Impact of Remote Blood Pressure Monitoring Device Connectivity on Engagement Among Pregnant Individuals Enrolled in the Delfina Care Platform: Observational Study.

Unlabelled: User engagement with remote blood pressure monitoring during pregnancy is critical to optimize the associated benefits of blood pressure control and early detection of hypertensive disorders of pregnancy. In our study population of pregnant individuals, we found that connected blood pressure cuffs, which automatically sync measures to a monitoring platform or health record, increase engagement (2.13 [95% CI 1.36-3.35] times more measures per day) with remote blood pressure monitoring compared to unconnected cuffs that require manual entry of measures.

Evaluating associations of bisphenol and phthalate exposure with time to pregnancy and subfecundity in a New York City pregnancy cohort.

It is important to understand the impact of consumer chemical exposure and fecundity, a couple's measure of probability of successful conception, given approximately 15% of couples experience infertility. Prior research has generally found null associations between bisphenol and phthalate exposure and fecundability, measured via time to pregnancy (TTP). However, this research has not been updated with current chemical exposures and have often lacked diversity in their study populations. We evaluated the associations between common bisphenol and phthalate chemical exposure groups and TTP as well as subfecundity (TTP>12 months) in the New York University Children's Health Study, a diverse pregnancy cohort from 2016 onward. Using first-trimester spot-urine samples to measure chemical exposure and self-reported TTP from first-trimester questionnaires, we observed a significant adverse association between total bisphenol exposure and certain phthalate groups on TTP and odds of subfecundity. Furthermore, in a mixtures analysis to explore the joint effects of the chemical groups on the outcomes, we found evidence of a potential interaction between total bisphenol exposure and low-molecular weight phthalates on TTP. Future research should continue to update our knowledge regarding the complex and potentially interacting effects of these chemicals on reproductive health.

Association of maternal education, neighborhood deprivation, and racial segregation with gestational age at birth by maternal race/ethnicity and United States Census region in the ECHO cohorts.

Background: In the United States, disparities in gestational age at birth by maternal race, ethnicity, and geography are theorized to be related, in part, to differences in individual- and neighborhood-level socioeconomic status (SES). Yet, few studies have examined their combined effects or whether associations vary by maternal race and ethnicity and United States Census region. Methods: We assembled data from 34 cohorts in the Environmental influences on Child Health Outcomes (ECHO) program representing 10,304 participants who delivered a liveborn, singleton infant from 2000 through 2019. We investigated the combined associations of maternal education level, neighborhood deprivation index (NDI), and Index of Concentration at the Extremes for racial residential segregation (ICERace) on gestational weeks at birth using linear regression and on gestational age at birth categories (preterm, early term, post-late term relative to full term) using multinomial logistic regression. Results: After adjustment for NDI and ICERace, gestational weeks at birth was significantly lower among those with a high school diploma or less (-0.31 weeks, 95% CI: -0.44, -0.18), and some college (-0.30 weeks, 95% CI: -0.42, -0.18) relative to a master's degree or higher. Those with a high school diploma or less also had an increased odds of preterm (aOR 1.59, 95% CI: 1.20, 2.10) and early term birth (aOR 1.26, 95% CI: 1.05, 1.51). In adjusted models, NDI quartile and ICERace quartile were not associated with gestational weeks at birth. However, higher NDI quartile (most deprived) associated with an increased odds of early term and late term birth, and lower ICERace quartile (least racially privileged) associated with a decreased odds of late or post-term birth. When stratifying by region, gestational weeks at birth was lower among those with a high school education or less and some college only among those living in the Northeast or Midwest. When stratifying by race and ethnicity, gestational weeks at birth was lower among those with a high school education or less only for the non-Hispanic White category. Conclusion: In this study, maternal education was consistently associated with shorter duration of pregnancy and increased odds of preterm birth, including in models adjusted for NDI and ICERace.

Structural racism and health: Assessing the mediating role of community mental distress and health care access in the association between mass incarceration and adverse birth outcomes.

