EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma.

The treatment of patients with recurrent glioblastoma remains a major oncologic problem, with median survival after progression of 7-9 months. To determine the maximum tolerated dose and dose-limiting toxicity (DLT), the combination of dasatinib and cyclonexyl-chloroethyl-nitrosourea (CCNU) was investigated in this setting. The study was designed as multicenter, randomized phase II trial, preceded by a lead-in safety phase. The safety component reported here, which also investigated pharmacokinetics and preliminary clinical activity, required expansion and is therefore considered a phase I part to establish a recommended dosing regimen of the combination of CCNU (90-110 mg/m(2)) and dasatinib (100-200 mg daily). Overall, 28 patients were screened, and 26 patients were enrolled. Five dose levels were explored. DLTs, mainly myelosuppression, occurred in 10 patients. Grade 3 or 4 neutropenia was recorded in 7 patients (26.9%) and thrombocytopenia in 11 patients (42.3%). No significant effect of CCNU coadministration on dasatinib pharmacokinetics was found. Median progression-free survival (PFS) was 1.35 months (95% confidence interval: 1.2-1.4) and 6-month PFS was 7.7%. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents.

A phase I pharmacokinetic study of hypoxic abdominal stop-flow perfusion with gemcitabine in patients with advanced pancreatic cancer and refractory malignant ascites

PURPOSE: As no curative treatment for advanced pancreatic and biliary cancer with malignant ascites exists, new modalities possibly improving the response to available chemotherapies must be explored. This phase I study assesses the feasibility, tolerability and pharmacokinetics of a regional treatment of gemcitabine administered in escalating doses by the stop-flow approach to patients with advanced abdominal malignancies (adenocarcinoma of the pancreas, n = 8, and cholangiocarcinoma of the liver, n = 1). EXPERIMENTAL DESIGN: Gemcitabine at 500, 750 and 1,125 mg/m(2) was administered to three patients at each dose level by loco-regional chemotherapy, using hypoxic abdominal stop-flow perfusion. This was achieved by an aorto-caval occlusion by balloon catheters connected to an extracorporeal circuit. Gemcitabine and its main metabolite 2',2'-difluorodeoxyuridine (dFdU) concentrations were measured by high performance liquid chromatography with UV detection in the extracorporeal circuit during the 20 min of stop-flow perfusion, and in peripheral plasma for 420 min. Blood gases were monitored during the stop-flow perfusion and hypoxia was considered stringent if two of the following endpoints were met: pH </= 7.2, pO(2) nadir ratio </=0.70 or pCO(2) peak ratio >/=1.35. The tolerability of this procedure was also assessed. RESULTS: Stringent hypoxia was achieved in four patients. Very high levels of gemcitabine were rapidly reached in the extracorporeal circuit during the 20 min of stop-flow perfusion, with C (max) levels in the abdominal circuit of 246 (+/-37%), 2,039 (+/-77%) and 4,780 (+/-7.3%) mug/ml for the three dose levels 500, 750 and 1,125 mg/m(2), respectively. These C (max) were between 13 (+/-51%) and 290 (+/-12%) times higher than those measured in the peripheral plasma. Similarly, the abdominal exposure to gemcitabine, calculated as AUC(t0-20), was between 5.5 (+/-43%) and 200 (+/-66%)-fold higher than the systemic exposure. Loco-regional exposure to gemcitabine was statistically higher in presence of stringent hypoxia (P < 0.01 for C (max) and AUC(t0-20), both normalised to the gemcitabine dose). Toxicities were acceptable considering the complexity of the procedure and were mostly hepatic; it was not possible to differentiate the respective contributions of systemic and regional exposures. A significant correlation (P < 0.05) was found between systemic C (max) of gemcitabine and the nadir of both leucocytes and neutrophils. CONCLUSIONS: Regional exposure to gemcitabine-the current standard drug for advanced adenocarcinoma of the pancreas-can be markedly enhanced using an optimised hypoxic stop-flow perfusion technique, with acceptable toxicities up to a dose of 1,125 mg/m(2). However, the activity of gemcitabine under hypoxic conditions is not as firmly established as that of other drugs such as mitomycin C, melphalan or tirapazamine. Further studies of this investigational modality, but with bioreductive drugs, are therefore warranted first to evaluate the tolerance in a phase I study and later on to assess whether it does improve the response to chemotherapy.

