Identifying priority sites for whale shark ship collision management globally.

The expansion of the world's merchant fleet poses a great threat to the ocean's biodiversity. Collisions between ships and marine megafauna can have population-level consequences for vulnerable species. The Endangered whale shark (Rhincodon typus), shares a circumglobal distribution with this expanding fleet and tracking of movement pathways has shown that large vessel collisions pose a major threat to the species. However, it is not yet known whether they are also at risk within aggregation sites, where up to 400 individuals can gather to feed on seasonal bursts of planktonic productivity. These "constellation" sites are of significant ecological, socio-economic and cultural value. Here, through expert elicitation, we gathered information from most known constellation sites for this species across the world (>50 constellations and >13,000 individual whale sharks). We defined the spatial boundaries of these sites and their overlap with shipping traffic. Sites were then ranked based on relative levels of potential collision danger posed to whale sharks in the area. Our results showed that researchers and resource managers may underestimate the threat posed by large ship collisions due to a lack of direct evidence, such as injuries or witness accounts, which are available for other, sub-lethal threat categories. We found that constellations in the Arabian Sea and adjacent waters, the Gulf of Mexico, the Gulf of California, and Southeast and East Asia, had the greatest level of vessel collision threat. We also identified 39 sites where peaks in shipping activity coincided with peak seasonal occurrences of whale sharks, sometimes across several months. Simulated potential collision mitigation options estimated a minimal impact to industry, as most whale shark core habitat areas were relatively small. Given the threat posed by vessel collisions, a coordinated, multi-national approach to collision mitigation is needed within priority whale shark habitats to ensure collision protection for the species.

Longitudinal Trends in Insurer Participation in Multisector Population Health Activities.

Healthcare organizations increasingly engage in activities to identify and address social determinants of health (SDOH) among their patients to improve health outcomes and reduce costs. While several studies to date have focused on the evolving role of hospitals and physicians in these types of population health activities, much less is known about the role health insurers may play. We used data from the National Longitudinal Survey of Public Health Systems for the period 2006 to 2018 to examine trends in health insurer participation in population health activities and in the multi-sector collaborative networks that support these activities. We also used a difference-in-differences approach to examine the impact of Medicaid expansion on insurer participation in population health networks. Insurer participation increased in our study period both in the delivery of population health activities and in the integration into collaborative networks that support these activities. Insurers were most likely to participate in activities focusing on community health assessment and policy development. Results from our adjusted difference-in-differences models showed variation in association between insurer participation in population health networks and Medicaid expansion (Table 2). Population health networks in expansion states experienced significant increases insurer participation in assessment (4.48 percentage points, P < .05) and policy and planning (7.66 percentage points, P < .05) activities. Encouraging insurance coverage gains through policy mechanisms like Medicaid expansion may not only improve access to healthcare services but can also act as a driver of insurer integration into population health networks.

Mapping of susceptibility loci for Ebola virus pathogenesis in mice.

Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays a critical role, yet the identity of host susceptibility loci in mammals remains unknown. Using genetic reference populations, we generate an F2 mapping cohort to identify host susceptibility loci that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible mice display severe liver pathology consistent with EVD-like disease and transcriptional signatures associated with inflammatory and liver metabolic processes. A significant quantitative trait locus (QTL) for virus RNA load in blood is identified in chromosome (chr)8, and a severe clinical disease and mortality QTL is mapped to chr7, which includes the Trim5 locus. Using knockout mice, we validate the Trim5 locus as one potential driver of liver failure and mortality after infection. The identification of susceptibility loci provides insight into molecular genetic mechanisms regulating EVD progression and severity, potentially informing therapeutics and vaccination strategies.

Efficacy of host cell serine protease inhibitor MM3122 against SARS-CoV-2 for treatment and prevention of COVID-19.

We developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases, including transmembrane protease serine 2 (TMPRSS2), matriptase, and hepsin. TMPRSS2 is a membrane-associated protease that is highly expressed in the upper and lower respiratory tracts and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell entry, replication, and dissemination of new virus particles. We have previously shown that compound MM3122 exhibited subnanomolar potency against all three proteases and displayed potent antiviral effects against SARS-CoV-2 in a cell viability assay. Herein, we demonstrate that MM3122 potently inhibits viral replication in human lung epithelial cells and is also effective against the EG.5.1 variant of SARS-CoV-2. Furthermore, we evaluated MM3122 in a mouse model of COVID-19 and demonstrated that MM3122 administered intraperitoneally (IP) before (prophylactic) or after (therapeutic) SARS-CoV-2 infection had significant protective effects against weight loss and lung congestion and reduced pathology. Amelioration of COVID-19 disease was associated with a reduction in proinflammatory cytokine and chemokine production after SARS-CoV-2 infection. Prophylactic, but not therapeutic, administration of MM3122 also reduced virus titers in the lungs of SARS-CoV-2-infected mice. Therefore, MM3122 is a promising lead candidate small-molecule drug for the treatment and prevention of infections caused by SARS-CoV-2 and other coronaviruses. IMPORTANCE: SARS-CoV-2 and other emerging RNA coronaviruses are a present and future threat in causing widespread endemic and pandemic infection and disease. In this paper, we have shown that the novel host cell protease inhibitor, MM3122, blocks SARS-CoV-2 viral replication and is efficacious as both a prophylactic and a therapeutic drug for the treatment of COVID-19 given intraperitoneally in mice. Targeting host proteins and pathways in antiviral therapy is an underexplored area of research, but this approach promises to avoid drug resistance by the virus, which is common in current antiviral treatments.

Technology, data, people, and partnerships in addressing unmet social needs within Medicaid Managed Care.

BACKGROUND: Individuals with unmet social needs experience adverse health outcomes and are subject to greater inequities in health and social outcomes. Given the high prevalence of unmet needs among Medicaid enrollees, many Medicaid managed care organizations (MCOs) are now screening enrollees for unmet social needs and connecting them to community-based organizations (CBOs) with knowledge and resources to address identified needs. The use of screening and referral technology and data sharing are often considered key components in programs integrating health and social services. Despite this emphasis on technology and data collection, research suggests substantial barriers exist in operationalizing effective systems. METHODS: We used qualitative methods to examine cross-sector perspectives on the use of data and technology to facilitate MCO and CBO partnerships in Kentucky, a state with high Medicaid enrollment, to address enrollee social needs. We recruited participants through targeted sampling, and conducted 46 in-depth interviews with 26 representatives from all six Kentucky MCOs and 20 CBO leaders. Qualitative descriptive analysis, an inductive approach, was used to identify salient themes. RESULTS: We found that MCOs and CBOs have differing levels of need for data, varying incentives for collecting and sharing data, and differing valuations of what data can or should do. Four themes emerged from interviewees' descriptions of how they use data, including 1) to screen for patient needs, 2) to case manage, 3) to evaluate the effectiveness of programs, and 4) to partner with each other. Underlying these data use themes were areas of alignment between MCOs/CBOs, areas of incongruence, and areas of tension (both practical and ideological). The inability to interface with community partners for data privacy and ownership concerns contributes to division. Our findings suggest a disconnect between MCOs and CBOs regarding terms of their technology interfacing despite their shared mission of meeting the unmet social needs of enrollees. CONCLUSIONS: While data and technology can be used to identify enrollee needs and determine the most critical need, it is not sufficient in resolving challenges. People and relationships across sectors are vital in connecting enrollees with the community resources to resolve unmet needs.

The Characterization of Violent Deaths Among Asian and Pacific Islander Americans.

INTRODUCTION: Health disparities in the Asian and Pacific Islander Americans (APIAs) community have not been well described, unlike non-Hispanic Black and Hispanic communities. However, there has been a rise in violence against the APIA community. This study explores and characterizes violent death by incident (e.g., homicide, suicide), weapon (e.g., firearm, strangulation), and location types among APIAs as they compare with other racial or ethnic groups. METHODS: We used the National Violent Death Reporting System from 2003 to 2018 to characterize violent deaths among APIA and compared them to all other races. We compared these racial categories in two ways. First, we compared all races as a categorical variable that included six non-Hispanic racial categories including "Other or unspecified" and "two or more races. We then created a binary variable of APIA versus All Other Races for analysis. We explored the incident type of death, substance abuse disorders, mental health history, and gang involvement among other variables. We used Chi-square tests for categorical variables and Mann-Whitney U-tests for continuous variables. RESULTS: Overall, APIAs had a unique pattern of violent death. APIAs were more likely to commit suicide (71.74%-62.21%, P<0.001) and less likely to die of homicide than other races (17.56%-24.31%, P<0.001). In the cases of homicide, APIAs were more likely to have their deaths precipitated by another crime (40.87% versus 27.87%, P < 0.001). APIAs were more than twice as likely to die of strangulation than other races (39.93%-18.06%, P<0.001). Conversely, APIAs were less likely to die by firearm than other races (29.69-51.51, P<0.001). CONCLUSIONS: APIAs have a unique pattern of violence based on analysis of data from the National Violent Death Reporting System. Our data reveal a significant difference in the incident, weapon and location type as compared to Americans of other races, which begs further inquiry into the patterns of change in time and factors that contribute to inter-racial differences in death patterns.

