University of Leeds

About: University of Leeds is a education organization based out in Leeds, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 43481 authors who have published 101856 publications receiving 3672065 citations. The organization is also known as: Leeds University.

p53 polymorphisms: cancer implications

Abstract: The normal functioning of p53 is a potent barrier to cancer. Tumour-associated mutations in TP53, typically single nucleotide substitutions in the coding sequence, are a hallmark of most human cancers and cause dramatic defects in p53 function. By contrast, only a small fraction, if any, of the >200 naturally occurring sequence variations (single nucleotide polymorphisms, SNPs) of TP53 in human populations are expected to cause measurable perturbation of p53 function. Polymorphisms in the TP53 locus that might have cancer-related phenotypical manifestations are the subject of this Review. Polymorphic variants of other genes in the p53 pathway, such as MDM2, which might have biological consequences either individually or in combination with p53 variants are also discussed.

Animal models of anxiety: an ethological perspective

Abstract: In the field of anxiety research, animal models are used as screening tools in the search for compounds with therapeutic potential and as simulations for research on mechanism underlying emotional behaviour. However, a solely pharmacological approach to the validation of such tests has resulted in distinct problems with their applicability to systems other than those involving the benzodiazepine/GABAA receptor complex. In this context, recent developments in our understanding of mammalian defensive behaviour have not only prompted the development of new models but also attempts to refine existing ones. The present review focuses on the application of ethological techniques to one of the most widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh approach to an established test has revealed a hitherto unrecognized multidimensionality to plus-maze behaviour and, as it yields comprehensive behavioural profiles, has many advantages over conventional methodology. This assertion is supported by reference to recent work on the effects of diverse manipulations including psychosocial stress, benzodiazepines, GABA receptor ligands, neurosteroids, 5-HT1A receptor ligands, and panicolytic/panicogenic agents. On the basis of this review, it is suggested that other models of anxiety may well benefit from greater attention to behavioural detail.

Psychological therapies for the management of chronic and recurrent pain in children and adolescents

Abstract: Background This is an update of the original Cochrane review first published in Issue 1, 2003, and previously updated in 2009 and 2012. Chronic pain affects many children, who report severe pain, disability, and distressed mood. Psychological therapies are emerging as effective interventions to treat children with chronic or recurrent pain. This update focuses specifically on psychological therapies delivered face-to-face, adds new randomised controlled trials (RCTs), and additional data from previously included trials. Objectives There were three objectives to this review. First, to determine the effectiveness on clinical outcomes of pain severity, disability, depression, and anxiety of psychological therapy delivered face-to-face for chronic and recurrent pain in children and adolescents compared with active treatment, waiting-list, or standard medical care. Second, to evaluate the impact of psychological therapies on depression and anxiety, which were previously combined as 'mood'. Third, we assessed the risk of bias of the included studies and the quality of outcomes using the GRADE criteria. Search methods Searches were undertaken of CENTRAL, MEDLINE, EMBASE, and PsycINFO. We searched for further RCTs in the references of all identified studies, meta-analyses, and reviews. Trial registry databases were also searched. The date of most recent search was January 2014. Selection criteria RCTs with at least 10 participants in each arm post-treatment comparing psychological therapies with active treatment, standard medical care, or waiting-list control for children or adolescents with episodic, recurrent or persistent pain were eligible for inclusion. Only trials conducted in person (face-to-face) were considered. Studies that delivered treatment remotely were excluded from this update. Data collection and analysis All included studies were analysed and the quality of outcomes were assessed. All treatments were combined into one class, psychological treatments. Pain conditions were split into headache and non-headache. Both conditions were assessed on four outcomes: pain, disability, depression, and anxiety. Data were extracted at two time points; post-treatment (immediately or the earliest data available following end of treatment) and at follow-up (between three and 12 months post-treatment). Main results Seven papers were identified in the updated search. Of these papers, five presented new trials and two presented follow-up data for previously included trials. Five studies that were previously included in this review were excluded as therapy was delivered remotely. The review thus included a total of 37 studies. The total number of participants completing treatments was 2111. Twenty studies addressed treatments for headache (including migraine); nine for abdominal pain; two for mixed pain conditions including headache pain, two for fibromyalgia, two for recurrent abdominal pain or irritable bowel syndrome, and two for pain associated with sickle cell disease. Analyses revealed psychological therapies to be beneficial for children with chronic pain on seven outcomes. For headache pain, psychological therapies reduced pain post-treatment and at follow-up respectively (risk ratio (RR) 2.47, 95% confidence interval (CI) 1.97 to 3.09, z = 7.87, p 0.05). At follow-up, only one study was eligible, therefore no analysis was possible and no conclusions can be drawn. Analyses revealed a small beneficial effect for anxiety post-treatment (SMD -0.33, 95% CI -0.61 to -0.04, z = 2.25, p 0.05). Analyses revealed two beneficial effects of psychological treatment for children with non-headache pain. Pain was found to improve post-treatment (SMD -0.57, 95% CI -0.86 to -0.27, z = 3.74, p 0.05). Psychological therapies also had a beneficial effect for disability post-treatment (SMD -0.45, 95% CI -0.71 to -0.19, z = 3.40, p 0.05). No effect was found for depression or anxiety post-treatment (SMD -0.07, 95% CI -0.30 to 0.17, z = 0.54, p > 0.05; SMD -0.15, 95% CI -0.36 to 0.07, z = 1.33, p > 0.05) or at follow-up (SMD 0.06, 95% CI -0.16 to 0.28, z = 0.53, p > 0.05; SMD 0.05, 95% CI -0.24 to 0.33, z = 0.32, p > 0.05). Authors' conclusions Psychological treatments delivered face-to-face are effective in reducing pain intensity and disability for children and adolescents (<18 years) with headache, and therapeutic gains appear to be maintained, although this should be treated with caution for the disability outcome as only two studies could be included in the follow-up analysis. Psychological therapies are also beneficial at reducing anxiety post-treatment for headache. For non-headache conditions, psychological treatments were found to be beneficial for pain and disability post-treatment but these effects were not maintained at follow-up. There is limited evidence available to estimate the effects of psychological therapies on depression and anxiety for children and adolescents with headache and non-headache pain. The conclusions of this update replicate and add to those of the previous review which found that psychological therapies were effective in reducing pain intensity for children with headache and non-headache pain conditions, and these effects were maintained at follow-up for children with headache conditions.