Astyanax mexicanus surface and cavefish chromosome-scale assemblies for trait variation discovery.

The ability of organisms to adapt to sudden extreme environmental changes produces some of the most drastic examples of rapid phenotypic evolution. The Mexican Tetra, Astyanax mexicanus, is abundant in the surface waters of northeastern Mexico, but repeated colonizations of cave environments have resulted in the independent evolution of troglomorphic phenotypes in several populations. Here, we present three chromosome-scale assemblies of this species, for one surface and two cave populations, enabling the first whole-genome comparisons between independently evolved cave populations to evaluate the genetic basis for the evolution of adaptation to the cave environment. Our assemblies represent the highest quality of sequence completeness with predicted protein-coding and non-coding gene metrics far surpassing prior resources and, to our knowledge, all long-read assembled teleost genomes, including zebrafish. Whole genome synteny alignments show highly conserved gene order among cave forms in contrast to a higher number of chromosomal rearrangements when compared to other phylogenetically close or distant teleost species. By phylogenetically assessing gene orthology across distant branches of amniotes, we discover gene orthogroups unique to A. mexicanus. When compared to a representative surface fish genome, we find a rich amount of structural sequence diversity, defined here as the number and size of insertions and deletions as well as expanding and contracting repeats across cave forms. These new more complete genomic resources ensure higher trait resolution for comparative, functional, developmental, and genetic studies of drastic trait differences within a species.

A chromosome-scale fishing cat reference genome for the evaluation of potential germline risk variants.

The fishing cat, Prionailurus viverrinus, faces a population decline, increasing the importance of maintaining healthy zoo populations. Unfortunately, zoo-managed individuals currently face a high prevalence of transitional cell carcinoma (TCC), a form of bladder cancer. To investigate the genetics of inherited diseases among captive fishing cats, we present a chromosome-scale assembly, generate the pedigree of the zoo-managed population, reaffirm the close genetic relationship with the Asian leopard cat (Prionailurus bengalensis), and identify 7.4 million single nucleotide variants (SNVs) and 23,432 structural variants (SVs) from whole genome sequencing (WGS) data of healthy and TCC cats. Only BRCA2 was found to have a high recurrent number of missense mutations in fishing cats diagnosed with TCC when compared to inherited human cancer risk variants. These new fishing cat genomic resources will aid conservation efforts to improve their genetic fitness and enhance the comparative study of feline genomes.

Astyanax mexicanus surface and cavefish chromosome-scale assemblies for trait variation discovery.

The ability of organisms to adapt to sudden extreme environmental changes produces some of the most drastic examples of rapid phenotypic evolution. The Mexican Tetra, Astyanax mexicanus, is abundant in the surface waters of northeastern Mexico, but repeated colonizations of cave environments have resulted in the independent evolution of troglomorphic phenotypes in several populations. Here, we present three chromosome-scale assemblies of this species, for one surface and two cave populations, enabling the first whole-genome comparisons between independently evolved cave populations to evaluate the genetic basis for the evolution of adaptation to the cave environment. Our assemblies represent the highest quality of sequence completeness with predicted protein-coding and non-coding gene metrics far surpassing prior resources and, to our knowledge, all long-read assembled teleost genomes, including zebrafish. Whole genome synteny alignments show highly conserved gene order among cave forms in contrast to a higher number of chromosomal rearrangements when compared to other phylogenetically close or distant teleost species. By phylogenetically assessing gene orthology across distant branches of amniotes, we discover gene orthogroups unique to A. mexicanus. When compared to a representative surface fish genome, we find a rich amount of structural sequence diversity, defined here as the number and size of insertions and deletions as well as expanding and contracting repeats across cave forms. These new more complete genomic resources ensure higher trait resolution for comparative, functional, developmental, and genetic studies of drastic trait differences within a species.

Single-haplotype comparative genomics provides insights into lineage-specific structural variation during cat evolution.

