Meta-Analysis of Genome-Wide Linkage Studies in Celiac Disease.

OBJECTIVE: A meta-analysis of genome-wide linkage studies allows us to summarize the extensive information available from family-based studies, as the field moves into genome-wide association studies. METHODS: Here we apply the genome scan meta-analysis (GSMA) method, a rank-based, model-free approach, to combine results across eight independent genome-wide linkages performed on celiac disease (CD), including 554 families with over 1,500 affected individuals. We also investigate the agreement between signals we identified from this meta-analysis of linkage studies and those identified from genome-wide association analysis using a hypergeometric distribution. RESULTS: Not surprisingly, the most significant result was obtained in the HLA region. Outside the HLA region, suggestive evidence for linkage was obtained at the telomeric region of chromosome 10 (10q26.12-qter; p = 0.00366), and on chromosome 8 (8q22.2-q24.21; p = 0.00491). Testing signals of association and linkage within bins showed no significant evidence for co-localization of results. CONCLUSION: This meta-analysis allowed us to pool the results from available genome-wide linkage studies and to identify novel regions potentially harboring predisposing genetic variation contributing to CD. This study also shows that linkage and association studies may identify different types of disease-predisposing variants

Ambulatory blood pressure monitoring during pregnancy: an Italian experience

Objective: To describe the impact of a collaborative Italian diagnostic pathway offering ambulatory blood pressure (BP) monitoring (ABPM) in High Risk Antenatal Clinic (HRAC) pregnant women. The study included 395 pregnant women evaluated at HRAC between 2012 and 2016, while analyzing demographic, clinical characteristics, and prescription of ABPM. Pregnant women were firstly seen when gestational age was 19.6 +/- 9.6 weeks. In at least one-third of cases, ABPM was followed by medical intervention aiming to modify the preexisting therapeutic treatment. Hypertension and overweight were the main reasons for performing ABPM. WCH: white-coat hypertension

Localisation of renin-angiotensin system (RAS) components in breast

Angiotensin II has mitogenic and angiogenic effects and its receptors are widespread, particularly in epithelial tissue. Tissue renin angiotensin systems (tRASs) may be a local source of angiotensin II that has specific paracrine functions. To investigate the presence of a tRAS in normal human breast and tumours. Immunocytochemistry, and quantitative RT–PCR was used to establish: (i) the presence and localisation of RAS components, (ii) the possibility of their involvement in cancer. (1) mRNA coding for angiotensinogen, prorenin, angiotensin converting enzyme (ACE), and both AT1 and AT2 receptors was demonstrated in normal and diseased breast tissues. (2) (pro)renin was identified in epithelial cells in both normal and diseased tissue, but in invasive carcinoma, its distribution was mostly confined to fibroblasts or could not be detected at all. (3) Angiotensin converting enzyme was shown in epithelial cells in both normal and malignant tissue. The results are consistent with the hypothesis that a tRAS is present in the breast, and is disrupted in invasive cancer

The effect of priority setting decisions for new cancer drugs on medical oncologists' practice in Ontario: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Health care policies, including drug-funding policies, influence physician practice. Funding policies are especially important in the area of cancer care since cancer is a leading cause of death that is responsible for a significant level of health care expenditures. Recognizing the rising cost of cancer therapies, Cancer Care Ontario (CCO) established a funding process to provide access to new, effective agents through a "New Drug Funding Program" (NDFP). The purpose of this study is to describe oncologists' perceptions of the impact of NDFP priority setting decisions on their practice.</p> <p>Methods</p> <p>This is a qualitative study involving semi-structured, in-depth interviews with 46 medical oncologists in Ontario. Oncologists were asked to describe the impact of CCO's NDFP drug funding decisions on their practice. Analysis of interview transcripts commenced with data collection.</p> <p>Results</p> <p>Our key finding is that many of the medical oncologists who participated in this study did not accept limits when policy decisions limit access to cancer drugs they feel would benefit their patients. Moreover, overcoming those limits had a significant impact on oncologists' practice in terms of how they spend their time and energy and their relationship with patients.</p> <p>Conclusion</p> <p>When priority setting decisions limit access to cancer medications, many oncologists' efforts to overcome those limits have a significant impact on their practice. Policy makers need to seriously consider the implications of their decisions on physicians, who may go to considerable effort to circumvent their policies in the name of patient advocacy.</p

Effective implementation of research into practice: an overview of systematic reviews of the health literature

