Patterns of Social Needs Predict Quality-of-Life and Healthcare Utilization Outcomes in Patients from a Large Hospital System.

BACKGROUND: Unmet social needs (SNs) often coexist in distinct patterns within specific population subgroups, yet these patterns are understudied. OBJECTIVE: To identify patterns of social needs (PSNs) and characterize their associations with health-related quality-of-life (HRQoL) and healthcare utilization (HCU). DESIGN: Observational study using data on SNs screening, HRQoL (i.e., low mental and physical health), and 90-day HCU (i.e., emergency visits and hospital admission). Among patients with any SNs, latent class analysis was conducted to identify unique PSNs. For all patients and by race and age subgroups, compared with no SNs, we calculated the risks of poor HRQoL and time to first HCU following SNs screening for each PSN. PATIENTS: Adult patients undergoing SNs screening at the Mass General Brigham healthcare system in Massachusetts, United States, between March 2018 and January 2023. MAIN MEASURES: SNs included: education, employment, family care, food, housing, medication, transportation, and ability to pay for household utilities. HRQoL was assessed using the Patient-Reported Outcomes Measurement Information System Global-10. KEY RESULTS: Six unique PSNs were identified: "high number of social needs," "food and utility access," "employment needs," "interested in education," "housing instability," and "transportation barriers." In 14,230 patients with HRQoL data, PSNs increased the risks of poor mental health, with risk ratios ranging from 1.07(95%CI:1.01-1.13) to 1.80(95%CI:1.74-1.86). Analysis of poor physical health yielded similar findings, except that the "interested in education" showed a mild protective effect (0.97[95%CI:0.94-1.00]). In 105,110 patients, PSNs increased the risk of 90-day HCU, with hazard ratios ranging from 1.09(95%CI:0.99-1.21) to 1.70(95%CI:1.52-1.90). Findings were generally consistent in subgroup analyses by race and age. CONCLUSIONS: Certain SNs coexist in distinct patterns and result in poorer HRQoL and more HCU. Understanding PSNs allows policymakers, public health practitioners, and social workers to identify at-risk patients and implement integrated, system-wide, and community-based interventions.

Social Determinants of Health Needs and Health-related Quality of Life Among Surgical Patients: A Retrospective Analysis of 8512 Patients.

OBJECTIVE: To assess associations between social determinants of health (SDOH) needs and health-related quality of life (HRQOL) among surgical patients. BACKGROUND: Despite the profound impact of SDOH on health outcomes, studies examining the effect of SDOH needs on HRQOL among surgical patients are limited. METHODS: A retrospective study was conducted using responses from the SDOH needs assessment and the Patient-Reported Outcomes Measurement Information Systems Global Health instrument of adults seen in surgical clinics at a single institution. Patient characteristics including socioeconomic status (insurance type, education level, and employment status) were extracted. Stepwise multivariable logistic regression analyses were performed to identify independent predictors of global health scores. RESULTS: A total of 8512 surgical patients (mean age: 55.6±15.8 years) were included. 25.2% of patients reported one or more SDOH needs. The likelihood of reporting at least one SDOH need varied by patient characteristics and socioeconomic status variables. In fully adjusted regression models, food insecurity [odds ratio (OR), 1.53; 95% CI, 1.38-1.70 and OR, 1.49; 95% CI, 1.22-1.81, respectively], housing instability (OR, 1.27; 95% CI, 1.12-1.43 and OR, 1.39; 95% CI, 1.13-1.70, respectively) lack of transportation (OR, 1.46; 95% CI, 1.27-1.68 and OR, 1.25; 95% CI, 1.00-1.57, respectively), and unmet medication needs (OR, 1.31; 95% CI, 1.13-1.52 and OR, 1.61; 95% CI, 1.28-2.03, respectively) were independent predictors of poor physical and mental health. CONCLUSIONS: SDOH needs are independent predictors of poor patient-reported physical and mental health among surgical patients. Assessing and addressing SDOH needs should be prioritized in health care settings and by policymakers to improve HRQOL.

Accumulation mechanisms for contaminants on weak-base hybrid ion exchange resins.