The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes of three interspecies F1 hybrids to generate near-gapless single-haplotype assemblies. We discerned that cat genomes have a paucity of segmental duplications relative to great apes, explaining their remarkable karyotypic stability. X chromosomes were hotspots of structural variation, including enrichment with inversions in a large recombination desert with characteristics of a supergene. The X-linked macrosatellite DXZ4 evolves more rapidly than 99.5% of the genome clarifying its role in felid hybrid incompatibility. Resolved sensory gene repertoires revealed functional copy number changes associated with ecomorphological adaptations, sociality and domestication. This study highlights the value of gapless genomes to reveal structural mechanisms underpinning karyotypic evolution, reproductive isolation and ecological niche adaptation.

Understanding the role of environmental and socioeconomic factors in the geographic variation of breast cancer risk in the US-wide Sister Study.

OBJECTIVE: To describe the geographic pattern of breast cancer incidence in a nationwide prospective cohort and investigate whether environmental exposures and/or neighborhood socioeconomic status explain observed geographic disparities. METHODS: Using accelerated failure time models with a spatial random effect term, we mapped the health region-level association between residential location and breast cancer incidence for 44,707 participants in the Sister Study after controlling for established individual-level breast cancer risk factors. We performed a variable selection process to select environmental exposures [i.e., ambient nitrogen dioxide (NO2) and fine particulate matter (PM2.5), PM2.5 chemical composition, outdoor light at night (LAN), ambient noise, ultraviolet radiation, and greenspace] and neighborhood-level factors [i.e., population density and area deprivation index (ADI)] that predicted breast cancer incidence and quantified the spatial variation explained by the selected factors. We also considered whether the geographic pattern and predictors were similar when restricting to estrogen receptor-positive (ER+) tumors. RESULTS: We observed a spatial patterning in the incidence of overall breast cancer (Moran's I = 16.7, p < 0.05) and ER+ breast cancer (Moran's I = 13.2, p < 0.05), with a lower risk observed in the South and Southeast and a greater risk in the Northwest and certain areas of the Midwest and Northeast. NO2, LAN, and ADI explained 21.4% of the spatial variation in overall breast cancer incidence whereas NO2, PM2.5 chemical composition, LAN, greenspace, and ADI together explained 63.3% of the spatial variation in ER+ breast cancer incidence. CONCLUSIONS: Our findings provide additional evidence for a role of environmental exposures in breast cancer incidence and suggest that geographic-based risk factors may vary according to breast cancer subtype. Our findings support the need for additional research to quantify the relative contributions of geographic-based risk factors for breast cancer.

The Vocal Priorities of College Students With and Without Self-Reported Voice Problems.

OBJECTIVES/HYPOTHESIS: To determine if the Vocal Priorities Questionnaire (VPQ) could be used in people who were not seeking treatment for a voice problem. To determine if the VPQ could be used to compare groups based on self-reported voice problems. To determine if vocal priorities (loudness, clarity, pitch, pitch range) vary based on self-reported voice problems. STUDY DESIGN: Prospective cross-sectional study. METHODS: An online survey that contained demographic questions, questions about self-reported voice problems, and the VPQ was distributed to undergraduate university students. Confirmatory factor analyses (CFA) and exploratory factor analysis (EFA) were completed to determine if the VPQ was appropriate for use in this population. Invariance testing determined if the VPQ could be used to compare groups. Cronbach's alpha determined internal consistency. An analysis of variance was conducted to compare the scores for each vocal priority across three self-reported voice problem categories: never, current, and past. RESULTS: Responses from 285 participants were analyzed. An initial CFA found that the four-priority VPQ originally proposed did not have adequate fit indices. An EFA and modified CFA revealed that four priorities were still present, but "not having a gravelly voice" fit better with the priority of pitch, not clarity. With this model, invariance was verified and Cronbach's alpha indicated internal consistency. Loudness was the top vocal priority for 34.8%. In those with a past voice problem, clarity was scored higher compared to those with a current voice problem, F(2, 284) = 5.298, P = 0.006, and pitch range was scored higher compared to those who had never experienced a voice problem, F(2, 284) = 5.431, P = 0.005. CONCLUSIONS: A modified four-priority version of the VPQ presented with acceptable dimensionality and invariance for college students with and without self-reported voice problems. Scores for clarity and pitch range were influenced by experiences with voice problems.

