Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process

Breakage-Fusion-Bridge cycles in cancer arise when a broken segment of DNA is duplicated and an end from each copy joined together. This structure then 'unfolds' into a new piece of palindromic DNA. This is one mechanism responsible for the localised amplicons observed in cancer genome data. The process has parallels with paper folding sequences that arise when a piece of paper is folded several times and then unfolded. Here we adapt such methods to study the breakage-fusion-bridge structures in detail. We firstly consider discrete representations of this space with 2-d trees to demonstrate that there are 2^(n(n-1)/2) qualitatively distinct evolutions involving n breakage-fusion-bridge cycles. Secondly we consider the stochastic nature of the fold positions, to determine evolution likelihoods, and also describe how amplicons become localised. Finally we highlight these methods by inferring the evolution of breakage-fusion-bridge cycles with data from primary tissue cancer samples

The INCLUDE study: INtegrating and improving Care for patients with infLammatory rheUmatological DisordErs in the community; identifying multimorbidity: Protocol for a pilot randomized controlled trial.

Background: Patients with inflammatory rheumatic conditions such as rheumatoid arthritis, polymyalgia rheumatica and ankylosing spondylitis are at increased risk of common comorbidities such as cardiovascular disease, osteoporosis and anxiety and depression which lead to increased morbidity and mortality. These associated morbidities are often un-recognized and under-treated. While patients with other long-term conditions such as diabetes are invited for routine reviews in primary care, which may include identification and management of co-morbidities, at present this does not occur for patients with inflammatory conditions, and thus, opportunities to diagnose and optimally manage these comorbidities are missed. Objective: To evaluate the feasibility and acceptability of a nurse-led integrated care review (the INtegrating and improving Care for patients with infLammatory rheUmatological DisordErs in the community (INCLUDE) review) for people with inflammatory rheumatological conditions in primary care. Design: A pilot cluster randomized controlled trial will be undertaken to test the feasibility and acceptability of a nurse-led integrated primary care review for identification, assessment and initial management of common comorbidities including cardiovascular disease, osteoporosis and anxiety and depression. A process evaluation will be undertaken using a mixed methods approach including participant self-reported questionnaires, a medical record review, an INCLUDE EMIS template, intervention fidelity checking using audio-recordings of the INCLUDE review consultation and qualitative interviews with patient participants, study nurses and study general practitioners (GPs). Discussion: Success of the pilot study will be measured against the engagement, recruitment and study retention rates of both general practices and participants. Acceptability of the INCLUDE review to patients and practitioners and treatment fidelity will be explored using a parallel process evaluation. Trial Registration: ISRCTN12765345

Memory consolidation in the cerebellar cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA(A) agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage

Religiousness and preoperative anxiety: a correlational study

<p>Abstract</p> <p>Background</p> <p>Major life changes are among factors that cause anxiety, and one of these changes is surgery. Emotional reactions to surgery have specific effects on the intensity and velocity as well as the process of physical disease. In addition, they can cause delay in patients recovery. This study is aimed at determining the relationship between religious beliefs and preoperative anxiety.</p> <p>Methods</p> <p>This survey is a correlational study to assess the relationship between religious beliefs and preoperative anxiety of patients undergoing abdominal, orthopaedic, and gynaecologic surgery in educational hospitals. We used the convenience sampling method. The data collection instruments included a questionnaire containing the Spielberger State-Trait Anxiety Inventory (STAI), and another questionnaire formulated by the researcher with queries on religious beliefs and demographic characteristics as well as disease-related information. Analysis of the data was carried out with SPSS software using descriptive and inferential statistics. Results were arranged in three tables.</p> <p>Results</p> <p>The findings showed that almost all the subjects had high level of religiosity and moderate level of anxiety. In addition, there was an inverse relationship between religiosity and intensity of anxiety, though this was not statistically significant.</p> <p>Conclusion</p> <p>The results of this study can be used as evidence for presenting religious counselling and spiritual interventions for individuals undergoing stress. Finally, based on the results of this study, the researcher suggested some recommendations for applying results and conducting further research.</p

Web-based alcohol intervention:study of systematic attrition of heavy drinkers

Background: Web-based alcohol interventions are a promising way to reduce alcohol consumption because of their anonymity and the possibility of reaching a high numbers of individuals including heavy drinkers. However, Web-based interventions are often characterized by high rates of attrition. To date, very few studies have investigated whether individuals with higher alcohol consumption show higher attrition rates in Web-based alcohol interventions as compared with individuals with lower alcohol consumption. Objectives: The aim of this study was to examine the attrition rate and predictors of attrition in a Web-based intervention study on alcohol consumption. Methods: The analysis of the predictors of attrition rate was performed on data collected in a Web-based randomized control trial. Data collection took place at the University of Konstanz, Germany. A total of 898 people, which consisted of 46.8% males (420/898) and 53.2% females (478/898) with a mean age of 23.57 years (SD 5.19), initially volunteered to participate in a Web-based intervention study to reduce alcohol consumption. Out of the sample, 86.9% (781/898) were students. Participants were classified as non-completers (439/898, 48.9%) if they did not complete the Web-based intervention. Potential predictors of attrition were self-reported: alcohol consumption in the last seven days, per week, from Monday to Thursday, on weekends, excessive drinking behavior measured with the Alcohol Use Disorder Identification Test (AUDIT), and drinking motives measured by the Drinking Motive Questionnaire (DMQ-R SF). Results: Significant differences between completers and non-completers emerged regarding alcohol consumption in the last seven days (B=-.02, P=.05, 95% CI [0.97-1.00]), on weekends (B=-.05, P=.003, 95% CI [0.92-0.98]), the AUDIT (B=-.06, P=.007, 95% CI [0.90-0.98], and the status as a student (B=.72, P=.001, 95% CI [1.35-3.11]). Most importantly, non-completers had a significantly higher alcohol consumption compared with completers. Conclusions: Hazardous alcohol consumption appears to be a key factor of the dropout rate in a Web-based alcohol intervention study. Thus, it is important to develop strategies to keep participants who are at high risk in Web-based interventions

A pilot randomised controlled trial of personalised care for depressed patients with symptomatic coronary heart disease in South London general practices: the UPBEAT-UK RCT protocol and recruitment.

