Blood Transfusion-Associated Infections in the Twenty-First Century: New Challenges
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ABSTRACT:
SUBMITTER: Fong I
PROVIDER: S-EPMC7120358 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:Biliary atresia (BA) is a fibroinflammatory disease of the intrahepatic and extrahepatic biliary tree. Surgical hepatic portoenterostomy (HPE) may restore bile drainage, but progression of the intrahepatic disease results in complications of portal hypertension and advanced cirrhosis in most children. Recognizing that further progress in the field is unlikely without a better understanding of the underlying cause(s) and pathogenesis of the disease, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored a research workshop focused on innovative and promising approaches and on identifying future areas of research. Investigators discussed recent advances using gestational ultrasound and results of newborn BA screening with serum direct (conjugated) bilirubin that support a prenatal onset of biliary injury. Experimental and human studies implicate the toxic properties of environmental toxins (e.g., biliatresone) and of viruses (e.g., cytomegalovirus) to the biliary system. Among host factors, sequence variants in genes related to biliary development and ciliopathies, a notable lack of a cholangiocyte glycocalyx and of submucosal collagen bundles in the neonatal extrahepatic bile ducts, and an innate proinflammatory bias of the neonatal immune system contribute to an increased susceptibility to damage and obstruction following epithelial injury. These advances form the foundation for a future research agenda focused on identifying the environmental and host factor(s) that cause BA, the potential use of population screening, studies of the mechanisms of prominent fibrosis in young infants, determinations of clinical surrogates of disease progression, and the design of clinical trials that target subgroups of patients with initial drainage following HPE. (Hepatology 2018; 00:000-000).
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Project description:This report provides an overview of current childhood cancer statistics to facilitate analysis of the impact of past research discoveries on outcome and provide essential information for prioritizing future research directions.Incidence and survival data for childhood cancers came from the Surveillance, Epidemiology, and End Results 9 (SEER 9) registries, and mortality data were based on deaths in the United States that were reported by states to the Centers for Disease Control and Prevention by underlying cause.Childhood cancer incidence rates increased significantly from 1975 through 2006, with increasing rates for acute lymphoblastic leukemia being most notable. Childhood cancer mortality rates declined by more than 50% between 1975 and 2006. For leukemias and lymphomas, significantly decreasing mortality rates were observed throughout the 32-year period, though the rate of decline slowed somewhat after 1998. For remaining childhood cancers, significantly decreasing mortality rates were observed from 1975 to 1996, with stable rates from 1996 through 2006. Increased survival rates were observed for all categories of childhood cancers studied, with the extent and temporal pace of the increases varying by diagnosis.When 1975 age-specific death rates for children are used as a baseline, approximately 38,000 childhood malignant cancer deaths were averted in the United States from 1975 through 2006 as a result of more effective treatments identified and applied during this period. Continued success in reducing childhood cancer mortality will require new treatment paradigms building on an increased understanding of the molecular processes that promote growth and survival of specific childhood cancers.
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Project description:The twentieth century ended with human African trypanosomiasis (HAT) epidemics raging across many parts of Africa. Resistance to existing drugs was emerging, and many programs aiming to contain the disease had ground to a halt, given previous success against HAT and the competing priorities associated with other medical crises ravaging the continent. A series of dedicated interventions and the introduction of innovative routes to develop drugs, involving Product Development Partnerships, has led to a dramatic turnaround in the fight against HAT caused by Trypanosoma brucei gambiense. The World Health Organization have been able to optimize the use of existing tools to monitor and intervene in the disease. A promising new oral medication for stage 1 HAT, pafuramidine maleate, ultimately failed due to unforeseen toxicity issues. However, the clinical trials for this compound demonstrated the possibility of conducting such trials in the resource-poor settings of rural Africa. The Drugs for Neglected Disease initiative (DNDi), founded in 2003, has developed the first all oral therapy for both stage 1 and stage 2 HAT in fexinidazole. DNDi has also brought forward another oral therapy, acoziborole, potentially capable of curing both stage 1 and stage 2 disease in a single dosing. In this review article, we describe the remarkable successes in combating HAT through the twenty first century, bringing the prospect of the elimination of this disease into sight.
