Predicting reptile distributions at the mesoscale: relation to climate and topography

Aim To explore the respective power of climate and topography to predict the distribution of reptiles in Switzerland, hence at a mesoscale level. A more detailed knowledge of these relationships, in combination with maps of the potential distribution derived from the models, is a valuable contribution to the design of conservation strategies. Location All of Switzerland. Methods Generalized linear models are used to derive predictive habitat distribution models from eco-geographical predictors in a geographical information system, using species data from a field survey conducted between 1980 and 1999. Results The maximum amount of deviance explained by climatic models is 65%, and 50% by topographical models. Low values were obtained with both sets of predictors for three species that are widely distributed in all parts of the country (Anguis fragilis , Coronella austriaca , and Natrix natrix), a result that suggests that including other important predictors, such as resources, should improve the models in further studies. With respect to topographical predictors, low values were also obtained for two species where we anticipated a strong response to aspect and slope, Podarcis muralis and Vipera aspis . Main conclusions Overall, both models and maps derived from climatic predictors more closely match the actual reptile distributions than those based on topography. These results suggest that the distributional limits of reptile species with a restricted range in Switzerland are largely set by climatic, predominantly temperature-related, factors.

Sound Texture Modelling

In the PhD thesis “Sound Texture Modeling” we deal with statistical modelling or textural sounds like water, wind, rain, etc. For synthesis and classification. Our initial model is based on a wavelet tree signal decomposition and the modeling of the resulting sequence by means of a parametric probabilistic model, that can be situated within the family of models trainable via expectation maximization (hidden Markov tree model ). Our model is able to capture key characteristics of the source textures (water, rain, fire, applause, crowd chatter ), and faithfully reproduces some of the sound classes. In terms of a more general taxonomy of natural events proposed by Graver, we worked on models for natural event classification and segmentation. While the event labels comprise physical interactions between materials that do not have textural propierties in their enterity, those segmentation models can help in identifying textural portions of an audio recording useful for analysis and resynthesis. Following our work on concatenative synthesis of musical instruments, we have developed a pattern-based synthesis system, that allows to sonically explore a database of units by means of their representation in a perceptual feature space. Concatenative syntyhesis with “molecules” built from sparse atomic representations also allows capture low-level correlations in perceptual audio features, while facilitating the manipulation of textural sounds based on their physical and perceptual properties. We have approached the problem of sound texture modelling for synthesis from different directions, namely a low-level signal-theoretic point of view through a wavelet transform, and a more high-level point of view driven by perceptual audio features in the concatenative synthesis setting. The developed framework provides unified approach to the high-quality resynthesis of natural texture sounds. Our research is embedded within the Metaverse 1 European project (2008-2011), where our models are contributting as low level building blocks within a semi-automated soundscape generation system.

Immigration and the school system

Immigration is an important problem in many societies, and it has wide-ranging effects on the educational systems of host countries. There is a now a large empirical literature, but very little theoretical work on this topic. We introduce a model of family immigration in a framework where school quality and student outcomes are determined endogenously. This allows us to explain the selection of immigrants in terms of parental motivation and the policies which favor a positive selection. Also, we can study the effect of immigration on the school system and how school quality may self-reinforce immigrants' and natives' choices.

Adaptive Privacy Management System Design For Context-Aware Mobile Devices

While mobile technologies can provide great personalized services for mobile users, they also threaten their privacy. Such personalization-privacy paradox are particularly salient for context aware technology based mobile applications where user's behaviors, movement and habits can be associated with a consumer's personal identity. In this thesis, I studied the privacy issues in the mobile context, particularly focus on an adaptive privacy management system design for context-aware mobile devices, and explore the role of personalization and control over user's personal data. This allowed me to make multiple contributions, both theoretical and practical. In the theoretical world, I propose and prototype an adaptive Single-Sign On solution that use user's context information to protect user's private information for smartphone. To validate this solution, I first proved that user's context is a unique user identifier and context awareness technology can increase user's perceived ease of use of the system and service provider's authentication security. I then followed a design science research paradigm and implemented this solution into a mobile application called "Privacy Manager". I evaluated the utility by several focus group interviews, and overall the proposed solution fulfilled the expected function and users expressed their intentions to use this application. To better understand the personalization-privacy paradox, I built on the theoretical foundations of privacy calculus and technology acceptance model to conceptualize the theory of users' mobile privacy management. I also examined the role of personalization and control ability on my model and how these two elements interact with privacy calculus and mobile technology model. In the practical realm, this thesis contributes to the understanding of the tradeoff between the benefit of personalized services and user's privacy concerns it may cause. By pointing out new opportunities to rethink how user's context information can protect private data, it also suggests new elements for privacy related business models.

