42 research outputs found

    External validation of multidimensional prognostic indices (ADO, BODEx and DOSE) in a primary care international cohort (PROEPOC/COPD cohort)

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    Background: Due to the heterogeneous and systemic nature of the chronic obstructive pulmonary disease (COPD), the new guidelines are oriented toward individualized attention. Multidimensional scales could facilitate its proper clinical and prognostic assessment, but not all of them were validated in an international primary care cohort, different from the original ones used for model development. Therefore, our main aim is to assess the prognostic capacity of the ADO, BODEx and DOSE indices in primary care for predicting mortality in COPD patients and to validate the models obtained in subgroups of patients, classified by revised Global Initiative for Chronic Obstructive Lung Disease (2011) and updated Spanish Guideline (2014). Besides, we want to confirm that the prognostic capacity of all indices increases if the number of exacerbations is substituted by the interval between them and to assess the impact on health of the patient''s lifestyle, social network and adherence to treatment. Methods: Design: External validation of scales, open and prospective cohort study in primary care. Setting: 36 health centres in 6 European high, medium and low income countries. Subjects: 477 patients diagnosed with COPD, captured in clinical visit by their General Practitioner/Nurse. Predictors: Detailed patient history, exacerbations, lung function test and questionnaires at baseline. Outcomes: Exacerbations, all-cause mortality and specific mortality, within 5 years of recruitment. Analysis: Multivariate logistic regression and Cox regression will be used. Possible non-linear effect of the indices will be studied by using Structured Additive Regression models with penalised splines. Subsequently, we will assess different aspects of the regression models: discrimination, calibration and diagnostic precision. Clinical variables modulated in primary care and the interval between exacerbations will be considered and incorporated into the analysis. Discussion: The Research Agenda for General Practice/Family Medicine highlights that the evidence on predictive values of prognostic indices in primary care is scarce. A prospective cohort like that of PROEPOC/COPD provides good opportunities for research into COPD and make communication easier between family practitioners, nursing staff, pneumologists and other professionals, supporting a multi-disciplinary approach to the treatment of these patients. Trial registration:ISRCTN52402811. Date: 15/01/2015. Prospectively registered

    Deep drilling reveals massive shifts in evolutionary dynamics after formation of ancient ecosystem

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    The scarcity of high-resolution empirical data directly tracking diversity over time limits our understanding of speciation and extinction dynamics and the drivers of rate changes. Here, we analyze a continuous species-level fossil record of endemic diatoms from ancient Lake Ohrid, along with environmental and climate indicator time series since lake formation 1.36 million years (Ma) ago. We show that speciation and extinction rates nearly simultaneously decreased in the environmentally dynamic phase after ecosystem formation and stabilized after deep-water conditions established in Lake Ohrid. As the lake deepens, we also see a switch in the macroevolutionary trade-off, resulting in a transition from a volatile assemblage of short-lived endemic species to a stable community of long-lived species. Our results emphasize the importance of the interplay between environmental/climate change, ecosystem stability, and environmental limits to diversity for diversification processes. The study also provides a new understanding of evolutionary dynamics in long-lived ecosystems

    ICDP workshop on the Lake Tanganyika Scientific Drilling Project: a late Miocene–present record of climate, rifting, and ecosystem evolution from the world's oldest tropical lake

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    The Neogene and Quaternary are characterized by enormous changes in global climate and environments, including global cooling and the establishment of northern high-latitude glaciers. These changes reshaped global ecosystems, including the emergence of tropical dry forests and savannahs that are found in Africa today, which in turn may have influenced the evolution of humans and their ancestors. However, despite decades of research we lack long, continuous, well-resolved records of tropical climate, ecosystem changes, and surface processes necessary to understand their interactions and influences on evolutionary processes. Lake Tanganyika, Africa, contains the most continuous, long continental climate record from the mid-Miocene (∼10 Ma) to the present anywhere in the tropics and has long been recognized as a top-priority site for scientific drilling. The lake is surrounded by the Miombo woodlands, part of the largest dry tropical biome on Earth. Lake Tanganyika also harbors incredibly diverse endemic biota and an entirely unexplored deep microbial biosphere, and it provides textbook examples of rift segmentation, fault behavior, and associated surface processes. To evaluate the interdisciplinary scientific opportunities that an ICDP drilling program at Lake Tanganyika could offer, more than 70 scientists representing 12 countries and a variety of scientific disciplines met in Dar es Salaam, Tanzania, in June 2019. The team developed key research objectives in basin evolution, source-to-sink sedimentology, organismal evolution, geomicrobiology, paleoclimatology, paleolimnology, terrestrial paleoecology, paleoanthropology, and geochronology to be addressed through scientific drilling on Lake Tanganyika. They also identified drilling targets and strategies, logistical challenges, and education and capacity building programs to be carried out through the project. Participants concluded that a drilling program at Lake Tanganyika would produce the first continuous Miocene–present record from the tropics, transforming our understanding of global environmental change, the environmental context of human origins in Africa, and providing a detailed window into the dynamics, tempo and mode of biological diversification and adaptive radiations.© Author(s) 2020. This open access article is distributed under the Creative Commons Attribution 4.0 License

