Evolution of immune genes is associated with the Black Death.

Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

Genetic resiliency and the Black Death: No apparent loss of mitogenomic diversity due to the Black Death in medieval London and Denmark.

OBJECTIVES: In the 14th century AD, medieval Europe was severely affected by the Great European Famine as well as repeated bouts of disease, including the Black Death, causing major demographic shifts. This high volatility led to increased mobility and migration due to new labor and economic opportunities, as evidenced by documentary and stable isotope data. This study uses ancient DNA (aDNA) isolated from skeletal remains to examine whether evidence for large-scale population movement can be gleaned from the complete mitochondrial genomes of 264 medieval individuals from England (London) and Denmark. MATERIALS AND METHODS: Using a novel library-conserving approach to targeted capture, we recovered 264 full mitochondrial genomes from the petrous portion of the temporal bones and teeth and compared genetic diversity across the medieval period within and between English (London) and Danish populations and with contemporary populations through population pairwise ΦST analysis. RESULTS: We find no evidence of significant differences in genetic diversity spatially or temporally in our dataset, yet there is a high degree of haplotype diversity in our medieval samples with little exact sequence sharing. DISCUSSION: The mitochondrial genomes of both medieval Londoners and medieval Danes suggest high mitochondrial diversity before, during and after the Black Death. While our mitochondrial genomic data lack geographically correlated signals, these data could be the result of high, continual female migration before and after the Black Death or may simply indicate a large female effective population size unaffected by the upheaval of the medieval period. Either scenario suggests a genetic resiliency in areas of northwestern medieval Europe.

Health care utilization following a homeless medical respite pilot program.

OBJECTIVE: The purpose of this study was to evaluate a homeless medical respite pilot program to determine if program participants had health care utilization pattern changes and improved connection to income, housing, and health care resources post program. DESIGN: This is a quantitative descriptive pre-/post-program evaluation. SAMPLE: A total of 29 patients experiencing homelessness and discharged from an acute care hospital in the southeastern United States were provided with housing and nursing case management. MEASUREMENTS: Demographics including age, sex, race, and ethnicity were collected. Connection to primary care, mental health, substance abuse services, income, insurance, and housing were assessed at program entry and completion. Health care utilization and charge and payment data were collected 1 year prior and 1 year post-respite stay. RESULTS: Participants demonstrated reduced hospital admissions (-36.7%) and when admitted, fewer inpatient days (-70.2%) and increased outpatient provider visits (+192.6%). Health care charges for the cohort decreased by 48.6% from the year prior to the program. Housing and income improved. CONCLUSIONS: The medical respite pilot program was successful in guiding patients to community resources for more appropriate health care at a demonstrated cost savings. Participants also derived benefits in the form of improved housing and income.

Assessing the need for a medical respite: perceptions of service providers and homeless persons.

For homeless persons, posthospitalization care is increasingly provided in formal medical respite programs, and their success is now reported in the literature. However, there is a dearth of literature on posthospitalization transitional care for homeless persons in the absence of a respite program. Through this formative study, we sought to understand the process of securing posthospitalization care in the absence of a formal homeless medical respite. Results demonstrated a de facto patchwork respite process that has emerged. We describe both human and monetary costs associated with patchwork respite and demonstrate opportunities for improvement in homeless health care transitions.

Opportunities for Nurses to Decrease the Stigma Associated with Housing Instability and Homelessness.

The number of people experiencing homelessness (PEH) in the United States has increased in the past 5 years. PEH have a higher disease burden and early mortality compared to people who are housed. Stigma adds to the burden of disease and disease management for PEH. In this article the authors review stigma, define housing and homelessness, describe the health and health care disparities PEH experience, and using the socio-ecological model as a framework, offer opportunities for nurses to intervene in efforts to decrease the stigma that PEH and housing instability encounter to improve health outcomes.

Emergence, continuity, and evolution of Yersinia pestis throughout medieval and early modern Denmark.