Reduced physical activity level and cardiorespiratory fitness in children with chronic diseases.

We aimed to compare physical activity level and cardiorespiratory fitness in children with different chronic diseases, such as type 1 diabetes mellitus (T1DM), obesity (OB) and juvenile idiopathic arthritis (JIA), with healthy controls (HC). We performed a cross-sectional study including 209 children: OB: n = 45, T1DM: n = 48, JIA: n = 31, and HC: n = 85. Physical activity level was assessed by accelerometer and cardiorespiratory fitness by a treadmill test. ANOVA, linear regressions and Pearson correlations were used. Children with chronic diseases had reduced total daily physical activity counts (T1DM 497 +/- 54 cpm, p = 0.003; JIA 518 +/- 28, p < 0.001, OB 590 +/- 25, p = 0.003) and cardiorespiratory fitness (JIA 39.3 +/- 1.7, p = 0.001, OB 41.7 +/- 1.2, p = 0.020) compared to HC (668 +/- 35 cpm; 45.3 +/- 0.9 ml kg(-1) min(-1), respectively). Only 60.4% of HC, 51.6% of OB, 38.1% of JIA and 38.5% of T1DM children met the recommended daily 60 min of moderate-to-vigorous physical activity. Low cardiorespiratory fitness was associated with female gender and low daily PA. Children with chronic diseases had reduced physical activity and cardiorespiratory fitness. As the benefits of PA on health have been well demonstrated during growth, it should be encouraged in those children to prevent a reduction of cardiorespiratory fitness and the development of comorbidities.

Health Care Quality Indicators in the Irish Health System

  Public reporting of quality indicators promotes the principle of a transparent and accountable health care system that encourages a continuing focus on improving the quality of care it provides. This work brings us a step further in enhancing the quality and safety of our system. It is important that this report is not relied upon to draw conclusions on quality of care. That was not the purpose of the exercise. The data is mostly over five years old and was collected from the system before the improvements to collection and reporting of information that the hospitals were asked to put in place as part of the work to prepare this report. The Department of Health will produce a report of quality indicators based on data from 2011 to 2013 inclusive later in 2014 which will identify regions and hospitals. A governance process will shortly be established to oversee the selection and reporting of these indicators. This system will report at national and regional level and will be aligned with international systems so that international comparisons can be reported. The publication of this report is an important step in the development of this national reporting system. It shows that we can use a major IT system called HIPE which captures information on all hospital stays in all public hospitals to examine quality and safety of care. Health Care Quality Indicators in the Irish Health System

Evaluation of indirect susceptibility testing of Mycobacterium tuberculosis to the first- and second-line, and alternative drugs by the newer MB/BacT system

In order to evaluate the Organon Teknika MB/BacT system used for testing indirect susceptibility to the alternative drugs ofloxacin (OFLO), amikacin (AMI), and rifabutin (RIF), and to the usual drugs of standard treatment regimes such as rifampin (RMP), isoniazid (INH), pyrazinamide (PZA), streptomycin (SM), ethambutol (EMB), and ethionamide (ETH), cultures of clinical specimens from 117 patients with pulmonary tuberculosis under multidrug-resistant investigation, admitted sequentially for examination from 2001 to 2002, were studied. Fifty of the Mycobacterium tuberculosis cultures were inoculated into the gold-standard BACTEC 460 TB (Becton Dickinson) for studying resistance to AMI, RIF, and OFLO, and the remaining 67 were inoculated into Lowenstein Jensen (LJ) medium (the gold standard currently used in Brazil) for studying resistance to RMP, INH, PZA, SM, EMB, and ETH. We observed 100% sensitivity for AMI (80.8-100), RIF (80.8-100), and OFLO (78.1-100); and 100% specificity for AMI (85.4-100), RIF (85.4-100), and OFLO (86.7-100) compared to the BACTEC system. Comparing the results obtained in LJ we observed 100% sensitivity for RMP (80-100), followed by INH - 95% (81.8-99.1), EMB - 94.7% (71.9-99.7), and 100% specificity for all drugs tested except for PZA - 98.3 (89.5-99.9) at 95% confidence interval. The results showed a high level of accuracy and demonstrated that the fully automated, non-radiometric MB/BacT system is indicated for routine use in susceptibility testing in public health laboratories.

