The Military Health System: Minimizing Disparities in Breast Cancer Treatment.

BACKGROUND: The Military Health System (MHS) is a universal health care system, in which health care disparities are theoretically minimized. This study aimed to identify disparities and assess their impact on the initiation of timely treatment for breast cancer within a universally insured population. METHODS: A retrospective cohort study was performed to evaluate the treatment of female breast cancer patients ≥18 years of age within the MHS from January 1, 2014, to December 31, 2018. Incident breast cancer was defined as ≥2 breast cancer diagnoses without a prior diagnosis of breast cancer during the three continuous years before index diagnosis. Time from index diagnosis to initial treatment was calculated and dichotomized as receiving treatment within a clinically acceptable time course. Poisson regression was used to estimate relative risk (RR) with 95% CIs. RESULTS: Among the 30,761 female breast cancer patients identified in the MHS, only 6% of patients had a prolonged time to initial treatment. Time to initial treatment decreased during the study period from a mean (SD) of 63.2 (152.0) days in 2014 to 37.1 (28.8) days in 2018 (P < 0.0001). Age, region, and military characteristics remained significantly associated with receiving timely treatment even after the adjustment of confounders. Patients 70-79 years old were twice as likely as 18-39 years olds to receive timely treatment (RR: 2.0100, 95% CI, 1.52-2.6563, P < 0.0001). Senior officers and their dependents were more likely to receive timely initial treatment compared to junior enlisted patients and their dependents (RR: 1.5956, 95% CI, 1.2119-2.1005, P = 0.004). CONCLUSIONS: There have been significant improvements in the timely initiation of breast cancer treatment within the MHS. However, demographic and socioeconomic disparities can be identified that affect the timely initiation of therapy.

Rye: genetic ancestry inference at biobank scale.

Biobank projects are generating genomic data for many thousands of individuals. Computational methods are needed to handle these massive data sets, including genetic ancestry (GA) inference tools. Current methods for GA inference do not scale to biobank-size genomic datasets. We present Rye-a new algorithm for GA inference at biobank scale. We compared the accuracy and runtime performance of Rye to the widely used RFMix, ADMIXTURE and iAdmix programs and applied it to a dataset of 488221 genome-wide variant samples from the UK Biobank. Rye infers GA based on principal component analysis of genomic variant samples from ancestral reference populations and query individuals. The algorithm's accuracy is powered by Metropolis-Hastings optimization and its speed is provided by non-negative least squares regression. Rye produces highly accurate GA estimates for three-way admixed populations-African, European and Native American-compared to RFMix and ADMIXTURE (${R}^2 = \ 0.998 - 1.00$), and shows 50× runtime improvement compared to ADMIXTURE on the UK Biobank dataset. Rye analysis of UK Biobank samples demonstrates how it can be used to infer GA at both continental and subcontinental levels. We discuss user consideration and options for the use of Rye; the program and its documentation are distributed on the GitHub repository: https://github.com/healthdisparities/rye.

Ethnic disparities in mortality and group-specific risk factors in the UK Biobank.

Despite a substantial overall decrease in mortality, disparities among ethnic minorities in developed countries persist. This study investigated mortality disparities and their associated risk factors for the three largest ethnic groups in the United Kingdom: Asian, Black, and White. Study participants were sampled from the UK Biobank (UKB), a prospective cohort enrolled between 2006 and 2010. Genetics, biological samples, and health information and outcomes data of UKB participants were downloaded and data-fields were prioritized based on participants with death registry records. Kaplan-Meier method was used to evaluate survival differences among ethnic groups; survival random forest feature selection followed by Cox proportional-hazard modeling was used to identify and estimate the effects of shared and ethnic group-specific mortality risk factors. The White ethnic group showed significantly worse survival probability than the Asian and Black groups. In all three ethnic groups, endoscopy and colonoscopy procedures showed significant protective effects on overall mortality. Asian and Black women show lower relative risk of mortality than men, whereas no significant effect of sex was seen for the White group. The strongest ethnic group-specific mortality associations were ischemic heart disease for Asians, COVID-19 for Blacks, and cancers of respiratory/intrathoracic organs for Whites. Mental health-related diagnoses, including substance abuse, anxiety, and depression, were a major risk factor for overall mortality in the Asian group. The effect of mental health on Asian mortality, particularly for digestive cancers, was exacerbated by an observed hesitance to answer mental health questions, possibly related to cultural stigma. C-reactive protein (CRP) serum levels were associated with both overall and cause-specific mortality due to COVID-19 and digestive cancers in the Black group, where elevated CRP has previously been linked to psychosocial stress due to discrimination. Our results point to mortality risk factors that are group-specific and modifiable, supporting targeted interventions towards greater health equity.