Supply and quality of colonoscopy according to the characteristics of gastroenterologists in the French population-based colorectal-cancer screening program.

BACKGROUND: Since its complete roll-out in 2009, the French colorectal cancer screening program (CRCSP) experienced 3 major constraints [use of a less efficient Guaiac-test (gFOBT), stopping the supply of Fecal-Immunochemical-Test kits (FIT), and suspension of the program due to the coronavirus disease 2019 (COVID-19)] affecting its effectiveness. AIM: To describe the impact of the constraints in terms of changes in the quality of screening-colonoscopy (Quali-Colo). METHODS: This retrospective cohort study included screening-colonoscopies performed by gastroenterologists between Jan-2010 and Dec-2020 in people aged 50-74 living in Ile-de-France (France). The changes in Quali-colo (Proportion of colonoscopies performed beyond 7 mo (Colo_7 mo), Frequency of serious adverse events (SAE) and Colonoscopy detection rate) were described in a cohort of Gastroenterologists who performed at least one colonoscopy over each of the four periods defined according to the chronology of the constraints [gFOBT: Normal progress of the CRCSP using gFOBT (2010-2014); FIT: Normal progress of the CRCSP using FIT (2015-2018); STOP-FIT: Year (2019) during which the CRCSP experienced the cessation of the supply of test kits; COVID: Program suspension due to the COVID-19 health crisis (2020)]. The link between each dependent variable (Colo_7 mo; SAE occurrence, neoplasm detection rate) and the predictive factors was analyzed in a two-level multivariate hierarchical model. RESULTS: The 533 gastroenterologists (cohort) achieved 21509 screening colonoscopies over gFOBT period, 38352 over FIT, 7342 over STOP-FIT and 7995 over COVID period. The frequency of SAE did not change between periods (gFOBT: 0.3%; FIT: 0.3%; STOP-FIT: 0.3%; and COVID: 0.2%; P = 0.10). The risk of Colo_7 mo doubled between FIT [adjusted odds ratio (aOR): 1.2 (1.1; 1.2)] and STOP-FIT [aOR: 2.4 (2.1; 2.6)]; then, decreased by 40% between STOP-FIT and COVID [aOR: 2.0 (1.8; 2.2)]. Regardless of the period, this Colo_7 mo's risk was twice as high for screening colonoscopy performed in a public hospital [aOR: 2.1 (1.3; 3.6)] compared to screening-colonoscopy performed in a private clinic. The neoplasm detection, which increased by 60% between gFOBT and FIT [aOR: 1.6 (1.5; 1.7)], decreased by 40% between FIT and COVID [aOR: 1.1 (1.0; 1.3)]. CONCLUSION: The constraints likely affected the time-to-colonoscopy as well as the colonoscopy detection rate without impacting the SAE's occurrence, highlighting the need for a respectable reference time-to-colonoscopy in CRCSP.

Examining Mental Health Disorders in Overweight and Obese Pediatric Patients.

INTRODUCTION: We investigated the frequency and variation in three mental health diagnoses among obese or overweight children and adolescents. METHOD: Logistic regression was used to examine the association between the outcome variables-anxiety, depression, and adjustment disorders-with the following covariates: overweight/obesity status, sex, age, and race. RESULTS: Findings show anxiety, depressive, and adjustment disorder diagnoses were significantly higher for overweight or obese youth in our sample. In addition, diagnosis rates for one or more of these disorders increase as children grow into adolescence. Furthermore, we found significantly higher rates of depression and significantly lower rates of anxiety among youth who live in places with higher rates of poverty. DISCUSSION: Findings indicate a target age for providers to focus on mental health screening among overweight/obese patients: (1) early adolescence (aged 11-14 years) for depressive and adjustment disorders and (2) early childhood (aged 2-4 years) for anxiety disorder.

Implications for health system resilience: Quantifying the impact of the COVID-19-related stay at home orders on cancer screenings and diagnoses in southeastern North Carolina, USA.

