Suture-method versus Through-the-needle Catheters for Continuous Popliteal-sciatic Nerve Blocks: A Randomized Clinical Trial.

BACKGROUND:The basic perineural catheter design has changed minimally since inception, with the catheter introduced through or over a straight needle. The U.S. Food and Drug Administration recently cleared a novel perineural catheter design comprising a catheter attached to the back of a suture-shaped needle that is inserted, advanced along the arc of its curvature pulling the catheter past the target nerve, and then exited through the skin in a second location. The authors hypothesized that analgesia would be noninferior using the new versus traditional catheter design in the first two days after painful foot/ankle surgery with a primary outcome of average pain measured with the Numeric Rating Scale. METHODS:Subjects undergoing painful foot or ankle surgery with a continuous supraparaneural popliteal-sciatic nerve block 5 cm proximal to the bifurcation were randomized to either a suture-type or through-the-needle catheter and subsequent 3-day 0.2% ropivacaine infusion (basal 6 ml/h, bolus 4 ml, lockout 30 min). Subjects received daily follow-up for the first four days after surgery, including assessment for evidence of malfunction or dislodgement of the catheters. RESULTS:During the first two postoperative days the mean ± SD average pain scores were lower in subjects with the suture-catheter (n = 35) compared with the through-the-needle (n = 35) group (2.7 ± 2.4 vs. 3.4 ± 2.4) and found to be statistically noninferior (95% CI, -1.9 to 0.6; P < 0.001). No suture-style catheter was completely dislodged (0%), whereas the tips of three (9%) traditional catheters were found outside of the skin before purposeful removal on postoperative day 3 (P = 0.239). CONCLUSIONS:Suture-type perineural catheters provided noninferior analgesia compared with traditional catheters for continuous popliteal-sciatic blocks after painful foot and ankle surgery. The new catheter design appears to be a viable alternative to traditional designs used for the past seven decades

Pheromone-Dependent Destruction of the Tec1 Transcription Factor Is Required for MAP Kinase Signaling Specificity in Yeast

AbstractThe yeast MAPK pathways required for mating versus filamentous growth share multiple components yet specify distinct programs. The mating-specific MAPK, Fus3, prevents crosstalk between the two pathways by unknown mechanisms. Here we show that pheromone signaling induces Fus3-dependent degradation of Tec1, the transcription factor specific to the filamentation pathway. Degradation requires Fus3 kinase activity and a MAPK phosphorylation site in Tec1 at threonine 273. Fus3 associates with Tec1 in unstimulated cells, and active Fus3 phosphorylates Tec1 on T273 in vitro. Destruction of Tec1 requires the F box protein Dia2 (Digs-into-agar-2), and Cdc53, the Cullin of SCF (Skp1-Cdc53-F box) ubiquitin ligases. Notably, mutation of the phosphoacceptor site in Tec1, deletion of FUS3, or deletion of DIA2 results in a loss of signaling specificity such that pheromone pathway signaling erroneously activates filamentation pathway gene expression and invasive growth. Signal-induced destruction of a transcription factor for a competing pathway provides a mechanism for signaling specificity

Janus kinases to jakinibs : from basic insights to clinical practice

Cytokines are critical mediators of diverse immune and inflammatory diseases. Targeting cytokines and cytokine receptors with biologics has revolutionized the treatment of many of these diseases, but targeting intracellular signalling with Janus kinase (JAK) inhibitors (jakinibs) now represents a major new therapeutic advance. We are still in the first decade since these drugs were approved and there is still much to be learned about the mechanisms of action of these drugs and the practical use of these agents. Herein we will review cytokines that do, and just as importantly, do not signal by JAKs, as well as explain how this relates to both efficacy and side effects in various diseases. We will review new, next-generation selective jakinibs, as well as the prospects and challenges ahead in targeting JAKs.Peer reviewe

Porcine Reproductive and Respiratory Syndrome virus reduces feed efficiency, digestibility, and lean tissue accretion in grow-finish pigs