Multiplex Real-time PCR Assay for the Detection of all Chlamydia Species and Simultaneous Differentiation of C. psittaci and C. pneumoniae in Human Clinical Specimens.

We developed and assessed the performance of a new multiplex real-time PCR assay for the detection of all Chlamydia species and simultaneous differentiation of Chlamydia psittaci and Chlamydia pneumoniae-two important human respiratory pathogens-in human clinical specimens. Next-generation sequencing was used to identify unique targets to design real-time PCR assays targeting all Chlamydia species, C. psittaci, and C. pneumoniae. To validate the assay, we used a panel of 49 culture isolates comprising seven C. psittaci genotypes, eight C. pneumoniae isolates, seven other Chlamydia species, and 22 near-neighbor bacterial and viral isolates, along with 22 specimens from external quality assessment (EQA) panels and 34 nasopharyngeal and oropharyngeal swabs and cerebrospinal fluid, stool, and sputum specimens previously identified as positive or negative for C. psittaci or C. pneumoniae. The assays were 100% specific, with limits of detection of 7.64- 9.02 fg/µL. The assay results matched with historical assay results for all specimens, except for one owing to the increased sensitivity of the new C. psittaci assay; the results of the EQA specimens were 100% accurate. This assay may improve the timely and accurate clinical diagnosis of Chlamydia infections and provide a greater understanding of the burden of disease caused by these agents.

Genomics and metagenomics of Madurella mycetomatis, a causative agent of black grain mycetoma in Sudan.

Madurella mycetomatis is one of the main causative agents of mycetoma, a debilitating neglected tropical disease. Improved understanding of the genomic diversity of the fungal and bacterial causes of mycetoma is essential to advances in diagnosis and treatment. Here, we describe a high-quality genome assembly of M. mycetomatis and results of the whole genome sequence analysis of 26 isolates from Sudan. We demonstrate evidence of at least seven genetically diverse lineages and extreme clonality among isolates within these lineages. We also performed shotgun metagenomic analysis of DNA extracted from mycetoma grains and showed that M. mycetomatis reads were detected in all sequenced samples with the average of 11,317 reads (s.d. +/- 21,269) per sample. In addition, 10 (12%) of the 81 tested grain samples contained bacterial reads including Streptococcus sp., Staphylococcus sp. and others.

Comorbidities and ethnic health disparities in the UK biobank.

Objective: The goal of this study was to investigate the relationship between comorbidities and ethnic health disparities in a diverse, cosmopolitan population. Materials and Methods: We used the UK Biobank (UKB), a large progressive cohort study of the UK population. Study participants self-identified with 1 of 5 ethnic groups and participant comorbidities were characterized using the 31 disease categories captured by the Elixhauser Comorbidity Index. Ethnic disparities in comorbidities were quantified as the extent to which disease prevalence within categories varies across ethnic groups and the extent to which pairs of comorbidities co-occur within ethnic groups. Disease-risk factor comorbidity pairs were identified where one comorbidity is known to be a risk factor for a co-occurring comorbidity. Results: The Asian ethnic group shows the greatest average number of comorbidities, followed by the Black and then White groups. The Chinese group shows the lowest average number of comorbidities. Comorbidity prevalence varies significantly among the ethnic groups for almost all disease categories, with diabetes and hypertension showing the largest differences across groups. Diabetes and hypertension both show ethnic-specific comorbidities that may contribute to the observed disease prevalence disparities. Discussion: These results underscore the extent to which comorbidities vary among ethnic groups and reveal group-specific disease comorbidities that may underlie ethnic health disparities. Conclusion: The study of comorbidity distributions across ethnic groups can be used to inform targeted group-specific interventions to reduce ethnic health disparities.

