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.

Recruitment to randomised trials: strategies for trial enrolment and participation study. The STEPS study

Abstract: Objectives To identify factors associated with good and poor recruitment to multicentre trials. Data sources Part A: database of trials started in or after 1994 and were due to end before 2003 held by the Medical Research Council and Health Technology Assessment Programmes. Part B: interviews with people playing a wide range of roles within four trials that their funders identified as 'exemplars'. Part C: a large multicentre trial (the CRASH trial) of treatment for head injury. Review methods The study used a number of different perspectives ('multiple lenses'), and three components. Part A: an epidemiological review of a cohort of trials. Part B: case studies of trials that appeared to have particularly interesting lessons for recruitment. Part C: a single, in-depth case study to examine the feasibility of applying a business-orientated analytical framework as a reference model in future trials. Results In the 114 trials found in Part A, less than one-third recruited their original target within the time originally specified, and around one-third had extensions. Factors observed more often in trials that recruited successfully were: having a dedicated trial manager, being a cancer or drug trial, and having interventions only available inside the trial. The most commonly reported strategies to improve recruitment were newsletters and mailshots, but it was not possible to assess whether they were causally linked to changes in recruitment. The analyses in Part B suggested that successful trials were those addressing clinically important questions at a timely point. The investigators were held in high esteem by the interviewees, and the trials were firmly grounded in existing clinical practices, so that the trial processes were not alien to clinical collaborators, and the results could be easily applicable to future practice. The interviewees considered that the needs of patients were well served by participation in the trials. Clinical collaborators particularly appreciated clear delineation of roles, which released them from much of the workload associated with trial participation. There was a strong feeling from interviewees that they were proud to be part of a successful team. This pride fed into further success. Good groundwork and excellent communications across many levels of complex trial structures were considered to be extremely important, including training components for learning about trial interventions and processes, and team building. All four trials had faced recruitment problems, and extra insights into the working of trials were afforded by strategies invoked to address them. The process of the case study in Part C was able to draw attention to a body of research and practice in a different discipline (academic business studies). It generated a reference model derived from a combination of business theory and work within CRASH. This enabled identification of weaker managerial components within CRASH, and initiatives to strengthen them. Although it is not clear, even within CRASH, whether the initiatives that follow from developing and applying the model will be effective in increasing recruitment or other aspects of the success of the trial, the reference model could provide a template, with potential for those managing other trials to use or adapt it, especially at foundation stages. The model derived from this project could also be used as a diagnostic tool if trials have difficulties and hence as a basis for deciding what type of remedial action to take. It may also be useful for auditing the progress of trials, such as during external review. Conclusions While not producing sufficiently definitive results to make strong recommendations, the work here suggests that future trials should consider the different needs at different phases in the life of trials, and place greater emphasis on 'conduct' (the process of actually doing trials). This implies learning lessons from successful trialists and trial managers, with better training for issues relating to trial conduct. The complexity of large trials means that unanticipated difficulties are highly likely at some time in every trial. Part B suggested that successful trials were those flexible and robust enough to adapt to unexpected issues. Arguably, the trialists should also expect agility from funders within a proactive approach to monitoring ongoing trials. Further research into different recruitment patterns (including 'failures') may help to clarify whether the patterns seen in the 'exemplar' trials differ or are similar. The reference model from Part C needs to be further considered in other similar and different trials to assess its robustness. These and other strategies aimed at increasing recruitment and making trials more successful need to be formally evaluated for their effectiveness in a range of trials.

Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk

Abstract: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.

Carrier concentrations and relaxation spectroscopy : new information from scaling properties of conductivity spectra in ionically conducting glasses

Abstract: A new kind of scaling analysis for the conductivity spectra of glasses without any arbitrary parameters is presented. By applying this method to sodium borate glasses of different compositions, we find strong indications for the existence of a universal ionic relaxation process as well as for a strong electrolyte behavior. Our results enable us to show that the often used electric modulus formalism is misleading when relaxation mechanisms on a microscopic level are concerned. A more meaningful discussion can be based on the log-log dependence of the conductivity on frequency.

Carbon-isotope stratigraphy recorded by the Cenomanian–Turonian Oceanic Anoxic Event: correlation and implications based on three key localities

Abstract: We present new, detailed carbon-isotope records for bulk carbonate, total organic carbon (TOC) and phytane from three key sections spanning the Cenomanian–Turonian boundary interval (Eastbourne, England; Gubbio, Italy; Tarfaya, Morocco), with the purpose of establishing a common chemostratigraphic framework for Oceanic Anoxic Event (OAE) 2. Isotope curves from all localities are characterized by a positive carbon-isotope excursion of c . 4‰ for TOC and phytane and c . 2.5‰ for carbonate, although diagenetic overprinting appears to have obliterated the primary carbonate carbon-isotope signal in at least part of the Tarfaya section. Stratigraphically, peak δ 13 C values for all components are followed by intervals of high, near-constant δ 13 C in the form of an isotopic plateau. Recognition of an unambiguous return to background δ 13 C values above the plateau is, however, contentious in all sections, hence no firm chemostratigraphic marker for the end-point of the positive isotopic excursion can be established. The stratigraphically consistent first appearance of the calcareous nannofossil Quadrum gartneri at or near the Cenomanian–Turonian boundary as established by ammonite stratigraphy, in conjunction with the end of the δ 13 C maximum characteristic of the isotopic plateau, provides a potentially powerful tool for delimiting the stratigraphic extent and duration of OAE 2. This Oceanic Anoxic Event is demonstrated to be largely, if not wholly, confined to the latest part of the Cenomanian stage.