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

The Use of Flagella and Motility for Plant Colonization and Fitness by Different Strains of the Foodborne Pathogen Listeria monocytogenes

The role of flagella and motility in the attachment of the foodborne pathogen Listeria monocytogenes to various surfaces is mixed with some systems requiring flagella for an interaction and others needing only motility for cells to get to the surface. In nature this bacterium is a saprophyte and contaminated produce is an avenue for infection. Previous studies have documented the ability of this organism to attach to and colonize plant tissue. Motility mutants were generated in three wild type strains of L. monocytogenes by deleting either flaA, the gene encoding flagellin, or motAB, genes encoding part of the flagellar motor, and tested for both the ability to colonize sprouts and for the fitness of that colonization. The motAB mutants were not affected in the colonization of alfalfa, radish, and broccoli sprouts; however, some of the flaA mutants showed reduced colonization ability. The best colonizing wild type strain was reduced in colonization on all three sprout types as a result of a flaA deletion. A mutant in another background was only affected on alfalfa. The third, a poor alfalfa colonizer was not affected in colonization ability by any of the deletions. Fitness of colonization was measured in experiments of competition between mixtures of mutant and parent strains on sprouts. Here the flaA and motAB mutants of the three strain backgrounds were impaired in fitness of colonization of alfalfa and radish sprouts, and one strain background showed reduced fitness of both mutant types on broccoli sprouts. Together these data indicate a role for flagella for some strains to physically colonize some plants, while the fitness of that colonization is positively affected by motility in almost all cases

Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk

Consumption of ≤10% total energy from fat as saturated fatty acids (SFA) is recommended for cardiovascular disease risk reduction in the UK; however there is no clear guidance on the optimum replacement nutrient. Lipid-associated single-nucleotide polymorphisms (SNPs) have been shown to modify the lipid responses to dietary fat interventions. Hence, we performed a retrospective analysis in 120 participants from the Dietary Intervention and VAScular function (DIVAS) study to investigate whether lipoprotein lipase (LPL) and apolipoprotein E (APOE) SNPs modify the fasting lipid response to replacement of SFA with monounsaturated (MUFA) or n-6 polyunsaturated (PUFA) fatty acids. The DIVAS study was a randomized, single-blinded, parallel dietary intervention study performed in adults with a moderate cardiovascular risk who received one of three isoenergetic diets rich in SFA, MUFA or n-6 PUFA for 16 weeks. After the 16-week intervention, a significant diet-gene interaction was observed for changes in fasting total cholesterol (P = 0.001). For the APOE SNP rs1064725, only TT homozygotes showed a significant reduction in total cholesterol after the MUFA diet (n = 33; -0.71 ± 1.88 mmol/l) compared to the SFA (n = 38; 0.34 ± 0.55 mmol/l) or n-6 PUFA diets (n = 37; -0.08 ± 0.73 mmol/l) (P = 0.004). None of the interactions were statistically significant for the other SNPs. In summary, our findings have demonstrated a greater sensitivity of the APOE SNP rs1064725 to dietary fat composition, with a total cholesterol lowering effect observed following substitution of SFA with MUFA but not n-6 PUFA. Further large intervention studies incorporating prospective genotyping are required to confirm or refute our findings. The trial was registered at www.clinicaltrials.gov as NCT01478958

The bodily social self: a link between phenomenal and narrative selfhood

The Phenomenal Self (PS) is widely considered to be dependent on body representations, whereas the Narrative Self (NS) is generally thought to rely on abstract cognitive representations. The concept of the Bodily Social Self (BSS) might play an important role in explaining how the high level cognitive self-representations enabling the NS might emerge from the bodily basis of the PS. First, the phenomenal self (PS) and narrative self (NS), are briefly examined. Next, the BSS is defined and its potential for explaining aspects of social cognition is explored. The minimal requirements for a BSS are considered, before reviewing empirical evidence regarding the development of the BSS over the first year of life. Finally, evidence on the involvement of the body in social distinctions between self and other is reviewed to illustrate how the BSS is affected by both the bottom up effects of multisensory stimulation and the top down effects of social identification