Mutations in SORL1 and MTHFDL1 possibly contribute to the development of Alzheimer's disease in a multigenerational Colombian Family.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 50 million people worldwide in 2020 and this number will triple to 152 million by 2050. Much of the increase will be in developing countries like Colombia. In familial forms, highly penetrant mutations have been identified in three genes, APP, PSEN1, and PSEN2, supporting a role for amyloid-ß peptide. In sporadic forms, more than 30 risk genes involved in the lipid metabolism, the immune system, and synaptic functioning mechanisms. We used whole-exome sequencing (WES) to evaluate a family of 97 members, spanning three generations, with a familiar AD, and without mutations in APP, PSEN1, or PSEN2. We sequenced two affected and one unaffected member with the aim of identifying genetic variants that could explain the presence of the disease in the family and the candidate variants were validated in eleven members. We also built a structural model to try to determine the effect on protein function. WES analysis identified two rare variants in SORL1 and MTHFD1L genes segregating in the family with other potential risk variants in APOE, ABCA7, and CHAT, suggesting an oligogenic inheritance. Additionally, the structural 3D models of SORL1 and MTHFD1L variants shows that these variants produce polarity changes that favor hydrophobic interactions, resulting in local structural changes that could affect the protein function and may contribute to the development of the disease in this family.

Building trauma capability: using geospatial analysis to consider military treatment facilities for trauma center development.

Background: The Military Health System must develop and sustain experienced surgical trauma teams while facing decreased surgical volumes both during and between deployments. Military trauma resources may enhance local trauma systems by accepting civilian patients for care at military treatment facilities (MTFs). Some MTFs may be able to augment their regional trauma systems by developing trauma center (TC) capabilities. The aim of this study was to evaluate the geographical proximity of MTFs to the continental US (CONUS) population and relative to existing civilian adult TCs, and then to determine which MTFs might benefit most from TC development. Methods: Publicly available data were used to develop a list of CONUS adult civilian level 1 and level 2 TCs and also to generate a list of CONUS MTFs. Census data were used to estimate adult population densities across zip codes. Distances were calculated between zip codes and civilian TCs and MTFs. The affected population sizes and reductions in distance were tabulated for every zip code that was found to be closer to an MTF than an existing TC. Results: 562 civilian adult level 1 and level 2 TCs and 33 military medical centers and hospitals were identified. Compared with their closest civilian TCs, MTFs showed mean reductions in distance ranging from 0 to 30 miles, affecting populations ranging from 12 000 to over 900 000 adults. Seven MTFs were identified that would offer clinically significant reductions in distance to relatively large population centers. Discussion: Some MTFs may offer decreased transit times and improved care to large adult populations within their regional trauma systems by developing level 1 or level 2 TC capabilities. The results of this study provide recommendations to focus further study on seven MTFs to identify those that merit further development and integration with their local trauma systems. Level of evidence: IV.

The health impacts of the COVID-19 pandemic on adults who experience imprisonment globally: A mixed methods systematic review.

