Obtenció de matrius poroses d'àcid polilàctic (PDLLA) mitjançant fluids comprimits per a ús en regeneració tissular

En aquest treball es pretén obtenir material porós de PDLLA, amb ús potencial com a bastida en enginyeria tissular, mitjançant l’ús de freó R-134a com a fluid escumant. Per aquest motiu, s’ha realitzat un estudi on es valoren diferents variables com la temperatura de procés, la pressió de treball i l’ús de N2 en la despressurització que poden modificar la microestructura final de la bastida.

Anàlisi i disseny d'un reflector per banda W

Les ones passives mil·limètriques (30 a 300GHz) tenen la peculiaritat de propagar-se en medis com la boira o la roba, a diferència del rang visible o l’infraroig. D’aquesta peculiaritat, surt l’interès de reproduir imatges per diverses aplicacions (seguretat, vigilància, etc...). És per aquest motiu que es treballa en el disseny d’un reflector per aquest tipus d’aplicació, treballant a una de les finestres de propagació d’aquest rang, la de la banda W. Es dissenyen i analitzen tres tipus de reflector: parabòlic simètric, offset i Cassegrain. D’aquests, s’estudien les seves figures de mèrit i directivitats buscant que aquestes siguin el més elevades possibles per obtenir una bona resolució, així com l’escaneig de l’escena de la qual es vol obtenir una imatge, veient aquí els efectes de les aberracions més comunes.

The Original Risk: Over-Theologizing Ethics and Under-Theologizing Sin

The project of articulating a theological ethics on the basis of liturgical anthropology is bound to fail if the necessary consequence is that one has to quit the forum of critical modern rationality. The risk of Engelhardt's approach is to limit rationality to a narrow vision of reason. Sin is not to be understood as the negation of human holiness, but as the negation of divine holiness. The only way to renew theological ethics is to understand sin as the anthropological and ethical expression of the biblical message of the justification by faith only. Sin is therefore a secondary category, which can only by interpreted in light of the positive manifestation of liberation, justification, and grace. The central issue of Christian ethics is not ritual purity or morality, but experience, confession and recognition of our own injustice in our dealing with God and men.

Adolescent substance-use assessment: methodological issues in the use of the Adolescent Drug Abuse Diagnosis (ADAD).

During the past twenty years, various instruments have been developed for the assessment of substance use in adolescents, mainly in the United States. However, few of them have been adapted to, and validated in, French-speaking populations. Consequently, although increasing alcohol and drug use among teenagers has become a major concern, the various health and social programs developed in response to this specific problem have received little attention with regard to follow-up and outcome assessment. A standardized multidimensional assessment instrument adapted for adolescents is needed to assess the individual needs of adolescents and assign them to the most appropriate treatment setting, to provide a single measurement within and across health and social systems, and to conduct treatment outcome evaluations. Moreover, having an available instrument makes it possible to develop longitudinal and transcultural research studies. For this reason, a French version of the Adolescent Drug Abuse Diagnosis (ADAD) was developed and validated at the University Child and Adolescent Psychiatric Clinic in Lausanne, Switzerland. This article aims to discuss the methodological issues that we faced when using the ADAD instrument in a 4-year longitudinal study including adolescent substance users. Methodological aspects relating to the content and format of the instrument, the assessment administration and the statistical analyses are discussed.

