Contamination in complex healthcare trials:the falls in care homes (FinCH) study experience

BACKGROUND: Trials are at risk of contamination bias which can occur when participants in the control group are inadvertently exposed to the intervention. This is a particular risk in rehabilitation studies where it is easy for trial interventions to be either intentionally or inadvertently adopted in control settings. The Falls in Care Homes (FinCH) trial is used in this paper as an example of a large randomised controlled trial of a complex intervention to explore the potential risks of contamination bias. We outline the FinCH trial design, present the potential risks from contamination bias, and the strategies used in the design of the trial to minimise or mitigate against this. The FinCH trial was a multi-centre randomised controlled trial, with embedded process evaluation, which evaluated whether systematic training in the use of the Guide to Action Tool for Care Homes reduced falls in care home residents. Data were collected from a number of sources to explore contamination in the FinCH trial. Where specific procedures were adopted to reduce risk of, or mitigate against, contamination, this was recorded. Data were collected from study e-mails, meetings with clinicians, research assistant and clinician network communications, and an embedded process evaluation in six intervention care homes. During the FinCH trial, there were six new falls prevention initiatives implemented outside the study which could have contaminated our intervention and findings. Methods used to minimise contamination were: cluster randomisation at the level of care home; engagement with the clinical community to highlight the risks of early adoption; establishing local collaborators in each site familiar with the local context; signing agreements with NHS falls specialists that they would maintain confidentiality regarding details of the intervention; opening additional research sites; and by raising awareness about the importance of contamination in research among participants. CONCLUSION: Complex rehabilitation trials are at risk of contamination bias. The potential for contamination bias in studies can be minimized by strengthening collaboration and dialogue with the clinical community. Researchers should recognise that clinicians may contaminate a study through lack of research expertise

Analyzing the HCP Datasets using GPUs: The Anatomy of a Science Engagement

This paper documents the experience improving the performance of a data processing workflow for analysis of the Human Connectome Project's HCP900 data set. It describes how network and compute bottlenecks were discovered and resolved during the course of a science engagement. A series of computational enhancements to the stock FSL BedpostX workflow are described. These enhancements migrated the workflow from a slow serial execution of computations resulting from Slurm scheduler incompatibilities to eventual execution on GPU resources, going from a 21-day execution on a single CPU core to a 2 hour execution on a GPU. This workflow contributed a vital use-case to the build-out of the campus compute cluster with additional GPUs and resulted in enhancements to network bandwidth. It also shares insights on potential improvements to distribution of scientific software to avoid stagnation in site-specific deployment decisions. The discussion highlights the advantages of open licenses and popular code collaboration sites like GitHub.com in feeding contributions upstream.Comment: 6 pages, 3 figures, PEARC '18: Practice and Experience in Advanced Research Computing, July 22--26, 2018, Pittsburgh, PA, US

The dynamics of individual nucleosomes controls the chromatin condensation pathway: direct AFM visualization of variant chromatin

Chromatin organization and dynamics is studied in this work at scales ranging from single nucleosome to nucleosomal array by using a unique combination of biochemical assays, single molecule imaging technique and numerical modeling. We demonstrate that a subtle modification in the nucleosome structure induced by the histone variant H2A.Bbd drastically modifies the higher order organization of the nucleosomal arrays. Importantly, as directly visualized by AFM, conventional H2A nucleosomal arrays exhibit specific local organization, in contrast to H2A.Bbd arrays, which show "beads on a string" structure. The combination of systematic image analysis and theoretical modeling allows a quantitative description relating the observed gross structural changes of the arrays to their local organization. Our results strongly suggest that higher-order organization of H1-free nucleosomal arrays is mainly determined by the fluctuation properties of individual nucleosomes. Moreover, numerical simulations suggest the existence of attractive interactions between nucleosomes to provide the degree of compaction observed for conventional chromatin fibers.Comment: Biophys J. in pres

From planning to deployment - insights into installing publicly-accessible journey EV charging infrastructure

Deploying publicly accessible electric vehicle charging infrastructure involves engaging with multiple stakeholders from various organisations to ensure successful project delivery. When installing a fleet of charging points across a wide area, the number of stakeholders increases often resulting in a disjointed or non-standardised experience for EV infrastructure developers. Based on real-world learnings, this paper suggests several improvements that could be implemented by distribution network operators that would help streamline infrastructure deployment and help accelerate the uptake of zero-carbon transport solutions

Autistic Traits Moderate the Impact of Reward Learning on Social Behaviour

A deficit in empathy has been suggested to underlie social behavioural atypicalities in autism. A parallel theoretical account proposes that reduced social motivation (i.e., low responsivity to social rewards) can account for the said atypicalities. Recent evidence suggests that autistic traits modulate the link between reward and proxy metrics related to empathy. Using an evaluative conditioning paradigm to associate high and low rewards with faces, a previous study has shown that individuals high in autistic traits show reduced spontaneous facial mimicry of faces associated with high vs. low reward. This observation raises the possibility that autistic traits modulate the magnitude of evaluative conditioning. To test this, we investigated (a) if autistic traits could modulate the ability to implicitly associate a reward value to a social stimulus (reward learning/conditioning, using the Implicit Association Task, IAT); (b) if the learned association could modulate participants' prosocial behaviour (i.e., social reciprocity, measured using the cyberball task); (c) if the strength of this modulation was influenced by autistic traits. In 43 neurotypical participants, we found that autistic traits moderated the relationship of social reward learning on prosocial behaviour but not reward learning itself. This evidence suggests that while autistic traits do not directly influence social reward learning, they modulate the relationship of social rewards with prosocial behaviour

