The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.

Beginning in late 2023, Oropouche virus was identified as the cause of large outbreaks in Amazon regions with known endemic transmission and in new areas in South America and the Caribbean. The virus is spread to humans by infected biting midges and some mosquito species. Although infection typically causes a self-limited febrile illness, reports of two deaths in patients with Oropouche virus infection and vertical transmission associated with adverse pregnancy outcomes have raised concerns about the threat of this virus to human health. In addition to approximately 8,000 locally acquired cases in the Americas, travel-associated Oropouche virus disease cases have recently been identified in European travelers returning from Cuba and Brazil. As of August 16, 2024, a total of 21 Oropouche virus disease cases were identified among U.S. travelers returning from Cuba. Most patients initially experienced fever, myalgia, and headache, often with other symptoms including arthralgia, diarrhea, nausea or vomiting, and rash. At least three patients had recurrent symptoms after the initial illness, a common characteristic of Oropouche virus disease. Clinicians and public health jurisdictions should be aware of the occurrence of Oropouche virus disease in U.S. travelers and request testing for suspected cases. Travelers should prevent insect bites when traveling, and pregnant persons should consider deferring travel to areas experiencing outbreaks of Oropouche virus disease.

As public health laboratories expand their genomic sequencing and bioinformatics capacity for the surveillance of different pathogens, labs must carry out robust validation, training, and optimization of wet- and dry-lab procedures. Achieving these goals for algorithms, pipelines and instruments often requires that lower quality datasets be made available for analysis and comparison alongside those of higher quality. This range of data quality in reference sets can complicate the sharing of sub-optimal datasets that are vital for the community and for the reproducibility of assays. Sharing of useful, but sub-optimal datasets requires careful annotation and documentation of known issues to enable appropriate interpretation, avoid being mistaken for better quality information, and for these data (and their derivatives) to be easily identifiable in repositories. Unfortunately, there are currently no standardized attributes or mechanisms for tagging poor-quality datasets, or datasets generated for a specific purpose, to maximize their utility, searchability, accessibility and reuse. The Public Health Alliance for Genomic Epidemiology (PHA4GE) is an international community of scientists from public health, industry and academia focused on improving the reproducibility, interoperability, portability, and openness of public health bioinformatic software, skills, tools and data. To address the challenges of sharing lower quality datasets, PHA4GE has developed a set of standardized contextual data tags, namely fields and terms, that can be included in public repository submissions as a means of flagging pathogen sequence data with known quality issues, increasing their discoverability. The contextual data tags were developed through consultations with the community including input from the International Nucleotide Sequence Data Collaboration (INSDC), and have been standardized using ontologies - community-based resources for defining the tag properties and the relationships between them. The standardized tags are agnostic to the organism and the sequencing technique used and thus can be applied to data generated from any pathogen using an array of sequencing techniques. The tags can also be applied to synthetic (lab created) data. The list of standardized tags is maintained by PHA4GE and can be found at https://github.com/pha4ge/contextual_data_QC_tags. Definitions, ontology IDs, examples of use, as well as a JSON representation, are provided. The PHA4GE QC tags were tested, and are now implemented, by the FDA's GenomeTrakr laboratory network as part of its routine submission process for SARS-CoV-2 wastewater surveillance. We hope that these simple, standardized tags will help improve communication regarding quality control in public repositories, in addition to making datasets of variable quality more easily identifiable. Suggestions for additional tags can be submitted to PHA4GE via the New Term Request Form in the GitHub repository. By providing a mechanism for feedback and suggestions, we also expect that the tags will evolve with the needs of the community.

