Decoy peptide targeted to Toll-IL-1R domain inhibits LPS and TLR4-active metabolite morphine-3 glucuronide sensitization of sensory neurons

Accumulating evidence indicates that Toll-like receptor (TLR) signaling adapter protein interactions with Toll/Interleukin-1 Receptor (TIR) domains present in sensory neurons may modulate neuropathic pain states. Following ligand interaction with TLRs, TIR serves to both initiate intracellular signaling and facilitate recruitment of signaling adapter proteins to the intracytoplasmic domain. Although TLR TIR is central to a number of TLR signaling cascades, its role in sensory neurons is poorly understood. In this study we investigated the degree to which TLR TIR decoy peptide modified to include a TAT sequence (Trans-Activator of Transcription gene in HIV; TAT-4BB) affected LPS-induced intracellular calcium flux and excitation in sensory neurons, and behavioral changes due to TLR4 active metabolite, morphine-3-glucuronide (M3G) exposure in vivo. TAT-4BB inhibited LPS-induced calcium changes in a majority of sensory neurons and decreased LPS-dependent neuronal excitability in small diameter neurons. Acute systemic administration of the TAT-4BB reversed M3G-induced tactile allodynia in a dose-dependent manner but did not affect motor activity, anxiety or responses to noxious thermal stimulus. These data suggest that targeting TLR TIR domains may provide novel pharmacological targets to reduce or reverse TLR4-dependent pain behavior in the rodent

Factors affecting patterns of tick parasitism on forest rodents in tick-borne encephalitis risk areas, Germany

Identifying factors affecting individual vector burdens is essential for understanding infectious disease systems. Drawing upon data of a rodent monitoring programme conducted in nine different forest patches in southern Hesse, Germany, we developed models which predict tick (Ixodes spp. and Dermacentor spp.) burdens on two rodent species Apodemus flavicollis and Myodes glareolus. Models for the two rodent species were broadly similar but differed in some aspects. Patterns of Ixodes spp. burdens were influenced by extrinsic factors such as season, unexplained spatial variation (both species), relative humidity and vegetation cover (A. flavicollis). We found support for the ‘body mass’ (tick burdens increase with body mass/age) and for the ‘dilution’ hypothesis (tick burdens decline with increasing rodent densities) and little support for the ‘sex-bias’ hypothesis (both species). Surprisingly, roe deer densities were not correlated with larvae counts on rodents. Factors influencing the mean burden did not significantly explain the observed dispersion of tick counts. Co-feeding aggregations, which are essential for tick-borne disease transmission, were mainly found in A. flavicollis of high body mass trapped in areas with fast increase in spring temperatures. Locally, Dermacentor spp. appears to be an important parasite on A. flavicollis and M. glareolus. Dermacentor spp. was rather confined to areas with higher average temperatures during the vegetation period. Nymphs of Dermacentor spp. mainly fed on M. glareolus and were seldom found on A. flavicollis. Whereas Ixodes spp. is the dominant tick genus in woodlands of our study area, the distribution and epidemiological role of Dermacentor spp. should be monitored closely

Astrometry with the Keck-Interferometer: the ASTRA project and its science

The sensitivity and astrometry upgrade ASTRA of the Keck Interferometer is introduced. After a brief overview of the underlying interferometric principles, the technology and concepts of the upgrade are presented. The interferometric dual-field technology of ASTRA will provide the KI with the means to observe two objects simultaneously, and measure the distance between them with a precision eventually better than 100 uas. This astrometric functionality of ASTRA will add a unique observing tool to fields of astrophysical research as diverse as exo-planetary kinematics, binary astrometry, and the investigation of stars accelerated by the massive black hole in the center of the Milky Way as discussed in this contribution.Comment: 22 pages, 10 figures (low resolution), contribution to the summerschool "Astrometry and Imaging with the Very Large Telescope Interferometer", 2 - 13 June, 2008, Keszthely, Hungary, corrected authorlis

A Methodological Review of the Articles Publishes in Georgia Educational Researcher from 2003-2010

Methodological reviews, reviews that concentrate on research methods rather than research outcomes, have been used in a variety of fields to improve research practice, inform debate, and identify islands of practice. In this article, we report on the results of a methodological review of all of the articles published in Georgia Educational Researcher from 2003-2010. We examined the methodological characteristics, authorial characteristics, and methodological quality of those articles using quantitative content analysis. The major findings were that (a) the proportions of the type and traditions of articles published in Georgia Educational Researcher were similar to the proportions in education research articles in general, (b) case study research and correlational research were most prominent, (c) a few universities accounted for most of the articles published, (d) male and female authors’ articles were published in equitable proportions, and (e) there were no statistically significant differences in methodological quality between genders, university affiliations, types of research, or years of publication. We end with a few suggestions for improving the quality of qualitative research articles in the Georgia Educational Researcher

