Uncertainty Analyses of Advanced Fuel Cycles

The Department of Energy is developing technology, experimental protocols, computational methods, systems analysis software, and many other capabilities in order to advance the nuclear power infrastructure through the Advanced Fuel Cycle Initiative (AFDI). Our project, is intended to facilitate will-informed decision making for the selection of fuel cycle options and facilities for development

Improving Informed Consent: The Medium Is Not the Message

An important type of research on informed consent involves empirically testing interventions designed to improve the consent process. Here we report on the experience of eight teams that conducted research involving interventions designed primarily to impact one of three categories: decision-making, knowledge, and the therapeutic misconception

A Summary of the Endocrine Society Clinical Practice Guidelines on Congenital Adrenal Hyperplasia due to Steroid 21-Hydroxylase Deficiency

Steroid 21-hydroxylase deficiency accounts for about 95% of cases of congenital adrenal hyperplasia (CAH). Newborns are currently being screened for the classical forms of this disease throughout the United States and in 12 other countries. As such, it seems important to develop the best practice guidelines for treating not only infants and children, but affected adults as well. This report gives a brief overview of the most recent expert opinion and clinical practice guidelines for CAH as formulated by The Endocrine Society Task Force

An exploratory cluster randomised trial of a university halls of residence based social norms marketing campaign to reduce alcohol consumption among 1st year students

<p>Aims: This exploratory trial examines the feasibility of implementing a social norms marketing campaign to reduce student drinking in universities in Wales, and evaluating it using cluster randomised trial methodology.</p> <p>Methods: Fifty residence halls in 4 universities in Wales were randomly assigned to intervention or control arms. Web and paper surveys were distributed to students within these halls (n = 3800), assessing exposure/contamination, recall of and evaluative responses to intervention messages, perceived drinking norms and personal drinking behaviour. Measures included the Drinking Norms Rating Form, the Daily Drinking Questionnaire and AUDIT-C.</p> <p>Results: A response rate of 15% (n = 554) was achieved, varying substantially between sites. Intervention posters were seen by 80% and 43% of students in intervention and control halls respectively, with most remaining materials seen by a minority in both groups. Intervention messages were rated as credible and relevant by little more than half of students, though fewer felt they would influence their behaviour, with lighter drinkers more likely to perceive messages as credible. No differences in perceived norms were observed between intervention and control groups. Students reporting having seen intervention materials reported lower descriptive and injunctive norms than those who did not.</p> <p>Conclusions: Attention is needed to enhancing exposure, credibility and perceived relevance of intervention messages, particularly among heavier drinkers, before definitive evaluation can be recommended. A definitive evaluation would need to consider how it would achieve sufficient response rates, whilst hall-level cluster randomisation appears subject to a significant degree of contamination.</p&gt

An exploratory cluster randomised trial of a university halls of residence based social norms intervention in Wales, UK

Background: Excessive alcohol consumption amongst university students has received increasing attention. A social norms approach to reducing drinking behaviours has met with some success in the USA. Such an approach is based on the assumption that student's perceptions of the norms of their peers are highly influential, but that these perceptions are often incorrect. Social norms interventions therefore aim to correct these inaccurate perceptions, and in turn, to change behaviours. However, UK studies are scarce and it is increasingly recognised that social norm interventions need to be supported by socio ecological approaches that address the wider determinants of behaviour. Objectives: To describe the research design for an exploratory trial examining the acceptability, hypothesised process of change and implementation of a social norm marketing campaign designed to correct misperceptions of normative alcohol use and reduce levels of misuse, implemented alongside a university wide alcohol harm reduction toolkit. It also assesses the feasibility of a potential large scale effectiveness trial by providing key trial design parameters including randomisation, recruitment and retention, contamination, data collection methods, outcome measures and intracluster correlations. Methods/design: The study adopts an exploratory cluster randomised controlled trial design with halls of residence as the unit of allocation, and a nested mixed methods process evaluation. Four Welsh (UK) universities participated in the study, with residence hall managers consenting to implementation of the trial in 50 university owned campus based halls of residence. Consenting halls were randomised to either a phased multi channel social norm marketing campaign addressing normative discrepancies (n = 25 intervention) or normal practice (n = 25 control). The primary outcome is alcohol consumption (units per week) measured using the Daily Drinking Questionnaire. Secondary outcomes assess frequency of alcohol consumption, higher risk drinking, alcohol related problems and change in perceptions of alcohol-related descriptive and injunctive norms. Data will be collected for all 50 halls at 4 months follow up through a cross-sectional on line and postal survey of approximately 4000 first year students. The process evaluation will explore the acceptability and implementation of the social norms intervention and toolkit and hypothesised process of change including awareness, receptivity and normative changes. Discussion: Exploratory trials such as this are essential to inform future definitive trials by providing crucial methodological parameters and guidance on designing and implementing optimum interventions

Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer

This multicenter, randomized, open-label phase III trial (planned enrollment: 700 patients) was conducted to test the hypothesis that single-agent sunitinib improves progression-free survival (PFS) compared with capecitabine as treatment for advanced breast cancer (ABC). Patients with HER2-negative ABC that recurred after anthracycline and taxane therapy were randomized (1:1) to sunitinib 37.5 mg/day or capecitabine 1,250 mg/m2 (1,000 mg/m2 in patients >65 years) BID on days 1–14 q3w. The independent data-monitoring committee (DMC) determined during the first interim analysis (238 patients randomized to sunitinib, 244 to capecitabine) that the trial be terminated due to futility in reaching the primary endpoint. No statistical evidence supported the hypothesis that sunitinib improved PFS compared with capecitabine (one-sided P = 0.999). The data indicated that PFS was shorter with sunitinib than capecitabine (median 2.8 vs. 4.2 months, respectively; HR, 1.47; 95% CI, 1.16–1.87; two-sided P = 0.002). Median overall survival (15.3 vs. 24.6 months; HR, 1.17; two-sided P = 0.350) and objective response rates (11 vs. 16%; odds ratio, 0.65; P = 0.109) were numerically inferior with sunitinib versus capecitabine. While no new or unexpected safety findings were reported, sunitinib treatment was associated with higher frequencies and greater severities of many common adverse events (AEs) compared with capecitabine, resulting in more temporary discontinuations due to AEs with sunitinib (66 vs. 51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam

Modeling Boundary Vector Cell Firing Given Optic Flow as a Cue

Boundary vector cells in entorhinal cortex fire when a rat is in locations at a specific distance from walls of an environment. This firing may originate from memory of the barrier location combined with path integration, or the firing may depend upon the apparent visual input image stream. The modeling work presented here investigates the role of optic flow, the apparent change of patterns of light on the retina, as input for boundary vector cell firing. Analytical spherical flow is used by a template model to segment walls from the ground, to estimate self-motion and the distance and allocentric direction of walls, and to detect drop-offs. Distance estimates of walls in an empty circular or rectangular box have a mean error of less than or equal to two centimeters. Integrating these estimates into a visually driven boundary vector cell model leads to the firing patterns characteristic for boundary vector cells. This suggests that optic flow can influence the firing of boundary vector cells

Effect of prostaglandin E2 injection on the structural properties of the rat patellar tendon

Background: Increased tendon production of the inflammatory mediator prostaglandin E2 (PGE2) has been suggested to be a potential etiologic agent in the development of tendinopathy. Repeated injection of PGE2 into tendon has been proposed as a potential animal model for studying treatments for tendinopathy. In contrast, nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit PGE2 production and are commonly prescribed in treating tendinopathy have been shown to impair the healing of tendon after acute injury in animal models. The contradictory literature suggests the need to better define the functional effects of PGE2 on tendon. Our objective was to characterize the effects of PGE2 injection on the biomechanical and biochemical properties of tendon and the activity of the animals. Our hypothesis was that weekly PGE2 injection to the rat patellar tendon would lead to inferior biomechanical properties. Methods: Forty rats were divided equally into four groups. Three groups were followed for 4 weeks with the following peritendinous injection procedures: No injection (control), 4 weekly injections of saline (saline), 4 weekly injections of 800 ng PGE2 (PGE2-4 wks). The fourth group received 4 weekly injections of 800 ng PGE2 initially and was followed for a total of 8 weeks. All animals were injected bilaterally. The main outcome measurements included: the structural and material properties of the patellar tendon under tensile loading to failure, tendo