Time trials on second-order and variable-learning-rate algorithms

The performance of seven minimization algorithms are compared on five neural network problems. These include a variable-step-size algorithm, conjugate gradient, and several methods with explicit analytic or numerical approximations to the Hessian.

Inappropriate oral formulations and information in paediatric trials

Previously, quality of formulations information provided for oral medications used in paediatric clinical trials published in 10 highly cited journals between 2002 and 2004 raised concerns. This short report explores if there was any subsequent improvement on how the formulations used in trials involving children

First in-vivo trials of a fibre Bragg grating based temperature profiling system

We describe the results of in-vivo trials of a portable fiber Bragg grating based temperature profile monitoring system. The probe incorporates five Bragg gratings along a single fiber and prevents the gratings from being strained. Illumination is provided by a superluminescent diode, and a miniature CCD based spectrometer is used for demultiplexing. The CCD signal is read into a portable computer through a small A/D interface; the computer then calculates the positions of the center wavelengths of the Bragg gratings, providing a resolution of 0.2°C. Tests were carried out on rabbits undergoing hyperthermia treatment of the kidney and liver via inductive heating of metallic implants and comparison was made with a commercial Fluoroptic thermometry system.

First in-vivo trials of a fibre Bragg grating based temperature profiling system

We describe the results of in-vivo trials of a portable fiber Bragg grating based temperature profile monitoring system. The probe incorporates five Bragg gratings along a single fiber and prevents the gratings from being strained. Illumination is provided by a superluminescent diode, and a miniature CCD based spectrometer is used for demultiplexing. The CCD signal is read into a portable computer through a small A/D interface; the computer then calculates the positions of the center wavelengths of the Bragg gratings, providing a resolution of 0.2 °C. Tests were carried out on rabbits undergoing hyperthermia treatment of the kidney and liver via inductive heating of metallic implants and comparison was made with a commercial Fluoroptic thermometry system.

Psychological therapies for chronic pelvic pain:systematic review of randomized controlled trials

Chronic pelvic pain (CPP), a common cause of disability in women, is a condition best viewed in the biopsychosocial framework. Psychological interventions are frequently considered alongside medical and surgical treatments. Our objective was to evaluate the effectiveness of psychological therapies for the treatment of CPP. Electronic literature searches were conducted in Medline, Embase, PsycInfo and DARE databases from database inception to April 2010. Reference lists of selected articles were searched for further articles. The studies selected were randomized controlled trials of psychological therapies in patients with CPP compared with no treatment, standard gynecological treatment or another form of psychological therapy. Two reviewers independently selected articles without language restrictions and extracted data covering study characteristics, study quality and results. Reduction in pain, measured using visual analog scales or other measurements, was the main outcome measure. Of the 107 citations identified, four studies satisfied the inclusion criteria. Compared with no psychological intervention, therapy produced a standardized mean pain score of -3.27 [95% confidence interval (CI) -4.52 to -2.02] and 1.11 (95% CI -0.05 to 2.27) at 3 months and -3.95 (95% CI -5.35 to -2.55) and 0.54 (95% CI -0.78 to 1.86) at 6 months and greater, based on a visual analog scale score of 0-10. The current evidence does not allow us to conclude whether psychological interventions have an effect on self-reported pain scores in women with CPP.

Negotiating proximity:expert testimony and collective memory in the trials of environmental activists in France and the United Kingdom

This article analyzes the role of expert witness testimony in the trials of social movement actors, discussing the trial of the "Kingsnorth Six" in Britain and the trials of activists currently mobilising against airport construction at Notre Dame des Landes in western France. Though the study of expert testimony has so far overwhelmingly concentrated on fact-finding and admissibility, the cases here reveal the importance of expert testimony not simply in terms of legal argument, but in "moral" or political terms, as it reflects and constitutes movement cognitive praxis. In the so-called climate change defence presented by the Kingsnorth Six, I argue that expert testimony attained a "negotiation of proximity," connecting different types of contributory expertise to link the scales and registers of climate science with those of everyday understanding and meaning. Expert testimony in the trials of activists in France, however, whilst ostensibly able to develop similar bridging narratives, has instead been used to construct resistance to the airport siting as already proximate, material, and embedded. To explain this, I argue that attention to the symbolic, as well as instrumental, functions of expert testimony reveals the crucial role that collective memory plays in the construction of both knowledge and grievance in these cases. Collective memory is both a constraint on and catalyst for mobilisation, defining the boundaries of the sayable. Testimony in trials both reflects and reproduces these elements and is a vital explanatory tool for understanding the narrativisation and communication of movement identities and objectives. © 2013 The Author. Law & Policy © 2013 The University of Denver/Colorado Seminary.

