Malignant pleural mesothelioma: leukocyte recruitment is not required for drug delivery induced by photodynamic therapy in a human xenograft model

Objective: The pre-treatment of tumor neo-vessels by photodynamic therapy (PDT) was shown to improve the distribution of chemotherapy administered subsequently. However, the precise mechanism by which PDT modifies the tumor vasculature is unknown. We have recently shown that leukocyteendothelial cell interaction was essential for PDT induced drug delivery to normal tissue. Our purpose was to determine if PDT could enhance drug distribution in malignant mesothelioma and if a comparable role for leucocytes existed.Methods: We grew human mesothelioma xenografts (H-meso-1) in the dorsal skinfold chambers of nude mice (n = 28). The rolling, sticking and recruitment of leucocytes was assessed in tumor and normal vessels following PDT (Visudyne 0?4 mg/kg, fluence rate 200 mW/cm2, fluence 60 J/cm2) using intravital microscopy. In parallel, the distribution of a macromolecule (FITC dextran, 2000 kDa) administered after PDT was determined. We compared these variables in control (no PDT), PDT + IgG (non specific antibody) and PDT + pan-selectin antibody (monoclonal P-E-L selectin antibody).Results: PDT significantly enhanced the distribution of FITC dextran in mesothelioma xenografts compared to controls. Interestingly, PDT enhanced the leukocyte-endothelial interaction significantly (rolling and recruitment)in tumor and surrounding normal vessels compared to controls. Leukocyte recruitment was significantly down-regulated by pan-selectin antibodies in tumor tissues. However, the suppression of leucocyte recruitement did not affect the extravasation of FITC-dextran in tumor tissue.Conclusion:PDTpre-treatment of the mesothelioma vasculature can enhance the distribution of macromolecular drugs administered subsequently. However, unlike normal vessels, leukocyte-endothelial cell interaction is not required for PDT induced leakage.

Enhancing efficacy of anticancer vaccines by targeted delivery to tumor-draining lymph nodes.

The sentinel or tumor-draining lymph node (tdLN) serves as a metastatic niche for many solid tumors and is altered via tumor-derived factors that support tumor progression and metastasis. tdLNs are often removed surgically, and therapeutic vaccines against tumor antigens are typically administered systemically or in non-tumor-associated sites. Although the tdLN is immune-suppressed, it is also antigen experienced through drainage of tumor-associated antigens (TAA), so we asked whether therapeutic vaccines targeting the tdLN would be more or less effective than those targeting the non-tdLN. Using LN-targeting nanoparticle (NP)-conjugate vaccines consisting of TAA-NP and CpG-NP, we compared delivery to the tdLN versus non-tdLN in two different cancer models, E.G7-OVA lymphoma (expressing the nonendogenous TAA ovalbumin) and B16-F10 melanoma. Surprisingly, despite the immune-suppressed state of the tdLN, tdLN-targeting vaccination induced substantially stronger cytotoxic CD8+ T-cell responses, both locally and systemically, than non-tdLN-targeting vaccination, leading to enhanced tumor regression and host survival. This improved tumor regression correlated with a shift in the tumor-infiltrating leukocyte repertoire toward a less suppressive and more immunogenic balance. Nanoparticle coupling of adjuvant and antigen was required for effective tdLN targeting, as nanoparticle coupling dramatically increased the delivery of antigen and adjuvant to LN-resident antigen-presenting cells, thereby increasing therapeutic efficacy. This work highlights the tdLN as a target for cancer immunotherapy and shows how its antigen-experienced but immune-suppressed state can be reprogrammed with a targeted vaccine yielding antitumor immunity.

Administration intra-vitréenne de liposomes pour la vectorisation de principes actifs [The use of liposomes as intravitreal drug delivery system].