Background: Tubal sterilization is more commonly utilized by racial/ethnic minority groups and has been implicated in underscreening for cervical cancer. The objective is to determine if prior tubal sterilization is a risk factor for cervical cancer underscreening. Methods: National Survey of Family Growth dataset from 2015 to 2019 used for analysis; data were weighted to represent the 72 million women in the U.S. population aged 22-49. Chi-square tests, Fisher exact tests, and logistic regression were used for analysis. The primary predictor variable was tubal sterilization which was categorized into no previous sterilization, sterilization completed <5 years ago, and sterilization completed ≥5 years ago. The outcome variable was underscreened versus not underscreened. Other predictor variables included age, household income as a percent of federal poverty level, previous live birth, primary care provider, and insurance status. Results: Prevalence of tubal sterilization completed 5 or more years ago was 12.5% and varied by most measured characteristics in univariate analyses. Approximately 8% of women were underscreened for cervical cancer. In multivariable analyses, women with a tubal sterilization 5 or more years ago had 2.64 times the odds (95% confidence interval = 1.75-4.00) of being underscreened for cervical cancer compared with women who did not have a tubal sterilization. Conclusions: Approximately 4.3 million women ages 22-49 in the United States are potentially underscreened for cervical cancer and women with previous tubal ligation ≥5 years ago are more likely to be underscreened. These results may inform the need for culturally sensitive public health messages informing people who have had these procedures about the need for continued screening.

Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of human populations for centuries(1). A previous genomic study concluded that Shigella dysenteriae type 1 (Sd1), the epidemic dysentery bacillus, emerged and spread worldwide after the First World War, with no clear pattern of transmission(2). This is not consistent with the massive cyclic dysentery epidemics reported in Europe during the eighteenth and nineteenth centuries(1,3,4) and the first isolation of Sd1 in Japan in 1897(5). Here, we report a whole-genome analysis of 331 Sd1 isolates from around the world, collected between 1915 and 2011, providing us with unprecedented insight into the historical spread of this pathogen. We show here that Sd1 has existed since at least the eighteenth century and that it swept the globe at the end of the nineteenth century, diversifying into distinct lineages associated with the First World War, Second World War and various conflicts or natural disasters across Africa, Asia and Central America. We also provide a unique historical perspective on the evolution of antibiotic resistance over a 100-year period, beginning decades before the antibiotic era, and identify a prevalent multiple antibiotic-resistant lineage in South Asia that was transmitted in several waves to Africa, where it caused severe outbreaks of disease.

Nearly a century after the beginning of the antibiotic era, which has been associated with unparalleled improvements in human health and reductions in mortality associated with infection, the dwindling pipeline for new antibiotic classes coupled with the inevitable spread of antimicrobial resistance (AMR) poses a major global challenge. Historically, surveillance of bacteria with AMR typically relied on phenotypic analysis of isolates taken from infected individuals, which provides only a low-resolution view of the epidemiology behind an individual infection or wider outbreak. Recent years have seen increasing adoption of powerful new genomic technologies with the potential to revolutionise AMR surveillance by providing a high-resolution picture of the AMR profile of the bacteria causing infections and providing real-time actionable information for treating and preventing infection. However, many barriers remain to be overcome before genomic technologies can be adopted as a standard part of routine AMR surveillance around the world. Accordingly, the Surveillance and Epidemiology of Drug-resistant Infections Consortium convened an expert working group to assess the benefits and challenges of using genomics for AMR surveillance. In this Series, we detail these discussions and provide recommendations from the working group that can help to realise the massive potential benefits for genomics in surveillance of AMR.

Integration of genomic technologies into routine antimicrobial resistance (AMR) surveillance in health-care facilities has the potential to generate rapid, actionable information for patient management and inform infection prevention and control measures in near real time. However, substantial challenges limit the implementation of genomics for AMR surveillance in clinical settings. Through a workshop series and online consultation, international experts from across the AMR and pathogen genomics fields convened to review the evidence base underpinning the use of genomics for AMR surveillance in a range of settings. Here, we summarise the identified challenges and potential benefits of genomic AMR surveillance in health-care settings, and outline the recommendations of the working group to realise this potential. These recommendations include the definition of viable and cost-effective use cases for genomic AMR surveillance, strengthening training competencies (particularly in bioinformatics), and building capacity at local, national, and regional levels using hub and spoke models.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng

This article presented a new product development tool for adults with intellectual and developmental disabilities (IDD) developed by the Centers for Disease Control and Prevention (CDC). People with IDD who also have extreme low literacy (ELL) have unique communication needs; public health communicators often face challenges developing effective communication materials for this audience. To support CDC communication specialists with the development of communication products for adults with IDD/ELL, CDC, with its partners RTI International and CommunicateHealth, created a product development tool for this audience through literature review, expert input, and interviews with adults with IDD/ELL and caregivers of adults with IDD/ELL. To build evidence around the principles described in the tool, RTI conducted interviewer-administered surveys with 100 caregivers who support people with IDD/ELL. During the interviews, we presented caregivers with stimuli (portions of a communication product) that either did or did not apply a single principle and asked which would be easier for the person they support to understand. Across all 14 principles tested, the caregiver respondents indicated that the principle-based version would be easier for the person they support to understand compared with the non-principle-based version(s). These findings provide additional evidence to support the principles included in CDC's Tool for Developing Products for People with IDD/ELL.

INTRODUCTION: Local data are increasingly needed for public health practice. County-level data on disabilities can be a valuable complement to existing estimates of disabilities. The objective of this study was to describe the county-level prevalence of disabilities among US adults and identify geographic clusters of counties with a higher or lower prevalence of disabilities. METHODS: We applied a multilevel logistic regression and poststratification approach to geocoded 2018 Behavioral Risk Factor Surveillance System data, Census 2018 county-level population estimates, and American Community Survey 2014-2018 poverty estimates to generate county-level estimates for 6 functional disabilities and any disability type. We used cluster-outlier spatial statistical methods to identify clustered counties. RESULTS: Among 3,142 counties, median estimated prevalence was 29.5% for any disability and differed by type: hearing (8.0%), vision (4.9%), cognition (11.5%), mobility (14.9%), self-care (3.7%), and independent living (7.2%). The spatial autocorrelation statistic, Moran's I, was 0.70 for any disability and 0.60 or greater for all 6 types of disability, indicating that disabilities were highly clustered at the county level. We observed similar spatial cluster patterns in all disability types except hearing disability. CONCLUSION: The results suggest substantial differences in disability prevalence across US counties. These data, heretofore unavailable from a health survey, may help with planning programs at the county level to improve the quality of life for people with disabilities.

BACKGROUND: In this study, the authors report on the geospatial distributions of periodontists and adults with severe periodontitis in the United States. METHODS: The authors used geospatial analysis to describe the distribution of periodontists and adults, periodontists vis-à-vis estimated density of adults with severe periodontitis, and their ratios to adults with severe periodontitis. The authors identified locations of 5,415 practicing periodontists through the 2014 National Provider Identifier Registry, linked them with the weighted census number of adults, and estimated the number of adults within a series of circular distance zones. RESULTS: Approximately 60% of adults 30 through 79 years lived within 5 miles of a periodontist, 73% within 10 miles, 85% within 20 miles, and 97% within 50 miles. Proximity to a periodontist varied widely. In urban areas, 95% of adults resided within 10 miles of a periodontist and 100% within 20 miles. Only 24% of adults in rural areas lived within 10 miles of a periodontist. Most periodontists (96.1%) practiced in urban areas, clustering along the eastern and western coasts and in the Midwest, 3.1% in urban clusters elsewhere, and 0.8% in rural areas. Ratios of fewer than 8,000 adults with periodontitis to 1 or more periodontists within 10 miles were clustered mostly in the Northeast, central East Coast, Florida, West Coast, Arizona, and Midwest. CONCLUSIONS: In this study, the authors identified wide variations in geographic proximity to a practicing periodontist for adults with severe periodontitis. PRACTICAL IMPLICATIONS: Dental practitioners may provide preventive care and counseling for periodontitis and referrals for specialty care. Geographic proximity to specialized periodontal care may vary widely by locality.

As of March 7, 2023, a total of 30,235 confirmed and probable monkeypox (mpox) cases were reported in the United States,(†) predominantly among cisgender men(§) who reported recent sexual contact with another man (1). Although most mpox cases during the current outbreak have been self-limited, cases of severe illness and death have been reported (2-4). During May 10, 2022-March 7, 2023, 38 deaths among persons with probable or confirmed mpox(¶) (1.3 per 1,000 mpox cases) were reported to CDC and classified as mpox-associated (i.e., mpox was listed as a contributing or causal factor). Among the 38 mpox-associated deaths, 94.7% occurred in cisgender men (median age = 34 years); 86.8% occurred in non-Hispanic Black or African American (Black) persons. The median interval from symptom onset to death was 68 days (IQR = 50-86 days). Among 33 decedents with available information, 93.9% were immunocompromised because of HIV. Public health actions to prevent mpox deaths include integrated testing, diagnosis, and early treatment for mpox and HIV, and ensuring equitable access to both mpox and HIV prevention and treatment, such as antiretroviral therapy (ART) (5).

IMPORTANCE: Since 1996, the US Preventive Services Task Force has recommended against cervical cancer screening in average-risk women 65 years or older with adequate prior screening. Little is known about the use of cervical cancer screening-associated services in this age group. OBJECTIVE: To examine annual use trends in cervical cancer screening-associated services, specifically cytology and human papillomavirus (HPV) tests, colposcopy, and cervical procedures (loop electrosurgical excision procedure, cone biopsy, and ablation) in Medicare fee-for-service beneficiaries during January 1, 1999, to December 31, 2019, and estimate expenditures for services performed in 2019. DESIGN, SETTING, AND PARTICIPANTS: This population-based, cross-sectional analysis included health service use data across 21 years for women aged 65 to 114 years with Medicare fee-for-service coverage (15-16 million women per year). Data analysis was conducted between July 2021 and April 2022. MAIN OUTCOMES AND MEASURES: Proportion of testing modalities (cytology alone, cytology plus HPV testing [cotesting], HPV testing alone); annual use rate per 1 000 women of cytology and HPV testing, colposcopy, and cervical procedures from 1999 to 2019; Medicare expenditure for these services in 2019. RESULTS: There were 15 323 635 women 65 years and older with Medicare fee-for-service coverage in 1999 and 15 298 656 in 2019. In 2019, the mean (SD) age of study population was 76.2 (8.1) years, 5.1% were Hispanic, 0.5% were non-Hispanic American Indian/Alaska Native, 3.0% were non-Hispanic Asian/Pacific Islander, 7.4% were non-Hispanic Black, and 82.0% were non-Hispanic White. From 1999 to 2019, the percentage of women who received at least 1 cytology or HPV test decreased from 18.9% (2.9 million women) in 1999 to 8.5% (1.3 million women) in 2019, a reduction of 55.3%; use rates of colposcopy and cervical procedures decreased 43.2% and 64.4%, respectively. Trend analyses showed a 4.6% average annual reduction in use of cytology or HPV testing during 1999 to 2019 (P < .001). Use rates of colposcopy and cervical procedures decreased before 2015 then plateaued during 2015 to 2019. The total Medicare expenditure for all services rendered in 2019 was about $83.5 million. About 3% of women older than 80 years received at least 1 service at a cost of $7.4 million in 2019. CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study suggest that while annual use of cervical cancer screening-associated services in the Medicare fee-for-service population older than 65 years has decreased during the last 2 decades, more than 1.3 million women received these services in 2019 at substantial costs.

Background | One in four American adults reports having at least one disability. The COVID-19 pandemic has disproportionately impacted people with disabilities and widened already-existing health disparities and inequities. For many people with intellectual and developmental disabilities (IDD), these disparities are compounded by literacy limitations that make it challenging to access, understand, and act upon critical COVID-19 prevention information. | Methods | Using a design thinking framework, we conducted interviews with 27 caregivers of adults with IDD who also have extreme low literacy (ELL) to assess COVID-19 information needs and recommendations for how health care providers could best provide COVID-19 information. Based on our findings, we developed a draft tip sheet to help health care providers communicate with adults with IDD/ELL about COVID-19. We then tested the tip sheet with six health care providers via a focus group discussion. We refined and finalized the tip sheet based on our focus group findings. | Results | Caregivers noted the importance of visual aids, repetition, empathy and addressing the person with IDD/ELL directly when discussing COVID-19. Many health care providers indicated that the tip sheet would be most helpful for those with limited experience with patients with IDD/ELL and specific instructions for implementing the tips would be important. | Conclusions | We developed an evidence-informed tip sheet to facilitate communication between health care providers and adults with IDD/ELL and their caregivers, particularly around COVID-19.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

