Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations.

Facial morphology is highly variable, both within and among human populations, and a sizable portion of this variation is attributable to genetics. Previous genome scans have revealed more than 100 genetic loci associated with different aspects of normal-range facial variation. Most of these loci have been detected in Europeans, with few studies focusing on other ancestral groups. Consequently, the degree to which facial traits share a common genetic basis across diverse sets of humans remains largely unknown. We therefore investigated the genetic basis of facial morphology in an East African cohort. We applied an open-ended data-driven phenotyping approach to a sample of 2,595 3D facial images collected on Tanzanian children. This approach segments the face into hierarchically arranged, multivariate features that capture the shape variation after adjusting for age, sex, height, weight, facial size and population stratification. Genome scans of these multivariate shape phenotypes revealed significant (p < 2.5 × 10-8) signals at 20 loci, which were enriched for active chromatin elements in human cranial neural crest cells and embryonic craniofacial tissue, consistent with an early developmental origin of the facial variation. Two of these associations were in highly conserved regions showing craniofacial-specific enhancer activity during embryological development (5q31.1 and 12q21.31). Six of the 20 loci surpassed a stricter threshold accounting for multiple phenotypes with study-wide significance (p < 6.25 × 10-10). Cross-population comparisons indicated 10 association signals were shared with Europeans (seven sharing the same associated SNP), and facilitated fine-mapping of causal variants at previously reported loci. Taken together, these results may point to both shared and population-specific components to the genetic architecture of facial variation.

Genome-wide copy number variations in a large cohort of bantu African children.

BACKGROUND: Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies including people of African descent. METHODS: We carried out a genome-wide copy number analysis in > 3400 healthy Bantu Africans from Tanzania. Signal intensity data from high density (> 2.5 million probes) genotyping arrays were used for CNV calling with three algorithms including PennCNV, DNAcopy and VanillaICE. Stringent quality metrics and filtering criteria were applied to obtain high confidence CNVs. RESULTS: We identified over 400,000 CNVs larger than 1 kilobase (kb), for an average of 120 CNVs (SE = 2.57) per individual. We detected 866 large CNVs (≥ 300 kb), some of which overlapped genomic regions previously associated with multiple congenital anomaly syndromes, including Prader-Willi/Angelman syndrome (Type1) and 22q11.2 deletion syndrome. Furthermore, several of the common CNVs seen in our cohort (≥ 5%) overlap genes previously associated with developmental disorders. CONCLUSIONS: These findings may help refine the phenotypic outcomes and penetrance of variations affecting genes and genomic regions previously implicated in diseases. Our study provides one of the largest datasets of CNVs from individuals of African ancestry, enabling improved clinical evaluation and disease association of CNVs observed in research and clinical studies in African populations.

The role of Vitamin B12 and genetic risk factors in the etiology of neural tube defects: A systematic review.

Neural tube defects (NTDs) are birth defects that arise during embryogenesis when normal neural tube closure fails to occur. According to the World Health Organization, NTDs are detected annually in approximately 300,000 neonates worldwide. The exact etiology of NTDs remains complex and poorly understood. It is generally agreed that most NTD cases are of multifactorial origin, having a combination of multiple genes and a number of environmental risk factors. The role of folic acid, vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs, has also been extensively studied. This knowledge synthesis brings together different types of evidence to update the role of vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs. Following a PubMed search and screening for relevant articles, we included 40 studies in our review (30 case-control studies, 3 cross-sectional studies, 5 cohort studies, and 2 case reports). The available data showed that vitamin B12 levels were decreased in mothers and infants in NTD groups compared with control groups. Holo-transcobalamin, the active form of vitamin B12, was also found in lower levels in mothers with NTD-affected infants. Several studies reported elevated homocysteine levels in mothers and infants in NTD groups. Additionally, numerous studies reported links between genetic variants and increased NTD risk. These genes include GIF, LRP2, CUBN, TCb1R, MTHFR, and others. Several maternal factors have also been linked with significant NTD risk such as BMI, maternal diet, air pollutants, low maternal age, and many others. The majority of studies on NTDs have focused on the role of folic acid, hence there is a need for well-designed studies on the role of other risk factors like vitamin B12 deficiency in the etiology of NTDs.

