2,622 research outputs found

    An exploration into the client at the heart of therapy : a qualitative perspective

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    Over 50 years ago Eysenck challenged the existing base of research into psychotherapy. Since that time, a large number of investigations have been conducted to verify the efficacy of therapy. Recently however, an increasing number of studies have cast new doubts on this research base. Instead of therapy being a function of the therapist, it is now becoming ever more apparent that the client plays a prime role in the therapeutic process. The qualitative studies presented in this paper provide some examples of research that demonstrates that clients are actively involved in their therapy, even making counselling work despite their counsellor. These studies suggest that clients may not experience therapy as beneficially as traditional outcome studies indicate. This raises a new challenge to researchers to more fully explore the client's experience of therapy, a challenge to which qualitative methods of inquiry would appear well suited

    Identification of decomposition volatile organic compounds from surface deposited and submerged porcine remains

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    Cadaver dogs are routinely used internationally by police and civilian search organisations to locate human remains on land and in water, yet little is currently known about the volatile organic compounds (VOCs) that are released by a cadaver underwater; how this compares to those given off by a cadaver deposited on land; and ultimately, how this affects the detection of drowned victims by dogs. The aim of this study was to identify the VOCs released by whole porcine (Sus scrofa domesticus) cadavers deposited on the surface and submerged in water using solid phase microextraction gas chromatography mass spectrometry (SPME GC–MS) to ascertain if there are notable differences in decomposition odour depending on the deposition location. For the first time in the UK, the volatile organic compounds (VOCs) from the headspace of decomposing porcine cadavers deposited in both terrestrial and water environments have been detected and identified using SPME-GCMS, including thirteen new VOCs not previously detected from porcine cadavers. Distinct differences were found between the VOCs emitted by porcine cadavers in terrestrial and water environments. In total, seventy-four VOCs were identified from a variety of different chemical classes; carboxylic acids, alcohols, aromatics, aldehydes, ketones, hydrocarbons, esters, ethers, nitrogen compounds and sulphur compounds. Only forty-one VOCs were detected in the headspace of the submerged pigs with seventy detected in the headspace of the surface-deposited pigs. These deposition-dependent differences have important implications for the training of cadaver dogs in the UK. If dog training does not account for these depositional differences, there is potential for human remains to be missed. Whilst the specific odours that elicit a trained response from cadaver dogs remain unknown, this research means that recommendations can be made for the training of cadaver dogs to incorporate different depositions, to account for odour differences and mitigate the possibility of missed human remains operationally

    Metformin Treatment Attenuates Brain Inflammation and Rescues PACAP/VIP Neuropeptide Alterations in Mice Fed a High-Fat Diet.

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    High-fat diet (HFD)-induced comorbid cognitive and behavioural impairments are thought to be the result of persistent low-grade neuroinflammation. Metformin, a first-line medication for the treatment of type-2 diabetes, seems to ameliorate these comorbidities, but the underlying mechanism(s) are not clear. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective peptides endowed with anti-inflammatory properties. Alterations to the PACAP/VIP system could be pivotal during the development of HFD-induced neuroinflammation. To unveil the pathogenic mechanisms underlying HFD-induced neuroinflammation and assess metformin's therapeutic activities, (1) we determined if HFD-induced proinflammatory activity was present in vulnerable brain regions associated with the development of comorbid behaviors, (2) investigated if the PACAP/VIP system is altered by HFD, and (3) assessed if metformin rescues such diet-induced neurochemical alterations. C57BL/6J male mice were divided into two groups to receive either standard chow (SC) or HFD for 16 weeks. A further HFD group received metformin (HFD + M) (300 mg/kg BW daily for 5 weeks) via oral gavage. Body weight, fasting glucose, and insulin levels were measured. After 16 weeks, the proinflammatory profile, glial activation markers, and changes within the PI3K/AKT intracellular pathway and the PACAP/VIP system were evaluated by real-time qPCR and/or Western blot in the hypothalamus, hippocampus, prefrontal cortex, and amygdala. Our data showed that HFD causes widespread low-grade neuroinflammation and gliosis, with regional-specific differences across brain regions. HFD also diminished phospho-AKT(Ser473) expression and caused significant disruptions to the PACAP/VIP system. Treatment with metformin attenuated these neuroinflammatory signatures and reversed PI3K/AKT and PACAP/VIP alterations caused by HFD. Altogether, our findings demonstrate that metformin treatment rescues HFD-induced neuroinflammation in vulnerable brain regions, most likely by a mechanism involving the reinstatement of PACAP/VIP system homeostasis. Data also suggests that the PI3K/AKT pathway, at least in part, mediates some of metformin's beneficial effects

    A TPX2 Proteomimetic Has Enhanced Affinity for Aurora-A Due to Hydrocarbon Stapling of a Helix