Research has linked spatial concentrations of incarceration with racial disparities in adverse birth outcomes. However, little is known about the specific mechanisms of this association. This represents an important knowledge gap in terms of intervention. We theorize two pathways that may account for the association between county-level prison rates and adverse birth outcomes: (1) community-level mental distress and (2) reduced health care access. Examining these mechanisms, we conducted a cross-sectional study of county-level prison rates, community-level mental distress, health insurance, availability of primary care physicians (PCP) and mental health providers (MHP), and adverse birth outcomes (preterm birth, low birth weight, infant mortality). Our data set included 475 counties and represented 2,677,840 live U.S. births in 2016. Main analyses involved between 170 and 326 counties. All data came from publicly available sources, including the U.S. Census and the Centers for Disease Control and Prevention. Descriptive and regression results confirmed the link between prison rates and adverse birth outcomes and highlighted Black-White inequities in this association. Further, bootstrap mediation analyses indicated that the impact of spatially concentrated prison rates on preterm birth was mediated by PCP, MHP, community-level mental distress, and health insurance in both crude and adjusted models. Community-level mental distress and health insurance (but not PCP or MHP) similarly mediated low birthweight in both models. Mediators were less stable in the effect on infant mortality with only MHP mediating consistently across models. We conclude that mass incarceration, health care access, and community mental distress represent actionable and urgent targets for structural-, community-, and individual-level interventions targeting population inequities in birth outcomes.

Apolipoprotein-ε4 is associated with higher fecundity in a natural fertility population.

In many populations, the apolipoprotein-ε4 (APOE-ε4) allele increases the risk for several chronic diseases of aging, including dementia and cardiovascular disease; despite these harmful effects at later ages, the APOE-ε4 allele remains prevalent. We assess the impact of APOE-ε4 on fertility and its proximate determinants (age at first reproduction, interbirth interval) among the Tsimane, a natural fertility population of forager-horticulturalists. Among 795 women aged 13 to 90 (20% APOE-ε4 carriers), those with at least one APOE-ε4 allele had 0.3 to 0.5 more children than (ε3/ε3) homozygotes, while those with two APOE-ε4 alleles gave birth to 1.4 to 2.1 more children. APOE-ε4 carriers achieve higher fertility by beginning reproduction 0.8 years earlier and having a 0.23-year shorter interbirth interval. Our findings add to a growing body of literature suggesting a need for studies of populations living in ancestrally relevant environments to assess how alleles that are deleterious in sedentary urban environments may have been maintained by selection throughout human evolutionary history.

Assessing Medical Students' Attitudes and Knowledge Regarding LGBTQ Health Needs Across the United States.

BACKGROUND: The lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) community experiences health disparities. It is thus imperative that medical trainees receive training in the care of LGBTQ community. The objective of this study was to identify gaps in knowledge and comfort among medical school students in providing care for the LGBTQ community. METHODS: An online survey was administered to medical students at 3 institutions in the United States from December 2020 to March 2021. Using a Likert scale, the survey assessed attitudes, comfort, and knowledge in providing care for the LGBTQ community. The survey included questions for each specific LGBTQ population. Results were quantified using descriptive and stratified analyses, and an exploratory factor analysis was used to calculate attitude summary measure (ASM) scores. A total knowledge score was calculated, with higher values indicating greater knowledge. RESULTS: Among the 300 medical students who completed the survey, the majority were female (55.7%), White (54.7%), and heterosexual (64.3%). The majority of medical students felt comfortable (strongly agree/agree) participating in the care of lesbian (94.3%), gay (96.0%), and bisexual (96.3%) patients; this percentage dropped to 82.3% for non-binary and 71.3% for transgender patients. Only 27.0% of medical students reported confidence in their knowledge of health needs of transgender patients. LGBTQ self-identification, percent of core rotations completed in school, region of country, and friends and/or family who are part of the LGBTQ community were significantly associated with various ASM scores. Knowledge questions yielded high percentages of "neutral" responses, and medical students who identified as LGBTQ had significantly higher total knowledge scores. CONCLUSIONS: Overall, the surveyed medical students feel comfortable and willing to provide care for LGBTQ persons. But, there is limited knowledge about specific LGBTQ health needs. More education and training in the needs of transgender and non-binary patients, in particular, is indicated.