OBJECTIVE: To examine trends in the use of cervical cancer screening tests during 2013-2019 among commercially insured women. METHODS: The study population included women of all ages with continuous enrollment each year in the IBM MarketScan commercial or Medicare supplemental databases and without known history of cervical cancer or precancer (range = 6.9-9.8 million women per year). Annual cervical cancer screening test use was examined by three modalities: cytology alone, cytology plus HPV testing (cotesting), and HPV testing alone. Trends were assessed using 2-sided Poisson regression. RESULTS: Use of cytology alone decreased from 34.2% in 2013 to 26.4% in 2019 among women aged 21-29 years (P < .0001). Among women aged 30-64 years, use of cytology alone decreased from 18.9% in 2013 to 8.6% in 2019 (P < .0001), whereas cotesting use increased from 14.9% in 2013 to 19.3% in 2019 (P < .0001). Annual test use for HPV testing alone was below 0.5% in all age groups throughout the study period. Annually, 8.7%-13.6% of women aged 18-20 years received cervical cancer screening. There were persistent differences in screening test use by metropolitan residence and census regions despite similar temporal trends. CONCLUSIONS: Temporal changes in the use of cervical cancer screening tests among commercially insured women track changes in clinical guidelines. Screening test use among individuals younger than 21 years shows that many young women are inappropriately screened for cervical cancer.

Precision public health has been defined in many ways [1]. It can be viewed as an emerging multidisciplinary field that uses genomics, big data, and machine learning/artificial intelligence to predict health risks and outcomes and to improve health at the population level. Just like precision medicine seeks to provide the right intervention to the right patient at the right time, the aim of precision public health is to provide the right intervention to the right population at the right time, with the goal of improving health for all.

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.

The potential for a population at a given location to utilize a health service can be estimated using a newly developed measure called the supply-concentric demand accumulation (SCDA) spatial availability index. Spatial availability is the amount of demand at the given location that can be satisfied by the supply of services at a facility, after discounting the intervening demand among other populations that are located nearer to a facility location than the given population location. This differs from spatial accessibility measures which treat absolute distance or travel time as the factor that impedes utilization. The SCDA is illustrated using pulmonary rehabilitation (PR), which is a treatment for people with chronic obstructive pulmonary disease (COPD). The spatial availability of PR was estimated for each Census block group in Georgia using the 1105 residents who utilized one of 45 PR facilities located in or around Georgia. Data was provided by the Centers for Medicare & Medicaid Services. The geographic patterns of the SCDA spatial availability index and the two-step floating catchment area (2SFCA) spatial accessibility index were compared with the observed PR utilization rate using bivariate local indicators of spatial association. The SCDA index was more associated with PR utilization (Morans I = 0.607, P < 0.001) than was the 2SFCA (Morans I = 0.321, P < 0.001). These results suggest that the measures of spatial availability may be a better way to estimate the health care utilization potential than measures of spatial accessibility.

Multiple chronic conditions (MCC) reduce quality of life and are associated with high per capita health care spending. One potential way to reduce Medicare spending for MCC is to identify counties whose populations have high levels of spending compared to level of disease burden. Using a nationally representative sample of Medicare Fee-for-Service beneficiaries, this paper presents a method to measure the collective burden of several chronic conditions in a population, which the authors have termed the concentration of chronic conditions (CCC). The authors observed a significantly positive linear relationship between the CCC measure and county-level per capita Medicare spending. This area-level measure can be operationalized to identify counties that might benefit from targeted efforts designed to optimally manage and prevent chronic illness.