Porcine reproductive and respiratory syndrome (PRRS) virus is a major swine virus that causes reproductive impairment in sows, as well as respiratory disease, reduction in growth rates, and mortalities in all ages of pigs. The objective of this study was to quantify the impact PRRS has on grower-finisher pig feed efficiency and tissue accretion rates. Thirty PRRS naïve, littermate pairs of maternal line Choice Genetics gilts (33.6 ± 0.58 kg BW) were selected and pairs split across 2 barns consisting of 5 pens (n = 6 pigs/pen per barn). Pigs in both barns were fed corn-soybean-DDGS diets ad libitum. All pigs in one barn were inoculated (CHAL) via an i.m. injection of a live PRRS strain isolated from the region (0 d post inoculation, dpi), while pigs in the other barn were given a saline control injection (CONT). Pig performance (ADG, ADFI, G:F) was assessed from 35 kg BW until each group reached market BW (128 kg). Additionally, longitudinal apparent total tract digestibility (ATTD) and body composition was assessed using Dual-energy X-ray absorptiometry (DXA) post inoculation (dpi) to estimate lean, protein, fat and bone accretion rates. Serological data from CHAL pigs showed that PRRS titers peaked 7 dpi and these pigs seroconverted by 35 dpi. According to both genomic and protein PRRS titers, CONT pigs were naïve to CHAL throughout the study. The PRRS infection reduced (P \u3c 0.001) ATTD of dry matter, energy and nitrogen by 3 to 5% at 21 dpi and the reduction in ATTD persisted after 65 dpi. Compared to the CONT, CHAL pigs had decreased ADG (0.89 vs. 0.80 kg/d, P \u3c 0.001), ADFI (2.05 vs. 1.93 kg/d, P \u3c 0.001), and G:F (0.44 vs. 0.41 kg/d, P \u3c 0.001) over the entire test period. The CHAL pigs also had attenuated DXA predicted whole body accretion of lean (547 vs. 633 g/d, P = 0.001), protein (109 vs. 126 g/d, P = 0.001) and fat (169 vs. 205 g/d, P = 0.001) compared to their CONT counterparts from dpi 0 to 80. Based on carcass data at slaughter (and consistent with the DXA data), CHAL pigs had leaner carcasses and reduced yields. These data clearly demonstrate that PRRS infection reduces digestibility, feed efficiency and protein accretion rates in grower-finisher pigs

Longitudinal genetic analysis for loneliness in Dutch twins.

In previous studies we obtained evidence that variation in loneliness has a genetic component. Based on adult twin data, the heritability estimate for loneliness, which was assessed as an ordinal trait, was 48%. These analyses were done on loneliness scores averaged over items ('I feel lonely' and 'Nobody loves me') and over time points. In this article we present a longitudinal analysis of loneliness data assessed in 5 surveys (1991 through 2002) in Dutch twins (N = 8389) for the two separate items of the loneliness scale. From the longitudinal growth modeling it was found sufficient to have non-zero variance for the intercept only, while the other effects (linear, quadratic and cubic slope) had zero variance. For the item 'I feel lonely' we observed an increasing age trend up to age 30, followed by a decline to age 50. Heritability for individual differences in the intercept was estimated at 77%. For the item 'Nobody loves me' no significant trend over age was seen; the heritability of the intercept was estimated at 70%

An Integrated Approach for Characterizing Aerosol Climate Impacts and Environmental Interactions