State-specific fertility rate changes across the USA following the first two waves of COVID-19.

STUDY QUESTION: How did the first two coronavirus disease 2019 (COVID-19) waves affect fertility rates in the USA? SUMMARY ANSWER: States differed widely in how their fertility rates changed following the COVID-19 outbreak and these changes were influenced more by state-level economic, racial, political, and social factors than by COVID-19 wave severity. WHAT IS KNOWN ALREADY: The outbreak of the COVID-19 pandemic contributed to already declining fertility rates in the USA, but not equally across states. Identifying drivers of differential changes in fertility rates can help explain variations in demographic shifts across states in the USA and motivate policies that support families in general, not only during crises. STUDY DESIGN, SIZE, DURATION: This is an ecological study using state-level data from 50 US states and the District of Columbia (n = 51). The study period extends from 2020 to 2021 with historical data from 2016 to 2019. We identified Wave 1 as the first apex for each state after February 2020 and Wave 2 as the second apex, during Fall/Winter 2020-2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: State-level COVID-19 wave severity, defined as case acceleration during each 3-month COVID-19 wave (cases/100 000 population/month), was derived from 7-day weekly moving average COVID-19 case rates from the US Centers for Disease Control and Prevention (CDC). State-level fertility rate changes (change in average monthly fertility rate/100 000 women of reproductive age (WRA)/year) were derived from the CDC Bureau of Vital Statistics and from 2020 US Census and University of Virginia 2021 population estimates 9 months after each COVID-19 wave. We performed univariate analyses to describe national and state-level fertility rate changes following each wave, and simple and multivariable linear regression analyses to assess the relation of COVID-19 wave severity and other state-level characteristics with fertility rate changes. MAIN RESULTS AND THE ROLE OF CHANCE: Nationwide, fertility dropped by 17.5 births/month/100 000 WRA/year following Wave 1 and 9.2 births/month/100 000 WRA/year following Wave 2. The declines following Wave 1 were largest among majority-Democrat, more non-White states where people practiced greater social distancing. Greater COVID-19 wave severity was associated with steeper fertility rate decline post-Wave 1 in simple regression, but the association was attenuated when adjusted for other covariates. Adjusting for the economic impact of the pandemic (hypothesized mediator) also attenuated the effect. There was no relation between COVID-19 wave severity and fertility rate change following Wave 2. LIMITATIONS, REASONS FOR CAUTION: Our study harnesses state-level data so individual-level conclusions cannot be inferred. There may be residual confounding in our multivariable regression and we were underpowered to detect some effects. WIDER IMPLICATIONS OF THE FINDINGS: The COVID-19 pandemic initially impacted the national fertility rate but, overall, the fertility rate rebounded to the pre-pandemic level following Wave 2. Consistent with prior literature, COVID-19 wave severity did not appear to predict fertility rate change. Economic, racial, political, and social factors influenced state-specific fertility rates during the pandemic more than the severity of the outbreak alone. Future studies in other countries should also consider whether these factors account for internal heterogeneity when examining the impact of the COVID-19 pandemic and other crises on fertility. STUDY FUNDING/COMPETING INTEREST(S): L.G.K. received funding from the National Institute of Environmental Health Sciences (R00ES030403), M.C. from the National Science Foundation Graduate Research Fellowship Program (20-A0-00-1005789), and M.L. and E.S. from the National Institute of Environmental Health Sciences (R01ES032808). None of the authors have competing interests. TRIAL REGISTRATION NUMBER: N/A.

Chronotype and sleep duration interact to influence time to pregnancy: Results from a New York City cohort.