Glycaemic control and cardiovascular outcome trials in type 2 diabetes

Large prospective trials designed to assess the relationship between metabolic control and CV outcomes in type 2 diabetes have entered a new phase of scrutiny due to strict requirements imposed by the FDA to assess new anti-diabetic agents. So what have we learned from recently completed trials and what do we expect to learn from on-going trials?

The atypical bilingual courtroom:an exploratory study of the interactional dynamics in interpreter-mediated trials in Hong Kong

This study investigates the communication process in the atypical bilingual Hong Kong courtroom, where, unlike in most other jurisdictions, interpreting services are routinely provided for the linguistic majority instead of the linguistic minority and the interpreter usually has to work with court actors who share his/her bilingual knowledge. It sets out to explore how the unique nature of the bilingual Hong Kong courtroom impacts on interactional dynamics in communicative process in the courtroom and potentially on the administration of justice, using authentic recordings of nine criminal trials from three court levels, supplemented by a survey administered to court interpreters. It compares the participant roles of different court actors in different court settings, monolingual and bilingual, using Goffman’s (1981) participation framework and Bell’s (1984) audience design as the conceptual framework. It is found that the notion of recipientship in the atypical bilingual Hong Kong courtroom is complicated by the presence of other bilinguals, which inevitably changes the interactional dynamics and impacts on the power of court interpreter as these bilinguals take on more participant roles in the process. The findings of this study show that the power of court actors is realised in the participant role(s) they and the other co-present court actors take on or are capable of playing. The findings also indicate that a change in the participant role of a court actor has an impact on the participation status other actors, which may in turn hamper the administration of justice. It is also found that the notion of power asymmetry in the courtroom has an effect on the footings adopted by the interpreter and thus on his/her neutrality. This thesis identifies training needs and makes recommendations for best practice in the courtroom and for institutional administrative practice.

Form follows function:model-driven engineering for clinical trials

We argue that, for certain constrained domains, elaborate model transformation technologies-implemented from scratch in general-purpose programming languages-are unnecessary for model-driven engineering; instead, lightweight configuration of commercial off-the-shelf productivity tools suffices. In particular, in the CancerGrid project, we have been developing model-driven techniques for the generation of software tools to support clinical trials. A domain metamodel captures the community's best practice in trial design. A scientist authors a trial protocol, modelling their trial by instantiating the metamodel; customized software artifacts to support trial execution are generated automatically from the scientist's model. The metamodel is expressed as an XML Schema, in such a way that it can be instantiated by completing a form to generate a conformant XML document. The same process works at a second level for trial execution: among the artifacts generated from the protocol are models of the data to be collected, and the clinician conducting the trial instantiates such models in reporting observations-again by completing a form to create a conformant XML document, representing the data gathered during that observation. Simple standard form management tools are all that is needed. Our approach is applicable to a wide variety of information-modelling domains: not just clinical trials, but also electronic public sector computing, customer relationship management, document workflow, and so on. © 2012 Springer-Verlag.

Children's views on unlicensed/off-label paediatric prescribing and paediatric clinical trials

Objectives - To explore the views and perspectives of children on the unlicensed/off-label use of medicines in children and on the participation of children in clinical trials. Methods - Focus-group discussions, involving school children, were carried out in a range of primary and secondary schools in Northern Ireland. A purposeful sample was chosen to facilitate representation of various socioeconomic groupings. Results - A total of 123 pupils, aged from 10 to 16 years, from six schools, participated in 16 focus groups. In general, pupils viewed the unlicensed/off-label use of medicines in children as unsafe and unethical and felt it is necessary to test medicines in children to improve the availability of licensed products. The majority felt that older children should be told, and that parents should be told, about the unlicensed/off-label use of medicines in children, yet they recognised some implications of this, such as potential medication non-adherence. Conclusions - This is the first study to explore the views of healthy children on unlicensed medicine use in children. Children were able to recognise potential risks associated with the unlicensed use of medicines and felt it is necessary to test and license more medicines in children. Practice implications - Health care professionals should consider the views of children in decisions that affect their health.

