115 research outputs found
Extracting Dense and Connected Subgraphs in Dual Networks by Network Alignment
The use of network based approaches to model and analyse large datasets is
currently a growing research field. For instance in biology and medicine,
networks are used to model interactions among biological molecules as well as
relations among patients. Similarly, data coming from social networks can be
trivially modelled by using graphs. More recently, the use of dual networks
gained the attention of researchers. A dual network model uses a pair of graphs
to model a scenario in which one of the two graphs is usually unweighted (a
network representing physical associations among nodes) while the other one is
edge-weighted (a network representing conceptual associations among nodes). In
this paper we focus on the problem of finding the Densest Connected sub-graph
(DCS) having the largest density in the conceptual network which is also
connected in the physical network. The problem is relevant but also
computationally hard, therefore the need for introducing of novel algorithms
arises. We formalise the problem and then we map DCS into a graph alignment
problem. Then we propose a possible solution. A set of experiments is also
presented to support our approach
DESENVOLVIMENTO DE UM PROTÓTIPO DE EMISSOR-RECEPTOR INFRAVERMELHO PARA APLICAÇÃO DA TÉCNICA FNIR
Construímos um protótipo de baixo custo, de um equipamento que utilizando sistemas de filtros e amplificadores analógicos, emite e detecta sinais eletromagnéticos na faixa de espectro do infravermelho, digitalizados pela plataforma National Instruments e modelados matematicamente através do sistema LabVIEW (plataforma de software da National Instruments). Resultados preliminares apontam para a possibilidade de o equipamento ser aplicado na prática de aquisição de biosinais por espectroscopia funcional infravermelha – fNIR
Zeranol y metabolitos urinarios de zearalenona en bovinos para carne
El noreste argentino es, por sus características geográficas y ambientales, una región con fuerte potencial para la actividad ganadera. Los rodeos vacunos de esta zona tienen como base alimenticia pastizales y pasturas mejoradas, las que suelen suplementarse con granos, fuentes proteicas y reservas en forma de rollos o silaje. Estos alimentos son sustratos ricos para que especies de hongos produzcan micotoxinas como zearalenona (ZEA). El consumo de ZEA por los animales hace que se excreten diferentes metabolitos en orina entre los que se encuentra el zeranol. Por su parte, la presencia de zeranol en orina es utilizada como indicador del uso indebido de promotores de crecimiento que se hallan prohibidos en el país. El objetivo de este trabajo fue analizar los metabolitos relacionados con la ZEA excretados en la orina de novillos según los siguientes tratamientos: alimentación con un concentrado de ZEA, exposición a la aplicación de zeranol inyectable y acción simultánea de alimentación con un concentrado de ZEA más exposición a la aplicación de zeranol inyectable. Se presentan los perfiles de metabolitos excretados en orina y su evolución en el tiempo.The northern east Argentinean region is, on the basis of its geographic and environmental features, an area with a strong growing cattle potential. Supplementation of natural feeding with protein sources and silage constitutes a usual practice. The feeding supplements supports fungal growth and subsequent micotoxins evolvement as well. Production of zearalenone (ZEA) is particularly relevant because, among its related metabolites excreted in urine there is the zeranol. The zeranol presence in urine is strongly regulated by Argentinean law because it is considered an indicator of forbidden growing promoters using. The objective of the present work was to analyze the ZEA related metabolites excreted in urine of cows exposed to ZEA and/or zeranol in three ways: ZEA concentrated feeding, zeranol injection, and a combined exposure to ZEA concentrate feeding plus zeranol injection. The urine ZEA metabolites profiles and their time evolvement are given.Inst. de PatobiologíaFil: Salvat, Adriana Elisabeth. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Comerio, Ricardo Mario. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Balbuena, Osvaldo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Colonia Benitez; ArgentinaFil: Rosello Brajovich, José Emilio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Colonia Benitez; ArgentinaFil: Ricca, Alejandra Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; ArgentinaFil: Rojas, Dante Emanuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; ArgentinaFil: Cristos, Diego Sebastian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; ArgentinaFil: Ronco, S. Servicio Nacional de Sanidad y Calidad Agroalimentaria (SENASA); ArgentinaFil: Salerno, Juan Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentin
Presencia de zearalenona en pasturas del este de Chaco
Se estudió la presencia de zearalenona en pasturas y alimentos que son utilizados para la producción de bovinos de carne de la zona este de la provincia del Chaco. Asimismo, se realizó el aislamiento e identificación de diversas especies de Fusarium y se determinó su capacidad de producir zearalenona en condiciones de laboratorio. La determinación química de la toxina se realizó mediante las metodologías HPLC y ensayo inmunoenzimático (ELISA). Se analizaron 29 muestras y en 17 de ellas se confirmó la ocurrencia natural de zearalenona en cantidades variables. Se identificaron 63 aislamientos que correspondieron a Fusarium cf. acuminatum, F. chlamydosporum, F. equiseti, F. oxysporum y F. semitectum, confirmándose además la producción in vitro de zearalenona en 34 de éstos aislamientosNatural occurrence of zearalenone in grassland, improved pastures and feeds for cattle in eastern Chaco province (Argentina) was surveyed. Besides, isolation, identification and toxicogenic capacity of several Fusarium
species were carried out. HPLC and ELISA techniques were used for detection of the toxin. In 17 of 29 samples zearalenone presence was confirmed. Sixty- three Fusarium isolates corresponding to Fusarium cf. acuminatum F. chlamydosporum, F. equiseti, F. oxysporum and F. semitectum were identified. On the other hand, in vitro production of zearalenone was verified in 34 of these isolates.Inst. de PatobiologíaFil: Salvat, Adriana Elisabeth. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Balbuena, Osvaldo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Colonia Benitez; ArgentinaFil: Ricca, Alejandra Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; ArgentinaFil: Comerio, Ricardo Mario. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Rosello Brajovich, José Emilio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Colonia Benitez; ArgentinaFil: Rojas, Dante Emanuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; ArgentinaFil: Berretta, Marcelo Facundo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Microbiología y Zoología Agrícola; ArgentinaFil: Delssin, Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Colonia Benitez; ArgentinaFil: Bedascarrasbure, Enrique Luciano. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; ArgentinaFil: Salerno, Juan Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentin
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Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.
Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Zearalenone content in animal fodder samples in relation to weather conditions in Colonia Benítez, northeastern Argentina
The northeast of Argentina is a livestock production area. Generally cattle in this area feed on grasslands and improved pastures, but their food is often supplemented with grains, protein sources and reserves in the form of hay and/or silage. However, these food sources may be colonised by fungi including Fusarium, which produce mycotoxins, one of which is zearalenone (ZEA). The aim of this study was to relate the natural occurrence of ZEA in Colonia Benítez (Chaco Province) to the temperature and moisture of the autumn preceding the winter collection of fodder samples in 2012 and 2013. The forage resources of 2012 had high ZEA contents (310 to 6279 μg/kg) in 47 % of the samples, whereas those from 2013 exhibited intermediate values of ZEA contents (131 to 296 μg/kg) in 41.6 % of the samples and low contents (< 2 to 91 μg/kg) in 50 % of the samples. The incidence of F. semitectum was higher in 2012 compared to 2013. The high concentration of ZEA found in many of the forage samples collected in July 2012 was preceded by autumn weather conditions that were exceptionally conducive to plant stress. In contrast, when meteorological factors were within normal values (as in the autumn of 2013), the pasture and feed collected in winter showed intermediate to low concentrations of ZEA. The temperature and moisture conditions prevailing during the autumn of 2012 accelerated canopy senescence of the forage plants available for livestock at the beginning of the winter. Consequently, the weather conditions during the autumn 2012 likely favoured the sharp increase in ZEA content in these pastures when compared to the other two seasons.Fil: Salvat, Adriana Elisabeth. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Moschini, Ricardo Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Clima y Agua; ArgentinaFil: Comerio, Ricardo Mario. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Anguil; ArgentinaFil: Balbuena, Osvaldo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Colonia Benítez; ArgentinaFil: Rosello Brajovich, José Emilio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Colonia Benítez; ArgentinaFil: Cristos, Diego Sebastian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; ArgentinaFil: Rojas, Dante Emanuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; ArgentinaFil: Ricca, Alejandra Patricia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Tecnología de Alimentos; ArgentinaFil: Salerno, Juan Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentin
The ethical challenges and opportunities of implementing engagement strategies in health research
Biocompatibilidad posimplante de matrices fibrosas nanocompuestas electrohiladas de policapronolactona
Tissue engineering aims regenerating de novo lost tissue. Our objective was to analyze the biocompatibility of the implant of PCL-nHAp, an electro-spun scaffold prepared by mixtures of a biocompatible and bioabsorbable polyester, poly(caprolactone), and a bioactive ceramic of nanofibrous structure (nanohydroxyapatite particles), in an in vivo model (New Zealand female rabbits). Scaffolds were 5 mm diameter PCL-nHAp discs, superficially modified to increase hydrophilicity by alkaline treatment and sterilized (peracetic acid). Treatments were (I) control, no bone lesion, (II) metaphyseal femoral bone lesion 3 mm deep and 5 mm diameter and PCL-nHAp implant; (III) lesion but no implant (n=6). Rabbit?s clinical evolution was adequate, without affecting gait. No differences in biochemical values (hemograms and transaminases) were detected after 1; 5 and 90 days. Histological studies (90days, 4n) showed that PCL-nHAp scaffold with a corrugated appearance, surrounded, from the outside inwards: A-Hematopoietic bone marrow with megakaryocytes and / or fat with congestive areas; B- few incipiently formed trabeculae, of varied forms;and C- presence of multinucleated giant cells, macrophages, lymphocytes combined with areas of hemorrhage and congestion. An adequate biocompatibility of the scaffolds can be observed, which in its imminent degradation process has not affected the biochemical parameters studied. A non-toxic and biologically active histological response is observed, with moderate levels of inflammation. We believe that longer post-implant periods will allow definitive conclusions.Fil: Missana, Liliana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Moreno Garcia, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: García, L. A.. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Osteoarticular, Ingeniería Tisular y Terapias Emergentes; ArgentinaFil: Aimone, M.. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Osteoarticular, Ingeniería Tisular y Terapias Emergentes; ArgentinaFil: Santiago, O.. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Osteoarticular, Ingeniería Tisular y Terapias Emergentes; ArgentinaFil: Melián Salerno, Emanuel José. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Osteoarticular, Ingeniería Tisular y Terapias Emergentes; ArgentinaFil: Camal Ruggieri, I. N.. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Osteoarticular, Ingeniería Tisular y Terapias Emergentes; ArgentinaFil: Ramallo, M.. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Osteoarticular, Ingeniería Tisular y Terapias Emergentes; ArgentinaFil: Rivero, Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Abraham, Gustavo Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Feldman, Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaXXXVI Reunión Anual AAOMMCiudad Autónoma de Buenos AiresArgentinaAsociación Argentina de Osteología y Metabolismo Minera
A Comparison of General Medical and Clinical Ethics Consultations: What Can We Learn From Each Other?
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