Localization and characterization of an active fault in an urbanized area in central Guatemala by means of geoelectrical imaging

The Polochic and Motagua faults define the active plate boundary between the North American and Caribbean plates in central Guatemala. A splay of the Polochic Fault traverses the rapidly growing city of San Miguel Uspantan that is periodically affected by destructive earthquakes. This fault splay was located using a 2D electrical resistivity tomography (ERT) survey that also characterized the fault damage zone and evaluated the thickness and nature of recent deposits upon which most of the city is built. ERT images show the fault as a similar to 50 m wide, near-vertical low-resistivity anomaly, bounded within a few meters by high resistivity anomalies. Forward modeling reproduces the key aspects of the observed electrical resistivity data with remarkable fidelity thus defining the overall location, geometry, and internal structure of the fault zone as well as the affected lithologies. Our results indicate that the city is constructed on a similar to 20 m thick surficial layer consisting of poorly consolidated, highly porous, water-logged pumice. This soft layer is likely to amplify seismic waves and to liquefy upon moderate to strong ground shaking. The electrical conductivity as well as the major element chemistry of the groundwater provides evidence to suggest that the local aquifer might, at least in part, be fed by water rising along the fault. Therefore, the potential threat posed by this fault splay may not be limited to its seismic activity per se, but could be compounded its potential propensity to enhance seismic site effects by injecting water into the soft surficial sediments. The results of this study provide the basis for a rigorous analysis of seismic hazard and sustainable development of San Miguel Uspantan and illustrate the potential of ERT surveying for paleoseismic studies.

An EORTC phase I itudy of bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer.

The combination of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4) is still a reference regimen in advanced colorectal cancer; however, the addition of new biologic compounds represents a significant way forward. Bortezomib is an inhibitor of proteasome, a multicatalytic enzyme complex that degrades several intracellular proteins. In this study, escalating doses of Bortezomib were administered along with the standard FOLFOX-4 doses, in order to evaluate the dose-limiting toxicity (DLT), toxicity profile and activity of the combination. Patients with advanced colorectal cancer, unpretreated for metastatic disease, were enroled in the study. Bortezomib starting dose was 1.3mg/m(2), which was to be escalated in the subsequent steps according to the toxicities observed after first cycle. Exploratory pharmacogenetics research was conducted by analysing the association between clinical outcomes and polymorphisms in candidate genes for response to each of the used drugs. Correlation between tumour marker changes and response was also investigated. One mg/m(2) (DL-1) was defined as being the maximum tolerated dose since only 1 DLT was observed in 6 patients. The main toxicities were haematologic, neuropathy, diarrhoea and fatigue. Amongst 13 evaluable patients, five had a partial response, five had a stable disease and three patients progressed. Two patients are long-term survivors after a combined chemosurgical approach. Further trials of the current combination may be justified.

Looking for orders of magnitude : five essays in trade and the environment and economic geography

