Accuracy of clinical pallor in the diagnosis of anaemia in children: a meta-analysis

BACKGROUND: Anaemia is highly prevalent in children of developing countries. It is associated with impaired physical growth and mental development. Palmar pallor is recommended at primary level for diagnosing it, on the basis of few studies. The objective of the study was to systematically assess the accuracy of clinical signs in the diagnosis of anaemia in children. METHODS: A systematic review on the accuracy of clinical signs of anaemia in children. We performed an Internet search in various databases and an additional reference tracking. Studies had to be on performance of clinical signs in the diagnosis of anaemia, using haemoglobin as the gold standard. We calculated pooled diagnostic likelihood ratios (LR's) and odds ratios (DOR's) for each clinical sign at different haemoglobin thresholds. RESULTS: Eleven articles met the inclusion criteria. Most studies were performed in Africa, in children underfive. Chi-square test for proportions and Cochran Q for DOR's and for LR's showed heterogeneity. Type of observer and haemoglobin technique influenced the results. Pooling was done using the random effects model. Pooled DOR at haemoglobin <11 g/dL was 4.3 (95% CI 2.6–7.2) for palmar pallor, 3.7 (2.3–5.9) for conjunctival pallor, and 3.4 (1.8–6.3) for nailbed pallor. DOR's and LR's were slightly better for nailbed pallor at all other haemoglobin thresholds. The accuracy did not vary substantially after excluding outliers. CONCLUSION: This meta-analysis did not document a highly accurate clinical sign of anaemia. In view of poor performance of clinical signs, universal iron supplementation may be an adequate control strategy in high prevalence areas. Further well-designed studies are needed in settings other than Africa. They should assess inter-observer variation, performance of combined clinical signs, phenotypic differences, and different degrees of anaemia

Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8×10−5), establishing a novel phenotype for this genetic variant

Planning for precarity? Experiencing the carceral continuum of imprisonment and reentry

Drawing on qualitative interviews with formerly imprisoned people in Canada, we show that most prisoners experience reentry into communities with little to no pre-release planning, and must rely upon their own resourcefulness to navigate fragmented social services and often informal supports. In this respect, our research findings contrast with U.S. punishment and society scholarship that highlights a complex shadow carceral state that extends the reach of incarceration into communities. Our participants expressed a critical analysis of the failure of the prison to address the needs of prisoners for release planning and supports in the community. Our findings concur with other empirical studies that demonstrate the enduring effects of the continuum of carceral violence witnessed and experienced by prisoners after release. Thus, reentry must be understood in relation to the conditions of confinement and the experience of incarceration itself. We conclude that punishment and society scholarship needs to attend to a nuanced understanding of prisoner reentry and connect reentry studies to a wider critique of the prison industrial complex, offering more empirical evidence of the failure of prisons

Whole genome sequence analysis of platelet traits in the NHLBI Trans-Omics for Precision Medicine (TOPMed) initiative

Platelets play a key role in thrombosis and hemostasis. Platelet count (PLT) and mean platelet volume (MPV) are highly heritable quantitative traits, with hundreds of genetic signals previously identified, mostly in European ancestry populations. We here utilize whole genome sequencing (WGS) from NHLBI's Trans-Omics for Precision Medicine initiative (TOPMed) in a large multi-ethnic sample to further explore common and rare variation contributing to PLT (n = 61 200) and MPV (n = 23 485). We identified and replicated secondary signals at MPL (rs532784633) and PECAM1 (rs73345162), both more common in African ancestry populations. We also observed rare variation in Mendelian platelet-related disorder genes influencing variation in platelet traits in TOPMed cohorts (not enriched for blood disorders). For example, association of GP9 with lower PLT and higher MPV was partly driven by a pathogenic Bernard-Soulier syndrome variant (rs5030764, p.Asn61Ser), and the signals at TUBB1 and CD36 were partly driven by loss of function variants not annotated as pathogenic in ClinVar (rs199948010 and rs571975065). However, residual signal remained for these gene-based signals after adjusting for lead variants, suggesting that additional variants in Mendelian genes with impacts in general population cohorts remain to be identified. Gene-based signals were also identified at several genome-wide association study identified loci for genes not annotated for Mendelian platelet disorders (PTPRH, TET2, CHEK2), with somatic variation driving the result at TET2. These results highlight the value of WGS in populations of diverse genetic ancestry to identify novel regulatory and coding signals, even for well-studied traits like platelet traits

Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program

Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3 bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders

Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: The NHLBI TOPMed program

Many common and rare variants associated with hematologic traits have been discovered through imputation on large-scale reference panels. However, the majority of genome-wide association studies (GWASs) have been conducted in Europeans, and determining causal variants has proved challenging. We performed a GWAS of total leukocyte, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts generated from 109,563,748 variants in the autosomes and the X chromosome in the Trans-Omics for Precision Medicine (TOPMed) program, which included data from 61,802 individuals of diverse ancestry. We discovered and replicated 7 leukocyte trait associations, including (1) the association between a chromosome X, pseudo-autosomal region (PAR), noncoding variant located between cytokine receptor genes (CSF2RA and CLRF2) and lower eosinophil count; and (2) associations between single variants found predominantly among African Americans at the S1PR3 (9q22.1) and HBB (11p15.4) loci and monocyte and lymphocyte counts, respectively. We further provide evidence indicating that the newly discovered eosinophil-lowering chromosome X PAR variant might be associated with reduced susceptibility to common allergic diseases such as atopic dermatitis and asthma. Additionally, we found a burden of very rare FLT3 (13q12.2) variants associated with monocyte counts. Together, these results emphasize the utility of whole-genome sequencing in diverse samples in identifying associations missed by European-ancestry-driven GWASs

Resource-use efficiency in okra production among smallholder farmers in Ika south and north east local government areas of Delta state, Nigeria

This study examined the efficiency of resource use among smallholder okra farmers in Ika South and North Local Government Areas of Delta State, Nigeria. A two-stage sampling procedure was adopted in the selection of 113 okra farmers for the study using questionnaire. Data were analysed using descriptive statistics, multiple regression and marginal analyses. The result shows that most of the okra farmers were female. The mean age of the okra farmers was 47 year, while majority (90.3%) of the respondents were married. The mean household size was 5 persons, while the average farming experience was 20 years. The average farms size was 20.3 hectares. Three functional forms were tested and the linear function was chosen based on the number and significance of the parameters. The coefficient of multiple determination (R2) was 0.501which indicates that 50.1% of the variation in the output of Okra was accounted for by the independent variables in the model. The result of the marginal analysis showed that labour, farm size, fertilizer and planting material were underutilized as their ratios were greater than one, while herbicide on the other hand was over utilized. The study recommended that in other to increase the output of okra in the study area farmers have to increase the use of farm size, labour, fertilizer and planting materials since they are technically operating in stage 1 of the production process. Also, the use of herbicide should be decreased in other for these resources to be efficiently utilized.Key word: Resource-use. Okra production, multiple regression, marginal analysi

Perceived effect of climate change on crop production by farmers in Edo state, Nigeria

The study analyzed farmers’ perception of climate change effect on production and examined the perceived effect of climate change on farmers’ livelihood, Data was collected from 270 farmers sampled from nine Local Government Areas in the three agricultural zones of Edo state. The data were analyzed using descriptive statistics involving frequency distribution, percentages and mean, Binomial test and Friedman test were used to test the hypotheses of the study. The result of the analysis showed that most of the respondents were female (52.6%), married (87.8%) and relatively young (mean age 53 years), had formal education (73.7%) and having an average family size of nine. The major crops produced by the respondents were maize (65.6%), cassava (64.4%), melon (49.6%) and yam (47.4%). Weather conditions such as early rainfall (84.44%), late rainfall (62.96%), frequency of rainfall (53.30%), and drought (50%) were seen as unpredictable by respondents. The climate change parameters experienced by the respondents were increase in excessive heat at night (88.15%), flooding (71.11%), incidence of gully erosion (61.85%) and increase in temperature (50%). A major effect of climate change on the farmers’ livelihood was reduction in farm income (mean=3.31), while the most perceived effects of climate change on the farmers production were land slide/erosion of farm (mean = 2.6) and damages to crop (mean = 2.6). The study recommended that weather forecasts and predictions should be made available to the farmers right on time and enlightenment campaign on how to cope with climate change should be embarked upon by members of the Agricultural Development Program.Key words: Binomial test., Climate change., crop production., Friedman test., perceptio