BACKGROUND: The prison setting and health status of people who experience imprisonment increase the risks of COVID-19 infection and sequelae, and other health impacts of the COVID-19 pandemic. OBJECTIVES: To conduct a mixed methods systematic review on the impacts of the COVID-19 pandemic on the health of people who experience imprisonment. DATA SOURCES: We searched Medline, PsycINFO, Embase, the Cochrane Library, Social Sciences Abstracts, CINAHL, Applied Social Sciences Index and Abstracts, Sociological Abstracts, Sociology Database, Coronavirus Research Database, ERIC, Proquest Dissertations and Theses, Web of Science, and Scopus in October 2021. We reviewed reference lists for included studies. STUDY ELIGIBILITY CRITERIA: Original research conducted in or after December 2019 on health impacts of the COVID-19 pandemic on adults in prisons or within three months of release. STUDY APPRAISAL AND SYNTHESIS METHODS: We used the Joanna Briggs Institute's Critical Appraisal Checklist for Qualitative Research for qualitative studies and the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data for quantitative studies. We qualitized quantitative data and extracted qualitative data, coded data, and collated similar data into categories. RESULTS: We identified 62 studies. People in prisons had disproportionately high rates of COVID-19 infection and COVID-19 mortality. During the pandemic, all-cause mortality worsened, access to health care and other services worsened, and there were major impacts on mental wellbeing and on relationships with family and staff. There was limited evidence regarding key primary and secondary prevention strategies. LIMITATIONS: Our search was limited to databases. As the COVID-19 pandemic is ongoing, more evidence will emerge. CONCLUSIONS: Prisons and people who experience imprisonment should be prioritized for COVID-19 response and recovery efforts, and an explicit focus on prisons is needed for ongoing public health work including emergency preparedness. PROSPERO REGISTRATION NUMBER: 239324.

Vitamin D and socioeconomic deprivation mediate COVID-19 ethnic health disparities.

Ethnic minorities in developed countries suffer a disproportionately high burden of COVID-19 morbidity and mortality, and COVID-19 ethnic disparities have been attributed to social determinants of health. Vitamin D has been proposed as a modifiable risk factor that could mitigate COVID-19 health disparities. We investigated the relationship between vitamin D and COVID-19 susceptibility and severity using the UK Biobank, a large progressive cohort study of the United Kingdom population. Structural equation modelling was used to evaluate the ability of vitamin D, socioeconomic deprivation, and other known risk factors to mediate COVID-19 ethnic health disparities. Asian ethnicity is associated with higher COVID-19 susceptibility, compared to the majority White population, and Asian and Black ethnicity are both associated with higher COVID-19 severity. Socioeconomic deprivation mediates all three ethnic disparities and shows the highest overall signal of mediation for any COVID-19 risk factor. Vitamin supplements, including vitamin D, mediate the Asian disparity in COVID-19 susceptibility, and serum 25-hydroxyvitamin D (calcifediol) levels mediate Asian and Black COVID-19 severity disparities. Several measures of overall health also mediate COVID-19 ethnic disparities, underscoring the importance of comorbidities. Our results support ethnic minorities' use of vitamin D as both a prophylactic and a supplemental therapeutic for COVID-19.

Health Status of Females Who Experience Incarceration: A Population-Based Retrospective Cohort Study.

Background: People who experience incarceration have poor health across a variety of indicators, but we lack population-level data on the health of females in particular. We examined the health status of females released from provincial prison, and compared their data with data for males released from provincial prison and females in the general population in Ontario, Canada in 2010. Methods: We conducted a retrospective cohort study using linked correctional and health administrative data. We compared sociodemographic data, morbidity, mortality, and use of health care for (1) females released from provincial prison in 2010, (2) males released from provincial prison in 2010, and (3) age-matched females in the general population. Results: Females in the incarceration group (N = 6,107) were more likely to have higher morbidity and specific psychiatric conditions compared with the male incarceration group (N = 42,754) and the female general population group (N = 24,428). Their mortality rate postrelease was several times higher than that for the female general population group. They used primary care more often than both comparator groups across all time periods, and they used emergency departments more often compared with the female general population group and in most periods postrelease compared with the male incarceration group. They also tended to have higher rates of medical-surgical and psychiatric hospitalization. Conclusion: Females who experience incarceration have worse health overall than males who experience incarceration and females in the general population. Efforts should be made to reform programs and policies in the criminal justice and health care systems to support and promote health for females who experience incarceration.

Comparison of 10- versus 14-gauge angiocatheter for treatment of tension pneumothorax and tension-induced pulseless electrical activity with hemorrhagic shock: Bigger is still better.