General Summary Although the chapters of this thesis address a variety of issues, the principal aim is common: test economic ideas in an international economic context. The intention has been to supply empirical findings using the largest suitable data sets and making use of the most appropriate empirical techniques. This thesis can roughly be divided into two parts: the first one, corresponding to the first two chapters, investigates the link between trade and the environment, the second one, the last three chapters, is related to economic geography issues. Environmental problems are omnipresent in the daily press nowadays and one of the arguments put forward is that globalisation causes severe environmental problems through the reallocation of investments and production to countries with less stringent environmental regulations. A measure of the amplitude of this undesirable effect is provided in the first part. The third and the fourth chapters explore the productivity effects of agglomeration. The computed spillover effects between different sectors indicate how cluster-formation might be productivity enhancing. The last chapter is not about how to better understand the world but how to measure it and it was just a great pleasure to work on it. "The Economist" writes every week about the impressive population and economic growth observed in China and India, and everybody agrees that the world's center of gravity has shifted. But by how much and how fast did it shift? An answer is given in the last part, which proposes a global measure for the location of world production and allows to visualize our results in Google Earth. A short summary of each of the five chapters is provided below. The first chapter, entitled "Unraveling the World-Wide Pollution-Haven Effect" investigates the relative strength of the pollution haven effect (PH, comparative advantage in dirty products due to differences in environmental regulation) and the factor endowment effect (FE, comparative advantage in dirty, capital intensive products due to differences in endowments). We compute the pollution content of imports using the IPPS coefficients (for three pollutants, namely biological oxygen demand, sulphur dioxide and toxic pollution intensity for all manufacturing sectors) provided by the World Bank and use a gravity-type framework to isolate the two above mentioned effects. Our study covers 48 countries that can be classified into 29 Southern and 19 Northern countries and uses the lead content of gasoline as proxy for environmental stringency. For North-South trade we find significant PH and FE effects going in the expected, opposite directions and being of similar magnitude. However, when looking at world trade, the effects become very small because of the high North-North trade share, where we have no a priori expectations about the signs of these effects. Therefore popular fears about the trade effects of differences in environmental regulations might by exaggerated. The second chapter is entitled "Is trade bad for the Environment? Decomposing worldwide SO2 emissions, 1990-2000". First we construct a novel and large database containing reasonable estimates of SO2 emission intensities per unit labor that vary across countries, periods and manufacturing sectors. Then we use these original data (covering 31 developed and 31 developing countries) to decompose the worldwide SO2 emissions into the three well known dynamic effects (scale, technique and composition effect). We find that the positive scale (+9,5%) and the negative technique (-12.5%) effect are the main driving forces of emission changes. Composition effects between countries and sectors are smaller, both negative and of similar magnitude (-3.5% each). Given that trade matters via the composition effects this means that trade reduces total emissions. We next construct, in a first experiment, a hypothetical world where no trade happens, i.e. each country produces its imports at home and does no longer produce its exports. The difference between the actual and this no-trade world allows us (under the omission of price effects) to compute a static first-order trade effect. The latter now increases total world emissions because it allows, on average, dirty countries to specialize in dirty products. However, this effect is smaller (3.5%) in 2000 than in 1990 (10%), in line with the negative dynamic composition effect identified in the previous exercise. We then propose a second experiment, comparing effective emissions with the maximum or minimum possible level of SO2 emissions. These hypothetical levels of emissions are obtained by reallocating labour accordingly across sectors within each country (under the country-employment and the world industry-production constraints). Using linear programming techniques, we show that emissions are reduced by 90% with respect to the worst case, but that they could still be reduced further by another 80% if emissions were to be minimized. The findings from this chapter go together with those from chapter one in the sense that trade-induced composition effect do not seem to be the main source of pollution, at least in the recent past. Going now to the economic geography part of this thesis, the third chapter, entitled "A Dynamic Model with Sectoral Agglomeration Effects" consists of a short note that derives the theoretical model estimated in the fourth chapter. The derivation is directly based on the multi-regional framework by Ciccone (2002) but extends it in order to include sectoral disaggregation and a temporal dimension. This allows us formally to write present productivity as a function of past productivity and other contemporaneous and past control variables. The fourth chapter entitled "Sectoral Agglomeration Effects in a Panel of European Regions" takes the final equation derived in chapter three to the data. We investigate the empirical link between density and labour productivity based on regional data (245 NUTS-2 regions over the period 1980-2003). Using dynamic panel techniques allows us to control for the possible endogeneity of density and for region specific effects. We find a positive long run elasticity of density with respect to labour productivity of about 13%. When using data at the sectoral level it seems that positive cross-sector and negative own-sector externalities are present in manufacturing while financial services display strong positive own-sector effects. The fifth and last chapter entitled "Is the World's Economic Center of Gravity Already in Asia?" computes the world economic, demographic and geographic center of gravity for 1975-2004 and compares them. Based on data for the largest cities in the world and using the physical concept of center of mass, we find that the world's economic center of gravity is still located in Europe, even though there is a clear shift towards Asia. To sum up, this thesis makes three main contributions. First, it provides new estimates of orders of magnitudes for the role of trade in the globalisation and environment debate. Second, it computes reliable and disaggregated elasticities for the effect of density on labour productivity in European regions. Third, it allows us, in a geometrically rigorous way, to track the path of the world's economic center of gravity.