COVID-19 impacted hospital systems across the globe. Focus shifted to responding to increased healthcare demand while mitigating COVID-19 spread on their campuses. Mitigation efforts limited medical professional-patient interactions, including patient access to preventive cancer screenings. Data were gleaned from a health information exchange containing records on over 2 million patients in southeastern North Carolina, USA. This study tested five hypotheses: H1: Weekly cancer screenings significantly decreased during North Carolina's (NC) Stay-At-Home (SAH) orders; H2: Weekly cancer diagnoses significantly decreased during NC's SAH orders; H3: Weekly cancer screenings significantly increased after the end of NC's SAH orders; H4: Weekly cancer diagnoses significantly increased after the end of NC's SAH orders; and H5: Weekly advanced cancer diagnoses significantly increased after the end of NC's SAH orders. Time series regression analysis was employed to quantify trends. Results suggested strong support of H1 and H3, moderate support of H4, mixed support of H5, and no support of H2. For example, compared to before the SAH orders, we estimated 662.3 fewer weekly breast cancer screenings during the SAH orders (H1). After the SAH orders (H3), we estimated 232.5 more breast cancer screenings and 10.6 more breast cancer diagnoses. This work quantifies the impact of COVID-19 associated SAH orders on cancer screenings and diagnoses and suggests the potential for delayed or missed cancer diagnoses. This evident disruption in providing routine medical care also highlights the importance of strengthening health systems (or organizations) and improving resilience to natural disasters and infectious disease outbreaks.

The Quantitative Examination of the Relationship Between Job Satisfaction and Organizational Fit in Athletic Trainers.

CONTEXT: Athletic trainers' (ATs') job satisfaction has been extensively researched, yet little is known about how satisfaction relates to organizational culture. OBJECTIVE: To examine ATs' level of job satisfaction with and organizational-fit perceptions of their employment setting. DESIGN: Cross-sectional study. SETTING: Web-based questionnaire. PATIENTS OR OTHER PARTICIPANTS: A total of 5704 ATs (full-time employment, nonacademic appointment) were contacted via email; 841 participants began our survey (access rate = 14.7%), and 285 completed it (5.0% response rate; 33.9% completion rate). Demographic characteristics were men = 107 (37.5%), women = 178 (62.5%); age = 34.8 ± 9.9 years; and employment setting = 34.7% (n = 99) from National Collegiate Athletic Association Division I, 18.9% (n = 54) from Division II, 29.5% (n = 84) from Division III, and 16.9% (n = 48) other. MAIN OUTCOME MEASURE(S): Participants responded to an online survey consisting of demographic questions, a 36-item Likert-scale Job Satisfaction Survey, and the Cable and Judge revision of the O'Reilly, Chatman, and Caldwell 40-item ranking Organizational Culture Profile survey. Multiple linear regression models for total or subscale job satisfaction were used to analyze the data. All models adjusted for the same demographic measures, and the independent variables of interest were created from the organizational culture survey responses. RESULTS: Coworkers (minimum [min] = 9, maximum [max] = 24, ρ = .79), communications (min = 9, max = 24, ρ = .78), and work itself (min = 4, max = 24, ρ = .71) were most correlated with the total job satisfaction score (min = 96, max = 175). Of the respondents, 54% selected adaptability, stability, and taking individual responsibility as 1 of their 2 most characteristic attributes in the organizational culture profile. In addition, 83% of respondents indicated being aggressive, receiving high pay for good performance, and being distinctive or different from others as their 2 least characteristic traits. CONCLUSIONS: The job satisfaction of these ATs was affected most by organizational factors, such as coworkers and communication, as well as by individual attributes such as adaptability, stability, and taking personal responsibility.

Successful Perioperative Management of Orthotopic Cardiac Transplantation in a Pediatric Patient With Concurrent Congenital von Willebrand Disease and Acquired von Willebrand Syndrome Using Recombinant von Willebrand Factor.

