3,570 research outputs found

    Is the national living wage improving living standards?

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    Although the national living wage has led to a significant pay boost for Britain's least well-off workers, significant challenges remain, writes George Bangham. He argues that the quality of work is still an issue and that the government must find ways to work with businesses so as to ensure people don't keep getting trapped at the very lowest end of the pay spectrum

    Making the 'genetic counsellor' in the UK, 1980-1995.

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    The professional identity of the 'genetic counsellor' first took shape in the UK in the early 1990s, when the University of Manchester established the country's first masters-level training course. Postwar, genetic counselling had been carried out by (male) clinical geneticists, who, alongside their research, clinical and field-building activities, met patients and families to discuss inherited conditions and risk estimates, and who sometimes advised parents whether to attempt or continue pregnancies. By contrast, the new cohort of students in Manchester in the 1990s were not medically trained, were mostly women, and were schooled in the psychological and social consequences of genetic testing and diagnosis, as well as methods for the care, support and emotional management of patients and families. This was a significant change both in the practices of 'genetic counselling' and who was expected to practise it. Focusing on a small section of this history, between 1980 and 1995, this paper describes some of the historical threads that contributed to this change. It charts the early work of genetic nurses and social workers, who in the 1980s carved out distinctive roles within National Health Service genetics centres. It describes the separate, specialist provision developed by sickle cell and thalassaemia counsellors, who developed new approaches in dialogue with racialised and underserved patient communities. It examines growing interest in the late 1980s and early 1990s in the tacit social and cultural conditions of genetic counselling encounters, and how this cohered with attention from disability scholars, psychologists and social scientists. By describing these historical contributions, this paper explores how the intersecting gendered, racialised and disciplinary politics of clinical genetics shaped the new professional role of the 'genetic counsellor'

    New Meanings in the Archive: Privacy, Technological Change and the Status of Sources

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    This essay reflects on how technological changes in biomedicine can affect what archival sources are available for historical research. Historians and anthropologists have examined the ways in which old biomedical samples can be made to serve novel scientific purposes, such as when decades‐old frozen tissue specimens are analyzed using new genomic techniques. Those uses are also affected by shifting ethical regimes, which affect who can do what with old samples, or whether anything can be done with them at all. Archival collections are subject to similar dynamics, as institutional change and shifts in ethical guidelines and privacy laws affect which sources can be accessed and which are closed. I witnessed just such a change during my research into human genetics using archives in the Wellcome Collection. A few years into my project, those archives had their privacy conditions reassessed, and I saw how some sources previously seen as neutral were now understood to contain personal sensitive information. This paper describes the conditions of this shift—including the effects of technological change, new ethical considerations, and changing laws around privacy. I reflect on how these affected my understanding of the history of human genetics, and how I and others might narrate it

    A Study of the Durability of Concrete in Sea Water

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    The durability of concrete in sea water has been a very widely debated question from the time that disintegration of concrete in sea water first became evident. Numerous investigations and reports have been made of isolated structures in various parts of the country and from these, hasty conclusions have been reached which engineers, situated where different conditions prevail, have not been warranted in accepting. A few engineers have made investigations of a much wider scope and consequently their conclusions should be given greater weight

    HTLV-1: Regulating the Balance Between Proviral Latency and Reactivation

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    HTLV-1 plus-strand transcription begins with the production of doubly-spliced tax/rex transcripts, the levels of which are usually undetectable in freshly isolated peripheral blood mononuclear cells (PBMCs) from HTLV-1-infected individuals. However, the presence of a sustained chronically active cytotoxic T-cell response to HTLV-1 antigens in virtually all HTLV-1-infected individuals, regardless of their proviral load, argues against complete latency of the virus in vivo. There is an immediate burst of plus-strand transcription when blood from infected individuals is cultured ex vivo. How is the HTLV-1 plus strand silenced in PBMCs? Is it silenced in other anatomical compartments within the host? What reactivates the latent provirus in fresh PBMCs? While plus-strand transcription of the provirus appears to be intermittent, the minus-strand hbz transcripts are present in a majority of cells, albeit at low levels. What regulates the difference between the 5′- and 3′-LTR promoter activities and thereby the tax-hbz interplay? Finally, T lymphocytes are a migratory population of cells that encounter variable environments in different compartments of the body. Could these micro-environment changes influence the reactivation kinetics of the provirus? In this review we discuss the questions raised above, focusing on the early events leading to HTLV-1 reactivation from latency, and suggest future research directions

    Is there a role for HTLV-1-specific CTL in adult T-cell Leukemia/Lymphoma?

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    ATLL is an aggressive malignancy of T cells that affects about 5% of individuals infected with HTLV-1. The precise mechanism of oncogenesis is not known, but there is evidence that two regulatory viral proteins, Tax and HBZ, are involved. A high set point proviral load is associated with development of ATLL or a chronic inflammatory condition, HAM/TSP. Several lines of evidence, including HLA class 1 association studies and in vitro killing assays, indicate that cytotoxic T lymphocytes are instrumental in determining this proviral load set point. Prior studies have focused chiefly on the CTL response to the immunodominant Tax protein: efficient lysis of Tax-expressing cells inversely correlates with proviral load in nonmalignant infection. However, a recent study showed that strong binding of peptides from HBZ, but not Tax, to HLA class 1 molecules was associated with a low proviral load and a reduced risk of developing HAM/TSP, indicating an important role for HBZ-specific CTL in determining infection outcome. In comparison with nonmalignant infection, HTLV-1-specific CTLs in ATLL patients are reduced in frequency and functionally deficient. Here we discuss the nature of protective CTL responses in nonmalignant HTLV-1 infection and explore the potential of CTLs to protect against ATLL

    Integration Site and Clonal Expansion in Human Chronic Retroviral Infection and Gene Therapy

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    Retroviral vectors have been successfully used therapeutically to restore expression of genes in a range of single-gene diseases, including several primary immunodeficiency disorders. Although clinical trials have shown remarkable results, there have also been a number of severe adverse events involving malignant outgrowth of a transformed clonal population. This clonal expansion is influenced by the integration site profile of the viral integrase, the transgene expressed, and the effect of the viral promoters on the neighbouring host genome. Infection with the pathogenic human retrovirus HTLV-1 also causes clonal expansion of cells containing an integrated HTLV-1 provirus. Although the majority of HTLV-1-infected people remain asymptomatic, up to 5% develop an aggressive T cell malignancy. In this review we discuss recent findings on the role of the genomic integration site in determining the clonality and the potential for malignant transformation of cells carrying integrated HTLV-1 or gene therapy vectors, and how these results have contributed to the understanding of HTLV-1 pathogenesis and to improvements in gene therapy vector safety
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