Protective effect of intravitreal administration of tresperimus, an immunosuppressive drug, on experimental autoimmune uveoretinitis.

PURPOSE: To test the efficiency of locally administrated tresperimus in experimental autoimmune uveoretinitis (EAU). METHODS: EAU was induced in Lewis rats by S-antigen (S-Ag) immunization. Three intravitreal injections of tresperimus (prevention or prevention/treatment protocols) were performed at different time points after immunization. The pharmacokinetics of tresperimus was evaluated in the ocular tissues and plasma. The in vitro effect of tresperimus was evaluated on macrophages. EAU was graded clinically and histologically. Blood ocular barrier permeability was evaluated by protein concentration in ocular fluids. Immune response to S-Ag was examined by delayed type hypersensitivity, the expression of inflammatory cytokines in lymph nodes, ocular fluids and serum by multiplex ELISA, and in ocular cells by RT-PCR. RESULTS: In vitro, tresperimus significantly reduced the production of inflammatory cytokines by lipopolysaccharide-stimulated macrophages. In vivo, in the treatment protocol, efficient tresperimus levels were measured in the eye but not in the plasma up to 8 days after the last injection. Tresperimus efficiently reduced inflammation, retinal damage, and blood ocular barrier permeability breakdown. It inhibited nitric oxide synthase-2 and nuclear factor κBp65 expression in ocular macrophages. IL-2 and IL-17 were decreased in ocular media, while IL-18 was increased. By contrast, IL-2 and IL-17 levels were not modified in inguinal lymph nodes draining the immunization site. Moreover, cytokine levels in serum and delayed type hypersensitivity to S-Ag were not different in control and treated rats. In the prevention/treatment protocol, ocular immunosuppressive effects were also observed. CONCLUSIONS: Locally administered tresperimus appears to be a potential immunosuppressive agent in the management of intraocular inflammation.

Identifying genetic signatures of selection in a non-model species, alpine gentian (Gentiana nivalis L.), using a landscape genetic approach

It is generally accepted that most plant populations are locally adapted. Yet, understanding how environmental forces give rise to adaptive genetic variation is a challenge in conservation genetics and crucial to the preservation of species under rapidly changing climatic conditions. Environmental variation, phylogeographic history, and population demographic processes all contribute to spatially structured genetic variation, however few current models attempt to separate these confounding effects. To illustrate the benefits of using a spatially-explicit model for identifying potentially adaptive loci, we compared outlier locus detection methods with a recently-developed landscape genetic approach. We analyzed 157 loci from samples of the alpine herb Gentiana nivalis collected across the European Alps. Principle coordinates of neighbor matrices (PCNM), eigenvectors that quantify multi-scale spatial variation present in a data set, were incorporated into a landscape genetic approach relating AFLP frequencies with 23 environmental variables. Four major findings emerged. 1) Fifteen loci were significantly correlated with at least one predictor variable (R (adj) (2) > 0.5). 2) Models including PCNM variables identified eight more potentially adaptive loci than models run without spatial variables. 3) When compared to outlier detection methods, the landscape genetic approach detected four of the same loci plus 11 additional loci. 4) Temperature, precipitation, and solar radiation were the three major environmental factors driving potentially adaptive genetic variation in G. nivalis. Techniques presented in this paper offer an efficient method for identifying potentially adaptive genetic variation and associated environmental forces of selection, providing an important step forward for the conservation of non-model species under global change.

Tackling Fuel Poverty can Improve Health, but needs Resources

Fuel poverty is a significant threat to public health with its links to heart disease, respiratory illness and mental health. People on low incomes are most likely to live in fuel poverty. The Fuel Poverty Strategy, which was launched 23 November, 2004, needed to be adequately resourced to help reduce the devastating effects of health inequalities in our society, according to the Institute of Public Health in Ireland. The Institute of Public Health recently completed research which showed that locally based projects are an effective way of improving the energy efficiency of homes. The findings from the research conducted by the Institute of Public Health showed that local fuel poverty interventions can reduce fuel poverty and improve health: - The energy efficiency of homes were significantly improved - There was a statistically significant increase in levels of benefit uptake - People reported spending less on fuel after intervention - There were significant reductions in the presence of condensation, mould and damp, which is where we have the strongest evidence of links to ill-health - There was a significant reduction in the number of illnesses (associated with fuel poverty) reported by those who received the heating conversion and insulation - People reported reductions in the use of health services after intervention

IPH Response to Draft planning policy statement 18 Renewable energy - March 2008

IPH welcomes the Planning Policy Statement 18 Renewable Energy (PPS18) and the opportunity to comment on the publication.  IPH applies a holistic model of health which emphasises a wide range of social determinants, including economic, environmental, social and biological factors. IPH considers that the health impacts of renewable energy should be considered as part of PPS18. We wish to make the following general observations in relation to the Proposed Plan:  IPH welcomes the sustainable approach by the Department of the Environment to encourage and facilitate the provision of renewal energy in Northern Ireland. PPS18 can support the move to reduce pollutants entering the environment. However there is a need to consider wider public health concerns in the adoption of PPS18. Encouraging renewable energy (while balancing this with environmental and conservation concerns) will benefit health locally, and on a global scale. Climate change has been identified as one of the most important public health challenges of the 21st Century and therefore any policy which seeks to address this major issue is welcomed.

Eimeria curvata n. sp.(Apicomplexa: Eimeriidae) in Columbina talpacoti and Scardafella squammata (Aves: Columbidae) from Brazil

Eimeria curvata is a new coccidian described in the doves Columbina talpacoti and Scardafella squammata from western of the State of São Paulo, Brazil. The oocysts are ovoid to ellipsoid, 18.3 (17-19) µm x 15.5 (15-17) µm, with a shape index of 1.2 (1.1-1.3). The wall is colorless, smooth and double-layered. A polar granule is present, but there is no micropyle or oocyst residuum. The sporocysts are elongate, 12.3 (11.5-13) µm x 5.8 (5.5-6) µm with a curved anterior portion and a smooth, thin, single-layered wall. The Stieda body is protuberant and nipple-like; there is no substieda body. The sporozoites lie head-to-tail in the sporocyst and contain a large refractile body at the extremities. The sporocyst residuum contains small granules uniformly distributed in the middle of the sporocyst. The prevalence of E. curvata n. sp. was 17.4% and 12.8% in C. talpacoti and S. squammata, respectively.

A review of the ticks (Acari, Ixodida) of Brazil, their hosts and geographic distribution - 1. The State of Rio Grande do Sul, Southern Brazil

A review of the ticks (Acari, Ixodida) of the State of Rio Grande do Sul, southern Brazil, was completed as a step towards a definitive list (currently indicated as 12) of such species, their hosts and distribution. The ticks: Argas miniatus (poultry), Ixodes loricatus (opossums), Amblyomma aureolatum (dogs), A. calcaratum (anteaters), A. cooperi (capybaras), A. nodosum (anteaters), A. tigrinum (dogs) (Neotropical) and Rhipicephalus sanguineus (dogs) (introduced, cosmopolitan, Afrotropical) were confirmed as present, in addition to the predominant, Boophilus microplus (cattle) (introduced, pan-tropical, Oriental). Of the further 18 species thus far reported in the literature as present in the state, but unavailable for examination: only Ornithodoros brasiliensis (humans and their habitations) (Neotropical), Ixodes affinis (deer) (Nearctic/Neotropical) and I. auritulus (birds) (Nearctic/Neotropical/Afrotropical/ Australasian) are considered likely; 13 species would benefit from corroborative local data but the majority appear unlikely; reports of A. maculatum (Nearctic/Neotropical, but circum-Caribbean) are considered erroneous; the validity of A. fuscum is in doubt. The very recent, first known report of the tropical Anocentor nitens (horses)(Nearctic/Neotropical), but still apparent absence of the tropical A. cajennense (catholic) (Nearctic/Neotropical) and the sub-tropical/temperate Ixodes pararicinus (cattle) (Neotropical) in Rio Grande do Sul are important for considerations on their current biogeographical distribution and its dynamics in South America. The state has relatively long established, introduced ("exotic"), Old World tick species (B. microplus, R. sanguineus) that continue to represent significant pests and disease vectors to their traditional, introduced domestic animal hosts, cattle and urban dogs. There are also indigenous, New World ticks (A. miniatus, O. brasiliensis, A. aureolatum, A. nitens), as both long established and possibly newly locally introduced species in the state, that should be considered as potential and emergent pests and pathogen vectors to humans and their more recently acquired, introduced domestic animal hosts; rural poultry, dogs and horses.

Prevención, seguimiento y evaluación de la descontaminación de percloroetileno en suelo y aguas subterráneas en un terreno industrial

La contaminación de suelos y aguas subterráneas es uno de los problemas ambientales más extendidos en gran parte de los terrenos industriales de Cataluña. En este proyecto se ha analizado el proceso de gestión de la contaminación: caracterización, remediación y seguimiento de la descontaminación en suelos y aguas subterráneas por un caso de afección por organoclorados (percloroetileno) y otros contaminantes (hidrocarburos, selenio y cromo) en un emplazamiento industrial situado en una zona agroforestal (superficie de 81.462 m2). A partir de la implantación en la empresa del sistema de gestión ISO 14.001 en 1.996, se abrieron diferentes proyectos de gestión para los posibles contaminantes. Por las mismas fechas, también se detectó una afección por selenio en aguas subterráneas, ajena a la empresa de estudio. Por el momento, el único contaminante que ha requerido de un proceso de descontaminación ha sido el percloroetileno. En suelos se emplea el método “soil vapor extraction” y en aguas subterráneas el método “airstripping”. Finalmente, se ha llevado a cabo una comparación de los costes reales derivados del proceso de descontaminación del percloroetileno en contra de los costes que se hubiesen derivado la implantación de medidas de prevención de la contaminación. El resultado de la valoración indica que la descontaminación de éste compuesto requiere de una inversión económica importante, unas 10 veces más elevada que los costes derivados de las medidas de prevención.

Strategies to promote translational research within the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group: a report from the Translational Research Subcommittee.

Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer-related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies-(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician-scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framework.

Deciding where to belong: gender differences in educational trajectories and migration in a rural Spanish town

From an anthropological perspective, formal post-secondary schooling is not an abstractentity with an intrinsic value that everyone finds desirable, but rather one alternative among many that young people evaluate from their different positions in the social field. The problem discussed in this paper is the diverging life trajectories that young men and women in a concrete rural context, at the end of the 20th century, shape for themselves at the ages of 14-16, a moment of decision created by national legislation regarding mandatory education (LGE, 1970, General Education Law, and LOGSE, 1990, General Organic Law of the Education System). Despite a strong cultural norm of equal inheritance divided among all children, male and female, and despite the equal educational opportunities provided by the Spanish State, different meanings of possession and use-rights over land and the resulting culturally accepted gendered division of work converge to orient men and women differently towards post-secondary schooling. Observation of the age, gender, and civil status structure of the population led to the preliminary query: Why do men and women, in this town, behave differently with respect to migration and marriage? The main hypothesis was that women’s longer school trajectories and resulting migration and men’s anchoring in the town and their higher rates of celibacy were not drastic changes in values, in the positional-relational sense of Bourdieu (1988, 2002), but the current outcome of previously existing dissimilar relations to property that produce dissimilar mobility. Through their schooling and work choices, young men and women, at very early ages, locate themselves in, or decide to belong to, different contexts that later reveal very different possibilities of finding marriage partners. This paper is based on an ethnographic study of a small rural town (302 inhabitants in 1950; 193 in 2000) near Leon. Although this paper deals with the situation in the final decades of the 20th century, we must also consider the first half of the century, where some elements that shape this situation have their roots. Fieldwork was carried out between 1988 and 2001, in periods of differing length and intensity. The social subjects discussed here are the domestic unit and its component members. They were studied in conjunction, analyzing the life-trajectory decisions of specific persons in the framework of the domestic unit and the relations among people and property which comprise it. The tried-and-true methods of ethnographic research –participant observation, interviews, and life-histories, etc.- were employed. Archival research was also important for producing demographic data. Demographic analysis, the analysis of the composition and transformation of domestic units, and the creation of life trajectories were among the principal techniques used. The theoretical analysis was oriented by Bourdieu’s (2002) framework of the social field, habitus, and difference.

