Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

Atrial fibrillation in a primary care practice: prevalence and management

BACKGROUND: Atrial fibrillation is a common serious cardiac arrhythmia. Knowing the prevalence of atrial fibrillation and documentation of medical management are important in the provision of primary care. This study sought to determine the prevalence of atrial fibrillation in a primary care population and to identify and quantify the treatments being used for stroke prevention in this group of patients. METHODS: A prevalence study through chart audit was conducted in the family medicine practice at the Sunnybrook campus of the Sunnybrook and Women's College Health Sciences Centre. The main outcome measures were the prevalence of atrial fibrillation in our primary care practice and the use of warfarin for stroke prevention in this population. RESULTS: 261 patients in our practice have atrial fibrillation. The overall prevalence in our family practice unit is 3.9%. When considering patients aged 60 and over, the prevalence rises to 12.2%. 204 of our patients with atrial fibrillation (78.2%) are currently being treated with warfarin. Another 21 patients were previously treated and discontinued for a number of reasons. Of the 57 patients not currently treated with warfarin, 44 are treated with ASA, 2 with ticlopidine, and 11 are receiving no preventative treatment. CONCLUSIONS: The prevalence of atrial fibrillation in our practice is higher than the range of prevalence reported in the general literature. However, our coverage with warfarin treatment exceeds previous reports in the literature

Designing Adverse Event Forms for Real-World Reporting: Participatory Research in Uganda

The wide-scale roll-out of artemisinin combination therapies (ACTs) for the treatment of malaria should be accompanied by continued surveillance of their safety. Post-marketing pharmacovigilance (PV) relies on adverse event (AE) reporting by clinicians, but as a large proportion of treatments are provided by non-clinicians in low-resource settings, the effectiveness of such PV systems is limited. To facilitate reporting, AE forms should be easily completed; however, most are challenging for lower-level health workers and non-clinicians to complete. Through participatory research, we sought to develop user-friendly AE report forms to capture information on events associated with ACTs

(Re)Moralizing the suicide debate

Contemporary approaches to the study of suicide tend to examine suicide as a medical or public health problem rather than a moral problem, avoiding the kinds of judgements that have historically characterised discussions of the phenomenon. But morality entails more than judgement about action or behaviour, and our understanding of suicide can be enhanced by attending to its cultural, social, and linguistic connotations. In this work, I offer a theoretical reconstruction of suicide as a form of moral experience that delineates five distinct, yet interrelated domains of understanding – the temporal, the relational, the existential, the ontological, and the linguistic. Attention to each of these domains, I argue, not only enriches our understanding of the moral realm, but provides a heuristic for examining the moral traditions and practices which constitute contemporary understandings of suicide. Keywords: Suicide; philosophy; social values; humanitie

Does General Parenting Context Modify Adolescents' Appraisals and Coping with a Situation of Parental Regulation? The Case of Autonomy-Supportive Parenting

Theory and research suggest that adolescents differ in their appraisals and coping reactions in response to parental regulation. Less is known, however, about factors that determine these differences in adolescents’ responses. In this study, we examined whether adolescents' appraisals and coping reactions depend upon parents’ situation-specific autonomy-supportive or controlling communication style (i.e., the situation) in interaction with adolescents’ past experiences with general autonomy-supportive parenting (i.e., the parenting context). Whereas in Study 1 (N = 176) adolescents’ perceived general autonomy-supportive parenting context was assessed at one point in time, in Study 2 (N = 126) it was assessed multiple times across a 6-year period, allowing for an estimation of trajectories of perceived autonomy-supportive parenting context. In each study, adolescents read a vignette-based scenario depicting a situation of maternal regulation (i.e., a request to study more), which was communicated in either an autonomy-supportive or a controlling way. Following this scenario, they reported upon their appraisals and their anticipated coping reactions. Results of each study indicated that both the autonomy-supportive (relative to the controlling) situation and the perceived autonomy-supportive parenting context generally related to more positive appraisals (i.e., more autonomy need satisfaction, less autonomy need frustration), as well as to more constructive coping responses (i.e., less oppositional defiance and submission, more negotiation and accommodation). In addition, situation × context interactions were found, whereby adolescents growing up in a more autonomy-supportive context seemed to derive greater benefits from the exposure to an autonomy-supportive situation and reacted more constructively to a controlling situation