Mechanism of hexavalent chromium removal (Cr(VI) as CrO42-) by the weak-base ion exchange (IX) resin ResinTech® SIR-700-HP (SIR-700) from simulated groundwater is assessed in the presence of radioactive contaminants iodine-129 (as IO3-), uranium (U as uranyl UO22+), and technetium-99 (as TcO4-), and common environmental anions sulfate (SO42-) and chloride (Cl-). Batch tests using the acid sulfate form of SIR-700 demonstrated Cr(VI) and U(VI) removal exceeded 97%, except in the presence of high SO42- concentrations (536 mg/L) where Cr(VI) and U(VI) removal decreased to ≥ 80%. However, Cr(VI) removal notably improved with co-mingled U(VI) that complexes with SO42- at the protonated amine sites. These U-SO42- complexes are integral to U(VI) removal, as confirmed by the decrease in U(VI) removal (<40%) when the acid chloride form of SIR-700 was used instead. Solid phase characterization revealed that CrO42- is removed by IX with SO42- complexes and/or reduced to amorphous Cr(III)(OH)3 at secondary alcohol sites. Tc(VII)O4- and I(V)O3- also undergo chemical reduction, following a similar removal mechanism. Oxyanion removal preference is determined by the anion reduction potential (CrO42->TcO4->IO3-), geometry, and charge density. For these reasons, 39% and 69% of TcO4- and 17% and 39% of IO3- are removed in the presence and absence of Cr(VI), respectively.

Impact of Service-Based Student Loan Repayment Program on the Primary Care Workforce.

PURPOSE: As the average level of medical education indebtedness rises, physicians look to programs such as Public Service Loan Forgiveness (PSLF) and National Health Service Corps (NHSC) to manage debt burden. Both represent service-dependent loan repayment programs, but the requirements and program outcomes diverge, and assessing the relative uptake of each program may help to inform health workforce policy decisions. We sought to describe variation in the composition of repayment program participant groups and measure relative impact on patient access to care. METHODS: In this bivariate analysis, we analyzed data from 10,677 respondents to the American Board of Family Medicine's National Graduate Survey to study differences in loan repayment program uptake as well as the unique participant demographics, scope of practice, and likelihood of practicing with a medically underserved or rural population in each program cohort. RESULTS: The rate of PSLF uptake tripled between 2016 and 2020, from 7% to 22% of early career family physicians, while NHSC uptake remained static at 4% to 5%. Family physicians reporting NHSC assistance were more likely than those reporting PSLF assistance to come from underrepresented groups, demonstrated a broader scope of practice, and were more likely to practice in rural areas (23.3% vs 10.8%) or whole-county Health Professional Shortage Areas (12.5% vs 3.7%) and with medically underserved populations (82.2% vs 24.2%). CONCLUSIONS: Although PSLF supports family physicians intending to work in public service, their peers who choose NHSC are much more likely to work in underserved settings. Our findings may prompt a review of the goals of service loan forgiveness programs with potential to better serve health workforce needs.

Divergent diapause life history timing drives both allochronic speciation and reticulate hybridization in an adaptive radiation of Rhagoletis flies.

Divergent adaptation to new ecological opportunities can be an important factor initiating speciation. However, as niches are filled during adaptive radiations, trait divergence driving reproductive isolation between sister taxa may also result in trait convergence with more distantly related taxa, increasing the potential for reticulated gene flow across the radiation. Here, we demonstrate such a scenario in a recent adaptive radiation of Rhagoletis fruit flies, specialized on different host plants. Throughout this radiation, shifts to novel hosts are associated with changes in diapause life history timing, which act as "magic traits" generating allochronic reproductive isolation and facilitating speciation-with-gene-flow. Evidence from laboratory rearing experiments measuring adult emergence timing and genome-wide DNA-sequencing surveys supported allochronic speciation between summer-fruiting Vaccinium spp.-infesting Rhagoletis mendax and its hypothesized and undescribed sister taxon infesting autumn-fruiting sparkleberries. The sparkleberry fly and R. mendax were shown to be genetically discrete sister taxa, exhibiting no detectable gene flow and allochronically isolated by a 2-month average difference in emergence time corresponding to host availability. At sympatric sites across the southern USA, the later fruiting phenology of sparkleberries overlaps with that of flowering dogwood, the host of another more distantly related and undescribed Rhagoletis taxon. Laboratory emergence data confirmed broadly overlapping life history timing and genomic evidence supported on-going gene flow between sparkleberry and flowering dogwood flies. Thus, divergent phenological adaptation can drive the initiation of reproductive isolation, while also enhancing genetic exchange across broader adaptive radiations, potentially serving as a source of novel genotypic variation and accentuating further diversification.