Anaesthetics, Pain Relief and Critical Care Follow Up (PDF 797 KB)

In 2003/2004 the Department of Health, Social Services and Public Safety commissioned a value for money follow-up audit of Anaesthetics, Pain Relief and Critical Care (APRCC) services at twelve Trusts and covering fourteen hospital sites. The original study had reported in 1999/2000. Detailed follow-up reports, together with action plans have been agreed locally with Trusts. The objectives of the follow-up review were to: • Ascertain the progress made in implementing recommendations from the original study; • Provide data to compare performance across Trusts in areas such as: - Pre-operative assessments; - Organisation of post-operative pain relief; - Organisation of chronic pain services; - Levels of admissions to critical care units; - Occupancy in critical care units; and åÊ • Assess the extent of progress made by Trusts in the implementation of the Chief Medical Officer’s (CMO) recommendations from ‘Facing the Future –Building on the Lessons of Winter 1999/2000’. To enable comparisons across Trusts, data was collected for the financial year 2002/2003. In addition, relevant findings from the Audit Commission’s Acute Hospitals Portfolio have also been included. The Acute Hospital Portfolio is a collection of reviews that are undertaken at acute and specialist Trusts. They focus on key service areas and are reported along the key performance criteria of patient experience, efficiency and capacity. åÊ

Valor pronóstico de la densidad microvascular y de la expresión del VEGF, EGFR y HIF-1 en pacientes con cáncer de cérvix localmente avanzado tratados con quimioradiación

Introducción: Colombia cuenta con poca información sobre el comportamiento del cáncer, no obstante, el carcinoma de cuello uterino representa la segunda causa de muerte por la enfermedad entre las mujeres de nuestro entorno. El patrón epidemiológico de la enfermedad es preocupante porque los estados localmente avanzados constituyen el estado más frecuente al momento del diagnóstico y la mortalidad siendo bastante alta a pesar de la presencia de un programa de cribado organizado. Objetivo: Describir el valor pronóstico de la densidad microvascular (DMV) y de la expresión proteica de varios genes relacionados con la supervivencia y proliferación del cáncer de cérvix localmente avanzado en un grupo de mujeres tratadas con quimioradiación y braquiterapia intracavitaria. Se estimaron la tasa de respuesta global (TRG), la supervivencia libre de progresión (SLP) y la supervivencia global (SG). Resultados: Se incluyeron 61 mujeres con una edad media de 52 ± 10 años; todas tenían diagnóstico de cáncer de cérvix localmente avanzado (IIA 2.3%/IIB 47.5%/IIIA 4.9%/IIIB 37.7%/IVA 3.3%/no definido 3.3%), con un volumen tumoral promedio de 6.4cm (DE ± 1.8cm) e infección por VPH en 46% de los casos; 58 sujetos (95%) tenían un patrón escamoso, dos fueron adenocarcinomas y &50% presentaba neoplasias moderada o pobremente diferenciadas. Todas fueron tratadas con quimioradiación (interrupción transitoria en teleterapia por toxicidad y otras causas en 19% y 21.4%, respectivamente/media de ciclos de platino concomitante 4.8 series ± 1.0) y braquiterapia (77% completaron el tratamiento intracavitario). La mediana para la SLP y global fue de 6.6 meses (r, 4.0-9.1) y 30 meses (r, 11-48), respectivamente. Ninguna de las variables tuvo un efecto positivo sobre la SLP, mientras el análisis multivariado demostró que los niveles de expresión del VEGF (P=0.026), EGFR (P=0.030), y el volumen tumoral menor de 6 cm (P=0.02) influyeron positivamente sobre éste desenlace. Conclusión: Existe una influencia positiva sobre el pronóstico, de la tipificación en el cáncer de cérvix localmente avanzado tratado con quimioradiación basada en platino.