Els jocs populars i tradicionals a les classes d'educació física de primària i secundària de Guatemala

El jocs populars i tradicionals són un element educatiu i cultural molt important. Des de sempre han estat una font d’activitat física i comporten tota una sèrie de components motors i de valors que haurien de ser tinguts en compte a l’hora d’incloure’ls a les sessions d’educació física. Aquest estudi té com a objectiu conèixer la situació d’aquesta tipologia de jocs a les sessions d’educació física de dos centres educatius del municipi de San Juan la Laguna. Alhora es pretén comparar el paper que tenen els jocs populars i tradicionals en un centre de primària i en un de secundària de la població esmentada. A través de l’anàlisi dels currículums, de l’observació de les sessions d’educació física i de les entrevistes amb diversos docents, s’arriba a la conclusió que les pràctiques lúdiques populars i tradicionals tenen poca presència a l’educació física guatemalenca.

Elements ressaltats per infants i mestres en la creació d'un conte integrant les TIC i intercanvi d'aquest entre dues escoles a través d'una videoconferència

Les noves tecnologies de la Informació i la Comunicació esdevenen el tema principal d’aquesta investigació. L’objectiu primordial del treball és donar resposta al següent interrogant: què destaquen els infants i mestres d’una experiència d’aula en la qual s’integren les TIC? Aquesta recerca s’aproxima a la Grounded Theory, que es centra en crear la teoria a partir de l’anàlisi de les dades. En aquest treball és a partir de les dades analitzades que es defineixen les dimensions i indicadors per tal de donar resposta a la pregunta formulada inicialment. La intervenció que s’ha realitzat ha estat portada a terme amb les classes de P-4 i P-5 de dues escoles. Consisteix en explicar el mateix conte, sense final, a les dues aules i que aquestes s’inventin un final per tal d’explicar-se’l a través d’una videoconferència. Els resultats obtinguts amb els instruments de recollida de dades utilitzats en la investigació (dibuix infantil, grups de discussió i entrevistes) mostren que infants i mestres no destaquen el mateix d’una intervenció d’aula utilitzant les TIC. Els infants es centren més en el contingut, mentre que les mestres destaquen la metodologia i la tecnologia emprada.

Organització del temps de pràctica motriu en la programació i desenvolupament de les sessions d'E.F a l'IES Monsacopa d'Olot

L’educació física és una matèria que presenta diferències estructurals i organitzatives significatives respecte la resta d’àrees. L’anàlisi de la pràctica diària durant les sessions, ens demostra els pocs minuts que els alumnes realment disposen per practicar i poder assolir els objectius marcats. Aquesta recerca, pretén fer veure als professors la importància d’una adequada gestió del temps a l’aula amb l’objectiu d’augmentar el temps de pràctica motriu dels alumnes. Per fer-ho, es durà a terme un procés d’investigació on, primerament es definiran els diferents temps que existeixen en una sessió d’educació física, i després, s’analitzaran i es buscaran possibles relacions entre l’organització d’aquests temps dins la programació del professor i durant la realització de les sessions. Per últim, es presenten una sèrie d’estratègies d’intervenció, que poden ajudar al professorat a augmentar el temps dedicat a la pràctica, temps essencial per a l’aprenentatge.

Pluralité des corps. 1. Les corps de La medicine [Multifaceted body. I. The bodies of medicine].