Genomically correlated trait combinations and antagonistic selection contributing to counterintuitive genetic patterns of adaptive diapause divergence in Rhagoletis flies.

Adaptation to novel environments can result in unanticipated genomic responses to selection. Here, we illustrate how multifarious, correlational selection helps explain a counterintuitive pattern of genetic divergence between the recently derived apple- and ancestral hawthorn-infesting host races of Rhagoletis pomonella (Diptera: Tephritidae). The apple host race terminates diapause and emerges as adults earlier in the season than the hawthorn host race, to coincide with the earlier fruiting phenology of their apple hosts. However, alleles at many loci associated with later emergence paradoxically occur at higher frequencies in sympatric populations of the apple compared to the hawthorn race. We present genomic evidence that historical selection over geographically varying environmental gradients across North America generated genetic correlations between two life history traits, diapause intensity and diapause termination, in the hawthorn host race. Moreover, the loci associated with these life history traits are concentrated in genomic regions in high linkage disequilibrium (LD). These genetic correlations are antagonistic to contemporary selection on local apple host race populations that favours increased initial diapause depth and earlier, not later, diapause termination. Thus, the paradox of apple flies appears due, in part, to pleiotropy or linkage of alleles associated with later adult emergence and increased initial diapause intensity, the latter trait strongly selected for by the earlier phenology of apples. Our results demonstrate how understanding of multivariate trait combinations and the correlative nature of selective forces acting on them can improve predictions concerning adaptive evolution and help explain seemingly counterintuitive patterns of genetic diversity in nature.

Genome-wide variation and transcriptional changes in diverse developmental processes underlie the rapid evolution of seasonal adaptation.

Many organisms enter a dormant state in their life cycle to deal with predictable changes in environments over the course of a year. The timing of dormancy is therefore a key seasonal adaptation, and it evolves rapidly with changing environments. We tested the hypothesis that differences in the timing of seasonal activity are driven by differences in the rate of development during diapause in Rhagoletis pomonella, a fly specialized to feed on fruits of seasonally limited host plants. Transcriptomes from the central nervous system across a time series during diapause show consistent and progressive changes in transcripts participating in diverse developmental processes, despite a lack of gross morphological change. Moreover, population genomic analyses suggested that many genes of small effect enriched in developmental functional categories underlie variation in dormancy timing and overlap with gene sets associated with development rate in Drosophila melanogaster Our transcriptional data also suggested that a recent evolutionary shift from a seasonally late to a seasonally early host plant drove more rapid development during diapause in the early fly population. Moreover, genetic variants that diverged during the evolutionary shift were also enriched in putative cis regulatory regions of genes differentially expressed during diapause development. Overall, our data suggest polygenic variation in the rate of developmental progression during diapause contributes to the evolution of seasonality in R. pomonella We further discuss patterns that suggest hourglass-like developmental divergence early and late in diapause development and an important role for hub genes in the evolution of transcriptional divergence.

Can the genomics of ecological speciation be predicted across the divergence continuum from host races to species? A case study in Rhagoletis.

Studies assessing the predictability of evolution typically focus on short-term adaptation within populations or the repeatability of change among lineages. A missing consideration in speciation research is to determine whether natural selection predictably transforms standing genetic variation within populations into differences between species. Here, we test whether and how host-related selection on diapause timing associates with genome-wide differentiation during ecological speciation by comparing ancestral hawthorn and newly formed apple-infesting host races of Rhagoletis pomonella to their sibling species Rhagoletis mendax that attacks blueberries. The associations of 57 857 single nucleotide polymorphisms in a diapause genome-wide-association study (GWAS) on the hawthorn race strongly predicted the direction and magnitude of genomic divergence among the three fly populations at a field site in Fennville, MI, USA. The apple race and R. mendax show parallel changes in the frequencies of putative inversions on three chromosomes associated with the earlier fruiting times of apples and blueberries compared to hawthorns. A diapause GWAS on R. mendax revealed compensatory changes throughout the genome accounting for the earlier eclosion of blueberry, but not apple flies. Thus, a degree of predictability, although not complete, exists in the genomics of diapause across the ecological speciation continuum in Rhagoletis. The generality of this result is placed in the context of other similar systems. This article is part of the theme issue 'Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers'.