Quantitative integration of geophysical and hydraulic data : from the local towards the regional scale range

Des progrès significatifs ont été réalisés dans le domaine de l'intégration quantitative des données géophysique et hydrologique l'échelle locale. Cependant, l'extension à de plus grandes échelles des approches correspondantes constitue encore un défi majeur. Il est néanmoins extrêmement important de relever ce défi pour développer des modèles fiables de flux des eaux souterraines et de transport de contaminant. Pour résoudre ce problème, j'ai développé une technique d'intégration des données hydrogéophysiques basée sur une procédure bayésienne de simulation séquentielle en deux étapes. Cette procédure vise des problèmes à plus grande échelle. L'objectif est de simuler la distribution d'un paramètre hydraulique cible à partir, d'une part, de mesures d'un paramètre géophysique pertinent qui couvrent l'espace de manière exhaustive, mais avec une faible résolution (spatiale) et, d'autre part, de mesures locales de très haute résolution des mêmes paramètres géophysique et hydraulique. Pour cela, mon algorithme lie dans un premier temps les données géophysiques de faible et de haute résolution à travers une procédure de réduction déchelle. Les données géophysiques régionales réduites sont ensuite reliées au champ du paramètre hydraulique à haute résolution. J'illustre d'abord l'application de cette nouvelle approche dintégration des données à une base de données synthétiques réaliste. Celle-ci est constituée de mesures de conductivité hydraulique et électrique de haute résolution réalisées dans les mêmes forages ainsi que destimations des conductivités électriques obtenues à partir de mesures de tomographic de résistivité électrique (ERT) sur l'ensemble de l'espace. Ces dernières mesures ont une faible résolution spatiale. La viabilité globale de cette méthode est testée en effectuant les simulations de flux et de transport au travers du modèle original du champ de conductivité hydraulique ainsi que du modèle simulé. Les simulations sont alors comparées. Les résultats obtenus indiquent que la procédure dintégration des données proposée permet d'obtenir des estimations de la conductivité en adéquation avec la structure à grande échelle ainsi que des predictions fiables des caractéristiques de transports sur des distances de moyenne à grande échelle. Les résultats correspondant au scénario de terrain indiquent que l'approche d'intégration des données nouvellement mise au point est capable d'appréhender correctement les hétérogénéitées à petite échelle aussi bien que les tendances à gande échelle du champ hydraulique prévalent. Les résultats montrent également une flexibilté remarquable et une robustesse de cette nouvelle approche dintégration des données. De ce fait, elle est susceptible d'être appliquée à un large éventail de données géophysiques et hydrologiques, à toutes les gammes déchelles. Dans la deuxième partie de ma thèse, j'évalue en détail la viabilité du réechantillonnage geostatique séquentiel comme mécanisme de proposition pour les méthodes Markov Chain Monte Carlo (MCMC) appliquées à des probmes inverses géophysiques et hydrologiques de grande dimension . L'objectif est de permettre une quantification plus précise et plus réaliste des incertitudes associées aux modèles obtenus. En considérant une série dexemples de tomographic radar puits à puits, j'étudie deux classes de stratégies de rééchantillonnage spatial en considérant leur habilité à générer efficacement et précisément des réalisations de la distribution postérieure bayésienne. Les résultats obtenus montrent que, malgré sa popularité, le réechantillonnage séquentiel est plutôt inefficace à générer des échantillons postérieurs indépendants pour des études de cas synthétiques réalistes, notamment pour le cas assez communs et importants où il existe de fortes corrélations spatiales entre le modèle et les paramètres. Pour résoudre ce problème, j'ai développé un nouvelle approche de perturbation basée sur une déformation progressive. Cette approche est flexible en ce qui concerne le nombre de paramètres du modèle et lintensité de la perturbation. Par rapport au rééchantillonage séquentiel, cette nouvelle approche s'avère être très efficace pour diminuer le nombre requis