Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory.

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory.The authors’ research is funded by the Wellcome Trust (grant number 086871/Z/08/Z), the MRC (G0701500), a joint award from the MRC (G1000183) and Wellcome Trust (093875/Z/10/ Z) in support of the Behavioral and Clinical Neuroscience Institute at Cambridge University, and an MRC strategic award to the Imperial College-Cambridge University-Manchester University (ICCAM) addiction cluster (G1000018).This is the final version of the article. It first appeared from Springer at http://dx.doi.org/10.1007/s00213-016-4405-8

Ultrasound morphology of carotid plaque and its link with lipid: protein content and 3d microstructure of the plaque.

the 22nd Meeting of the European Society of Neurosonology and Cerebral Hemodynamics (ESNCH), 19-21 May 2017. Berlin, Germany, and published in the International Journal of Stroke 12(1S): 57 (Poster 101), May 2017. ISSN: 1747-4930, eISSN: 1747-4949

Dengue outlook for the World Cup in Brazil: an early warning model framework driven by real-time seasonal climate forecasts.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: With more than a million spectators expected to travel among 12 different cities in Brazil during the football World Cup, June 12-July 13, 2014, the risk of the mosquito-transmitted disease dengue fever is a concern. We addressed the potential for a dengue epidemic during the tournament, using a probabilistic forecast of dengue risk for the 553 microregions of Brazil, with risk level warnings for the 12 cities where matches will be played. METHODS: We obtained real-time seasonal climate forecasts from several international sources (European Centre for Medium-Range Weather Forecasts [ECMWF], Met Office, Meteo-France and Centro de Previsão de Tempo e Estudos Climáticos [CPTEC]) and the observed dengue epidemiological situation in Brazil at the forecast issue date as provided by the Ministry of Health. Using this information we devised a spatiotemporal hierarchical Bayesian modelling framework that enabled dengue warnings to be made 3 months ahead. By assessing the past performance of the forecasting system using observed dengue incidence rates for June, 2000-2013, we identified optimum trigger alert thresholds for scenarios of medium-risk and high-risk of dengue. FINDINGS: Our forecasts for June, 2014, showed that dengue risk was likely to be low in the host cities Brasília, Cuiabá, Curitiba, Porto Alegre, and São Paulo. The risk was medium in Rio de Janeiro, Belo Horizonte, Salvador, and Manaus. High-risk alerts were triggered for the northeastern cities of Recife (p(high)=19%), Fortaleza (p(high)=46%), and Natal (p(high)=48%). For these high-risk areas, particularly Natal, the forecasting system did well for previous years (in June, 2000-13). INTERPRETATION: This timely dengue early warning permits the Ministry of Health and local authorities to implement appropriate, city-specific mitigation and control actions ahead of the World Cup. FUNDING: European Commission's Seventh Framework Research Programme projects DENFREE, EUPORIAS, and SPECS; Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro.DENFREE projectEUPORIAS projectSPECS projectEuropean Commission's Seventh Framework Research ProgrammeConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado do Rio de Janeir

Dengue epidemic early warning system for Brazil

Copyright © 2015 UNISDR (United Nations International Strategy for Disaster Reduction)The problem Brazil has reported more cases of dengue fever than anywhere else in the world this century1. Many cities have tropical and sub-tropical climate conditions that allow the dengue mosquito to thrive during warmer, wetter and more humid months, particularly in densely populated urban areas. Dengue epidemics depend on mosquito abundance, virus circulation and human susceptibility. In order to prepare for dengue epidemics, early warning systems, which take into account multiple dengue risk factors, are required to implement timely control measures. Seasonal climate forecasts provide an opportunity to anticipate dengue epidemics several months in advance ...European Commission’s Seventh Framework Research Programme project DENFREEEuropean Commission’s Seventh Framework Research Programme project EUPORIASEuropean Commission’s Seventh Framework Research Programme project SPECSConselho Nacional de Desenvolvimento Científico e TecnológicoFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ

Social Capital and Housing Tenure in an Adelaide Neighbourhood

Author version made available in accordance with publisher copyright policy.In this paper we compare and contrast elements of social capital across different housing tenures in an Adelaide neighbourhood. Using the results of 530 self-completion questionnaires and in-depth qualitative interviews with 16 people we assess perceptions of conflict across housing tenures and between socioeconomic groups, feelings of acceptance and belonging in the local neighbourhood, and levels of involvement in local formal and informal networks. While only a small number of questionnaire respondents reported negative views of socioeconomic diversity in the area a common theme emerging in the qualitative data indicated that housing tenure was relevant to some of these negative perceptions. Respondents from across different tenure types also reported differences in feelings of acceptance in the neighbourhood, and involvement in formal and informal networks. The study findings suggest that housing tenure is relevant to the development of neighbourhood-based social capital, and that this factor needs to be considered by social planners, housing policy makers and others involved in implementing social mix policies. In addition, the findings indicate the need to consider the community housing and public housing tenures in their own right, given the different models of housing provision, rather than collectively under the common banner of social housing as most research studies do. It is recommended that the full diversity of housing tenure is considered in any future analysis

