567 research outputs found

    Faecal haemoglobin can define risk of colorectal neoplasia at surveillance colonoscopy in patients at increased risk of colorectal cancer.

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    Background: Quantitative faecal immunochemical tests measure faecal haemoglobin concentration (f-Hb), which increases in the presence of colorectal neoplasia.Objective: We examined the diagnostic accuracy of faecal immunochemical test (FIT)in patients at increased risk of colorectal cancer (CRC) attending for surveillance colonoscopy as per national guidelines.Methods: A total of 1103 consecutive patients were prospectively invited to complete a FIT before their scheduled colonoscopy in two university hospitals in 2014– 2016. F-Hb was analysed on an OC-Sensor io automated analyser (Eiken Chemical Co., Ltd, Tokyo, Japan) with a limit of detection of 2 µg Hb/g faeces. The diagnostic accuracy of f-Hb for CRC and higher-risk adenoma was examined.Results: A total of 643 patients returned a faecal test. After excluding 4 patients with known inflammatory bowel disease, 639 (57.9%) remained in the study: age range: 25–90 years (median: 64 years, interquartile range (IQR): 55–71): 54.6% male. Of 593 patients who also completed colonoscopy, 41 (6.9%) had advanced neoplasia (4 CRC, 37 higher-risk adenoma). Of the 238 patients (40.1%) who had detectable f-Hb, 31 (13.0%) had advanced neoplasia (2 CRC, 29 higher-risk adenoma) compared with 10 (2.8%) in those with undetectable f-Hb (2 CRC, 8 higher-risk adenoma). Detectable f-Hb gave negative predictive values of 99.4% for CRC and 97.2% for CRC plus higher-risk adenoma.Conclusion: In patients at increased risk of CRC under colonoscopy surveillance, a test measuring faecal haemoglobin can provide an objective estimate of the risk of advanced neoplasia, and could enable tailored scheduling of colonoscopy.</p

    You Can't Get Through Szekeres Wormholes - or - Regularity, Topology and Causality in Quasi-Spherical Szekeres Models

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    The spherically symmetric dust model of Lemaitre-Tolman can describe wormholes, but the causal communication between the two asymptotic regions through the neck is even less than in the vacuum (Schwarzschild-Kruskal-Szekeres) case. We investigate the anisotropic generalisation of the wormhole topology in the Szekeres model. The function E(r, p, q) describes the deviation from spherical symmetry if \partial_r E \neq 0, but this requires the mass to be increasing with radius, \partial_r M > 0, i.e. non-zero density. We investigate the geometrical relations between the mass dipole and the locii of apparent horizon and of shell-crossings. We present the various conditions that ensure physically reasonable quasi-spherical models, including a regular origin, regular maxima and minima in the spatial sections, and the absence of shell-crossings. We show that physically reasonable values of \partial_r E \neq 0 cannot compensate for the effects of \partial_r M > 0 in any direction, so that communication through the neck is still worse than the vacuum. We also show that a handle topology cannot be created by identifying hypersufaces in the two asymptotic regions on either side of a wormhole, unless a surface layer is allowed at the junction. This impossibility includes the Schwarzschild-Kruskal-Szekeres case.Comment: zip file with LaTeX text + 6 figures (.eps & .ps). 47 pages. Second replacement corrects some minor errors and typos. (First replacement prints better on US letter size paper.