Von Willebrand disease (VWD) is the most common bleeding disorder and reportedly affects 1:1,000 of the world's population. There are three subtypes of VWD characterized by a quantitative defect (types 1 and 3 VWD) or a qualitative defect (type 2 VWD). Type 1 VWD results in a partial deficiency of von Willebrand factor (VWF) and affects approximately 75% of individuals with VWD, whereas type 3 VWD results in a severe or complete deficiency of VWF. Individuals with type 2 VWD subtypes (types 2A, 2B, 2M, and 2N VWD) express a dysfunctional VWF protein that has impaired interactions with platelets or factor VIII. The majority of individuals with VWD have mild type 1 VWD and occasionally require bolus infusions of VWF for severe bleeding or major surgery. A subset of patients, especially those with type 2A or 3 VWD, may require more frequent VWF replacement or prophylaxis for refractory bleeding or bleeding prevention, respectively. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that primarily occurs as a result of an underlying disease or other pathologic mechanism. Cases of AVWS associated with heart valve defects, left ventricular assist devices, or congenital cardiac disease result from high shear stress in the circulation that induces VWF unfolding and subsequent proteolysis of high-molecular-weight multimers by ADAMTS-13. In rare instances, plasma-derived factor VIII-containing VWF concentrates have been administered to individuals with AVWS for persistent or challenging bleeding events. In this case report, the hemostatic challenges and the perioperative management of cardiac transplantation surgery using a novel recombinant VWF product in a pediatric patient diagnosed with AVWS concomitant with congenital type 1 VWD are described. Written informed consent was obtained from the patient's mother for this case report. The diagnosis of congenital VWD remains a challenge because of multiple potential modifiers that can alter VWF laboratory results. Concurrent conditions, such as congenital heart disease and the rare secondary condition of AVWS, in addition to congenital VWD, can further affect interpretation of coagulation studies. This can result in delays in diagnosis, increase severity of the bleeding phenotype, and complicate hemostatic management in individuals at risk for bleeding and thrombosis. A multidisciplinary approach, including anesthesiologists, cardiologists, cardiovascular surgeons, hematologists, and pharmacists, is critical to achieving optimal patient outcomes, as highlighted in this case report. As diagnostic capabilities and understanding of VWD broaden, future studies evaluating alternative treatment approaches for individuals with various types of VWD would be of great benefit to the medical community.

Community vulnerability and mobility: What matters most in spatio-temporal modeling of the COVID-19 pandemic?

Community vulnerability is widely viewed as an important aspect to consider when modeling disease. Although COVID-19 does disproportionately impact vulnerable populations, human behavior as measured by community mobility is equally influential in understanding disease spread. In this research, we seek to understand which of four composite measures perform best in explaining disease spread and mortality, and we explore the extent to which mobility account for variance in the outcomes of interest. We compare two community mobility measures, three composite measures of community vulnerability, and one composite measure that combines vulnerability and human behavior to assess their relative feasibility in modeling the US COVID-19 pandemic. Extensions - via temporally dependent fixed effect coefficients - of the commonly used Bayesian spatio-temporal Poisson disease mapping models are implemented and compared in terms of goodness of fit as well as estimate precision and viability. A comparison of goodness of fit measures nearly unanimously suggests the human behavior-based models are superior. The duration at residence mobility measure indicates two unique and seemingly inverse relationships between mobility and the COVID-19 pandemic: the findings indicate decreased COVID-19 presence with decreased mobility early in the pandemic and increased COVID-19 presence with decreased mobility later in the pandemic. The early indication is likely influenced by a large presence of state-issued stay at home orders and self-quarantine, while the later indication likely emerges as a consequence of holiday gatherings in a country under limited restrictions. This study implements innovative statistical methods and furnishes results that challenge the generally accepted notion that vulnerability and deprivation are key to understanding disparities in health outcomes. We show that human behavior is equally, if not more important to understanding disease spread. We encourage researchers to build upon the work we start here and continue to explore how other behaviors influence the spread of COVID-19.

Using spatial and temporal modeling to visualize the effects of U.S. state issued stay at home orders on COVID-19.