Soil transmitted helminth infection in primary school children varies with ecozone in the Ngorongoro Conservation Area, Tanzania.

BACKGROUND: Soil-transmitted helminthiasis is a neglected tropical disease, thriving in environments of poverty and disadvantage. Our objective was to determine the prevalence and intensity of four soil transmitted helminths (STH) among primary school children in the Ngorongoro Conservation Area (NCA), Tanzania. METHODS: A cross-sectional study was performed between May 15th and June 2nd, 2014. Six of 20 primary schools were chosen, based on elevation, designated low elevation ecozone (LEE) or high elevation ecozone (HEE). A total of 340 children from standards one to four were recruited. Height and weight of each child was determined and body mass index (BMI) was calculated. Stool samples were analyzed using the Kato-Katz, Wisconsin, and Baermann techniques to detect STH eggs and larvae. An interviewer-administered questionnaire on socio-demographic variables was used to capture information from the school's headmaster and a checklist was used to assess sanitation facilities. RESULTS: STHs identified included Ascaris (presumably lumbricoides), Trichuris (presumably trichiura), hookworms (presumably Ancylostoma duodenale and/or Necator americanus), and Strongyloides (presumably stercoralis). The overall prevalence of STH infection was 29.0% in LEE and 34.0% in HEE. Prevalence was 34.3% and 28.2% in males versus females, respectively. Ascaris sp. were only identified in HEE, prevalence of Trichuris sp. and hookworms were significantly higher in HEE compared to LEE, and Strongyloides spp. prevalence was lower in HEE. Intensity of Trichuris sp. was significantly higher in HEE and lower for hookworms. We did not detect a significant relationship between BMI and helminth intensity; however, BMI was lower in lower elevations and in males vs. females. Sanitation practices are taught at the schools, but challenges were identified when implementing. Latrine facilities were available and latrine-cleaning routines were practiced; however, hand washing practices were challenging due to restricted water availability. CONCLUSIONS: Significant differences in prevalence in HEE and LEE exist, and STH infections are still very common among school children suggesting that anthelminthic intervention and education may be necessary in this region. Based on this outcome, the study area in the NCA would be classified as a medium risk area, where periodic treatment recommendations should be based on prevalence estimations in the different ecozones. TRIAL REGISTRATION: Ethics approval was obtained from the Catholic University of Health and Allied Sciences (CUHAS; Lake Zone Institutional Review Board MR/53/100/307)); the Conjoint Health Research Ethics Board (CHREB) at the University of Calgary in Canada (Study ID REB14-0127); the National Institute of Medical Research (NIMR) of Tanzania; and the Tanzania Commission for Science and Technology (COSTEC).

Effects of prenatal exposure and co-exposure to metallic or metalloid elements on early infant neurodevelopmental outcomes in areas with small-scale gold mining activities in Northern Tanzania.

BACKGROUND: Artisanal and small-scale gold mining (ASGM) is associated with release of neurotoxic metallic or metalloid chemical elements including lead (Pb), mercury (Hg), cadmium (Cd) and arsenic (As). OBJECTIVE: To examine associations between prenatal exposure and co-exposure to total lead (T-Pb), total mercury (T-Hg), total cadmium (T-Cd) and total arsenic (T-As) and infant neurodevelopment at 6 to 12 months of age in areas with ASGM activities in Tanzania. METHODS: Women in their second trimester of pregnancy who resided in ASGM areas were enrolled from 2015 to 2017 (n = 883). At 6 to 12 months of age, children were assessed with the Malawi Developmental Assessment Tool (MDAT) (n = 439). We measured T-Pb, T-Hg, and T-Cd in maternal dried blood spots and T-As in maternal urines. Poisson regression was used to examine associations between prenatal concentrations of these elements and neurodevelopmental outcomes. RESULTS: Prenatal T-Hg concentration was associated with global neurodevelopment status (aPR 1.03, CI:1.01-1.04; p < 0.001) and language impairment (aPR 1.05, CI:1.03-1.07; p < 0.001) on the MDAT. When prenatal T-Hg and T-As values were at or above the human biomonitoring reference values (≥95%) of the German Environmental Survey for Human Biomonitoring, that is 0.80 µg/L and 15 µg/L, respectively, the prevalence ratio of global neurodevelopmental impairment was two times higher (aPR 2.1, CI:1.0-4.3; p = 0.034). There was a 40% increase in the prevalence ratio of global neurodevelopmental impairment (aPR 1.4, CI:0.90-2.10, p = 0.027), when prenatal T-Hg was at or above the reference value of 0.80 µg/L and T-Pb was at or above the reference value of 35 µg/L. When prenatal T-Hg was at or above the reference value of 0.80 µg/L and T-As was at or above the reference value of 15 µg/L, the prevalence ratio of global neurodevelopmental impairment was two times higher (aPR 2.1, CI:1.0-4.3; p < 0.034). DISCUSSION: Infants born to women in areas with ASGM activities are at significant risk for neurodevelopmental impairment and this is associated with exposure to higher concentrations of Hg prenatally. Co-exposure to high concentrations of Hg and Pb, or Hg and As appeared to have negative potentiated effects on infants' neurodevelopment.

Lack of head sparing following third-trimester caloric restriction among Tanzanian Maasai.

The reduction of food intake during pregnancy is part of many cultural and religious traditions around the world. The impact of such practices on fetal growth and development are poorly understood. Here, we examined the patterns of diet intake among Maasai pregnant women and assessed their effect on newborn morphometrics. We recruited 141 mother-infant pairs from Ngorongoro Conservation Area (NCA) in Northern Tanzania and quantified dietary intake and changes in maternal diet during pregnancy. We obtained measurements of body weight (BW) and head circumference (HC) at birth. We found that Maasai women significantly reduced their dietary intake during the third trimester, going from an average of 1601 kcal/day during the first two trimesters to 799 kcal/day in the final trimester. The greatest proportion of nutrient reduction was in carbohydrates. Overall, 40% of HC Z-scores of the NCA sample were more than 2 standard deviations below the WHO standard. Nearly a third of neonates classify as low birth weight (< 2500g). HC was smaller relative to BW in this cohort than predicted using the WHO standard. This contrasts markedly to a Tanzanian birth cohort obtained at the same time in an urban context in which only 12% of infants exhibited low weight, only two individuals had HC Z-scores < 2 and HC's relative to birth weight were larger than predicted using the WHO standards. The surprising lack of head sparing in the NCA cohort suggests that the impact of third trimester malnutrition bears further investigation in both animal models and human populations, especially as low HC is negatively associated with long term health outcomes.

Maternal exposure to arsenic and mercury and associated risk of adverse birth outcomes in small-scale gold mining communities in Northern Tanzania.

BACKGROUND: Exposure to arsenic and mercury in artisanal and small-scale gold mining (ASGM) communities is an issue that predominantly affects low and middle-income countries. Large epidemiology studies in these communities are rare, and the impact of such exposures on reproductive outcomes are not well understood. OBJECTIVE: To examine associations between prenatal maternal arsenic and mercury exposure and birth outcomes in both ASGM and non-ASGM communities in Northern Tanzania. METHODS: This longitudinal prospective study included 961 women (ASGM = 788, non-ASGM = 173) of the original cohort of 1056 who were followed until a pregnancy outcome was registered. Maternal spot urine samples and dried blood spots were used to measure total arsenic (T-As) and total mercury (T-Hg) in the second trimester of pregnancy. Data on adverse birth outcomes were collected in 5 categories: spontaneous abortion, stillbirth, preterm birth, low birth weight, and visible congenital anomalies. Mann-Whitney U-tests were used to test for differences between median T-As and T-Hg by area of residence. Logistic regression models were used to estimate the odds of stillbirth and visible congenital anomalies given maternal T-As and T-Hg levels. Modified Poisson regressions were used to estimate relative risk ratios between maternal T-As and T-Hg levels and composite adverse birth outcome, spontaneous abortion, low birth weight, and preterm birth. RESULTS: Statistically significant differences were found in median T-As (9.6 vs. 6.3 µg/L, Mann-Whitney U-tests, Z = -3.50, p < 0.001) and median T-Hg blood concentrations (1.2 vs. 0.70 µg/L, Z = -9.88, p-value < 0.001) between women living in ASGM and non-ASGM areas respectively. In ASGM areas, the adjusted relative risk (aRR) of a composite adverse birth outcome increased with increasing T-As (aRR 1.23, 95%CI: 1.14-1.33, p < 0.0001) and T-Hg (aRR 1.17, 95%CI: 1.1-1.25, p < 0.0001) exposure. Spontaneous abortion (aRR 1.53, 95%CI: 1.28-1.83), stillbirth (adjusted odds ratio (aOR) 1.97, 95%CI: 1.45-2.66) and preterm birth (1.17, 95%CI: 1.01-1.36) were significantly associated with elevated T-As, whereas elevated T-Hg was significantly associated with stillbirth (aOR 2.49, 95%CI: 1.88-3.29) and visible congenital anomalies (aOR 2.24, 95%CI: 1.3-3.87). CONCLUSION: Over half (54.7%) of women in ASGM areas of Northern Tanzania had adverse birth outcomes and the risk of adverse birth outcomes was significantly associated with increased prenatal exposure to arsenic and mercury.

