University of Aberdeen

About: University of Aberdeen is a education organization based out in Aberdeen, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 21174 authors who have published 49962 publications receiving 2105479 citations. The organization is also known as: Aberdeen University.

Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia.

Abstract: Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurines, including 6-mercaptopurine and 6-thioguanine. TPMT activity exhibits genetic polymorphism, with about 1/300 inheriting TPMT deficiency as an autosomal recessive trait. If treated with standard doses of thiopurines, TPMT-deficient patients accumulate excessive thioguanine nucleotides in hematopoietic tissues, leading to severe hematological toxicity that can be fatal. However, TPMT-deficient patients can be successfully treated with a 10- to 15-fold lower dosage of these medications. The molecular basis for altered TPMT activity has been defined, with rapid and inexpensive assays available for the three signature mutations which account for the majority of mutant alleles. TPMT genotype correlates well with in vivo enzyme activity within erythrocytes and leukemic blast cells and is clearly associated with risk of toxicity. The impact of 6-mercaptopurine dose intensity is also being clarified as an important determinate of event-free survival in childhood leukemia. In addition, there are emerging data that TPMT genotype may influence the risk of secondary malignancies, including brain tumors and acute myelogenous leukemia. Ongoing studies aim to clarify the influence of TPMT on thiopurine efficacy, acute toxicity, and risk for delayed toxicity. Together, these advances hold the promise of improving the safety and efficacy of thiopurine therapy.

Theories and techniques of behaviour change: Developing a cumulative science of behaviour change

Abstract: As behaviour contributes to the cause of much current mortality and morbidity (Mokdad, Marks, Stroup, & Gerberding, 2000; Parkin, Boyd, & Walker, 2011), interventions to change behaviour are essent...

Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate.

Abstract: The mycobacterial cord factor trehalose-6,6-dimycolate (TDM) and its synthetic analog trehalose-6,6-dibehenate (TDB) are potent adjuvants for Th1/Th17 vaccination that activate Syk-Card9 signaling in APCs. In this study, we have further investigated the molecular mechanism of innate immune activation by TDM and TDB. The Syk-coupling adapter protein FcRgamma was essential for macrophage activation and Th17 adjuvanticity. The FcRgamma-associated C-type lectin receptor Mincle was expressed in macrophages and upregulated by TDM and TDB. Recombinant Mincle-Fc fusion protein specifically bound to the glycolipids. Genetic ablation of Mincle abolished TDM/TDB-induced macrophage activation and induction of T cell immune responses to a tuberculosis subunit vaccine. Macrophages lacking Mincle or FcRgamma were impaired in the inflammatory response to Mycobacterium bovis bacillus Calmette-Guerin. These results establish that Mincle is a key receptor for the mycobacterial cord factor and controls the Th1/Th17 adjuvanticity of TDM and TDB.

The importance of conducting and reporting pilot studies: the example of the Scottish Births Survey.

Abstract: The importance of conducting and reporting pilot studies: the example of the Scottish Births Survey Background. In many research papers, pilot studies are only reported as a means of justifying the methods. This justification might refer to the overall research design, or simply to the validity and reliability of the research tools. It is unusual for reports of pilot studies to include practical problems faced by the researcher(s). Pilot studies are relevant to best practice in research, but their potential for other researchers appears to be ignored. Objective. The primary aim of this study was to identify the most appropriate method for conducting a national survey of maternity care. Methods. Pilot studies were conducted in five hospitals to establish the best of four possible methods of approaching women, distributing questionnaires and encouraging the return of these questionnaires. Variations in the pilot studies included (a) whether or not the questionnaires were anonymous, (b) the staff involved in distributing the questionnaires and (c) whether questionnaires were distributed via central or local processes. For this purpose, five maternity hospitals of different sizes in Scotland were included. Results. Problems in contacting women as a result of changes in the Data Protection Act (1998) required us to rely heavily on service providers. However, this resulted in a number of difficulties. These included poor distribution rates in areas where distribution relied upon service providers, unauthorized changes to the study protocol and limited or inaccurate information regarding the numbers of questionnaires distributed. Conclusions. The pilot raised a number of fundamental issues related to the process of conducting a large-scale survey, including the method of distributing the questionnaire, gaining access to patients, and reliance on ‘gatekeepers’. This paper highlights the lessons learned as well as the balancing act of using research methods in the most optimal way under the combined pressure of time, ethical considerations and the influences of stakeholders. Reporting the kinds of practical issues that occur during pilot studies might help others avoid similar pitfalls and mistakes.

The PRaCTICaL study of nurse led, intensive care follow-up programmes for improving long term outcomes from critical illness: a pragmatic randomised controlled trial

Abstract: Objectives To test the hypothesis that nurse led follow-up programmes are effective and cost effective in improving quality of life after discharge from intensive care. Design A pragmatic, non-blinded, multicentre, randomised controlled trial. Setting Three UK hospitals (two teaching hospitals and one district general hospital). Participants 286 patients aged ≥18 years were recruited after discharge from intensive care between September 2006 and October 2007. Intervention Nurse led intensive care follow-up programmes versus standard care. Main outcome measure(s) Health related quality of life (measured with the SF-36 questionnaire) at 12 months after randomisation. A cost effectiveness analysis was also performed. Results 286 patients were recruited and 192 completed one year follow-up. At 12 months, there was no evidence of a difference in the SF-36 physical component score (mean 42.0 (SD 10.6) v 40.8 (SD 11.9), effect size 1.1 (95% CI −1.9 to 4.2), P=0.46) or the SF-36 mental component score (effect size 0.4 (−3.0 to 3.7), P=0.83). There were no statistically significant differences in secondary outcomes or subgroup analyses. Follow-up programmes were significantly more costly than standard care and are unlikely to be considered cost effective. Conclusions A nurse led intensive care follow-up programme showed no evidence of being effective or cost effective in improving patients’ quality of life in the year after discharge from intensive care. Further work should focus on the roles of early physical rehabilitation, delirium, cognitive dysfunction, and relatives in recovery from critical illness. Intensive care units should review their follow-up programmes in light of these results. Trial registration ISRCTN 24294750