An experimental study on the shallow-level migmatization of ferrogabbros from the Fuerteventura Basal Complex, Canary Islands

Spectacular shallow-level migmatization of ferrogabbroic rocks occurs in a metamorphic contact aureole of a gabbroic pluton of the Tierra Mala massif (TM) on Fuerteventura (Canary Islands). In order to improve our knowledge of the low pressure melting behavior of gabbroic rocks and to constrain the conditions of migmatization of the TM gabbros, we performed partial melting experiments on a natural ferrogabbro, which is assumed as protolith of the migmatites. The experiments were performed in an internally heated pressure vessel (IHPV) at 200 MPa, 930-1150 degreesC at relatively oxidizing conditions. Distinct amounts of water were added to the charge. From 930 to 1000 degreesC, the observed experimental phases are plagioclase (An(60-70)), clinopyroxene, amphibole (titanian magnesiohastingsites), two Fe-Ti oxides, and a basaltic, K-poor melt. Above 1000 degreesC, amphibole is no longer stable. The first melts are very rich in non-native plagioclase (>70 wt.%). This indicates that at the beginning of partial melting plagioclase is the major phase which is consumed to produce melt. In the experiments, plagioclase is stable up to high temperatures (1060 degreesC) showing increasing An content with temperature. This is not compatible with the natural migmatites, in which An-rich plagioclase is absent in the melanosomes, while amphibole is stable. Our results show that the partial melting of the natural rocks cannot be regarded as an ``in-situ'' process that occurred in a closed system. Considerable amounts of alkalis probably transported by water-rich fluids, derived from the mafic pluton underplating the TM gabbro, were necessary to drive the melting reaction out of the stability range of plagioclase. A partial melting experiment with a migmatite gabbro showing typical ``in-situ'' textures as starting material supports this assumption. Crystallization experiments performed at 1000 degreesC on a glass of the fitised ferrogabbro with different water contents added to the charge show that generally high water activities could be achieved (crystallization of amphibole), independently of the bulk water content, even in a system with very low initial bulk water content (0.3 wt.%). Increasing water contents produce plagioclase richer in An, reduces the modal proportion of plagioclase in the crystallizing assemblage and extends the melt fraction. High melt fractions of >30 wt.% could only be observed in systems with high bulk water contents (> - 2 wt.%). This indicates that the migmatites were generated under water-rich conditions (probably water-saturated), since those migmatites, which are characterized as ``in-situ'' formations, show generally high amounts of leucosomes (>30 wt.%). (C) 2003 Elsevier B.V. All rights reserved.

Effect of low-level pathogenic helminth infection on energy metabolism in Gambian children.

The aim of the present study was to determine whether an increase in resting energy expenditure (REE) contributes to the impaired nutritional status of Gambian children infected by a low level of infection with pathogenic helminths. The REE of 24 children infected with hookworm, Ascaris, Strongyloides, or Trichuris (mean +/- SEM age = 11.9 +/- 0.1 years) and eight controls without infection (mean +/- SEM age = 11.8 +/- 0.1 years) were measured by indirect calorimetry with a hood system (test A). This measurement was repeated after treatment with 400 mg of albendazole (patients) or a placebo (controls) (test B). When normalized for fat free mass, REE in test A was not different in the patients (177 +/- 2 kJ/kg x day) and in the controls (164 +/- 7 kJ/kg x day); furthermore, REE did not change significantly after treatment in the patients (173 +/- 3 kJ/kg x day) or in the controls (160 +/- 8 kJ/kg x day). There was no significant difference in the respiratory quotient between patients and controls, nor between tests A and B. It is concluded that a low level of helminth infection does not affect significantly the energy metabolism of Gambian children.

Les deux visages de l'autophagie dans le système nerveux [The two faces of autophagy in the nervous system].

Autophagy is a cellular mechanism for degrading proteins and organelles. It was first described as a physiological process essential for maintaining homeostasis and cell survival, but understanding its role in conditions of stress has been complicated by the recognition of a new type of cell death ("type 2") characterized by deleterious autophagic activity. This paradox is important in the central nervous system where the activation of autophagy seems to be protective in certain neurodegenerative diseases but deleterious in cerebral ischemia. The development of new therapeutic strategies based on the manipulation of autophagy will need to take into account these opposing roles of autophagy.