<p>Abstract</p> <p>Background</p> <p>The gap between research findings and clinical practice is well documented and a range of interventions has been developed to increase the implementation of research into clinical practice.</p> <p>Findings</p> <p>A review of systematic reviews of the effectiveness of interventions designed to increase the use of research in clinical practice. A search for relevant systematic reviews was conducted of Medline and the Cochrane Database of Reviews 1998-2009. 13 systematic reviews containing 313 primary studies were included. Four strategy types are identified: audit and feedback; computerised decision support; opinion leaders; and multifaceted interventions. Nine of the reviews reported on multifaceted interventions. This review highlights the small effects of single interventions such as audit and feedback, computerised decision support and opinion leaders. Systematic reviews of multifaceted interventions claim an improvement in effectiveness over single interventions, with effect sizes ranging from small to moderate. This review found that a number of published systematic reviews fail to state whether the recommended practice change is based on the best available research evidence.</p> <p>Conclusions</p> <p>This overview of systematic reviews updates the body of knowledge relating to the effectiveness of key mechanisms for improving clinical practice and service development. Multifaceted interventions are more likely to improve practice than single interventions such as audit and feedback. This review identified a small literature focusing explicitly on getting research evidence into clinical practice. It emphasizes the importance of ensuring that primary studies and systematic reviews are precise about the extent to which the reported interventions focus on changing practice based on research evidence (as opposed to other information codified in guidelines and education materials).</p

Generalized alignment-based trace clustering of process behavior

Process mining techniques use event logs containing real process executions in order to mine, align and extend process models. The partition of an event log into trace variants facilitates the understanding and analysis of traces, so it is a common pre-processing in process mining environments. Trace clustering automates this partition; traditionally it has been applied without taking into consideration the availability of a process model. In this paper we extend our previous work on process model based trace clustering, by allowing cluster centroids to have a complex structure, that can range from a partial order, down to a subnet of the initial process model. This way, the new clustering framework presented in this paper is able to cluster together traces that are distant only due to concurrency or loop constructs in process models. We show the complexity analysis of the different instantiations of the trace clustering framework, and have implemented it in a prototype tool that has been tested on different datasets.Peer ReviewedPostprint (author's final draft

Types of psychosocial job demands and adverse events due to dental mismanagement: a cross sectional study

BACKGROUND: A harsh work environment including psychosocial job demands might cause adverse events due to medical mismanagement, but the association has not been explored. The purpose of the study was to investigate whether some types of psychosocial job demands are associated with adverse events due to dental mismanagement experienced by general dental practitioners. METHODS: A self-administered questionnaire was mailed to members of a local branch of the Japan dental association. A total of 261 dental practitioners responded anonymously (response rate 53%). Psychosocial job demands were measured by a Japanese version of the Copenhagen Psychosocial Questionnaire, which comprises five sub-scales: quantitative demands, cognitive demands, emotional demands, demands for hiding emotions, and sensorial demands. The outcome was defined according to whether the respondent's patients experienced one of the following adverse events due to dental mismanagement at least once during the previous one year: dropping of dental instrument or broken injection needle, soft tissue or nerve injury, accidental bleeding, loss of a tooth root into the maxillary sinus, and emphysema. Associations between each demand index and experience of adverse events were examined by logistic regression analyses adjusting for potential confounders. RESULTS: Emotional demands and sensorial demands were significantly associated with the experience of adverse events (odds ratio = 3.9 for each). Other than the indices, male gender, younger age, practice alone, many dental chairs (five or more), and many patients (30 or more per day) were the risks. Working hours per week and number of paramedical staff had no significant associations. CONCLUSION: Emotional and sensorial job demands are a potential target for the reduction of adverse events due to dental mismanagement

MicroRNA-277 Modulates the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats

Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder, has been recognized in older male fragile X premutation carriers and is uncoupled from fragile X syndrome. Using a Drosophila model of FXTAS, we previously showed that transcribed premutation repeats alone are sufficient to cause neurodegeneration. MiRNAs are sequence-specific regulators of post-transcriptional gene expression. To determine the role of miRNAs in rCGG repeat-mediated neurodegeneration, we profiled miRNA expression and identified selective miRNAs, including miR-277, that are altered specifically in Drosophila brains expressing rCGG repeats. We tested their genetic interactions with rCGG repeats and found that miR-277 can modulate rCGG repeat-mediated neurodegeneration. Furthermore, we identified Drep-2 and Vimar as functional targets of miR-277 that could modulate rCGG repeat-mediated neurodegeneration. Finally, we found that hnRNP A2/B1, an rCGG repeat-binding protein, can directly regulate the expression of miR-277. These results suggest that sequestration of specific rCGG repeat-binding proteins could lead to aberrant expression of selective miRNAs, which may modulate the pathogenesis of FXTAS by post-transcriptionally regulating the expression of specific mRNAs involved in FXTAS

Effect of mitratapide on body composition, body measurements and glucose tolerance in obese Beagles

The objective of this study was to confirm that weight loss after treatment with mitratapide (Yarvitan®) is loss of adipose tissue. Obese dogs were treated with the recommended treatment schedule of mitratapide. Dual-energy X-ray absorptiometry (DEXA) was done before and after the treatment schedule. Body weight, feed consumption and pelvic circumference were recorded and a glucose tolerance test was performed. Dual-energy X-ray absorptiometry measurements showed an impressive loss of fat tissue, corresponding to a mean loss of approximately 41.6% of the body fat mass recorded before treatment. After treatment with mitratapide, the mean body fat percentage had returned within the normal range. At the end of the study, the dogs had lost on average 14.2% of their body weight and 15.2% of their pelvic circumference compared to baseline. The results also suggest that losing weight with mitratapide might help to reverse insulin resistance