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

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

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Does bathymetry drive coastal whale shark (Rhincodon typus) aggregations?

Background The whale shark (Rhincodon typus) is known to aggregate in a number of coastal locations globally, however what causes these aggregations to form where they do is largely unknown. This study examines whether bathymetry is an important driver of coastal aggregation locations for R. typus through bathymetry’s effect on primary productivity and prey availability. This is a global study taking into account all coastal areas within R. typus’ range. Methods R. typus aggregation locations were identified through an extensive literature review. Global bathymetric data were compared at R. typus aggregation locations and a large random selection of non-aggregation areas. Generalised linear models were used to assess which bathymetric characteristic had the biggest influence on aggregation presence. Results Aggregation sites were significantly shallower than non-aggregation sites and in closer proximity to deep water (the mesopelagic zone) by two orders of magnitude. Slope at aggregation sites was significantly steeper than non-aggregation sites. These three bathymetric variables were shown to have the biggest association with aggregation sites, with up to 88% of deviation explained by the GLMs. Discussion The three key bathymetric characteristics similar at the aggregation sites are known to induce upwelling events, increase primary productivity and consequently attract numerous other filter feeding species. The location of aggregation sites in these key areas can be attributed to this increased prey availability, thought to be the main reason R. typus aggregations occur, extensively outlined in the literature. The proximity of aggregations to shallow areas such as reefs could also be an important factor why whale sharks thermoregulate after deep dives to feed. These findings increase our understanding of whale shark behaviour and may help guide the identification and conservation of further aggregation sites

A joint geochemical–geophysical record of time-dependent mantle convection south of Iceland

The North Atlantic V-Shaped Ridges (VSRs) provide a spatially extensive and clear record of unsteady mantle convective circulation over >40 My>40 My. VSRs are diachronous ridges of thick crust formed with a periodicity of ∼5 My∼5 My along the Mid Atlantic Ridge, south of Iceland. We present data from a set of dredged basalt samples that shows chemical variation associated with two complete VSR crustal thickness cycles where they intersect the Mid Atlantic Ridge. The new dataset also records chemical variation associated with a VSR crustal thickness cycle along a plate spreading flow-line. Inverse correlations between crustal thickness and both incompatible trace element concentrations and incompatible element ratios such as Nb/Y and La/Sm are observed. Geochemical and crustal thickness observations can be matched using a time-dependent mid-ocean ridge melting model with a basal boundary condition of sinusoidally varying potential temperature. Our observations and models suggest that VSRs are generated when hot patches are carried up the plume stem beneath SE Iceland and spread radially outward within the asthenosphere. These patches are then drawn upward into the melting region when passing beneath the Mid Atlantic Ridge. The geometry of the VSRs and the size of the dynamically supported swell suggest that the Iceland Plume is the strongest plume in the Earth at present, with a volume flux of View the MathML source49±14 km3yr−1

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

A model of fractional cointegration, and tests for cointegration using the bootstrap

The paper proposes a framework for modelling cointegration in fractionally integrated processes, and considers methods for testing the existence of cointegrating relationships using the parametric bootstrap. In these procedures, ARFIMA models are fitted to the data, and the estimates used to simulate the null hypothesis of non-cointegration in a vector autoregressive modelling framework. The simulations are used to estimate p-values for alternative regression-based test statistics, including the F goodness-of-fit statistic, the Durbin–Watson statistic and estimates of the residual d. The bootstrap distributions are economical to compute, being conditioned on the actual sample values of all but the dependent variable in the regression. The procedures are easily adapted to test stronger null hypotheses, such as statistical independence. The tests are not in general asymptotically pivotal, but implemented by the bootstrap, are shown to be consistent against alternatives with both stationary and nonstationary cointegrating residuals. As an example, the tests are applied to the series for UK consumption and disposable income. The power properties of the tests are studied by simulations of artificial cointegrating relationships based on the sample data. The F test performs better in these experiments than the residual-based tests, although the Durbin–Watson in turn dominates the test based on the residual d

“I was a full time proper smoker”: A qualitative exploration of smoking in the home after childbirth among women who relapse postpartum

Background: Many women stop smoking during pregnancy but relapse shortly afterwards, potentially putting their infants at risk of secondhand smoke (SHS) exposure. Women who were able to stop during pregnancy may be a motivated group, receptive to making behaviour changes postpartum to protect their infant from SHS exposure. Understanding more about their experiences of relapse, and if this influences home smoking behaviours and children’s exposure to SHS in the home may help to inform intervention development to prevent infant SHS exposure. Methods: Guided by interpretative phenomenological methodology we conducted and analysed nine semi-structured interviews with women who quit smoking during pregnancy, but relapsed ≤3 months postpartum. Findings: Central to mothers’ accounts of their smoking behaviours during pregnancy and postpartum was their desire to be a ‘responsible mother’. Mothers described using strategies to protect their infant from SHS exposure, and held strong negative attitudes towards other smoking parents. After relapsing, mothers appeared to reposition themselves as ‘social’ or ‘occasional’ smokers rather than ‘regular’ smokers Conclusions: Findings suggest that interventions to prevent/reduce infants' home SHS exposure should build on mothers' intentions to be responsible parents. As mothers who relapse principally view themselves as ‘social’ or ‘occasional’ smokers, interventions that are highlighted as relevant for women with these types of smoking patterns may be more likely to be responded to, and, ultimately, be effective

Autistic traits modulate mimicry of social but not nonsocial rewards

Autism Spectrum Conditions (ASC) are associated with diminished responsiveness to social stimuli, and especially to social rewards such as smiles. Atypical responsiveness to social rewards, which reinforce socially appropriate behavior in children, can potentially lead to a cascade of deficits in social behavior. Individuals with ASC often show diminished spontaneous mimicry of social stimuli in a natural setting. In the general population, mimicry is modulated both by the reward value and the sociality of the stimulus (i.e., whether the stimulus is perceived to belong to a conspecific or an inanimate object). Since empathy and autistic traits are distributed continuously in the general population, this study aimed to test if and how these traits modulated automatic mimicry of rewarded social and nonsocial stimuli. High and low rewards were associated with human and robot hands using a conditioned learning paradigm. Thirty-six participants from the general population then completed a mimicry task involving performing a prespecified hand movement which was either compatible or incompatible with a hand movement presented to the participant. High autistic traits (measured using the Autism Spectrum Quotient, AQ) predicted lesser mimicry of high-reward than low-reward conditioned human hands, whereas trait empathy showed an opposite pattern of correlations. No such relations were observed for high-reward vs. low-reward conditioned robot hands. These results demonstrate how autistic traits and empathy modulate the effects of reward on mimicry of social compared to nonsocial stimuli. This evidence suggests a potential role for the reward system in underlying the atypical social behavior in individuals with ASC, who constitute the extreme end of the spectrum of autistic traits

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy