Consultation activities of clinical ethics committees in the United Kingdom: an empirical study and wake-up call.

Objective: To identify the consultation activities of clinical ethics committees (CECs) in the UK and the views of CEC chairpersons regarding such activities.

Methods: An anonymous, password-protected online questionnaire was sent by e-mail to 70 CEC chairpersons. The questionnaire contained 14 items.

Single-Molecule Force Spectroscopy of DNA-Based Reversible Polymer Bridges: Surface Robustness and Homogeneity.

Single-molecule force spectroscopy, as implemented in an atomic force microscope, provides a rarely-used method by which to monitor dynamic processes that occur near surfaces. Here, a methodology is presented and characterized that facilitates the study of polymer bridging across nanometer-sized gaps. The model system employed is that of DNA-based reversible polymers, and an automated procedure is introduced that allows the AFM tip-surface contact point to be automatically determined, and the distance d between opposing surfaces to be actively controlled.

Intestinal alkaline phosphatase: the molecular link between rosacea and gastrointestinal disease?

Rosacea is a common inflammatory condition of the facial skin of unknown etiology, which frequently occurs in combination with gastrointestinal disorders. Many dietary and hormonal factors are known to affect the severity of rosacea symptoms, several of which also modulate the activity of the enzyme intestinal alkaline phosphatase (IAP). The role of IAP in inhibiting an inflammatory response to intestinal bacteria suggests a mechanism by which intestinal pathologies may be linked to the skin inflammation characteristic of rosacea.

Inhibition of inosine monophosphate dehydrogenase reduces adipogenesis and diet-induced obesity.

We previously described a putative role for inosine monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme in de novo guanine nucleotide biosynthesis, in lipid accumulation. Here we present data which demonstrate that IMPDH activity is required for differentiation of preadipocytes into mature, lipid-laden adipocytes and maintenance of adipose tissue mass. In 3T3-L1 preadipocytes inhibition of IMPDH with mycophenolic acid (MPA) reduced intracellular GTP levels by 60% (p<0.

Mechanical factors activate beta-catenin-dependent oncogene expression in APC mouse colon.

beta-catenin acts as a critical regulator of gastrointestinal homeostasis through its control of the Wnt signaling pathway, and genetic or epigenetic lesions which activate Wnt signaling are the primary feature of colon cancer. beta-catenin is also a key element of mechanotranscription pathways, leading to upregulation of master developmental gene expression during Drosophila gastrulation, or regulating mammalian bone development and maintenance. Here we investigate the impact of mechanical stimulation on the initiation of colon cancer.

The long and the short of it: RNA-directed chromatin asymmetry in mammalian X-chromosome inactivation.

Mammalian X-chromosome inactivation is controlled by a multilayered silencing pathway involving both short and long non-coding RNAs, which differentially recruit the epigenetic machinery to establish chromatin asymmetries. In response to developmentally regulated small RNAs, dicer, a key effector of RNA interference, locally silences Xist on the active X-chromosome and establishes the heterochromatin conformation along the silent X-chromosome. The 1.

Effects of captan on Apis mellifera brood development under field conditions in California almond orchards.

Three almond field trials were conducted during 2003 and 2004 at two locations in central (Fresno County) and northern (Yolo County) California to evaluate the potential effects of commercial applications of Captan on honey bees, Apis mellifera L. Captan was applied at 5.0 kg (AI)/ha during bloom.

Using historical lesion volume data in the design of a new phase II clinical trial in acute stroke.

Background And Purpose: Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume.

Why good leaders make bad decisions.

Decision making lies at the heart of our personal and professional lives. Yet the daunting reality is that enormously important decisions made by intelligent, responsible people with the best information and intentions are nevertheless hopelessly flawed at times. In part, that's due to the way our brains work.

Caring for people with type 1 diabetes mellitus engaging in disturbed eating or weight control: a qualitative study of practitioners' attitudes and practices.

Aims And Objectives: To explore the attitudes and practices of hospital-based healthcare professionals toward people with type 1 diabetes mellitus (T1DM) exhibiting disturbed eating or weight control.

Background: Eating disturbances and insulin manipulation are common among individuals with T1DM, although little is known about how these behaviors are assessed and managed in practice.

Design: Qualitative study.

Action following the discovery of a global association between the whole genome and adverse event risk in a clinical drug-development programme.

Observation of adverse drug reactions during drug development can cause closure of the whole programme. However, if association between the genotype and the risk of an adverse event is discovered, then it might suffice to exclude patients of certain genotypes from future recruitment. Various sequential and non-sequential procedures are available to identify an association between the whole genome, or at least a portion of it, and the incidence of adverse events.