Developing new approaches for detecting and preventing Aedes aegypti population outbreaks: basis for surveillance, alert and control system

A new approach to dengue vector surveillance based on permanent egg-collection using a modified ovitrap and Bacillus thuringiensis israelensis(Bti) was evaluated in different urban landscapes in Recife, Northeast Brazil. From April 2004 to April 2005, 13 egg-collection cycles of four weeks were carried out. Geo-referenced ovitraps containing grass infusion, Bti and three paddles were placed at fixed sampling stations distributed over five selected sites. Continuous egg-collections yielded more than four million eggs laid into 464 sentinel-ovitraps over one year. The overall positive ovitrap index was 98.5% (over 5,616 trap observations). The egg density index ranged from 100 to 2,500 eggs per trap-cycle, indicating a wide spread and high density of Aedes aegypti (Diptera: Culicidae) breeding populations in all sites. Fluctuations in population density over time were observed, particularly a marked increase from January on, or later, according to site. Massive egg-collection carried out at one of the sites prevented such a population outbreak. At intra-site level, egg counts made it possible to identify spots where the vector population is consistently concentrated over the time, pinpointing areas that should be considered high priority for control activities. The results indicate that these could be promising strategies for detecting and preventing Ae. aegypti population outbreaks.

Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study

Objective. To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. Design Nested case-control study. Setting. The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. Participants: 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls. Main outcome measures. Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. Results. 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); ≥100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. Conclusions The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

New genetic models and mesenchymal cells as tools to ameliorate anti-tumor immunity

Résumé Le but final de ce projet est d'utiliser des cellules T ou des cellules souches mésenchymateuses modifiées génétiquement afin de surexprimer localement les deux chémokines CXCL13 et CCL2 ensemble ou chacune séparément à l'intérieur d'une tumeur solide. CXCL13 est supposé induire des structures lymphoïdes ectopiques. Un niveau élevé de CCL2 est présumé initier une inflammation aiguë. La combinaison des deux effets amène à un nouveau modèle d'étude des mécanismes régulateur de la tolérance périphérique et de l'immunité tumorale. Les connaissances acquises grâce à ce modèle pourraient permettre le développement ou l'amélioration des thérapies immunes du cancer. Le but premier de ce travail a été l'établissement d'un modèle génétique de la souris permettant d'exprimer spécifiquement dans la tumeur les deux chémokines d'intérêt à des niveaux élevés. Pour accomplir cette tâche, qui est en fait une thérapie génétique de tumeurs solides, deux types de cellules porteuses potentielles ont été évaluées. Des cellules CD8+ T et des cellules mésenchymateuses de la moelle osseuse transférées dans des receveurs portant une tumeur. Si on pouvait répondre aux besoins de la thérapie génétique, indépendamment de la thérapie immune envisagée, on posséderait là un outil précieux pour bien d'autres approches thérapeutiques. Plusieurs lignées de souris transgéniques ont été générées comme source de cellules CD8+ T modifiées afin d'exprimer les chémokines d'intérêt. Dans une approche doublement transgénique les propriétés de deux promoteurs spécifiques de cellules T ont été combinées en utilisant la technologie Cre-loxP. Le promoteur de granzyme B confère une dépendance d'activation et le promoteur distal de lck assure une forte expression constitutive dès que les cellules CD8+ T ont été activées. Les transgènes construits ont montré une bonne performance in vivo et des souris qui expriment CCL2 dans des cellules CD8+ T activées ont été obtenues. Ces cellules peuvent maintenant être utilisées avec différents protocoles pour transférer des cellules T cytotoxiques (CTL) dans des receveurs porteur d'une tumeur, permettant ainsi d'évaluer leur capacité en tant que porteuse de chémokine d'infiltrer la tumeur. L'établissement de souris transgéniques, qui expriment pareillement CXCL13 est prévu dans un avenir proche. L'évaluation de cellules mésenchymateuses de la moelle osseuse a démontré que ces cellules se greffent efficacement dans le stroma tumoral suite à la co-injection avec des cellules tumorales. Cela représente un outil précieux pour la recherche, vu qu'il permet d'introduire des cellules manipulées dans un modèle tumoral. Les résultats confirment partiellement d'autres résultats rapportés dans un modèle amélioré. Cependant, l'efficacité et la spécificité suggérées de la migration systémique de cellules mésenchymateuses de la moelle osseuse dans une tumeur n'ont pas été observées dans notre modèle, ce qui indique, que ces cellules ne se prêtent pas à une utilisation thérapeutique. Un autre résultat majeur de ce travail est l'établissement de cultures de cellules mésenchymateuses de la moelle osseuse in vitro conditionnées par des tumeurs, ce qui a permis à ces cellules de s'étendre plus rapidement en gardant leur capacité de migration et de greffe. Cela offre un autre outil précieux, vu que la culture in vitro est un pas nécessaire pour une manipulation thérapeutique. Abstract The ultimate aim of the presented project is to use genetically modified T cells or mesenchymal stem cells to locally overexpress the two chemokines CXCL13 and CCL2 together or each one alone inside a solid tumor. CXCL13 is supposed to induce ectopic lymphoid structures and a high level of CCL2 is intended to trigger acute inflamation. The combination of these two effects represents a new model for studying mechanisms that regulate peripheral tolerance and tumor immunity. Gained insights may help developing or improving immunotherapy of cancer. The primary goal of the executed work was the establishment of a genetic mouse model that allows tumor-specific expression of high levels of the two chemokines of interest. For accomplishing this task, which represents gene therapy of solid tumors, two types of potentially useful carrier cells were evaluated. CD8+ T cells and mesenchymal bone marrow cells to be used in adoptive cell transfers into tumor-bearing mice. Irrespectively of the envisaged immunotherapy, satisfaction of so far unmet needs of gene therapy would be a highly valuable tool that may be employed by many other therapeutic approaches, too. Several transgenic mouse lines were generated as a source of CD8+ T cells modified to express the chemokines of interest. In a double transgenic approach the properties of two T cell-specific promoters were combined using Cre-loxP technology. The granzyme B promoter confers activation-dependency and the lck distal promoter assures strong constitutive expression once the CD8+ T cell has been activated. The constructed transgenes showed a good performance in vivo and mice expressing CCL2 in activated CD8+ T cells were obtained. These cells can now be used with different protocols for adoptively transferring cytotoxic T cells (CTL) into tumor-bearing recipients, thus allowing to study their capacity as tumor-infiltrating chemokine carrier. The establishment of transgenic mice likewisely expressing CXCL13 is expected in the near future. In addition, T cells from generated single transgenic mice that have high expression of an EGFP reporter in both CD4+ and CD8+ cells can be easily traced in vivo when setting up adoptive transfer conditions. The evaluation of mesenchymal bone marrow cells demonstrated that these cells can efficiently engraft into tumor stroma upon local coinjection with tumor cells. This represents a valuable tool for research purposes as it allows to introduce manipulated stromal cells into a tumor model. Therefore, the established engraftment model is suited for studying the envisaged immunotherapy. These results confirm to some extend previously reported results in an improved model, however, the suggested systemic tumor homing efficiency and specificity of mesenchymal bone marrow cells was not observed in our model indicating that these cells may not be suited for therapeutic use. Another major result of the presented work is the establishment oftumor-conditioned in vitro culture of mesenchymal bone marrow cells, which allowed to more rapidly expand these cells while maintaining their tumor homing and engrafting capacities. This offers another valuable tool as in vitro culture is a necessary step for therapeutic manipulations.