Le corps humain est l'objet privilégié d'action de la médecine, mais aussi réalité vécue, image, symbole, représentation et l'objet d'interprétation et de théorisation. Tous ces éléments constitutifs du corps influencent la façon dont la médecine le traite. Dans cette série de trois articles, nous abordons le corps sous différentes perspectives : médicale (1), phénoménologique (2), psychosomatique et socio-anthropologique (3). Ce premier article traite des représentations du corps en médecine, dont nous décrivons quatre types distincts, qui renvoient à autant de démarches scientifiques spécifiques et de formes de légitimité clinique : le corps-objet de l'anatomie, le corps-machine de la physiologie, le corps cybernétique de la biologie et le corps statistique de l'épidémiologie. The human body is the object upon which medicine is acting, but also lived reality, image, symbol, representation and the object of elaboration and theory. All these elements which constitute the body influence the way medicine is treating it. In this series of three articles, we address the human body from various perspectives: medical (1), phenomenological (2), psychosomatic and socio-anthropological (3). This first article discusses four distinct types of representation of the body within medicine, each related to a specific epistemology and shaping a distinct kind of clinical legitimacy: the body-object of anatomy, the body-machine of physiology, the cybernetic body of biology, the statistical body of epidemiology.

Knowledge Licensing in a Model of R&D-driven Endogenous Growth

In this paper I present an endogenous growth model where the engine of growth is in-house R&D performed by high-tech firms. I model knowledge (patent) licensing among high-tech firms. I show that if there is knowledge licensing, high-tech firms innovate more and economic growth is higher than in cases when there are knowledge spillovers or there is no exchange of knowledge among high-tech firms. However, in case when there is knowledge licensing the number of high-tech firms is lower than in cases when there are knowledge spillovers or there is no exchange of knowledge.

Knowledge Licensing in a Model of R&D-driven Endogenous Growth

In this paper I present an endogenous growth model where the engine of growth is in-house R&D performed by high-tech firms. I model knowledge (patent) licensing among high-tech firms. I show that if there is knowledge licensing, high-tech firms innovate more and economic growth is higher than in cases when there are knowledge spillovers or there is no exchange of knowledge among high-tech firms. However, in case when there is knowledge licensing the number of high-tech firms is lower than in cases when there are knowledge spillovers or there is no exchange of knowledge.

R&D Performance Analysis: Case Studies on the Challenges and Promotion of the Evaluation and Measurement of R&D

Due to the intense international competition, demanding, and sophisticated customers, and diverse transforming technological change, organizations need to renew their products and services by allocating resources on research and development (R&D). Managing R&D is complex, but vital for many organizations to survive in the dynamic, turbulent environment. Thus, the increased interest among decision-makers towards finding the right performance measures for R&D is understandable. The measures or evaluation methods of R&D performance can be utilized for multiple purposes; for strategic control, for justifying the existence of R&D, for providing information and improving activities, as well as for the purposes of motivating and benchmarking. The earlier research in the field of R&D performance analysis has generally focused on either the activities and considerable factors and dimensions - e.g. strategic perspectives, purposes of measurement, levels of analysis, types of R&D or phases of R&D process - prior to the selection of R&Dperformance measures, or on proposed principles or actual implementation of theselection or design processes of R&D performance measures or measurement systems. This study aims at integrating the consideration of essential factors anddimensions of R&D performance analysis to developed selection processes of R&D measures, which have been applied in real-world organizations. The earlier models for corporate performance measurement that can be found in the literature, are to some extent adaptable also to the development of measurement systemsand selecting the measures in R&D activities. However, it is necessary to emphasize the special aspects related to the measurement of R&D performance in a way that make the development of new approaches for especially R&D performance measure selection necessary: First, the special characteristics of R&D - such as the long time lag between the inputs and outcomes, as well as the overall complexity and difficult coordination of activities - influence the R&D performance analysis problems, such as the need for more systematic, objective, balanced and multi-dimensional approaches for R&D measure selection, as well as the incompatibility of R&D measurement systems to other corporate measurement systems and vice versa. Secondly, the above-mentioned characteristics and challenges bring forth the significance of the influencing factors and dimensions that need to be recognized in order to derive the selection criteria for measures and choose the right R&D metrics, which is the most crucial step in the measurement system development process. The main purpose of this study is to support the management and control of the research and development activities of organizations by increasing the understanding of R&D performance analysis, clarifying the main factors related to the selection of R&D measures and by providing novel types of approaches and methods for systematizing the whole strategy- and business-based selection and development process of R&D indicators.The final aim of the research is to support the management in their decision making of R&D with suitable, systematically chosen measures or evaluation methods of R&D performance. Thus, the emphasis in most sub-areas of the present research has been on the promotion of the selection and development process of R&D indicators with the help of the different tools and decision support systems, i.e. the research has normative features through providing guidelines by novel types of approaches. The gathering of data and conducting case studies in metal and electronic industry companies, in the information and communications technology (ICT) sector, and in non-profit organizations helped us to formulate a comprehensive picture of the main challenges of R&D performance analysis in different organizations, which is essential, as recognition of the most importantproblem areas is a very crucial element in the constructive research approach utilized in this study. Multiple practical benefits regarding the defined problemareas could be found in the various constructed approaches presented in this dissertation: 1) the selection of R&D measures became more systematic when compared to the empirical analysis, as it was common that there were no systematic approaches utilized in the studied organizations earlier; 2) the evaluation methods or measures of R&D chosen with the help of the developed approaches can be more directly utilized in the decision-making, because of the thorough consideration of the purpose of measurement, as well as other dimensions of measurement; 3) more balance to the set of R&D measures was desired and gained throughthe holistic approaches to the selection processes; and 4) more objectivity wasgained through organizing the selection processes, as the earlier systems were considered subjective in many organizations. Scientifically, this dissertation aims to make a contribution to the present body of knowledge of R&D performance analysis by facilitating dealing with the versatility and challenges of R&D performance analysis, as well as the factors and dimensions influencing the selection of R&D performance measures, and by integrating these aspects to the developed novel types of approaches, methods and tools in the selection processes of R&D measures, applied in real-world organizations. In the whole research, facilitation of dealing with the versatility and challenges in R&D performance analysis, as well as the factors and dimensions influencing the R&D performance measure selection are strongly integrated with the constructed approaches. Thus, the research meets the above-mentioned purposes and objectives of the dissertation from the scientific as well as from the practical point of view.

Role of vitamin D deficiency in extraskeletal complications : predictor of health outcome or marker of health status?

The relationship of vitamin D with extraskeletal complications, such as cardiovascular disease, cancer, and autoimmune disease, is of major interest considering its roles in key biological processes and the worldwide high prevalence of vitamin D deficiency. However, the causal relationships between vitamin D and most extraskeletal complications are weak. Currently, a heated debate over vitamin D is being conducted according to two hypotheses. In this review, we first present the different arguments that suggest a major role of vitamin D in a very broad type of extraskeletal complications (hypothesis #1). We then present results from recent meta-analyses of randomized controlled trials indicating a lack of association of vitamin D with major extraskeletal complications (hypothesis #2). We discuss different issues (e.g., causality, confounding, reverse causation, misclassification, and Mendelian randomization) that contribute to the favoring of one hypothesis over the other. While ultimately only one hypothesis is correct, we anticipate that the results from the ongoing randomized controlled trials will be unlikely to reconcile the divided experts.

Anàlisi de l'estat de canvis en el patrimoni net i l'estat de fluxos d'efectiu : interpretació i anàlisi 2007-2011

L’objectiu d’aquest treball ha estat l’anàlisi dels dos nous documents comptables, l’Estat de Canvis en el Patrimoni Net – ECPN – i l’Estat de Fluxos d’Efectiu – EFE‐, introduïts amb la reforma comptable de 2007 [Reial Decret 1514/2007 de 16 de novembre i Reial Decret 1515/2007 per a petites i mitjanes empreses]. Aquest anàlisis s’ha portat a terme amb la finalitat d’analitzar com ha millorat i augmentat la informació per la presa de millors decisions tant per les empreses com per analistes externs. El treball consta de dues parts, la primera part està formada per un anàlisis teòric d’aquests dos documents. La segona part està formada per un anàlisis pràctic de les empreses del sector de Materials Bàsics, Indústria i Construcció de la Borsa de Madrid. D’aquestes empreses s’ha realitzat un anàlisis convencional i l’ anàlisis dels corresponents ECPN i EFE de cadascuna de les empreses, amb l’objectiu de comprovar la millora de la informació.