A variant source of arterial supply to the ascending, transverse and descending colon.

Anatomic variations involving arterial supply of the large intestines are of clinical significance. Variations range from the pattern of origin, branching and territorial supply. The colon, the part of the large intestine, usually receives its arterial blood supply from branches of the superior and inferior mesenteric arteries. However, anatomic variation in this vascular arrangement has been reported, with vascular anatomy of the right colon being described as complex and more variable compared with the left colon. During routine cadaveric dissection of the supracolic and infracolic viscera, we encountered an additional mesenteric artery originating directly from the anterior surface of the abdominal aorta between the origins of the superior and inferior mesenteric arteries. This additional "inferior mesenteric artery" ran obliquely superiorly toward the left colon giving rise to two branches supplying the distal part of the ascending colon, the transverse colon and the proximal part of the descending colon. Awareness and knowledge of this anatomic variation are important for radiologists and surgeons to improve the quality of surgery and avoid both intra- and postoperative complications during surgical procedures of the colon.

Maternal exposure to arsenic and mercury in small-scale gold mining areas of Northern Tanzania.

Artisanal and small-scale gold mining (ASGM) in Tanzania results in occupational exposures and environmental contamination to toxic chemical elements such as arsenic and mercury. Populations living in such areas may be exposed by various routes, and prenatal exposure to arsenic and mercury has been associated with adverse birth outcomes and developmental delays. The aim of this study was to determine if levels of arsenic and mercury differed among pregnant women living in areas with and without ASGM activities in Northern Tanzania. This cross-sectional study is part of the ongoing Mining and Health prospective longitudinal study. Spot urine samples and dried blood spots were collected at the antenatal health clinics from pregnant women (n = 1056) at 16-27 weeks gestation. Urine samples were analyzed for total arsenic (T-As) and dried blood spots were analyzed for total mercury (T-Hg). Women in the ASGM cohort had median T-As levels (9.4 µg/L; IQR: 4.9-15.1) and T-Hg levels (1.2 µg/L; IQR: 0.8-1.86) that were significantly higher than the median T-As levels (6.28 µg/L; IQR: 3.7-14.1) and T-Hg levels (0.66 µg/L; IQR: 0.3-1.2) of women in the non-ASGM cohort (Mann-Whitney U test, T-As: z = -9.881, p = 0.0005; T-Hg: z = -3.502, p < 0.0001). Among pregnant women from ASGM areas, 25% had urinary T-As and 75% had blood T-Hg above the established human biomonitoring reference values of 15 and 0.80 µg/L. In the ASGM cohort, lower maternal education and low socioeconomic status increased the odds of higher T-As levels by 20% (p < 0.05) and 10% (p < 0.05), respectively. Women involved in mining activities and those of low socioeconomic status had increased odds of higher T-Hg by 70% (p < 0.001) and 10% (p < 0.05), respectively. Arsenic and mercury concentrations among women in non-ASGM areas suggest exposure sources beyond ASGM activities that need to be identified. Arsenic and mercury levels in women in Tanzania are of public health concern and their association with adverse birth and child developmental outcomes will be examined in future studies on this cohort.

