Multi institutional phase II study of concomitant stereotactic reirradiation and cetuximab for recurrent head and neck cancer.

PURPOSE: Recurrent head and neck cancer is associated to a poor survival prognosis. A high toxicity rate is demonstrated when surgery and/or radiotherapy and/or chemotherapy are combined. Furthermore, the duration of treatment is often not ethically compatible with the expected survival (median survival<1year). Normal tissues tolerance limits the use of reirradiation and stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. After completion of a feasibility study, results of a multicentric study (Lille, Nancy & Nice) using SBRT with cetuximab are reported. The aim of the study was to deliver non toxic short course SBRT (2weeks) in order to get the same local control as the one demonstrated with longer protocols. METHODS AND MATERIALS: Patients with inoperable recurrent, or new primary tumor in a previously irradiated area, were included (WHO<3). Reirradiation (RT) dose was 36Gy in six fractions of 6Gy to the 85% isodose line covering 95% of the PTV with 5 injections of concomitant cetuximab (CT). All patients had previous radiotherapy, 85% had previous surgery and 48% previous chemotherapy. RESULTS: Between 11/2007 and 08/2010, 60 were included (46 men and 14 women), 56 received CT+RT, 3 were not treated and 1 received only CT. Median age was 60 (42-87)) and all 56 patients had squamous carcinoma and received concomitant cetuximab. Mean time between previous radiotherapy and the start of SBRT was 38months. Cutaneous toxicity was observed for 41 patients. There was one toxic death from hemorrhage and denutrition. Median follow-up was 11.4months. At 3months, response rate was 58.4% (95% CI: 43.2-72.4%) and disease control rate was 91.7% (95% CI: 80.0-97.7%). The one-year OS rate was 47.5% (95% CI: 30.8-62.4). CONCLUSION: These results suggest that short SBRT with cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. This combination may be the reference treatment is this population.

Characterisation of the putative effector interaction site of the regulatory HbpR protein from Pseudomonas azelaica by site-directed mutagenesis.

Bacterial transcription activators of the XylR/DmpR subfamily exert their expression control via σ(54)-dependent RNA polymerase upon stimulation by a chemical effector, typically an aromatic compound. Where the chemical effector interacts with the transcription regulator protein to achieve activation is still largely unknown. Here we focus on the HbpR protein from Pseudomonas azelaica, which is a member of the XylR/DmpR subfamily and responds to biaromatic effectors such as 2-hydroxybiphenyl. We use protein structure modeling to predict folding of the effector recognition domain of HbpR and molecular docking to identify the region where 2-hydroxybiphenyl may interact with HbpR. A large number of site-directed HbpR mutants of residues in- and outside the predicted interaction area was created and their potential to induce reporter gene expression in Escherichia coli from the cognate P(C) promoter upon activation with 2-hydroxybiphenyl was studied. Mutant proteins were purified to study their conformation. Critical residues for effector stimulation indeed grouped near the predicted area, some of which are conserved among XylR/DmpR subfamily members in spite of displaying different effector specificities. This suggests that they are important for the process of effector activation, but not necessarily for effector specificity recognition.

Endothelial cells as key determinants of the tumor microenvironment: interaction with tumor cells, extracellular matrix and immune killer cells.

Besides tumor cells, the tumor microenvironment harbors a variety of host-derived cells, such as endothelial cells, fibroblasts, innate and adaptive immune cells. It is a complex and highly dynamic environment, providing very important cues to tumor development and progression. Tumor-associated endothelial cells play a key role in this process. On the one hand, they form tumor-associated (angiogenic) vessels through sprouting from locally preexisting vessels or recruitment of bone marrow-derived endothelial progenitor cells, to provide nutritional support to the growing tumor. On the other hand, they are the interface between circulating blood cells, tumor cells and the extracellular matrix, thereby playing a central role in controlling leukocyte recruitment, tumor cell behavior and metastasis formation. Hypoxia is a critical parameter modulating the tumor microenvironment and endothelial/tumor cell interactions. Under hypoxic stress, tumor cells produce factors that promote tumor angiogenesis, tumor cell motility and metastasis. Among these factors, VEGF, a main angiogenesis modulator, can also play a critical role in the control of immune tolerance. This review discusses some aspects of the role of endothelial cells within tumor microenvironment and emphasizes their interaction with tumor cells, the extracellular matrix and with immune killer cells. We will also address the role played by circulating endothelial progenitor cells and illustrate their features and mechanism of recruitment to the tumor microenvironment and their role in tumor angiogenesis.

TL1A-DR3 interaction regulates Th17 cell function and Th17-mediated autoimmune disease.

T helper type 17 (Th17) cells play an important pathogenic function in autoimmune diseases; their regulation, however, is not well understood. We show that the expression of a tumor necrosis factor receptor family member, death receptor 3 (DR3; also known as TNFRSF25), is selectively elevated in Th17 cells, and that TL1A, its cognate ligand, can promote the proliferation of effector Th17 cells. To further investigate the role of the TL1A-DR3 pathway in Th17 regulation, we generated a TL1A-deficient mouse and found that TL1A(-/-) dendritic cells exhibited a reduced capacity in supporting Th17 differentiation and proliferation. Consistent with these data, TL1A(-/-) animals displayed decreased clinical severity in experimental autoimmune encephalomyelitis (EAE). Finally, we demonstrated that during EAE disease progression, TL1A was required for the optimal differentiation as well as effector function of Th17 cells. These observations thus establish an important role of the TL1A-DR3 pathway in promoting Th17 cell function and Th17-mediated autoimmune disease.

