Length 3 Complexes of Abelian Sheaves and Picard 2-Stacks

We define a tricategory T of length 3 complexes of abelian sheaves, whose hom-bigroupoids consist of weak morphisms of such complexes. We also define a 3-category 2PIC(S) of Picard 2-stacks, whose hom-2-groupoids consist of additive 2-functors. We prove that these categories are triequivalent as tricategories. As a consequence we obtain a generalization of Deligne's analogous result about Picard stacks in SGA4, Exp. XVIII.Comment: 46 pages, the proof of proposition 6.2 is added as appendi

Nerves and classifying spaces for bicategories

This paper explores the relationship amongst the various simplicial and pseudo-simplicial objects characteristically associated to any bicategory C. It proves the fact that the geometric realizations of all of these possible candidate `nerves of C' are homotopy equivalent. Any one of these realizations could therefore be taken as the classifying space BC of the bicategory. Its other major result proves a direct extension of Thomason's `Homotopy Colimit Theorem' to bicategories: When the homotopy colimit construction is carried out on a diagram of spaces obtained by applying the classifying space functor to a diagram of bicategories, the resulting space has the homotopy type of a certain bicategory, called the `Grothendieck construction on the diagram'. Our results provide coherence for all reasonable extensions to bicategories of Quillen's definition of the `classifying space' of a category as the geometric realization of the category's Grothendieck nerve, and they are applied to monoidal (tensor) categories through the elemental `delooping' construction.Comment: 42 page

Levosimendan for the prevention of acute organ dysfunction in sepsis

BACKGROUND Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. METHODS We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events. RESULTS The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04). CONCLUSIONS The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials number, ISRCTN12776039.

Development of a brain metastatic canine prostate cancer cell line

BACKGROUND Prostate cancer in men has a high mortality and morbidity due to metastatic disease. The pathobiology of prostate cancer metastasis is not well understood and cell lines and animal models that recapitulate the complex nature of the disease are needed. Therefore, the goal of the study was to establish and characterize a new prostate cancer line derived from a dog with spontaneous prostate cancer. METHODS A new cell line (Leo) was derived from a dog with spontaneous prostate cancer. Immunohistochemistry and PCR were used to characterize the primary prostate cancer and xenografts in nude mice. Subcutaneous tumor growth and metastases in nude mice were evaluated by bioluminescent imaging, radiography and histopathology. In vitro chemosensitivity of Leo cells to therapeutic agents was measured. RESULTS Leo cells expressed the secretory epithelial cytokeratins (CK)8, 18, and ductal cell marker, CK7. The cell line grew in vitro (over 75 passages) and was tumorigenic in the subcutis of nude mice. Following intracardiac injection, Leo cells metastasized to the brain, spinal cord, bone, and adrenal gland. The incidence of metastases was greatest to the central nervous system (80%) with a lower incidence to bone (20%) and the adrenal glands (16%). In vitro chemosensitivity assays demonstrated that Leo cells were sensitive to Velcade and an HDAC‐42 inhibitor with IC 50 concentrations of 1.9 nm and 0.95 µm, respectively. CONCLUSION The new prostate cancer cell line (Leo) will be a valuable model to investigate the mechanisms of the brain and bone metastases. Prostate 71:1251–1263, 2011. © 2011 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87007/1/21341_ftp.pd

Cognitive decline and quality of life in incident Parkinson's disease: The role of attention.

INTRODUCTION: Parkinson's disease dementia (PDD) is associated with poorer quality of life (QoL). Prior to the onset of PDD, many patients experience progressive cognitive impairment. There is a paucity of longitudinal studies investigating the effects of cognitive decline on QoL. This study aimed to determine the longitudinal impact of cognitive change on QoL in an incident PD cohort. METHODS: Recently diagnosed patients with PD (n = 212) completed a schedule of neuropsychological assessments and QoL measures; these were repeated after 18 (n = 190) and 36 months (n = 158). Mild cognitive impairment (PD-MCI) was classified with reference to the Movement Disorder Society criteria. Principal component analysis was used to reduce 10 neuropsychological tests to three cognitive factors: attention, memory/executive function, and global cognition. RESULTS: Baseline PD-MCI was a significant contributor to QoL (β = 0.2, p < 0.01). For those subjects (9%) who developed dementia, cognitive function had a much greater impact on QoL (β = 10.3, p < 0.05). Multivariate modelling showed attentional deficits had the strongest predictive power (β = -2.3, p < 0.01); brief global tests only modestly predicted decline in QoL (β = -0.4, p < 0.01). CONCLUSIONS: PD-MCI was associated with poorer QoL over three years follow up. Cognitive impairment had a greater impact on QoL in individuals who developed dementia over follow-up. Impaired attention was a significant determinant of QoL in PD. Interventions which improve concentration and attention in those with PD could potentially improve QoL

Differentiated Regulation:the case of charities

The increasing number and influence of charities in the economy, evidence of mismanagement and the need for information for policymaking are all reasons for establishing charity regulators. Public interest and public choice theories explain charity regulation which aims to increase public trust and confidence in charities (and thus increase voluntarism and philanthropy) and to limit tax benefits to specific organisations and donors. Nevertheless, regulation is resource intensive, and growing pressure on government budgets requires efficiencies to be found. This study proposes regulation differentiated according to charities' main resource providers, to reduce costs and focus regulatory effort, and provides a feasible segmentation

Attribute Controlled Reconstruction and Adaptive Mathematical Morphology

ISBN : 978-3-642-38293-2International audienceIn this paper we present a reconstruction method controlled by the evolution of attributes. The process begins from a marker, propagated over increasing quasi-flat zones. The evolution of several increasing and non-increasing attributes is studied in order to select the appropriate region. Additionally, the combination of attributes can be used in a straightforward way. To demonstrate the performance of our method, three applications are presented. Firstly, our method successfully segments connected objects in range images. Secondly, input-adaptive structuring elements (SE) are defined computing the controlled propagation for each pixel on a pilot image. Finally, input-adaptive SE are used to assess shape features on the image. Our approach is multi-scale and auto-dual. Compared with other methods, it is based on a given attribute but does not require a size parameter in order to determine appropriate regions. It is useful to extract objects of a given shape. Additionally, our reconstruction is a connected operator since quasi-flat zones do not create new contours on the image

ACCESS II: A Complete Census of Star Formation in the Shapley Supercluster - UV and IR Luminosity Functions

We present panoramic Spitzer/MIPS mid- and far-infrared and GALEX ultraviolet imaging of the the most massive and dynamically active system in the local Universe, the Shapley supercluster at z=0.048, covering the 5 clusters which make up the supercluster core. We combine these data with existing spectroscopic data from 814 confirmed supercluster members to produce the first study of a local rich cluster including both ultraviolet and infrared luminosity functions (LFs). This joint analysis allows us to produce a complete census of star-formation (both obscured and unobscured), extending down to SFRs~0.02-0.05Msun/yr, and quantify the level of obscuration of star formation among cluster galaxies, providing a local benchmark for comparison to ongoing and future studies of cluster galaxies at higher redshifts with Spitzer and Herschel. The GALEX NUV and FUV LFs obtained have steeper faint-end slopes than the local field population, due largely to the contribution of massive, quiescent galaxies at M_FUV>-16. The 24um and 70um galaxy LFs for the Shapley supercluster instead have shapes fully consistent with those obtained for the Coma cluster and for the local field galaxy population. This apparent lack of environmental dependence for the shape of the FIR luminosity function suggests that the bulk of the star-forming galaxies that make up the observed cluster infrared LF have been recently accreted from the field and have yet to have their star formation activity significantly affected by the cluster environment. We estimate a global SFR of 327 Msun/yr over the whole supercluster core, of which just ~20% is visible directly in the UV continuum and ~80% is reprocessed by dust and emitted in the infrared. The level of obscuration (L_IR/L_FUV) in star-forming galaxies is seen to increase linearly with L_K over two orders of magnitude in stellar mass.Comment: 19 pages, 17 figures. Accepted for publication in MNRA

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P &lt; 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P &lt; 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder