Low doses of ionizing radiation promote tumor growth and metastasis by enhancing angiogenesis.

Radiotherapy is a widely used treatment option in cancer. However, recent evidence suggests that doses of ionizing radiation (IR) delivered inside the tumor target volume, during fractionated radiotherapy, can promote tumor invasion and metastasis. Furthermore, the tissues that surround the tumor area are also exposed to low doses of IR that are lower than those delivered inside the tumor mass, because external radiotherapy is delivered to the tumor through multiple radiation beams, in order to prevent damage of organs at risk. The biological effects of these low doses of IR on the healthy tissue surrounding the tumor area, and in particular on the vasculature remain largely to be determined. We found that doses of IR lower or equal to 0.8 Gy enhance endothelial cell migration without impinging on cell proliferation or survival. Moreover, we show that low-dose IR induces a rapid phosphorylation of several endothelial cell proteins, including the Vascular Endothelial Growth Factor (VEGF) Receptor-2 and induces VEGF production in hypoxia mimicking conditions. By activating the VEGF Receptor-2, low-dose IR enhances endothelial cell migration and prevents endothelial cell death promoted by an anti-angiogenic drug, bevacizumab. In addition, we observed that low-dose IR accelerates embryonic angiogenic sprouting during zebrafish development and promotes adult angiogenesis during zebrafish fin regeneration and in the murine Matrigel assay. Using murine experimental models of leukemia and orthotopic breast cancer, we show that low-dose IR promotes tumor growth and metastasis and that these effects were prevented by the administration of a VEGF receptor-tyrosine kinase inhibitor immediately before IR exposure. These findings demonstrate a new mechanism to the understanding of the potential pro-metastatic effect of IR and may provide a new rationale basis to the improvement of current radiotherapy protocols.

Avaluació de nous algorismes per a la creació de camins entre nodes de la xarxa TOR

En este proyecto se presenta un estudio y una implementación sobre estrategias de selección de nodos de la red TOR. Para esto en una primera parte teorica se da a conocer todo lo que comportan las redes anónimas y su implementación en diferentes entornos. A continuación se estudian los requerimientos y la viabilidad del proyecto. Finalmente exponemos el diseño y desarrollo de los distintos algoritmos propuestos juntamente con las pruebas realizadas y las conclusiones a las que se ha llegado.

Eficàcia predictiva de l’HCR-20 i del PCL:SV en contexts institucionals

L’estudi es dirigeix a avaluar la capacitat predictiva sobre la violència dels instruments de judici clínic estructurat, amb una metodologia que aporti resultats comparables a estudis de l’àmbit internacional. La investigació es va portar a terme en un hospital civil de salut mental i la mostra està composta per 114 pacients de les unitats de crònics i subaguts. A l’avaluació inicial, l’HCR-20, el PCL:SV i el Protocol 7 van ser els instruments utilitzats per a la recollida d’informació de les variables predictors. La variable depenent o resultat va ser registrada prospectivament per part de l’equip d’infermeria amb un instrument observacional de fàcil ús, el MOAS. Mitjançant índexs de correlació, càlcul de riscos relatius, i anàlisis de regressió logística i corbes ROC va ser possible conèixer que l’HCR-20 i el PCL-SV són mesures vàlides per a la predicció de la violència intrahospitalària en el curt i mig termini en una mostra espanyola de persones amb malaltia mental severa. L’HCR-20 i particularment els ítems clínics van ser els millors predictors de la violència física envers a persones i objectes. Tant la puntuació numèrica de l’HCR-20 com el judici clínic estructurat van demostrar una precisió predictiva alta i comparable a l'obtinguda amb la versió original de l'instrument. El PCL:SV va arribar una precisió predictiva moderada que va anar disminuint al llarg del seguiment. Altres factors de risc com les agressions o la ira prèvies a l’avaluació també van augmentar significativament el risc de violència durant l’any de seguiment.

Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data

BACKGROUND: Individually, randomised trials have not shown conclusively whether adjuvant chemotherapy benefits adult patients with localised resectable soft-tissue sarcoma.METHODS: A quantitative meta-analysis of updated data from individual patients from all available randomised trials was carried out to assess whether adjuvant chemotherapy improves overall survival, recurrence-free survival, and local and distant recurrence-free intervals (RFI) and whether chemotherapy is differentially effective in patients defined by age, sex, disease status at randomisation, disease site, histology, grade, tumour size, extent of resection, and use of radiotherapy.FINDINGS: 1568 patients from 14 trials of doxorubicin-based adjuvant chemotherapy were included (median follow-up 9.4 years). Hazard ratios of 0.73 (95% CI 0.56-0.94, p = 0.016) for local RFI, 0.70 (0.57-0.85, p = 0.0003) for distant RFI, and 0.75 (0.64-0.87, p = 0.0001) for overall recurrence-free survival, correspond to absolute benefits from adjuvant chemotherapy of 6% (95% CI 1-10), 10% (5-15), and 10% (5-15), respectively, at 10 years. For overall survival the hazard ratio of 0.89 (0.76-1.03) was not significant (p = 0.12), but represents an absolute benefit of 4% (1-9) at 10 years. These results were not affected by prespecified changes in the groups of patients analysed. There was no consistent evidence that the relative effect of adjuvant chemotherapy differed for any subgroup of patients for any endpoint. However, the best evidence of an effect of adjuvant chemotherapy for survival was seen in patients with sarcomas of the extremities.INTERPRETATION: The meta-analysis provides evidence that adjuvant doxorubicin-based chemotherapy significantly improves the time to local and distant recurrence and overall recurrence-free survival. There is a trend towards improved overall survival.

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We describe here the potential of viral-mediated gene transfer for the modeling and treatment of Huntington's disease, focusing in particular on strategies for the tissue-specific targeting of various CNS cells. The protocols described here cover the design of lentiviral vectors, strategies for modifying their tropism, including the use of various envelopes and tissue-specific promoters, and the potential of miRNA to regulate transgene expression.

Decision-theoretic analysis of forensic sampling criteria using Bayesian decision networks

Sampling issues represent a topic of ongoing interest to the forensic science community essentially because of their crucial role in laboratory planning and working protocols. For this purpose, forensic literature described thorough (Bayesian) probabilistic sampling approaches. These are now widely implemented in practice. They allow, for instance, to obtain probability statements that parameters of interest (e.g., the proportion of a seizure of items that present particular features, such as an illegal substance) satisfy particular criteria (e.g., a threshold or an otherwise limiting value). Currently, there are many approaches that allow one to derive probability statements relating to a population proportion, but questions on how a forensic decision maker - typically a client of a forensic examination or a scientist acting on behalf of a client - ought actually to decide about a proportion or a sample size, remained largely unexplored to date. The research presented here intends to address methodology from decision theory that may help to cope usefully with the wide range of sampling issues typically encountered in forensic science applications. The procedures explored in this paper enable scientists to address a variety of concepts such as the (net) value of sample information, the (expected) value of sample information or the (expected) decision loss. All of these aspects directly relate to questions that are regularly encountered in casework. Besides probability theory and Bayesian inference, the proposed approach requires some additional elements from decision theory that may increase the efforts needed for practical implementation. In view of this challenge, the present paper will emphasise the merits of graphical modelling concepts, such as decision trees and Bayesian decision networks. These can support forensic scientists in applying the methodology in practice. How this may be achieved is illustrated with several examples. The graphical devices invoked here also serve the purpose of supporting the discussion of the similarities, differences and complementary aspects of existing Bayesian probabilistic sampling criteria and the decision-theoretic approach proposed throughout this paper.

Research needs in allergy: an EAACI position paper, in collaboration with EFA.

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.