Liposomes are vesicular lipidic systems allowing encapsulation of drugs. This article reviews the relevant issues in liposome structure (composition and size), and their influence on intravitreal pharmacokinetics. Liposome-mediated drug delivery to the posterior segment of the eye via intravitreal administration has been addressed by several authors and remains experimental. Liposomes have been used for intravitreal delivery of antibiotics, antivirals, antifungal drugs, antimetabolites, and cyclosporin. Encapsulation of these drugs within liposomes markedly increased their intravitreal half-life, and reduced their retinal toxicity. Liposomes have also shown an attractive potential for retinal gene transfer by intravitreal delivery of plasmids or oligonucleotides.

Implementing statistical learning methods through Bayesian networks (Part 2): bayesian evaluations for results of black toner analyses in forensic document examination

This paper presents and discusses the use of Bayesian procedures - introduced through the use of Bayesian networks in Part I of this series of papers - for 'learning' probabilities from data. The discussion will relate to a set of real data on characteristics of black toners commonly used in printing and copying devices. Particular attention is drawn to the incorporation of the proposed procedures as an integral part in probabilistic inference schemes (notably in the form of Bayesian networks) that are intended to address uncertainties related to particular propositions of interest (e.g., whether or not a sample originates from a particular source). The conceptual tenets of the proposed methodologies are presented along with aspects of their practical implementation using currently available Bayesian network software.

Document Tècnic de l'Edificació i annexes : cobertes, lluernaris i claraboies

El document és una recopilació de tota una informació prèvia per tal derealitzar un Document Tècnic de l’Edificació que s’ha servit de guia de les actuals NTE(Normes Tecnològiques de l’Edificació), però sense posar en dubte les NTE ni substituir-les.Aquest DTE consisteix en refer la NTE-QLC-1973 (NormaTecnològica de l’Edificació – Cubiertas Lucernarios Claraboyas), que passaràanomenar-se DTE-CLC-CP / CLC-CT. (Document Tècnic de l’Edificació – CobertesLluernaris Claraboies – Claraboies de Catàleg / Claraboies Tubulars).El meu interès per la llum natural va fer que em decidís per triar el tema de lesClaraboies, i el meu estudi es base en les claraboies de catàleg, de les quals ja parlade l’actual NTE i, a més a més, el DTE incorpora un nou tipus de claraboia com són lestubulars

Iowa Airport Directory, 2003 ***NOTE*** This document is for historical viewing, the internal information is no longer current or accurate! ***NOTE*** Current information can be found at http://www.iowadot.gov/aviation/aircraftregistration/registration.aspx ***NOTE***

Iowa has 8 commercial service airports and 105 general aviation airports, of which three serve as reliever airports. ***NOTE*** This document is for historical viewing, the internal information is no longer current or accurate! ***NOTE*** Current information can be found at http://www.iowadot.gov/aviation/aircraftregistration/registration.aspx ***NOTE***

Missed opportunities among HIV-positive women to control viral replication during pregnancy and to have a vaginal delivery.

INTRODUCTION: Most national guidelines for the prevention of mother-to-child transmission of HIV in Europe updated between 2001 and 2010 recommend vaginal deliveries for women with undetectable or very low viral load (VL). Our aim was to explore the impact of these new guidelines on the rates of vaginal deliveries among HIV-positive women in Europe. METHODS: In a pooled analysis of data on HIV-positive pregnant women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study 2000 to 2010, deliveries were classified as occurring pre- or postpublication of national guidelines recommending vaginal delivery. RESULTS: Overall, 2663 women with 3013 deliveries were included from 10 countries; 28% women were diagnosed with HIV during pregnancy. Combination antiretroviral therapy was used in most pregnancies (2020, 73%), starting during the first or second trimester in 78% and during the third trimester in 22%; in 25% pregnancies, the woman conceived on combination antiretroviral therapy. Overall, in 86% pregnancies, a VL < 400 copies per milliliter was achieved before delivery. The proportion of vaginal deliveries increased from 17% (414/2377) before the change in guidelines to 52% (313/600) after; elective Caesarean section rates decreased from 65% to 27%. The proportion of women with undetectable VL having a Caesarean section was 55% after implementation of new guidelines. We observed a decrease of late preterm deliveries from 16% (377/2354) before to 7% (42/599) after the change in guidelines (P < 0.001). CONCLUSION: There are still missed opportunities for women with HIV to fully suppress their VL and to deliver vaginally in Europe.

