Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer.

BACKGROUND: To improve the efficacy of first-line therapy for advanced non-small cell lung cancer (NSCLC), additional maintenance chemotherapy may be given after initial induction chemotherapy in patients who did not progress during the initial treatment, rather than waiting for disease progression to administer second-line treatment. Maintenance therapy may consist of an agent that either was or was not present in the induction regimen. The antifolate pemetrexed is efficacious in combination with cisplatin for first-line treatment of advanced NSCLC and has shown efficacy as a maintenance agent in studies in which it was not included in the induction regimen. We designed a phase III study to determine if pemetrexed maintenance therapy improves progression-free survival (PFS) and overall survival (OS) after cisplatin/pemetrexed induction therapy in patients with advanced nonsquamous NSCLC. Furthermore, since evidence suggests expression levels of thymidylate synthase, the primary target of pemetrexed, may be associated with responsiveness to pemetrexed, translational research will address whether thymidylate synthase expression correlates with efficacy outcomes of pemetrexed. METHODS/DESIGN: Approximately 900 patients will receive four cycles of induction chemotherapy consisting of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day 1 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 who have not progressed during induction therapy will randomly receive (in a 2:1 ratio) one of two double-blind maintenance regimens: pemetrexed (500 mg/m2 on day 1 of a 21-day cycle) plus best supportive care (BSC) or placebo plus BSC. The primary objective is to compare PFS between treatment arms. Secondary objectives include a fully powered analysis of OS, objective tumor response rate, patient-reported outcomes, resource utilization, and toxicity. Tumor specimens for translational research will be obtained from consenting patients before induction treatment, with a second biopsy performed in eligible patients following the induction phase. DISCUSSION: Although using a drug as maintenance therapy that was not used in the induction regimen exposes patients to an agent with a different mechanism of action, evidence suggests that continued use of an agent present in the induction regimen as maintenance therapy enables the identification of patients most likely to benefit from maintenance treatment.

Nous processos i formes de creixement urbà: el cas del districte industrial de Montebelluna a Itàlia

This article analyses the spatial organization of Montebelluna's industrial district (Italy) as an exemple of the dinamics of urbanization phenomenon in small urban areas. The study is divided in two parts: in the first one I present the social organisation's model of production named «industrial district» and its relation with the space, which is characterizeded by the rising of diffused urbanization settlements; in the second part I try to verify some explanatory factors pointed out by different autors in this specific area with an historical analysis of processes point of view. The diffused organisation of economic and housing activity show a change in the urban morphology

El concepte de districte industrial: un repàs des de l'òptica de la tradició italiana

L’ article fa un repàs de l’evolució del concepte de districte industrial des de l’ òptica de l’experiència italiana. Partint de la constatació dels canvis que hi ha hagut en les formes d’organització de la producció en els tres darrers decennis, s’exposa l’evolució del model del districte industrial com a paradigma d’ Alfred Marshall, de principis del segle XX, s’ha anat enriquint a mesura que ha madurat l’ experiència districtual, que avui afronta els reptes de la globalització econòmica

Actin filament dynamics impacts keratinocyte stem cell maintenance.

Cultured human epidermal keratinocyte stem cells (holoclones) are crucial for regenerative medicine for burns and genetic disorders. In serial culture, holoclones progressively lose their proliferative capacity to become transient amplifying cells with limited growth (paraclones), a phenomenon termed clonal conversion. Although it negatively impacts the culture lifespan and the success of cell transplantation, little is known on the molecular mechanism underlying clonal conversion. Here, we show that holoclones and paraclones differ in their actin filament organization, with actin bundles distributed radially in holoclones and circumferentially in paraclones. Moreover, actin organization sets the stage for a differing response to epidermal growth factor (EGF), since EGF signalling induces a rapid expansion of colony size in holoclones and a significant reduction in paraclones. Furthermore, inhibition of PI3K or Rac1 in holoclones results in the reorganization of actin filaments in a pattern that is similar to that of paraclones. Importantly, continuous Rac1 inhibition in holoclones results in clonal conversion and reduction of growth potential. Together, our data connect loss of stem cells to EGF-induced colony dynamics governed by Rac1.

