882 research outputs found

    Theorising Disability: Beyond Common Sense

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    This article seeks to introduce the topic of disability to political theory via a discussion of some of the literature produced by disability theorists. The author argues that these more radical approaches conceptualise disability in ways that conflict with ‘common-sense’ notions of disability that tend to underpin political theoretical considerations of the topic. Furthermore, the author suggests that these more radical conceptualisations have profound implications for current debates on social justice, equality and citizenship that highlight the extent to which these notions are also currently underpinned by ‘common-sense’ notions of ‘normality’

    Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2

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    Deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in humans leads to the syndrome of apparent mineralocorticoid excess (SAME), in which cortisol illicitly occupies mineralocorticoid receptors, causing sodium retention, hypokalemia, and hypertension. However, the disorder is usually incompletely corrected by suppression of cortisol, suggesting additional and irreversible changes, perhaps in the kidney. To examine this further, we produced mice with targeted disruption of the 11β-HSD2 gene. Homozygous mutant mice (11β-HSD2(–/–)) appear normal at birth, but ∼50% show motor weakness and die within 48 hours. Both male and female survivors are fertile but exhibit hypokalemia, hypotonic polyuria, and apparent mineralocorticoid activity of corticosterone. Young adult 11β-HSD2(–/–) mice are markedly hypertensive, with a mean arterial blood pressure of 146 ± 2 mmHg, compared with 121 ± 2 mmHg in wild-type controls and 114 ± 4 mmHg in heterozygotes. The epithelium of the distal tubule of the nephron shows striking hypertrophy and hyperplasia. These histological changes do not readily reverse with mineralocorticoid receptor antagonism in adulthood. Thus, 11β-HSD2(–/–) mice demonstrate the major features of SAME, providing a unique rodent model to study the molecular mechanisms of kidney resetting leading to hypertension. J. Clin. Invest. 103:683–689 (1999

    Ice surface changes during recent glacial cycles along the Jutulstraumen and Penck Trough ice streams in western Dronning Maud Land, East Antarctica

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    Reconstructing past ice-sheet surface changes is key to testing and improving ice-sheet models. Data constraining the past behaviour of the East Antarctic Ice Sheet are sparse, limiting our understanding of its response to past, present and future climate change. Here, we report the first cosmogenic multi-nuclide (10Be, 26Al, 36Cl) data from bedrock and erratics on nunataks along the Jutulstraumen and Penck Trough ice streams in western Dronning Maud Land, East Antarctica. Spanning elevations between 741 and 2394 m above sea level, the samples have apparent exposure ages between 2 ka and 5 Ma. The highest-elevation bedrock sample indicates (near-) continuous minimum exposure since the Pliocene, with a low apparent erosion rate of 0.15 ± 0.03 m Ma−1, which is similar to results from eastern Dronning Maud Land. In contrast to studies in eastern Dronning Maud Land, however, our data show clear indications of a thicker-than-present ice sheet within the last glacial cycle, with a thinning of ∼35–120 m during the Holocene (∼2–11 ka). Difficulties in separating suitable amounts of quartz from the often quartz-poor rock-types in the area, and cosmogenic nuclides inherited from exposure prior to the last deglaciation, prevented robust thinning estimates from elevational profiles. Nevertheless, the results clearly demonstrate ice-surface fluctuations of several hundred meters between the current grounding line and the edge of the polar plateau for the last glacial cycle, a constraint that should be considered in future ice-sheet model simulations

    Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases

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    BACKGROUND: In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. METHODS: To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in ≥2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. RESULTS: In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing; while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. CONCLUSIONS: The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group

    Natural law, non-voluntary euthanasia, and public policy

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    © 2019 by Emerald Publishing Limited. Natural Law philosophy asserts that there are universally binding and universally evident principles that can be determined to guide the actions of persons. Moreover, many of these principles have been enshrined in both statute and common law, thus ensuring their saliency for staff and institutions charged with palliative care. The authors examine the often emotive and politicized matter of (non-voluntary) euthanasia – acts or omissions made with the intent of causing or hastening death – with reference to Natural Law philosophy. This leads us to propose a number of important public policy remedies to ensure dignity in dying for the patient, and their associates
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