Cricotracheal resection for adult and pediatric subglottic stenoses: Similarities and differences

Since the mid-1970s thoracic surgeons have used cricotracheal resection (CTR) in the adult population. Similar positive results have from then on been reported by different investigators using this technique. In contrast, otolaryngologists have typically used an anterior midline approach to the larynx and trachea for their laryngotracheal reconstructions (LTRs), both in adults and children. The fear of injury to the recurrent laryngeal nerve (RLN), the risk of a dehiscence of the anastomosis, and the interference with normal growth of the larynx in the pediatric age group were the main reasons put forward for not using a CTR for the cure of subglottic stenosis. In this article, we describe the similarities and differences in CTRs performed for adult and pediatric cases. The high rate (>90%) of success for severe pediatric SGS using CTR compares most favorably with LTR, which is still used in most otolaryngology departments. The reasons lie in the full resection of the stenosis and the restoration of a steady cartilaginous framework of the larynx and trachea with full mucosal lining on both sides of the anastomosis. Furthermore, CTR can be associated with a Rethi procedure for the cure of combined posterior glottic and subglottic stenoses. Good results from series of two different centers suggest that CTR will become the treatment of choice for pediatric severe SGS, as is presently the case in the adult population.

Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index.

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P<0.0027) compared to the respective maternal alleles. Real-time PCR experiments of lymphoblastoid cell lines from the CEPH families showed that expression of both genes was dependent on parental origin of the SNPs alleles (P<0.01). Our scheme opens new opportunities to exploit GWAS data of unrelated individuals to identify POEs and demonstrates that they play an important role in adult obesity.

Implementation of raltegravir in routine clinical practice: selection criteria for choosing this drug, virologic response rates, and characteristics of failures.

BACKGROUND: Raltegravir (RAL) achieved remarkable virologic suppression rates in randomized-clinical trials, but today efficacy data and factors for treatment failures in a routine clinical care setting are limited. METHODS: First, factors associated with a switch to RAL were identified with a logistic regression including patients from the Swiss HIV Cohort Study with a history of 3 class failure (n = 423). Second, predictors for virologic outcome were identified in an intent-to-treat analysis including all patients who received RAL. Last observation carried forward imputation was used to determine week 24 response rate (HIV-1 RNA >or= 50 copies/mL). RESULTS: The predominant factor associated with a switch to RAL in patients with suppressed baseline RNA was a regimen containing enfuvirtide [odds ratio 41.9 (95% confidence interval: 11.6-151.6)]. Efficacy analysis showed an overall response rate of 80.9% (152/188), whereas 71.8% (84/117) and 95.8% (68/71) showed viral suppression when stratified for detectable and undetectable RNA at baseline, respectively. Overall CD4 cell counts increased significantly by 42 cells/microL (P < 0.001). Characteristics of failures were a genotypic sensitivity score of the background regimen <or=1, very low RAL plasma concentrations, poor adherence, and high viral load at baseline. CONCLUSIONS: Virologic suppression rates in our routine clinical care setting were promising and comparable with data from previously published randomized-controlled trials.

Improving plant functional groups for dynamic models of biodiversity: at the crossroads between functional and community ecology

The pace of on-going climate change calls for reliable plant biodiversity scenarios. Traditional dynamic vegetation models use plant functional types that are summarized to such an extent that they become meaningless for biodiversity scenarios. Hybrid dynamic vegetation models of intermediate complexity (hybrid-DVMs) have recently been developed to address this issue. These models, at the crossroads between phenomenological and process-based models, are able to involve an intermediate number of well-chosen plant functional groups (PFGs). The challenge is to build meaningful PFGs that are representative of plant biodiversity, and consistent with the parameters and processes of hybrid-DVMs. Here, we propose and test a framework based on few selected traits to define a limited number of PFGs, which are both representative of the diversity (functional and taxonomic) of the flora in the Ecrins National Park, and adapted to hybrid-DVMs. This new classification scheme, together with recent advances in vegetation modeling, constitutes a step forward for mechanistic biodiversity modeling.

Hégémonie du modèle de l'autisme: carrefour epistémologique entre médecine, familles et politique [Hegemonic model of autism: epistemological crossroads between medicine, family and politics].