Validation of Dried Blood Spots for Maternal Biomonitoring of Nonessential Elements in an Artisanal and Small-Scale Gold Mining Area of Tanzania.

Biomonitoring studies of vulnerable populations in low- and middle-income countries are limited because traditional sampling methods are challenging to implement in low-resource settings. The present study examined the feasibility, precision, and accuracy of dried blood spots (DBS) for human biomonitoring of nonessential elements (cadmium [Cd], mercury [Hg], and lead [Pb]) in an area of northern Tanzania with artisanal and small-scale gold mining activities. Pregnant women (n = 44) were recruited in Geita during antenatal clinic visits, and DBS from capillary blood were collected on filter paper. As a gold-standard comparison, venous blood was sampled from the same participants and compared with the DBS. Venous blood, DBS, and quality control samples were analyzed for chemical elements by inductively coupled plasma mass spectrometry. Field blanks were very clean for most elements, generally only twice as high as corresponding laboratory filter blanks. No significant differences were found between duplicate DBS samples taken from the same participants, with near perfect intraclass correlation coefficients (0.99) for Cd, Hg, and Pb, indicating excellent reliability. Moreover, correlation was strong (r2 > 0.9) and significant (p < 0.0001) between DBS and the quantitative venous blood, with regression line slopes close to 1.0 (0.847, 0.976, and 0.969 for Cd, Hg, and Pb, respectively), indicating high accuracy of the DBS method compared with the gold-standard approach. The DBS method is minimally invasive and was a feasible, precise, and accurate means of measuring exposure to Cd, Hg, and Pb in pregnant women in a low-resource setting. Environ Toxicol Chem 2019;38:1285-1293. © 2019 SETAC.

Facial shape manifestations of growth faltering in Tanzanian children.

Variation in the shape of the human face and in stature is determined by complex interactions between genetic and environmental influences. One such environmental influence is malnourishment, which can result in growth faltering, usually diagnosed by means of comparing an individual's stature with a set of age-appropriate standards. These standards for stature, however, are typically ascertained in groups where people are at low risk for growth faltering. Moreover, genetic differences among populations with respect to stature are well established, further complicating the generalizability of stature-based diagnostic tools. In a large sample of children aged 5-19 years, we obtained high-resolution genomic data, anthropometric measures and 3D facial images from individuals within and around the city of Mwanza, Tanzania. With genome-wide complex trait analysis, we partitioned genetic and environmental variance for growth outcomes and facial shape. We found that children with growth faltering have faces that look like those of older and taller children, in a direction opposite to the expected allometric trajectory, and in ways predicted by the environmental portion of covariance at the community and individual levels. The environmental variance for facial shape varied subtly but significantly among communities, whereas genetic differences were minimal. These results reveal that facial shape preserves information about exposure to undernourishment, with important implications for refining assessments of nutritional status in children and the developmental-genetics of craniofacial variation alike.

Body size and allometric variation in facial shape in children.

OBJECTIVES: Morphological integration, or the tendency for covariation, is commonly seen in complex traits such as the human face. The effects of growth on shape, or allometry, represent a ubiquitous but poorly understood axis of integration. We address the question of to what extent age and measures of size converge on a single pattern of allometry for human facial shape. METHODS: Our study is based on two large cross-sectional cohorts of children, one from Tanzania and the other from the United States (N = 7,173). We employ 3D facial imaging and geometric morphometrics to relate facial shape to age and anthropometric measures. RESULTS: The two populations differ significantly in facial shape, but the magnitude of this difference is small relative to the variation within each group. Allometric variation for facial shape is similar in both populations, representing a small but significant proportion of total variation in facial shape. Different measures of size are associated with overlapping but statistically distinct aspects of shape variation. Only half of the size-related variation in facial shape can be explained by the first principal component of four size measures and age while the remainder associates distinctly with individual measures. CONCLUSIONS: Allometric variation in the human face is complex and should not be regarded as a singular effect. This finding has important implications for how size is treated in studies of human facial shape and for the developmental basis for allometric variation more generally.

