711 research outputs found

    parfm : Parametric Frailty Models in R

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    Frailty models are getting more and more popular to account for overdispersion and/or clustering in survival data. When the form of the baseline hazard is somehow known in advance, the parametric estimation approach can be used advantageously. Nonetheless, there is no unified widely available software that deals with the parametric frailty model. The new parfm package remedies that lack by providing a wide range of parametric frailty models in R. The gamma, inverse Gaussian, and positive stable frailty distributions can be specified, together with five different baseline hazards. Parameter estimation is done by maximising the marginal log-likelihood, with right-censored and possibly left-truncated data. In the multivariate setting, the inverse Gaussian may encounter numerical difficulties with a huge number of events in at least one cluster. The positive stable model shows analogous difficulties but an ad-hoc solution is implemented, whereas the gamma model is very resistant due to the simplicity of its Laplace transform

    Restructurations : Regard sur ses répercussions humaines et organisationnelles

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    International audienceThis study has been carried out in a multinational company and which is currently undergoing a restructuring. This analysis puts the emphasis on the human and organizational effects generated by this singular context. Drawing on three theoretical concepts, the aim of this study is to check if a degree of " stress perceived " as high associated with an " organizational support perceived " as weak questions the " affective commitment " of the employees leading to bad outcomes for the company in terms of productivity and efficiency. The results confirm our predictions. Indeed, a correlation between a stress perceived as " pathological " , an organizational support perceived as weak and a moderate affective commitment is to be found for the employees surveyed.Réalisée au sein d'une multinationale en restructuration, cette étude met l'accent sur les répercussions humaines et organisationnelles générées par ce contexte singulier. En conjuguant trois concepts théoriques, l'objectif de cette recherche est de vérifier si un " stress perçu " élevé associé à un faible " soutien organisationnel perçu " remet en question " l'implication organisationnelle affective " des salariés, engendrant fatalement des conséquences négatives en termes de productivité et d'efficacité de l'entreprise. Les résultats obtenus confirment nos prédictions, témoignant d'une corrélation entre un stress perçu dit " pathologique " , un faible soutien organisationnel perçu et une implication organisationnelle affective modérée des salariés sondés

    Campesinos y asalariados en la zona bananera de santa marta (1900 - 1935)

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    Los conflictos sociales marcaron las zonas de producción bananera desarrolladas bajo los auspicios de la United Fruit Company a partir de 1900. La mayoría de los estudios sobre las protestas contra la Compañía se ha centrado en las luchas de los asalariados para conseguir mejores condiciones de trabajo en las plantaciones bananeras. Sin embargo, estos estudios descuidan la existencia del campesinado en tales regiones y su participación en la formación  de las modalidades de protesta local que surgieron

    The 1999-2000 seismic experiment of Macas swarm (Ecuador) in relation with rift inversion in Subandean foothills

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    International audienceWe propose to explain the origin of the double trend in seismicity of the Macas swarm in the Subandean Cordillera of Cutucú (Ecuador) and characterize the corresponding active deformation of that region. For that purpose, seismological and geological data have been used, with the deployment of a temporary seismological array, with geological field observations and image processing. We found that some earthquakes are aligned on a well known NNE SSW trend corresponding to the orientation of the nodal planes of the reverse focal mechanism of the Mw=7.0 1995 Macas earthquake as for its aftershocks. Nevertheless, many smaller events are aligned on an unexpected NNW SSE trend inside the Cutucú Cordillera. We interpret these two orientations of the Macas swarm as linked to Subandean basement thrusts inherited from the inversion tectonics of a NNE SSW trending Triassic Jurassic rift, which has been uplifted and partly extruded in the Cutucú Cordillera. The present partitioning of this part of the Subandean deformation is controlled by pre-existing NNE SSW to NNW SSE Triassic Jurassic normal faults that have been subsequently compressed transpressed and reactivated into reverse faults. Major boundary faults of the rift were NNE SSW oriented and correspond now to some main Subandean thrusts as confirms the focal mechanism of the 1995 main shock located on the eastern border (Morona frontal thrust) and the orientation of its aftershocks. In the Cutucú Cordillera, the double orientation of present swarm can be interpreted as the result of accommodation of deformation along NNW SSE pre-existing faults inside the inverted rift system, linked to the motion of the Morona frontal NNE SSW thrust

    The PHD Finger of Human UHRF1 Reveals a New Subgroup of Unmethylated Histone H3 Tail Readers

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    The human UHRF1 protein (ubiquitin-like containing PHD and RING finger domains 1) has emerged as a potential cancer target due to its implication in cell cycle regulation, maintenance of DNA methylation after replication and heterochromatin formation. UHRF1 functions as an adaptor protein that binds to histones and recruits histone modifying enzymes, like HDAC1 or G9a, which exert their action on chromatin. In this work, we show the binding specificity of the PHD finger of human UHRF1 (huUHRF1-PHD) towards unmodified histone H3 N-terminal tail using native gel electrophoresis and isothermal titration calorimetry. We report the molecular basis of this interaction by determining the crystal structure of huUHRF1-PHD in complex with the histone H3 N-terminal tail. The structure reveals a new mode of histone recognition involving an extra conserved zinc finger preceding the conventional PHD finger region. This additional zinc finger forms part of a large surface cavity that accommodates the side chain of the histone H3 lysine K4 (H3K4) regardless of its methylation state. Mutation of Q330, which specifically interacts with H3K4, to alanine has no effect on the binding, suggesting a loose interaction between huUHRF1-PHD and H3K4. On the other hand, the recognition appears to rely on histone H3R2, which fits snugly into a groove on the protein and makes tight interactions with the conserved aspartates D334 and D337. Indeed, a mutation of the former aspartate disrupts the formation of the complex, while mutating the latter decreases the binding affinity nine-fold