Coronavirus disease 2019 dominated and augmented many aspects of life beginning in early 2020. Related research and data generation developed alongside its spread. We developed a Bayesian spatio-temporal Poisson disease mapping model for estimating real-time characteristics of the coronavirus disease in the United States. We also created several dashboards for visualization of the statistical model for fellow researchers and simpler spatial and temporal representations of the disease for consumption by analysts and data scientists in the policymaking community in our region. Findings suggest that the risk of confirmed cases is higher for health regions under partial stay at home orders and lower in health regions under full stay at home orders, when compared to before stay at home orders were declared. These results confirm the benefit of state-issued stay at home orders as well as suggest compliance to the directives towards the older population for adhering to social distancing guidelines.

A systematic review of spatial habitat associations and modeling of marine fish distribution: A guide to predictors, methods, and knowledge gaps.

As species distribution models, and similar techniques, have emerged in marine ecology, a vast array of predictor variables have been created and diverse methodologies have been applied. Marine fish are vital food resources worldwide, yet identifying the most suitable methodology and predictors to characterize spatial habitat associations, and the subsequent distributions, often remains ambiguous. Our objectives were to identify knowledge gaps in fish guilds, identify research themes, and to determine how data sources, statistics, and predictor variables differ among fish guilds. Data were obtained from an international literature search of peer-reviewed articles (2007-2018; n = 225) and research themes were determined based on abstracts. We tested for differences in data sources and modeling techniques using multinomial regressions and used a linear discriminant analysis to distinguish differences in predictors among fish guilds. Our results show predictive studies increased over time, but studies of forage fish, sharks, coral reef fish, and other fish guilds remain sparse. Research themes emphasized habitat suitability and distribution shifts, but also addressed abundance, occurrence, stock assessment, and biomass. Methodologies differed by fish guilds based on data limitations and research theme. The most frequent predictors overall were depth and temperature, but most fish guilds were distinguished by their own set of predictors that focused on their specific life history and ecology. A one-size-fits-all approach is not suitable for predicting marine fish distributions. However, given the paucity of studies for some fish guilds, researchers would benefit from utilizing predictors and methods derived from more commonly studied fish when similar habitat requirements are expected. Overall, the findings provide a guide for determining predictor variables to test and identifies novel opportunities to apply non-spatial knowledge and mechanisms to models.

Use of Factor VIIa and Anti-inhibitor Coagulant Complex in Pediatric Cardiac Surgery Patients.

OBJECTIVES: Postoperative bleeding is a common cause of morbidity and mortality in cardiac patients who undergo cardiopulmonary bypass (CPB). Pediatric patients are especially at risk for adverse effects of surgery and CPB on the coagulation system. This can result in bleeding, transfusions, and poor outcomes. Excessive bleeding unresponsive to blood products can warrant the off-label use of recombinant activated clotting factor VIIa (rFVIIa) and/or anti-inhibitor coagulant complex (FEIBA). Several studies have shown the utility in these agents off-label in patients who have undergone cardiac bypass surgery with acute bleeding episodes that are refractory to blood products. However, data regarding use of these agents in pediatrics are sparse. The purpose of this study is to report the use of rFVIIa and FEIBA in pediatric cardiac surgery patients in our institution. METHODS: This was a retrospective chart review of pediatric cardiothoracic surgery patients who received rFVIIa or FEIBA at Children's Healthcare of Atlanta during the study period. RESULTS: Thirty-three patients received rFVIIa and 9 patients received FEIBA either intraoperatively or postoperatively for bleeding related to the cardiac procedure. Approximately 13% of rFVIIa patients and 55% of FEIBA patients required repeat doses. There were decreases for all blood products administered after rFVIIa and FEIBA were given. However, the doses used did not correlate with either positive or negative outcomes. Seventeen percent (n = 7) of rFVIIa patients experienced a thrombus and 22% (n = 2) of FEIBA patients experienced a thrombus. CONCLUSIONS: Both rFVIIa and FEIBA reduced blood product usage in pediatric patients following cardiac procedures.

