Altered brainstem responses to modafinil in schizophrenia: implications for adjunctive treatment of cognition.

Candidate pro-cognitive drugs for schizophrenia targeting several neurochemical systems have consistently failed to demonstrate robust efficacy. It remains untested whether concurrent antipsychotic medications exert pharmacodynamic interactions that mitigate pro-cognitive action in patients. We used functional MRI (fMRI) in a randomized, double-blind, placebo-controlled within-subject crossover test of single-dose modafinil effects in 27 medicated schizophrenia patients, interrogating brainstem regions where catecholamine systems arise to innervate the cortex, to link cellular and systems-level models of cognitive control. Modafinil effects were evaluated both within this patient group and compared to a healthy subject group. Modafinil modulated activity in the locus coeruleus (LC) and ventral tegmental area (VTA) in the patient group. However, compared to the healthy comparison group, these effects were altered as a function of task demands: the control-independent drug effect on deactivation was relatively attenuated (shallower) in the LC and exaggerated (deeper) in the VTA; in contrast, again compared to the comparison group, the control-related drug effects on positive activation were attenuated in LC, VTA and the cortical cognitive control network. These altered effects in the LC and VTA were significantly and specifically associated with the degree of antagonism of alpha-2 adrenergic and dopamine-2 receptors, respectively, by concurrently prescribed antipsychotics. These sources of evidence suggest interacting effects on catecholamine neurons of chronic antipsychotic treatment, which respectively increase and decrease sustained neuronal activity in LC and VTA. This is the first direct evidence in a clinical population to suggest that antipsychotic medications alter catecholamine neuronal activity to mitigate pro-cognitive drug action on cortical circuits

The Potential for a GPU-Like Overlay Architecture for FPGAs

We propose a soft processor programming model and architecture inspired by graphics processing units (GPUs) that are well-matched to the strengths of FPGAs, namely, highly parallel and pipelinable computation. In particular, our soft processor architecture exploits multithreading, vector operations, and predication to supply a floating-point pipeline of 64 stages via hardware support for up to 256 concurrent thread contexts. The key new contributions of our architecture are mechanisms for managing threads and register files that maximize data-level and instruction-level parallelism while overcoming the challenges of port limitations of FPGA block memories as well as memory and pipeline latency. Through simulation of a system that (i) is programmable via NVIDIA's high-level Cg language, (ii) supports AMD's CTM r5xx GPU ISA, and (iii) is realizable on an XtremeData XD1000 FPGA-based accelerator system, we demonstrate the potential for such a system to achieve 100% utilization of a deeply pipelined floating-point datapath

Rates of species introduction to a remote oceanic island

The introduction of species to areas beyond the limits of their natural distributions has a major homogenizing influence, making previously distinct biotas more similar. The scale of introductions has frequently been commented on, but their rate and spatial pervasiveness have been less well quantified. Here, we report the findings of a detailed study of pterygote insect introductions to Gough Island, one of the most remote and supposedly pristine temperate oceanic islands, and estimate the rate at which introduced species have successfully established. Out of 99 species recorded from Gough Island, 71 are established introductions, the highest proportion documented for any Southern Ocean island. Estimating a total of approximately 233 landings on Gough Island since first human landfall, this equates to one successful establishment for every three to four landings. Generalizations drawn from other areas suggest that this may be only one-tenth of the number of pterygote species that have arrived at the island, implying that most landings may lead to the arrival of at least one alien. These rates of introduction of new species are estimated to be two to three orders of magnitude greater than background levels for Gough Island, an increase comparable to that estimated for global species extinctions (many of which occur on islands) as a consequence of human activities

Wissensmanagement - quo vadis? Case Positions zur Umsetzung in den Unternehmen ; eine selektive Bestandsaufnahme

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Parenting in sport

This paper provides a brief summary and commentary on the growing literature on parenting in sport, with a particular emphasis on literature from the last 2–3 years. Following a brief introduction overviewing the topic area, we firstly focus on the influence of parental involvement on children. Specifically, we examine the range of factors that influence children's perceptions of parental involvement and the consequences of different behaviors. Next we discuss the factors influencing parental involvement, such as the challenges and stressors associated with parenting children in sport and the culture within different sports. Finally, our review focuses upon the strategies developed by parents to facilitate their involvement in their children's sport, as well as the few papers focused upon parent education and support. We conclude by examining the need for further research and examination of support strategies for parents

