4,876 research outputs found

    QLI: QUALITY OF LIFE, UTILITY, AND WILLINGNESS TO PAY IN PATIENTS WITH DIABETES

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    Cloud feedback mechanisms and their representation in global climate models

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    Cloud feedback – the change in top-of-atmosphere radiative flux resulting from the cloud response to warming – constitutes by far the largest source of uncertainty in the climate response to CO2 forcing simulated by global climate models (GCMs). We review the main mechanisms for cloud feedbacks, and discuss their representation in climate models and the sources of inter-model spread. Global-mean cloud feedback in GCMs results from three main effects: (1) rising free- tropospheric clouds (a positive longwave effect); (2) decreasing tropical low cloud amount (a positive shortwave effect); (3) increasing high-latitude low cloud optical depth (a negative shortwave effect). These cloud responses simulated by GCMs are qualitatively supported by theory, high-resolution modeling, and observations. Rising high clouds are consistent with the Fixed Anvil Temperature (FAT) hypothesis, whereby enhanced upper-tropospheric radiative cooling causes anvil cloud tops to remain at a nearly fixed temperature as the atmosphere warms. Tropical low cloud amount decreases are driven by a delicate balance between the effects of vertical turbulent fluxes, radiative cooling, large-scale subsidence, and lower-tropospheric stability on the boundary-layer moisture budget. High-latitude low cloud optical depth increases are dominated by phase changes in mixed- phase clouds. The causes of inter-model spread in cloud feedback are discussed, focusing particularly on the role of unresolved parameterized processes such as cloud microphysics, turbulence, and convection

    Cell sorting in a Petri dish controlled by computer vision.

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    Fluorescence-activated cell sorting (FACS) applying flow cytometry to separate cells on a molecular basis is a widespread method. We demonstrate that both fluorescent and unlabeled live cells in a Petri dish observed with a microscope can be automatically recognized by computer vision and picked up by a computer-controlled micropipette. This method can be routinely applied as a FACS down to the single cell level with a very high selectivity. Sorting resolution, i.e., the minimum distance between two cells from which one could be selectively removed was 50-70 micrometers. Survival rate with a low number of 3T3 mouse fibroblasts and NE-4C neuroectodermal mouse stem cells was 66 +/- 12% and 88 +/- 16%, respectively. Purity of sorted cultures and rate of survival using NE-4C/NE-GFP-4C co-cultures were 95 +/- 2% and 62 +/- 7%, respectively. Hydrodynamic simulations confirmed the experimental sorting efficiency and a cell damage risk similar to that of normal FACS

    Heterogeneity in multistage carcinogenesis and mixture modeling

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    Carcinogenesis is commonly described as a multistage process, in which stem cells are transformed into cancer cells via a series of mutations. In this article, we consider extensions of the multistage carcinogenesis model by mixture modeling. This approach allows us to describe population heterogeneity in a biologically meaningful way. We focus on finite mixture models, for which we prove identifiability. These models are applied to human lung cancer data from several birth cohorts. Maximum likelihood estimation does not perform well in this application due to the heavy censoring in our data. We thus use analytic graduation instead. Very good fits are achieved for models that combine a small high risk group with a large group that is quasi immune

    Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: Different boosting intervals and implications for efficacy trials

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    Objectives. To investigate the safety and immunogenicity of boosting BCG with modified vaccinia Ankara expressing antigen 85A (MVA85A), shortly after BCG vaccination, and to compare this first with the immunogenicity of BCG vaccination alone and second with a previous clinical trial where MVA85A was administered more than 10 years after BCG vaccination. Design. There are two clinical trials reported here: a Phase I observational trial with MVA85A; and a Phase IV observational trial with BCG. These clinical trials were all conducted in the UK in healthy, HIV negative, BCG naı¨ve adults. Subjects were vaccinated with BCG alone; or BCG and then subsequently boosted with MVA85A four weeks later (short interval). The outcome measures, safety and immunogenicity, were monitored for six months. The immunogenicity results from this short interval BCG prime–MVA85A boost trial were compared first with the BCG alone trial and second with a previous clinical trial where MVA85A vaccination was administered many years after vaccination with BCG. Results. MVA85A was safe and highly immunogenic when administered to subjects who had recently received BCG vaccination. When the short interval trial data presented here were compared with the previous long interval trial data, there were no significant differences in the magnitude of immune responses generated when MVA85A was administered shortly after, or many years after BCG vaccination. Conclusions. The clinical trial data presented here provides further evidence of the ability of MVA85A to boost BCG primed immune responses. This boosting potential is not influenced by the time interval between prior BCG vaccination and boosting with MVA85A. These findings have important implications for the design of efficacy trials with MVA85A. Boosting BCG induced anti-mycobacterial immunity in either infancy or adolescence are both potential applications for this vaccine, given the immunological data presented here. Trial Registration. ClinicalTrials.Oxford University was the sponsor for all the clinical trials reported here

    The biosocial event : responding to innovation in the life sciences

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    Innovation in the life sciences calls for reflection on how sociologies separate and relate life processes and social processes. To this end we introduce the concept of the ‘biosocial event’. Some life processes and social processes have more mutual relevance than others. Some of these relationships are more negotiable than others. We show that levels of relevance and negotiability are not static but can change within existing relationships. Such changes, or biosocial events, lie at the heart of much unplanned biosocial novelty and much deliberate innovation. We illustrate and explore the concept through two examples – meningitis infection and epidemic, and the use of sonic ‘teen deterrents’ in urban settings. We then consider its value in developing sociological practice oriented to critically constructive engagement with innovation in the life sciences

    Determinants of Natural Mating Success in the Cannibalistic Orb-Web Spider Argiope bruennichi

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    Monogynous mating systems (low male mating rates) occur in various taxa and have evolved several times independently in spiders. Monogyny is associated with remarkable male mating strategies and predicted to evolve under a male-biased sex ratio. While male reproductive strategies are well documented and male mating rates are easy to quantify, especially in sexually cannibalistic species, female reproductive strategies, the optimal female mating rate, and the factors that affect the evolution of female mating rates are still unclear. In this study, we examined natural female mating rates and tested the assumption of a male-biased sex ratio and female polyandry in a natural population of Argiope bruennichi in which we controlled female mating status prior to observations. We predicted variation in female mating frequencies as a result of spatial and temporal heterogeneity in the distribution of mature females and males. Females had a low average mating rate of 1.3 and the majority copulated only once. Polyandry did not entirely result from a male-biased sex-ratio but closely matched the rate of male bigamy. Male activity and the probability of polyandry correlated with factors affecting pheromone presence such as virgin females' density. We conclude that a strong sex ratio bias and high female mating rates are not necessary components of monogynous mating systems as long as males protect their paternity effectively and certain frequencies of bigyny stabilise the mating system

    G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

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    Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

    Electric-field control of spin waves at room temperature in multiferroic BiFeO3

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    To face the challenges lying beyond current CMOS-based technology, new paradigms for information processing are required. Magnonics proposes to use spin waves to carry and process information, in analogy with photonics that relies on light waves, with several advantageous features such as potential operation in the THz range and excellent coupling to spintronics. Several magnonic analog and digital logic devices have been proposed, and some demonstrated. Just as for spintronics, a key issue for magnonics is the large power required to control/write information (conventionally achieved through magnetic fields applied by strip lines, or by spin transfer from large spin-polarized currents). Here we show that in BiFeO3, a room-temperature magnetoelectric material, the spin wave frequency (>600 GHz) can be tuned electrically by over 30%, in a non-volatile way and with virtually no power dissipation. Theoretical calculations indicate that this effect originates from a linear magnetoelectric effect related to spin-orbit coupling induced by the applied electric field. We argue that these properties make BiFeO3 a promising medium for spin wave generation, conversion and control in future magnonics architectures.Comment: 3 figure

    On the non-abelian Brumer-Stark conjecture and the equivariant Iwasawa main conjecture

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    We show that for an odd prime p, the p-primary parts of refinements of the (imprimitive) non-abelian Brumer and Brumer-Stark conjectures are implied by the equivariant Iwasawa main conjecture (EIMC) for totally real fields. Crucially, this result does not depend on the vanishing of the relevant Iwasawa mu-invariant. In combination with the authors' previous work on the EIMC, this leads to unconditional proofs of the non-abelian Brumer and Brumer-Stark conjectures in many new cases.Comment: 33 pages; to appear in Mathematische Zeitschrift; v3 many minor updates including new title; v2 some cohomological arguments simplified; v1 is a revised version of the second half of arXiv:1408.4934v
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