Intermediary and structural determinants of early childhood health in Colombia: exploring the role of communities

This study examines how structural determinants influence intermediary factors of child health inequities and how they operate through the communities where children live. In particular, we explore individual, family and community level characteristics associated with a composite indicator that quantitatively measures intermediary determinants of early childhood health in Colombia. We use data from the 2010 Colombian Demographic and Health Survey (DHS). Adopting the conceptual framework of the Commission on Social Determinants of Health (CSDH), three dimensions related to child health are represented in the index: behavioural factors, psychosocial factors and health system. In order to generate the weight of the variables and take into account the discrete nature of the data, principal component analysis (PCA) using polychoric correlations are employed in the index construction. Weighted multilevel models are used to examine community effects. The results show that the effect of household’s SES is attenuated when community characteristics are included, indicating the importance that the level of community development may have in mediating individual and family characteristics. The findings indicate that there is a significant variance in intermediary determinants of child health between-community, especially for those determinants linked to the health system, even after controlling for individual, family and community characteristics. These results likely reflect that whilst the community context can exert a greater influence on intermediary factors linked directly to health, in the case of psychosocial factors and the parent’s behaviours, the family context can be more important. This underlines the importance of distinguishing between community and family intervention programmes.

Peripheral inflammation increases the damage in animal models of nigrostriatal dopaminergic neurodegeneration: possible implication in Parkinson's disease incidence.

Inflammatory processes described in Parkinson’s disease (PD) and its animal models appear to be important in the progression of the pathogenesis, or even a triggering factor. Here we review that peripheral inflammation enhances the degeneration of the nigrostriatal dopaminergic system induced by different insults; different peripheral inflammations have been used, such as IL-1β and the ulcerative colitis model, as well as insults to the dopaminergic system such as 6-hydroxydopamine or lipopolysaccharide. In all cases, an increased loss of dopaminergic neurons was described; inflammation in the substantia nigra increased, displaying a great activation of microglia along with an increase in the production of cytokines such as IL-1β and TNF-α. Increased permeability or disruption of the BBB, with overexpression of the ICAM-1 adhesion molecule and infiltration of circulating monocytes into the substantia nigra, is also involved, since the depletion of circulating monocytes prevents the effects of peripheral inflammation. Data are reviewed in relation to epidemiological studies of PD.