A catalog of explosion source parameters is valuable for testing methods of source classification in seismically active regions. We develop a manually reviewed catalog of explosions in the Utah region for 1 October 2012 to 30 June 2018 and use it to assess a newly proposed, magnitude-based depth discriminant. Within the Utah region we define 26 event clusters that are primarily associated with mine blasts but also include explosions from weapons testing and disposal. The catalog refinement process consists of confirming the explosion source labels, revising the local (ML) and coda duration (MC) magnitudes, and relocating the hypocenters. The primary features used to determine source labels are waveform characteristics such as frequency content, the proximity of the preliminary epicenter to a permitted blast region, the time of day, and prior notification from mine operators. We reviewed 2199 seismic events of which 1545 are explosions, 459 are local earthquakes, and 195 are other event types. Of the reviewed events, 127 (5.8%) were reclassified with new labels. Over 74% of the reviewed explosions have both ML and MC, a sizable improvement over the unreviewed catalog (65%). The mean MLMC value for the new explosion catalog is -0:196 +/- 0:017 (95% confidence interval) compared with a previously determined value of 0:048 +/- 0:008 for naturally occurring earthquakes in the Utah region. The shallow depths of the explosions lead to enhanced coda production, which in turn leads to anomalously large MC values. This finding confirms that ML-MC is a useful metric for discriminating explosions from deeper tectonic earthquakes in Utah. However, there is significant variation in MLMC among the 26 explosion source regions, suggesting that MLMC observations should be combined with other classification metrics to achieve the best performance in distinguishing explosions from earthquakes.

On behalf of the Saving Mothers, Giving Life (SMGL) Technical Working Group, we would like to thank Holt and Simpson1 for their valuable insights. We also appreciate their interest in finding out more about the planning and implementation process of the initiative, the challenges encountered, and the adaptations needed to account for contextual factors in each country. | | We agree with the authors on the importance of bringing attention to the valuable experiences and lessons learned during the implementation and course of the SMGL activities, including the activities directly related to health systems strengthening (HSS). We generally agree with the points raised regarding a lesser focus on the evaluation of the process of implementation of the SMGL initiative in the supplement in favor of highlighting the outcomes and impacts of the initiative on maternal and newborn health. However, we beg to differ that the implementation experiences of SGML are “not well documented.” | | The articles constituting the supplement do not represent an exhaustive account of all aspects of the SMGL initiative. The select articles published in the supplement have largely focused on the outcomes of the initiative at its conclusion after 5 years of implementation. They add to already published accounts about the initial planning, implementation, and monitoring and evaluation of the SMGL interventions, including a comprehensive external evaluation of inputs and processes undertaken during the first year of the initiative.2 They also add to the article by Kruk and colleagues that focused on the effects of the SMGL on the health systems in Uganda and Zambia during Phase 1.3

Objectives. To demonstrate a flexible and practical method to obtain near real-time estimates of the number of at-risk community-dwelling adults with a chronic condition in a defined area potentially affected by a public health emergency.Methods. We used small area estimation with survey responses from the 2016 Behavioral Risk Factor Surveillance System together with a geographic information system to predict the number of adults with chronic obstructive pulmonary disease who lived in the forecasted path of Hurricane Florence in North and South Carolina in 2018.Results. We estimated that a range of 32 002 to 676 536 adults with chronic obstructive pulmonary disease resided between 50 and 200 miles of 3 consecutive daily forecasted landfalls. The number of affected counties ranged from 8 to 10 (at 50 miles) to as many as 119 to 127 (at 200 miles).Conclusions. Community preparedness is critical to anticipating, responding to, and ameliorating these health threats. We demonstrated the feasibility of quickly producing detailed estimates of the number of residents with chronic conditions who may face life-threatening situations because of a natural disaster. These methods are applicable to a range of planning and response scenarios.