Reinfection in American Cutaneous Leishmaniasis: Evaluation of Clinical Outcomes in the Hamster Model

There is no clear understanding of the outcome of reinfection in New World cutaneous leishmaniasis, and its role in the relationship to the development of protection or secondary disease. For this reason, reinfection experiments with homologous (Leishmania panamensis-L. panamensis) and heterologous (L. major-L. panamensis) species of leishmaniae were conducted in the hamster model. The different protocols for primary infections prior to the challenge with L. panamensis were as follows: (a) L. major, single promastigote injection, (b) L. major, three booster infections, (c) L. panamensis, followed by antimonial treatment to achieve subclinical infection, (d) L. panamensis, with active lesions, (e) sham infected, naive controls. Although all reinfected hamsters developed lesions upon challenge, animals with active primary lesions due to L. panamensis, and receiving booster infections of L. major had the most benign secondary lesions (58-91% and 69-76% smaller than controls, respectively, P<0.05). Subclinically infected animals had intermediate lesions (40-64% smaller than controls, P<0.05), while hamsters which received a single dose of L. major had no significant improvement over controls. Our results suggested that L. major could elicit a cross protective response to L. panamensis, and that the presence and number of amastigotes persisting after a primary infection may influence the clinical outcome of reinfections.

Characterization of the effects of IL-17F on CHO cell line generation

CHO is the most commonly used mammalian host for the generation of cell lines allowing for the production of high quality therapeutic proteins. The generation of such cell lines is a lengthy and resource-intensive process requiring extensive screening in order to isolate candidates with optimal characteristics, such as growth, stability and productivity. For this reason, the biotechnology industry invests much effort in attempts to optimize CHO expression systems in order to streamline and shorten the cell line selection process. Based on preliminary observations of a facilitated selection of CHO-GS cell lines expressing members of the IL-17 cytokine family, this study investigates the use of IL-17F as a novel enhancing factor for CHO cell line generation. Using two different CHO expression systems (exploiting GS and DHFR-based selection), we demonstrated that IL-17F expression caused a significant increase in the occurrence of colonies during the selection process. All colonies selected produced substantial amounts of IL-17F, suggesting that benefits were conferred, during selection, to those cells expressing the cytokine. Furthermore, transgene expression levels were significantly increased when the selection pressure was raised to a level that would not normally be permissive for colony selection (i.e. 100 |o.M MSX for the CHO-GS expression system or 1000 nM MTX for the CHO-DHFR system). Finally, IL-17F expression was also found to enhance the rate of appearance of clones during single cell subcloning in the absence of selection pressure. Overall, these benefits have the potential to allow a substantial reduction in the length of cell line generation while significantly increasing cell line productivity. Nevertheless, we found that the high IL-17F expression levels required to convey enhancing effects was a limitation when attempting to co-express IL-17F and a recombinant soluble protein of therapeutic interest from independent CMV promoters within the same expression vector. In order to understand and overcome this limitation, studies were designed to characterize the IL-17F enhancing effect at the molecular and cellular level. Regular supplementation of recombinant biologically-active IL-17F into the culture medium during cell line selection was not able to reproduce the enhancing effects of endogenous IL-17F expression. In addition, increased IL-17F expression correlated with increased CHO-GS selection transgene expression at the single cell level. This data suggested a possible effect of IL-17F on viral promoter activity or transgene mRNA stability. It also provided direct evidence that the cells expressing the highest amounts of IL-17F obtained the most benefit. Overall data obtained from these study implied that IL-17F may act through an intracellular mechanism, possibly exerted during secretion. We therefore initiated experiments designed to determine the specific compartment(s) within