BACKGROUND: Little is known regarding the effect of hemorrhagic shock on the diagnosis and treatment of tension pneumothorax (tPTX). Recently, the Tactical Combat Casualty Care guidelines included the 10-gauge angiocatheter (10-g AC) as an acceptable alternative to the 14-g AC. This study sought to compare these two devices for decompression of tPTX and rescue from tension-induced pulseless electric activity (tPEA) in the setting of a concomitant 30% estimated blood volume hemorrhage. METHODS: Following a controlled hemorrhage, carbon dioxide was insufflated into the chest to induce either tPTX or tPEA. Tension pneumothorax was defined as a reduction in cardiac output by 50%, and tPEA was defined as a loss of arterial waveform with mean arterial pressure less than 20 mm Hg. The affected hemithorax was decompressed using a randomized 14-g AC or 10-g AC while a persistent air leak was maintained after decompression. Successful rescue from tPTX was defined as 80% recovery of baseline systolic blood pressure, while successful return of spontaneous circulation following tPEA was defined as a mean arterial pressure greater than 20 mm Hg. Primary outcome was success of device. RESULTS: Eighty tPTX and 50 tPEA events were conducted in 38 adult Yorkshire swine. There were no significant differences in the baseline characteristics between animals or devices. In the tPTX model, the 10-g AC successfully rescued 90% of events, while 14-g AC rescued 80% of events (p = 0.350). In the tPEA model, the 10-g AC rescued 87% of events while the 14 AC rescued only 48% of events (p = 0.006). CONCLUSION: The 10-g AC was vastly superior to the 14-g AC for return of spontaneous circulation following tPEA in the setting of 30% hemorrhage. These findings further support the importance of larger caliber devices that facilitate rapid recovery from tPTX, particularly in the setting of polytrauma. LEVEL OF EVIDENCE: Therapeutic, level II.

From far and wide: Geographic distance to pediatric surgical care across Canada.

PURPOSE: Canada is the second largest country in the world, with most of the population located in the southern-most portion of its geography. We sought to define the relative distribution of pediatric surgeons to potential pediatric patients using data from the Canadian census. METHODS: The 2011 Canadian Census and a convenience sample of current Canadian pediatric surgeons were used to calculate straight-line distances between pediatric surgeon postal code centroids and census dissemination block centroids. RESULTS: Currently, there are 74 practicing pediatric surgeons in Canada; 493,345 populated census blocks were identified, and 7,752,075 children were enumerated. The median (IQR) kilometers to the closest pediatric surgeon was 27.99 (11.35, 85.47) kilometers, and 22.7% of Canadian children lived more than 100 km from care. Nearly 13% of children lived greater than 200 km from the nearest pediatric surgeon. CONCLUSION: More than 1.7 million Canadian children, nearly one quarter of all Canadian children, live greater than 100 km from the closest pediatric surgeon. This identifies a disparate group of patients who do not have an equal access-to-care as compared to others in the country. LEVEL OF EVIDENCE: Level IV.

Admixture-enabled selection for rapid adaptive evolution in the Americas.

BACKGROUND: Admixture occurs when previously isolated populations come together and exchange genetic material. We hypothesize that admixture can enable rapid adaptive evolution in human populations by introducing novel genetic variants (haplotypes) at intermediate frequencies, and we test this hypothesis through the analysis of whole genome sequences sampled from admixed Latin American populations in Colombia, Mexico, Peru, and Puerto Rico. RESULTS: Our screen for admixture-enabled selection relies on the identification of loci that contain more or less ancestry from a given source population than would be expected given the genome-wide ancestry frequencies. We employ a combined evidence approach to evaluate levels of ancestry enrichment at single loci across multiple populations and multiple loci that function together to encode polygenic traits. We find cross-population signals of African ancestry enrichment at the major histocompatibility locus on chromosome 6, consistent with admixture-enabled selection for enhanced adaptive immune response. Several of the human leukocyte antigen genes at this locus, such as HLA-A, HLA-DRB51, and HLA-DRB5, show independent evidence of positive selection prior to admixture, based on extended haplotype homozygosity in African populations. A number of traits related to inflammation, blood metabolites, and both the innate and adaptive immune system show evidence of admixture-enabled polygenic selection in Latin American populations. CONCLUSIONS: The results reported here, considered together with the ubiquity of admixture in human evolution, suggest that admixture serves as a fundamental mechanism that drives rapid adaptive evolution in human populations.