Results of the Anaconda endovascular graft in abdominal aortic aneurysm with a severe angulated infrarenal neck

Objective: Proximal neck anatomy of an abdominal aortic aneurysm (AAA), especially a severe angulated neck of more than 60 degrees, predicts adverse outcome in endovascular aneurysm repair. In the present study, we evaluate the feasibility of the use of the Anaconda endovascular graft (Vascutec, Terumo, Inchinnan, Scotland) for treating infrarenal AAA with a severe angulated neck (>60 degrees) and report the midterm outcomes. Methods: In total, nine Dutch hospitals participated in this prospective cohort study. From December 2005 to January 2011, a total of 36 AAA patients, 30 men and six women, were included. Mean and median follow-up were both 40 months. Results: Mean infrarenal neck angulation was 82 degrees. Successful deployment was reached in 34 of 36 patients. Primary technical success was achieved in 30 of 36 patients (83%). There was no aneurysm-related death. Four-year primary clinical success was 69%. In the first year, eight clinical failures were reported including four leg occlusions which could be solved using standard procedures. After the first year, three patients with additional failures occurred; two of them were leg occlusions. Four patients needed conversion to open AAA exclusion. In six of 36 patients, one or more reinterventions were necessary. Three of them were performed for occlusion of one Anaconda leg and two were for occlusion of the body. Conclusions: The use of the Anaconda endovascular graft in AAA with a severe angulated infrarenal neck is feasible but has its side effects. Most clinical failures occur in the first year. Thereafter, few problems occur, and midterm results are acceptable. Summarizing the present experiences, we conclude that open AAA repair is still a preferable option in patients with challenging aortic neck anatomy and fit for open surgery

Sketch-To-Solution: An Exploration of Viscous CFD with Automatic Grids

Numerical simulation of the Reynolds-averaged NavierStokes (RANS) equations has become a critical tool for the design of aerospace vehicles. However, the issues that affect the grid convergence of three dimensional RANS solutions are not completely understood, as documented in the AIAA Drag Prediction Workshop series. Grid adaption methods have the potential for increasing the automation and discretization error control of RANS solutions to impact the aerospace design and certification process. The realization of the CFD Vision 2030 Study includes automated management of errors and uncertainties of physics-based, predictive modeling that can set the stage for ensuring a vehicle is in compliance with a regulation or specification by using analysis without demonstration in flight test (i.e., certification or qualification by analysis). For example, the Cart3D inviscid analysis package has automated Cartesian cut-cell gridding with output-based error control. Fueled by recent advances in the fields of anisotropic grid adaptation, error estimation, and geometry modeling, a similar work flow is explored for viscous CFD simulations; where a CFD application engineer provides geometry, boundary conditions, and flow parameters, and the sketch-to-solution process yields a CFD simulation through automatic, error-based, grid adaptation

Targeting autophagy: a novel anticancer strategy with therapeutic implications for imatinib resistance

Autophagy is an ancient, intracellular degradative system which plays important roles in regulating protein homeostasis and which is essential for survival when cells are faced with metabolic stress. Increasing evidence suggests that autophagy also functions as a tumor suppressor mechanism that harnesses the growth and/or survival of cells as they transition towards a rapidly dividing malignant state. However, the impact of autophagy on cancer progression and on the efficacy of cancer therapeutics is controversial. In particular, although the induction of autophagy has been reported after treatment with a number of therapeutic agents, including imatinib, this response has variously been suggested to either impair or contribute to the effects of anticancer agents. More recent studies support the notion that autophagy compromises the efficacy of anticancer agents, where agents such as chloroquine (CQ) that impair autophagy augment the anticancer activity of histone deacetylase (HDAC) inhibitors and alkylating agents. Inhibition of autophagy is a particularly attractive strategy for the treatment of imatinib-refractory chronic myelogenous leukemia (CML) since a combination of CQ with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) compromises the survival of even BCR-ABL-T315I+ imatinib-resistant CML. Additional studies are clearly needed to establish the clinical utility of autophagy inhibitors and to identify patients most likely to benefit from this novel therapeutic approach