The aim of this article is to make a contribution to the regional reflection with regard to autism spectrum disorders (ASDs) at a key moment in which the authorities are requested by the users, professionals in the fields of health, pedagogy and education to put forward a structured answer to a multitude of expressed needs. The question for the creation of a competence pole of an academic tertiary level is posed in order to advise in the best possible way the families who do not know how to orient themselves in the maze and contradictions of the proposed solutions and to help the professionals who are submerged by an ever increasing demand of services exceeding the means of the existing institutions and who cannot justify their choices among the various existing theoretical and scientific models.

THE USEFUL SIDE OF AMBIVALENCE: Ambivalent attitudes can be adaptive and socially valued

En s'inspirant de la littérature récente qui a dépeint l'ambivalence comme étant adaptative et en lien avec des comportements stratégiques, cette thèse examine le versant utile des attitudes ambivalentes. Elle met tout d'abord en évidence que son expression peut-être sciemment contrôlée et mise en avant pour des raisons d'auto-présentation. De plus, elle démontre que les individus peuvent présenter une attitude ambivalente afin de gagner l'approbation sociale sur un objet d'attitude controversé alors que l'inverse a été observé sur des objets consensuels (Première ligne de recherche). Cette thèse a également révélé que l'expression d'attitudes ambivalentes pouvait amener à être valorisé socialement. En effet, contrairement à des attitudes plus tranchées (pro-normatives ou contre-normatives), les attitudes ambivalentes ont été évaluées de façon plus importante sur la dimension de l'utilité sociale (une dimension qui indique la compétence d'autrui ou encore la propension à évoluer dans la hiérarchie sociale). La valorisation de l'ambivalence n'est apparue que sur la dimension de l'utilité sociale et non sur la dimension de la désirabilité sociale (une dimension qui indique la sympathie d'autrui ainsi que la propension à être apprécié socialement). De plus, ce résultat a été observé sur des thèmes controversés et non sur des thèmes consensuels (Seconde ligne de recherche). Dans l'ensemble cette thèse soutient une approche de l'ambivalence comme donnant lieu à des bénéfices. Elle peut également ouvrir la voie à l'étude de l'ambivalence en lien avec la pensée critique. - Drawing on the recent literature that portrayed ambivalence as being adaptive and linked with strategic behaviors, this thesis examines the useful side of ambivalent attitudes. It first revealed that the expression of ambivalent attitudes could be controlled and purposely displayed for self-presentational concerns. Furthermore, it demonstrated that people could put ambivalence forward to gain social approval when expressing it on controversial social issues, whereas the opposite was true on consensual social issues (First line of research). The thesis also revealed that the expression of ambivalent attitudes could lead to be socially valued. Indeed, contrary to clear-cut attitudes (either pro-normative or counter-normative attitudes), ambivalent attitudes have been evaluated the highest on the social utility dimension (a dimension indicating people's competence as well as the extent to which they are likely to climb in social hierarchy). The valorization of ambivalent attitudes only appeared on social utility and not on social desirability (a dimension indicating people's niceness as well as the extent to which they are likely to be socially appreciated). This effect was true on controversial social issues but not on consensual ones (Second line of research). Overall, this thesis provides support for an approach that conceives attitudinal ambivalence as leading to benefits. It also may open avenues for the study of ambivalence in relation with critical thinking.

Stochastic inversion of tracer test and electrical geophysical data to estimate hydraulic conductivities.

Quantifying the spatial configuration of hydraulic conductivity (K) in heterogeneous geological environments is essential for accurate predictions of contaminant transport, but is difficult because of the inherent limitations in resolution and coverage associated with traditional hydrological measurements. To address this issue, we consider crosshole and surface-based electrical resistivity geophysical measurements, collected in time during a saline tracer experiment. We use a Bayesian Markov-chain-Monte-Carlo (McMC) methodology to jointly invert the dynamic resistivity data, together with borehole tracer concentration data, to generate multiple posterior realizations of K that are consistent with all available information. We do this within a coupled inversion framework, whereby the geophysical and hydrological forward models are linked through an uncertain relationship between electrical resistivity and concentration. To minimize computational expense, a facies-based subsurface parameterization is developed. The Bayesian-McMC methodology allows us to explore the potential benefits of including the geophysical data into the inverse problem by examining their effect on our ability to identify fast flowpaths in the subsurface, and their impact on hydrological prediction uncertainty. Using a complex, geostatistically generated, two-dimensional numerical example representative of a fluvial environment, we demonstrate that flow model calibration is improved and prediction error is decreased when the electrical resistivity data are included. The worth of the geophysical data is found to be greatest for long spatial correlation lengths of subsurface heterogeneity with respect to wellbore separation, where flow and transport are largely controlled by highly connected flowpaths.