Evaluation of Surgical Caseload Aboard the USNS COMFORT (T-AH 20) During Enduring Promise 2018.

The USNS COMFORT (T-AH-20) deployed in support of Enduring Promise 2018 (EP-18) for an 11-week humanitarian mission providing care to the residents of four host nations in Central and South America. The COMFORT provides the capability of providing medical, dental, and surgical care in humanitarian aid missions.

Assortative Mating on Ancestry-Variant Traits in Admixed Latin American Populations.

Assortative mating is a universal feature of human societies, and individuals from ethnically diverse populations are known to mate assortatively based on similarities in genetic ancestry. However, little is currently known regarding the exact phenotypic cues, or their underlying genetic architecture, which inform ancestry-based assortative mating. We developed a novel approach, using genome-wide analysis of ancestry-specific haplotypes, to evaluate ancestry-based assortative mating on traits whose expression varies among the three continental population groups - African, European, and Native American - that admixed to form modern Latin American populations. Application of this method to genome sequences sampled from Colombia, Mexico, Peru, and Puerto Rico revealed widespread ancestry-based assortative mating. We discovered a number of anthropometric traits (body mass, height, and facial development) and neurological attributes (educational attainment and schizophrenia) that serve as phenotypic cues for ancestry-based assortative mating. Major histocompatibility complex (MHC) loci show population-specific patterns of both assortative and disassortative mating in Latin America. Ancestry-based assortative mating in the populations analyzed here appears to be driven primarily by African ancestry. This study serves as an example of how population genomic analyses can yield novel insights into human behavior.

Population Pharmacogenomics for Precision Public Health in Colombia.

While genomic approaches to precision medicine hold great promise, they remain prohibitively expensive for developing countries. The precision public health paradigm, whereby healthcare decisions are made at the level of populations as opposed to individuals, provides one way for the genomics revolution to directly impact health outcomes in the developing world. Genomic approaches to precision public health require a deep understanding of local population genomics, which is still missing for many developing countries. We are investigating the population genomics of genetic variants that mediate drug response in an effort to inform healthcare decisions in Colombia. Our work focuses on two neighboring populations with distinct ancestry profiles: Antioquia and Chocó. Antioquia has primarily European genetic ancestry followed by Native American and African components, whereas Chocó shows mainly African ancestry with lower levels of Native American and European admixture. We performed a survey of the global distribution of pharmacogenomic variants followed by a more focused study of pharmacogenomic allele frequency differences between the two Colombian populations. Worldwide, we found pharmacogenomic variants to have both unusually high minor allele frequencies and high levels of population differentiation. A number of these pharmacogenomic variants also show anomalous effect allele frequencies within and between the two Colombian populations, and these differences were found to be associated with their distinct genetic ancestry profiles. For example, the C allele of the single nucleotide polymorphism (SNP) rs4149056 [Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1)∗5], which is associated with an increased risk of toxicity to a commonly prescribed statin, is found at relatively high frequency in Antioquia and is associated with European ancestry. In addition to pharmacogenomic alleles related to increased toxicity risk, we also have evidence that alleles related to dosage and metabolism have large frequency differences between the two populations, which are associated with their specific ancestries. Using these findings, we have developed and validated an inexpensive allele-specific PCR assay to test for the presence of such population-enriched pharmacogenomic SNPs in Colombia. These results serve as an example of how population-centered approaches to pharmacogenomics can help to realize the promise of precision medicine in resource-limited settings.