Genetic loci regulate Sarbecovirus pathogenesis: A comparison across mice and humans.

Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although poorly characterized, natural genetic variation in human and other mammals modulate virus pathogenesis, as reflected by the spectrum of clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple human epidemic and zoonotic Sarbecoviruses, coupled with murine Collaborative Cross genetic reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B CoV pathogenesis and replication. Under a Chr4 QTL, we deleted a candidate interferon stimulated gene, Trim14 which resulted in enhanced SARS-CoV titers and clinical disease, suggesting an antiviral role during infection. Importantly, about 60 % of the murine QTL encode susceptibility genes identified as priority candidates from human genome-wide association studies (GWAS) studies after SARS-CoV-2 infection, suggesting that similar selective forces have targeted analogous genes and pathways to regulate Sarbecovirus disease across diverse mammalian hosts. These studies provide an experimental platform in rodents to investigate the molecular-genetic mechanisms by which potential cross mammalian susceptibility loci and genes regulate type-specific and cross-SARS-like group 2B CoV replication, immunity, and pathogenesis in rodent models. Our study also provides a paradigm for identifying susceptibility loci for other highly heterogeneous and virulent viruses that sporadically emerge from zoonotic reservoirs to plague human and animal populations.

Efficacy of Host Cell Serine Protease Inhibitor MM3122 against SARS-CoV-2 for Treatment and Prevention of COVID-19.

We have developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases including transmembrane protease serine 2 (TMPRSS2), matriptase and hepsin. TMPRSS2 is a membrane associated protease which is highly expressed in the upper and lower respiratory tract and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell receptor binding, entry, replication, and dissemination of new virion particles. We have previously shown that compound MM3122 exhibited sub nanomolar potency against all three proteases and displayed potent antiviral effects against SARS-CoV-2 in a cell-viability assay. Herein, we demonstrate that MM3122 potently inhibits viral replication in human lung epithelial cells and is also effective against the EG.5.1 variant of SARS-CoV-2. Further, we have evaluated MM3122 in a mouse model of COVID-19 and have demonstrated that MM3122 administered intraperitoneally (IP) before (prophylactic) or after (therapeutic) SARS-CoV-2 infection had significant protective effects against weight loss and lung congestion, and reduced pathology. Amelioration of COVID-19 disease was associated with a reduction in pro-inflammatory cytokines and chemokines production after SARS-CoV-2 infection. Prophylactic, but not therapeutic, administration of MM3122 also reduced virus titers in the lungs of SARS-CoV-2 infected mice. Therefore, MM3122 is a promising lead candidate small molecule drug for the treatment and prevention of infections caused by SARS-CoV-2 and other coronaviruses. IMPORTANCE: SARS-CoV-2 and other emerging RNA coronaviruses are a present and future threat in causing widespread endemic and pandemic infection and disease. In this paper, we have shown that the novel host-cell protease inhibitor, MM3122, blocks SARS-CoV-2 viral replication and is efficacious as both a prophylactic and therapeutic drug for the treatment of COVID-19 in mice. Targeting host proteins and pathways in antiviral therapy is an underexplored area of research but this approach promises to avoid drug resistance by the virus, which is common in current antiviral treatments.

Association Between Community Social Vulnerability and Preventable Hospitalizations.

Preventable hospitalizations are common and costly events that burden patients and our health care system. While research suggests that these events are strongly linked to ambulatory care access, emerging evidence suggests they may also be sensitive to a patient's social, environmental, and economic conditions. This study examines the association between variations in social vulnerability and preventable hospitalization rates. We conducted a cross-sectional analysis of county-level preventable hospitalization rates for 33 states linked with data from the 2020 Social Vulnerability Index (SVI). Preventable hospitalizations were 40% higher in the most vulnerable counties compared with the least vulnerable. Adjusted regression results confirm the strong relationship between social vulnerability and preventable hospitalizations. Our results suggest wide variation in community-level preventable hospitalization rates, with robust evidence that variation is strongly related to a community's social vulnerability. The human toll, societal cost, and preventability of these hospitalizations make understanding and mitigating these inequities a national priority.