Cultura, identitat i diversitat: projecte de creació d'un centre d'experimentació cultural i artística

Quin hauria de ser el paper de les pràctiques artístiques i la cultura contemporània a la societat? I les institucions artístiques, quin rol haurien d’assolir? Aquest treball final de màster és una indagació entorn els fets més significatius al llarg de la història del món occidental pel que fa a la cultura que s’ha desenvolupat al marge dels poders. Una anàlisi de les relacions que s’estableixen entre aquests diversos àmbits, on es planteja un projecte que compleix les característiques de ser un laboratori per a les pràctiques artístiques contemporànies i la seva recerca. Partint, a més a més, de la base teòrica de la historia cultural que ens porta fins on som ara i com a conformadora de les identitats

L’erotisme a les Cartes a les Senyores dels Àngels i de Jerusalem, de Francesc Fontanella = Eroticism in Cartes a les Senyores dels Àngels i de Jerusalem, of Francesc Fontanella

This article focuses on the study of the treatment of eroticism in some of the poetic compositions from Francesc Fontanella (1622-1682/3). The paper studies fiften literary epistles whisch Fontanella dedicated to the nuns of the convent of Els Àngels and Jerusalem of Barcelona during the 1640s. It is divided into two parts; to first, the compositions under study are identified and presented briefly, and some issues related to the transmission of these textes are clarified. The second part discusses in detail all erotic references present in text. This analysis, on one hand, allows to present an interpretation of the meaning of the whole story contained in the letters. Moreover, it allows to present a characterization of the erotic vision of Fontanella. This is done by comparing this vision with the usual one at the time of baroque, as well as by analyzing the rhetorical strategies and the representation strategies that the author uses in the treatment of eroticism

Projecte P.I.T.O.S (Projecte d'informació telefònica d'orientació al S.A.T)

JCM és una empresa dedicada al disseny de sistemes de control d’accés. Disposa d’uns equips elèctrics amb molts paràmetres configurables, així es poden utilitzar en molts tipus d’instal•lació. Aquets paràmetres són configurables pels clients. JCM, disposa d’un servei d’atenció telefònica (SAT), que intenta donar solucions a tots els problemes que puguin sorgir als clients. Sovint, no poden donar suport als dubtes dels clients per culpa de la poca informació que reben a través del client. L'objectiu del projecte és resoldre el problema de falta d'informació i mala comunicació per millorar la qualitat del servei que ofereix el SAT. La solució, no ha d’alterar el cost de producció del producte. S’ha de tenir en compte també que els equips poden estar instal•lats en qualsevol part del món i que només es poden utilitzar recursos de fàcil accés per tots els clients. Per complir amb aquests objectius, emetrem un missatge, a través del brunzidor del equip, amb la informació de configuració de l'equip. Aquest missatge viatjarà a través de la xarxa telefònica fins al SAT. Un cop allà, el descodificarem i n'enviarem les dades a un PC perquè pugui presentar les dades sobre la configuració de una forma clara pel SAT.

Efficacy of the d-phenothrin/pyriproxyfen association against mites in naturally co-infested rabbits

The aim of the present study was to evaluate the efficacy of the d-phenothrin/pyriproxyfen association against Psoroptes ovis, Cheyletiella parasitivorax, and Leporacarus gibbus infestations in naturally co-infested rabbits. Twenty crossbreed (New Zealand White x California) rabbits concurrently infested by the three mite species were randomly divided in two groups. All rabbits presented with hyperemia, erythema and formation of crusts in the ear canals caused by P. ovis. Infestations by both C. parasitivorax and L. gibbus were considered asymptomatic in all animals.Ten animals were treated with a 4.4% d-phenothrin and 0.148% pyriproxyfen spray formulation until have their body surface uniformly sprayed, including external ear canals. The other ten rabbits remained untreated, serving as control group. Observations were done on days +7, +14, +21, +28, and +35 post-treatment. The d-phenothrin/pyriproxyfen association showed 100% efficacy against the three mite species and was responsible for the remission of psoroptic mange lesions on treated animals. No signs of intoxication were observed. The results indicate that d-phenothrin/pyriproxyfen spray formulation in a single application is an effective and clinically safe option for the control of different mite infestations in rabbits.