which IL-17F triggers its effect. This work has identified IL-17F as a potentially powerful tool to optimize the CHO cell line generation process. The characterization of this enhancing effect at the molecular level has given us several insights into overcoming the current limitations, thus paving the way for the development of a viable technology that can be exploited within the biotechnology industry. - La CHO est la cellule hôte de mammifere la plus couramment utilisée dans la création de lignée cellulaire produisant des protéines thérapeutiques de haute qualité. La génération de ces lignées cellulaires est un processus long et exigeant l'utilisation de techniques de sélection robustes afin d'isoler des candidats possédants les caractéristiques optimales de croissance, de productivité et de stabilité d'expression. Les industries biopharmaceutiques ont investi beaucoup d'efforts afin d'optimiser les systèmes d'expression CHO dans le but raccourcir la longueur du procédé de sélection de lignées cellulaires et aussi d'en augmenter l'efficacité. A partir d'observations préliminaires obtenues lors de la génération de lignées cellulaires CHO- GS exprimant une cytokine appartenant à la famille des IL-17, nous avons réalisé une étude portant sur l'utilisation de l'IL-17F humaine (IL-17F) comme nouveau facteur d'optimisation pour la génération de lignées cellulaires CHO. Nous avons démontré, en utilisant les deux systèmes de sélection et d'expression CHO couramment utilisés (le premier exploitant la GS et l'autre basée sur la DHFR), que l'expression de l'IL-17F permet une augmentation significative de la fréquence d'apparition de colonies durant le processus de sélection de lignées cellulaires. Les différentes colonies sélectionnées expriment des quantités substantielles d'IL-17F, suggérant un effet bénéfique lors de la sélection qui serait exclusivement conféré aux cellules exprimant la cytokine. En outre, le niveau d'expression du transgene se trouve significativement augmenté lorsque la pression de sélection est portée à un niveau habituellement trop élevé pour permettre la sélection de colonies (soit 100 |JM MSX pour le système d'expression CHO-GS ou 1000 nM MTX pour le système CHO- DHFR). Enfin, l'expression d'IL-17F permet également d'améliorer la vitesse d'apparition de clones pendant une étape de sous-clonage en l'absence de pression de sélection. L'ensemble de ces effets bénéfiques permettent une réduction substantielle de la durée de génération de lignées cellulaires tout en augmentant considérablement la productivité des lignées obtenues. Néanmoins, nous avons constaté que la nécessité d'exprimer des niveaux élevés d'IL-17F afin obtenir l'ensemble de ses effets bénéfiques devient une contrainte lors de l'utilisation d'un vecteur d'expression composé de deux promoteurs CMV indépendants pour la co-expression de la cytokine et d'une protéine soluble présentant un intérêt thérapeutique. Afin de mieux comprendre et de surmonter cette limitation, plusieurs études ont été effectuées dans le but de mieux caractériser l'effet de IL-17F au niveau subcellulaire. L'apport régulier en IL-17F recombinante et biologiquement active dans le milieu de culture lors de la sélection de lignées cellulaires ne permet pas de reproduire les effets bénéfiques observés par l'expression endogène d'IL-17F. En outre, nous avons constaté que, lors de l'utilisation du système CHO- GS, l'augmentation d'expression de 1TL-17F est corrélée à un accroissement de l'expression du marqueur de sélection au niveau cellulaire. Ces résultats suggèrent un possible effet d'IL- 17F sur l'activité des promoteurs viraux et ainsi fournissent une preuve directe que les cellules exprimant de haut niveau d'IL-17F sont celles qui en profitent le plus. L'ensemble de ces observations mettrait en avant que l'effet d'IL-17F se ferait selon un mécanisme intracellulaire. Nous avons donc étudié le(s) compartiment(s) spécifique(s) dans lequel IL-17F pourrait exercer son effet. Ce travail a permis de définir IL-17F comme un puissant outil pour l'optimisation des procédés de génération de lignées cellulaires CHO. La caractérisation de cette amélioration de l'effet au niveau moléculaire nous a donné plusieurs indications sur la manière de dépasser les limitations actuelles, ouvrant ainsi la voie au développement d'une technologie viable qui peut être exploitée pars l'industrie biotechnologique.

Short term evolution of a highly transmissible methicillin-resistant Staphylococcus aureus clone (ST228) in a tertiary care hospital.