Brain architecture in the terrestrial hermit crab Coenobita clypeatus (Anomura, Coenobitidae), a crustacean with a good aerial sense of smell

<p>Abstract</p> <p>Background</p> <p>During the evolutionary radiation of Crustacea, several lineages in this taxon convergently succeeded in meeting the physiological challenges connected to establishing a fully terrestrial life style. These physiological adaptations include the need for sensory organs of terrestrial species to function in air rather than in water. Previous behavioral and neuroethological studies have provided solid evidence that the land hermit crabs (Coenobitidae, Anomura) are a group of crustaceans that have evolved a good sense of aerial olfaction during the conquest of land. We wanted to study the central olfactory processing areas in the brains of these organisms and to that end analyzed the brain of <it>Coenobita clypeatus </it>(Herbst, 1791; Anomura, Coenobitidae), a fully terrestrial tropical hermit crab, by immunohistochemistry against synaptic proteins, serotonin, FMRFamide-related peptides, and glutamine synthetase.</p> <p>Results</p> <p>The primary olfactory centers in this species dominate the brain and are composed of many elongate olfactory glomeruli. The secondary olfactory centers that receive an input from olfactory projection neurons are almost equally large as the olfactory lobes and are organized into parallel neuropil lamellae. The architecture of the optic neuropils and those areas associated with antenna two suggest that <it>C. clypeatus </it>has visual and mechanosensory skills that are comparable to those of marine Crustacea.</p> <p>Conclusion</p> <p>In parallel to previous behavioral findings of a good sense of aerial olfaction in C. clypeatus, our results indicate that in fact their central olfactory pathway is most prominent, indicating that olfaction is a major sensory modality that these brains process. Interestingly, the secondary olfactory neuropils of insects, the mushroom bodies, also display a layered structure (vertical and medial lobes), superficially similar to the lamellae in the secondary olfactory centers of <it>C. clypeatus</it>. More detailed analyses with additional markers will be necessary to explore the question if these similarities have evolved convergently with the establishment of superb aerial olfactory abilities or if this design goes back to a shared principle in the common ancestor of Crustacea and Hexapoda.</p

H3 Lysine 4 Is Acetylated at Active Gene Promoters and Is Regulated by H3 Lysine 4 Methylation

Methylation of histone H3 lysine 4 (H3K4me) is an evolutionarily conserved modification whose role in the regulation of gene expression has been extensively studied. In contrast, the function of H3K4 acetylation (H3K4ac) has received little attention because of a lack of tools to separate its function from that of H3K4me. Here we show that, in addition to being methylated, H3K4 is also acetylated in budding yeast. Genetic studies reveal that the histone acetyltransferases (HATs) Gcn5 and Rtt109 contribute to H3K4 acetylation in vivo. Whilst removal of H3K4ac from euchromatin mainly requires the histone deacetylase (HDAC) Hst1, Sir2 is needed for H3K4 deacetylation in heterochomatin. Using genome-wide chromatin immunoprecipitation (ChIP), we show that H3K4ac is enriched at promoters of actively transcribed genes and located just upstream of H3K4 tri-methylation (H3K4me3), a pattern that has been conserved in human cells. We find that the Set1-containing complex (COMPASS), which promotes H3K4me2 and -me3, also serves to limit the abundance of H3K4ac at gene promoters. In addition, we identify a group of genes that have high levels of H3K4ac in their promoters and are inadequately expressed in H3-K4R, but not in set1Δ mutant strains, suggesting that H3K4ac plays a positive role in transcription. Our results reveal a novel regulatory feature of promoter-proximal chromatin, involving mutually exclusive histone modifications of the same histone residue (H3K4ac and H3K4me)