Participatory science and innovation for improved sanitation and hygiene: process and outcome evaluation of project SHINE, a school-based intervention in Rural Tanzania.

BACKGROUND: Diarrheal disease is a major cause of mortality and morbidity in low and middle income countries with children being disproportionately affected. Project SHINE (Sanitation & Hygiene INnovation in Education) is a grassroots participatory science education and social entrepreneurship model to engage youth and the wider community in the development of sustainable strategies to improve sanitation and hygiene. METHODS: Based in rural and remote Tanzania, this pilot study engaged pastoralist high-school students and communities in the development and evaluation of culturally and contextually relevant strategies to improve sanitation and hygiene. Using a train-the-trainer approach, key activities included teacher workshops, school-based lessons, extra-curricular activities, community events and a One Health sanitation science fair which showcased projects related to water, sanitation and hygiene in relation to human and animal health. The process and outcome of the study were evaluated through qualitative interviews and focus group discussions with diverse project participants, as well as pre- and post- questionnaires completed by students on knowledge, attitudes and practices concerning sanitation and hygiene. RESULTS: The questionnaire results at baseline and follow-up showed statistically significant improvements on key measures including a decrease in unhygienic behaviors, an increase in the perceived importance of handwashing and intention to use the toilet, and increased communication in the social network about the importance of clean water and improved sanitation and hygiene practices, however there were no significant changes in sanitation related knowledge. Qualitative data highlighted strong leadership emerging from youth and enthusiasm from teachers and students concerning the overall approach in the project, including the use of participatory methods. There was a high degree of community engagement with hundreds of community members participating in school-based events. Sanitation science fair projects addressed a range of pastoralist questions and concerns regarding the relationship between water, sanitation and hygiene. Several projects, such as making soap from local materials, demonstrate potential as a sustainable strategy to improve health and livelihoods in the long-term. CONCLUSIONS: The Project SHINE model shows promise as an innovative capacity building approach and as an engagement and empowerment strategy for youth and communities to develop locally sustainable strategies to improve sanitation and hygiene.

Rapid automated landmarking for morphometric analysis of three-dimensional facial scans.

Automated phenotyping is essential for the creation of large, highly standardized datasets from anatomical imaging data. Such datasets can support large-scale studies of complex traits or clinical studies related to precision medicine or clinical trials. We have developed a method that generates three-dimensional landmark data that meet the requirements of standard geometric morphometric analyses. The method is robust and can be implemented without high-performance computing resources. We validated the method using both direct comparison to manual landmarking on the same individuals and also analyses of the variation patterns and outlier patterns in a large dataset of automated and manual landmark data. Direct comparison of manual and automated landmarks reveals that automated landmark data are less variable, but more highly integrated and reproducible. Automated data produce covariation structure that closely resembles that of manual landmarks. We further find that while our method does produce some landmarking errors, they tend to be readily detectable and can be fixed by adjusting parameters used in the registration and control-point steps. Data generated using the method described here have been successfully used to study the genomic architecture of facial shape in two different genome-wide association studies of facial shape.

Human Facial Shape and Size Heritability and Genetic Correlations.

The human face is an array of variable physical features that together make each of us unique and distinguishable. Striking familial facial similarities underscore a genetic component, but little is known of the genes that underlie facial shape differences. Numerous studies have estimated facial shape heritability using various methods. Here, we used advanced three-dimensional imaging technology and quantitative human genetics analysis to estimate narrow-sense heritability, heritability explained by common genetic variation, and pairwise genetic correlations of 38 measures of facial shape and size in normal African Bantu children from Tanzania. Specifically, we fit a linear mixed model of genetic relatedness between close and distant relatives to jointly estimate variance components that correspond to heritability explained by genome-wide common genetic variation and variance explained by uncaptured genetic variation, the sum representing total narrow-sense heritability. Our significant estimates for narrow-sense heritability of specific facial traits range from 28 to 67%, with horizontal measures being slightly more heritable than vertical or depth measures. Furthermore, for over half of facial traits, >90% of narrow-sense heritability can be explained by common genetic variation. We also find high absolute genetic correlation between most traits, indicating large overlap in underlying genetic loci. Not surprisingly, traits measured in the same physical orientation (i.e., both horizontal or both vertical) have high positive genetic correlations, whereas traits in opposite orientations have high negative correlations. The complex genetic architecture of facial shape informs our understanding of the intricate relationships among different facial features as well as overall facial development.