Hybrid Sorbents for 129I Capture from Contaminated Groundwater.

Radioiodine (129I) poses a risk to the environment due to its long half-life, toxicity, and mobility. It is found at the U.S. Department of Energy Hanford Site due to legacy releases of nuclear wastes to the subsurface where 129I is predominantly present as iodate (IO3-). To date, a cost-effective and scalable cleanup technology for 129I has not been identified, with hydraulic containment implemented as the remedial approach. Here, novel high-performing sorbents for 129I remediation with the capacity to reduce 129I concentrations to or below the US Environmental Protection Agency (EPA) drinking water standard and procedures to deploy them in an ex-situ pump and treat (P&T) system are introduced. This includes implementation of hybridized polyacrylonitrile (PAN) beads for ex-situ remediation of IO3--contaminated groundwater for the first time. Iron (Fe) oxyhydroxide and bismuth (Bi) oxyhydroxide sorbents were deployed on silica substrates or encapsulated in porous PAN beads. In addition, Fe-, cerium (Ce)-, and Bi-oxyhydroxides were encapsulated with anion-exchange resins. The PAN-bismuth oxyhydroxide and PAN-ferrihydrite composites along with Fe- and Ce-based hybrid anion-exchange resins performed well in batch sorption experiments with distribution coefficients for IO3- of >1000 mL/g and rapid removal kinetics. Of the tested materials, the Ce-based hybrid anion-exchange resin was the most efficient for removal of IO3- from Hanford groundwater in a column system, with 50% breakthrough occurring at 324 pore volumes. The functional amine groups on the parent resin and amount of active sorbent in the resin can be customized to improve the iodine loading capacity. These results highlight the potential for IO3- remediation by hybrid sorbents and represent a benchmark for the implementation of commercially available materials to meet EPA standards for cleanup of 129I in a large-scale P&T system.

Improving Quality of Care in Rheumatoid Arthritis Through Mobile Patient-Reported Outcome Measurement: Focus Group Study.

BACKGROUND: Patient-reported outcomes (PROs) for chronic disease management can be integrated into the routine workflow by leveraging mobile technology. OBJECTIVE: The objective of our study was to describe the process of our quality improvement (QI) efforts using tablets for PRO collection in a busy, academic rheumatology practice to support a treat-to-target (TTT) approach for rheumatoid arthritis (RA) management. METHODS: Our QI team designed a process for routine collection of PROs for RA patients at the Arthritis Center, employing information technology and an electronic medical record (EMR) system. Patients received a tablet at the clinic check-in desk to complete the Routine Assessment of Patient Index Data 3 (RAPID3) survey, a validated RA PRO. RAPID3 scores were uploaded to the EMR in real time and available for use in shared decision making during routine office visits. Weekly data were collected on RAPID3 completion rates and shared with front desk staff and medical assistants to drive improvement. Patients in our patient family advisory council and focus groups provided informal feedback on the process. RESULTS: From May 1, 2017, to January 31, 2019, a total of 4233 RAPID3 surveys were completed by 1691 patients. The mean age of patients was 63 (SD 14) years; 84.00% (1420/1691) of the patients were female, and 83.00% (1403/1691) of the patients were white. The rates of RAPID3 completion increased from 14.3% (58/405) in May 2017 to 68.00% (254/376) in September 2017 and were sustained over time through January 2019. Informal feedback from patients was positive and negative, relating to the usability of the tablet and the way rheumatologists used and explained the RAPID3 data in shared decision making during the office visit. CONCLUSIONS: We designed a sustainable and reliable process for collecting PROs from patients with RA in the waiting room and integrated these data through the EMR during office visits.

Factors Associated With Increased Collection of Patient-Reported Outcomes Within a Large Health Care System.

