness, based on utilization of homeless services in the Veterans Health Administration or International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Homelessness was measured during the 2-year baseline period prior to the index date of incident CKD. MAIN OUTCOMES AND MEASURES: The primary outcomes were ESKD, based on initiation of kidney replacement therapy, and all-cause death. Adjusted hazard ratios (HRs) were calculated to compare veterans with a history of homelessness with those without a history of homelessness. RESULTS: Among 836 361 veterans, the largest proportion were aged 65 to 74 years (274 371 veterans [32.8%]) or 75 to 84 years (270 890 veterans [32.4%]), and 809 584 (96.8%) were male. A total of 26 037 veterans (3.1%) developed ESKD, and 359 991 (43.0%) died. Compared with veterans who had not experienced homelessness, those with a history of homelessness showed a significantly greater risk of ESKD (adjusted HR, 1.15; 95% CI, 1.10-1.20). A greater risk of all-cause death was also observed (HR, 1.48; 95% CI, 1.46-1.50). After further adjustment for body mass index, comorbidities, and medication use, results were attenuated for all-cause death (HR, 1.09; 95% CI, 1.07-1.11) and were no longer significant for ESKD (HR, 1.04; 95% CI, 0.99-1.09). CONCLUSIONS AND RELEVANCE: In this cohort study of veterans with incident stage 3 to 5 CKD, a history of homelessness was significantly associated with a greater risk of ESKD and death, underscoring the role of housing as a social determinant of health.

The epidemiologic and genetic characteristics of mumps viruses detected in China from 1995 to 2010 were analyzed in this study. Mumps remains endemic in China with a high overall incidence rate. The incidence of mumps in Western China was higher than that in other regions of the country. Each year, most of mumps cases occurred between April and July, but a small peak also occurred in November and December. Mumps cases primarily affected the under 15 year old age group. Virologic data demonstrated that genotype F was the predominant circulating genotype throughout China for at least 15 years and no other genotype was detected between 1995 and 2010. Analysis of sequence data from the small hydrophobic (SH) gene indicated that multiple transmission chains of genotype F were found in various provinces of China, with no apparent chronologic and geographic restriction. This is the first report describing the epidemiology of mumps and genetic characterization of mumps viruses at the national level in China.

INTRODUCTION: Wisconsin experienced overlapping and accelerating epidemics of opioid use and COVID-19 after March 2020. We hypothesized that Wisconsin neonatal abstinence syndrome rates increased after March 2020 alongside other markers of opioid burden. METHODS: Retrospective cohort analysis examined deidentified Wisconsin census, birth certificate, death certificate, hospital discharge, Prescription Drug Monitoring Program, emergency medical service run, and COVID-19 diagnosis records spanning January 1, 2019, through December 31, 2021. January 2019 through March 2020 was considered before the onset of COVID-19 (pre); April 2020 through December 2021 was considered post-onset of COVID-19 (post). Wisconsin Department of Health Services guidelines defined 5 Wisconsin regions. Rates pre- to post-onset were compared with P values < 0.05 considered statistically significant. RESULTS: Of 1362 patients, 83.3% completed a COVID-19 vaccination series. Younger patients had increased odds of not completing a COVID-19 vaccination series (mean [SD] 46.7 [14.7] vs 54.3 [15.8]; OR 1.03; 95% CI, 1.02-1.04; P < 0.001). Those who identified as non-White (1.88; 95% CI, 1.16-3.04; P = 0.010) or current smoker (1.85, 95% CI, 1.85-2.79; P = 0.004) had increased odds of not completing a COVID-19 vaccination series. Those who resided in rural ZIP codes (1.81; 95% CI, 1.35-2.43; P < 0.001), had not received a 2019-2020 influenza vaccine (5.13; 95% CI, 3.79-6.96; P < 0.001), or had lower comorbidity scores (2.95; 95% CI, 1.98-4.41; P < 0.001) had higher odds of not completing a COVID-19 vaccination series. CONCLUSIONS: Opioid-associated morbidity and mortality increased in Wisconsin during the study period, including among females age 15 to 44 years. Despite increased opioid burden, neonatal abstinence syndrome incidence decreased in the Southeastern Region. Ongoing neonatal abstinence syndrome and opioid analysis may benefit from region-based contextualization.

A breathable air source is required for a confined space such as an underground refuge alternative (RA) when it is occupied. To minimize the risk of suffocation, federal regulations require that mechanisms be provided and procedures be included so that, within the refuge alternative, the oxygen concentration is maintained at levels between 18.5% and 23% for 96 h. The regulation also requires that, during use of the RA, the concentration of carbon dioxide should not exceed 1%, and the concentration of carbon monoxide should not exceed 25 ppm. The National Institute for Occupational Safety and Health (NIOSH) evaluated the cryogenic air supply's ability to provide breathable air for a refuge alternative. A propane smoker was used to simulate human breathing by burning propane gas which will consume O(2) and generate CO(2) and H(2)O. The rate of propane burned at the smoker was controlled to represent the O(2) consumption rate for the breathing of a certain number of people. Two 96-h tests were conducted in a sealed shipping container, which was used as a surrogate for a refuge alternative. While burning propane gas to simulate human oxygen consumption, cryogenic air was provided to the shipping container to determine if the cryogenic air supply would keep the O(2) level above 18.5% and CO(2) level below 1% inside the shipping container as required by the federal regulations pertaining to refuge alternatives. Both of the 96-h tests simulated the breathing of 21 persons. The first test used the oxygen consumption rate (1.32 cu ft of pure oxygen per hour per person) specified in federal regulations, while the second test used the oxygen consumption rate specified by (Bernard et al. 2018, "Estimation of Metabolic Heat Input for Refuge Alternative Thermal Testing and Simulation," Min. Eng., 70(8), pp. 50-54) (0.67 cu ft of pure oxygen per hour per person). The test data shows that during both 96-h tests, the oxygen level was maintained within a 21-23% range, and the CO(2) level was maintained below 1% (0.2-0.45%). The information in this paper could be useful when applying a cryogenic air supply as a breathable air source for an underground refuge alternative or other confined space. [DOI: 10.1115/1.4064062].

Since its beginning more than 75 years ago [1], epigenetics has been an evolving field with growing applications to the study of cancer, aging, and gene expression in response to environmental exposures. The emergence of high-throughput technology for measuring epigenetic markers has enabled population-based studies [2]. The relatively new field of epigenetic epidemiology investigates epigenetic associations from a population perspective for insights into disease risk, prevention, and progression. Unlike genetic variants, epigenetic markers are dynamic, offering epidemiologists a new approach to linking early life and environmental exposures with disease risk [3]. | | Scientific publications on epigenetic epidemiology have been rapidly increasing in number and variety over the past 20 years. The literature now includes studies of epigenetic markers beyond DNA methylation (DNAm), such as histone modification and non-coding RNA, and consists of a variety of study designs including epigenome-wide association studies (EWAS), candidate gene studies, and clinical trials. Epigenetic markers are investigated as risk factors, such as DNAm in association with type 2 diabetes incidence [4], or outcomes, such as DNAm changes in response to air pollution [5]. The objective of the Epigenetic Epidemiology Publications Database (EEPD) is to offer a user-friendly website to explore the expanding literature in epigenetics, epidemiology, and public health.

This cross-sectional study systematically examines the contributions of COVID-19 and other underlying causes of death to the widened gender life expectancy gap from 2010 to 2021. | eng

Declining response rates and rising costs have prompted the search for alternatives to traditional random-digit dialing (RDD) interviews. In 2021, three Behavioral Risk Factor Surveillance System (BRFSS) pilots were conducted in Texas: data collection using an RDD short message service (RDD SMS) text-messaging push-to-web pilot, an address-based push-to-web pilot, and an internet panel pilot. We used data from the three pilots and from the concurrent Texas BRFSS Computer Assisted Telephone Interview (CATI). We compared unweighted data from these four sources to demographic information from the American Community Survey (ACS) for Texas, comparing respondents' health information across the protocols as well as cost and response rates. Non-Hispanic White adults and college graduates disproportionately responded in all survey protocols. Comparing costs across protocols was difficult due to the differences in methods and overhead, but some cost comparisons could be made. The cost per complete for BRFSS/CATI ranged from $75 to $100, compared with costs per complete for address-based sampling ($31 to $39), RDD SMS ($12 to $20), and internet panel (approximately $25). There were notable differences among survey protocols and the ACS in age, race/ethnicity, education, and marital status. We found minimal differences in respondents' answers to heart disease-related questions; however, responses to flu vaccination questions differed by protocol. Comparable responses were encouraging. Properly weighted web-based data collection may help use data collected by new protocols as a supplement to future BRFSS efforts.

BACKGROUND: Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function. OBJECTIVES: This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility. METHODS: Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data. RESULTS: Seven metabolites were associated with paraben concentration (variable importance to projection score  > 1, false discovery rate-corrected q-value < 0.1). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were unidentified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations. DISCUSSION: This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment. https://doi.org/10.1289/EHP12125.

