Chemical generation and modification of peptides containing multiple dehydroalanines

Chemical formation of dehydroalanine has been widely used for the post-translational modification of protein and peptides, however methods to incorporate multiple dehydroalanine residues into a single peptide have not been defined. We report the use of methyl 2,5-dibromovalerate which can be used to cleanly carry out this transformation

Cloud adjustment and its role in CO 2 radiative forcing and climate sensitivity: a review

Understanding the role of clouds in climate change remains a considerable challenge. Traditionally, this challenge has been framed in terms of understanding cloud feedback. However, recent work suggests that under increasing levels of atmospheric carbon dioxide, clouds not only amplify or dampen climate change through global feedback processes, but also through rapid (days to weeks) tropospheric temperature and land surface adjustments. In this article, we use the Met Office Hadley Centre climate model HadGSM1 to review these recent developments and assess their impact on radiative forcing and equilibrium climate sensitivity. We estimate that cloud adjustment contributes ~0.8 K to the 4.4 K equilibrium climate sensitivity of this particular model. We discuss the methods used to evaluate cloud adjustments, highlight the mechanisms and processes involved and identify low level cloudiness as a key cloud type. Looking forward, we discuss the outstanding issues, such as the application to transient forcing scenarios. We suggest that the upcoming CMIP5 multi-model database will allow a comprehensive assessment of the significance of cloud adjustments in fully coupled atmosphere-ocean-general-circulation models for the first time, and that future research should exploit this opportunity to understand cloud adjustments/feedbacks in non-idealised transient climate change scenarios

Fasting leptin is a metabolic determinant of food reward in overweight and obese individuals during chronic aerobic exercise training

Changes in food reward have been implicated in exercise-induced compensatory eating behaviour. However, the underlying mechanisms of food reward, and the physiological correlates of exercise-induced changes in food reward, are unknown. Methods. Forty-six overweight and obese individuals completed 12 weeks of aerobic exercise. Body composition, food intake, and fasting metabolic-related hormones were measured at baseline, week six, and postintervention. On separate days, the reward value of high-and-low-fat food (explicit liking and implicit wanting) was also assessed at baseline, week six, and postintervention. Results. Following the intervention, FM, FFM, and V O 2 peak improved significantly, while fasting leptin decreased. However, food intake or reward did not change significantly. Cross-sectional analyses indicated that FM (P = 0.022) and FFM (P = 0.046) were associated with explicit liking for high-fat food, but implicit wanting was associated with FM only (P = 0.005). Fasting leptin was associated with liking (P = 0.023) and wanting (P = 0.021) for high-fat food. Furthermore, a greater exercise-induced decline in fasting leptin was associated with increased liking (P = 0.018). Conclusion. These data indicate that food reward has a number of physiological correlates. In particular, fasting leptin appears to play an active role in mediating food reward during exercise-induced weight loss. © 2014 Mark Hopkins et al

Blood pressure variability and cardiovascular risk in the PROspective study of pravastatin in the elderly at risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects

The development of a theory-based intervention to promote appropriate disclosure of a diagnosis of dementia

Background: The development and description of interventions to change professional practice are often limited by the lack of an explicit theoretical and empirical basis. We set out to develop an intervention to promote appropriate disclosure of a diagnosis of dementia based on theoretical and empirical work. Methods: We identified three key disclosure behaviours: finding out what the patient already knows or suspects about their diagnosis; using the actual words 'dementia' or 'Alzheimer's disease' when talking to the patient; and exploring what the diagnosis means to the patient. We conducted a questionnaire survey of older peoples' mental health teams (MHTs) based upon theoretical constructs from the Theory of Planned Behaviour (TPB) and Social Cognitive Theory (SCT) and used the findings to identify factors that predicted mental health professionals' intentions to perform each behaviour. We selected behaviour change techniques likely to alter these factors. Results: The change techniques selected were: persuasive communication to target subjective norm; behavioural modelling and graded tasks to target self-efficacy; persuasive communication to target attitude towards the use of explicit terminology when talking to the patient; and behavioural modelling by MHTs to target perceived behavioural control for finding out what the patient already knows or suspects and exploring what the diagnosis means to the patient. We operationalised these behaviour change techniques using an interactive 'pen and paper' intervention designed to increase intentions to perform the three target behaviours. Conclusion : It is feasible to develop an intervention to change professional behaviour based upon theoretical models, empirical data and evidence based behaviour change techniques. The next step is to evaluate the effect of such an intervention on behavioural intention. We argue that this approach to development and reporting of interventions will contribute to the science of implementation by providing replicable interventions that illuminate the principles and processes underlying change.This project is funded by UK Medical Research Council, Grant reference number G0300999. Jeremy Grimshaw holds a Canada Research Chair in Health Knowledge Transfer and Uptake. Jill Francis is funded by the Chief Scientist Office of the Scottish Government Health Directorate. The views expressed in this study are those of the authors

The Effects of Two Planning Interventions on the Oral Health Behavior of Iranian Adolescents: A Cluster Randomized Controlled Trial.