Refrigeració de les gillettes d’ una talladora industrial

L’empresa Proslit Equipment forma part del Grup Comexi i la seva activitat consisteix en la fabricació de màquines talladores de material flexible. Degut als avenços tecnològics, s’han incrementat les prestacions de les seves màquines, entre altres coses, s’ha augmentat la velocitat de tall del film fins a 800 m/min. Aquest factor afegit a condicionants com per exemple treballar amb materials gruixuts i abrasius, a temperatures ambientals elevades, etc. fa que sorgeixi una problemàtica en el tall gillette. Degut a la fricció entre el film que circula i les gillettes que el tallen, es crea una energia calorífica que fa augmentar la temperatura de les gillettes fins a tal extrem que aquestes provoquen petites fusions del plàstic, aquest s’incrusta a les gillettes que s’acaben trencant. L’objecte principal d’aquest projecte és fer una anàlisi tècnica mitjançant elements finits de la problemàtica que s’ha detectat a les màquines talladores de l’empresa Proslit Equipment, concretament de l’escalfament de les gillettes utilitzades en el sistema de tall. Es pretén crear un model teòric que s’aproximi al màxim a la realitat de manera que es pugui observar el comportament tèrmic del sistema de tall en funció de les condicions que es determinin com a més desfavorables. Una vegada s’obtinguin aquests resultats teòrics, es valoraran i es proposaran solucions

5

The nervous system is a frequent target of industrial chemicals, pharmaceuticals, and environmental pollutants. To screen large numbers of compounds for their neurotoxic potential, in vitro systems are required which combine organ-specific traits with robustness and high reproducibility. These requirements are met by serum-free aggregating brain cell cultures derived from mechanically dissociated embryonic rat brain. The initial cell suspension, composed of neural stem cells, neural progenitor cells, immature postmitotic neurons, glioblasts, and microglial cells, is kept under continuous gyratory agitation. Spherical aggregates form spontaneously and are maintained in suspension culture for several weeks. Within the aggregates, the cells rearrange and mature, reproducing critical morphogenic events such as migration, proliferation, differentiation, synaptogenesis, and myelination. In addition to the spontaneous reconstitution of histotypic brain architecture, the cultures acquire organ-specific functionality as indicated by activity-dependent glucose consumption, spontaneous electrical activity, and brain-specific inflammatory responses. These three-dimensional primary cell cultures offer therefore a unique model for neurotoxicity testing both during development and at advanced cellular differentiation. The high number of aggregates available and the excellent reproducibility of the cultures facilitate routine test procedures. This chapter presents a detailed description of the preparation and maintenance of these cultures as well as their use for routine toxicity testing.

Finca-Museo agroindustrial San Julián : proyecto para la difusión y la conservación del patrimonio industrial de Guatemala

Disseny d'un espai multidisciplinar que permeti l'interpretació del Patrimoni Industrial i Cultural de la Finca agroindustrial de San Julián (Guatemala), amb l'objectiu de fomentar la difusió i la conservació del Patrimonio Industrial del país

Projecte de nau industrial sostenible

La majoria de naus industrials són edificis contenidors, senzills, modulars i, sobretot, concebuts com a edificis rendibles, sense tenir en compte criteris de protecció del medi ambient. En el projecte s’ha optat per fer el disseny i càlcul d’una nau industrial prefabricada de formigó armat per a la fabricació de maquinària per la indústria agroalimentària, amb dos nivells d’oficines, zona de producció amb pont grua, laboratoris i magatzems amb una superfície total aproximada de 1800 m². Per tal que sigui un edifici sostenible, s’ha optat per la instal·lació de plaques solars fotovoltaiques, aïllament tèrmic, aprofitament d’aigües plujanes, gestió de residus, aprofitament òptim, il·luminació natural, estalvi d’energia a causa d'una bona gestió dels recursos energètics

Induction and maintenance of protective CD8+ T cells against malaria liver stages: implications for vaccine development

CD8+ T cells against malaria liver stages represent a major protective immune mechanism against infection. Following induction in the peripheral lymph nodes by dendritic cells (DCs), these CD8+ T cells migrate to the liver and eliminate parasite infected hepatocytes. The processing and presentation of sporozoite antigen requires TAP mediated transport of major histocompatibility complex class I epitopes to the endoplasmic reticulum. Importantly, in DCs this process is also dependent on endosome-mediated cross presentation while this mechanism is not required for epitope presentation on hepatocytes. Protective CD8+ T cell responses are strongly dependent on the presence of CD4+ T cells and the capacity of sporozoite antigen to persist for a prolonged period of time. While human trials with subunit vaccines capable of inducing antibodies and CD4+ T cell responses have yielded encouraging results, an effective anti-malaria vaccine will likely require vaccine constructs designed to induce protective CD8+ T cells against malaria liver stages.