STUDY OBJECTIVE: To study associations between nighttime sleep characteristics and time to pregnancy. METHODS: Pregnant people age ≥18 years and<18 weeks' gestation were recruited from 3 New York University Grossman School of Medicine affiliated hospitals in Manhattan and Brooklyn (n = 1428) and enrolled into the New York University Children's Health and Environment Study. Participants in the first trimester of pregnancy were asked to recall their time to pregnancy and their sleep characteristics in the 3 months before conception. RESULTS: Participants who reported sleeping<7 hours per night tended to have shorter time to pregnancy than those who slept 7-9 hours per night (adjusted fecundability odds ratio = 1.16, 95% confidence interval: 0.94, 1.41). Participants with a sleep midpoint of 4 AM or later tended to have longer time to pregnancy compared with those with earlier sleep midpoints (before 4 AM) (adjusted fecundability odds ratio = 0.88, 95% confidence interval: 0.74, 1.04). When stratified by sleep midpoint, sleeping<7 hours was significantly associated with shorter time to pregnancy only among those whose sleep midpoint was before 4 AM (adjusted fecundability odds ratio = 1.33, 95% confidence interval: 1.07, 1.67). CONCLUSIONS: The association of sleep duration with time to pregnancy was modified by chronotype, suggesting that both biological and behavioral aspects of sleep may influence fecundability.

Survey of Clinical Providers and Allied Health Staff at a National Cancer Institute-Designated Comprehensive Cancer Center: Cultural Awareness in the Care of LGBTQ2S + Patients with Cancer.

To identify potential gaps in attitudes, knowledge, and practices towards LGBTQ2S + patients with a cancer diagnosis, a survey of clinical providers (CP) and allied health staff (AHS) was conducted to identify areas of improvement and guide development for future education and training. A previously published, validated survey was adapted at the direction of a LGBTQ2S + Patient and Family Advisory Council, and modified to include AHS. The survey was disseminated to all faculty and staff, and was adapted to the participants' self-identified level of patient interaction/care responsibilities. Subsections consisted of questions related to demographics, knowledge, attitudes, and practice behaviors towards participating in the care of LGBTQ2S + patients. Results were quantified using stratified analysis and an attitude summary measure. Of the 311 respondents, 179 self-identified as CPs and 132 as AHS. There was high agreement in comfort treating or assisting LGBTQ2S + patients by CP and AHS respondents, respectively. CPs possessed significantly higher knowledge regarding LGBTQ2S + health when compared to AHS; however, there remained high percentages of "neutral" and "do not know or prefer not to answer" responses regardless of clinical role. There was high agreement regarding the importance of knowing a patient's gender identity (GI) and pronouns (CP vs. AHS; 76.9% vs. 73.5% and 89.4% vs. 84.1%, respectively), whereas patient's sexual orientation and sex assigned at birth (CP vs. AHS; 51.1% vs. 53.5% and 58.6% vs. 62.9%, respectively) were viewed as less important. There was high interest in receiving education regarding the unique needs of LGBTQ2S + patients regardless of clinical role. Stratified analyses of CPs revealed early-career physicians (< 1-5 years from graduation) expressed higher interest in additional education and involvement with LGBTQ2S + -focused trainings when compared to mid- and late-career providers. This is the first study, to our knowledge, assessing the attitudes, knowledge, and practices of CPs and AHS regarding the care of LGBTQ2S + patients with cancer. Overall, there was high comfort treating/assisting LGBTQ2S + patients among CP and AHS respondents, respectively; yet, both groups possessed significant gaps in LGBTQ2S + -focused knowledge.

A comprehensive framework for operationalizing structural racism in health research: The association between mass incarceration of Black people in the U.S. and adverse birth outcomes.