PURPOSE: The aim of this study was to investigate the effectiveness of a planning intervention (specifying when, where, and how to act) and an implementation intention intervention (specifying the same in the format of an if-then plan) in increasing self-reported brushing in adolescents. METHODS: The study adopted a cluster randomized controlled trial design, and 1158 students in 48 schools were randomized to planning, implementation intention, or active control conditions. After baseline assessment, all participants received a leaflet containing information and recommendations on oral health and instructions on correct brushing behavior. After reading the leaflets, they were provided with a toothbrush and toothpaste plus a calendar in which to record their brushing. Participants in the planning condition and in the implementation intention condition also received instructions to form specific plans regarding brushing behavior. Self-reported brushing, perceived behavioral control, self-monitoring, intention, frequency of planning, oral health-related quality of life, and dental plaque and periodontal status were measured 1 and 6 months later. RESULTS: Both intervention conditions showed a significant improvement in the frequency of self-reported brushing, self-monitoring, frequency of planning, intention, perceived behavioral control, plaque index, periodontal health, and oral health-related quality of life compared to the control condition at both follow-ups. Comparing the two intervention conditions revealed that adolescents who received the implementation intention intervention had significantly greater improvement in the frequency of self-reported brushing, intention, frequency of planning, and periodontal health than those in planning condition. CONCLUSIONS: Taken together, the findings suggest that forming implementation intentions as well as planning has the potential to increase dental self-reported brushing rates in adolescents, but that forming implementation intentions has the strongest impact on dental hygiene behavior and is, therefore, recommended. TRIAL REGISTRATION NUMBER: The trial was registered with the ClinicalTrials.gov database (NCT02066987) https://www.clinicaltrials.gov/ct2/show/NCT02066987

A genome-wide association study to identify genetic markers associated with endometrial cancer grade

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Do self-reported intentions predict clinicians behaviour: a systematic review.

Background: Implementation research is the scientific study of methods to promote the systematic uptake of clinical research findings into routine clinical practice. Several interventions have been shown to be effective in changing health care professionals' behaviour, but heterogeneity within interventions, targeted behaviours, and study settings make generalisation difficult. Therefore, it is necessary to identify the 'active ingredients' in professional behaviour change strategies. Theories of human behaviour that feature an individual's "intention" to do something as the most immediate predictor of their behaviour have proved to be useful in non-clinical populations. As clinical practice is a form of human behaviour such theories may offer a basis for developing a scientific rationale for the choice of intervention to use in the implementation of new practice. The aim of this review was to explore the relationship between intention and behaviour in clinicians and how this compares to the intention-behaviour relationship in studies of non-clinicians. Methods: We searched: PsycINFO, MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Science/Social science citation index, Current contents (social & behavioural med/clinical med), ISI conference proceedings, and Index to Theses. The reference lists of all included papers were checked manually. Studies were eligible for inclusion if they had: examined a clinical behaviour within a clinical context, included measures of both intention and behaviour, measured behaviour after intention, and explored this relationship quantitatively. All titles and abstracts retrieved by electronic searching were screened independently by two reviewers, with disagreements resolved by discussion. Discussion: Ten studies were found that examined the relationship between intention and clinical behaviours in 1623 health professionals. The proportion of variance in behaviour explained by intention was of a similar magnitude to that found in the literature relating to non-health professionals. This was more consistently the case for studies in which intention-behaviour correspondence was good and behaviour was self-reported. Though firm conclusions are limited by a smaller literature, our findings are consistent with that of the non-health professional literature. This review, viewed in the context of the larger populations of studies, provides encouragement for the contention that there is a predictable relationship between the intentions of a health professional and their subsequent behaviour. However, there remain significant methodological challenges

Functional diversity of marine ecosystems after the Late Permian mass extinction event

Article can be accessed from http://www.nature.com/ngeo/journal/v7/n3/full/ngeo2079.htmlThe Late Permian mass extinction event was the most severe such crisis of the past 500 million years and occurred during an episode of global warming. It is assumed to have had significant ecological impact, but its effects on marine ecosystem functioning are unknown and the patterns of marine recovery are debated. We analysed the fossil occurrences of all known Permian-Triassic benthic marine genera and assigned each to a functional group based on their inferred life habit. We show that despite the selective extinction of 62-74% of marine genera there was no significant loss of functional diversity at the global scale, and only one novel mode of life originated in the extinction aftermath. Early Triassic marine ecosystems were not as ecologically depauperate as widely assumed, which explains the absence of a Cambrian-style Triassic radiation in higher taxa. Functional diversity was, however, significantly reduced in particular regions and habitats, such as tropical reefs, and at these scales recovery varied spatially and temporally, probably driven by migration of surviving groups. Marine ecosystems did not return to their pre-extinction state, however, and radiation of previously subordinate groups such as motile, epifaunal grazers led to greater functional evenness by the Middle Triassic

The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies