Efficacy and safety of certolizumab pegol in an unselected crohn's disease population: 26-week data of the FACTS II survey.

BACKGROUND: Certolizumab pegol (Cimzia, CZP) was approved for the treatment of Crohn's disease (CD) patients in 2007 in Switzerland as the first country worldwide. This prospective phase IV study aimed to evaluate the efficacy and safety of CZP over 26 weeks in a multicenter cohort of practice-based patients. METHODS: Evaluation questionnaires at baseline, week 6, and week 26 were completed by gastroenterologists in hospitals and private practices. Adverse events were evaluated according to World Health Organization (WHO) guidelines. RESULTS: Sixty patients (38F/22M) were included; 53% had complicated disease (stricturing or penetrating), 45% had undergone prior CD-related surgery. All patients had prior exposure to systemic steroids, 96% to immunomodulators, 73% to infliximab, and 43% to adalimumab. A significant decrease of the Harvey-Bradshaw Index (HBI) was observed under CZP therapy (12.2 ± 4.9 at week 0 versus 6.3 ± 4.7 at week 6 and 6.7 ± 5.3 at week 26, both P < 0.001). Response and remission rates were 70% and 40% (week 6) and 67% and 36%, respectively (week 26). The complete perianal fistula closure rate was 36% at week 6 and 55% at week 26. The frequency of adverse drug reactions attributed to CZP was 5%. CZP was continued in 88% of patients beyond week 6 and in 67% beyond week 26. CONCLUSIONS: In a population of CD patients with predominantly complicated disease behavior, CZP proved to be effective in induction and maintenance of response and remission. This series provides the first evidence of CZP's effectiveness in perianal fistulizing CD in clinical practice.

Variació dels estatges vegetals a l'àrea de la Bruguera (Girona) en els darrers cent anys

Treball de recerca realitzat per alumnes d'ensenyament secundari i guardonat amb un Premi CIRIT per fomentar l'esperit cientí­fic del Jovent l'any 2009. Aquest treball s'ha basat en la comparació altitudinal de determinades espècies vegetals (i per tant dels estatges) respecte els últims cent anys en una zona de la vall de Ribes; concretament des de la serra de St. Amanç fins a la població de Bruguera, passant per els Llisos del Taga. La realització del treball implica primerament la recerca d'estudis i dades anteriors fets sobre el tema, que generalment es basaria en dos estudis ja esmentats en el treball, els quals són un catàleg florístic de la vall de Ribes (de Josep Vigo) i un article de característiques molt semblants al nostre treball (de Jonathan Lenoir), així com també l¡elecció de la metodologia i de les espècies a estudiar. L'altra part es basa en fer un comptatge i identificació de les espècies trobades en diferents zones. En el moment de fer la delimitació de les zones hem tingut en compte l'alçada i l'orientació i s'han subdividit aquestes zones en quadrants per facilitar el comptatge i identificació. Una vegada comparats els resultats amb els estudis fets anteriorment s'ha arribat a la conclusió que hi havia un canvi altitudinal de les espècies prou significatiu. Unes de les interpretacions d'aquest resultat observat podria lligar-se al canvi de temperatures que ha sofert la vall en els últims anys degut al canvi climàtic.

A malaria merozoite surface protein (MSP1)-structure, processing and function

Merozoite surface protein-1 (MSP-1, also referred to as P195, PMMSA or MSA 1) is one of the most studied of all malaria proteins. The proteins. The protein is found in all malaria species investigated and structural studies on the gene indicate that parts of the molecule are well-conserved. Studies on Plasmodium falciparum have shown that the protein is in a processed form on the merozoite surface, a result of proteolytic cleavage of the large percursor molecule. Recent studies have identified some of these cleavage sites. During invasion of the new red cell most of the MSP1 molecule is shed from the parasite surface except for a small C-terminal fragment which can be detected in ring stages. Analysis of the structure of this fragment suggests that it contains two growth factor-like domains that may have a functional role.

T cell responses to repeat and non-repeat regions of the circumsporozoite protein detected in volunteers immunized with Plasmodium falciparum sporozoites

The design of malarial vaccine based on the circumsporozoite (CS) protein, a majuor surface antigen of the sporozoite stage of the malaria parasite, requires the identification of T and B cell epitopes for inclusion in recombinant or synthetic vaccine candidates. We have investigated the specificity and function of a series of T cell clones, derived from volunteers immunized with Plasmodium falciparum sporozoites in an effort to identify relevant epitopes in the immune response to the pre-erythrocytic stages of the parasite. CD4+ T cell clones were obtained wich specifically recognized a repetitive epitope located in the 5'repeat region of the CS protein. This epitope, when conjugated to the 3'repeat region in a synthetic MAPs construct, induced high titers of antisporozoite antibodies in C57B1 mice. A second T cell epitope, which mapped to aa 326-345 of the carboxy terminal, was recognized by lytic, as well as non-lytic, CD4+ T cells derived from the sporozoite-immunized volunteers. The demonstration of CD4+ CTL in the volunteers, and the recent studies inthe rodent model (Renia et al., 1991; Tsuji et al., 1990), suggested that CS-specific CD4+ T cells, in addition to their indirect role as helper cells in the induction of antibody and CD8 + effector cells, may also play a direct role in protection against sporozoite challenge by targeting EEF within the liver.

Mathematical description of bacterial traveling pulses

The Keller-Segel system has been widely proposed as a model for bacterial waves driven by chemotactic processes. Current experiments on E. coli have shown precise structure of traveling pulses. We present here an alternative mathematical description of traveling pulses at a macroscopic scale. This modeling task is complemented with numerical simulations in accordance with the experimental observations. Our model is derived from an accurate kinetic description of the mesoscopic run-and-tumble process performed by bacteria. This model can account for recent experimental observations with E. coli. Qualitative agreements include the asymmetry of the pulse and transition in the collective behaviour (clustered motion versus dispersion). In addition we can capture quantitatively the main characteristics of the pulse such as the speed and the relative size of tails. This work opens several experimental and theoretical perspectives. Coefficients at the macroscopic level are derived from considerations at the cellular scale. For instance the stiffness of the signal integration process turns out to have a strong effect on collective motion. Furthermore the bottom-up scaling allows to perform preliminary mathematical analysis and write efficient numerical schemes. This model is intended as a predictive tool for the investigation of bacterial collective motion.

Los buscavidas: nómadas del capitalismo

Esta investigación se propone describir los rasgos esenciales de un tipo de personajes que hemos denominado, a efectos de generalización teórica, como “buscavidas”, peregrinos antihéroes del sistema laboral contemporáneo, deficientemente integrados a los valores del capitalismo e irreductibles a sus principios disciplinarios, que podemos hallar en la novelística del s. XX. He escogido a título de ejemplo cuatro novelas emblemáticas: Viaje al fin de la noche (1932), de Louis-Ferdinand Celine (1894-1961); La Conjura de los Necios (1980), de John Kennedy Toole (1937-1969); Factotum (1975), de Charles Bukowski (1920-1994) y Los Hermanos Tanner (1907), de Robert Walser (1878-1956). Asimismo, en el tercer capítulo de esta investigación, tendremos en cuenta la novela El Desaparecido (1927), de Franz Kafka (1883-1924), como un contrapunto iluminador que contribuye a analizar el tejido problemático de las dinámicas laborales en el pasado siglo. Karl Rossman, “el desaparecido”, no pertenece a la categoría de los buscavidas, porque a diferencia de estos, aspira a progresar en su carrera, pero sufre los golpes bajos de un sistema que tiene reservado a su condición de emigrante la misma suerte ingrata.

Abraham, fin de l'éthique ? Une méditation

(Résumé de l'ouvrage) Les trois grandes religions monothéistes se partagent un même ancêtre: Abraham. Pour les juifs, il est le Juste; les chrétiens voient en lui le Père des croyants et les musulmans le nomment Ami de Dieu. Il n'y a donc pas un discours sur Abraham, mais une multitude de lectures des textes fondamentaux et superbes qui racontent le destin d'Abraham dans la Bible. Dans ce livre, on propose quelques relectures du personnage et de son accueil dans l'histoire. Les auteurs permettent ainsi de redonner à la figure emblématique d'Abraham une jeunesse oh! combien nécessaire. Auteurs: Thomas Römer, David Banon, Jean-Daniel Kaestli, Daniel Marguerat, Jean-Claude Basset, Thierry de Saussure, Bernard Reymond, Denis Müller, Pierre Gisel, Abraham Segal.

Temperament in Bach’s Well-tempered clavier: a historical survey and a new evaluation according to dissonance theory

After a historical survey of temperament in Bach’s Well-Tempered Clavier by Johann Sebastian Bach, an analysis of the work has been made by applying a number of historical good temperaments as well as some recent proposals. The results obtained show that the global dissonance for all preludes and fugues in major keys can be minimized using the Kirnberger II temperament. The method of analysis used for this research is based on the mathematical theories of sensory dissonance, which have been developed by authors such as Hermann Ludwig Ferdinand von Helmholtz, Harry Partch, Reinier Plomp, Willem J. M. Levelt and William A. Sethares

CRM : Centro Metalúrgico de Sabadell

El proyecto está basado en la creación de una herramienta para poder gestionar las relaciones que el Centro Metalúrgico de Sabadell tiene con sus clientes. La tarea a desarrollar es un CRM (Custom Relationship Management) para gestionar todos los servicios y ofertas que ofrece el centro con sus clientes, desde cursos impartidos u organizados, consultas que tienen los empleados de los socios, asesoramientos, acciones de los clientes pero también información útil para conocer el estado de acciones comerciales con un cliente, contactos de un socio, así como sus empleados.

