Chronic voluntary alcohol consumption causes persistent cognitive deficits and cortical cell loss in a rodent model

Chronic alcohol use is associated with cognitive decline that impedes behavioral change during rehabilitation. Despite this, addiction therapy does not address cognitive deficits, and there is poor understanding regarding the mechanisms that underlie this decline. We established a rodent model of chronic voluntary alcohol use to measure ensuing cognitive effects and underlying pathology. Rats had intermittent access to alcohol or an isocaloric solution in their home cage under voluntary 2-bottle choice conditions. In Experiments 1 and 2 cognition was assessed using operant touchscreen chambers. We examined performance in a visual discrimination and reversal task (Experiment 1), and a 5-choice serial reaction time task (Experiment 2). For Experiment 3, rats were perfused immediately after cessation of alcohol access period, and volume, cell density and microglial populations were assessed in the prefrontal cortex and striatum. Volume was assessed using the Cavalieri probe, while cell and microglial counts were estimated using unbiased stereology with an optical fractionator. Alcohol-exposed and control rats showed comparable acquisition of pairwise discrimination; however, performance was impaired when contingencies were reversed indicating reduced behavioral flexibility. When tested in a 5-choice serial reaction time task alcohol-exposed rats showed increased compulsivity and increased attentional bias towards a reward associated cue. Consistent with these changes, we observed decreased cell density in the prefrontal cortex. These findings confirm a detrimental effect of chronic alcohol and establish a model of alcohol-induced cognitive decline following long-term voluntary intake that may be used for future intervention studies

Process evaluation of the Bristol girls dance project

Background: The Bristol Girls Dance Project was a cluster randomised controlled trial that aimed to increase objectively measured moderate-to-vigorous physical activity (MVPA) levels of Year 7 (age 11–12) girls through a dance-based after-school intervention. The intervention was delivered in nine schools and consisted of up to forty after-school dance sessions. This paper reports on the main findings from the detailed process evaluation that was conducted. / Methods: Quantitative and qualitative data were collected from intervention schools. Dose and fidelity were reported by dance instructors at every session. Intervention dose was defined as attending two thirds of sessions and was measured by attendance registers. Fidelity to the intervention manual was reported by dance instructors. On four randomly-selected occasions, participants reported their perceived level of exertion and enjoyment. Reasons for non-attendance were self-reported at the end of the intervention. Semi-structured interviews were conducted with all dance instructors who delivered the intervention (n = 10) and school contacts (n = 9) in intervention schools. A focus group was conducted with girls who participated in each intervention school (n = 9). / Results: The study did not affect girls’ MVPA. An average of 31.7 girls participated in each school, with 9.1 per school receiving the intervention dose. Mean attendance and instructors’ fidelity to the intervention manual decreased over time. The decline in attendance was largely attributed to extraneous factors common to after-school activities. Qualitative data suggest that the training and intervention manual were helpful to most instructors. Participant ratings of session enjoyment were high but perceived exertion was low, however, girls found parts of the intervention challenging. / Conclusions: The intervention was enjoyed by participants. Attendance at the intervention sessions was low but typical of after-school activities. Participants reported that the intervention brought about numerous health and social benefits and improved their dance-based knowledge and skills. The intervention could be improved by reducing the number of girls allowed to participate in each school and providing longer and more in-depth training to those delivering the intervention. / Trial registration: ISRCTN52882523 Registered 25th April 2013

Using self-determination theory to promote adolescent girls' physical activity: Exploring the theoretical fidelity of the Bristol Girls Dance Project

OBJECTIVES: To report the theory-based process evaluation of the Bristol Girls' Dance Project, a cluster-randomised controlled trial to increase adolescent girls' physical activity. DESIGN: A mixed-method process evaluation of the intervention's self-determination theory components comprising lesson observations, post-intervention interviews and focus groups. METHOD: Four intervention dance lessons per dance instructor were observed, audio recorded and rated to estimate the use of need-supportive teaching strategies. Intervention participants (n = 281) reported their dance instructors' provision of autonomy-support. Semi-structured interviews with the dance instructors (n = 10) explored fidelity to the theory and focus groups were conducted with participants (n = 59) in each school to explore their receipt of the intervention and views on the dance instructors' motivating style. RESULTS: Although instructors accepted the theory-based approach, intervention fidelity was variable. Relatedness support was the most commonly observed need-supportive teaching behaviour, provision of structure was moderate and autonomy-support was comparatively low. The qualitative findings identified how instructors supported competence and developed trusting relationships with participants. Fidelity was challenged where autonomy provision was limited to option choices rather than input into the pace or direction of lessons and where controlling teaching styles were adopted, often to manage disruptive behaviour. CONCLUSION: The successes and challenges to achieving theoretical fidelity in the Bristol Girls' Dance Project may help explain the intervention effects and can more broadly inform the design of theory-based complex interventions aimed at increasing young people's physical activity in after-school settings

Bristol Girls Dance Project: a cluster randomised controlled trial of an after-school dance programme to increase physical activity among 11- to 12-year-old girls

BACKGROUND: Many children do not meet UK physical activity (PA) guidelines. Girls are less active than boys, and the age-related decline in activity is steeper for girls. Dance is the favourite form of PA among adolescent girls in the UK. Participation in after-school dance classes could significantly contribute to girls’ PA. Therefore, after-school dance may be effective for increasing PA levels. OBJECTIVES: To determine the effectiveness and cost-effectiveness of a dance-based intervention to increase the objectively assessed mean weekday minutes of moderate- to vigorous-intensity physical activity (MVPA) of Year 7 girls (11- and 12-year olds) 1 year after baseline measurement. DESIGN:Two-arm cluster randomised controlled trial and economic evaluation. Year 7 girls in participant schools received a ‘taster’ session and were invited to participate. Up to 33 girls per school were able to participate. Schools were randomly assigned (equal numbers) to intervention or control arms. SETTING:A total of 18 mainstream secondary schools across greater Bristol. PARTICIPANTS: Year 7 girls in participating schools who could participate in physical education. INTERVENTION: Nine intervention schools received an after-school dance intervention (40 × 75-minute sessions) underpinned by self-determination theory, which attempts to improve intrinsic motivation for being active, and delivered by external dance instructors. Control schools continued as normal. MAIN OUTCOME MEASURES: The main outcome was accelerometer-assessed mean minutes of MVPA at T2. Measures were assessed at baseline (T0), the end of the intervention (T1) and at T0 + 52 weeks (T2). RESULTS:Baseline MVPA levels were high. A total of 508 girls were included in the primary analysis, which found no difference in weekday MVPA between trial arms. There was no effect on secondary accelerometer outcomes. Data were subjected to a per-protocol analysis and no effect was found. However, at T1, girls who attended dance classes had 4.61 minutes more of MVPA and 14.27 minutes more of light-intensity activity between 15.00 and 17.00 on the days on which they attended intervention sessions. The intervention was inexpensive at £73 per participant (£63 when excluding dance instructor travel) but was not cost-effective owing to the ineffectiveness of the intervention. The European Quality of Life-5 Dimensions Youth survey data were unresponsive to changes in the sample. The process evaluation reported that girls in attendance enjoyed the sessions, that exertion levels were low during sessions and that attendance was low and declined. Fidelity to the session-plan manual was low but theoretical fidelity (to self-determination theory) was good. Qualitative information provides information for improving future interventions. CONCLUSIONS: The intervention was enjoyed by participants. However, there was no difference in the MVPA levels (which were high at baseline) of girls allocated to receive dance compared with girls receiving the control. High baseline MVPA levels indicate that the study appealed to an already active cohort and, therefore, may not have targeted those most in need of an intervention. Dance is an enjoyable activity for adolescent girls and could be further trialled as a means by which to increase PA. Research might consider the impact of dividing the intervention period into smaller blocks. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52882523. FUNDING: The National Institute for Health Research Public Health Research programme. The work was also undertaken with the support of the Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer), a UK Clinical Research Collaboration (UKCRC) PHR Centre of Excellence. Joint funding (MR/KO232331/1) from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the Welsh Government and the Wellcome Trust, under the auspices of the UKCRC, is gratefully acknowledged. This study was designed and delivered in collaboration with the Bristol Randomised Trials Collaboration, a UKCRC Registered Clinical Trials Unit in receipt of NIHR Clinical Trials Unit support funding. All intervention costs were funded by the respective councils to which the participant schools were affiliated, namely North Somerset Council, Bristol City Council, and Bath and North East Somerset Council

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting

Stochastic population growth in spatially heterogeneous environments

Classical ecological theory predicts that environmental stochasticity increases extinction risk by reducing the average per-capita growth rate of populations. To understand the interactive effects of environmental stochasticity, spatial heterogeneity, and dispersal on population growth, we study the following model for population abundances in $n$ patches: the conditional law of $X_{t+dt}$ given $X_t=x$ is such that when $dt$ is small the conditional mean of $X_{t+dt}^i-X_t^i$ is approximately $[x^i\mu_i+\sum_j(x^j D_{ji}-x^i D_{ij})]dt$, where $X_t^i$ and $\mu_i$ are the abundance and per capita growth rate in the $i$-th patch respectivly, and $D_{ij}$ is the dispersal rate from the $i$-th to the $j$-th patch, and the conditional covariance of $X_{t+dt}^i-X_t^i$ and $X_{t+dt}^j-X_t^j$ is approximately $x^i x^j \sigma_{ij}dt$. We show for such a spatially extended population that if $S_t=(X_t^1+...+X_t^n)$ is the total population abundance, then $Y_t=X_t/S_t$, the vector of patch proportions, converges in law to a random vector $Y_\infty$ as $t\to\infty$, and the stochastic growth rate $\lim_{t\to\infty}t^{-1}\log S_t$ equals the space-time average per-capita growth rate \sum_i\mu_i\E[Y_\infty^i] experienced by the population minus half of the space-time average temporal variation \E[\sum_{i,j}\sigma_{ij}Y_\infty^i Y_\infty^j] experienced by the population. We derive analytic results for the law of $Y_\infty$, find which choice of the dispersal mechanism $D$ produces an optimal stochastic growth rate for a freely dispersing population, and investigate the effect on the stochastic growth rate of constraints on dispersal rates. Our results provide fundamental insights into "ideal free" movement in the face of uncertainty, the persistence of coupled sink populations, the evolution of dispersal rates, and the single large or several small (SLOSS) debate in conservation biology.Comment: 47 pages, 4 figure

