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"Rees, David"
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Basic engineering plasticity : an introduction with engineering and manufacturing applications
Plasticity is concerned with understanding the behavior of metals and alloys when loaded beyond the elastic limit, whether as a result of being shaped or as they are employed for load bearing structures.Basic Engineering Plasticity delivers a comprehensive and accessible introduction to the theories of plasticity.
eBook
The association between silica exposure, silicosis and tuberculosis: a systematic review and meta-analysis
Background
While the association between occupational inhalation of silica dust and pulmonary tuberculosis has been known for over a century, there has never been a published systematic review, particularly of experience in the current era of less severe silicosis and treatable tuberculosis. We undertook a systematic review of the evidence for the association between (1) silicosis and pulmonary tuberculosis, and (2) silica exposure and pulmonary tuberculosis controlling for silicosis, and their respective exposure-response gradients.
Methods
We searched PUBMED and EMBASE, and selected studies according to a priori inclusion criteria. We extracted, summarised and pooled the results of published case-control and cohort studies of silica exposure and/or silicosis and incident active tuberculosis. Study quality was assessed on the Newcastle-Ottawa Scale. Where meta-analysis was possible, effect estimates were pooled using inverse-variance weighted random-effects models. Otherwise narrative and graphic synthesis was undertaken. Confidence regarding overall effect estimates was assessed using the GRADE schema.
Results
Nine studies met the inclusion criteria. Meta-analysis of eight studies of silicosis and tuberculosis yielded a pooled relative risk of 4.01 (95% confidence interval (CI) 2.88, 5.58). Exposure-response gradients were strong with a low silicosis severity threshold for increased risk. Our GRADE assessment was high confidence in a strong association. Meta-analysis of five studies of silica exposure controlling for or excluding silicosis yielded a pooled relative risk of 1.92 (95% CI 1.36, 2.73). Exposure-response gradients were observable in individual studies but not finely stratified enough to infer an exposure threshold. Our GRADE assessment was low confidence in the estimated effect owing to inconsistency and use of proxies for silica exposure.
Conclusions
The evidence is robust for a strongly elevated risk of tuberculosis with radiological silicosis, with a low disease severity threshold. The effect estimate is more uncertain for silica exposure without radiological silicosis. Research is needed, particularly cohort studies measuring silica exposure in different settings, to characterise the effect more accurately as well as the silica exposure threshold that could be used to prevent excess tuberculosis risk.
Journal Article
القوة البحرية السوفيتية : الأسطول المساند المقنع
يتناول كتاب (القوة البحرية السوفيتية : الأسطول المساند المقنع) والذي قام بتأليفه (دافيد ريز) في حوالي (50) صفحة من القطع المتوسط موضوع (القوات البحرية للاتحاد السوفيتي) ؛ الكتاب يتحدث عن القوات البحرية السوفيتية هي الذراع البحري للقوات المسلحة السوفيتية. امتد نطاق عملياتها ليشمل بحار المحيط الهادي والقارة القطبية الشمالية والمحيط الأطلنطي.
Book
Sickle Cell Disease
Sickle cell disease is caused by an alteration in a single DNA base, but its clinical manifestations are influenced by other genes and behavioral and environmental factors. Recent findings may indicate an acceleration in the discovery of interventions that alter the disease course.
Sickle cell disease is an increasing global health problem. Estimates suggest that every year approximately 300,000 infants are born with sickle cell anemia, which is defined as homozygosity for the sickle hemoglobin (HbS) gene (i.e., for a missense mutation [Glu6Val, rs334] in the β-globin gene [
HBB
]) and that this number could rise to 400,000 by 2050.
1
Although early diagnosis, penicillin prophylaxis, blood transfusion, transcranial Doppler imaging, hydroxyurea, and hematopoietic stem-cell transplantation can dramatically improve survival and quality of life for patients with sickle cell disease, our understanding of the role of genetic and nongenetic factors in explaining the . . .
Journal Article
Organic synthesis provides opportunities to transform drug discovery
Despite decades of ground-breaking research in academia, organic synthesis is still a rate-limiting factor in drug-discovery projects. Here we present some current challenges in synthetic organic chemistry from the perspective of the pharmaceutical industry and highlight problematic steps that, if overcome, would find extensive application in the discovery of transformational medicines. Significant synthesis challenges arise from the fact that drug molecules typically contain amines and N-heterocycles, as well as unprotected polar groups. There is also a need for new reactions that enable non-traditional disconnections, more C–H bond activation and late-stage functionalization, as well as stereoselectively substituted aliphatic heterocyclic ring synthesis, C–X or C–C bond formation. We also emphasize that syntheses compatible with biomacromolecules will find increasing use, while new technologies such as machine-assisted approaches and artificial intelligence for synthesis planning have the potential to dramatically accelerate the drug-discovery process. We believe that increasing collaboration between academic and industrial chemists is crucial to address the challenges outlined here.
Journal Article
Sickle-cell disease
Sickle-cell disease is one of the most common severe monogenic disorders in the world. Haemoglobin polymerisation, leading to erythrocyte rigidity and vaso-occlusion, is central to the pathophysiology of this disease, although the importance of chronic anaemia, haemolysis, and vasculopathy has been established. Clinical management is basic and few treatments have a robust evidence base. One of the main problems of sickle-cell disease in children is the development of cerebrovascular disease and cognitive impairment, and the role of blood transfusion and hydroxycarbamide for prevention of these complications is starting to be understood. Recurrent episodes of vaso-occlusion and inflammation result in progressive damage to most organs, including the brain, kidneys, lungs, bones, and cardiovascular system, which becomes apparent with increasing age. Most people with sickle-cell disease live in Africa, where little is known about this disease; however, we do know that the disorder follows a more severe clinical course in Africa than for the rest of the world and that infectious diseases have a role in causing this increased severity of sickle-cell disease. More work is needed to develop effective treatments that specifically target pathophysiological changes and clinical complications of sickle-cell disease.
Journal Article