d'itérations pour générer des échantillons indépendants à partir de la distribution postérieure bayésienne. - Significant progress has been made with regard to the quantitative integration of geophysical and hydrological data at the local scale. However, extending corresponding approaches beyond the local scale still represents a major challenge, yet is critically important for the development of reliable groundwater flow and contaminant transport models. To address this issue, I have developed a hydrogeophysical data integration technique based on a two-step Bayesian sequential simulation procedure that is specifically targeted towards larger-scale problems. The objective is to simulate the distribution of a target hydraulic parameter based on spatially exhaustive, but poorly resolved, measurements of a pertinent geophysical parameter and locally highly resolved, but spatially sparse, measurements of the considered geophysical and hydraulic parameters. To this end, my algorithm links the low- and high-resolution geophysical data via a downscaling procedure before relating the downscaled regional-scale geophysical data to the high-resolution hydraulic parameter field. I first illustrate the application of this novel data integration approach to a realistic synthetic database consisting of collocated high-resolution borehole measurements of the hydraulic and electrical conductivities and spatially exhaustive, low-resolution electrical conductivity estimates obtained from electrical resistivity tomography (ERT). The overall viability of this method is tested and verified by performing and comparing flow and transport simulations through the original and simulated hydraulic conductivity fields. The corresponding results indicate that the proposed data integration procedure does indeed allow for obtaining faithful estimates of the larger-scale hydraulic conductivity structure and reliable predictions of the transport characteristics over medium- to regional-scale distances. The approach is then applied to a corresponding field scenario consisting of collocated high- resolution measurements of the electrical conductivity, as measured using a cone penetrometer testing (CPT) system, and the hydraulic conductivity, as estimated from electromagnetic flowmeter and slug test measurements, in combination with spatially exhaustive low-resolution electrical conductivity estimates obtained from surface-based electrical resistivity tomography (ERT). The corresponding results indicate that the newly developed data integration approach is indeed capable of adequately capturing both the small-scale heterogeneity as well as the larger-scale trend of the prevailing hydraulic conductivity field. The results also indicate that this novel data integration approach is remarkably flexible and robust and hence can be expected to be applicable to a wide range of geophysical and hydrological data at all scale ranges. In the second part of my thesis, I evaluate in detail the viability of sequential geostatistical resampling as a proposal mechanism for Markov Chain Monte Carlo (MCMC) methods applied to high-dimensional geophysical and hydrological inverse problems in order to allow for a more accurate and realistic quantification of the uncertainty associated with the thus inferred models. Focusing on a series of pertinent crosshole georadar tomographic examples, I investigated two classes of geostatistical resampling strategies with regard to their ability to efficiently and accurately generate independent realizations from the Bayesian posterior distribution. The corresponding results indicate that, despite its popularity, sequential resampling is rather inefficient at drawing independent posterior samples for realistic synthetic case studies, notably for the practically common and important scenario of pronounced spatial correlation between model parameters. To address this issue, I have developed a new gradual-deformation-based perturbation approach, which is flexible with regard to the number of model parameters as well as the perturbation strength. Compared to sequential resampling, this newly proposed approach was proven to be highly effective in decreasing the number of iterations required for drawing independent samples from the Bayesian posterior distribution.