Staphylococcus aureus is recognized as one of the major human pathogens and is by far one of the most common nosocomial organisms. The genetic basis for the emergence of highly epidemic strains remains mysterious. Studying the microevolution of the different clones of S. aureus is essential for identifying the forces driving pathogen emergence and spread. The aim of the present study was to determine the genetic changes characterizing a lineage belonging to the South German clone (ST228) that spread over ten years in a tertiary care hospital in Switzerland. For this reason, we compared the whole genome of eight isolates recovered between 2001 and 2008 at the Lausanne hospital. The genetic comparison of these isolates revealed that their genomes are extremely closely related. Yet, a few more important genetic changes, such as the replacement of a plasmid, the loss of large fragments of DNA, or the insertion of transposases, were observed. These transfers of mobile genetic elements shaped the evolution of the ST228 lineage that spread within the Lausanne hospital. Nevertheless, although the strains analyzed differed in their dynamics, we have not been able to link a particular genetic element with spreading success. Finally, the present study showed that new sequencing technologies improve considerably the quality and quantity of information obtained for a single strain; but this information is still difficult to interpret and important investments are required for the technology to become accessible for routine investigations.

Factores de rendimiento en entornos multicore

Este documento refleja el estudio de investigación para la detección de factores que afectan al rendimiento en entornos multicore. Debido a la gran diversidad de arquitecturas multicore se ha definido un marco de trabajo, que consiste en la adopción de una arquitectura específica, un modelo de programación basado en paralelismo de datos, y aplicaciones del tipo Single Program Multiple Data. Una vez definido el marco de trabajo, se han evaluado los factores de rendimiento con especial atención al modelo de programación. Por este motivo, se ha analizado la librería de threads y la API OpenMP para detectar aquellas funciones sensibles de ser sintonizadas al permitir un comportamiento adaptativo de la aplicación al entorno, y que dependiendo de su adecuada utilización han de mejorar el rendimiento de la aplicación.

Modelos de viento aplicados a la mejora en la predicción de incendios forestales

La predicción de incendios forestales es uno de los grandes retos de la comunidad científica debido al impacto medioambiental, humano y económico que tienen en la sociedad. El comportamiento de este fenómeno es difícil de modelar debido a la gran cantidad de variables que intervienen y la dificultad que implica su correcta medición. Los simuladores de fuego son herramientas muy útiles pero, actualmente, los resultados que obtenemos tienen un alto grado de imprecisión. Desde nuestro grupo se ha trabajado en la predicción en dos etapas, donde antes de realizar cualquier predicción, se incorpora una etapa de ajuste de los parámetros de entrada para obtener mejores predicciones. Pese a la mejora que supone este nuevo paradigma de predicción, las simulaciones sobre incendios reales tienen un alto grado de error por el efecto de las condiciones meteorológicas que, usualmente, varían de manera notable durante el transcurso de la simulación. Uno de los factores más determinantes en el comportamiento de un incendio, junto con las características del terreno, es el viento. Los modelos de predicción son extremadamente sensibles al cambio en los componentes de dirección y velocidad del viento por lo que cualquier mejora que podamos introducir para mejorar la calidad de estas componentes influye directamente en la calidad de la predicción. Nuestro sistema de predicción utiliza la dirección y velocidad del viento de forma global en todo el terreno, y lo que proponemos con este trabajo es introducir un modelo de vientos que nos permita generar vientos locales en todas las celdas en las que se divide el terreno. Este viento local dependerá del viento general y de las características del terreno de dichas celdas. Consideramos que la utilización de un viento general no es suficiente para realizar una buena predicción del comportamiento de un incendio y hemos comprobado que la inclusión de un simulador de campo de vientos en nuestro sistema puede llegar a mejorar nuestras predicciones considerablemente. Los resultados obtenidos en los experimentos sintéticos que hemos realizado nos hacen ser optimistas, puesto que consideramos que la inclusión de componentes de viento locales permitirá mejorar nuestras predicciones en incendios reales.

Prevalence of victims of violence admitted to an emergency department.

