Opioid prescribing for acute postoperative pain : an overview of systematic reviews related to two consensus statements relevant at patient, prescriber, system and public health levels

Peer reviewedPublisher PD

A Fast Parallel Poisson Solver on Irregular Domains Applied to Beam Dynamic Simulations

We discuss the scalable parallel solution of the Poisson equation within a Particle-In-Cell (PIC) code for the simulation of electron beams in particle accelerators of irregular shape. The problem is discretized by Finite Differences. Depending on the treatment of the Dirichlet boundary the resulting system of equations is symmetric or `mildly' nonsymmetric positive definite. In all cases, the system is solved by the preconditioned conjugate gradient algorithm with smoothed aggregation (SA) based algebraic multigrid (AMG) preconditioning. We investigate variants of the implementation of SA-AMG that lead to considerable improvements in the execution times. We demonstrate good scalability of the solver on distributed memory parallel processor with up to 2048 processors. We also compare our SAAMG-PCG solver with an FFT-based solver that is more commonly used for applications in beam dynamics

Spatial Distribution of Petroleum Hydrocarbons in Sediment Cores from Blind Pass, St. Pete Beach, Florida

One hundred and one sediment cores were collected to characterize the spatial distribution of petroleum hydrocarbons within and just outside Blind Pass, St. Pete Beach, Florida. Twenty-five percent of the cores exhibited levels of petroleum hydrocarbons above detection limits of the gas chromatograph/flame ionization detector (GC/FID) (0.01 mg/Kg), but at generally low concentrations. Petroleum hydrocarbon speciation studies of these samples (gas chromatography/mass spectroscopy [GC/MS]) indicate above-detection level (1 μg/Kg) petroleum hydrocarbons are similar to the non-volatile petroleum hydrocarbons found in a Bouchard 155 reference sample collected after the 1993 oil spill in the area, but are in a much degraded and weathered state. Individual petroleum hydrocarbons were, in all but one case, below the threshold effective level (TEL) described in the literature (MacDonald, 1994). The petroleum hydrocarbons were primarily found at 100-300 cm depth in Blind Pass cores. Above-detection level petroleum hydrocarbons were generally found in samples from cores in the center of the channel, near the edges of the shoal, and just outside of Blind Pass. A second mixture of hydrocarbons, primarily phthalates, ketones, and ether, was found at relatively shallow core depths (0-99 cm) in the Mid- and North End Channel cores. These suggest a separate source of contamination, possibly storm water runoff. The fuel fluorescence detector (FFD) probe was investigated for its ability to detect petroleum hydrocarbons in marine sediments. When analyzed with the FFD, all sediments from the cores produced peaks of fluorescence, but none above the background levels of Blind Pass native sediments. All but two samples analyzed by GC/FID were below the detection limits (100 ppm) of the FFD. These samples were found in dark-colored sediments. The combination of the detection limits of the instrument, sediment color, and the degraded nature of the heavier weight petroleum hydrocarbons may have resulted in fluorescence outputs below background levels. These studies demonstrate that the distribution of petroleum hydrocarbons within Blind Pass sediments is generally low and patchy. However, 25% of the cores exhibited levels above detection using GC/FID/MS. These cores could be subjected to individual speciation studies which indicate generally below TEL levels and an association of some, but not all, with the 1993 oil spill in Blind Pass. Appendix A provides photographs and tables for sediment subsamples which exhibited total petroleum hydrocarbon concentrations above detection limits, while Appendix B presents the results from fuel fluorescence detector probe analyses. A discussion of the results of the study in relation to sediment quality guidelines and soil cleanup target level guidance documents is included as Appendix C. Some preliminary results using the above techniques on core samples from the nearby John’s Pass are presented in Appendix D

A generative approach for image-based modeling of tumor growth

22nd International Conference, IPMI 2011, Kloster Irsee, Germany, July 3-8, 2011. ProceedingsExtensive imaging is routinely used in brain tumor patients to monitor the state of the disease and to evaluate therapeutic options. A large number of multi-modal and multi-temporal image volumes is acquired in standard clinical cases, requiring new approaches for comprehensive integration of information from different image sources and different time points. In this work we propose a joint generative model of tumor growth and of image observation that naturally handles multi-modal and longitudinal data. We use the model for analyzing imaging data in patients with glioma. The tumor growth model is based on a reaction-diffusion framework. Model personalization relies only on a forward model for the growth process and on image likelihood. We take advantage of an adaptive sparse grid approximation for efficient inference via Markov Chain Monte Carlo sampling. The approach can be used for integrating information from different multi-modal imaging protocols and can easily be adapted to other tumor growth models.German Academy of Sciences Leopoldina (Fellowship Programme LPDS 2009-10)Academy of Finland (133611)National Institutes of Health (U.S.) (NIBIB NAMIC U54-EB005149)National Institutes of Health (U.S.) (NCRR NAC P41- RR13218)National Institutes of Health (U.S.) (NINDS R01-NS051826)National Institutes of Health (U.S.) (NIH R01-NS052585)National Institutes of Health (U.S.) (NIH R01-EB006758)National Institutes of Health (U.S.) (NIH R01-EB009051)National Institutes of Health (U.S.) (NIH P41-RR014075)National Science Foundation (U.S.) (CAREER Award 0642971