    Instability of black hole formation under small pressure perturbations

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    We investigate here the spectrum of gravitational collapse endstates when arbitrarily small perfect fluid pressures are introduced in the classic black hole formation scenario as described by Oppenheimer, Snyder and Datt (OSD) [1]. This extends a previous result on tangential pressures [2] to the more physically realistic scenario of perfect fluid collapse. The existence of classes of pressure perturbations is shown explicitly, which has the property that injecting any smallest pressure changes the final fate of the dynamical collapse from a black hole to a naked singularity. It is therefore seen that any smallest neighborhood of the OSD model, in the space of initial data, contains collapse evolutions that go to a naked singularity outcome. This gives an intriguing insight on the nature of naked singularity formation in gravitational collapse.Comment: 7 pages, 1 figure, several modifications to match published version on GR

    Gender, climate change, agriculture, and food security: a CCAFS training-of-trainers (TOT) manual to prepare South Asian rural women to adapt to climate change

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    This training-of-trainers manual is designed to train you to be able to deliver a capacity enhancement workshop (CEW) to rural women on climate change and gender. It has been designed by the CGIAR Research Program on Climate Change, Agriculture and Food Security (CCAFS) and is appropriate to the South Asian context

    Organisational barriers to the facilitation of overseas volunteering and training placements in the NHS

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    Background Undertaking a period of voluntary work or a professional placement overseas has long been a feature of medical training in the UK. There are now a number of high profile National Health Service (NHS) initiatives aimed at increasing access to such opportunities for staff at all levels. We present findings from a qualitative study involving a range of NHS staff and other stakeholders which explored barriers to participation in these activities. Methods A grounded theory methodology was drawn upon to conduct thematic based analysis. Our data included in-depth, semi-structured interviews with a range of returned volunteers, non-volunteers and other stakeholders (n=51) who were, or had been, employed by the NHS. Results There are significant barriers to placement and volunteering activity stemming from structural and organisational shortcomings within the NHS. Difficulties in filling clinical roles has a significant impact on the ability of staff to plan and undertake independent placements. There is currently no clearly defined pathway within the NHS by which the majority of grades can apply for, or organise, a period of overseas voluntary or professional placement activity. There were divergent views on the relevance and usefulness of overseas professional placements. Conclusions We argue that in the context of current UK policy initiatives aimed at facilitating overseas volunteer and professional placement activity, urgent attention needs to be given to the structural and organisational framework within which such initiatives will be required to work

    Stellar structure and compact objects before 1940: Towards relativistic astrophysics

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    Since the mid-1920s, different strands of research used stars as "physics laboratories" for investigating the nature of matter under extreme densities and pressures, impossible to realize on Earth. To trace this process this paper is following the evolution of the concept of a dense core in stars, which was important both for an understanding of stellar evolution and as a testing ground for the fast-evolving field of nuclear physics. In spite of the divide between physicists and astrophysicists, some key actors working in the cross-fertilized soil of overlapping but different scientific cultures formulated models and tentative theories that gradually evolved into more realistic and structured astrophysical objects. These investigations culminated in the first contact with general relativity in 1939, when J. Robert Oppenheimer and his students George Volkoff and Hartland Snyder systematically applied the theory to the dense core of a collapsing neutron star. This pioneering application of Einstein's theory to an astrophysical compact object can be regarded as a milestone in the path eventually leading to the emergence of relativistic astrophysics in the early 1960s.Comment: 83 pages, 4 figures, submitted to the European Physical Journal

    Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

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    Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins

    Sustainable Strategies for Teaching and Learning Online

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    Investigating students’ lived experiences of online learning can inform us on how best to teach them. In this paper, we harness the insights gained from pandemic teaching and learning to inform sustainable approaches. Theorized in relation to Ben-Eliyahu’s sustainable learning in education (SLE), this article offers insight into what tertiary teachers can do to support students with sustainable strategies, as well as how students can develop long-term learning strategies. We draw upon the research on the perspectives and experiences of New Zealand university students studying online in 2020 to inform SLE in online teaching and learning in the long term. The researchers collaborated with student associations to undertake a survey exploring the students’ experiences of online learning. There were 952 valid survey responses from all 8 New Zealand universities, complemented by 20 individual interviews and 9 focus groups involving 43 student participants, both on and offshore. Our findings indicate that students regard support, communication, and engagement as key areas where they experienced challenges or helpful practices, and where there are sustainable directions for future teaching and learning. We propose support that institutions can provide to both students and staff for sustainable strategies
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