Deforestation, leakage and avoided deforestation policies: a spatial analysis

This paper analyses the impact of several avoided deforestation policies within a patchy forested landscape. Central is the idea that deforestation choices in one area influence deforestation decisions in nearby patches. We explore the interplay between forest landscapes comprising heterogeneous patches, localised spatial displacement, and avoided deforestation policies. Avoided deforestation policies at a landscape level are respectively: two Payments for Environmental Services (PES) policies, one focused on deforestation hotspots, the second being equally available to all agents; a conservation area; and, an agglomeration bonus. We demonstrate how the "best" policy, in terms of reduced leakage, depends on landscape heterogeneity. Agglomeration bonuses are shown to be more effective where there is less landscape heterogeneity, whilst conservation areas are most effective where there is more spatial heterogeneity

The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains

The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain. Here, we show the DNA-binding domain is required for Saccharomyces cerevisiae Chd1 to bind and remodel nucleosomes. The crystal structure of this domain reveals the presence of structural homology to SANT and SLIDE domains previously identified in ISWI remodelling enzymes. The presence of these domains in ISWI and Chd1 chromatin-remodelling enzymes may provide a means of efficiently harnessing the action of the Snf2-related ATPase domain for the purpose of nucleosome spacing and provide an explanation for partial redundancy between these proteins. Site directed mutagenesis was used to identify residues important for DNA binding and generate a model describing the interaction of this domain with DNA. Through inclusion of Chd1 sequences in homology searches SLIDE domains were identified in CHD6–9 proteins. Point mutations to conserved amino acids within the human CHD7 SLIDE domain have been identified in patients with CHARGE syndrome

Reduced reward-related neural response to mimicry in individuals with autism

Mimicry is a facilitator of social bonds in humans, from infancy. This facilitation is made possible through changing the rewardvalue of social stimuli; for example, we like and affiliate more with people who mimic us. Autism spectrum disorders (ASD) aremarked by difficulties in forming social bonds. In this study, we investigate whether the reward-related neural response to beingmimicked is altered in individuals with ASD, using a simple conditioning paradigm. Multiple studies in humans and nonhuman pri-mates have established a crucial role for the ventral striatal (VS) region in responding to rewards. In this study, adults with ASDand matched controls first underwent a conditioning task outside the scanner, where they were mimicked by one face and‘anti-mimicked’ by another. In the second part, participants passively viewed the conditioned faces in a 3T MRI scanner using amulti-echo sequence. The differential neural response towards mimicking vs. anti-mimicking faces in the VS was tested for groupdifferences as well as an association with self-reported autistic traits. Multiple regression analysis revealed lower left VS responseto mimicry (mimicking > anti-mimicking faces) in the ASD group compared to controls. The VS response to mimicry was nega-tively correlated with autistic traits across the whole sample. Our results suggest that for individuals with ASD and high autistictraits, being mimicked is associated with lower reward-related neural response. This result points to a potential mechanism under-lying the difficulties reported by many of individuals with ASD in building social rapport

Young off-axis volcanism along the ultraslow-spreading Southwest Indian Ridge

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 3 (2010): 286-292, doi:10.1038/ngeo824.Mid-ocean ridge crustal accretion occurs continuously at all spreading rates through a combination of magmatic and tectonic processes. Fast to slow spreading ridges are largely built by adding magma to narrowly focused neovolcanic zones. In contrast, ultraslow spreading ridge construction significantly relies on tectonic accretion, which is characterized by thin volcanic crust, emplacement of mantle peridotite directly to the seafloor, and unique seafloor fabrics with variable segmentation patterns. While advances in remote imaging have enhanced our observational understanding of crustal accretion at all spreading rates, temporal information is required in order to quantitatively understand mid-ocean ridge construction. However, temporal information does not exist for ultraslow spreading environments. Here, we utilize U-series eruption ages to investigate crustal accretion at an ultraslow spreading ridge for the first time. Unexpectedly young eruption ages throughout the Southwest Indian ridge rift valley indicate that neovolcanic activity is not confined to the spreading axis, and that magmatic crustal accretion occurs over a wider zone than at faster spreading ridges. These observations not only suggest that crustal accretion at ultraslow spreading ridges is distinct from faster spreading ridges, but also that the magma transport mechanisms may differ as a function of spreading rate.This work was supported by the following NSF grants: NSF-OCE 0137325; NSF-OCE 060383800; and NSF-OCE 062705300