Aerosols exert myriad influences on the earth's environment and climate, and on human health. The complexity of aerosol-related processes requires that information gathered to improve our understanding of climate change must originate from multiple sources, and that effective strategies for data integration need to be established. While a vast array of observed and modeled data are becoming available, the aerosol research community currently lacks the necessary tools and infrastructure to reap maximum scientific benefit from these data. Spatial and temporal sampling differences among a diverse set of sensors, nonuniform data qualities, aerosol mesoscale variabilities, and difficulties in separating cloud effects are some of the challenges that need to be addressed. Maximizing the long-term benefit from these data also requires maintaining consistently well-understood accuracies as measurement approaches evolve and improve. Achieving a comprehensive understanding of how aerosol physical, chemical, and radiative processes impact the earth system can be achieved only through a multidisciplinary, inter-agency, and international initiative capable of dealing with these issues. A systematic approach, capitalizing on modern measurement and modeling techniques, geospatial statistics methodologies, and high-performance information technologies, can provide the necessary machinery to support this objective. We outline a framework for integrating and interpreting observations and models, and establishing an accurate, consistent, and cohesive long-term record, following a strategy whereby information and tools of progressively greater sophistication are incorporated as problems of increasing complexity are tackled. This concept is named the Progressive Aerosol Retrieval and Assimilation Global Observing Network (PARAGON). To encompass the breadth of the effort required, we present a set of recommendations dealing with data interoperability; measurement and model integration; multisensor synergy; data summarization and mining; model evaluation; calibration and validation; augmentation of surface and in situ measurements; advances in passive and active remote sensing; and design of satellite missions. Without an initiative of this nature, the scientific and policy communities will continue to struggle with understanding the quantitative impact of complex aerosol processes on regional and global climate change and air quality

Cyclotron motion in graphene

We investigate cyclotron motion in graphene monolayers considering both the full quantum dynamics and its semiclassical limit reached at high carrier energies. Effects of zitterbewegung due to the two dispersion branches of the spectrum dominate the irregular quantum motion at low energies and are obtained as a systematic correction to the semiclassical case. Recent experiments are shown to operate in the semiclassical regime.Comment: 6 pages, 1 figure include

Using gene expression data to identify certain gastro-intestinal diseases

BACKGROUND: Inflammatory bowel diseases, ulcerative colitis and Crohn’s disease are considered to be of autoimmune origin, but the etiology of irritable bowel syndrome remains elusive. Furthermore, classifying patients into irritable bowel syndrome and inflammatory bowel diseases can be difficult without invasive testing and holds important treatment implications. Our aim was to assess the ability of gene expression profiling in blood to differentiate among these subject groups. METHODS: Transcript levels of a total of 45 genes in blood were determined by quantitative real-time polymerase chain reaction (RT-PCR). We applied three separate analytic approaches; one utilized a scoring system derived from combinations of ratios of expression levels of two genes and two different support vector machines. RESULTS: All methods discriminated different subject cohorts, irritable bowel syndrome from control, inflammatory bowel disease from control, irritable bowel syndrome from inflammatory bowel disease, and ulcerative colitis from Crohn’s disease, with high degrees of sensitivity and specificity. CONCLUSIONS: These results suggest these approaches may provide clinically useful prediction of the presence of these gastro-intestinal diseases and syndromes

Multivariate discrimination and the Higgs + W/Z search

A systematic method for optimizing multivariate discriminants is developed and applied to the important example of a light Higgs boson search at the Tevatron and the LHC. The Significance Improvement Characteristic (SIC), defined as the signal efficiency of a cut or multivariate discriminant divided by the square root of the background efficiency, is shown to be an extremely powerful visualization tool. SIC curves demonstrate numerical instabilities in the multivariate discriminants, show convergence as the number of variables is increased, and display the sensitivity to the optimal cut values. For our application, we concentrate on Higgs boson production in association with a W or Z boson with H -> bb and compare to the irreducible standard model background, Z/W + bb. We explore thousands of experimentally motivated, physically motivated, and unmotivated single variable discriminants. Along with the standard kinematic variables, a number of new ones, such as twist, are described which should have applicability to many processes. We find that some single variables, such as the pull angle, are weak discriminants, but when combined with others they provide important marginal improvement. We also find that multiple Higgs boson-candidate mass measures, such as from mild and aggressively trimmed jets, when combined may provide additional discriminating power. Comparing the significance improvement from our variables to those used in recent CDF and DZero searches, we find that a 10-20% improvement in significance against Z/W + bb is possible. Our analysis also suggests that the H + W/Z channel with H -> bb is also viable at the LHC, without requiring a hard cut on the W/Z transverse momentum.Comment: 41 pages, 5 tables, 29 figure