The use and limitations of ultrasonography in the diagnosis of liver morbidity attributable to Schistosoma mansoni infection in community-based surveys

The objective of this population-based study was to estimate the liver morbidity attributable to Schistosoma mansoni infection by ultrasonography adopting the proposed standard protocols of the Cairo Meeting on Ultrasonography, 1991. We examined 2384 individuals representing 20 of the households of the rural population of the Ismailia Governorate, East of Delta, Egypt. Prevalence of S. mansoni and S. haematobium infections were 40.3 and 1.7 respectively. Portal tract thickening (PTT) grade 1, 2 and 3 considered diagnostic of schistosomal liver morbidity was detected in 35.1, 1.3 and 0.2 individuals respectively. Generally, ultrasonographically-detected pathological changes increased with age, but correlated with intensity of infection only in age group 20-59 years. Comparing individuals with and without S. mansoni infections in an endemic and a non-endemic community indicated no significant difference between the former and the latter in either case. In conclusion: ultrasonography had a limited value in estimating schistosomal liver morbidity in our population-based study where early grades of liver morbidly were prevalent. The criteria of diagnosing grade I portal fibrosis need to be revised as well as the staging system proposed by the Cairo Meeting on ultrasonography in schistosomiasis.

Time-Course In Vivo Trafficking Pattern and Effector Function of Donor-Specific Regulatory T Cells in Response to an Allograft.

Background: Experimental data have suggested that adoptive transfer of CD4+CD25+Foxp3+ regulatory T cells (Tregs), capable of controlling immune responses to specifi c auto- or alloantigens, could be used as a therapeutic strategy to promote specifi c tolerance in T-cell mediated diseases and in organ transplantation (Tx). However, before advocating the application of immunotherapy with Tregs in Tx, we need to improve our understanding of their in vivo homeostasis, traffi cking pattern and effector function in response to alloantigens. Methods : Donor-antigen specifi c murine Tregs were generated and characterized in vitro following our described protocols. Using an adoptive transfer and skin allotransplantation model, we have analyzed the in vivo expansion and homing of fl uorescent-labeled effector T cells (Teff) and Tregs, at different time-points after Tx, using fl ow-cytometry as well as fl uorescence microscopy techniques. Results: Tregs expressed CD62L, CCR7 and CD103 allowing their homing into lymphoid and non-lymphoid tissues (gut, skin) after intravenous injection. While hyporesponsive to TCR stimulation in vitro, transferred Tregs survived, migrated to secondary lymphoid organs and preferentially expanded within the allograft draining lymph nodes. Furthermore, Foxp3+ cells could be detected inside the allograft as early as day 3-5 after Tx. At a much later time-point (day 60 after Tx), graft-infi ltrating Foxp3+ cells were also detectable in tolerant recipients. When transferred alone, CD4+CD25- Teff cells expanded within secondary lymphoid organs and infi ltrated the allograft by day 3-5 after Tx. The co-transfer of Tregs limited the expansion of alloreactive Teff cells as well as their recruitment into the allograft. The promotion of graft survival observed in the presence of Tregs was in part mediated by the inhibition of the production of effector cytokines by CD4+CD25- T cells. Conclusion: Taken together, our results suggest that the suppression of allograft rejection and the induction of Tx tolerance are in part dependant on the alloantigendriven homing and expansion of Tregs. Thus, the appropriate localization of Tregs may be critical for their suppressive function in vivo.

