Evaluation of a standard provision versus an autonomy promotive exercise referral programme: rationale and study design

Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials. Recent empirical evidence in health care and physical activity promotion contexts provides a foundation for testing the utility of a Self Determination Theory (SDT) -based exercise referral consultation. Methods/Design Design: An exploratory cluster randomised controlled trial comparing standard provision exercise on prescription with a Self Determination Theory-based (SDT) exercise on prescription intervention. Participants: 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008. The 13 exercise on prescription sites in Birmingham were randomised to current practice (n=7) or to the SDT-based intervention (n=6). Outcomes measured at 3 and 6-months: Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall; physical health: blood pressure and weight; health status measured using the Dartmouth CO-OP charts; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score; motivation and processes of change: perceptions of autonomy support from the advisor, satisfaction of the needs for competence, autonomy, and relatedness via physical activity, and motivational regulations for exercise. Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a standard programme and will test the underlying SDT-based process model (perceived autonomy support, need satisfaction, motivation regulations, outcomes) via structural equation modelling. Trial registration The trial is registered as Current Controlled trials ISRCTN07682833

Therapeutic opportunities within the DNA damage response

The DNA damage response (DDR) is essential for maintaining the genomic integrity of the cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have been exploited therapeutically in the treatment of cancer with radiation therapies or genotoxic chemotherapies. More recently, protein components of the DDR systems have been identified as promising avenues for targeted cancer therapeutics. Here, we present an in-depth analysis of the function, role in cancer and therapeutic potential of 450 expert-curated human DDR genes. We discuss the DDR drugs that have been approved by the US Food and Drug Administration (FDA) or that are under clinical investigation. We examine large-scale genomic and expression data for 15 cancers to identify deregulated components of the DDR, and we apply systematic computational analysis to identify DDR proteins that are amenable to modulation by small molecules, highlighting potential novel therapeutic targets

Impulsivity and self-harm in adolescence: a systematic review

Research supports an association between impulsivity and self-harm, yet inconsistencies in methodology across studies have complicated understanding of this relationship. This systematic review examines the association between impulsivity and self-harm in community-based adolescents aged 11-25 years and aims to integrate findings according to differing concepts and methods. Electronic searches of EMBASE, MEDLINE, PsychINFO, CINAHL, PubMed and The Cochrane Library, and manual searches of reference lists of relevant reviews, identified 4,496 articles published up to July 2015, of which 28 met inclusion criteria. Twenty-four of the studies reported an association between broadly specified impulsivity and self-harm. However, findings varied according to the conception and measurement of impulsivity and the precision with which self-harm behaviours were specified. Specifically, lifetime non-suicidal self-injury was most consistently associated with mood-based impulsivity related traits. However, cognitive facets of impulsivity (relating to difficulties maintaining focus or acting without forethought) differentiated current self-harm from past self-harm. These facets also distinguished those with thoughts of self-harm (ideation) from those who acted on thoughts (enaction). The findings suggested that mood-based impulsivity is related to the initiation of self-harm, while cognitive facets of impulsivity are associated with the maintenance of self-harm. In addition, behavioural impulsivity is most relevant to self-harm under conditions of negative affect. Collectively, the findings indicate that distinct impulsivity facets confer unique risks across the life-course of self-harm. From a clinical perspective, the review suggests that interventions focusing on reducing rash reactivity to emotions or improving self-regulation and decision-making may offer most benefit in supporting those who self-harm

Psychometric properties of multicomponent tools designed to assess frailty in older adults: A systematic review

Background: Frailty is widely recognised as a distinct multifactorial clinical syndrome that implies vulnerability. The links between frailty and adverse outcomes such as death and institutionalisation have been widely evidenced. There is currently no gold standard frailty assessment tool; optimizing the assessment of frailty in older people therefore remains a research priority. The objective of this systematic review is to identify existing multi-component frailty assessment tools that were specifically developed to assess frailty in adults aged ≥60 years old and to systematically and critically evaluate the reliability and validity of these tools. Methods: A systematic literature review was conducted using the standardised COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) checklist to assess the methodological quality of included studies. Results: Five thousand sixty-three studies were identified in total: 73 of which were included for review. 38 multi-component frailty assessment tools were identified: Reliability and validity data were available for 21 % (8/38) of tools. Only 5 % (2/38) of the frailty assessment tools had evidence of reliability and validity that was within statistically significant parameters and of fair-excellent methodological quality (the Frailty Index-Comprehensive Geriatric Assessment [FI-CGA] and the Tilburg Frailty Indicator [TFI]). Conclusions: The TFI has the most robust evidence of reliability and validity and has been the most extensively examined in terms of psychometric properties. However, there is insufficient evidence at present to determine the best tool for use in research and clinical practice. Further in-depth evaluation of the psychometric properties of these tools is required before they can fulfil the criteria for a gold standard assessment tool

