152 research outputs found

    Column adsorption studies for the removal of U by phosphonated cross-linked polyethylenimine: modelling and optimization.

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    A continuous fixed-bed adsorption study was carried out by using phosphonated cross-linked polyethylenimine as an adsorbent for the removal of uranium (U) from aqueous solutions. The effect of inlet metal ion concentration (40, 70, and 100 mg L-1), feed flow rate (1, 2, and 3 mL min(-1)), and polymer bed height (2.5, 3.2 and 4.5 cm) on the breakthrough characteristics of the fixed-bed adsorption system at pH 2 were studied. The results showed that the breakthrough time appeared to increase with increase of bed height but decreased with increase of both influent U concentration and flow rate. Modelling of the dynamics of the fixed-bed adsorption process was studied and the application of different models to describe the breakthrough curves showed that the Thomas and Yoon-Nelson model gave better results for the operating conditions.SP201

    β-thalassemia Intermedia In A Brazilian Patient With - 101 (c > T) And Codon 39 (c > T) Mutations

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    Context: We verified molecular alterations in a 72-year-old Brazilian male patient with a clinical course of homozygous β-thalassemia intermedia, who had undergone splenectomy and was surviving without regular blood transfusions. The blood cell count revealed microcytic and hypochromic anemia (hemoglobin = 6.5 g/dl, mean cell volume = 74 ft, mean cell hemoglobin = 24 pg) and hemoglobin electrophoresis showed fetal hemoglobin = 1.3%, hemoglobin A 2 = 6.78% and hemoglobin A = 79.4%. Objective: To identify mutations in a patient with the symptoms of β-thalassemia intermedia. Design: Molecular inquiry into the mutations possibly responsible for the clinical picture described. Setting: The structural molecular biology and genetic engineering center of the Universidade Estadual de Campinas, Campinas, Brazil. Procedures: DNA extraction was performed on the patient's blood samples. The polymerase chain reaction (PCR) was done using five specific primers that amplified exons and the promoter region of the β globin gene. The samples were sequenced and then analyzed via computer programs. Results: Two mutations that cause the disease were found: -101 (C > T) and codon 39 (C > T). Conclusions: This cases represents the first description of -101 (C > T) mutation in a Brazilian population and it is associated with a benign clinical course.12112830Baysal, E., Carver, M.F.H., The beta and delta-thalassemia repository (1995) Hemoglobin., 19 (3-4), pp. 213-236Zago, M.A., Costa, F., Bottura, C., Beta-thalassemia in Brazil (1981) Braz. J. Med. Biol. Res., 14 (6), pp. 383-388Ewing, B., Green, P., Base-calling of automated sequencer traces using Phred. II Error probabilities (1998) Genome Res., 8 (3), pp. 186-194Green, P., (2002), http://bozeman.genome.washington.edu/phrap.docs/phrap.html, The Phred/Phrap/Consed System Home Page. Phrap Assembler. Available at URL September 30Gordon, D., Abajian, C., Green, P., Consed: A graphical tool for sequence finishing (1998) Genome Res., 8 (3), pp. 195-20

    Eureka and beyond: mining's impact on African urbanisation

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    This collection brings separate literatures on mining and urbanisation together at a time when both artisanal and large-scale mining are expanding in many African economies. While much has been written about contestation over land and mineral rights, the impact of mining on settlement, notably its catalytic and fluctuating effects on migration and urban growth, has been largely ignored. African nation-states’ urbanisation trends have shown considerable variation over the past half century. The current surge in ‘new’ mining countries and the slow-down in ‘old’ mining countries are generating some remarkable settlement patterns and welfare outcomes. Presently, the African continent is a laboratory of national mining experiences. This special issue on African mining and urbanisation encompasses a wide cross-section of country case studies: beginning with the historical experiences of mining in Southern Africa (South Africa, Zambia, Zimbabwe), followed by more recent mineralizing trends in comparatively new mineral-producing countries (Tanzania) and an established West African gold producer (Ghana), before turning to the influence of conflict minerals (Angola, the Democratic Republic of Congo and Sierra Leone)

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Meta-analysis of type 2 Diabetes in African Americans Consortium

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    Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

    Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

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    Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US,2020US, 2020 US per capita, purchasing-power parity-adjusted USpercapita,andasaproportionofgrossdomesticproduct.Weusedvariousmodelstogeneratefuturehealthspendingto2050.FindingsIn2019,healthspendinggloballyreached per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached 8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or 1132(11191143)perperson.Spendingonhealthvariedwithinandacrossincomegroupsandgeographicalregions.Ofthistotal,1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, 40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that 54.8billionindevelopmentassistanceforhealthwasdisbursedin2020.Ofthis,54.8 billion in development assistance for health was disbursed in 2020. Of this, 13.7 billion was targeted toward the COVID-19 health response. 12.3billionwasnewlycommittedand12.3 billion was newly committed and 1.4 billion was repurposed from existing health projects. 3.1billion(22.43.1 billion (22.4%) of the funds focused on country-level coordination and 2.4 billion (17.9%) was for supply chain and logistics. Only 714.4million(7.7714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to 1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

    Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

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    Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

    Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

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    Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health
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