Projecte constructiu d’una nau industrial

Definició d’una nau industrial per a magatzem frigorífic mitjançant lamemòria tècnica, els plànols i els càlculs ubicada al terme municipal de Begur (Baix Empordà)

Gestió d'un magatzem recanvis industrial

El treball final de carrera tracta l'estudi i disseny de la gestió d'un magatzem, en particular enfocat a un magatzem de recanvis d'una empresa de caire industrial, que a banda d'utilitzar els materials per a realitzar el manteniment dels equips productius també els necessita per a la construcció d'automatismes per a la automatització del procés productiu. L'estudi esta enfocat a una posterior parametrització e implementació mitjançant SAP R/3, ja que aquest ERP és una de les eines més potents que existeixen al mercat mundial per la gestió de magatzems, amb el valor afegit d'integrar el sistema de emmagatzematge amb la resta de àrees funcionals de l'empresa.

Evaluation of work-related volatile organic compounds (VOCs) exposition in automotive painting cabins industrial cleanings

Automotive painting cabins are cleaned with several solvents, being great part of them mixtures of volatile organic compounds (VOCs), where the three xylene isomers are the most important constituents. To evaluate the work-related exposition of the cleaners that use these mixtures of solvents, xylenes have been determined in the working ambient air as well as its metabolite, o-m-p-methyl hippuric acid, has been analysed in urine to establish the dermal and respiratory exposition. This evaluation has been done in order to assess the occupational exposure to VOCs and to know the working conditions of the cleaners, but also to evaluate the effectiveness of personal protective equipment (PPE), the engineering control and the work practices.The xylenes have been chosen as indicators of exposition because they are the main components in the cleaning solvents used, with a level of concentration between 50% and 85%.The Xylenes have an occupational exposure limit (8 h TWA) of 50 ppm (221 mg/m3) and a short-term exposure limit (STEL) of 100 ppm (442 mg/m3). On the other hand, the biological exposure index (BEI) for xylenes is the sum of the total methyl hippuric acids in urine at the end of the work-shift, being the value 1500 mg/g creatinine.

Dashboard industrial: panell d'indicadors per gestionar una fàbrica d'una multinacional del sector d'automoció

En el context de globalització i competitivitat actuals, sobretot en el sectord’automoció, les diferències competitives entre empreses o companyies estàcada vegada més relacionada amb els factors immaterials, tals com elconeixement, la investigació, el desenvolupament tecnològic i la qualificaciódels recursos humans i l’eficiència en la gestió.L’eficiència en la gestió és bàsica per aconseguir un plus de competitivitatque és clau per satisfer els clients, i per tant, també per agilitzar lesorganitzacions i posar-les a punt per a nous reptes i per a nous models denegoci per donar resposta a la demanda de la canviant i exigent societat.Aquest treball exposa un exemple d’un sistema de gestió basat en el panelld’indicadors (“Dashboard Industrial”) per una planta d’una multinacional delsector d’automoció.Aquesta eina, que està alineada amb l’estratègia de la companyia, es potextrapolar altres empreses i a altres sectors. Està basada en lametodologia PDCA (Plan Do Check Act) és a dir planificant objectius,posant-los en pràctica mesurant-los periòdicament i prenent decisions per lamillora contínua dels resultats de cada una dels indicadors.Sens dubte, l’eficiència en la gestió és un dels factors clau per lesorganitzacions amb ànim innovador i competitiu.En el treball també es destaca la importància que té la tasca dels enginyersen la gestió al llarg de la seva vida laboral.

Mate choice evolution, dominance effects, and the maintenance of genetic variation.

Female mate choice influences the maintenance of genetic variation by altering the mating success of males with different genotypes. The evolution of preferences themselves, on the other hand, depends on genetic variation present in the population. Few models have tracked this feedback between a choice gene and its effects on genetic variation, in particular when genes that determine offspring viability and attractiveness have dominance effects. Here we build a population genetic model that allows comparing the evolution of various choice rules in a single framework. We first consider preferences for good genes and show that focused preferences for homozygotes evolve more easily than broad preferences, which allow heterozygous males high mating success too. This occurs despite better maintenance of genetic diversity in the latter scenario, and we discuss why empirical findings of superior mating success of heterozygous males consequently do not immediately lead to a better understanding of the lek paradox. Our results thus suggest that the mechanisms that help maintain genetic diversity also have a flipside of making female choice an inaccurate means of producing the desired kind of offspring. We then consider preferences for heterozygosity per se, and show that these evolve only under very special conditions. Choice for compatible genotypes can evolve but its selective advantage diminishes quickly due to frequency-dependent selection. Finally, we show that our model reproduces earlier results on selfing, when the female choice strategy produces assortative mating. Overall, our model indicates that various forms of heterozygote-favouring (or variable) female choice pose a problem for the theory of sexual ornamentation based on indirect benefits, rather than a solution.