ABSTRACT: Background: Community studies reveal people with coronary heart disease (CHD) are twice as likely to be depressed as the general population and that this co-morbidity negatively affects the course and outcome of both conditions. There is evidence for the efficacy of collaborative care and case management for depression treatment, and whilst NICE guidelines recommend these approaches only where depression has not responded to psychological, pharmacological, or combined treatments, these care approaches may be particularly relevant to the needs of people with CHD and depression in the earlier stages of stepped care in primary care settings. Methods: This pilot randomised controlled trial will evaluate whether a simple intervention involving a personalised care plan, elements of case management and regular telephone review is a feasible and acceptable intervention that leads to better mental and physical health outcomes for these patients. The comparator group will be usual general practitioner (GP) care. 81 participants have been recruited from CHD registers of 15 South London general practices. Eligible participants have probable major depression identified by a score of ≥8 on the Hospital Anxiety and Depression Scale depression subscale (HADS-D) together with symptomatic CHD identified using the Modified Rose Angina Questionnaire. Consenting participants are randomly allocated to usual care or the personalised care intervention which involves a comprehensive assessment of each participant’s physical and mental health needs which are documented in a care plan, followed by regular telephone reviews by the case manager over a 6-month period. At each review, the intervention participant’s mood, function and identified problems are reviewed and the case manager uses evidence based behaviour change techniques to facilitate achievement of goals specified by the patient with the aim of increasing the patient’s self efficacy to solve their problems. Depressive symptoms measured by HADS score will be collected at baseline and 1, 6- and 12 months post randomisation. Other outcomes include CHD symptoms, quality of life, wellbeing and health service utilisation. Discussion: This practical and patient-focused intervention is potentially an effective and accessible approach to the health and social care needs of people with depression and CHD in primary care. Trial registration: ISRCTN21615909

Be SMART:examining the experience of implementing the NHS Health Check in UK primary care

Background: The NHS Health Check was designed by UK Department of Health to address increased prevalence of cardiovascular disease by identifying risk levels and facilitating behaviour change. It constituted biomedical testing, personalised advice and lifestyle support. The objective of the study was to explore Health Care Professionals' (HCPs) and patients' experiences of delivering and receiving the NHS Health Check in an inner-city region of England. Methods: Patients and HCPs in primary care were interviewed using semi-structured schedules. Data were analysed using Thematic Analysis. Results: Four themes were identified. Firstly, Health Check as a test of 'roadworthiness' for people. The roadworthiness metaphor resonated with some patients but it signified a passive stance toward illness. Some patients described the check as useful in the theme, Health check as revelatory. HCPs found visual aids demonstrating levels of salt/fat/sugar in everyday foods and a 'traffic light' tape measure helpful in communicating such 'revelations' with patients. Being SMART and following the protocolrevealed that few HCPs used SMART goals and few patients spoke of them. HCPs require training to understand their rationale compared with traditional advice-giving. The need for further follow-up revealed disparity in follow-ups and patients were not systematically monitored over time. Conclusions: HCPs' training needs to include the use and evidence of the effectiveness of SMART goals in changing health behaviours. The significance of fidelity to protocol needs to be communicated to HCPs and commissioners to ensure consistency. Monitoring and measurement of follow-up, e.g., tracking of referrals, need to be resourced to provide evidence of the success of the NHS Health Check in terms of healthier lifestyles and reduced CVD risk

Predicting violent infractions in a Swiss state penitentiary: A replication study of the PCL-R in a population of sex and violent offenders

BACKGROUND: Research conducted with forensic psychiatric patients found moderate correlations between violence in institutions and psychopathy. It is unclear though, whether the PCL-R is an accurate instrument for predicting aggressive behavior in prisons. Results seem to indicate that the instrument is better suited for predicting verbal rather than physical aggression of prison inmates. METHODS: PCL-R scores were assessed for a sample of 113 imprisoned sex and violent offenders in Switzerland. Logistic regression analyses were used to estimate physical and verbal aggression as a function of the PCL-R sum score. Additionally, stratified analyses were conducted for Factor 1 and 2. Infractions were analyzed as to their motives and consequences. RESULTS: The mean score of the PCL-R was 12 points. Neither the relationship between physical aggression and the sum score of the PCL-R, nor the relationship between physical aggression and either of the two factors of the PCL-R were significant. Both the sum score and Factor 1 predicted the occurrence of verbal aggression (AUC=0.70 and 0.69), while Factor 2 did not. CONCLUSION: Possible explanations are discussed for the weak relationship between PCL-R scores and physically aggressive behavior during imprisonment. Some authors have discussed whether the low base rate of violent infractions can be considered an explanation for the non-significant relation between PCL-R-score and violence. The base rate in this study, however, with 27%, was not low. It is proposed that the distinction between reactive and instrumental motives of institutional violence must be considered when examining the usefulness of the PCL-R in predicting in-prison physical aggressive behavior