Interest and Satisfaction of Telemedicine Use Among Ambulatory Neurology Patients in Western North Carolina During the COVID-19 Pandemic.

Introduction: During the COVID-19 pandemic, care shifted from exclusively telemedicine to hybrid models with in-person, video, and telephone visits. We explored how patient satisfaction and visit preferences have changed by comparing in-person versus virtual visits (telephone and video) in an ambulatory neurology practice across three time points. Methods: Patients who completed a virtual visit in March 2020 (early-pandemic), May 2020 (mid-pandemic), and March 2021 (later-pandemic) were contacted. Patients were assessed for visit satisfaction and desire for future telemedicine. Univariate and multivariable logistic regression analysis was conducted to determine factors independently associated with video visit completion. Results: Four thousand seven hundred seventy-eight the number of ambulatory visits (n = 4,778) were performed (1,004 early; 1,265 mid; and 2,509 later); 1,724 patients (36%) assented to postvisit feedback; mean age 45.8 ± 24.4 years, 58% female, 79% white, and 56% with Medicare/Medicaid insurance. Patient satisfaction significantly increased (73% early, 79% mid, 81% later-pandemic, p = 0.008). Interest in telemedicine also increased for patients completing telephone visits (40% early, 50% mid, 59% later, p = 0.027) and video visits (52% early, 59% mid, 62% later, p = 0.035). Patients satisfied with telemedicine visits were younger (p < 0.001). White patients were more interested in future telemedicine (p = 0.037). Multivariable analysis showed that older patients (for each 1 year older), Black patients, and patients with Medicare/Medicaid were 2%, 45%, and 54% less likely to complete a video visit than telephone, respectively. Discussion: Patients, especially younger ones, have become more satisfied and more interested in hybrid care models during the COVID-19 pandemic. Barriers to conducting video visits persist for older, Black patients with Medicare or Medicaid insurance.

Contemporary Public Health Finance: Varied Definitions, Patterns, and Implications.

The financing of public health systems and services relies on a complex and fragmented web of partners and funding priorities. Both underfunding and "dys-funding" contribute to preventable mortality, increases in disease frequency and severity, and hindered social and economic growth. These issues were both illuminated and magnified by the COVID-19 pandemic and associated responses. Further complicating issues is the difficulty in constructing adequate estimates of current public health resources and necessary resources. Each of these challenges inhibits the delivery of necessary services, leads to inequitable access and resourcing, contributes to resource volatility, and presents other deleterious outcomes. However, actions may be taken to defragment complex funding paradigms toward more flexible spending, to modernize and standardize data systems, and to assure equitable and sustainable public health investments. Expected final online publication date for the Annual Review of Public Health, Volume 45 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Appalachian Gap in Preventable Hospitalizations: Are We Seeing Any Progress?

Introduction: Previous studies have documented geographic variation in preventable hospitalizations between rural and urban areas, but much less is known about preventable hospitalization patterns between heterogeneous rural areas. Unique challenges related to access of care and poverty may put the rural Appalachian Region at risk for higher rates of preventable hospitalizations. Purpose: This study examines whether within-rural differences in Kentucky's preventable hospitalization rates exist and how these differences may be changing over time. Methods: Longitudinal and geographic trends in county-level preventable hospitalization rates were examined using Kentucky hospital discharge data from 2016 to 2019. Regression models were run to determine whether changes over time in preventable hospitalization rates led to an increasing or decreasing gap in outcomes between rural Appalachian counties and their urban and rural non- Appalachian counterparts. Results: Rural Appalachian counties consistently had significantly higher preventable hospitalizations rates compared to their rural non-Appalachian and urban counterparts ( p < 0.01). A downward trend in overall preventable hospitalizations was observed for rural Appalachia over time, but trends were relatively stable for rural non-Appalachian and urban counties. Regression results indicate that there was no significant reduction in the "Appalachian gap" over time. Implications: The analyses confirm that rural areas within Kentucky experienced highly heterogeneous rates of preventable hospitalizations. Despite Medicaid expansion, there is little evidence of any narrowing of the "Appalachian gap." Focus on improving access to care alone may be insufficient to improve outcomes. Alternative strategies that leverage population health approaches may improve capacity to address complex health and social needs in rural Appalachia.

Association Between Insurer Connectivity in Appalachian Population Health Networks and Preventable Hospitalizations: Evidence from Kentucky.