Structural racism represents a key determinant of the racial health disparities that has characterized the U.S. population throughout its existence. While this reality has recently begun to gain increasing acknowledgment and acceptance within the health sciences, there are still considerable challenges related to defining the concept of structural racism and operationalizing it in empirical study. In this paper, building on the existing evidence base, we propose a comprehensive framework that centers structural racism in terms of its historical roots and continued manifestation in most domains of society, and offer solutions for the study of this phenomenon and the pathways that connect it to population-level health disparities. We showcase our framework by applying it to the known link between spatial and racialized clustering of incarceration - a previously cited representation of structural racism - and disparities in adverse birth outcomes. Through this process we hypothesize pathways that focus on social cohesion and community-level chronic stress, community crime and police victimization, as well as infrastructural community disinvestment. First, we contextualize these mechanisms within the relevant extant literature. Then, we make recommendations for future empirical pathway analyses. Finally, we identify key areas for policy, community, and individual-level interventions that target the impact of concentrated incarceration on birth outcomes among Black people in the U.S.

Prospective sampling bias in COVID-19 recruitment methods: experimental evidence from a national randomized survey testing recruitment materials.

BACKGROUND: In the context of the COVID-19 pandemic, social science research has required recruiting many prospective participants. Many researchers have explicitly taken advantage of widespread public interest in COVID-19 to advertise their studies. Leveraging this interest, however, risks creating unrepresentative samples due to differential interest in the topic. In this study, we investigate the design of survey recruitment materials with respect to the views of resultant participants. METHODS: Within a pan-Canadian survey (stratified random mail sampling, n = 1969), the design of recruitment invitations to prospective respondents was experimentally varied, with some prospective respondents receiving COVID-specific recruitment messages and others receiving more general recruitment messages (described as research about health and health policy). All respondents participated, however, in the same survey, allowing comparison of both demographic and attitudinal features between these groups. RESULTS: Respondents recruited via COVID-19 specific postcards were more likely to agree that COVID-19 is serious and believe that they were likely to contract COVID-19 compared to non-COVID respondents (odds = 0.71, p = 0.04; odds = 0.74, p = 0.03 respectively; comparing health to COVID-19 framed respondents). COVID-19 specific respondents were more likely to disagree that the COVID-19 threat was exaggerated compared to the non-COVID survey respondents (odds = 1.44, p = 0.02). CONCLUSIONS: COVID-19 recruitment framing garnered a higher response rate, as well as a sample with greater concern about coronavirus risks and impacts than respondents who received more neutrally framed recruitment materials.

Using Automation, Prioritization, and Collaboration to Manage a COVID-19 Case Surge in Maricopa County, Arizona, 2020.

During summer 2020, the Maricopa County Department of Public Health (MCDPH) responded to a surge in COVID-19 cases. We used internet-based platforms to automate case notifications, prioritized investigation of cases more likely to have onward transmission or severe COVID-19 based on available preinvestigation information, and partnered with Arizona State University (ASU) to scale investigation capacity. We assessed the speed of automated case notifications and accuracy of our investigation prioritization criteria. Timeliness of case notification-the median time between receipt of a case report at MCDPH and first case contact-improved from 11 days to <1 day after implementation of automated case notification. We calculated the sensitivity and positive predictive value (PPV) of the investigation prioritization system by applying our high-risk prioritization criteria separately to data available pre- and postinvestigation to determine whether a case met these criteria preinvestigation, postinvestigation, or both. We calculated the sensitivity as the percentage of cases classified postinvestigation as high risk that had also been classified as high risk preinvestigation. We calculated PPV as the percentage of all cases deemed high risk preinvestigation that remained so postinvestigation. During June 30 to July 31, 2020, a total of 55 056 COVID-19 cases with an associated telephone number (94% of 58 570 total cases) were reported. Preinvestigation, 8799 (16%) cases met high-risk criteria. Postinvestigation, 17 037 (31%) cases met high-risk criteria. Sensitivity was 52% and PPV was 98%. Automating case notifications, prioritizing investigations, and collaborating with ASU improved the timeliness of case contact, focused public health resources toward high-priority cases, and increased investigation capacity. Establishing partnerships between health departments and academia might be a helpful strategy for future surge capacity planning.