Minimal Length Scale Scenarios for Quantum Gravity

We review the question of whether the fundamental laws of nature limit our ability to probe arbitrarily short distances. First, we examine what insights can be gained from thought experiments for probes of shortest distances, and summarize what can be learned from different approaches to a theory of quantum gravity. Then we discuss some models that have been developed to implement a minimal length scale in quantum mechanics and quantum field theory. These models have entered the literature as the generalized uncertainty principle or the modified dispersion relation, and have allowed the study of the effects of a minimal length scale in quantum mechanics, quantum electrodynamics, thermodynamics, black-hole physics and cosmology. Finally, we touch upon the question of ways to circumvent the manifestation of a minimal length scale in short-distance physics.Comment: Published version available at http://www.livingreviews.org/lrr-2013-

Pathways towards coexistence with large carnivores in production systems

Coexistence between livestock grazing and carnivores in rangelands is a major challenge in terms of sustainable agriculture, animal welfare, species conservation and ecosystem function. Many effective non-lethal tools exist to protect livestock from predation, yet their adoption remains limited. Using a social-ecological transformations framework, we present two qualitative models that depict transformative change in rangelands grazing. Developed through participatory processes with stakeholders from South Africa and the United States of America, the models articulate drivers of change and the essential pathways to transition from routine lethal management of carnivores towards mutually beneficial coexistence. The pathways define broad actions that incorporate multiple values in grazing systems including changes to livestock management practices, financial support, industry capacity building, research, improved governance and marketing initiatives. A key fnding is the new concept of ‘Predator Smart Farming’, a holistic and conscientious approach to agriculture, which increases the resilience of landscapes, animals (domesticated and wild) and rural livelihoods. Implementation of these multiple pathways would lead to a future system that ensures thriving agricultural communities, secure livelihoods, reduced violence toward animals, and landscapes that are productive and support species conservation and coexistence

A Multisite Preregistered Paradigmatic Test of the Ego-Depletion Effect

We conducted a preregistered multilaboratory project (k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result (d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect (d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation

Ruxolitinib is effective in patients with intermediate-1 risk myelofibrosis: a summary of recent evidence

Ruxolitinib is the only therapy with an approved indication for myelofibrosis (MF), a myeloproliferative neoplasm associated with progressive bone marrow fibrosis and extramedullary hematopoiesis. Although the pivotal phase 3 COMFORT studies included only patients with intermediate-2 or high-risk MF, the US indication includes all patients with intermediate- or high-risk disease. Data from recent nonrandomized studies confirm that the benefits of ruxolitinib established in the COMFORT studies in terms of spleen size reduction and symptom improvement also extend to patients with intermediate-1 risk MF, who tend to have less advanced disease than patients with higher-risk MF. Given the disease-modifying potential of ruxolitinib therapy, timely initiation of ruxolitinib therapy may not only improve patients’ current clinical status but also lead to better long-term outcomes. The decision of whether or when to initiate ruxolitinib treatment should be based on the expected benefit–risk ratio for each patient, specifically considering potential adverse effects

Ruxolitinib is effective in patients with intermediate-1 risk myelofibrosis: a summary of recent evidence

Ruxolitinib is the only therapy with an approved indication for myelofibrosis (MF), a myeloproliferative neoplasm associated with progressive bone marrow fibrosis and extramedullary hematopoiesis. Although the pivotal phase 3 COMFORT studies included only patients with intermediate-2 or high-risk MF, the US indication includes all patients with intermediate- or high-risk disease. Data from recent nonrandomized studies confirm that the benefits of ruxolitinib established in the COMFORT studies in terms of spleen size reduction and symptom improvement also extend to patients with intermediate-1 risk MF, who tend to have less advanced disease than patients with higher-risk MF. Given the disease-modifying potential of ruxolitinib therapy, timely initiation of ruxolitinib therapy may not only improve patients’ current clinical status but also lead to better long-term outcomes. The decision of whether or when to initiate ruxolitinib treatment should be based on the expected benefit–risk ratio for each patient, specifically considering potential adverse effects