The historical epidemiology of plague is controversial due to the scarcity and ambiguity of available data.1,2 A common source of debate is the extent and pattern of plague re-emergence and local continuity in Europe during the 14th-18th century CE.3 Despite having a uniquely long history of plague (∼5,000 years), Scandinavia is relatively underrepresented in the historical archives.4,5 To better understand the historical epidemiology and evolutionary history of plague in this region, we performed in-depth (n = 298) longitudinal screening (800 years) for the plague bacterium Yersinia pestis (Y. pestis) across 13 archaeological sites in Denmark from 1000 to 1800 CE. Our genomic and phylogenetic data captured the emergence, continuity, and evolution of Y. pestis in this region over a period of 300 years (14th-17th century CE), for which the plague-positivity rate was 8.3% (3.3%-14.3% by site). Our phylogenetic analysis revealed that the Danish Y. pestis sequences were interspersed with those from other European countries, rather than forming a single cluster, indicative of the generation, spread, and replacement of bacterial variants through communities rather than their long-term local persistence. These results provide an epidemiological link between Y. pestis and the unknown pestilence that afflicted medieval and early modern Europe. They also demonstrate how population-scale genomic evidence can be used to test hypotheses on disease mortality and epidemiology and help pave the way for the next generation of historical disease research.

Reply to Barton et al: signatures of natural selection during the Black Death.

Barton et al.1 raise several statistical concerns regarding our original analyses2 that highlight the challenge of inferring natural selection using ancient genomic data. We show here that these concerns have limited impact on our original conclusions. Specifically, we recover the same signature of enrichment for high FST values at the immune loci relative to putatively neutral sites after switching the allele frequency estimation method to a maximum likelihood approach, filtering to only consider known human variants, and down-sampling our data to the same mean coverage across sites. Furthermore, using permutations, we show that the rs2549794 variant near ERAP2 continues to emerge as the strongest candidate for selection (p = 1.2×10-5), falling below the Bonferroni-corrected significance threshold recommended by Barton et al. Importantly, the evidence for selection on ERAP2 is further supported by functional data demonstrating the impact of the ERAP2 genotype on the immune response to Y. pestis and by epidemiological data from an independent group showing that the putatively selected allele during the Black Death protects against severe respiratory infection in contemporary populations.

Program Outcomes and Health Care Utilization of People Experiencing Homelessness and Substance Use Disorder after Transitional Care Program Engagement.

People experiencing homelessness (PEH) have a high prevalence of mental illness and substance use disorder (SUD) and substantial acute and chronic disease burden. Transitional care and medical respite programs facilitate a safe transfer for PEH from the acute care to community setting. Many medical respite programs practice harm reduction strategies that can increase the opportunity for positive program outcomes for PEH with SUD. This transitional care and medical respite program evaluation explored program outcomes, health care utilization patterns, and comorbid conditions of persons with and without SUD. People experiencing homelessness with SUD had similar program outcomes and both groups had decreased acute care utilization after program engagement. A high prevalence of trimorbidity, which is associated with early mortality, was noted. Opportunities for harm reduction strategies to promote both social and clinical outcomes are offered.

A life history approach to stature and body proportions in medieval Danes.

Developmental plasticity, or the ability of physiological development to change in response to environmental pressures (external and internal), results in permanent physiological changes that can shape the later life health experiences of an individual. The timing of non-specific stress in relation to growth and development is critical to this interaction. Dental enamel provides detailed information on the timing of non-specific stress experiences, which may be considered in relation to growth in other physiological systems developing at the same time to elucidate the impact of one on the other. Examples of parallel developing systems include the immune, nervous, cardiovascular, respiratory, renal, and digestive systems (Chamley et al. 2005; MacGregor 2008; Bee & Boyd 2010). This research investigates these patterns through the consideration markers of enamel growth disruption known as accentuated striae of Retzius (AS) in relation to stature and body proportions in human skeletal remains. Anthropometrics and dental samples were collected from two medieval Danish cemetery samples. Residuals were calculated using linear regression from stature in the grave and all metrics were considered in relation to a total number of AS for each individual. A life course approach was also taken by considering AS at different stages of crown development in relation to each metric. Results indicate potential associations between AS and skeletal metrics (particularly tibial length and stature). These are most apparent in relation to AS rates in enamel developing from approximately 2 to 4.8 years of age. These results point to the utility of taking a life course approach in which enamel development is considered in relation to patterns of skeletal growth. Certain limitations and the need for further developments are highlighted by the nature of the results.