The ongoing pursuit of neuroprotective therapies in Parkinson disease

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD

NMR Characterizations of the Ice Binding Surface of an Antifreeze Protein

Antifreeze protein (AFP) has a unique function of reducing solution freezing temperature to protect organisms from ice damage. However, its functional mechanism is not well understood. An intriguing question concerning AFP function is how the high selectivity for ice ligand is achieved in the presence of free water of much higher concentration which likely imposes a large kinetic barrier for protein-ice recognition. In this study, we explore this question by investigating the property of the ice binding surface of an antifreeze protein using NMR spectroscopy. An investigation of the temperature gradient of amide proton chemical shift and its correlation with chemical shift deviation from random coil was performed for CfAFP-501, a hyperactive insect AFP. A good correlation between the two parameters was observed for one of the two Thr rows on the ice binding surface. A significant temperature-dependent protein-solvent interaction is found to be the most probable origin for this correlation, which is consistent with a scenario of hydrophobic hydration on the ice binding surface. In accordance with this finding, rotational correlation time analyses combined with relaxation dispersion measurements reveals a weak dimer formation through ice binding surface at room temperature and a population shift of dimer to monomer at low temperature, suggesting hydrophobic effect involved in dimer formation and hence hydrophobic hydration on the ice binding surface of the protein. Our finding of hydrophobic hydration on the ice binding surface provides a test for existing simulation studies. The occurrence of hydrophobic hydration on the ice binding surface is likely unnecessary for enhancing protein-ice binding affinity which is achieved by a tight H-bonding network. Subsequently, we speculate that the hydrophobic hydration occurring on the ice binding surface plays a role in facilitating protein-ice recognition by lowering the kinetic barrier as suggested by some simulation studies

Multiple growth factor independence in rat mammary carcinoma cells

In previous studies we demonstrated that rat mammary tumor (RMT) cells that are serially transplantable consist of cells that are independent of growth factors strictly required by normal rat mammary epithelial (RME) cells for growth in serum-free culture. The present studies were designed to determine the extent of the growth factor independence of several cell lines derived from these tumors and to determine if the cells that expressed growth factor independence in vitro are also tumorigenic in vivo . Cells from a transplantable mammary carcinoma (8–12 RMT) were seeded into culture in serum-free medium in the absence of either insulin (IN), epidermal growth factor (EGF), or cholera toxin (CT), and cell populations independent of the individual factors were developed. Next, the three growth factor independent populations were tested for their ability to grow in the absence of multiple growth factors. 8–12 RMT cells did not lose proliferative potential when multiple growth factors were deleted from the medium. Indeed, 8–12 RMT cells could be serially propagated in serum-free medium supplemented solely with bovine serum albumin (BSA) and ethanolamine. Cell lines independent of single growth factors were also developed from two other transplantable tumors (1–9 RMT and 7–15 RMT). In contrast to the 8–12 RMT-derived cell lines, deletion of additional growth factors from the media of the 1–9 RMT and 7–15 RMT-derived cells resulted in dramatic losses in growth potential. These results suggest that independence of individual growth factors is mediated by different mechanisms, since cells from different tumors can stably express independence of one, two, or three or more factors. Examination of conditioned media of four different RMT cell lines indicates that independence of EGF is mediated by autocrine factors. By contrast, there is no evidence for an autocrine factor that mediates independence of insulin-like growth factors. Thus, cell lines derived from serially transplantable RMTs are independent of either single or multiple growth factors, and independence of individual growth factors appears to be mediated by separate mechanisms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44197/1/10549_2005_Article_BF01980969.pd

Does the mind map learning strategy facilitate information retrieval and critical thinking in medical students?