Introduction: Alzheimer's disease and related dementias (ADRD) cause a high burden of morbidity and mortality in the United States. Age, race, and ethnicity are important risk factors for ADRD. Method(s): We estimated the future US burden of ADRD by age, sex, and race and ethnicity by applying subgroup-specific prevalence among Medicare Fee-for-Service beneficiaries aged >=65 years in 2014 to subgroup-specific population estimates for 2014 and population projection data from the United States Census Bureau for 2015 to 2060. Result(s): The burden of ADRD in 2014 was an estimated 5.0 million adults aged >=65 years or 1.6% of the population, and there are significant disparities in ADRD prevalence among population subgroups defined by race and ethnicity. ADRD burden will double to 3.3% by 2060 when 13.9 million Americans are projected to have the disease. Discussion(s): These estimates can be used to guide planning and interventions related to caring for the ADRD population and supporting caregivers.

CONTEXT: Excessive alcohol use is responsible for 88 000 deaths in the United States annually and cost the United States $249 billion in 2010. There is strong scientific evidence that regulating alcohol outlet density is an effective intervention for reducing excessive alcohol consumption and related harms, but there is no standard method for measuring this exposure. PROGRAM: We overview the strategies available for measuring outlet density, discuss their advantages and disadvantages, and provide examples of how they can be applied in practice. IMPLEMENTATION: The 3 main approaches for measuring density are container-based (eg, number of outlets in a county), distance-based (eg, average distance between a college and outlets), and spatial access-based (eg, weighted distance between town center and outlets). EVALUATION: While container-based measures are the simplest to calculate and most intuitive, distance-based or spatial access-based measures are unconstrained by geopolitical boundaries and allow for assessment of clustering (an amplifier of certain alcohol-related harms). Spatial access-based measures can also be adjusted for population size/demographics but are the most resource-intensive to produce. DISCUSSION: Alcohol outlet density varies widely across and between locations and over time, which is why it is important to measure it. Routine public health surveillance of alcohol outlet density is important to identify problem areas and detect emerging ones. Distance- or spatial access-based measures of alcohol outlet density are more resource-intensive than container-based measures but provide a much more accurate assessment of exposure to alcohol outlets and can be used to assess clustering, which is particularly important when assessing the relationship between density and alcohol-related harms, such as violent crime.

CONTEXT: Excessive alcohol use is responsible for 88 000 deaths in the United States annually and cost the United States $249 billion in 2010. There is strong scientific evidence that regulating alcohol outlet density is an effective intervention for reducing excessive alcohol consumption and related harms, but there is no standard method for measuring this exposure. PROGRAM: We overview the strategies available for measuring outlet density, discuss their advantages and disadvantages, and provide examples of how they can be applied in practice. IMPLEMENTATION: The 3 main approaches for measuring density are container-based (eg, number of outlets in a county), distance-based (eg, average distance between a college and outlets), and spatial access-based (eg, weighted distance between town center and outlets). EVALUATION: While container-based measures are the simplest to calculate and most intuitive, distance-based or spatial access-based measures are unconstrained by geopolitical boundaries and allow for assessment of clustering (an amplifier of certain alcohol-related harms). Spatial access-based measures can also be adjusted for population size/demographics but are the most resource-intensive to produce. DISCUSSION: Alcohol outlet density varies widely across and between locations and over time, which is why it is important to measure it. Routine public health surveillance of alcohol outlet density is important to identify problem areas and detect emerging ones. Distance- or spatial access-based measures of alcohol outlet density are more resource-intensive than container-based measures but provide a much more accurate assessment of exposure to alcohol outlets and can be used to assess clustering, which is particularly important when assessing the relationship between density and alcohol-related harms, such as violent crime.

Foodborne diseases represent a major health problem in the United States. The Foodborne Diseases Active Surveillance Network (FoodNet) of CDC's Emerging Infections Program monitors cases of laboratory-diagnosed infection caused by eight pathogens transmitted commonly through food in 10 U.S. sites.* This report summarizes preliminary 2018 data and changes since 2015. During 2018, FoodNet identified 25,606 infections, 5,893 hospitalizations, and 120 deaths. The incidence of most infections is increasing, including those caused by Campylobacter and Salmonella, which might be partially attributable to the increased use of culture-independent diagnostic tests (CIDTs). The incidence of Cyclospora infections increased markedly compared with 2015-2017, in part related to large outbreaks associated with produce (1). More targeted prevention measures are needed on produce farms, food animal farms, and in meat and poultry processing establishments to make food safer and decrease human illness.