Genomewide Association Study of African Children Identifies Association of SCHIP1 and PDE8A with Facial Size and Shape.

The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each of us unique, distinguishable, and recognizable. Relatively little is known about the genetic underpinnings of normal human facial variation. To address this, we carried out a large genomewide association study and two independent replication studies of Bantu African children and adolescents from Mwanza, Tanzania, a region that is both genetically and environmentally relatively homogeneous. We tested for genetic association of facial shape and size phenotypes derived from 3D imaging and automated landmarking of standard facial morphometric points. SNPs within genes SCHIP1 and PDE8A were associated with measures of facial size in both the GWAS and replication cohorts and passed a stringent genomewide significance threshold adjusted for multiple testing of 34 correlated traits. For both SCHIP1 and PDE8A, we demonstrated clear expression in the developing mouse face by both whole-mount in situ hybridization and RNA-seq, supporting their involvement in facial morphogenesis. Ten additional loci demonstrated suggestive association with various measures of facial shape. Our findings, which differ from those in previous studies of European-derived whites, augment understanding of the genetic basis of normal facial development, and provide insights relevant to both human disease and forensics.

Developing a Pictorial Sisterhood Method in collaboration with illiterate Maasai traditional birth attendants in northern Tanzania.

OBJECTIVE: To study whether data on maternal mortality can be gathered while maintaining local ownership of data in a pastoralist setting where a scarcity of data sources and a culture of silence around maternal death amplifies limited awareness of the magnitude of maternal mortality. METHODS: As part of a participatory action research project, investigators and illiterate traditional birth attendants (TBAs) collaboratively developed a quantitative participatory tool-the Pictorial Sisterhood Method-that was pilot-tested between March 12 and May 30, 2011, by researchers and TBAs in a cross-sectional study. RESULTS: Fourteen TBAs interviewed 496 women (sample), which led to 2241 sister units of risk and a maternal mortality ratio of 689 deaths per 100000 live births (95% confidence interval 419-959). Researchers interviewed 474 women (sample), leading to 1487 sister units of risk and a maternal mortality ratio of 484 (95% confidence interval 172-795). CONCLUSION: The Pictorial Sisterhood Method is an innovative application that might increase the participation of illiterate individuals in maternal health research and advocacy. It offers interesting opportunities to increase maternal mortality data ownership and awareness, and warrants further study and validation.

What basic clinical procedures should be mastered by junior clerkship students? Experience at a single medical school in Tanzania.

BACKGROUND: Clinical training in most medical schools, including the Catholic University of Health and Allied Sciences (CUHAS), is offered in the form of junior and senior rotations. During these clinical rotations, students are expected to acquire and master the basic procedural skills. However, students' learning process should be evaluated for quality improvement. OBJECTIVES: This study was conducted to identify the basic medical procedural skills that third-year medical students should acquire and master and determine the level of students' exposure on these procedures at the end of junior rotation in internal medicine. Identification of the gap between clinicians' opinions, skills practiced by students, and third-year students' curriculum in the medical department at CUHAS was also done. METHODS: The descriptive cross-sectional study was used to collect data through a self-administered, structured questionnaire from clinicians in medicine. A review of logbooks was considered to determine level of students' exposure, and a document analysis was done using existing medical curriculum. RESULTS: The response of 71% (n=22) was obtained. Clinicians agreed on basic procedures that students should perform independently (ie, Foley catheter insertion, venipuncture, and intravenous drip insertion). Clinicians thought that lumbar punctures, abdominal paracentesis, and nasogastric tube insertion should be done under minimal supervision. A considerable number of students (25%, n=75) did not practice any procedure throughout their rotation. The majority of the students performed venipuncture independently (82.14%, n=56) and lumbar punctures (73.21%, n=56) under supervision. Less than 25% (n=56) of the students met the required number of exposures on the basic procedures. The procedures to be performed and the level of competency in the procedures are not specified in the current curriculum. CONCLUSION: The study identified the procedures that should be taught and practiced by students. It also highlighted the discrepancies in the existing curriculum and the need to monitor and supervise students' practice.

