355 research outputs found

    Inconvenientes de la teorĂ­a ortodoxa del trabajo

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    La teoría ortodoxa del trabajo representa en la actualidad el marco de referencia a partir de la cual se analizan los problemas laborales y se diseñan políticas económicas y sociales que tienen un impacto significativo en el sistema económico. Este marco analítico se construye a partir de la idea de que el trabajo representa una actividad meramente instrumental que únicamente le confiere un nivel de des-utilidad a los individuos, de modo que el bienestar de estos solo es influenciado positivamente por el consumo. En ese sentido, el objetivo de este artículo es discutir las razones por las que esta forma de conceptualizar el trabajo genera inconvenientes analíticos e introduce limitaciones explicativas sobre las cuestiones laborales en esta postura teórica

    A First Comparison Between LIGO and Virgo Inspiral Search Pipelines

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    This article reports on a project that is the first step the LIGO Scientific Collaboration and the Virgo Collaboration have taken to prepare for the mutual search for inspiral signals. The project involved comparing the analysis pipelines of the two collaborations on data sets prepared by both sides, containing simulated noise and injected events. The ability of the pipelines to detect the injected events was checked, and a first comparison of how the parameters of the events were recovered has been completed.Comment: GWDAW-9 proceeding

    Mathematical Model of Clonal Evolution Proposes a Personalised Multi-Modal Therapy for High-Risk Neuroblastoma

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    : Neuroblastoma is the most common extra-cranial solid tumour in children. Despite multi-modal therapy, over half of the high-risk patients will succumb. One contributing factor is the one-size-fits-all nature of multi-modal therapy. For example, during the first step (induction chemotherapy), the standard regimen (rapid COJEC) administers fixed doses of chemotherapeutic agents in eight two-week cycles. Perhaps because of differences in resistance, this standard regimen results in highly heterogeneous outcomes in different tumours. In this study, we formulated a mathematical model comprising ordinary differential equations. The equations describe the clonal evolution within a neuroblastoma tumour being treated with vincristine and cyclophosphamide, which are used in the rapid COJEC regimen, including genetically conferred and phenotypic drug resistance. The equations also describe the agents' pharmacokinetics. We devised an optimisation algorithm to find the best chemotherapy schedules for tumours with different pre-treatment clonal compositions. The optimised chemotherapy schedules exploit the cytotoxic difference between the two drugs and intra-tumoural clonal competition to shrink the tumours as much as possible during induction chemotherapy and before surgical removal. They indicate that induction chemotherapy can be improved by finding and using personalised schedules. More broadly, we propose that the overall multi-modal therapy can be enhanced by employing targeted therapies against the mutations and oncogenic pathways enriched and activated by the chemotherapeutic agents. To translate the proposed personalised multi-modal therapy into clinical use, patient-specific model calibration and treatment optimisation are necessary. This entails a decision support system informed by emerging medical technologies such as multi-region sequencing and liquid biopsies. The results and tools presented in this paper could be the foundation of this decision support system

    Permeability properties of a three-cell type in vitro model of blood-brain barrier.

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    We previously found that RBE4.B brain capillary endothelial cells (BCECs) form a layer with blood-brain barrier (BBB) properties if co-cultured with neurons for at least one week. As astrocytes are known to modulate BBB functions, we further set a culture system that included RBE4.B BCECs, neurons and astrocytes. In order to test formation of BBB, we measured the amount of 3H-sucrose able to cross the BCEC layer in this three-cell type model of BBB. Herein we report that both neurons and astrocytes induce a decrease in the permeability of the BCEC layer to sucrose. These effects are synergic as if BCECs are cultured with both neurons and astrocytes for 5 days, permeability to sucrose decreases even more. By Western analysis, we also found that, in addition to the canonical 60 kDa occludin, anti-occludin antibodies recognize a smaller protein of 48 kDa which accumulates during rat brain development. Interestingly this latter protein is present at higher amounts in endothelial cells cultured in the presence of both astrocytes and neurons, that is in those conditions in which sucrose permeation studies indicate formation of BBB

    Izdvajanje bakterije Escherichia coli O157:H7 i njezin dokaz lančanom reakcijom polimerazom u crijevima filipinskih šišmiša.

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    It is currently reported that bats in the Philippines harbor bacterial organism (Salmonella spp.) with pathogenic potential. The paper describes the conventional isolation and polymerase chain reaction (PCR) assay for the detection of another bacterium, Escherichia coli, from a sample population of 56 apparently healthy bats collected from Laguna and Quezon City, Philippines. Nineteen of the samples were positive for E. coli using the conventional method of isolation, while PCR molecularly detected the bacteria in 15 samples. The presence of hemolysin among the isolates was not observed. The isolates were subjected to E. coli O157:H7 serotype detection using the latex agglutination test and another PCR assay specific for this serotype. The data revealed that none of the isolates was positive for E. coli O157:H7 using serological and molecular diagnostic methods, which indicates that bats from Laguna and Quezon City, Philippines were not carriers of the pathogenic strain, E. coli O157:H7. The study also presents the first local report of conventional isolation and molecular detection of E. coli from Philippine bats.Poznato je da šišmiši na Filipinima mogu biti nositelji potencijalno patogenih bakterija, npr. salmonela. U radu je opisano izdvajanje i dokaz lančanom reakcijom polimerazom bakterije Escherichia coli iz 56 naizgled zdravih šišmiša uhvaćenih na području Laguna i Quezon City na Filipinima. E. coli bila je izdvojena iz 19 uzoraka, dok je lančanom reakcijom polimerazom ona bila dokazana u 15 uzoraka. Izolati nisu tvorili hemolizu, a lateks aglutinacija i specifični PCR rabljeni su za dokaz serovara O157:H7 bakterije E. coli. Nijedan izolat nije pripadao serovaru O157:H7, na osnovi čega se može zaključiti da šišmiši na području Laguna i Quezon City na Filipinima nisu nositelji patogenog soja E. coli O157:H7. Istraživanje je ujedno prvi dokaz o izdvajanju i molekularnoj identifikaciji bakterije E. coli u šišmiša na Filipinima