An analysis of hurricane impact across multiple cancers: Accessing spatio-temporal variation in cancer-specific survival with Hurricane Katrina and Louisiana SEER data.

Considering the impact of events such as natural disasters on disease risk is important. For this study, we examined temporal trends in multiple cancers available via Louisiana SEER data to understand how event impacts differ in timing and strength by cancer type. The specific event of interest for these Louisiana residents diagnosed with lung and bronchus, prostate, breast, colorectal, leukemia, or ovarian cancer in during the years 2000-2013 was Hurricane Katrina (August 2005). The results across multiple cancers showed similarities among trends, both spatial and temporal. With these results in mind, direct action could be made with the aim of improving survival after detrimental events or in detected Louisiana parishes with worse than average survival.

Spatial patterns in prostate Cancer-specific mortality in Pennsylvania using Pennsylvania Cancer registry data, 2004-2014.

BACKGROUND: Spatial heterogeneity of prostate cancer-specific mortality in Pennsylvania remains unclear. We utilized advanced geospatial survival regressions to examine spatial variation of prostate cancer-specific mortality in PA and evaluate potential effects of individual- and county-level risk factors. METHODS: Prostate cancer cases, aged ≥40 years, were identified in the 2004-2014 Pennsylvania Cancer Registry. The 2018 County Health Rankings data and the 2014 U.S. Environmental Protection Agency's Environmental Quality Index were used to extract county-level data. The accelerated failure time models with spatial frailties for geographical correlations were used to assess prostate cancer-specific mortality rates for Pennsylvania and by the Penn State Cancer Institute (PSCI) 28-county catchment area. Secondary assessment based on estimated spatial frailties was conducted to identify potential health and environmental risk factors for mortality. RESULTS: There were 94,274 cases included. The 5-year survival rate in PA was 82% (95% confidence interval, CI: 81.1-82.8%), with the catchment area having a lower survival rate 81% (95% CI: 79.5-82.6%) compared to the non-catchment area rate of 82.3% (95% CI: 81.4-83.2%). Black men, uninsured, more aggressive prostate cancer, rural and urban Appalachia, positive lymph nodes, and no definitive treatment were associated with lower survival. Several county-level health (i.e., poor physical activity) and environmental factors in air and land (i.e., defoliate chemical applied) were associated with higher mortality rates. CONCLUSIONS: Spatial variations in prostate cancer-specific mortality rates exist in Pennsylvania with a higher risk in the PSCI's catchment area, in particular, rural-Appalachia. County-level health and environmental factors may contribute to spatial heterogeneity in prostate cancer-specific mortality.

Latent classes for chemical mixtures analyses in epidemiology: an example using phthalate and phenol exposure biomarkers in pregnant women.

Latent class analysis (LCA), although minimally applied to the statistical analysis of mixtures, may serve as a useful tool for identifying individuals with shared real-life profiles of chemical exposures. Knowledge of these groupings and their risk of adverse outcomes has the potential to inform targeted public health prevention strategies. This example applies LCA to identify clusters of pregnant women from a case-control study within the LIFECODES birth cohort with shared exposure patterns across a panel of urinary phthalate metabolites and parabens, and to evaluate the association between cluster membership and urinary oxidative stress biomarkers. LCA identified individuals with: "low exposure," "low phthalates, high parabens," "high phthalates, low parabens," and "high exposure." Class membership was associated with several demographic characteristics. Compared with "low exposure," women classified as having "high exposure" had elevated urinary concentrations of the oxidative stress biomarkers 8-hydroxydeoxyguanosine (19% higher, 95% confidence interval [CI] = 7, 32%) and 8-isoprostane (31% higher, 95% CI = -5, 64%). However, contrast examinations indicated that associations between oxidative stress biomarkers and "high exposure" were not statistically different from those with "high phthalates, low parabens" suggesting a minimal effect of higher paraben exposure in the presence of high phthalates. The presented example offers verification of latent class assignments through application to an additional data set as well as a comparison to another unsupervised clustering approach, k-means clustering. LCA may be more easily implemented, more consistent, and more able to provide interpretable output.