Multicenter study of lumbar discectomy with Barricaid annular closure device for prevention of lumbar disc reherniation in US patients: A historically controlled post-market study protocol

BACKGROUND: Patients with large defects in the annulus fibrosus following lumbar discectomy have high rates of symptomatic reherniation. The Barricaid annular closure device provides durable occlusion of the annular defect and has been shown to significantly lower the risk of symptomatic reherniation in a large European randomized trial. However, the performance of the Barricaid device in a United States (US) population has not been previously reported. DESIGN AND METHODS: This is a historically controlled post-market multicenter study to determine the safety and efficacy of the Barricaid device when used in addition to primary lumbar discectomy in a US population. A total of 75 patients with large annular defects will receive the Barricaid device following lumbar discectomy at up to 25 sites in the US and will return for clinical and imaging follow-up at 4 weeks, 3 months, and 1 year. Trial oversight will be provided by a data safety monitoring board and imaging studies will be read by an independent imaging core laboratory. Patients treated with the Barricaid device in a previous European randomized trial with comparable eligibility criteria, surgical procedures, and outcome measures will serve as historical controls. Main outcomes will include back pain severity, leg pain severity, Oswestry Disability Index, health utility on the EuroQol-5 Dimension questionnaire, complications, symptomatic reherniation, and reoperation. Propensity score adjustment using inverse probability of treatment weighting will be used to adjust for differences in baseline patient characteristics between the US trial participants and European historical controls. ETHICS AND DISSEMINATION: This study was approved by a central institutional review board. The study results of this trial will be widely disseminated at conference proceedings and published in peer-reviewed journals. The outcomes of this study will have important clinical and economic implications for all stakeholders involved in treating patients with lumbar discectomy in the US. STUDY REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov): NCT03986580. LEVEL OF EVIDENCE: 3

An Initial Mass Function Study of the Dwarf Starburst Galaxy NGC 4214

The production rate of ionizing photons in young (≤8 Myr), unresolved stellar clusters in the nearby irregular galaxy NGC 4214 is probed using multi-wavelength Hubble Space Telescope WFC3 data. We normalize the ionizing photon rate by the cluster mass to investigate the upper end of the stellar initial mass function (IMF). We have found that within the uncertainties the upper end of the stellar IMF appears to be universal in this galaxy, and that deviations from a universal IMF can be attributed to stochastic sampling of stars in clusters with masses ≾ 10^3 M_☉. Furthermore, we have found that there does not seem to be a dependence of the maximum stellar mass on the cluster mass. We have also found that for massive clusters, feedback may cause an underrepresentation in Hα luminosities, which needs to be taken into account when conducting this type of analysis

Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node

The strongest mucosal immune responses are induced following mucosal Ag delivery and processing in the mucosal lymphoid tissues, and much is known regarding the immunological parameters which regulate immune induction via this pathway. Recently, experimental systems have been identified in which mucosal immune responses are induced following nonmucosal Ag delivery. One such system, footpad delivery of Venezuelan equine encephalitis virus replicon particles (VRP), led to the local production of IgA Abs directed against both expressed and codelivered Ags at multiple mucosal surfaces in mice. In contrast to the mucosal delivery pathway, little is known regarding the lymphoid structures and immunological components that are responsible for mucosal immune induction following nonmucosal delivery. In this study, we have used footpad delivery of VRP to probe the constituents of this alternative pathway for mucosal immune induction. Following nonmucosal VRP delivery, J chain-containing, polymeric IgA Abs were detected in the peripheral draining lymph node (DLN), at a time before IgA detection at mucosal surfaces. Further analysis of the VRP DLN revealed up-regulated α4β7 integrin expression on DLN B cells, expression of mucosal addressin cell adhesion molecule 1 on the DLN high endothelia venules, and production of IL-6 and CC chemokines, all characteristics of mucosal lymphoid tissues. Taken together, these results implicate the peripheral DLN as an integral component of an alternative pathway for mucosal immune induction. A further understanding of the critical immunological and viral components of this pathway may significantly improve both our knowledge of viral-induced immunity and the efficacy of viral-based vaccines

Facile synthesis and proposed mechanism of α,ω‐oxetanyl-telechelic poly(3-nitratomethyl-3-methyl oxetane) by an SN2(i) nitrato displacement method in basic media

The synthesis of a novel heterocyclic–telechelic polymer, α,ω-oxetanyl-telechelic poly(3-nitratomethyl-3-methyl oxetane), is described. Infrared spectroscopy (IR), gel permeation chromatography (GPC), and nuclear magnetic resonance (NMR) spectroscopy have been used to confirm the successful synthesis, demonstrating the presence of the telechelic-oxetanyl moieties. Synthesis of the terminal functionalities has been achieved via displacement of nitrato groups, in a manner similar to that employed with other leaving groups such as azido, bromo, and nitro, initiated by nucleophiles. In the present case, displacement occurs on the ends of a nitrato-functionalized polymer driven by the formation of sodium nitrate, which is supported by the polar aprotic solvent N,N-dimethyl formamide. The formation of an alkoxide at the polymer chain ends is favored and allows internal back-biting to the nearest carbon bearing the nitrato group, intrinsically in an SN2(i) reaction, leading to α,ω-oxetanyl functionalization. The telechelic-oxetanyl moieties have the potential to be cross-linked by chemical (e.g., acidic) or radiative (e.g., ultraviolet) curing methods without the use of high temperatures, usually below 100°C. This type of material was designed for future use as a contraband simulant, whereby it would form the predominant constituent of elastomeric composites comprising rubbery polymer with small quantities of solids, typically crystals of contraband substances, such as explosives or narcotics. This method also provides an alternative approach to ring closure and synthesis of heterocycles

Expression and purification of tau protein and its frontotemporal dementia variants using a cleavable histidine tag

Recombinant tau protein is widely used to study the biochemical, cellular and pathological aspects of tauopathies, including Alzheimer's disease and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTPD-17). Pure tau in high yield is a requirement for in vitro evaluation of the protein's physiological and toxic functions. However, the preparation of recombinant tau is complicated by the protein's propensity to aggregate and form truncation products, necessitating the use of multiple, time-consuming purification methods. In this study, we investigated parameters that influence the expression of wild type and FTPD-17 pathogenic tau, in an attempt to identify ways to maximise expression yield. Here, we report on the influence of the choice of host strain, induction temperature, duration of induction, and media supplementation with glucose on tau expression in Escherichia coli. We also describe a straightforward process to purify the expressed tau proteins using immobilised metal affinity chromatography, with favourable yields over previous reports. An advantage of the described method is that it enables high yield production of functional oligomeric and monomeric tau, both of which can be used to study the biochemical, physiological and toxic properties of the protein

Combining sequence-based prediction methods and circular dichroism and infrared spectroscopic data to improve protein secondary structure determinations

<p>Abstract</p> <p>Background</p> <p>A number of sequence-based methods exist for protein secondary structure prediction. Protein secondary structures can also be determined experimentally from circular dichroism, and infrared spectroscopic data using empirical analysis methods. It has been proposed that comparable accuracy can be obtained from sequence-based predictions as from these biophysical measurements. Here we have examined the secondary structure determination accuracies of sequence prediction methods with the empirically determined values from the spectroscopic data on datasets of proteins for which both crystal structures and spectroscopic data are available.</p> <p>Results</p> <p>In this study we show that the sequence prediction methods have accuracies nearly comparable to those of spectroscopic methods. However, we also demonstrate that combining the spectroscopic and sequences techniques produces significant overall improvements in secondary structure determinations. In addition, combining the extra information content available from synchrotron radiation circular dichroism data with sequence methods also shows improvements.</p> <p>Conclusion</p> <p>Combining sequence prediction with experimentally determined spectroscopic methods for protein secondary structure content significantly enhances the accuracy of the overall results obtained.</p

The Hubble Space Telescope Wide Field Camera 3 Early Release Science data: Panchromatic Faint Object Counts for 0.2-2 microns wavelength

We describe the Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) Early Release Science (ERS) observations in the Great Observatories Origins Deep Survey (GOODS) South field. The new WFC3 ERS data provide calibrated, drizzled mosaics in the UV filters F225W, F275W, and F336W, as well as in the near-IR filters F098M (Ys), F125W (J), and F160W (H) with 1-2 HST orbits per filter. Together with the existing HST Advanced Camera for Surveys (ACS) GOODS-South mosaics in the BViz filters, these panchromatic 10-band ERS data cover 40-50 square arcmin at 0.2-1.7 {\mu}m in wavelength at 0.07-0.15" FWHM resolution and 0.090" Multidrizzled pixels to depths of AB\simeq 26.0-27.0 mag (5-{\sigma}) for point sources, and AB\simeq 25.5-26.5 mag for compact galaxies. In this paper, we describe: a) the scientific rationale, and the data taking plus reduction procedures of the panchromatic 10-band ERS mosaics; b) the procedure of generating object catalogs across the 10 different ERS filters, and the specific star-galaxy separation techniques used; and c) the reliability and completeness of the object catalogs from the WFC3 ERS mosaics. The excellent 0.07-0.15" FWHM resolution of HST/WFC3 and ACS makes star- galaxy separation straightforward over a factor of 10 in wavelength to AB\simeq 25-26 mag from the UV to the near-IR, respectively.Comment: 51 pages, 71 figures Accepted to ApJS 2011.01.2

On the importance of the few most massive stars: the ionizing cluster of NGC 588

We present the results of a double analysis of the ionizing cluster in NGC 588, a giant HII region (GHR) in the outskirts of the nearby galaxy M33. For this purpose, we obtained ground based long-slit spectroscopy and combined it with archival ground based and space borne imaging and spectroscopy, in the wavelength range 1100-9800 A. A first modeling of the cluster was performed using integrated properties, such as the spectral energy distribution (SED), broad band colors, nebular emission Hbeta equivalent width, the main ultraviolet resonance lines, and the presence of Wolf-Rayet star features. By applying standard assumptions about the initial mass function (IMF), we were unable to fit satisfactorily these observational data. This contradictory result led us to carry out a second modeling, based on a resolved photometric analysis of individual stars in Hubble Space Telescope (HST) images, by means of finding the best fit isochrone in color-magnitude diagrams (CMD), and assigning a theoretical SED to each individual star. The overall SED of the cluster, obtained by integrating the individual stellar SEDs, is found to fit better the observed SED than the best solution found through the integrated first analysis, but at a significantly later stage of evolution of the cluster of 4.2 Myr, as obtained from the best fit to the CMD. A comparative analysis of both methods traces the different results to the effects of statistical fluctuations in the upper end of the IMF, which are significant in NGC 588, with a computed cluster mass of 5600 Msun, as predicted by Cervino et al (2002). We discuss the results in terms of the strong influence of the few most massive stars, six in the case of NGC 588, that dominate the overall SED and, in particular, the ionizing far ultraviolet range beyond the Lyman limit