<p>Abstract</p> <p>Background</p> <p>A learning strategy underutilized in medical education is mind mapping. Mind maps are multi-sensory tools that may help medical students organize, integrate, and retain information. Recent work suggests that using mind mapping as a note-taking strategy facilitates critical thinking. The purpose of this study was to investigate whether a relationship existed between mind mapping and critical thinking, as measured by the Health Sciences Reasoning Test (HSRT), and whether a relationship existed between mind mapping and recall of domain-based information.</p> <p>Methods</p> <p>In this quasi-experimental study, 131 first-year medical students were randomly assigned to a standard note-taking (SNT) group or mind map (MM) group during orientation. Subjects were given a demographic survey and pre-HSRT. They were then given an unfamiliar text passage, a pre-quiz based upon the passage, and a 30-minute break, during which time subjects in the MM group were given a presentation on mind mapping. After the break, subjects were given the same passage and wrote notes based on their group (SNT or MM) assignment. A post-quiz based upon the passage was administered, followed by a post-HSRT. Differences in mean pre- and post-quiz scores between groups were analyzed using independent samples <it>t</it>-tests, whereas differences in mean pre- and post-HSRT total scores and subscores between groups were analyzed using ANOVA. Mind map depth was assessed using the Mind Map Assessment Rubric (MMAR).</p> <p>Results</p> <p>There were no significant differences in mean scores on both the pre- and post-quizzes between note-taking groups. And, no significant differences were found between pre- and post-HSRT mean total scores and subscores.</p> <p>Conclusions</p> <p>Although mind mapping was not found to increase short-term recall of domain-based information or critical thinking compared to SNT, a brief introduction to mind mapping allowed novice MM subjects to perform similarly to SNT subjects. This demonstrates that medical students using mind maps can successfully retrieve information in the short term, and does not put them at a disadvantage compared to SNT students. Future studies should explore longitudinal effects of mind-map proficiency training on both short- and long-term information retrieval and critical thinking.</p

Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>Tuberculosis is a leading cause of death worldwide, yet the determinants of death are not well understood. We sought to determine risk factors for mortality during treatment of drug-susceptible pulmonary tuberculosis under program settings.</p> <p>Methods</p> <p>Retrospective chart review of patients with drug-susceptible tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990-2001.</p> <p>Results</p> <p>Of 565 patients meeting eligibility criteria, 37 (6.6%) died during the study period. Of 37 deaths, 12 (32.4%) had tuberculosis listed as a contributing factor. In multivariate analysis controlling for follow-up time, four characteristics were independently associated with mortality: HIV co-infection (HR = 2.57, p = 0.02), older age at tuberculosis diagnosis (HR = 1.52 per 10 years, p = 0.001); initial sputum smear positive for acid fast bacilli (HR = 3.07, p = 0.004); and experiencing an interruption in tuberculosis therapy (HR = 3.15, p = 0.002). The association between treatment interruption and risk of death was due to non-adherence during the intensive phase of treatment (HR = 3.20, p = 0.001). The median duration of treatment interruption did not differ significantly in either intensive or continuation phases between those who died and survived (23 versus 18 days, and 37 versus 29 days, respectively). No deaths were directly attributed to adverse drug reactions.</p> <p>Conclusions</p> <p>In addition to advanced age, HIV and characteristics of advanced tuberculosis, experiencing an interruption in anti-tuberculosis therapy, primarily due to non-adherence, was also independently associated with increased risk of death. Improving adherence early during treatment for tuberculosis may both improve tuberculosis outcomes as well as decrease mortality.</p

Evaluating the transport, health and economic impacts of new urban cycling infrastructure in Sydney, Australia – protocol paper

BACKGROUND: There are repeated calls to build better cycling paths in Australian cities if the proportion of people cycling is to increase. Yet the full range of transport, health, environmental and economic impacts of new cycling infrastructure and the extent to which observed changes are sustained is not well understood. The City of Sydney is currently building a new bicycle network, which includes a new bicycle path separated from road traffic in the south Sydney area. This protocol paper describes a comprehensive method to evaluate this new cycling infrastructure. METHOD: A cohort of residents within two kilometres of the new bicycle path will be surveyed at baseline before a new section of bicycle path is built, and again 12 and 24 months later to assess changes in travel behaviour, sense of community, quality of life and health behaviours. Residents in a comparable area of Sydney that will not get a new separated bike path will act as a comparison group. At baseline a sub-set of residents who volunteer will also take a small GPS device with them for one week to assess travel behaviour. DISCUSSION: This research should contribute to the advancement in evaluation and appraisal methods for cycling projects