Introduction: Addressing complex health and social needs requires cross-sector collaboration to deliver medical, social, and population health services at the community level. Capacity in community health and social services networks may be constrained in regions like Appalachia due to the combined effects of rurality and persistently poor health and social outcomes. One way that cross-sector networks serving low-resource communities can expand their capacity is by engaging partners, like health insurers, who can leverage resources from outside the local area. Purpose: This study examines insurer connectivity in cross-sector networks across Kentucky's geographic regions and the association between connectivity and the probability of an individual experiencing a preventable hospitalization. Methods: A cross-sectional design was used that linked data from the National Longitudinal Survey of Public Health Systems (NALSYS) with 2018 patient-level Kentucky hospital discharge data to examine the association between insurer connectivity in community networks and preventable hospitalizations across urban, rural non-Appalachian, and Appalachian regions. Results: Analysis of the data shows substantial geographic variation in the association between insurer connectivity in community networks and preventable hospitalization. Insurer connectivity in rural Appalachian communities was associated with lower likelihood that an individual was admitted for a preventable hospitalization ( p < 0.01). Implications: Findings suggest insurer connectivity in cross-sector community health and social services networks has the potential to strengthen network capacity to address preventable hospitalizations and improve health outcomes and well-being for the people of Appalachia.

Metatranscriptomics analysis reveals a novel transcriptional and translational landscape during Middle East respiratory syndrome coronavirus infection.

Among all RNA viruses, coronavirus RNA transcription is the most complex and involves a process termed "discontinuous transcription" that results in the production of a set of 3'-nested, co-terminal genomic and subgenomic RNAs during infection. While the expression of the classic canonical set of subgenomic RNAs depends on the recognition of a 6- to 7-nt transcription regulatory core sequence (TRS), here, we use deep sequence and metagenomics analysis strategies and show that the coronavirus transcriptome is even more vast and more complex than previously appreciated and involves the production of leader-containing transcripts that have canonical and noncanonical leader-body junctions. Moreover, by ribosome protection and proteomics analyses, we show that both positive- and negative-sense transcripts are translationally active. The data support the hypothesis that the coronavirus proteome is much vaster than previously noted in the literature.

1-O-Octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-GS-441524 (V2043). Evaluation of Oral V2043 in a Mouse Model of SARS-CoV-2 Infection and Synthesis and Antiviral Evaluation of Additional Phospholipid Esters with Enhanced Anti-SARS-CoV-2 Activity.

Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused by COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we describe the synthesis and evaluation of alkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (60 mg/kg orally, once daily for 5 days starting 12h after infection) reduced lung viral load by 1.5 log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Structure/activity evaluation of additional analogs that have hydrophobic ethers at the sn-2 of glycerol revealed improved in vitro antiviral activity by introduction of a 3-fluoro-4-methoxy-substituted benzyl or a 3- or 4-cyano-substituted benzyl. Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections.

A live dengue virus vaccine carrying a chimeric envelope glycoprotein elicits dual DENV2-DENV4 serotype-specific immunity.

The four dengue virus serotypes co-circulate globally and cause significant human disease. Dengue vaccine development is challenging because some virus-specific antibodies are protective, while others are implicated in enhanced viral replication and more severe disease. Current dengue tetravalent vaccines contain four live attenuated serotypes formulated to theoretically induce balanced protective immunity. Among the number of vaccine candidates in clinical trials, only Dengvaxia is licensed for use in DENV seropositive individuals. To simplify live-virus vaccine design, we identify co-evolutionary constraints inherent in flavivirus virion assembly and design chimeric viruses to replace domain II (EDII) of the DENV2 envelope (E) glycoprotein with EDII from DENV4. The chimeric DENV2/4EDII virus replicates efficiently in vitro and in vivo. In male macaques, a single inoculation of DENV2/4EDII induces type-specific neutralizing antibodies to both DENV2 and DENV4, thereby providing a strategy to simplify DENV vaccine design by utilizing a single bivalent E glycoprotein immunogen for two DENV serotypes.

COVID-19 and MCO-community partnerships to address enrollee social needs.

