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Background Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.

Methods We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R16...

Introduction: We have aimed to describe haemodynamic changes when haemodialysis is instituted in the critically ill. 3 hypotheses are tested: 1)The initial session is associated with cardiovascular instability, 2)The initial session is associated with more cardiovascular instability compared to subsequent sessions, and 3)Looking at unstable sessions alone, there will be a greater proportion of potentially harmful changes in the initial sessions compared to subsequent ones. Methods: Data was collected for 209 patients, identifying 1605 dialysis sessions. Analysis was performed on hourly records, classifying sessions as stable/unstable by a cutoff of >+/-20% change in baseline physiology (HR/MAP). Data from 3 hours prior, and 4 hours after dialysis was included, and average and minimum values derived. 3 time compa...

Background: Heart rate (HR) is an emerging risk factor in coronary artery disease (CAD). However, there is little contemporary data regarding HR and the use of HR-lowering medications, particularly beta-blockers, among patients with stable CAD in routine clinical practice. The goal of the present analysis was to describe HR in such patients, overall and in relation to beta-blocker use, and to describe the determinants of HR.

Methods and Findings: CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis of >50%, or chest pain associated with proven myocardial ischemia. A total of 33,438 patients from 45 countries in Europe, the Americas, Africa, Middle E...

Objective - This research examined cognitions and behaviour that are typically associated with social phobia, in people with paranoia. Content specificity of thoughts and beliefs, particular metacognitive processes, and behaviour were assessed in people with social phobia and persecutory delusions. The aim was to determine the extent to which socially anxious cognitions and behaviour are experienced by people with persecutory delusions, in order to further our understanding of paranoia and to consider the implications for therapeutic work. Design - We used a cross-sectional between-subjects design to compare participants with social phobia, persecutory delusions (without social phobia), a clinical control group with panic disorder, and a non-clinical control group. Method - Ten to 15 people were recruited to each of the four groups, wi...
Objective and design: to examine whether inhibitors of the MAPK pathways will influence the response of bovine chondrocytes cultured in agarose constructs to IL-1beta and dynamic compression. Methods: dose-response studies were conducted under IL-1beta conditions with either SB203580, SP600125, PDTC or curcumin. In separate experiments, constructs were treated with IL-1beta and an appropriate concentration of inhibitor and subjected to 15% dynamic compression. Nitrite and PGE2 release, 35SO4 and [3H]-thymidine incorporation were subsequently measured using biochemical assays. Results: all inhibitors reduced the IL-1beta induced nitrite and PGE2 release in a dose-dependent manner. The inhibition of [3H]-thymidine incorporation by IL-1beta was partially reversed with SB203580, SP600125 or curcumin, but not PDTC. In most cases, the inhi...
Summary Partial adherence in osteoporosis increases the risk for fragility fracture and has considerable impact on cost-effectiveness. This review highlights a number of avenues for further research, such as improved definition of thresholds of compliance and persistence, as well as gap length, offset times, and fraction of benefit. Introduction A number of economic models have been developed to evaluate osteoporosis therapies and support decisions regarding efficient allocation of health care resources. Adherence to treatment is seldom incorporated in these models, which may reduce their validity for decision-making since adherence is poor in real-world clinical practice. Methods An ad hoc working group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review key issues concerning the ...
Objective. To determine the prevalence and natural history of foot-related disability in patients with rheumatoid arthritis (RA). A secondary aim was to identify explanatory variables, including forefoot bursae, that are either associated with or predictive of disabling foot complications in patients with RA. Methods. A longitudinal prospective cohort study recruited patients with RA from a rheumatology outpatient clinic. Data were collected at baseline (n � 149) and 1-year (n � 120) and 3-year followup (n � 60). Patient-reported disabling foot complications were evaluated using the subscales of the Foot Impairment Score (FIS): foot impairment/footwear restriction (FISIF) and activity limitation/participation restriction (FISAP). Explanatory variables investigated included ultrasound-detectable forefoot pathology and markers of disease...
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