Predictors of HIV-protection behaviour in HIV-positive men who have sex with casual male partners: a test of the explanatory power of an extended Information-Motivation-Behavioural Skills model.

This prospective study applies an extended Information-Motivation-Behavioural Skills (IMB) model to establish predictors of HIV-protection behaviour among HIV-positive men who have sex with men (MSM) during sex with casual partners. Data have been collected from anonymous, self-administered questionnaires and analysed by using descriptive and backward elimination regression analyses. In a sample of 165 HIV-positive MSM, 82 participants between the ages of 23 and 78 (M=46.4, SD=9.0) had sex with casual partners during the three-month period under investigation. About 62% (n=51) have always used a condom when having sex with casual partners. From the original IMB model, only subjective norm predicted condom use. More important predictors that increased condom use were low consumption of psychotropics, high satisfaction with sexuality, numerous changes in sexual behaviour after diagnosis, low social support from friends, alcohol use before sex and habitualised condom use with casual partner(s). The explanatory power of the calculated regression model was 49% (p<0.001). The study reveals the importance of personal and social resources and of routines for condom use, and provides information for the research-based conceptualisation of prevention offers addressing especially people living with HIV ("positive prevention").

Characterization of metabolites in infiltrating gliomas using ex vivo &supl;H high-resolution magic angle spinning spectroscopy.

Gliomas are routinely graded according to histopathological criteria established by the World Health Organization. Although this classification can be used to understand some of the variance in the clinical outcome of patients, there is still substantial heterogeneity within and between lesions of the same grade. This study evaluated image-guided tissue samples acquired from a large cohort of patients presenting with either new or recurrent gliomas of grades II-IV using ex vivo proton high-resolution magic angle spinning spectroscopy. The quantification of metabolite levels revealed several discrete profiles associated with primary glioma subtypes, as well as secondary subtypes that had undergone transformation to a higher grade at the time of recurrence. Statistical modeling further demonstrated that these metabolomic profiles could be differentially classified with respect to pathological grading and inter-grade conversions. Importantly, the myo-inositol to total choline index allowed for a separation of recurrent low-grade gliomas on different pathological trajectories, the heightened ratio of phosphocholine to glycerophosphocholine uniformly characterized several forms of glioblastoma multiforme, and the onco-metabolite D-2-hydroxyglutarate was shown to help distinguish secondary from primary grade IV glioma, as well as grade II and III from grade IV glioma. These data provide evidence that metabolite levels are of interest in the assessment of both intra-grade and intra-lesional malignancy. Such information could be used to enhance the diagnostic specificity of in vivo spectroscopy and to aid in the selection of the most appropriate therapy for individual patients.

MyHits: a new interactive resource for protein annotation and domain identification.

The MyHits web server (http://myhits.isb-sib.ch) is a new integrated service dedicated to the annotation of protein sequences and to the analysis of their domains and signatures. Guest users can use the system anonymously, with full access to (i) standard bioinformatics programs (e.g. PSI-BLAST, ClustalW, T-Coffee, Jalview); (ii) a large number of protein sequence databases, including standard (Swiss-Prot, TrEMBL) and locally developed databases (splice variants); (iii) databases of protein motifs (Prosite, Interpro); (iv) a precomputed list of matches ('hits') between the sequence and motif databases. All databases are updated on a weekly basis and the hit list is kept up to date incrementally. The MyHits server also includes a new collection of tools to generate graphical representations of pairwise and multiple sequence alignments including their annotated features. Free registration enables users to upload their own sequences and motifs to private databases. These are then made available through the same web interface and the same set of analytical tools. Registered users can manage their own sequences and annotations using only web tools and freeze their data in their private database for publication purposes.