Population interconnectivity over the past 120,000 years explains distribution and diversity of Central African hunter-gatherers

The evolutionary history of African hunter-gatherers holds key insights into modern human diversity. Here, we combine ethnographic and genetic data on Central African hunter-gatherers (CAHG) to show that their current distribution and density are explained by ecology rather than by a displacement to marginal habitats due to recent farming expansions, as commonly assumed. We also estimate the range of hunter-gatherer presence across Central Africa over the past 120,000 years using paleoclimatic reconstructions, which were statistically validated by our newly compiled dataset of dated archaeological sites. Finally, we show that genomic estimates of divergence times between CAHG groups match our ecological estimates of periods favoring population splits, and that recoveries of connectivity would have facilitated subsequent gene flow. Our results reveal that CAHG stem from a deep history of partially connected populations. This form of sociality allowed the coexistence of relatively large effective population sizes and local differentiation, with important implications for the evolution of genetic and cultural diversity in Homo sapiens.

The evolutionary history of African hunter-gatherers may hold key insights into patterns and processes behind the evolution of modern human diversity. Recent genomic studies have revealed that these populations represent the oldest and most diverse human genetic lineages and have been genetically differentiated from one another since the origin of humans (1–3) (SI Appendix, Table S1). Therefore, a first question is whether their current ecological niches were also characteristic of early Homo sapiens populations. However, genetic data alone can neither determine the geographic distribution of hunter-gatherers in the past nor demonstrate a deep history of adaptation of hunter-gatherers to their current environments. In fact, various studies have proposed that farming expansions within the past 5,000 years (in particular by the ancestors of Bantu speakers) would have only recently displaced hunter-gatherers to marginalized regions less favorable to agriculture (such as rainforests and deserts) (4–7).For example, the central part of Africa, between latitudes 5°N and 5°S currently is inhabited by ∼20 scattered hunter-gatherer ethnic groups (8). These Central African hunter-gatherers (CAHG) form a genetic clade thought to have diverged from other African populations as far back as 120,000 to 200,000 years ago (2, 9). The lack of any major linguistic specificity between them is often implied to reflect extensive contacts with surrounding farmer populations (8, 10), and seen as evidence of recent displacement into marginal forest environments by expanding farming populations. However, anthropologists have remarked on the huge variability in lifestyle, habitat, techniques, and tools between CAHG (11), suggestive of long-term cultural diversification and adaptation to forest environments. Research on the drivers of demography and adaptation of CAHG populations remains extremely limited, which can be partially attributed to the lack of archaeological and osteological data resulting from a rapid disintegration of fossil remains in the rainforest’s acidic soils, in addition to social instability in the region (12). Therefore, we are still left with crucial questions regarding the time depth of occupation of Central Africa by hunter-gatherers, the breadth of the niche exploited by earlier populations in the region, and variations in levels of interconnectivity at different points in time.To address those questions, we first compiled ethnographic data on the distribution of 749 camps from 11 hunter-gatherer groups extending from West to East Central Africa. We used them as inputs for environmental niche models (ENMs) to determine the relative influence of several bioclimatic and ecological factors, as well as the presence of farming populations, on the distribution and abundance of CAHG (13, 14). Then, we used high-resolution paleoclimatic reconstructions and topographic maps to make continuous predictions about where CAHG could have lived over the past 120,000 years and the potential extension of their interaction networks. Next, we compiled all reliably dated archaeological assemblages ascribed to hunter-gatherer groups in the Congo Basin (n = 168) and confirmed the model’s ability to predict the location and date of the sites. We further contextualized genomic estimates of population divergences with changes in population densities and interpopulation connectivity predicted by our model. Last, we complemented these analyses with a detailed assessment of present and historical gene flow between nine CAHG populations (n = 265 individuals), which we used to assess recent interactions between previously diverged CAHG populations, after farming expansions. Our study therefore provides a causal link between past environmental changes and human population dynamics over evolutionary time, by predicting where and when populations across Central Africa could have exchanged genetic and/or cultural information throughout their evolutionary history.     

Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial

The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We ran a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as a risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancer-associated VTE. RI was graded as moderate (creatinine clearance between 30-59 mL/minute; 275 patients) and mild (between 60-89 mL/minute; 444 patients). In the 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06-95% CI: 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR=0.67, 95% CI: 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR=0.27, 95% CI: 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR=2.84, 95% CI: 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study, in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin. ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03045406","term_id":"NCT03045406"}}NCT03045406.     

Differential Effects of Three Nutritional Supplements on the Nutrient Intake of Pregnant Women Enrolled in a Conditional Cash Transfer Program in Mexico: A Cluster Randomized Trial

Supplementation in malnourished pregnant women should not displace natural healthy foods. Objective: To estimate the differential effects of three nutritional supplements on macro- and micronutrient intake of pregnant women beneficiaries of the conditional cash transfer program Prospera (CCT-POP). Methods: Prospective cluster randomized trial. Communities were randomly assigned to receive a fortified beverage (Beverage), micronutrient tablets (Tablets), or micronutrient powder (MNP). Pregnant women (at <25 weeks) were recruited. The food frequency questionnaire was applied at 25 and 37 weeks of pregnancy and at one and three months postpartum (mpp). Differential effects of the three supplements on the median change in nutrient intake from baseline to each follow-up stage were estimated. Results: Median change in protein intake from dietary and supplement sources were significantly lower for MNP and Tablets than for Beverages (baseline to 37 w: −7.80 ± 2.90 and −11.54 ± 3.00, respectively; baseline to 1 mpp: −7.34 ± 2.90 for MNP, p < 0.001). Compared to Beverages, median increases were higher for the MNP for vitamins C (31.2 ± 11.7, p < 0.01), E (1.67 ± 0.81, p < 0.05), and B12 (0.83 ± 0.27, p < 0.01) from baseline to 37 wk; from baseline to 1 mpp, there was a higher median increase in B12 (0.55 ± 0.25, p < 0.05) and folate (63.4 ± 24.3, p < 0.01); and from baseline to 3 mpp, a higher median increase in iron (2.38 ± 1.06, p < 0.05) and folate (94.4 ± 38.1, p < 0.05). Conclusions: Intake of micronutrients was higher for MNP and Tablets, likely due to food displacement among Beverage consumers. Although iron bioavailability and absorption inhibitors were not considered for the present analyses, the distribution of Tablets or MNP had several advantages in this context where micronutrient deficiency remains high among pregnant women, but macronutrient intake is generally adequate or even high.     

Understanding the patterns of adjustment to infertility of IVF users using narrative and autobiographical timeline

ObjectiveTo examine how Hong Kong Chinese women and men coped with and adjusted to the infertility problem over time.MethodsUsing purposive sampling and theoretical sampling, nine heterosexual couples and ten women who had completed IVF were recruited. Data were collected using a narrative interviewing technique and autobiographical timeline, based on a grounded theory approach.ResultsRegardless of the outcome of IVF, coping with infertility and treatment was emotionally taxing. Four themes relating to the coping experiences were identified and captured innovatively in pictorial and narrative forms. They were: ‘one of the many’, resilience, recovery and prolonged grief. The findings concurred with the existing literature – coping with infertility is emotionally taxing, and variability exists in the degree of adjustment to infertility, which in turn influences well-being. The study also demonstrated the advantages of creative use of clinical-interview methods in research on couples subjective and lived experience of infertility.ConclusionThe findings suggest that the participants varied in their coping and adjustment to the experience of infertility, with most of them demonstrated positive meanings and resiliency over time. The combined use of both clinical-interview methods helped to facilitate exploration and articulation of the lived experiences of infertility among participants, allowing both in-depth understanding of the phenomenon and adherence to methodological rigor. The clinical-interview research methods can also promote evidence-based reflective practice for researchers and an empowering experience for participants.     

Comparison of risk-adjusted 30-day postoperative mortality and morbidity in Department of Veterans Affairs hospitals and selected university medical centers: general surgical operations in men

BACKGROUND: We used data from the Patient Safety in Surgery Study to compare patient populations, operative characteristics, and unadjusted and risk-adjusted 30-day postoperative mortality and morbidity between the Veterans Affairs (VA) (n = 94,098) and private (n = 18,399) sectors for general surgery operations in men. STUDY DESIGN: This is a prospective cohort study. Trained nurses collected preoperative risk factors, operative variables, and 30-day postoperative mortality and morbidity outcomes in male patients undergoing major general surgery operations at 128 VA medical centers and 14 university medical centers from October 1, 2001, to September 30, 2004. Multiple logistic regression analysis was used to identify preoperative predictors of postoperative mortality and morbidity. An indicator variable for VA versus private-sector medical center was added to the model to determine if risk-adjusted outcomes were significantly different in the two systems. RESULTS: The unadjusted 30-day mortality rate was higher in the VA compared with the private sector (2.62% versus 2.03%, p = 0.0002); unadjusted morbidity rate was lower in the VA compared with the private sector (12.24% versus 13.99%, p < 0.0001). After risk adjustment, odds ratio for mortality for the VA versus private sector was 1.23 (95% CI, 1.08-1.41). For morbidity after risk adjustment, the indicator variable for health-care system just missed statistical significance (p = 0.0585). Thirty-day postoperative mortality was comparable in the VA and private sector for very common operations but was higher in the VA for less common, more complex operations. CONCLUSIONS: In general surgery operations in men, the VA appeared to have a higher risk-adjusted mortality rate compared with the private sector, but differences in mortality ascertainment in the two sectors might account for some of this effect. The higher mortality in the VA could be the result of higher mortality in the less common, more complex operations. There is a trend toward lower risk-adjusted morbidity in the VA compared with the private sector.     