Identifying Patients Experiencing Homelessness in an Electronic Health Record and Assessing Qualification for Medical Respite: A Five-Year Retrospective Review.

Our team developed a transitional care and medical respite program for people experiencing homelessness and designed a retrospective chart review study to more fully understand the unique needs of this population. Using four independent techniques, we identified individuals (N=1,656) who were experiencing homelessness during at least one hospital encounter (emergency department and/or in-patient admission) in a teaching hospital in the Southeastern United States over a five-year period. Data were manually abstracted from a random sample of patients to determine which patient encounters would or would not have qualified for medical respite if it had been available at the time. This article reports the methods used to identify people experiencing homelessness in the electronic health record, the data abstraction process, the cohort description, and the primary reasons patients would not have qualified for the medical respite program.

Stressing out in medieval Denmark: An investigation of dental enamel defects and age at death in two medieval Danish cemeteries.

The influence of early life stress on later life experiences has become a major focus of research in medicine and more recently in bioarchaeology. Dental enamel, which preserves a record of childhood stress events, represents an important resource for this investigation when paired with the information from adult skeletal remains, such as age at death. The purpose of this research was to use a life history approach to the exploration of sex differences in the relationship between childhood stress and adult longevity by examining accentuated striae of Retzius (AS). A medieval Danish sample (n=70) drawn from the rural cemetery of Sejet and the urban cemetery of Ole Wormsgade was considered for AS and age at death. The results suggest sex differences in survivorship, with more stress being associated with reduced survivorship in males and increased survivorship in females. A consideration of AS formation time also suggests a difference in the impact of developmental timing between males and females. These results are interpreted in terms of differential frailty and selective mortality, drawing in both biomedical and cultural perspectives.

Feasibility and acceptability of door-to-door rapid HIV testing among latino immigrants and their HIV risk factors in North Carolina.

Latino immigrants in the United States are disproportionally impacted by the HIV epidemic but face barriers to clinic-based testing. We assessed a community-based strategy for rapid HIV testing by conducting "door-to-door" outreaches in apartments with predominately Latino immigrants in Durham, North Carolina, that has experienced an exponential growth in its Latino population. Eligible persons were 18 years or older, not pregnant, and reported no HIV test in the previous month. Participants were asked to complete a survey and offered rapid HIV testing. Of the 228 Latino participants, 75.4% consented to HIV testing. There was a high prevalence of sexual risk behaviors among participants, with 42.5% acknowledging ever having sex with a commercial sex worker (CSW). Most (66.5%) had no history of prior HIV testing. In bivariate analysis, perceived HIV risk, no history of HIV testing, sex with a CSW, sex in exchange for drugs or money, living with a partner, and alcohol use were significantly associated with test acceptance. In the multivariate analysis, participants who had never been tested for HIV were more likely to consent to rapid HIV testing than those who had tested in the past (adjusted odds ratio 2.5; 95% confidence interval [CI], 1.1, 5.6). Most participants supported rapid HIV testing in the community (97%). Door-to-door rapid HIV testing is a feasible and acceptable strategy for screening high-risk Latino immigrants in the community. Factors associated with HIV risk among Latino migrants and immigrants in the United States should be considered along with novel testing strategies in HIV prevention programs.