Two Planets, One Species: Does a Mission to Mars Alter the Balance in Favour of Human Enhancement?

In this chapter we examine the implications of a crewed mission to Mars, possible colonisation of the planet, and the wider implications this may have on genetic enhancement in both a terrestrial and space context. We consider the usage of both somatic and germ-line genetic engineering, and its potential impact on the evolution of Homo sapiens. We acknowledge that a mission to Mars may require the usage of such technologies if it is to be successful. Our investigation suggests that the use of such technologies might ultimately be linked with the transformation of our own species. We also consider projected timescales for the development of these genetic enhancements and the ethical questions raised by the possibility of speciation. Cooperation among spacefaring nations in this context and the development of norms for the use of such technologies is desirable

A study of general practitioners' perspectives on electronic medical records systems in NHS Scotland

<b>Background</b> Primary care doctors in NHSScotland have been using electronic medical records within their practices routinely for many years. The Scottish Health Executive eHealth strategy (2008-2011) has recently brought radical changes to the primary care computing landscape in Scotland: an information system (GPASS) which was provided free-of-charge by NHSScotland to a majority of GP practices has now been replaced by systems provided by two approved commercial providers. The transition to new electronic medical records had to be completed nationally across all health-boards by March 2012. <p></p><b> Methods</b> We carried out 25 in-depth semi-structured interviews with primary care doctors to elucidate GPs' perspectives on their practice information systems and collect more general information on management processes in the patient surgical pathway in NHSScotland. We undertook a thematic analysis of interviewees' responses, using Normalisation Process Theory as the underpinning conceptual framework. <p></p> <b>Results</b> The majority of GPs' interviewed considered that electronic medical records are an integral and essential element of their work during the consultation, playing a key role in facilitating integrated and continuity of care for patients and making clinical information more accessible. However, GPs expressed a number of reservations about various system functionalities - for example: in relation to usability, system navigation and information visualisation. <b>Conclusion </b>Our study highlights that while electronic information systems are perceived as having important benefits, there remains substantial scope to improve GPs' interaction and overall satisfaction with these systems. Iterative user-centred improvements combined with additional training in the use of technology would promote an increased understanding, familiarity and command of the range of functionalities of electronic medical records among primary care doctors

Success of a suicidal defense strategy against infection in a structured habitat

Pathogen infection often leads to the expression of virulence and host death when the host-pathogen symbiosis seems more beneficial for the pathogen. Previously proposed explanations have focused on the pathogen's side. In this work, we tested a hypothesis focused on the host strategy. If a member of a host population dies immediately upon infection aborting pathogen reproduction, it can protect the host population from secondary infections. We tested this "Suicidal Defense Against Infection" (SDAI) hypothesis by developing an experimental infection system that involves a huge number of bacteria as hosts and their virus as pathogen, which is linked to modeling and simulation. Our experiments and simulations demonstrate that a population with SDAI strategy is successful in the presence of spatial structure but fails in its absence. The infection results in emergence of pathogen mutants not inducing the host suicide in addition to host mutants resistant to the pathogen

Control of magnetic anisotropy by orbital hybridization in (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattice

The asymmetry of chemical nature at the hetero-structural interface offers an unique opportunity to design desirable electronic structure by controlling charge transfer and orbital hybridization across the interface. However, the control of hetero-interface remains a daunting task. Here, we report the modulation of interfacial coupling of (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattices by manipulating the periodic thickness with n unit cells of SrTiO3 and n unit cells La0.67Sr0.33MnO3. The easy axis of magnetic anisotropy rotates from in-plane (n = 10) to out-of-plane (n = 2) orientation at 150 K. Transmission electron microscopy reveals enlarged tetragonal ratio > 1 with breaking of volume conservation around the (La0.67Sr0.33MnO3)n/(SrTiO3)n interface, and electronic charge transfer from Mn to Ti 3d orbitals across the interface. Orbital hybridization accompanying the charge transfer results in preferred occupancy of 3d3z2-r2 orbital at the interface, which induces a stronger electronic hopping integral along the out-of-plane direction and corresponding out-of-plane magnetic easy axis for n = 2. We demonstrate that interfacial orbital hybridization in superlattices of strongly correlated oxides may be a promising approach to tailor electronic and magnetic properties in device applications