Importance: The collection of patient-reported outcomes (PROs) has garnered intense interest, but dissemination of PRO programs has been limited, as have analyses of the factors associated with successful programs. Objective: To identify factors associated with improving PRO collection rates within a large health care system using a centralized PRO infrastructure. Design, Setting, and Participants: This cohort study included 205 medical and surgical clinics in the Partners Healthcare system in Massachusetts that implemented a PRO program between March 15, 2014, and December 31, 2018, using a standardized centralized infrastructure. Data were analyzed from March to April 2019. Exposures: Relevant clinical characteristics were recorded for each clinic launching a PRO program. Main Outcomes and Measures: The primary outcome was the mean PRO collection rate during each clinic's most recent 6 months of collection prior to January 2019. Data were analyzed using a linear regression model with the 6-month PRO collection rate as the dependent variable and clinic characteristics as independent variables. Secondary analysis used a logistic regression model to assess clinical factors associated with successful clinics, defined as those that collected PROs at a rate greater than 50%. Results: Between March 2014 and December 2018, 205 Partners Healthcare clinics were available for analysis, and 4 061 205 PRO measures from 745 028 encounters were collected. Among these, 103 clinics (50.2%) collected at a rate greater than 50%. Increased collection rates were associated with more than 50% of physicians in a clinic trained on PROs (change, 19.6% [95% CI, 9.9%-29.4%]; P < .001), routine administrative oversight of collection rates (change, 16.0% [95% CI, 6.6%-25.5%]; P = .001), previous collection of PROs on paper (change, 12.5% [95% CI, 4.7%-20.3%]; P = .002), presence of a clinical champion (change, 11.2% [95% CI, 2.5%-20.0%]; P = .01) and payer incentive (change, 10.5% [95% CI, 2.0%-18.9%]; P = .02). Conclusions and Relevance: These findings suggest that training physicians on the use of PROs, administrative surveillance of collection rates, and the presence of a local clinical champion may be promising interventions for increasing PRO collection. Clinics that have previously collected PROs may have greater success in increasing collections. Payer incentive for collection was associated with improved collections, but not associated with successful programs.

Rural Workforce Years: Quantifying the Rural Workforce Contribution of Family Medicine Residency Graduates.

BACKGROUND: Rural regions of the United States continue to experience a disproportionate shortage of physicians compared to urban regions despite decades of state and federal investments in workforce initiatives. The graduate medical education system effectively controls the size of the physician workforce but lacks effective mechanisms to equitably distribute those physicians. OBJECTIVE: We created a measurement tool called a "rural workforce year" to better understand the rural primary care workforce. It quantifies the rural workforce contributions of rurally trained family medicine residency program graduates and compares them to contributions of a geographically matched cohort of non-rurally trained graduates. METHODS: We identified graduates in both cohorts and tracked their practice locations from 2008-2018. We compared the average number of rural workforce years in 3 cross sections: 5, 8, and 10 years in practice after residency graduation. RESULTS: Rurally trained graduates practicing for contributed a higher number of rural workforce years in total and on average per graduate compared to a matched cohort of non-rural/rural training tack (RTT) graduates in the same practice intervals (P < .001 in all 3 comparison groups). In order to replace the rural workforce years produced by 1 graduate from the rural/RTT cohort, it would take 2.89 graduates from non-rural/RTT programs. CONCLUSIONS: These findings suggest that rural/RTT-trained physicians devote substantially more service to rural communities than a matched cohort of non-rural/RTT graduates and highlight the importance of rural/RTT programs as a major contributor to the rural primary care workforce in the United States.

Practice Intentions of Family Physicians Trained in Teaching Health Centers: The Value of Community-Based Training.

Family medicine residents who graduate from Federally Qualified Health Center-aligned Teaching Health Center (THC) training residencies are nearly twice as likely to pursue employment in safety-net settings compared with non-THC graduates. This trend has been consistent over the past few years, suggesting that the program is fulfilling its mission to strengthen primary care in underserved settings.

Standing geographic variation in eclosion time and the genomics of host race formation in Rhagoletis pomonella fruit flies.