Ecologia de les Invasions Ecològiques

La paradoxa de les invasions planteja com és possible que algunes espècies siguin capaces d'envair regions a les que no han evolucionat i, fins i tot, arribar a ser més abundants que espècies autòctones que han tingut més oportunitat d’adaptars’hi. Comprendre l’ecologia de les invasions és especialment interessant perquè algunes d’aquestes espècies causen greus impactes ecològics i econòmics arreu del món. Per intentar resoldre la paradoxa en aquest treball s’ha seguit dues aproximacions. Per una banda, mitjançant anàlisis comparatius s’ha volgut identificar aquelles característiques que afecten el resultat de les introduccions d’ocells, i utilitzar-les com a predictors en protocols d’avaluació de riscos per prevenir futures invasions. Seguint en aquest nivell d’aproximació també s’ha volgut validar si, tal com prediu la teoria ecològica, les estratègies vitals de les espècies afecten l'èxit en l'establiment de poblacions d'ocells exòtics. D'altra banda, a través d'aproximacions descriptives i experimentals, s’ha volgut investigar els mecanismes d’invasió en un cas d’estudi concret, el del Rossinyol del Japó (Leiothrix lutea) als boscos de Collserola (Barcelona). Els anàlisis comparatius han mostrat que és possible de predir la probabilitat d’establiment de les espècies introduïdes a partir d’unes poques característiques amb notable precisió. Altrament, l’anàlisi sobre l’efecte de les estratègies vitals sobre el resultat de les invasions sembla indicar que hi ha un biaix en el registre històric d’introduccions que impedeix descobrir la naturalesa d’aquesta relació i suggereixen buscar una aproximació alternativa per al problema. Respecte el cas del Rossinyol del Japó, els resultats preliminars suggereixen que les raons del seu èxit als boscos de Collserola podrien ser que ha trobat un nínxol ecològic que està poc aprofitat per les espècies natives. Aquest treball vol mostrar com a través de la integració de diferents aproximacions podem ser capaços d’aportar una visió més completa per comprendre la paradoxa de les invasions.

Proposta metodològica per afavorir el treball en equip en assignatures que contenen la realització de projectes de disseny d'enginyeria

Aquest projecte ha tingut com a finalitat principal impulsar un aprenentatge més efectiu dels alumnes en assignatures que, impartides en una modalitat semipresencial a les escoles de Terrassa i Manresa, comporten la realització d’un treball de curs amb un alt contingut de disseny. A més a més, paral·lelament es contribueix a millorar el rendiment acadèmic de l'estudiant, en el marc de la millora global de la docència i de l'aprenentatge a la UPC amb un horitzó d'aproximació als elements que conformen l’Espai Europeu d’Educació Superior. En el context de semipresencialitat, es pretén fomentar l'aprenentatge cooperatiu i donar solució als problemes comunicatius existents a nivell d’intercanvi d’opinions, valoracions i formulació de dubtes vinculats amb el disseny, etc. En aquest projecte, doncs, s’ha creat una metodologia de treball que permet intercanviar informació gràfica (per exemple en format Autocad) a partir de les aplicacions ja incloses en la plataforma virtual Atenea (campus virtual de la UPC). Aquest projecte es basa principalment en tres objectius principals: 1. Millorar l'intercanvi d'informació entre alumnes d’un grup i entre els alumnes i el professor mitjançant el desenvolupament de protocols. 2. Fomentar l’aprenentatge cooperatiu mitjançant la integrar d’eines d’interacció instantània per Internet. 3. Adaptar l’assignatura de "Complexos Industrials" al procés de convergència a l’EEES. L'activitat ha estat desenvolupada al quadrimestre de tardor 2008-2009 i la metodologia ha estat implantadas a l'assignatura Complexos Industrials d'Enginyeria en Organització Industrial de la ETSEIAT i de la EUPM.

Desenvolupament en Network Simulator 2: protocol de migració per simular agents mòbils

Avui en dia, estem assistint a una expansió de la tecnologia d’agents mòbils i noves aplicacions basades en aquesta s’estan obrint pas constantment. Les aplicacions han de demostrar la seva viabilitat sobretot en entorns heterogenis i complexos com les xarxes MANET. En aquest projecte es desenvolupa un sistema per simular el comportament dels agents mòbils, ampliant l’actual simulador de xarxa NS2, i també es comprova la viabilitat de l’implementació de l’ETTMA pel triatge de víctimes en situacions d’emergència.