Genetic ancestry, admixture and health determinants in Latin America.

BACKGROUND: Modern Latin American populations were formed via genetic admixture among ancestral source populations from Africa, the Americas and Europe. We are interested in studying how combinations of genetic ancestry in admixed Latin American populations may impact genomic determinants of health and disease. For this study, we characterized the impact of ancestry and admixture on genetic variants that underlie health- and disease-related phenotypes in population genomic samples from Colombia, Mexico, Peru, and Puerto Rico. RESULTS: We analyzed a total of 347 admixed Latin American genomes along with 1102 putative ancestral source genomes from Africans, Europeans, and Native Americans. We characterized the genetic ancestry, relatedness, and admixture patterns for each of the admixed Latin American genomes, finding a spectrum of ancestry proportions within and between populations. We then identified single nucleotide polymorphisms (SNPs) with anomalous ancestry-enrichment patterns, i.e. SNPs that exist in any given Latin American population at a higher frequency than expected based on the population's genetic ancestry profile. For this set of ancestry-enriched SNPs, we inspected their phenotypic impact on disease, metabolism, and the immune system. All four of the Latin American populations show ancestry-enrichment for a number of shared pathways, yielding evidence of similar selection pressures on these populations during their evolution. For example, all four populations show ancestry-enriched SNPs in multiple genes from immune system pathways, such as the cytokine receptor interaction, T cell receptor signaling, and antigen presentation pathways. We also found SNPs with excess African or European ancestry that are associated with ancestry-specific gene expression patterns and play crucial roles in the immune system and infectious disease responses. Genes from both the innate and adaptive immune system were found to be regulated by ancestry-enriched SNPs with population-specific regulatory effects. CONCLUSIONS: Ancestry-enriched SNPs in Latin American populations have a substantial effect on health- and disease-related phenotypes. The concordant impact observed for same phenotypes across populations points to a process of adaptive introgression, whereby ancestry-enriched SNPs with specific functional utility appear to have been retained in modern populations by virtue of their effects on health and fitness.

Sex and Relationships Education for Individuals with Cystic Fibrosis: A Service-Based Approach.

Increasing life expectancy within cystic fibrosis (CF) raises challenges around previously neglected topics such as sexual and reproductive health (SRH). The study aimed to gather retrospective experiences of service provision around SRH to consider the role of the CF service, age of information provision and unmet needs highlighting possible improvements to provision. A mixed-methods retrospective survey-based design was employed. An Adult CF team participated in a consultation session generating survey questions around SRH. A 20-item online survey was constructed and disseminated to adult CF patients. Unmet needs were found in SRH provision in pediatric and adult CF services, with further information required by patients on topics including parenthood and fertility. Results support previous research findings highlighting the need for standardized provision around SRH. Age of SRH provision suggested individual differences in need within the pediatric service. Further research could explore format and specific age of SRH information provision.

GlobAl Distribution of GEnetic Traits (GADGET) web server: polygenic trait scores worldwide.

Human populations from around the world show striking phenotypic variation across a wide variety of traits. Genome-wide association studies (GWAS) are used to uncover genetic variants that influence the expression of heritable human traits; accordingly, population-specific distributions of GWAS-implicated variants may shed light on the genetic basis of human phenotypic diversity. With this in mind, we developed the GlobAl Distribution of GEnetic Traits web server (GADGET http://gadget.biosci.gatech.edu). The GADGET web server provides users with a dynamic visual platform for exploring the relationship between worldwide genetic diversity and the genetic architecture underlying numerous human phenotypes. GADGET integrates trait-implicated single nucleotide polymorphisms (SNPs) from GWAS, with population genetic data from the 1000 Genomes Project, to calculate genome-wide polygenic trait scores (PTS) for 818 phenotypes in 2504 individual genomes. Population-specific distributions of PTS are shown for 26 human populations across 5 continental population groups, with traits ordered based on the extent of variation observed among populations. Users of GADGET can also upload custom trait SNP sets to visualize global PTS distributions for their own traits of interest.