Interpretation of CT studies: single-screen workstation versus film alternator

A prototype single-screen workstation with a 2,048 x 2,560-pixel high-brightness monitor, 0.11-second image display time, and simple ergonomic design was compared to a conventional horizontal film alternator in diagnostic interpretation of chest computed tomography (CT) studies. Four radiologists used either the workstation or film alternator in interpretation of studies obtained in 10 patients. A counterbalanced within-subject repeated measures experimental design was used. Response times were analyzed for both methods of interpretation. Grades of excellent, acceptable, and unacceptable were assigned by a blinded "grader" to reports of the radiologists. The average time needed for an interpretation at the workstation was 5.65 minutes. No interpretations were graded unacceptable. Retrospective power analysis showed that 16 observers rather than four would have been required to show that use of the workstation was faster than the alternator. With this 95% confidence interval, the workstation interpretation time is clinically equivalent to that with the alternator. These data show that this type of workstation has practical application in interpretation of CT, magnetic resonance imaging, and ultrasound studies

Baroclinic Transport Time Series of the Antarctic Circumpolar Current Measured in Drake Passage

The first multiyear continuous time series of Antarctic Circumpolar Current (ACC) baroclinic transport through Drake Passage measured by moored observations is presented. From 2007 to 2011, 19 current- and pressure-recording inverted echo sounders and 3 current-meter moorings were deployed in Drake Passage to monitor the transport during the cDrake experiment. Full-depth ACC baroclinic transport relative to the bottom has a mean strength of 127.7 ± 1.0 Sverdrups (Sv; 1 Sv ≡ 106 m3 s−1) with a standard deviation of 8.1 Sv. Mean annual baroclinic transport is remarkably steady. About 65% of the baroclinic transport variance is associated with time periods shorter than 60 days with peaks at 20 and 55 days. Nearly 28% of apparent energy in the spectrum computed from transport subsampled at the 10-day repeat cycle of the Jason altimeter results from aliasing of high-frequency signals. Approximately 80% of the total baroclinic transport is carried by the Subantarctic Front and the Polar Front. Partitioning the baroclinic transport among neutral density γn layers gives 39.2 Sv for Subantarctic Surface Water and Antarctic Intermediate Water (γn \u3c 27.5 kg m−3), 57.5 Sv for Upper Circumpolar Deep Water (27.5 \u3c γn \u3c 28.0 kg m−3), 27.7 Sv for Lower Circumpolar Deep Water (28.0 \u3c γn \u3c 28.2 kg m−3), and 3.3 Sv for Antarctic Bottom Water (γn \u3e 28.2 kg m−3). The transport standard deviation in these layers decreases with depth (4.0, 3.1, 2.1, and 1.1 Sv, respectively). The transport associated with each of these water masses is statistically steady. The ACC baroclinic transport exhibits considerable variability and is a major contributor to total ACC transport variability

TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) US clinical trial: Performance of a rapid deployment aortic valve

Background: The TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) trial (NCT01700439) evaluated the performance of the INTUITY rapid deployment aortic valve replacement (RDAVR) system in patients with severe aortic stenosis. Methods: TRANSFORM was a prospective, nonrandomized, multicenter (n 1�4 29), single-arm trial. INTUITY is comprised of a cloth-covered balloon- expandable frame attached to a Carpentier-Edwards PERIMOUNT Magna Ease aortic valve. Primary and effectiveness endpoints were evaluated at 1 year. Results: Between 2012 and 2015, 839 patients underwent RDAVR. Mean age was 73.5 8.3 years. Full sternotomy (FS) was used in 59% and minimally invasive surgical incisions in 41%. Technical success rate was 95%. For isolated RDAVR, mean crossclamp and cardiopulmonary bypass times for FS were 49.3 26.9 minutes and 69.2 34.7 minutes, respectively, and for minimally invasive surgical 63.1 25.4 minutes and 84.6 33.5 minutes, respectively. These times were favorable compared with Society of Thoracic Surgeons data- base comparators for FS: 76.3 minutes and 104.2 minutes, respectively, and for minimally invasive surgical, 82.9 minutes and 111.4 minutes, respectively (P<.001). At 30 days, all-cause mortality was 0.8%; valve explant, 0.1%; throm- boembolism, 3.5%; and major bleeding, 1.3%. In patients with isolated aortic valve replacement, the rate of permanent pacemaker implantation was 11.9%. At 1 year, mean effective orifice area was 1.7 cm2; mean gradient, 10.3 mm Hg; and moderate and severe paravalvular leak, 1.2% and 0.4%, respectively