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Project description:There is a growing need to develop novel processes to recover lead from end-of-life lead-acid batteries, due to increasing energy costs of pyrometallurgical lead recovery, the resulting CO2 emissions and the catastrophic health implications of lead exposure from lead-to-air emissions. To address these issues, we are developing an iono-metallurgical process, aiming to displace the pyrometallurgical process that has dominated lead production for millennia. The proposed process involves the dissolution of Pb salts into the deep eutectic solvent (DES) Ethaline 200, a liquid formed when a 1 : 2 molar ratio of choline chloride and ethylene glycol are mixed together. Once dissolved, the Pb can be recovered through electrodeposition and the liquid can then be recycled for further Pb recycling. Firstly, DESs are being used to dissolve the lead compounds (PbCO3, PbO, PbO2 and PbSO4) involved and their solubilities measured by inductively coupled plasma optical emission spectrometry (ICP-OES). The resulting Pb2+ species are then reduced and electrodeposited as elemental lead at the cathode of an electrochemical cell; cyclic voltammetry and chronoamperometry are being used to determine the electrodeposition behaviour and mechanism. The electrodeposited films were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). We discuss the implications and opportunities of such processes.
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Project description:BackgroundSome carcinogenic viruses are known to be transmissible by blood transfusion. Intensive viral screening of transfused blood now exists in most countries. In the UK, high-sensitivity nucleic acid amplification tests for hepatitis C virus were introduced in 1999 and it was thought that this would reduce, and possibly eliminate, transfusion-related liver cancer. We aimed to investigate cancer risk in recipients of blood transfusion in 2000 or after.MethodsA total of 1.3 million UK women recruited in 1998 on average were followed for hospital records of blood transfusion and for cancer registrations. After excluding women with cancer or precancerous conditions before or at the time of transfusion, Cox regression yielded adjusted relative risks of 11 site-specific cancers for women with compared to without prior blood transfusion.ResultsDuring follow up, 11 274 (0.9%) women had a first recorded transfusion in 2000 or after, and 1648 (14.6%) of them were subsequently diagnosed with cancer, a mean 6.8 years after the transfusion. In the first 5 years after transfusion there were significant excesses for most site-specific cancers examined, presumably because some had preclinical cancer. However, 5 or more years (mean 8 years) after blood transfusion, there were significant excess risks only for liver cancer (adjusted relative risk = 2.63, 95%CI 1.45-4.78) and for non-Hodgkin lymphoma (adjusted relative risk = 1.74, 1.21-2.51). When analyses were restricted to those undergoing hip or knee replacement surgery, the commonest procedure associated with transfusion, these relative risks were not materially altered.ConclusionsIn a large cohort of UK women, transfusions in the 21st century were associated with long-term increased risks of liver cancer and non-Hodgkin lymphoma. Some of these malignancies may have been caused by carcinogenic agents that are not currently screened for in transfused blood.
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Project description:Sandy coastlines adjacent to tidal inlets are highly dynamic and widespread landforms, where large changes are expected due to climatic and anthropogenic influences. To adequately assess these important changes, both oceanic (e.g., sea-level rise) and terrestrial (e.g., fluvial sediment supply) processes that govern the local sediment budget must be considered. Here, we present novel projections of shoreline change adjacent to 41 tidal inlets around the world, using a probabilistic, reduced complexity, system-based model that considers catchment-estuary-coastal systems in a holistic way. Under the RCP 8.5 scenario, retreat dominates (90% of cases) over the twenty-first century, with projections exceeding 100 m of retreat in two-thirds of cases. However, the remaining systems are projected to accrete under the same scenario, reflecting fluvial influence. This diverse range of response compared to earlier methods implies that erosion hazards at inlet-interrupted coasts have been inadequately characterised to date. The methods used here need to be applied widely to support evidence-based coastal adaptation.
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