Altered microRNA expression in frontotemporal lobar degeneration with TDP-43 pathology caused by progranulin mutations

<p>Abstract</p> <p>Background</p> <p>Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disorder that can be triggered through genetic or sporadic mechanisms. MicroRNAs (miRNAs) have become a major therapeutic focus as their pervasive expression and powerful regulatory roles in disease pathogenesis become increasingly apparent. Here we examine the role of miRNAs in FTLD patients with TAR DNA-binding protein 43 pathology (FTLD-TDP) caused by genetic mutations in the progranulin (<it>PGRN</it>) gene.</p> <p>Results</p> <p>Using miRNA array profiling, we identified the 20 miRNAs that showed greatest evidence (unadjusted P < 0.05) of dysregulation in frontal cortex of eight FTLD-TDP patients carrying <it>PGRN </it>mutations when compared to 32 FTLD-TDP patients with no apparent genetic abnormalities. Quantitative real-time PCR (qRT-PCR) analyses provided technical validation of the differential expression for 9 of the 20 miRNAs in frontal cortex. Additional qRT-PCR analyses showed that 5 out of 9 miRNAs (miR-922, miR-516a-3p, miR-571, miR-548b-5p, and miR-548c-5p) were also significantly dysregulated (unadjusted P < 0.05) in cerebellar tissue samples of <it>PGRN </it>mutation carriers, consistent with a systemic reduction in PGRN levels. We developed a list of gene targets for the 5 candidate miRNAs and found 18 genes dysregulated in a reported FTLD mRNA study to exhibit anti-correlated miRNA-mRNA patterns in affected cortex and cerebellar tissue. Among the targets is brain-specific angiogenesis inhibitor 3, which was recently identified as an important player in synapse biology.</p> <p>Conclusions</p> <p>Our study suggests that miRNAs may contribute to the pathogenesis of FTLD-TDP caused by <it>PGRN </it>mutations and provides new insight into potential future therapeutic options.</p

Genomic, Proteomic and Physiological Characterization of a T5-like Bacteriophage for Control of Shiga Toxin-Producing Escherichia coli O157:H7

Despite multiple control measures, Escherichia coli O157:H7 (STEC O157:H7) continues to be responsible for many food borne outbreaks in North America and elsewhere. Bacteriophage therapy may prove useful for controlling this pathogen in the host, their environment and food. Bacteriophage vB_EcoS_AKFV33 (AKFV33), a T5-like phage of Siphoviridae lysed common phage types of STEC O157:H7 and not non-O157 E. coli. Moreover, STEC O157:H7 isolated from the same feedlot pen from which the phage was obtained, were highly susceptible to AKFV33. Adsorption rate constant and burst size were estimated to be 9.31×10−9 ml/min and 350 PFU/infected cell, respectively. The genome of AKVF33 was 108,853 bp (38.95% G+C), containing 160 open reading frames (ORFs), 22 tRNA genes and 32 strong promoters recognized by host RNA polymerase. Of 12 ORFs without homologues to T5-like phages, 7 predicted novel proteins while others exhibited low identity (<60%) to proteins in the National Centre for Biotechnology Information database. AKVF33 also lacked the L-shaped tail fiber protein typical of T5, but was predicted to have tail fibers comprised of 2 novel proteins with low identity (37–41%) to tail fibers of E. coli phage phiEco32 of Podoviridae, a putative side tail fiber protein of a prophage from E. coli IAI39 and a conserved domain protein of E. coli MS196-1. The receptor-binding tail protein (pb5) shared an overall identify of 29–72% to that of other T5-like phages, with no region coding for more than 6 amino acids in common. Proteomic analysis identified 4 structural proteins corresponding to the capsid, major tail, tail fiber and pore-forming tail tip (pb2). The genome of AKFV33 lacked regions coding for known virulence factors, integration-related proteins or antibiotic resistance determinants. Phage AKFV33 is a unique, highly lytic STEC O157:H7-specific T5-like phage that may have considerable potential as a pre- and post-harvest biocontrol agent

Transcriptional and Post-Transcriptional Regulation of SPAST, the Gene Most Frequently Mutated in Hereditary Spastic Paraplegia

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ∼70–80% of cases, with additional cases being recessive or X-linked. The most common type of HSP is SPG4 with mutations in the SPAST gene, encoding spastin, which occurs in 40% of dominantly inherited cases and in ∼10% of sporadic cases. Both loss-of-function and dominant-negative mutation mechanisms have been described for SPG4, suggesting that precise or stoichiometric levels of spastin are necessary for biological function. Therefore, we hypothesized that regulatory mechanisms controlling expression of SPAST are important determinants of spastin biology, and if altered, could contribute to the development and progression of the disease. To examine the transcriptional and post-transcriptional regulation of SPAST, we used molecular phylogenetic methods to identify conserved sequences for putative transcription factor binding sites and miRNA targeting motifs in the SPAST promoter and 3′-UTR, respectively. By a variety of molecular methods, we demonstrate that SPAST transcription is positively regulated by NRF1 and SOX11. Furthermore, we show that miR-96 and miR-182 negatively regulate SPAST by effects on mRNA stability and protein level. These transcriptional and miRNA regulatory mechanisms provide new functional targets for mutation screening and therapeutic targeting in HSP