    Mediterranean winter rainfall in phase with African monsoons during the past 1.36 million years

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    Mediterranean climates are characterized by strong seasonal contrasts between dry summers and wet winters. Changes in winter rainfall are critical for regional socioeconomic development, but are difficult to simulate accurately1 and reconstruct on Quaternary timescales. This is partly because regional hydroclimate records that cover multiple glacial–interglacial cycles2,3 with different orbital geometries, global ice volume and atmospheric greenhouse gas concentrations are scarce. Moreover, the underlying mechanisms of change and their persistence remain unexplored. Here we show that, over the past 1.36 million years, wet winters in the northcentral Mediterranean tend to occur with high contrasts in local, seasonal insolation and a vigorous African summer monsoon. Our proxy time series from Lake Ohrid on the Balkan Peninsula, together with a 784,000-year transient climate model hindcast, suggest that increased sea surface temperatures amplify local cyclone development and refuel North Atlantic low-pressure systems that enter the Mediterranean during phases of low continental ice volume and high concentrations of atmospheric greenhouse gases. A comparison with modern reanalysis data shows that current drivers of the amount of rainfall in the Mediterranean share some similarities to those that drive the reconstructed increases in precipitation. Our data cover multiple insolation maxima and are therefore an important benchmark for testing climate model performance

    The geodynamic and limnological evolution of Balkan Lake Ohrid, possibly the oldest extant lake in Europe

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    Studies of the upper 447 m of the DEEP site sediment succession from central Lake Ohrid, Balkan Peninsula, North Macedonia and Albania provided important insights into the regional climate history and evolutionary dynamics since permanent lacustrine conditions established at 1.36 million years ago (Ma). This paper focuses on the entire 584-m-long DEEP sediment succession and a comparison to a 197-m-long sediment succession from the Pestani site ~5 km to the east in the lake, where drilling ended close to the bedrock, to unravel the earliest history of Lake Ohrid and its basin development. 26Al/10Be dating of clasts from the base of the DEEP sediment succession implies that the sedimentation in the modern basin started at c. 2 Ma. Geophysical, sedimentological and micropalaeontological data allow for chronological information to be transposed from the DEEP to the Pestani succession. Fluvial conditions, slack water conditions, peat formation and/or complete desiccation prevailed at the DEEP and Pestani sites until 1.36 and 1.21 Ma, respectively, before a larger lake extended over both sites. Activation of karst aquifers to the east probably by tectonic activity and a potential existence of neighbouring Lake Prespa supported filling of Lake Ohrid. The lake deepened gradually, with a relatively constant vertical displacement rate of ~0.2 mm a−1 between the central and the eastern lateral basin and with greater water depth presumably during interglacial periods. Although the dynamic environment characterized by local processes and the fragmentary chronology of the basal sediment successions from both sites hamper palaeoclimatic significance prior to the existence of a larger lake, the new data provide an unprecedented and detailed picture of the geodynamic evolution of the basin and lake that is Europe’s presumed oldest extant freshwater lake

    Regulation of the Proton-Activated ASIC1 Channels by Extracellular Organic Cations

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    Proton-activated channels (ASICs) are widely expressed in the central and peripheral nervous systems of mammals. ASIC1 and ASIC3 channels are potential targets for analgesia mainly due to their high expression in rat dorsal root ganglia neurons. In addition, ASIC1 is a potential target for stroke as it is highly expressed in the brain. Both channels belong to the epithelial amiloride-sensitive Na+ channel (ENaC/Degenerin) family of non-voltage gated Na+ channels. ASIC1 and ASIC3 currents can be evoked when extracellular pH drops to values observed during inflammatory response, stroke and ischemia. In HEK cell lines overexpressing human ASIC1 or ASIC3 channels, the current activated by sustained acidic pH rapidly (\u3c2 \u3es) inactivates due to channel desensitization. During prolonged (\u3e10 min) patch-clamp recording, accompanied with cell dialysis, current through ASIC1 (but not ASIC3) channels gradually decreases. This decrease or “rundown” of current is more pronounced at lower pH values. Here we demonstrate that extracellular polyamine spermine at micromolar concentrations has two effects on ASIC1 current: it drastically slows rundown and reduces its desensitization rate. Other polyamines, such as putrescine and spermidine do not mimic spermine’s effects. We propose a model where polyamine effects on ASIC1 current are explained by interaction with two different proton-binding sites. As spermine is a naturally occurring polyamine present both inside and outside of neurons, its effects on proton-gated channels may be physiologically relevant