Healthcare professional experiences and attitudes on unlicensed/off-label paediatric prescribing and paediatric clinical trials

To investigate the knowledge and views of a range of healthcare professionals (consultant paediatricians, general practitioners (GPs), community pharmacists and paediatric nurses) regarding the use of unlicensed/off-label medicines in children and the participation of children in clinical trials.

Age-related macular degeneration and nutritional supplementation:a review of randomised controlled trials

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in the developed world. The lack of effective treatment modalities, coupled with evidence supporting an oxidative pathogenesis, has increased interest in the potential preventative role of nutritional supplementation. This article reviews seven randomised controlled trials (RCTs) that have investigated the role of nutritional supplementation in AMD. Three of these trials reported a positive effect of nutritional supplementation on AMD; the Age-related eye study (AREDS), the Lutein Antioxidant Supplementation Trial (LAST), and the oral zinc trial by Newsome et al. (1988). However, the oral zinc trial by Newsome et al. (1988) was unlikely to detect any difference between treatments smaller than 72%, and the AREDS results were based on a subgroup of their study population. Lutein was considered for the AREDS formulation, but was not commercially available at that time. The findings of the LAST support a possible therapeutic role of lutein in AMD. © 2004 The College of Optometrists.

Pronounced reduction of postprandial glucagon by lixisenatide:a meta-analysis of randomized clinical trials

Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels. Methods: Six randomized, placebo-controlled studies of lixisenatide 20μg once daily were included in this analysis: lixisenatide as monotherapy (GetGoal-Mono), as add-on to oral antidiabetic drugs (OADs; GetGoal-M, GetGoal-S) or in combination with basal insulin (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Change in 2-h PPG and glucose excursion were evaluated across six studies. Change in 2-h glucagon and postprandial insulin were evaluated across two studies. A meta-analysis was performed on least square (LS) mean estimates obtained from analysis of covariance (ANCOVA)-based linear regression. Results: Lixisenatide significantly reduced 2-h PPG from baseline (LS mean difference vs. placebo: -4.9mmol/l, p<0.001) and glucose excursion (LS mean difference vs. placebo: -4.5mmol/l, p<0.001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs. placebo: -19.0ng/l, p<0.001) and insulin (LS mean difference vs. placebo: -64.8 pmol/l, p<0.001). There was a stronger correlation between 2-h postprandial glucagon and 2-h PPG with lixisenatide than with placebo. Conclusions: Lixisenatide significantly reduced 2-h PPG and glucose excursion together with a marked reduction in postprandial glucagon and insulin; thus, lixisenatide appears to have biological effects on blood glucose that are independent of increased insulin secretion. These effects may be, in part, attributed to reduced glucagon secretion. © 2014 John Wiley and Sons Ltd.

Systematic review investigating the reporting of comorbidities and medication in randomized controlled trials of people with dementia

Objectives: dementia is a debilitating condition characterised by global loss of cognitive and intellectual functioning, which reduces social and occupational performance. This population frequently presents with medical co-morbidities such as hypertension, cardiovascular disease and diabetes. The CONSORT statement outlines recommended guidance on reporting of participant characteristics in clinical trials. It is, however, unclear how much these are adhered to in trials assessing people with dementia. This paper assesses the reporting of medical co-morbidities and prescribed medications for people with dementia within randomised controlled trial (RCT) reports. Design: a systematic review of the published literature from the databases AMED, CINAHL, MEDLINE, EMBASE and the Cochrane Clinical Trial Registry from 1 January 1997 to 9 January 2014 was undertaken in order to identify RCTs detailing baseline medical co-morbidities and prescribed medications . Eligible studies were appraised using the Critical Appraisal Skills Programme (CASP) RCT appraisal tool, and descriptive statistical analyses were calculated to determine point prevalence. Results: nine trials, including 1474 people with dementia, were identified presenting medical co-morbidity data. These indicated neurological disorders ( prevalence 91%), vascular disorders (prevalence 91%), cardiac disorders ( prevalence 74%) and ischaemic cerebrovascular disease ( prevalence 53%) were most frequently seen. Conclusions: published RCTs poorly report medical co-morbidities and medications for people with dementia. Future trials should include the report of these items to allow interpretation of whether the results are generalisable to frailer older populations.