RATIONALE & OBJECTIVE: While some evidence exists of increased dementia risk from anemia, it is unclear if this association persists among adults with CKD. Anemia may be a key marker for dementia among adults with CKD. We therefore evaluated if anemia is associated with an increased risk of dementia among adults with CKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: The study included 620,095 veterans aged ≥45 years with incident stage 3 CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2)) between January 2005 and December 2016 in the US Veterans Health Administration system and followed through December 31, 2018 for incident dementia, kidney failure or death. EXPOSURES: Anemia was assessed based on the average of hemoglobin levels (g/L) during the two years prior to the date of incident CKD and categorized as normal, mild and moderate/severe anemia (≥12.0, 11.0-11.9, <11.0 g/dL, respectively for women and ≥13.0, 11.0-12.9, <11.0 g/dL for men). OUTCOMES: Dementia and the composite outcome of kidney failure or death. ANALYTICAL APPROACH: Adjusted cause-specific hazard ratios were estimated for each outcome. RESULTS: At the time of incident CKD, mean age was 72 years, 97% were male, and mean eGFR was 51 mL/min per 1.73 m(2). Over a median 4.1 years of follow-up, 92,306 (15%) veterans developed dementia before kidney failure or death. Compared to veterans with CKD without anemia, multivariable-adjusted models showed a 16% (95% confidence interval [CI] 14% to 17%) significantly higher risk of dementia for those with mild anemia and a 27% (95% CI 23% to 31%) higher risk with moderate/severe anemia. Combined risk of kidney failure or death was higher at 39% (95% CI 37% to 40%) and 115% (95% CI 112% to 119%) for mild and moderate/severe anemia, respectively, compared to no anemia. LIMITATIONS: Residual confounding from the observational study design. Findings may not be generalizable to the broader U.S. CONCLUSIONS: Anemia was significantly associated with increased risk of dementia among veterans with incident CKD, underscoring the role of anemia as a predictor of dementia risk.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. In 2020, the COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized hundreds of thousands of specific predictions from more than 50 different academic, industry, and independent research groups. This manuscript systematically evaluates 23 models that regularly submitted forecasts of reported weekly incident COVID-19 mortality counts in the US at the state and national level. One of these models was a multi-model ensemble that combined all available forecasts each week. The performance of individual models showed high variability across time, geospatial units, and forecast horizons. Half of the models evaluated showed better accuracy than a naïve baseline model. In combining the forecasts from all teams, the ensemble showed the best overall probabilistic accuracy of any model. Forecast accuracy degraded as models made predictions farther into the future, with probabilistic accuracy at a 20-week horizon more than 5 times worse than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.Competing Interest StatementAV, MC, and APP report grants from Metabiota Inc outside the submitted work.Funding StatementFor teams that reported receiving funding for their work, we report the sources and disclosures below. CMU-TimeSeries: CDC Center of Excellence, gifts from Google and Facebook. CU-select: NSF DMS-2027369 and a gift from the Morris-Singer Foundation. COVIDhub: This work has been supported by the US Centers for Disease Control and Prevention (1U01IP001122) and the National Institutes of General Medical Sciences (R35GM119582). The content is solely the responsibility of the authors and does not necessarily represent the official views of CDC, NIGMS or the National Institutes of Health. Johannes Bracher was supported by the Helmholtz Foundation via the SIMCARD Information&amp; Data Science Pilot Project. Tilmann Gneiting gratefully acknowledges support by the Klaus Tschira Foundation. DDS-NBDS: NSF III-1812699. EPIFORECASTS-ENSEMBLE1: Wellcome Trust (210758/Z/18/Z) GT_CHHS-COVID19: William W. George Endowment, Virginia C. and Joseph C. Mello Endowments, NSF DGE-1650044, NSF MRI 1828187, research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at Georgia Tech, and the following benefactors at Georgia Tech: Andrea Laliberte, Joseph C. Mello, Richard Rick E. &amp; Charlene Zalesky, and Claudia &amp; Paul Raines GT-DeepCOVID: CDC MInD-Healthcare U01CK000531-Supplement. NSF (Expeditions CCF-1918770, CAREER IIS-2028586, RAPID IIS-2027862, Medium IIS-1955883, NRT DGE-1545362), CDC MInD program, ORNL and funds/computing resources from Georgia Tech and GTRI. IHME: This work was supported by the Bill &amp; Melinda Gates Foundation, as well as funding from the state of Washington and the National Science Foundation (award no. FAIN: 2031096). IowaStateLW-STEM: Iowa State University Plant Sciences Institute Scholars Program, NSF DMS-1916204, NSF CCF-1934884, Laurence H. Baker Center for Bioinformatics and Biological Statistics. JHU_IDD-CovidSP: State of California, US Dept of Health and Human Services, US Dept of Homeland Security, US Office of Foreign Disaster Assistance, Johns Hopkins Health System, Office of the Dean at Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University Modeling and Policy Hub, Centers fo Disease Control and Prevention (5U01CK000538-03), University of Utah Immunology, Inflammation, &amp; Infectious Disease Initiative (26798 Seed Grant). LANL-GrowthRate: LANL LDRD 20200700ER. MOBS-GLEAM_COVID: COVID Supplement CDC-HHS-6U01IP001137-01. NotreDame-mobility and NotreDame-FRED: NSF RAPID DEB 2027718 UA-EpiCovDA: NSF RAPID Grant # 2028401. UCSB-ACTS: NSF RAPID IIS 2029626. UCSD-NEU: Google Faculty Award, DARPA W31P4Q-21-C-0014, COVID Supplement CDC-HHS-6U01IP001137-01. UMass-MechBayes: NIGMS R35GM119582, NSF 1749854. UMich-RidgeTfReg: The University of Michigan Physics Department and the University of Michigan Office of Research.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:UMass-Amherst IRBAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data and code referred to in the manuscript are publicly available. https://github.com/reichlab/covid19-forecast-hub/ https://github.com/reichlab/covidEnsembles https://zoltardata.com/project/44