    Regulation of the Proton-Activated ASIC1 Channels by Extracellular Organic Cations

    No full text
    Proton-activated channels (ASICs) are widely expressed in the central and peripheral nervous systems of mammals. ASIC1 and ASIC3 channels are potential targets for analgesia mainly due to their high expression in rat dorsal root ganglia neurons. In addition, ASIC1 is a potential target for stroke as it is highly expressed in the brain. Both channels belong to the epithelial amiloride-sensitive Na+ channel (ENaC/Degenerin) family of non-voltage gated Na+ channels. ASIC1 and ASIC3 currents can be evoked when extracellular pH drops to values observed during inflammatory response, stroke and ischemia. In HEK cell lines overexpressing human ASIC1 or ASIC3 channels, the current activated by sustained acidic pH rapidly (\u3c2 \u3es) inactivates due to channel desensitization. During prolonged (\u3e10 min) patch-clamp recording, accompanied with cell dialysis, current through ASIC1 (but not ASIC3) channels gradually decreases. This decrease or “rundown” of current is more pronounced at lower pH values. Here we demonstrate that extracellular polyamine spermine at micromolar concentrations has two effects on ASIC1 current: it drastically slows rundown and reduces its desensitization rate. Other polyamines, such as putrescine and spermidine do not mimic spermine’s effects. We propose a model where polyamine effects on ASIC1 current are explained by interaction with two different proton-binding sites. As spermine is a naturally occurring polyamine present both inside and outside of neurons, its effects on proton-gated channels may be physiologically relevant

    Regulation of the Proton-Activated ASIC1 Channels by Extracellular Organic Cations

    No full text
    Proton-activated channels (ASICs) are widely expressed in the central and peripheral nervous systems of mammals. ASIC1 and ASIC3 channels are potential targets for analgesia mainly due to their high expression in rat dorsal root ganglia neurons. In addition, ASIC1 is a potential target for stroke as it is highly expressed in the brain. Both channels belong to the epithelial amiloride-sensitive Na+ channel (ENaC/Degenerin) family of non-voltage gated Na+ channels. ASIC1 and ASIC3 currents can be evoked when extracellular pH drops to values observed during inflammatory response, stroke and ischemia. In HEK cell lines overexpressing human ASIC1 or ASIC3 channels, the current activated by sustained acidic pH rapidly (\u3c2 \u3es) inactivates due to channel desensitization. During prolonged (\u3e10 min) patch-clamp recording, accompanied with cell dialysis, current through ASIC1 (but not ASIC3) channels gradually decreases. This decrease or “rundown” of current is more pronounced at lower pH values. Here we demonstrate that extracellular polyamine spermine at micromolar concentrations has two effects on ASIC1 current: it drastically slows rundown and reduces its desensitization rate. Other polyamines, such as putrescine and spermidine do not mimic spermine’s effects. We propose a model where polyamine effects on ASIC1 current are explained by interaction with two different proton-binding sites. As spermine is a naturally occurring polyamine present both inside and outside of neurons, its effects on proton-gated channels may be physiologically relevant

    Betreuung von Online-Studierenden in der Hochschulweiterbildung - Annäherung an ein weites Themenfeld

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    Neben Forschung und Lehre erweitern mittlerweile auch Weiterbildungsangebote das Leistungsspektrum deutscher Universitäten und Fachhochschulen. Mit dem Bund-Länder-Wettbewerb „Aufstieg durch Bildung: offene Hochschulen“ wird seit dem Jahr 2011 das Lebenslange Lernen an Hochschulen durch den Aufbau neuer berufsbegleitender Studienangebote gefördert. Ziel dieser Qualifizierungsinitiative ist es, neuen Zielgruppen einen Zugang zu einer Hoch- und Fachhochschule zu ermöglichen (Hanft et al. 2016). Im Rahmen dieser Initiative sollten hauptsächlich für heterogene Zielgruppen neue Studiengangsformate (z.B. Online-Studiengänge) etabliert werden. Eine besondere Rolle nehmen dabei die berufstätigen Studierenden ein, die als hervorgehobener Ziel-adressat in dem Bund-Länder-Wettbewerb identifiziert worden sind (Hanft et al. 2013). Insbesondere für diese Zielgruppe wurden neue Weiterbildungsangebote konzipiert und erprobt, die meist ein Blended-Learning-Format oder sogar 100 Prozent online für ihre Form der Wissensvermittlung und Lehr-Lern-Interaktion nutzen
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