One- and two-stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint.

Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single-ordered categorical endpoint. The sample size requirements for one-stage and two-stage designs are derived, based on an approach similar to that of Dunnett.

Regulation of the mammalian epigenome by long noncoding RNAs.

Genomic analyses have demonstrated that although less than 2% of the mammalian genome encodes proteins, at least two thirds is transcribed. Many nontranslated RNAs have now been characterized, and several long transcripts, ranging from 0.5 to over 100 kb, have been shown to regulate gene expression by modifying chromatin structure.

Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes.

Excess glucocorticoids induce insulin resistance and reduce glucose uptake although the underlying mechanisms are unclear. Here we demonstrate that Dex (1 microM for 24h) inhibits basal and insulin (1 nM) stimulated glucose uptake in human and murine adipocytes by 50% with a concomitant reduction in the levels of GLUT1/4 at the plasma membrane but no change in total GLUT1/4 levels. Expression and phosphorylation of proximal insulin signalling molecules (IRS1, PI3K, AKT) was unaffected by Dex as was phosphorylation of mTOR and FOXO1.

Relationships among values, achievement orientations, and attitudes in youth sport.

This research examines the value-expressive function of attitudes and achievement goal theory in predicting moral attitudes. In Study 1, the Youth Sport Values Questionnaire (YSVQ; Lee, Whitehead, & Balchin, 2000) was modified to measure moral, competence, and status values. In Study 2, structural equation modeling on data from 549 competitors (317 males, 232 females) aged 12-15 years showed that moral and competence values predicted prosocial attitudes, whereas moral (negatively) and status values (positively) predicted antisocial attitudes.

A Linguistic Comparison of Letters of Recommendation for Male and Female Chemistry and Biochemistry Job Applicants.

Letters of recommendation are central to the hiring process. However, gender stereotypes could bias how recommenders describe female compared to male applicants. In the current study, text analysis software was used to examine 886 letters of recommendation written on behalf of 235 male and 42 female applicants for either a chemistry or biochemistry faculty position at a large U.

Fibroblast growth factor receptor 1 is a key regulator of early adipogenic events in human preadipocytes.

Cell number is an important determinant of adipose tissue mass, and the coordinated proliferation and differentiation of preadipocytes into mature lipid-laden adipocytes underpins the increased adipose tissue mass associated with obesity. Despite this, the molecular cues governing such adipose tissue expansion are poorly understood. We previously reported that fibroblast growth factor-1 (FGF-1) promotes both proliferation and differentiation of human preadipocytes and that the major adipogenic effect of FGF-1 occurs during proliferation, priming the cells for adipose conversion.

Enhancement of the destruction of propane in a low-temperature plasma by the addition of unsaturated hydrocarbons: experiment and modeling.

The oxidative destruction of propane at low temperature ( approximately 150 degrees C) in a nonthermal, atmospheric pressure plasma can be significantly enhanced without the use of a catalyst by the simple addition of an unsaturated alkene. An enhancement in the destruction of propane of up to 45% can be achieved by the addition of propene. Propene acts as a supply of OH radicals, which accelerate the breakdown of the propane.

Patients' experience of privacy and dignity. Part 2: An empirical study.

In May-June 2006, a self-report questionnaire was completed by 40 inpatients to assess their experience of privacy and dignity in hospital. The questionnaire comprised closed and open questions, where the latter, among other things, required the patient's own narrative. Results indicate that patients view privacy/dignity as crucial.

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain.

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to be stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase II and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size.

Evaluation of a sequential global test of improved recovery following stroke as applied to the ICTUS trial of citicoline.

The International Citicoline Trial in acUte Stroke is a sequential phase III study of the use of the drug citicoline in the treatment of acute ischaemic stroke, which was initiated in 2006 in 56 treatment centres. The primary objective of the trial is to demonstrate improved recovery of patients randomized to citicoline relative to those randomized to placebo after 12 weeks of follow-up. The primary analysis will take the form of a global test combining the dichotomized results of assessments on three well-established scales: the Barthel Index, the modified Rankin scale and the National Institutes of Health Stroke Scale.

A safety monitoring procedure for a clinical drug development program, with application to the assessment of a novel COX-2 inhibitor.

Formal safety monitoring procedures are well-developed for use in individual clinical trials and provide valuable guidance to Independent Data Monitoring Committees (IDMCs). Less has been written about procedures for use over the whole of a drug development program. It is becoming common for a single IDMC to be appointed for a whole series of studies involving a single compound.