A 2.5-year-old pediatric patient with acute flaccid paralysis was diagnosed with primary immunodeficiency (PID) in Ningxia Province, China, in 2011. Twelve consecutive stool specimens were collected from the patient over a period of 10 months (18 February 2011 to 20 November 2011), and 12 immunodeficiency vaccine-derived poliovirus (iVDPV) strains (CHN15017-1 to CHN15017-12) were subsequently isolated. Nucleotide sequencing analysis of the plaque-purified iVDPVs revealed 2%-3.5% VP1-region differences from their parental Sabin 3 strain. Full-length genome sequencing showed they were all Sabin 3/Sabin 1 recombinants, sharing a common 2C-region crossover site, and the two key determinants of attenuation (U472C in the 5' untranslated region and T2493C in the VP1 region) had reverted. Temperature-sensitive experiments demonstrated that the first two iVDPV strains partially retained the temperature-sensitive phenotype's nature, while the subsequent ten iVDPV strains distinctly lost it, possibly associated with increased neurovirulence. Nineteen amino-acid substitutions were detected between 12 iVDPVs and the parental Sabin strain, of which only one (K1419R) was found on the subsequent 10 iVDPV isolates, suggesting this site's potential as a temperature-sensitive determination site. A Bayesian Monte Carlo Markov Chain phylogenetic analysis based on the P1 coding region yielded a mean iVDPV evolutionary rate of 1.02 × 10(-2) total substitutions/site/year, and the initial oral-polio-vaccine dose was presumably administered around June 2009. Our findings provide valuable information regarding the genetic structure, high-temperature growth sensitivity, and antigenic properties of iVDPVs following long-term evolution in a single PID patient, thus augmenting the currently limited knowledge regarding the dynamic changes and evolutionary pathway of iVDPV populations with PID during long-term global replication.

Federal regulations require refuge alternatives (RAs) in underground coal mines to provide a life-sustaining environment for miners trapped underground when escape is impossible. A breathable air supply is among those requirements. For built-in-place (BIP) RAs, a borehole air supply (BAS) is commonly used to supply fresh air from the surface. Federal regulations require that such a BAS must supply fresh air at 12.5 cfm or more per person to maintain the oxygen concentration between 18.5% and 23% and carbon dioxide level below the 1% limit specified. However, it is unclear whether 12.5 cfm is indeed needed to maintain this carbon dioxide level. The minimal fresh air flow (FAF) rate needed to maintain the 1% CO2level will depend on multiple factors, including the number of people and the volume of the BIP RA. In the past, to predict the interior CO2concentration in an occupied RA, 96-h tests were performed using a physical human breathing simulator. However, given the infinite possibility of the combinations (number of people, size of the BIP RA), it would be impractical to fully investigate the range of parameters that can affect the CO2concentration using physical tests. In this paper, researchers at the National Institute for Occupational Safety and Health (NIOSH) developed a model that can predict how the %CO2in an occupied confined space changes with time given the number of occupants and the FAF rate. The model was then compared to and validated with test data. The benchmarked model can be used to predict the %CO2for any number of people and FAF rate without conducting a 96-h test. The methodology used in this model can also be used to estimate other gas levels within a confined space. © 2023 American Society of Mechanical Engineers (ASME). All rights reserved.

OBJECTIVE: to conduct a systematic review of the observational studies analyzing the association between ultra-processed food (UPF) intake and the risk of depression. DESIGN: the search adhered to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); a search for observational studies published until June 2020 was performed in PubMed, Embase, Cochrane Library, and Web of Science databases, followed by additional manual searches. Eight reviewers, working independently in teams of two, screened studies for eligibility, extracted data, and assessed risk of bias. We resolved disagreements through discussion or, if necessary, through adjudication by a third (LH). And the study assessed cross-sectional studies using the Agency for Healthcare Research and Quality (AHRQ) methodological checklist and cohort and case-control studies using the Newcastle-Ottawa Scale (NOS) for quality. We used a tabular format to summarize the articles. RESULTS: twenty-eight studies evaluating UPF intake and risk of depression were finally selected, 21 of which had a cross-sectional design, 6 studies had a cohort design, and 1 had a case-control design. Of these, 4 cohort studies and 17 cross-sectional studies found that consumption of UPF were positively associated with depression or depressive symptoms. CONCLUSIONS: our review demonstrated that most studies included in the systematic review showed that UPF consumption is associated with the risk of depression. Future studies should consider the use of validated food intake assessments and standardized depression assessment methods to promote comparability between studies.