    Response of Microbial Communities to Changing Climate Conditions During Summer Cyanobacterial Blooms in the Baltic Sea

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    Frequencies and biomass of Baltic Sea cyanobacterial blooms are expected to be higher in future climate conditions, but also of longer duration as a result of increased sea surface temperature. Concurrently, climate predictions indicate a reduced salinity in the Baltic Sea. These climate-driven changes are expected to alter not solely the phytoplankton community but also the role of microbial communities for nutrient remineralization. Here, we present the response of summer plankton communities (filamentous cyanobacteria, picocyanobacteria, and heterotrophic bacteria) to the interplay of increasing temperature (from 16 to 18°C and 20°C) and reduced salinity (from salinity 6.9 to 5.9) in the Baltic Proper (NW Gotland Sea) using a microcosm approach. Warmer temperatures led to an earlier peak of cyanobacterial biomass, while yields were reduced. These conditions caused a decrease of nitrogen-fixers (Dolichospermum sp.) biomass, while non nitrogen-fixers (Pseudanabaena sp.) increased. Salinity reduction did not affect cyanobacterial growth nor community composition. Among heterotrophic bacteria, Actinobacteria showed preference for high temperature, while Gammaproteobacteria thrived at in situ temperature. Heterotrophic bacteria community changed drastically at lower salinity and resembled communities at high temperature. Picocyanobacteria and heterotrophic bacterial biomass had a pronounced increase associated with the decay of filamentous cyanobacteria. This suggests that shifts in community composition of heterotrophic bacteria are influenced both directly by abiotic factors (temperature and salinity) and potentially indirectly by cyanobacteria. Our findings suggest that at warmer temperature, lower yield of photosynthetic cyanobacteria combined with lower proportion of nitrogen-fixers in the community could result in lower carbon export to the marine food web with consequences for the decomposer community of heterotrophic bacteria

    Cost-effectiveness analysis in melanoma detection: a transition model applied to dermoscopy

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    Abstract Aim: The main aim of this study is to demonstrate how our melanoma disease model (MDM) can be used for cost-effectiveness analyses (CEAs) in the melanoma detection field. In particular, we used the data of two cohorts of Belgian melanoma patients to investigate the cost-effectiveness of dermoscopy. Methods: A MDM, previously constructed to calculate the melanoma burden, was slightly modified to be suitable for CEAs. Two cohorts of patients entered into the model to calculate morbidity, mortality and costs. These cohorts were constituted by melanoma patients diagnosed by dermatologists adequately, or not adequately, trained in dermoscopy. Effectiveness and costs were calculated for each cohort and compared. Effectiveness was expressed in quality-adjusted life years (QALYs), a composite measure depending on melanoma-related morbidity and mortality. Costs included costs of treatment and follow-up as well as costs of detection in non-melanoma patients and costs of excision and pathology of benign lesions excised to rule out melanoma. Results: The result of our analysis concluded that melanoma diagnosis by dermatologists adequately trained in dermoscopy resulted in both a gain of QALYs (less morbidity and/or mortality) and a reduction in costs. Conclusion: This study demonstrates how our MDM can be used in CEAs in the melanoma detection field. The model and the methodology suggested in this paper were applied to two cohorts of Belgian melanoma patients. Their analysis concluded that adequate dermoscopy training is cost-effective. The results should be confirmed by a large-scale randomised study

    Seasonal dynamics in carbon cycling of marine bacterioplankton are lifestyle dependent

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    Although free-living (FL) and particle-attached (PA) bacteria are recognized as ecologically distinct compartments of marine microbial food-webs, few, if any, studies have determined their dynamics in abundance, function (production, respiration and substrate utilization) and taxonomy over a yearly cycle. In the Baltic Sea, abundance and production of PA bacteria (defined as the size-fraction >3.0 μm) peaked over 3 months in summer (6 months for FL bacteria), largely coinciding with blooms of Chitinophagales (Bacteroidetes). Pronounced changes in the growth efficiency (range 0.05–0.27) of FL bacteria (defined as the size-fraction <3.0 μm) indicated the magnitude of seasonal variability of ecological settings bacteria experience. Accordingly, 16S rRNA gene analyses of bacterial community composition uncovered distinct correlations between taxa, environmental variables and metabolisms, including Firmicutes associated with elevated hydrolytic enzyme activity in winter and Verrucomicrobia with utilization of algal-derived substrates during summer. Further, our results suggested a substrate-controlled succession in the PA fraction, from Bacteroidetes using polymers to Actinobacteria and Betaproteobacteria using monomers across the spring to autumn phytoplankton bloom transition. Collectively, our findings emphasize pronounced seasonal changes in both the composition of the bacterial community in the PA and FL size-fractions and their contribution to organic matter utilization and carbon cycling. This is important for interpreting microbial ecosystem function-responses to natural and human-induced environmental changes.Agencia Estatal de Investigación | Ref. PID2019-110011RB-C3
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