O2, the Oberta in Open Access : institutional repository

Tríptic informatiu sobre la publicació de documents amb accés obert en el repositori institucional de la UOC, O2 (La Oberta en obert). Aquest informa sobre quins documents hi poden publicar els membres de la comunitat UOC, com fer-ho i els serveis de valor afegit per a tots els usuaris (web 2.0, subscripció per RSS o correu electrònic, exportació al gestor bibliogràfic Refworks, etc.) i per a la recerca (lligam amb l'aplicació d'avaluació de la recerca GIR i informació del factor d'impacte de la revista a SCOPUS, IN-RECS/IN-RECJ i MIAR).

Standards and service offshoring in India: Moving beyond industry and institutional specificities

Résumé Cet article examine le rôle joué par les normes internationales techniques dans la mondialisation des activités de service. Différentes approches d'économie considèrent que les spécificités des activités de services sont un frein à leur délocalisation, à leur industrialisation et à leur normalisation. A l'opposé de ces approches centrées sur les spécificités des activités de services, les approches d'économie politique internationale mettent en avant l'existence de configurations conflictuelles de pouvoir à l'oeuvre dans l'internationalisation des activités de services et ce, au-delà des limites sectorielles et nationales. Cet article examine le cas du secteur des centres d'appels et, plus généralement, celui de la sous-traitance des services aux entreprises (BPO) en Inde. Nos résultats suggèrent que les normes techniques sont importantes dans le secteur étudié, alors même que ces types de services sont conventionnellement identifiés comme étant peu susceptibles d'être soumis à des normes. Une perspective d'économie politique sur la normalisation des activités de service souligne comment la problématique du pouvoir investit la normalisation technique d'une dimension plus progressive à travers les thématiques du "travailleur", du "consommateur", ou de "l'environnement". Abstract This paper explores the role of international standards in the much-debated globalisation of the service economy. Various strands of economic analyses consider that core attributes of services affect their ability to be reliably delocalised, industrialised, and standardised. In contrast, international political economy approaches draw attention to power configurations supporting conflicting use of standards across industries and nations. The paper examines the case of the rising Indian service industry in customer centres and business process outsourcing to probe these opposing views. Our findings suggest that standards matter in types of services that conventional economic analyses identify as unlikely to be standardised, and that the standards used in the Indian BPO industry are widely accepted. Despite little conflict in actual definitions of market requirements, an international political economy perspective on service standardisation highlights the importance of potential power issues related to workers', consumers', and environmental concerns likely to be included in more progressive forms of standardisation.

Institutional change and the evolution of the regulatory state: evidence from the Swiss case

This article examines institutional change in a case that was expected to be particularly resilient but showed considerable structural transformation: the institutionalization of the regulatory state in Switzerland. This process is illustrated through the establishment of independent regulatory agencies (IRAs) in four areas: banking and finance; telecommunications; electricity; and competition. The theoretical framework developed by Streeck, Thelen and Mahoney is used to explore hypotheses about the modes of institutional change, with the methodology of diachronic within-case study. Results confirm only partially the expectations, pointing to layering and displacement as the prevalent modes of change. The concluding part discusses the type and the direction of change as additional explanatory factors.

Vessel centerline tracking and boundary sgementation in coronary MRA with minimal manual interaction.

Magnetic resonance angiography (MRA) provides a noninvasive means to detect the presence, location and severity of atherosclerosis throughout the vascular system. In such studies, and especially those in the coronary arteries, the vessel luminal area is typically measured at multiple cross-sectional locations along the course of the artery. The advent of fast volumetric imaging techniques covering proximal to mid segments of coronary arteries necessitates automatic analysis tools requiring minimal manual interactions to robustly measure cross-sectional area along the three-dimensional track of the arteries in under-sampled and non-isotropic datasets. In this work, we present a modular approach based on level set methods to track the vessel centerline, segment the vessel boundaries, and measure transversal area using two user-selected endpoints in each coronary of interest. Arterial area and vessel length are measured using our method and compared to the standard Soap-Bubble reformatting and analysis tool in in-vivo non-contrast enhanced coronary MRA images.

Technology educational affordance: Bridging the gap between patterns of interaction and technology usage

Peer-reviewed

From institutional repositories to personal collections of learning resources

Institutional digital repositories are a basic piece to provide preservation and reutilization of learning resources. However, their creation and maintenance is usually performed following a top-down approach, causing limitations in the search and reutilization of learning resources. In order to avoid this problem we propose to use web 2.0 functionalities. In this paper we present how tagging can be used to enhance the search and reusability functionalities of institutional learning repositories as well as promoting their usage. The paper also describes the evaluation process that was performed in a pilot experience involving open educational resources.

Binary proposal for assessing quality of Open Access Institutional Repositories : the case of Spanish repositories

The reason for this study is to propose a new quantitative approach on how to assess the quality of Open Access University Institutional Repositories. The results of this new approach are tested in the Spanish University Repositories. The assessment method is based in a binary codification of a proposal of features that objectively describes the repositories. The purposes of this method are assessing the quality and an almost automatically system for updating the data of the characteristics. First of all a database was created with the 38 Spanish institutional repositories. The variables of analysis are presented and explained either if they are coming from bibliography or are a set of new variables. Among the characteristics analyzed are the features of the software, the services of the repository, the features of the information system, the Internet visibility and the licenses of use. Results from Spanish universities ARE provided as a practical example of the assessment and for having a picture of the state of the development of the open access movement in Spain.

A survey on automatic recommenders in the context of institutional repositories

Peer-reviewed