INTRODUCTION: Mortality is an important long-term indicator of the public health impact of chronic kidney disease (CKD). We investigated the role of individual comorbidities and multimorbidity on age-specific mortality risk among US veterans with new-onset CKD. METHODS: The cohort included 892,005 veterans aged 18 years with incident CKD stage 3 between January 2004 and April 2018 in the US Veterans Health Administration (VHA) system and followed until death, December 2018, or up to 10 years. Incident CKD was defined as the first-time estimated glomerular filtration rate (eGFR) was <60 mL/min/1.73 m2 for >3 months. Comorbidities were ascertained using inpatient and outpatient clinical records in the VHA system and Medicare claims. We estimated death rates for any cardiovascular disease (CVD, a composite of 6 CVD conditions) and 15 non-CVD comorbidities, and adjusted risks of death (hazard ratio [HR], 95% confidence interval [CI]) overall and by age group at CKD incidence. RESULTS: At CKD incidence, the mean age was 72 years, and 97% were male; the mean eGFR was 52 mL/min/1.73 m2, and 95% had 2 comorbidities (median, 4) in addition to CKD. During a median follow-up of 4.5 years, among the 16 comorbidities, CVD was associated with the highest relative risk of death in younger veterans (HR 1.96 [95% CI: 1.61-2.37] in ages 18-44 years and HR 1.66 [1.63-1.70] in ages 45-64 years). Dementia was associated with the highest relative risk of death among older veterans (HR 1.71 [1.68-1.74] in ages 65-84 years and HR 1.69 [1.65-1.73] in ages 85-100 years). The additive effect of multimorbidity on risk of death was stronger in younger than older veterans. Compared to having 1 or no comorbidity at CKD onset, the risk of death with 5 comorbidities was >7-fold higher among veterans aged 18-44 years and >2-fold higher among veterans aged 85-100 years. CONCLUSION: The large burden of comorbidities in US veterans with newly identified CKD places them at the risk of premature death. Compared with older veterans, younger veterans with multiple comorbidities, particularly with CVD, at CKD onset are at an even higher relative risk of death.

Evaluation of the very-low frequency, ultralow frequency, or extremely low frequency magnetic field (H-field) due to a buried or on-surface magnetic dipole or antenna is important for applications such as geophysical exploration and through-the-Earth (TTE) wireless communications. In this study, we develop an explicit form of magnetic field over multi-layer Earth medium (N > 3). The generalized solution is derived for operating frequency, mine depth, and Earth conductivity that would be typically related to TTE applications. Published 2022. This article is a U.S. Government work and is in the public domain in the USA.

SignificanceThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the United States. Results show high variation in accuracy between and within stand-alone models and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public-health action.

Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.

Standard machine smoking protocols provide useful information for examining the impact of design parameters, such as filter ventilation, on mainstream smoke delivery. Unfortunately, their results do not accurately reflect human smoke exposure. Clinical research and topography devices in human studies yield insights into how products are used, but a clinical setting or smoking a cigarette attached to such a device may alter smoking behavior. To better understand smokers' use of filtered cigarette products in a more natural environment, we developed a low-cost, high-throughput approach to estimate mainstream cigarette smoke exposure on a per-cigarette basis. This approach uses an inexpensive flatbed scanner to scan smoked cigarette filter butts and custom software to analyze tar-staining patterns. Total luminosity, or optical staining density, of the scanned images provides quantitative information proportional to mainstream smoke-constituent deliveries on a cigarette-by-cigarette basis. Duplicate sample analysis using this new approach and our laboratory's gold-standard liquid chromatography/tandem mass spectrometry (LC/MS/MS) solanesol method yielded comparable results (+7% bias) from the analysis of 20 commercial cigarettes brands (menthol and nonmentholated). The brands varied in design parameters such as length, filter ventilation, and diameter. Plots correlating the luminosity to mainstream smoked-nicotine deliveries on a per-cigarette basis for these cigarette brands were linear (average R(2) > 0.91 for nicotine and R(2) > 0.83 for the tobacco-specific nitrosamine NNK), on a per-brand basis, with linearity ranging from 0.15 to 3.00 mg nicotine/cigarette. Analysis of spent cigarette filters allows exposures to be characterized on a per-cigarette basis or a "daily dose" via summing across results from all filter butts collected over a 24 h period. This scanner method has a 100-fold lower initial capital cost for equipment than the LC/MS/MS solanesol method and provides high-throughput results (~200 samples per day). Thus, this new method is useful for characterizing exposure related to filtered tobacco-product use.

BACKGROUND: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions. METHODS: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100% × (1 - hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation. RESULTS: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.).