Facturación de servicios

Este proyecto se ha realizado mediante un convenio de prácticas con la empresa UNIT4 (Barberà del Vallès). Se basa en el desarrollo de un nuevo módulo enfocado hacia compañías distribuidoras de productos, que será incorporado en el software de gestión que vende la empresa. Este módulo consistirá en facturar algunos servicios ofrecidos en los envíos de paquetes, que se incluirán en el albarán de entrega de los mismos.

IL-6 activated integrated BATF/IRF4 functions in lymphocytes are T-bet-independent and reversed by subcutaneous immunotherapy.

IL-6 plays a central role in supporting pathological TH2 and TH17 cell development and inhibiting the protective T regulatory cells in allergic asthma. TH17 cells have been demonstrated to regulate allergic asthma in general and T-bet-deficiency-induced asthma in particular. Here we found an inverse correlation between T-bet and Il-6 mRNA expression in asthmatic children. Moreover, experimental subcutaneous immunotherapy (SIT) in T-bet((-/-)) mice inhibited IL-6, IL-21R and lung TH17 cells in a setting of asthma. Finally, local delivery of an anti-IL-6R antibody in T-bet((-/-)) mice resulted in the resolution of this allergic trait. Noteworthy, BATF, crucial for the immunoglobulin-class-switch and TH2,TH17 development, was found down-regulated in the lungs of T-bet((-/-)) mice after SIT and after treatment with anti-IL-6R antibody, indicating a critical role of IL-6 in controlling BATF/IRF4 integrated functions in TH2, TH17 cells and B cells also in a T-bet independent fashion in allergic asthma.

Program, Highlights & Budget Summaries, 2004

Budget in Brief from the Governor's Office

Budget Report Fiscal Year 2005

Budget from the Governor's Office

Managing diabetes in Switzerland : a systemic approach

Executive summaryThe increasing prevalence of chronic diseases is one of the major causes of rising health expenditure, as stated by the WHO. Not only chronic diseases are very costly, but they are by far the leading cause of mortality in the world, representing 60% of all deaths. Diabetes in particular is becoming a major burden of disease. In Switzerland around 5% of the population suffer of type 2 diabetes and 5 to 10% of the annual health care budget is attributable to diabetes. If the predictions of WHO do realise, the prevalence of diabetes will double until 2030 and so is expected the attributable health expenditure.The objective of this thesis is to provide policy recommendations as to slow down the disease progression and its costly complication. We study the factors that influence diabetes dynamics and the interventions that improve health outcomes while decreasing costs according to different time horizon and use systems thinking and system dynamic.Our results show that managing diabetes requires using integrated care interventions that are effective on three fronts: (1) delaying the onset of complications, (2) slowing down the disease progression and (3) accelerating the time to diagnosis of diabetes and its complications. We recommend firstly the implementation of those interventions targeted at changing patients' behaviour which are also less expensive, but require a change in the delivery of care and medical practices. Then policies targeted at an earlier diagnosis of diabetes, its prevention and the diagnosis of complications are to be considered. This sequence of interventions allows saving money, as total costs decrease, even including the costs of interventions and result in longer life expectancy of diabetics in the long term.In diabetes management there is therefore a trade-off between medical costs and patients' benefits on the one hand and between the objectives of obtaining results in the short or long term on the other hand. Decision makers need to deliver acceptable outcomes in the short term. Considering this criterion, the preferred policy may be to focus only on diagnosed diabetics, thus attempting to slow down the progression of their disease, compared to an integrated care approach addressing all the aspects of the disease. Such a policy also yields desirable results in terms of costs and patients' benefits.

Document Tècnic Edificació: instal·lacions d'electricitat Baixa Tensió

El projecte es basa en una proposta de modificació d’una Norma Tecnològica d’Edificació sobre les instal•lacions elèctriques de baixa tensió del 1973, per tal de donar-li un caire més actual

Annual Report and Budget Summary, 2003-2004

Annual report for the Department of Public Health