Anti-angiogenic therapies in cancer: achievements and open questions.

The approval in 2004 of bevacizumab (Avastin), a neutralizing monoclonal antibody directed against vascular endothelial growth factor (VEGF) as the first anti-angiogenic systemic drug to treat cancer patients validated the notion introduced 33 years earlier by Dr. Judah Folkman, that inhibition of tumor angiogenesis might be a valid approach to control tumor growth. Anti-angiogenic therapy was greeted in the clinic a major step forward in cancer treatment. At the same time this success recently boosted the field to the quest for new anti-angiogenic targets and drugs. In spite of this success, however, some old questions in the field have remained unanswered and new ones have emerged. They include the identification for surrogate markers of angiogenesis and anti-angiogenesis, the understanding about how anti-angiogenic therapy and chemotherapy synergize, the characterization of the biological consequences of sustained suppression of angiogenesis on tumor biology and normal tissue homeostasis, and the mechanisms of tumor escape from anti-angiogenesis. In this review we summarize some of these outstanding questions, and highlight future challenges in clinical, translational and experimental research in anti-angiogenic therapy that need to be addressed in order to improve current treatments and to design new drugs.

Are there control processes, and (if so) can they be studied?

Generally, so-called control processes are thought to be necessary when we must perform one out of several competing actions. Some examples include performance of a less well-practiced action instead of a well-practiced one (prepotency); learning a new action (novelty); and rapidly switching from one action to another (task-switching). While it certainly is difficult to perform the desired action in these circumstances, it is less clear that a separate set of processes (e.g., control processes) are necessary to explain the observed behavior. Another way to approach the study of control processes is to investigate physiological dependent measures (e.g., electrophysiological or neuroimaging measures). Although these offer another avenue of inquiry into control processes, they have yet to furnish unambiguous evidence that control processes exist. While this might suggest that there are no control processes, it is also possible that our methods are insufficiently sensitive to measure control processes. We have investigated this latter possibility using tasks that are neuroanatomically distinct, though within the same modality (vision). This approach did not yield evidence for a separable set of control processes. However, recent works using a task-switching paradigm in which subjects switch between a visual and an auditory task suggest that switching both task and modality may be importantly different than switching task within a given modality. This may represent a way forward in the study of control processes.

Neuronal inputs and outputs of aging and longevity.

An animal's survival strongly depends on its ability to maintain homeostasis in response to the changing quality of its external and internal environment. This is achieved through intracellular and intercellular communication within and among different tissues. One of the organ systems that plays a major role in this communication and the maintenance of homeostasis is the nervous system. Here we highlight different aspects of the neuronal inputs and outputs of pathways that affect aging and longevity. Accordingly, we discuss how sensory inputs influence homeostasis and lifespan through the modulation of different types of neuronal signals, which reflects the complexity of the environmental cues that affect physiology. We also describe feedback, compensatory, and feed-forward mechanisms in these longevity-modulating pathways that are necessary for homeostasis. Finally, we consider the temporal requirements for these neuronal processes and the potential role of natural genetic variation in shaping the neurobiology of aging.

CR1Dmod: A Matlab program to model 1D complex resistivity effects in electrical and electromagnetic surveys

We have constructed a forward modelling code in Matlab, capable of handling several commonly used electrical and electromagnetic methods in a 1D environment. We review the implemented electromagnetic field equations for grounded wires, frequency and transient soundings and present new solutions in the case of a non-magnetic first layer. The CR1Dmod code evaluates the Hankel transforms occurring in the field equations using either the Fast Hankel Transform based on digital filter theory, or a numerical integration scheme applied between the zeros of the Bessel function. A graphical user interface allows easy construction of 1D models and control of the parameters. Modelling results are in agreement with other authors, but the time of computation is less efficient than other available codes. Nevertheless, the CR1Dmod routine handles complex resistivities and offers solutions based on the full EM-equations as well as the quasi-static approximation. Thus, modelling of effects based on changes in the magnetic permeability and the permittivity is also possible.