Short-term in vitro genotoxicity assays are useful tools to assess whether new and emerging tobacco products potentially have reduced toxicity. We previously demonstrated that potency ranking by benchmark dose (BMD) analysis quantitatively identifies differences among several known carcinogens and toxic chemicals representing different chemical classes found in cigarette smoke. In this study, six whole smoke solution (WSS) samples containing both the particulate and gas phases of tobacco smoke were generated from two commercial cigarette brands under different smoking-machine regimens. Sixty test cigarettes of each brand were machine-smoked according to the International Organization for Standardization (ISO) puffing protocol. In addition, either 60 or 20 test cigarettes of each brand were machine-smoked with the Canadian Intense (CI) puffing protocol. All six WSSs were evaluated in the bacterial reverse mutation (Ames) test using Salmonella typhimurium strains, in the presence or absence of S9 metabolic activation. The resulting S9-mediated mutagenic concentration-responses for the four WSSs from 60 cigarettes were then compared using BMD modeling analysis and the mutagenic potency expressed as number of revertants per μl of the WSS. The quantitative approaches resulted in a similar rank order of mutagenic potency for the Ames test in both TA98 and TA100. Under the conditions of this study, these results indicate that quantitative analysis of the Ames test data can discriminate between the mutagenic potencies of WSSs on the basis of smoking-machine regimen (ISO vs. CI), and cigarette product (differences in smoke chemistry).

Mammalian orthoreovirus (MRV) infects multiple mammalian species including humans. A United States Midwest swine farm with approximately one thousand 3-month-old pigs experienced an event, in which more than 300 pigs showed neurological signs, like "down and peddling", with approximately 40% mortality. A novel MRV was isolated from the diseased pigs. Sequence and phylogenetic analysis revealed that the isolate was a reassortant virus containing viral gene segments from three MRV serotypes that infect human, bovine and swine. The M2 and S1 segment of the isolate showed 94% and 92% nucleotide similarity to the M2 of the MRV2 D5/Jones and the S1 of the MRV1 C/bovine/Indiana/MRV00304/2014, respectively; the remaining eight segments displayed 93%-94% nucleotide similarity to those of the MRV3 FS-03/Porcine/USA/2014. Pig studies showed that both MRV-infected and native contact pigs displayed fever, diarrhea and nasal discharge. MRV RNA was detected in different intestinal locations of both infected and contact pigs, indicating that the MRV isolate is pathogenic and transmissible in pigs. Seroconversion was also observed in experimentally infected pigs. A prevalence study on more than 180 swine serum samples collected from two states without disease revealed 40-52% positive to MRV. All results warrant the necessity to monitor MRV epidemiology and reassortment as the MRV could be an important pathogen for the swine industry and a novel MRV might emerge to threaten animal and public health.

BACKGROUND: Respiratory tract infections are common, often seasonal, and caused by multiple pathogens. We assessed whether seasonal respiratory illness patterns changed during the COVID-19 pandemic. METHODS: We categorized emergency department (ED) visits reported to the National Syndromic Surveillance Program according to chief complaints and diagnosis codes, excluding visits with diagnosed SARS-CoV-2 infections. For each week during March 1, 2020 through December 26, 2020 ("pandemic period"), we compared the proportion of ED visits in each respiratory category with the proportion of visits in that category during the corresponding weeks of 2017-2019 ("pre-pandemic period"). We analyzed positivity of respiratory viral tests from two independent clinical laboratories. RESULTS: During March 2020, cough, shortness of breath, and influenza-like illness accounted for twice as many ED visits compared with the pre-pandemic period. During the last four months of 2020, all respiratory conditions, except shortness of breath, accounted for a smaller proportion of ED visits than during the pre-pandemic period. Percent positivity for influenza virus, respiratory syncytial virus, human parainfluenza virus, adenoviruses, and human metapneumovirus were lower in 2020 than 2019. Although test volume decreased, percent positivity was higher for rhinovirus/enterovirus during the final weeks of 2020 compared with 2019; with ED visits similar to the pre-pandemic period. DISCUSSION: Broad reductions in respiratory test positivity and respiratory emergency department visits (excluding COVID-19) occurred during 2020. Interventions for mitigating spread of SARS-CoV-2 likely also reduced transmission of other pathogens. Timely surveillance is needed to understand community health threats, particularly when current trends deviate from seasonal norms.

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated >100 million children in 2010. An increasing proportion of infections now occur among adults and there is concern that persistent susceptibility in adults is an obstacle to measles elimination in China. We performed a case-control study in six Chinese provinces between January 2012 to June 2013 to identify risk factors for measles virus infection and susceptibility among adults. METHODS: Persons ≥15 years old with laboratory-confirmed measles were age and neighborhood matched with three controls. Controls had blood specimens collected to determine their measles IgG serostatus. We interviewed case-patients and controls about potential risk factors for measles virus infection and susceptibility. Unadjusted and adjusted matched odds ratios and 95% confidence intervals (CIs) were calculated via conditional logistic regression. We calculated attributable fractions for infection for risk factors that could be interpreted as causal. RESULTS: 899 cases and 2498 controls were enrolled. Among controls, 165 (6.6%) were seronegative for measles IgG indicating persistent susceptibility to infection. In multivariable analysis, hospital visit and travel outside the prefecture in the prior 1-3 weeks were significant risk factors for measles virus infection. Occupation and reluctance to accept measles vaccination were significant risk factors for measles susceptibility. The calculated attributable fraction of measles cases from hospital visitation was 28.6% (95% CI: 20.6-38.8%). CONCLUSIONS: Exposure to a healthcare facility was the largest risk factor for measles virus infection in adults in China. Improved adherence to hospital infection control practices could reduce risk of ongoing measles virus transmission and increase the likelihood of achieving and sustaining measles elimination in China. The use of control groups stratified by serological status identified distinct risk factors for measles virus infection and susceptibility among adults.