Taxa harboring high levels of standing variation may be more likely to adapt to rapid environmental shifts and experience ecological speciation. Here, we characterize geographic and host-related differentiation for 10,241 single nucleotide polymorphisms in Rhagoletis pomonella fruit flies to infer whether standing genetic variation in adult eclosion time in the ancestral hawthorn (Crataegus spp.)-infesting host race, as opposed to new mutations, contributed substantially to its recent shift to earlier fruiting apple (Malus domestica). Allele frequency differences associated with early vs. late eclosion time within each host race were significantly related to geographic genetic variation and host race differentiation across four sites, arrayed from north to south along a 430-km transect, where the host races co-occur in sympatry in the Midwest United States. Host fruiting phenology is clinal, with both apple and hawthorn trees fruiting earlier in the North and later in the South. Thus, we expected alleles associated with earlier eclosion to be at higher frequencies in northern populations. This pattern was observed in the hawthorn race across all four populations; however, allele frequency patterns in the apple race were more complex. Despite the generally earlier eclosion timing of apple flies and corresponding apple fruiting phenology, alleles on chromosomes 2 and 3 associated with earlier emergence were paradoxically at lower frequency in the apple than hawthorn host race across all four sympatric sites. However, loci on chromosome 1 did show higher frequencies of early eclosion-associated alleles in the apple than hawthorn host race at the two southern sites, potentially accounting for their earlier eclosion phenotype. Thus, although extensive clinal genetic variation in the ancestral hawthorn race exists and contributed to the host shift to apple, further study is needed to resolve details of how this standing variation was selected to generate earlier eclosing apple fly populations in the North.

Genomic Differentiation during Speciation-with-Gene-Flow: Comparing Geographic and Host-Related Variation in Divergent Life History Adaptation in Rhagoletis pomonella.

A major goal of evolutionary biology is to understand how variation within populations gets partitioned into differences between reproductively isolated species. Here, we examine the degree to which diapause life history timing, a critical adaptation promoting population divergence, explains geographic and host-related genetic variation in ancestral hawthorn and recently derived apple-infesting races of Rhagoletis pomonella. Our strategy involved combining experiments on two different aspects of diapause (initial diapause intensity and adult eclosion time) with a geographic survey of genomic variation across four sites where apple and hawthorn flies co-occur from north to south in the Midwestern USA. The results demonstrated that the majority of the genome showing significant geographic and host-related variation can be accounted for by initial diapause intensity and eclosion time. Local genomic differences between sympatric apple and hawthorn flies were subsumed within broader geographic clines; allele frequency differences within the races across the Midwest were two to three-fold greater than those between the races in sympatry. As a result, sympatric apple and hawthorn populations displayed more limited genomic clustering compared to geographic populations within the races. The findings suggest that with reduced gene flow and increased selection on diapause equivalent to that seen between geographic sites, the host races may be recognized as different genotypic entities in sympatry, and perhaps species, a hypothesis requiring future genomic analysis of related sibling species to R. pomonella to test. Our findings concerning the way selection and geography interplay could be of broad significance for many cases of earlier stages of divergence-with-gene flow, including (1) where only modest increases in geographic isolation and the strength of selection may greatly impact genetic coupling and (2) the dynamics of how spatial and temporal standing variation is extracted by selection to generate differences between new and discrete units of biodiversity.

International Continence Society supported pelvic physiotherapy education guideline.

AIM: To provide a guideline of desired knowledge, clinical skills and education levels in Pelvic Physiotherapy (PT). Physiotherapy (PT) involves "using knowledge and skills unique to physiotherapists" and, "is the service only provided by, or under the direction and supervision of a physiotherapist."1 METHODS: The PT Committee, within the body of the International Continence Society (ICS), collected information regarding existing educational levels for pelvic floor PT. Through face to face and on on-line discussion consensus was reached which was summarized in three progressive educational levels based on knowledge and skills and brought together in a guideline. The guideline was submitted to all physiotherapists and the Educational Committee of the ICS, and after approval, submitted to the Executive Board of the ICS. RESULT: The guideline lists, in a progressive way, knowledge areas and skills to be achieved by education. It is broad and allows for individual interpretation based on local situations regarding education and healthcare possibilities. It is intended to be dynamic and updated on a regular basis. CONCLUSION: The proposed Pelvic PT education guideline is a dynamic document that allows course creators to plan topics for continuing course work and to recognize educational level of a therapist in the field of Pelvic PT. This education guideline can be used to set minimum worldwide standards resulting in higher skill levels for local pelvic physiotherapists and thereby better patient care outcome.