    Izdvajanje bakterije Escherichia coli O157:H7 i njezin dokaz lančanom reakcijom polimerazom u crijevima filipinskih šišmiša.

    Get PDF
    It is currently reported that bats in the Philippines harbor bacterial organism (Salmonella spp.) with pathogenic potential. The paper describes the conventional isolation and polymerase chain reaction (PCR) assay for the detection of another bacterium, Escherichia coli, from a sample population of 56 apparently healthy bats collected from Laguna and Quezon City, Philippines. Nineteen of the samples were positive for E. coli using the conventional method of isolation, while PCR molecularly detected the bacteria in 15 samples. The presence of hemolysin among the isolates was not observed. The isolates were subjected to E. coli O157:H7 serotype detection using the latex agglutination test and another PCR assay specific for this serotype. The data revealed that none of the isolates was positive for E. coli O157:H7 using serological and molecular diagnostic methods, which indicates that bats from Laguna and Quezon City, Philippines were not carriers of the pathogenic strain, E. coli O157:H7. The study also presents the first local report of conventional isolation and molecular detection of E. coli from Philippine bats.Poznato je da šišmiši na Filipinima mogu biti nositelji potencijalno patogenih bakterija, npr. salmonela. U radu je opisano izdvajanje i dokaz lančanom reakcijom polimerazom bakterije Escherichia coli iz 56 naizgled zdravih šišmiša uhvaćenih na području Laguna i Quezon City na Filipinima. E. coli bila je izdvojena iz 19 uzoraka, dok je lančanom reakcijom polimerazom ona bila dokazana u 15 uzoraka. Izolati nisu tvorili hemolizu, a lateks aglutinacija i specifični PCR rabljeni su za dokaz serovara O157:H7 bakterije E. coli. Nijedan izolat nije pripadao serovaru O157:H7, na osnovi čega se može zaključiti da šišmiši na području Laguna i Quezon City na Filipinima nisu nositelji patogenog soja E. coli O157:H7. Istraživanje je ujedno prvi dokaz o izdvajanju i molekularnoj identifikaciji bakterije E. coli u šišmiša na Filipinima

    Peroral Amphotericin B Polymer Nanoparticles Lead to Comparable or Superior In Vivo Antifungal Activity to That of Intravenous Ambisome® or Fungizone™

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    Background: Despite advances in the treatment, the morbidity and mortality rate associated with invasive aspergillosis remains unacceptably high (70–90%) in immunocompromised patients. Amphotericin B (AMB), a polyene antibiotic with broad spectrum antifungal activity appears to be a choice of treatment but is available only as an intravenous formulation; development of an oral formulation would be beneficial as well as economical. Methodology: Poly(lactide-co-glycolode) (PLGA) nanoparticles encapsulating AMB (AMB-NPs) were developed for oral administration. The AMB-NPs were 113±20 nm in size with ~70% entrapment efficiency at 30% AMB w/w of polymer. The in vivo therapeutic efficacy of oral AMB-NPs was evaluated in neutropenic murine models of disseminated and invasive pulmonary aspergillosis. AMB-NPs exhibited comparable or superior efficacy to that of Ambisome® or Fungizone™ administered parenterally indicating potential of NPs as carrier for oral delivery. Conclusions: The present investigation describes an efficient way of producing AMB-NPs with higher AMB pay-load and entrapment efficiency employing DMSO as solvent and ethanol as non-solvent. The developed oral formulation was highly efficacious in murine models of disseminated aspergillosis as well as an invasive pulmonary aspergillosis, which is refractory to treatment with IP Fungizone™and responds only modestly to AmBisome®

    Samarium-153-EDTMP (Quadramet®) With or Without Vaccine in Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase 2 Trial

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    PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone metastases, prior docetaxel and no visceral disease. The primary endpoint was the proportion of patients without radiographic disease progression at 4 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and immune responses. Forty-four patients enrolled. Eighteen and 21 patients were evaluable for the primary endpoint in Sm-153-EDTMP alone and combination arms, respectively. There was no statistical difference in the primary endpoint, with two of 18 (11.1%) and five of 21 (23.8%) in Sm-153-EDTMP alone and combination arms, respectively, having stable disease at approximately the 4-month evaluation time point (P = 0.27). Median PFS was 1.7 vs. 3.7 months in the Sm-153-EDTMP alone and combination arms (P = 0.041, HR = 0.51, P = 0.046). No patient in the Sm-153-EDTMP alone arm achieved prostate-specific antigen (PSA) decline \u3e 30% compared with four patients (of 21) in the combination arm, including three with PSA decline \u3e 50%. Toxicities were similar between arms and related to number of Sm-153-EDTMP doses administered. These results provide the rationale for clinical evaluation of new radiopharmaceuticals, such as Ra-223, in combination with PSA-TRICOM
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