BACKGROUND: To inform prevention strategies, we assessed the extent of SARS-CoV-2 transmission and settings in which transmission occurred in a Georgia public school district. METHODS: During December 1, 2020-January 22, 2021, SARS-CoV-2-infected index cases and their close contacts in schools were identified by school and public health officials. For in-school contacts, we assessed symptoms and offered SARS-CoV-2 RT-PCR testing; performed epidemiologic investigations and whole-genome sequencing to identify in-school transmission; and calculated secondary attack rate (SAR) by school setting (e.g., sports, elementary school classroom), index case role (i.e., staff, student), and index case symptomatic status. RESULTS: We identified 86 index cases and 1,119 contacts, 688 (63.1%) of whom received testing. Fifty-nine (8.7%) of 679 contacts tested positive; 15 (17.4%) of 86 index cases resulted in ≥2 positive contacts. Among 55 persons testing positive with available symptom data, 31 (56.4%) were asymptomatic. Highest SAR were in indoor, high-contact sports settings (23.8%, 95% confidence interval [CI] 12.7, 33.3), staff meetings/lunches (18.2%, CI 4.5-31.8), and elementary school classrooms (9.5%, CI 6.5-12.5). SAR was higher for staff (13.1%, CI 9.0-17.2) versus student index cases (5.8%, CI 3.6-8.0) and for symptomatic (10.9%, CI 8.1-13.9) versus asymptomatic index cases (3.0%, CI 1.0-5.5). CONCLUSIONS: Indoor sports may pose a risk to the safe operation of in-person learning. Preventing infection in staff members, through measures that include COVID-19 vaccination, is critical to reducing in-school transmission. Because many positive contacts were asymptomatic, contact tracing should be paired with testing, regardless of symptoms.

OBJECTIVES: In late June 2020, a large outbreak of coronavirus disease 2019 (COVID-19) occurred at a sleep-away youth camp in Georgia, affecting primarily persons </=21 years. We conducted a retrospective cohort study among campers and staff (attendees) to determine the extent of the outbreak and assess factors contributing to transmission. METHODS: Attendees were interviewed to ascertain demographic characteristics, known exposures to COVID-19 and community exposures, and mitigation measures before, during, and after attending camp. COVID-19 case status was determined for all camp attendees on the basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results and reported symptoms. We calculated attack rates and instantaneous reproduction numbers and sequenced SARS-CoV-2 viral genomes from the outbreak. RESULTS: Among 627 attendees, the median age was 15 years (interquartile range: 12-16 years); 56% (351 of 627) of attendees were female. The attack rate was 56% (351 of 627) among all attendees. On the basis of date of illness onset or first positive test result on a specimen collected, 12 case patients were infected before arriving at camp and 339 case patients were camp associated. Among 288 case patients with available symptom information, 45 (16%) were asymptomatic. Despite cohorting, 50% of attendees reported direct contact with people outside their cabin cohort. On the first day of camp session, the instantaneous reproduction number was 10. Viral genomic diversity was low. CONCLUSIONS: Few introductions of SARS-CoV-2 into a youth congregate setting resulted in a large outbreak. Testing strategies should be combined with prearrival quarantine, routine symptom monitoring with appropriate isolation and quarantine, cohorting, social distancing, mask wearing, and enhanced disinfection and hand hygiene. Promotion of mitigation measures among younger populations is needed.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of SARS-CoV-2 tropism and replication in various tissues. METHODS: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case-patients (age range: 1 month to 84 years; COVID-19 confirmed n=21, suspected n=43) by SARS-CoV-2 RT-PCR. For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in-situ hybridization (ISH), subgenomic RNA RT-PCR, and whole genome sequencing. RESULTS: SARS-CoV-2 was identified by RT-PCR in 32 case-patients (confirmed n=21 and suspected n=11). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case-patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes and macrophages of lungs, epithelial cells of airways, and in endothelial cells and vessels wall of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. D614G variant was detected in 9 RT-PCR-positive case-patients. CONCLUSIONS: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes.