Improving gross anatomy learning using reciprocal peer teaching.

BACKGROUND: The use of cadavers in human anatomy teaching requires adequate number of anatomy instructors who can provide close supervision of the students. Most medical schools are facing challenges of lack of trained individuals to teach anatomy. Innovative techniques are therefore needed to impart adequate and relevant anatomical knowledge and skills. This study was conducted in order to evaluate the traditional teaching method and reciprocal peer teaching (RPT) method during anatomy dissection. METHODS: Debriefing surveys were administered to the 227 first year medical students regarding merits, demerits and impact of both RPT and Traditional teaching experiences on student's preparedness prior to dissection, professionalism and communication skills. Out of this, 159 (70 %) completed the survey on traditional method while 148 (65.2 %) completed survey on RPT method. An observation tool for anatomy faculty was used to assess collaboration, professionalism and teaching skills among students. Student's scores on examinations done before introduction of RPT were compared with examinations scores after introduction of RPT. RESULTS: Our results show that the mean performance of students on objective examinations was significantly higher after introduction of RPT compared to the performance before introduction of RPT [63.7 ± 11.4 versus 58.6 ± 10, mean difference 5.1; 95 % CI = 4.0-6.3; p-value < 0.0001]. Students with low performance prior to RPT benefited more in terms of examination performance compared to those who had higher performance [Mean difference 7.6; p-value < 0.0001]. Regarding student's opinions on traditional method versus RPT, 83 % of students either agreed or strongly agreed that they were more likely to read the dissection manual before the RPT dissection session compared to 35 % for the traditional method. Over 85 % of respondents reported that RPT improved their confidence and ability to present information to peers and faculty compared to 38 % for the tradition method. The majority of faculty reported that the learning environment of the dissection groups was very active learning during RPT sessions and that professionalism was observed by most students during discussions. CONCLUSIONS: Introduction of RPT in our anatomy dissection laboratory was generally beneficial to both students and faculty. Both objective (student performance) and subjective data indicate that RPT improved student's performance and had a positive learning experience impact. Our future plan is to continue RPT practice and continually evaluate the RPT protocol.

Household-level predictors of maternal mental health and systemic inflammation among infants in Mwanza, Tanzania.

OBJECTIVES: Household conditions and culturally/socially variable childcare practices influence priming of the inflammatory response during infancy. Maternal mental health may partially mediate that effect. Among mother-infant dyads in Mwanza, Tanzania, we hypothesized that poorer maternal mental health would be associated with adverse household ecology, lower social capital, and greater inflammation among infants under the age of one; and that mental health would mediate any effects of household ecology/social capital on inflammation. METHODS: We collected dried blood spots from mother-infant dyads (N = 88) at health centers near Mwanza, Tanzania. To assess household ecology and social capital, we conducted interviews with mothers using the Household Food Insecurity Access Scale, the MacArthur Subjective Social Status Scale, and a household wealth inventory. We employed the Hopkins Symptom Checklist to assess maternal mental health. A high-sensitivity C-reactive protein (CRP) assay was used to quantify inflammation. RESULTS: Severe food insecurity (OR: 5.16), lower subjective social status (r = -0.32), and lower household wealth (r = -0.26) were associated with high symptoms of maternal depression. Lower household wealth (r = -0.21) and severe food insecurity (OR: 2.52) were associated with high anxiety. High depression symptoms (OR: 2.56) and severe food insecurity (OR: 2.77) each were associated with greater-than-median infant CRP. However, mediation was not supported. CONCLUSIONS: Maternal mental health should be considered alongside nutritional status, pathogen exposure, and education as a potential driver of very early innate immune system development. Proximal mechanisms warrant further investigation. Am. J. Hum. Biol. 28:461-470, 2016. © 2015 Wiley Periodicals, Inc.