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    Inhibition of protein kinases using ATP-competitive compounds is an important strategy in drug discovery. In contrast, the allosteric regulation of kinases through the disruption of protein-protein interactions has not been widely adopted, despite the potential for selective targeting. Aurora-A kinase regulates mitotic entry and mitotic spindle assembly and is a promising target for anticancer therapy. The microtubule-associated protein TPX2 activates Aurora-A through binding to two sites. Aurora-A recognition is mediated by two motifs within the first 43 residues of TPX2, connected by a flexible linker. To characterize the contributions of these three structural elements, we prepared a series of TPX2 proteomimetics and investigated their binding affinity for Aurora-A using isothermal titration calorimetry. A novel stapled TPX2 peptide was developed that has improved binding affinity for Aurora-A and mimics the function of TPX2 in activating Aurora-A's autophosphorylation. We conclude that the helical region of TPX2 folds upon binding Aurora-A, and that stabilization of this helix does not compromise Aurora-A activation. This study demonstrates that the preparation of these proteomimetics using modern synthesis methods is feasible and their biochemical evaluation demonstrates the power of proteomimetics as tool compounds for investigating PPIs involving intrinsically disordered regions of proteins

    Association of specific chromosome alterations with tumour phenotype in posterior uveal melanoma

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    Posterior uveal melanomas have recurrent alterations of chromosomes 1, 3, 6 and 8. In particular, changes of chromosomes 3 and 8 occur in association, appear to characterize those tumours with a ciliary body component, and have been shown to be of prognostic significance. The relevance of other chromosome alterations is less certain. We have performed cytogenetic analysis on 42 previously untreated primary posterior uveal melanomas. Of interest was the observation that as tumour size increased the involvement of specific chromosome changes, and the amount of chromosome abnormalities likewise increased. Loss, or partial deletions, of the short arm of chromosome 1 were found to associate with larger ciliary body melanomas; typically, loss of the short arm resulted from unbalanced translocations, the partners of which varied. Trisomy of chromosome 21 occurred more often in ciliary body melanomas, whilst rearrangements of chromosomes 6 and 11 were primarily related to choroidal melanomas. Our results imply that alterations of chromosome 1 are important in the progression of some uveal melanomas, and that other chromosome abnormalities, besides those of chromosomes 3 and 8, are associated with ocular tumours of particular locations. © 2000 Cancer Research Campaig

    ОПТИМАЛЬНЕ ЗА ШВИДКОДІЄЮ КЕРУВАННЯ КОМПЕНСАЦІЙНИМИ СИМЕТРУВАЛЬНИМИ ПРИСТРОЯМИ

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    Обґрунтований алгоритм оптимального за швидкодією керування компенсаційними симетрувальними пристроями, який рекомендується для застосування за умови істотного зниження напруги у вузлі приєднання споживача.Обоснован алгоритм оптимального по быстродействию управления компенсационными симметрирую- щими устройствами, который рекомендуется для применения при условии существенного снижения на- пряжения в узле присоединения потребител

    On Spectral Triples in Quantum Gravity II

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    A semifinite spectral triple for an algebra canonically associated to canonical quantum gravity is constructed. The algebra is generated by based loops in a triangulation and its barycentric subdivisions. The underlying space can be seen as a gauge fixing of the unconstrained state space of Loop Quantum Gravity. This paper is the second of two papers on the subject.Comment: 43 pages, 1 figur

    New Lower Bounds on the Self-Avoiding-Walk Connective Constant

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    We give an elementary new method for obtaining rigorous lower bounds on the connective constant for self-avoiding walks on the hypercubic lattice ZdZ^d. The method is based on loop erasure and restoration, and does not require exact enumeration data. Our bounds are best for high dd, and in fact agree with the first four terms of the 1/d1/d expansion for the connective constant. The bounds are the best to date for dimensions d3d \geq 3, but do not produce good results in two dimensions. For d=3,4,5,6d=3,4,5,6, respectively, our lower bound is within 2.4\%, 0.43\%, 0.12\%, 0.044\% of the value estimated by series extrapolation.Comment: 35 pages, 388480 bytes Postscript, NYU-TH-93/02/0

    Where is the community dimension in the updated common rule?

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    The Problem: Changes to the Federal Policy for the Protection of Human Subjects (the Common Rule) as presented in the Notice of Proposed Rulemaking (NPRM) are both logical and necessary. However, the proposed changes continue to focus entirely on the individual and fail to take into account the rapidly-emerging types of research that involve patients and communities directly in the research process. Purpose of Article: We propose several changes and amendments that address the interests of communities and underscore the principle of justice, especially social justice. Key Points: Our recommendations seek to revise human sub-jects’ protections that currently overemphasize individualism and autonomy to reflect a collectivist ethos that would extend protections to communities engaged in medical research. Conclusion: We believe this is necessary to effectively and efficiently conduct the types of research that will ultimately rectify health inequities that continue to exist in many communities, but particularly communities of color
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