OBJECTIVE: To collect data on the consultation frequency and demographic profile of victims of violence attending an emergency department (ED) in Switzerland. METHODS: We undertook screening of all admitted adult patients (>16 years) in the ED of the CHUV, Lausanne, Switzerland, over a 1 month period, using a modified version of the Partner Violence Screen questionnaire. Exclusionary criteria were: life threatening injury (National Advisory Committee on Aeronautics score > or =4), or inability to understand or speak French, to give oral informed consent, or to be questioned without a family member or accompanying person being present. Data were collected on history of physical and/or psychological violence during the previous 12 months, the type of violence experienced by the patient, and if violence was the reason for the current consultation. Sociodemographic data were obtained from the registration documents. RESULTS: The final sample consisted of 1602 patients (participation rate of 77.2%), with a refusal rate of 1.1%. Violence during the past 12 months was reported by 11.4% of patients. Of the total sample, 25% stated that violence was the reason for the current consultation; of these, 95% of patients were confirmed as victims of violence by the ED physicians. Patients reporting violence were more likely to be young and separated from their partner. Men were more likely to be victims of public violence and women more commonly victims of domestic violence. CONCLUSIONS: Based on this monthly prevalence rate, we estimate that over 3000 adults affected by violence consult our ED per annum. This underlines the importance of the problem and the need to address it. Health services organisations should establish measures to improve quality of care for victims. Guidelines and educational programmes for nurses and physicians should be developed in order to enhance providers' skills and basic knowledge of all types of violence, how to recognise and interact appropriately with victims, and where to refer these patients for follow up care in their local networks.

Seroprevalence of Trypanosoma cruzi Infection in Students at the Seven-Fourteen Age Range, Londrina, PR, Brazil, in 1995

Seropositivity for Chagas disease was evaluated in 834 children aged between 7 and 14 from the Municipal Teaching System in the district of Londrina, State of Paraná. A seroprevalence rate of 0.1% was found through the use of an indirect immunofluorescent test and an enzyme-linked immunosorbent assay. This low rate of seroprevalence provides evidence that the vectorial transmission of Chagas disease has been eliminated in Londrina. The main reason for the elimination of vectorial transmission of Trypanosoma cruzi infection, as evaluated by serological tests, may be a remarkable change in the economic structure of the northern region of Paraná in the 1960's. At that time coffee production was almost completely replaced by soy beans, wheat and grazing in the rural areas. This change deeply affected the rural ecology and caused an exodus of the population from rural to urban areas as well as a decrease in the total number of the population of that region. The measures introduced for controlling the disease through the Program of Chagas Disease Control established by the Fundação Nacional de Saúde of the Brazilian Ministry of Health, certainly, had a positive impact on the reduction of American trypanosomiasis prevalence in the area under study. However, it does not seem that this was the most relevant factor responsible for the elimination of vectorial transmission of Chagas disease in Londrina.

Long-term follow-up of four patients with Langer-Giedion syndrome: clinical course and complications.

Long-term observations of individuals with the so-called Langer-Giedion (LGS) or tricho-rhino-phalangeal type II (TRPS2) are scarce. We report here a on follow-up of four LGS individuals, including one first described by Andres Giedion in 1969, and review the sparse publications on adults with this syndrome which comprises ectodermal dysplasia, multiple cone-shaped epiphyses prior to puberty, multiple cartilaginous exostoses, and mostly mild intellectual impairment. LGS is caused by deletion of the chromosomal segment 8q24.11-q24.13 containing among others the genes EXT1 and TRPS1. Most patients with TRPS2 are only borderline or mildly cognitively delayed, and few are of normal intelligence. Their practical skills are better than their intellectual capability, and, for this reason and because of their low self-esteem, they are often underestimated. Some patients develop seizures at variable age. Osteomas on processes of cervical vertebrae may cause pressure on cervical nerves or dissection of cerebral arteries. Joint stiffness is observed during childhood and changes later to joint laxity causing instability and proneness to trauma. Perthes disease is not rare. Almost all males become bald at or soon after puberty, and some develop (pseudo) gynecomastia. Growth hormone deficiency was found in a few patients, TSH deficiency so far only in one. Puberty and fertility are diminished, and no instance of transmission of the deletion from a non-mosaic parent to a child has been observed so far. Several affected females had vaginal atresia with consequent hydrometrocolpos.