Learning Disabilities and Health

This factsheet on learning disability has been compiled by the Department of Health South East. It highlights the health inequalities experienced by those with learning disabilities and summarises the main health-related issues. It details key publications such as 'Valuing People Now', which was launched in Jan-09, and provides information about strategies, resources and national drivers including Local Area Agreements. It can serve as a useful tool for PCTs, commissioners, those involved in service development, and those with a public health remit in order to improve practice and health outcomes among those with learning disability at both local and regional levels. For further information contact: Jonathan Campion (jonathan.campion@dh.gsi.gov.uk) or Jo Nurse (jo.nurse@dh.gsi.gov.uk)

Gestió acadèmica d'un centre de formació amb .NET

El projecte Gestió acadèmica d'un centre de formació amb .NET té com a finalitat informatitzar tot el procés de control de les matriculacions dels alumnes i gestió dels cursos que s'imparteixen i dels recursos del centre. Amb això es pretén aconseguir una solució completa que permeti fer el seguiment de totes les matriculacions als cursos dels alumnes, portar un manteniment exhaustiu dels cursos que s'imparteixen i fer un seguiment dels recursos del centre des de que es fa una petició fins que es fa servir.

Toxoplasma gondii and the Immunity-Related GTPase (IRG) resistance system in mice: a review

The Immunity Related GTPases (IRG proteins) constitute a large family of interferon-inducible proteins that mediate early resistance to Toxoplasma gondii infection in mice. At least six members of this family are required for resistance of mice to virulent T. gondii strains. Recent results have shown that the complexity of the resistance arises from complex regulatory interactions between different family members. The mode of action against T. gondii depends on the ability of IRG proteins to accumulate on the parasitophorous vacuole of invading tachyzoites and to induce local damage to the vacuole resulting in disruption of the vacuolar membrane. Virulent strains of T. gondiiovercome the IRG resistance system, probably by interfering with the loading of IRG proteins onto the parasitophorous vacuole membrane. It may be assumed that T. gondii strains highly virulent for mice will be disadvantaged in the wild due to the rapid extinction of the infected host, while it is self-evident that susceptibility to virulent strains is disadvantageous to the mouse host. We consider the possibility that this double disadvantage is compensated in wild populations by segregating alleles with different resistance and susceptibility properties in the IRG system.

An evaluation of p16INK4a expression in cervical intraepithelial neoplasia specimens, including women with HIV-1

Although several studies have evaluated the role of p16INK4a as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16INK4a in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16INK4a as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16INK4a was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16INK4a expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16INK4a in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16INK4a under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16INK4a expression in CIN 2-3.

Infliximab for Crohn's disease in the Swiss IBD Cohort Study: clinical management and appropriateness.

OBJECTIVE: Antitumor necrosis factor a agents have significantly improved the management of Crohn's disease (CD), but not all patients benefit from this therapy. We used data from the Swiss Inflammatory Bowel Disease Cohort Study and predefined appropriateness criteria to examine the appropriateness of use of infliximab (IFX) in CD patients. METHODS: EPACT II (European Panel on the Appropriateness of CD Therapy, 2007; www.epact.ch) appropriateness criteria have been developed using a formal explicit panel process combining evidence from the published literature and expert opinion. Questionnaires relating to EPACT II criteria were used at enrollment and follow-up of all Swiss Inflammatory Bowel Disease Cohort Study patients. A step-by-step analysis of all possible indications for IFX therapy in a given patient allowed identification of the most appropriate indication and final classification in a single appropriateness category (appropriate, uncertain, inappropriate). RESULTS: Eight hundred and twenty-one CD patients were prospectively enrolled between November 2006 and March 2009. IFX was administered to 146 patients (18%) at enrollment and was most frequently used for complex fistulizing disease and for the maintenance of remission induced by biological therapy. IFX therapy was considered appropriate in 44%, uncertain in 44%, and inappropriate in 10% of patients. CONCLUSION: In this cohort, 9 out of 10 indications for IFX therapy were clinically generally acceptable (appropriate or uncertain) according to EPACT II criteria. Uncertain indications resulted mainly from the current more liberal use of IFX in clinical practice as compared with the EPACT II criteria.