Young people, crime and school exclusion: a case of some surprises

During the 1990s the number of young people being permanently excluded from schools in England and Wales increased dramatically from 2,910 (1990/91) to a peak of 12,700 (1996/97). Coinciding with this rise was a resurgence of the debate centring on lawless and delinquent youth. With the publication of Young People and Crime (Graham and Bowling 1995) and Misspent Youth (Audit Commission 1996) the 'common sense assumption' that exclusion from school inexorably promoted crime received wide support, with the school excludee portrayed as another latter day 'folk devil'. This article explores the link between school exclusion and juvenile crime, and offers some key findings from a research study undertaken with 56 young people who had experience of being excluded from school. Self-report interview questions reveal that whilst 40 of the young people had offended, 90% (36) reported that the onset of their offending commenced prior to their first exclusion. Moreover, 50 (89.2% of the total number of young people in the sample), stated that they were no more likely to offend subsequent to being excluded and 31 (55.4%) stated that they were less likely to offend during their exclusion period. Often, this was because on being excluded, they were 'grounded' by their parents

Predicting Distribution of Aedes Aegypti and Culex Pipiens Complex, Potential Vectors of Rift Valley Fever Virus in Relation to Disease Epidemics in East Africa.

The East African region has experienced several Rift Valley fever (RVF) outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. DIVERSE ECOLOGICAL NICHE MODELLING TECHNIQUES HAVE BEEN DEVELOPED FOR THIS PURPOSE: we present a maximum entropy (Maxent) approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex) responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods

Rank-based model selection for multiple ions quantum tomography

The statistical analysis of measurement data has become a key component of many quantum engineering experiments. As standard full state tomography becomes unfeasible for large dimensional quantum systems, one needs to exploit prior information and the "sparsity" properties of the experimental state in order to reduce the dimensionality of the estimation problem. In this paper we propose model selection as a general principle for finding the simplest, or most parsimonious explanation of the data, by fitting different models and choosing the estimator with the best trade-off between likelihood fit and model complexity. We apply two well established model selection methods -- the Akaike information criterion (AIC) and the Bayesian information criterion (BIC) -- to models consising of states of fixed rank and datasets such as are currently produced in multiple ions experiments. We test the performance of AIC and BIC on randomly chosen low rank states of 4 ions, and study the dependence of the selected rank with the number of measurement repetitions for one ion states. We then apply the methods to real data from a 4 ions experiment aimed at creating a Smolin state of rank 4. The two methods indicate that the optimal model for describing the data lies between ranks 6 and 9, and the Pearson $\chi^{2}$ test is applied to validate this conclusion. Additionally we find that the mean square error of the maximum likelihood estimator for pure states is close to that of the optimal over all possible measurements.Comment: 24 pages, 6 figures, 3 table

From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior.

Impulsivity is an endophenotype of vulnerability for compulsive behaviors. However, the neural mechanisms whereby impulsivity facilitates the development of compulsive disorders, such as addiction or obsessive compulsive disorder, remain unknown. We first investigated, in rats, anatomical and functional correlates of impulsivity in the anterior insular (AI) cortex by measuring both the thickness of, and cellular plasticity markers in, the AI with magnetic resonance imaging and in situ hybridization of the immediate early gene zif268, respectively. We then investigated the influence of bilateral AI cortex lesions on the high impulsivity trait, as measured in the five-choice serial reaction time task (5-CSRTT), and the associated propensity to develop compulsivity as measured by high drinking levels in a schedule-induced polydipsia procedure (SIP). We demonstrate that the AI cortex causally contributes to individual vulnerability to impulsive-compulsive behavior in rats. Motor impulsivity, as measured by premature responses in the 5-CSRTT, was shown to correlate with the thinness of the anterior region of the insular cortex, in which highly impulsive (HI) rats expressed lower zif268 mRNA levels. Lesions of AI reduced impulsive behavior in HI rats, which were also highly susceptible to develop compulsive behavior as measured in a SIP procedure. AI lesions also attenuated both the development and the expression of SIP. This study thus identifies the AI as a novel neural substrate of maladaptive impulse control mechanisms that may facilitate the development of compulsive disorders.This research was carried-out within the Department of Psychology and the Department of Pharmacology of the University of Cambridge as well as the INSERM AVENIR team Psychobiology of Compulsive Disorders of the University of Poitiers. It was supported by an INSERM AVENIR grant and a FYSSEN foundation grant to DB. MLD was supported by a PhD fellowship from the Fondation pour la Recherche Médicale (FRM) and ABR was supported by a post-doctoral fellowship from the INSERM. BJE was supported by the United Kingdom Medical Research Council (MRC) Grant 9536855.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/mp.2015.14