Rapid antigen tests, such as the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW), offer results more rapidly (approximately 15-30 minutes) and at a lower cost than do highly sensitive nucleic acid amplification tests (NAATs) (1). Rapid antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in symptomatic persons (2), but data are lacking on test performance in asymptomatic persons to inform expanded screening testing to rapidly identify and isolate infected persons (3). To evaluate the performance of the BinaxNOW rapid antigen test, it was used along with real-time reverse transcription-polymerase chain reaction (RT-PCR) testing to analyze 3,419 paired specimens collected from persons aged ≥10 years at two community testing sites in Pima County, Arizona, during November 3-17, 2020. Viral culture was performed on 274 of 303 residual real-time RT-PCR specimens with positive results by either test (29 were not available for culture). Compared with real-time RT-PCR testing, the BinaxNOW antigen test had a sensitivity of 64.2% for specimens from symptomatic persons and 35.8% for specimens from asymptomatic persons, with near 100% specificity in specimens from both groups. Virus was cultured from 96 of 274 (35.0%) specimens, including 85 (57.8%) of 147 with concordant antigen and real-time RT-PCR positive results, 11 (8.9%) of 124 with false-negative antigen test results, and none of three with false-positive antigen test results. Among specimens positive for viral culture, sensitivity was 92.6% for symptomatic and 78.6% for asymptomatic individuals. When the pretest probability for receiving positive test results for SARS-CoV-2 is elevated (e.g., in symptomatic persons or in persons with a known COVID-19 exposure), a negative antigen test result should be confirmed by NAAT (1). Despite a lower sensitivity to detect infection, rapid antigen tests can be an important tool for screening because of their quick turnaround time, lower costs and resource needs, high specificity, and high positive predictive value (PPV) in settings of high pretest probability. The faster turnaround time of the antigen test can help limit transmission by more rapidly identifying infectious persons for isolation, particularly when used as a component of serial testing strategies.

BACKGROUND: Myopericarditis after vaccination has been sporadically reported in the medical literature. Here, we present a thorough descriptive analysis of reports to a national passive vaccine safety surveillance system (VAERS) of myopericarditis after vaccines licensed for use in the United States. METHODS: We identified U.S. reports of myopericarditis received by VAERS during 1990-2018 that met a published case definition for myopericarditis or were physician-diagnosed. We stratified analysis by age group (<19, 19-49, ≥50 years), describing reports by serious/non-serious status, sex, time to symptom onset after vaccination, vaccine(s) administered, and exposure to other known causes of myopericarditis. We used Empirical Bayesian data mining to detect disproportionate reporting of myopericarditis after vaccination. RESULTS: VAERS received 620,195 reports during 1990-2018: 708 (0.1%) met the case definition or were physician-diagnosed as myopericarditis. Most (79%) myopericarditis reports described males; 69% were serious; 72% had symptom onset ≤ 2 weeks postvaccination. Overall, smallpox (59%) and anthrax (23%) vaccines were most commonly reported. By age, among persons aged < 19 years, Haemophilus influenzae type b (22, 22%) and hepatitis B (18, 18%); among persons aged 19-49 years smallpox (387, 79%); among persons aged ≥ 50 years inactivated influenza (31, 36%) and live attenuated zoster (19, 22%) vaccines were most commonly reported. The vaccines most commonly reported remained unchanged when excluding 138 reports describing other known causes of myopericarditis. Data mining revealed disproportionate reporting of myopericarditis only after smallpox vaccine. CONCLUSIONS: Despite the introduction of new vaccines over the years, myopericarditis remains rarely reported after vaccines licensed for use in the United States. In this analysis, myopericarditis was most commonly reported after smallpox vaccine, and less commonly after other vaccines.

Habitat disturbance, a common consequence of anthropogenic land use practices, creates human–animal interfaces where humans, wildlife, and domestic species can interact. These altered habitats can influence host–microbe dynamics, leading to potential downstream effects on host physiology and health. Here, we explored the effect of ecological overlap with humans and domestic species and infection with the protozoan parasite Giardia duodenalis on the bacteria of black and gold howler monkeys (Alouatta caraya), a key sentinel species, in northeastern Argentina. Fecal samples were screened for Giardia duodenalis infection using a nested PCR reaction, and the gut bacterial community was characterized using 16S rRNA gene amplicon sequencing. Habitat type was correlated with variation in A. caraya gut bacterial community composition but did not affect gut bacterial diversity. Giardia presence did not have a universal effect on A. caraya gut bacteria across habitats, perhaps due to the high infection prevalence across all habitats. However, some bacterial taxa were found to vary with Giardia infection. While A. caraya's behavioral plasticity and dietary flexibility allow them to exploit a range of habitat conditions, habitats are generally becoming more anthropogenically disturbed and, thus, less hospitable. Alterations in gut bacterial community dynamics are one possible indicator of negative health outcomes for A. caraya in these environments, since changes in host–microbe relationships due to stressors from habitat disturbance may lead to negative repercussions for host health. These dynamics are likely relevant for understanding organism responses to environmental change in other mammals.

Huang Yunfeng, Hui Qin, Gwinn Marta, Hu Yi-Juan, Quyyumi Arshed A, Vaccarino Viola, Sun Yan V. Circulation. Genomic and precision medicine 2020 14(1) e003147