Design and Implementation of a COVID-19 Case Investigation Program: An Academic-Public Health Partnership, Arizona, 2020.

From May through July 2020, Arizona was a global hotspot for new COVID-19 cases. In response to the surge of cases, local public health departments looked for innovative ways to form external partnerships to address their staffing needs. In collaboration with the Maricopa County Department of Public Health, the Arizona State University Student Outbreak Response Team (SORT) created and implemented a virtual call center to conduct public health case investigations for COVID-19. SORT officially launched a dedicated COVID-19 case investigation program after 3 weeks of program design and training. From June 29 through November 8, 2020, SORT recruited and trained 218 case investigators, completed 5000 case patient interviews, and closed 10 000 cases. Our team also developed process improvements to address disparities in case investigation timeliness. A strong infrastructure designed to accommodate remote case investigations, paired with a large workforce, enabled SORT to provide additional surge capacity for the county's high volume of cases. University-driven multidisciplinary case investigator teams working in partnership with state, tribal, and local public health staff members can be an effective tool for supporting a diverse and growing public health workforce. We discuss the essential design factors involved in building a university program to complement local COVID-19 response efforts, including workflows for case management, volunteer case investigator recruitment and training, secure technology platforms for conducting case investigations remotely, and robust data-tracking procedures for maintaining quality control and timely case reporting.

Racialized economic segregation and health outcomes: A systematic review of studies that use the Index of Concentration at the Extremes for race, income, and their interaction.

Extensive research shows that residential segregation has severe health consequences for racial and ethnic minorities. Most research to date has operationalized segregation in terms of either poverty or race/ethnicity rather than a synergy of these factors. A novel version of the Index of Concentration at the Extremes (ICERace-Income) specifically assesses racialized economic segregation in terms of spatial concentrations of racial and economic privilege (e.g., wealthy white people) versus disadvantage (e.g., poor Black people) within a given area. This multidimensional measure advances a more comprehensive understanding of residential segregation and its consequences for racial and ethnic minorities. The aim of this paper is to critically review the evidence on the association between ICERace-Income and health outcomes. We implemented the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct a rigorous search of academic databases for papers linking ICERace-Income with health. Twenty articles were included in the review. Studies focused on the association of ICERace-Income with adverse birth outcomes, cancer, premature and all-cause mortality, and communicable diseases. Most of the evidence indicates a strong association between ICERace-Income and each health outcome, underscoring income as a key mechanism by which segregation produces health inequality along racial and ethnic lines. Two of the reviewed studies examined racial disparities in comorbidities and health care access as potential explanatory factors underlying this relationship. We discuss our findings in the context of the extant literature on segregation and health and propose new directions for future research and applications of the ICERace-Income measure.

APOE4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population.

In post-industrial settings, apolipoprotein E4 (APOE4) is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N = 1266, 50% female), APOE4 is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized LDL and inflammation which were limited to obese adults. Further, APOE4 carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between APOE4 and lipids may be beneficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.