STUDY OBJECTIVE: Quantitative data suggest that adolescent users of long-acting reversible contraception (LARC), as compared to short-acting methods (pill, patch, ring, depot medroxyprogesterone acetate [DMPA]), may be less likely to use condoms. We qualitatively describe and explain adolescent contraceptive users' motivations for condom use, including variation by contraceptive type. DESIGN: Individual, in-depth qualitative interviews, analyzed thematically. PARTICIPANTS: Sexually active contraceptive users 17-19 years old (n=30), including LARC (n=10), DMPA (n=10), and oral contraceptive (n=10) users. SETTING: Participants were recruited from public family planning clinics and an adolescent medicine clinic as well as university and other community settings in Atlanta, GA. RESULTS: Overall, most participants (n=25; 83.3%) used condoms with their more effective contraceptive method, although many used them inconsistently (n=11; 44%). Oral contraceptive users were particularly motivated to use condoms for pregnancy prevention, given concerns about contraceptive method efficacy and a desire to be on "the safe side". In contrast, LARC users were primarily motivated by sexually transmitted infection (STI) prevention. DMPA users' motivations were more mixed. Across contraceptive type, factors influencing condom use motivations included sexual health education, personal awareness and/or experience, and perceived consequences and risk. CONCLUSIONS: Given that all participants were using an effective contraceptive method, it is notable that pregnancy prevention was a prominent motivator for using condoms, although LARC users reported STI prevention to be a more important motivation. Parental and school-based sexual health education that clearly addresses STI prevention in addition to pregnancy prevention has the potential to influence condom use motivations and behavior.

A spatially adaptive floating catchment is a circular area that expands outward from a provider location until the estimated demand for services in the nearest population locations exceeds the observed number of health care services performed at the provider location. This new way of creating floating catchments was developed to address the change of spatial support problem (COSP) by upscaling the availability of the service observed at a provider location to the county-level so that its geographic association with utilization could be measured using the same spatial support. Medicare Fee-for-Service claims data were used to identify beneficiaries aged >/=65 years who received outpatient pulmonary rehabilitation (PR) in the Southeastern United States in 2014 (n=8798), the number of PR treatments these beneficiaries received (n=132,508), and the PR providers they chose (n=426). The positive correlation between PR availability and utilization was relatively low, but statistically significant (r=0.619, p<0.001) indicating that most people use the nearest available PR services, but some travel long distances. SAFCs can be created using data from health care systems that collect claim-level utilization data that identifies the locations of providers chosen by beneficiaries of a specific health care procedure.

BACKGROUND: School-based extracurricular activity participation is one of the primary avenues for prosocial activity engagement during adolescence. In this study, we test the "overscheduling hypothesis" or whether the negative relationship between structured activity intensity (ie, hours) and adolescent bullying and fighting levels off or declines at moderate to high intensity (ie, threshold effects). METHODS: This study uses the Dane County Youth Survey (N = 14,124) to investigate the relationship between school-based extracurricular activity participation intensity and bullying perpetration and physical fighting and whether there are threshold effects of activity participation intensity. RESULTS: The results indicate that there is a negative relationship between extracurricular activity participation intensity and bullying perpetration and physical fighting and that there are threshold effects in these relationships at 3 to 4 hours per week. Results also suggest that low-income adolescents engage in more fighting than other youth and the negative relationship between activity participation intensity and physical fighting was mainly concentrated among low-income adolescents. CONCLUSIONS: School-based extracurricular activity participation-in moderation (ie, up to 3-4 hours per week)-may provide a positive, supportive context that could be a promising prevention strategy for bullying and fighting. Implications for future research on how school-based extracurricular activity participation intensity benefits adolescent functioning are discussed.