OBJECTIVES: Many Medicaid managed care organizations (MCOs) now screen enrollees and connect them to community-based organizations (CBOs) to address unmet social needs. COVID-19 has significantly disrupted health care delivery and overall economic activity in the United States. We examined how partnerships between Medicaid MCOs and CBOs to address social determinants of health have been affected by the pandemic. STUDY DESIGN: Guided by questions and recruitment strategies developed with our stakeholder advisory board, we conducted 26 interviews with representatives from all 6 of Kentucky's Medicaid MCOs. METHODS: In-depth, structured interviews for data collection and iterative content analyses to identify themes. RESULTS: Several themes emerged, including substantial increases in enrollees' unmet needs and the demand to find new ways to be responsive, changing funding patterns, disruptions to and evolving modes of communication, and shifting partner relationships. In virtually all areas of impact, COVID-19 has been associated with both negative and positive change. CONCLUSIONS: Unmet social needs associated with the pandemic placed tremendous strain on CBOs, limiting their capacity to sustain some programs and partnerships. Isolation associated with COVID-19 also had wide-ranging effects on service delivery, communication with enrollees and partners, and the ability to maintain relationships. Nonetheless, the pandemic also had some silver linings, including additional resources and flexibility for addressing unmet needs. Federal and state agencies, along with MCO leaders, should carefully evaluate what innovations have been particularly effective during the pandemic and craft new flexibilities into their policies, procedures, and regulations.

Impact of state Medicaid expansion on cross-sector health and social service networks: Evidence from a longitudinal cohort study.

OBJECTIVE: To examine the impact of state Medicaid expansion on the delivery of population health activities in cross-sector health and social services networks. Community networks are multisector, interorganizational networks that provide services ranging from the direct provision of individual social services to the implementation of population-level initiatives addressing community outcomes. DATA SOURCES: We used data measuring the composition of cross-sector population health networks 2006-2018 National Longitudinal Survey of Public Health Systems (NALSYS) linked with the Area Health Resource File. STUDY DESIGN: A difference-in-differences approach was used to examine the impact of expansion on organization engagement in population health activities and network structure. DATA COLLECTION/EXTRACTION METHODS: Stratified random sampling of local public health jurisdictions in the United States. We restricted our data to jurisdictions serving populations of 100,000 or more and states that had NALSYS observations across all time periods, resulting in a final sample size of 667. PRINCIPAL FINDINGS: Results from our adjusted difference-in-differences estimates indicated that Medicaid expansion was associated with a 2.3 percentage point increase in the density of population health networks (p < 0.10). Communities in states that expanded Medicaid experienced significant increases in the participation of local public health, local government, hospital, nonprofit, insurer, and K-12 schools. Of the organizations with significant increases in expansion communities, nonprofits (7.7 percentage points, p < 0.01), local public health agencies (6.5 percentage points, p < 0.01), hospitals (5.8 percentage points, p < 0.01), and local government agencies (6.0 percentage points, p < 0.05) had the largest gains. CONCLUSIONS: Our study found increases in cross-sector participation in population health networks in states that expanded Medicaid compared with nonexpansion states, suggesting that additional coverage gains are associated with positive changes in population health network structure.

Assessment of Kentucky's Local Health Department Cross-Jurisdictional Sharing: Strategy for Maximizing Efficiency.

OBJECTIVE: The purpose of this study was to examine patterns of cross-jurisdictional sharing across the 61 local public health jurisdictions (LHJs) in Kentucky. The opportunities to reduce the cost-of-service delivery for Kentucky's LHJs via cross-jurisdictional sharing present a mechanism to address financial instability across the state by achieving economies of scale, especially among smaller jurisdictions. DESIGN: A cross-sectional study design was used to examine patterns of cross-jurisdictional sharing across the 61 LHJs in Kentucky. The survey tool utilized was designed by the Center for Sharing Public Health Services, an initiative managed by the Kansas Health Institute with support from the Robert Wood Johnson Foundation. RESULTS: Seventy-two percent of the 61 LHJs in Kentucky responded to the survey. The majority of responding jurisdictions sharing services were rural, single-county jurisdictions, utilizing service-related informal sharing arrangements. The majority of health departments, when asked to identify which programmatic areas shared service arrangements were focused in, listed those services requiring intensive staff training such as Health Access Nurturing Development Services (HANDS) and epidemiology. Of particular interest were the services most infrequently shared such as communicable disease screening and treatment. CONCLUSIONS: This study suggests that, pre-COVID-19, a core group of primarily rural, single-county Kentucky local health departments has experience with cross-jurisdictional sharing. Among this group, engagement in informal arrangements was the form of cross-jurisdictional sharing predominantly used, with few jurisdictions reporting shared functions with joint oversight. When considering the potential benefits and efficiencies that cross-jurisdictional sharing can provide to public health departments and their communities, for some, COVID-19 may have been a catalyst to engage in sharing across health department jurisdictional lines.

A Multitrait Locus Regulates Sarbecovirus Pathogenesis.

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.