Genes contain the instructions needed for a cell to make molecules called proteins, which perform various roles in the body. Different variants of a gene can affect how the protein works, and in some cases, can increase a person's risk to develop certain diseases. For example, people who carry a version of the apolipoprotein E gene called APOE4 have a greater risk of developing Alzheimer's disease or heart disease. Individuals with two copies of this genetic variant have a 45% higher risk of heart disease and 12 times higher risk of Alzheimer's disease. Studies in industrialized countries suggest this increased risk may be the result of higher cholesterol and inflammation in people with APOE4. But if APOE4 is harmful, why does it continue to be so common worldwide? One potential explanation is that APOE4, which has been around since before modern humans, may be beneficial in some contexts. Cholesterol is essential for many vital tasks in the body. In physically demanding environments where parasitic infections are common ­ conditions similar to those experienced by early humans ­ APOE4 might be beneficial. Under those circumstances, having more cholesterol might help fuel metabolic activities, fight infections, or reduce inflammation caused by infections. Garcia et al. investigated the link between the APOE4 genetic variant, cholesterol and inflammation in 1,266 Indigenous Tsimane people from 80 villages in Bolivia. Tsimane people live an active lifestyle foraging and farming for food. Parasite infections are a common problem in their communities, but obesity rates are very low. Garcia et al. found that Tsimane people with at least one copy of the APOE4 have lower levels of inflammation and higher levels of cholesterol than those who have two copies of the APOE3 version of the gene. Very lean people with APOE4 had especially high levels of the so called "bad" low density lipoprotein (LDL) cholesterol compared to people with APOE3 only. However, in this situation, storing a little extra cholesterol may not be so bad. The findings contradict other studies that have linked obesity to higher LDL levels and APOE4 to higher levels of inflammation. For the majority of human history, humans lived in more physically strenuous and calorically restrictive environments, with less access to clean water. Garcia et al. suggest that the harmful effects of APOE4 seen in studies in more industrialized societies ­ where people tend to be more sedentary and have less exposure to pathogens ­ may reflect a mismatch between a person's environment and their genes. More studies that capture the diversity of environmental conditions under which people live will help clarify the role of APOE4 health and disease.

Neurodevelopmental shifts in learned value transfer on cognitive control during adolescence.

Value-associated cues in the environment often enhance subsequent goal-directed behaviors in adults, a phenomenon supported by the integration of motivational and cognitive neural systems. Given that the interactions among these systems change throughout adolescence, we tested when the beneficial effects of value associations on subsequent cognitive control performance emerge during adolescence. Participants (N = 81) aged 13-20 completed a reinforcement learning task with four cue-incentive pairings that could yield high gain, low gain, high loss, or low loss outcomes. Next, participants completed a Go/NoGo task during fMRI where the NoGo targets comprised the previously learned cues, which tested how prior value associations influence cognitive control performance. Improved accuracy for previously learned high gain relative to low gain cues emerged with age. Older adolescents exhibited enhanced recruitment of the dorsal striatum and ventrolateral prefrontal cortex during cognitive control execution to previously learned high gain relative to low gain cues. Older adolescents also expressed increased coupling between the dorsal striatum and dorsolateral prefrontal cortex for high gain cues, whereas younger adolescents expressed increased coupling between the striatum and ventromedial prefrontal cortex. These findings reveal that learned high value cue-incentive associations enhance cognitive control in late adolescence in parallel with value-selective recruitment of corticostriatal systems.

Evolutionary origins of polycystic ovary syndrome: An environmental mismatch disorder.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder and has important evolutionary implications for female reproduction and health. PCOS presents an interesting paradox, as it results in significant anovulation and potential sub-fecundity in industrialized populations, yet it has a surprisingly high prevalence and has a high heritability. In this review, we discuss an overview of PCOS, current diagnostic criteria, associated hormonal pathways and a review of proposed evolutionary hypotheses for the disorder. With a multifactorial etiology that includes ovarian function, metabolism, insulin signaling and multiple genetic risk alleles, PCOS is a complex disorder. We propose that PCOS is a mismatch between previously neutral genetic variants that evolved in physically active subsistence settings that have the potential to become harmful in sedentary industrialized environments. Sedentary obesogenic environments did not exist in ancestral times and exacerbate many of these pathways, resulting in the high prevalence and severity of PCOS today. Overall, the negative impacts of PCOS on reproductive success would likely have been minimal during most of human evolution and unlikely to generate strong selection. Future research and preventative measures should focus on these gene-environment interactions as a form of evolutionary mismatch, particularly in populations that are disproportionately affected by obesity and metabolic disorders. LAY SUMMARY: The most severe form of polycystic ovary syndrome (PCOS) is likely a result of interactions between genetic predispositions for PCOS and modern obesogenic environments. PCOS would likely have been less severe ancestrally and the fitness reducing effects of PCOS seen today are likely a novel product of sedentary, urban environments.