A test of genomic modularity among life-history adaptations promoting speciation with gene flow.

Speciation with gene flow may require adaptive divergence of multiple traits to generate strong ecologically based reproductive isolation. Extensive negative pleiotropy or physical linkage of genes in the wrong phase affecting these diverging traits may therefore hinder speciation, while genetic independence or "modularity" among phenotypic traits may reduce constraints and facilitate divergence. Here, we test whether the genetics underlying two components of diapause life history, initial diapause intensity and diapause termination timing, constrain differentiation between sympatric hawthorn and apple-infesting host races of the fly Rhagoletis pomonella through analysis of 10,256 SNPs measured via genotyping-by-sequencing (GBS). Loci genetically associated with diapause termination timing were mainly observed for SNPs mapping to chromosomes 1-3 in the genome, most notably for SNPs displaying higher levels of linkage disequilibrium (LD), likely due to inversions. In contrast, selection on initial diapause intensity affected loci on all five major chromosomes of the genome, specifically those showing low levels of LD. This lack of overlap in genetically associated loci suggests that the two diapause phenotypes are largely modular. On chromosome 2, however, intermediate level LD loci and a subgroup of high LD loci displayed significant negative relationships between initial diapause intensity and diapause termination time. These gene regions on chromosome 2 therefore affected both traits, while most regions were largely independent. Moreover, loci associated with both measured traits also tended to exhibit highly divergent allele frequencies between the host races. Thus, the presence of nonoverlapping genetic modules likely facilitates simultaneous, adaptive divergence for the measured life-history components.

Divergence of the diapause transcriptome in apple maggot flies: winter regulation and post-winter transcriptional repression.

The duration of dormancy regulates seasonal timing in many organisms and may be modulated by day length and temperature. Though photoperiodic modulation has been well studied, temperature modulation of dormancy has received less attention. Here, we leverage genetic variation in diapause in the apple maggot fly, Rhagoletis pomonella, to test whether gene expression during winter or following spring warming regulates diapause duration. We used RNAseq to compare transcript abundance during and after simulated winter between an apple-infesting population and a hawthorn-infesting population where the apple population ends pupal diapause earlier than the hawthorn-infesting population. Marked differences in transcription between the two populations during winter suggests that the 'early' apple population is developmentally advanced compared with the 'late' hawthorn population prior to spring warming, with transcripts participating in growth and developmental processes relatively up-regulated in apple pupae during the winter cold period. Thus, regulatory differences during winter ultimately drive phenological differences that manifest themselves in the following summer. Expression and polymorphism analysis identify candidate genes in the Wnt and insulin signaling pathways that contribute to population differences in seasonality. Both populations remained in diapause and displayed a pattern of up- and then down-regulation (or vice versa) of growth-related transcripts following warming, consistent with transcriptional repression. The ability to repress growth stimulated by permissive temperatures is likely critical to avoid mismatched phenology and excessive metabolic demand. Compared with diapause studies in other insects, our results suggest some overlap in candidate genes/pathways, though the timing and direction of changes in transcription are likely species specific.

Medical Student Decision Making Regarding Pursuit of a Public Health Degree.

BACKGROUND AND OBJECTIVES: Few US medical school graduates receive a public health degree. We sought to identify factors involved in medical students' decisions to pursue dual medical and public health degrees and describe the decision-making process. METHODS: We conducted focus group discussions and telephone interviews with medical students considering, or enrolled in, a public health degree program. Participants described early exposures to public health, perspectives on physician public health roles, advantages and disadvantages of a public health degree, and the relative importance of factors influencing their decision to pursue a public health degree. Data were coded using open codes, and thematic analysis was performed. RESULTS: Medical students' decisions about pursuing a public health degree are based on consideration of advantages and disadvantages of academic, personal, and financial factors. Students place weights on various factors and value guidance. CONCLUSIONS: Access to training and information about public health programs and career opportunities may facilitate decision-making. Knowledge of factors involved in students' decisions and the decision-making process will allow mentors, advisors, faculty, and staff working to recruit students into MPH programs to support students interested in earning dual medical and public health degrees. Future research should explore avenues for supporting medical student decision-making and further reducing barriers to public health training.