'Hearts and bones': the ups and downs of 'plasticity' in stem cell biology.

More than a decade ago, 'plasticity' suddenly became a 'fashionable' topic with overemphasized implications for regenerative medicine. The concept of 'plasticity' is supported by old transplantation work, at least for embryonic cells, and metaplasia is a classic example of plasticity observed in patients. Nevertheless, the publication of a series of papers showing rare conversion of a given cell type into another unrelated cell raised the possibility of using any unaffected tissue to create at will new cells to replace a different failing tissue or organ. This resulted in disingenuous interpretations and a reason not to fund anymore research on embryonic stem cells (ESc). Moreover, many papers on plasticity were difficult to reproduce and thus questioned; raising issues about plasticity as a technical artefact or a consequence of rare spontaneous cells fusion. More recently, reprogramming adult differentiated cells to a pluripotent state (iPS) became possible, and later, one type of differentiated cell could be directly reprogrammed into another (e.g. fibroblasts into neurons) without reverting to pluripotency. Although the latter results from different and more robust experimental protocols, these phenomena also exemplify 'plasticity'. In this review, we want to place 'plasticity' in a historical perspective still taking into account ethical and political implications.

Re-opening the black box in societal metabolism: the application of MuSIASEM to water

In this paper we address the complexity of the analysis of water use in relation to the issue of sustainability. In fact, the flows of water in our planet represent a complex reality which can be studied using many different perceptions and narratives referring to different scales and dimensions of analysis. For this reason, a quantitative analysis of water use has to be based on analytical methods that are semantically open: they must be able to define what we mean with the term “water” when crossing different scales of analysis. We propose here a definition of water as a resource that deal with the many services it provides to humans and ecosystems. WE argue that water can fulfil so many of them since the element has many characteristics that allow for the resource to be labelled with different attributes, depending on the end use –such as drinkable. Since the services for humans and the functions for ecosystems associated with water flows are defined on different scales but still interconnected it is necessary to organize our assessment of water use across different hierarchical levels. In order to do so we define how to approach the study of water use in the Societal Metabolism, by proposing the Water Metabolism, tganized in three levels: societal level, ecosystem level and global level. The possible end uses we distinguish for the society are: personal/physiological use, household use, economic use. Organizing the study of “water use” across all these levels increases the usefulness of the quantitative analysis and the possibilities of finding relevant and comparable results. To achieve this result, we adapted a method developed to deal with multi-level, multi-scale analysis - the Multi-Scale Integrated Analysis of Societal and Ecosystem Metabolism (MuSIASEM) approach - to the analysis of water metabolism. In this paper, we discuss the peculiar analytical identity that “water” shows within multi-scale metabolic studies: water represents a flow-element when considering the metabolism of social systems (at a small scale, when describing the water metabolism inside the society) and a fund-element when considering the metabolism o ecosystems (at a larger scale when describing the water metabolism outside the society). The theoretical analysis is illustrated using two case which characterize the metabolic patterns regarding water use of a productive system in Catalonia and a water management policy in Andarax River Basin in Andalusia.

Els delictes contra la seguretat viària: aspectes substantius, processals i criminològics

Les infraccions penals en matèria de seguretat viària constitueixen un dels grups delictius que més interès teòric i pràctic han despertat en la doctrina i la jurisprudència. Per aquest motiu, al llarg de la recerca s'ha dut a terme l'anàlisi dels diferents il·lícits penals des d'una perspectiva interdisciplinar i transversal on no tan sols han tingut cabuda les reflexions teòriques i pràctiques sobre els arts. 379 i ss. CP, sinó també la valoració dels problemes processals i criminològics que són propis d'aquests fets justiciables que es vinculen amb la seguretat viària