Risk-adjusted morbidity in teaching hospitals correlates with reported levels of communication and collaboration on surgical teams but not with scale measures of teamwork climate, safety climate, or working conditions

BACKGROUND: Since the Institute of Medicine patient safety reports, a number of survey-based measures of organizational climate safety factors (OCSFs) have been developed. The goal of this study was to measure the impact of OCSFs on risk-adjusted surgical morbidity and mortality. STUDY DESIGN: Surveys were administered to staff on general/vascular surgery services during a year. Surveys included multiitem scales measuring OCSFs. Additionally, perceived levels of communication and collaboration with coworkers were assessed. The National Surgical Quality Improvement Program was used to assess risk-adjusted morbidity and mortality. Correlations between outcomes and OCSFs were calculated and between outcomes and communication/collaboration with attending and resident doctors, nurses, and other providers. RESULTS: Fifty-two sites participated in the survey: 44 Veterans Affairs and 8 academic medical centers. A total of 6,083 surveys were returned, for a response rate of 52%. The OCSF measures of teamwork climate, safety climate, working conditions, recognition of stress effects, job satisfaction, and burnout demonstrated internal validity but did not correlate with risk-adjusted outcomes. Reported levels of communication/collaboration with attending and resident doctors correlated with risk-adjusted morbidity. CONCLUSIONS: Survey-based teamwork, safety climate, and working conditions scales are not confirmed to measure organizational factors that influence risk-adjusted surgical outcomes. Reported communication/collaboration with attending and resident doctors on surgical services influenced patient morbidity. This suggests the importance of doctors' coordination and decision-making roles on surgical teams in providing high-quality and safe care. We propose risk-adjusted morbidity as an effective measure of surgical patient safety.     

High prevalence of self-reported depressive mood during the winter season among Swedish senior high school students

OBJECTIVE: There are few studies regarding the prevalence of seasonal variation in mood among children and adolescents. The main objective of this study was to estimate the prevalence of self-reported depressive mood during the winter season among Swedish adolescents and to investigate gender differences. Another aim was to analyze the factor structure and internal consistency of the Kiddie SPAQ (K-SPAQ), a pediatric version of the Seasonal Pattern Questionnaire (SPAQ). METHOD: All students 17 to 18 years old, registered in the second year of senior high school in Falun, a district in central Sweden, were screened with the K-SPAQ in January 2003 (response rate 87.3%, n = 756). RESULTS: The prevalence of self-reported depressive mood during the winter season was estimated at 20.1% (n = 151/751) and was higher among girls (25.5%) than boys (13.8%). Approximately 8% reported more severe depressive symptoms. Depressive mood during the summer was rare (0.1%, n = 1/751). Factor analysis of the General Seasonal Score items in the K-SPAQ revealed a two-factor structure. A Cronbach's alpha of 0.87 demonstrated a good internal consistency. CONCLUSIONS: Depressive symptoms during autumn and winter were common among Swedish senior high school students, especially among girls. This is probably an underdiagnosed condition among adolescents that ought to receive more attention from the health and school authorities.     

Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy

OBJECTIVE: Defects in glycosylation of alpha-dystroglycan are associated with several forms of muscular dystrophy, often characterized by congenital onset and severe structural brain involvement, collectively known as dystroglycanopathies. Six causative genes have been identified in these disorders including fukutin. Mutations in fukutin cause Fukuyama congenital muscular dystrophy. This is the second most common form of muscular dystrophy in Japan and is invariably associated with mental retardation and structural brain defects. The aim of this study was to determine the genetic defect in two white families with a dystroglycanopathy. METHODS: The six genes responsible for dystroglycanopathies were studied in three children with a severe reduction of alpha-dystroglycan in skeletal muscle. RESULTS: We identified pathogenic fukutin mutations in these two families. Affected children had normal intelligence and brain structure and shared a limb girdle muscular dystrophy (LGMD) phenotype, had marked elevation of serum creatine kinase, and were all ambulant with remarkable steroid responsiveness. INTERPRETATION: Our data suggest that fukutin mutations occur outside Japan and can be associated with much milder phenotypes than Fukuyama congenital muscular dystrophy. These findings significantly expand the spectrum of phenotypes associated with fukutin mutations to include this novel form of limb girdle muscular dystrophy that we propose to name LGMD2L.