Impact of anti-epileptic drug choice on discharge in acute traumatic brain injury patients

Background Anti-epileptic drug (AED) prophylaxis in the first-seven days post-traumatic brain injury (TBI) is known to reduce seizure frequency acutely. AED efficacy is equivalent; therefore, choice of AED may rest with their side-effects. We hypothesise that AEDs that impair balance will prolong recovery, shown by a longer hospital stay. We compared length of hospital stay (and reported dizziness) in TBI patients receiving the commonest AEDs used in our TBI patients, Phenytoin (which may cause imbalance), and Levetiracetam (which does not affect balance). Method A retrospective observational study was performed on TBI patients admitted to a Major Trauma Unit between October 2013 and June 2018. 100 of 278 patients treated with phenytoin or levetiracetam monotherapy for seizure prophylaxis were included. The inclusion criteria of admission Glasgow Coma Score of 14 or more and length of stay less than 3 weeks minimised confounding variables such as non-ambulant patients. Length of hospital stay and incidence of dizziness were assessed. Results The length of hospital stay was longer for patients on Phenytoin versus Levetiracetam, i.e., 10.74 vs. 7.58 days (p = 0.015; unpaired, two-sided t test). Dizziness reported by patients on phenytoin was 24% and levetiracetam was 8% (p = 0.018; Chi-squared test). Conclusion In this cohort, using Phenytoin for acute TBI, seizure prophylaxis was associated with longer length of stay and more dizziness compared to Levetiracetam. Given their equivalent AED efficacy in acute TBI seizure prophylaxis, our data suggest that Levetiracetam is preferable to Phenytoin for early seizure prophylaxis in TBI. This requires evaluation in larger, prospective studies

Quantitative imaging assay for NF-kappa B nuclear translocation in primary human macrophages

Quantitative measurement of NF-kappa B nuclear translocation is an important research tool in cellular immunology. Established methodologies have a number of limitations, such as poor sensitivity, high cost or dependence on cell lines. Novel imaging methods to measure nuclear translocation of transcriptionally active components of NF-kappa B are being used but are also partly limited by the need for specialist imaging equipment or image analysis software. Herein we present a method for quantitative detection of NF-kappa B rel A nuclear translocation, using immunofluorescence microscopy and the public domain image analysis software ImageJ that can be easily adopted for cellular immunology research without the need for specialist image analysis expertise and at low cost. The method presented here is validated by demonstrating the time course and dose response of NF-kappa B nuclear translocation in primary human macrophages stimulated with LPS, and by comparison with a commercial NF-kappa B activation reporter cell line

Error, reproducibility and sensitivity : a pipeline for data processing of Agilent oligonucleotide expression arrays

Background Expression microarrays are increasingly used to obtain large scale transcriptomic information on a wide range of biological samples. Nevertheless, there is still much debate on the best ways to process data, to design experiments and analyse the output. Furthermore, many of the more sophisticated mathematical approaches to data analysis in the literature remain inaccessible to much of the biological research community. In this study we examine ways of extracting and analysing a large data set obtained using the Agilent long oligonucleotide transcriptomics platform, applied to a set of human macrophage and dendritic cell samples. Results We describe and validate a series of data extraction, transformation and normalisation steps which are implemented via a new R function. Analysis of replicate normalised reference data demonstrate that intrarray variability is small (only around 2% of the mean log signal), while interarray variability from replicate array measurements has a standard deviation (SD) of around 0.5 log2 units ( 6% of mean). The common practise of working with ratios of Cy5/Cy3 signal offers little further improvement in terms of reducing error. Comparison to expression data obtained using Arabidopsis samples demonstrates that the large number of genes in each sample showing a low level of transcription reflect the real complexity of the cellular transcriptome. Multidimensional scaling is used to show that the processed data identifies an underlying structure which reflect some of the key biological variables which define the data set. This structure is robust, allowing reliable comparison of samples collected over a number of years and collected by a variety of operators. Conclusions This study outlines a robust and easily implemented pipeline for extracting, transforming normalising and visualising transcriptomic array data from Agilent expression platform. The analysis is used to obtain quantitative estimates of the SD arising from experimental (non biological) intra- and interarray variability, and for a lower threshold for determining whether an individual gene is expressed. The study provides a reliable basis for further more extensive studies of the systems biology of eukaryotic cells

Virtual Reality Applications in Rehabilitation

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-39510-4_1One of the most valuable applications of virtual reality (VR) is in the domain of rehabilitation. After brain injuries or diseases, many patients suffer from impaired physical and/or cognitive capabilities, such as difficulties in moving arms or remembering names. Over the past two decades, VR has been tested and examined as a technology to assist patients’ recovery and rehabilitation, both physical and cognitive. The increasing prevalence of low-cost VR devices brings new opportunities, allowing VR to be used in practice. Using VR devices such as head-mounted displays (HMDs), special virtual scenes can be designed to assist patients in the process of re-training their brain and reorganizing their functions and abilities. However, such VR interfaces and applications must be comprehensively tested and examined for their effectiveness and potential side effects. This paper presents a review of related literature and discusses the new opportunities and challenges. Most of existing studies examined VR as an assessment method rather than a training/exercise method. Nevertheless, promising cases and positive preliminary results have been shown. Considering the increasing need for self-administered, home-based, and personalized rehabilitation, VR rehabilitation is potentially an important approach. This area requires more studies and research effort

Vestibular dysfunction in acute traumatic brain injury

Traumatic brain injury (TBI) is the commonest cause of disability in under-40-year-olds. Vestibular features of dizziness (illusory self-motion) or imbalance which affects 50% of TBI patients at 5 years, increases unemployment threefold in TBI survivors. Unfortunately, vestibular diagnoses are cryptogenic in 25% of chronic TBI cases, impeding therapy. We hypothesized that chronic adaptive brain mechanisms uncouple vestibular symptoms from signs. This predicts a masking of vestibular diagnoses chronically but not acutely. Hence, defining the spectrum of vestibular diagnoses in acute TBI should clarify vestibular diagnoses in chronic TBI. There are, however, no relevant acute TBI data. Of 111 Major Trauma Ward adult admissions screened (median 38-years-old), 96 patients (87%) had subjective dizziness (illusory self-motion) and/or objective imbalance were referred to the senior author (BMS). Symptoms included: feeling unbalanced (58%), headache (50%) and dizziness (40%). In the 47 cases assessed by BMS, gait ataxia was the commonest sign (62%) with half of these cases denying imbalance when asked. Diagnoses included BPPV (38%), acute peripheral unilateral vestibular loss (19%), and migraine phenotype headache (34%), another potential source of vestibular symptoms. In acute TBI, vestibular signs are common, with gait ataxia being the most frequent one. However, patients underreport symptoms. The uncoupling of symptoms from signs likely arises from TBI affecting perceptual mechanisms. Hence, the cryptogenic nature of vestibular symptoms in TBI (acute or chronic) relates to a complex interaction between injury (to peripheral and central vestibular structures and perceptual mechanisms) and brain-adaptation, emphasizing the need for acute prospective, mechanistic studies

A parathyroid-hormone-related-protein (PTH-rP)-specific cytotoxic T cell response induced by in vitro stimulation of tumour-infiltrating lymphocytes derived from prostate cancer metastases, with epitope peptide-loaded autologous dendritic cells and low-dose IL-2

Bone metastases are one of the most common events in patients with prostate carcinoma. PTH-rP, a protein produced by prostate carcinoma and other epithelial cancers, is a key agent for the development of bone metastases. A PTH-rP-derived peptide, designated PTR-4 was identified, which is capable to bind HLA-A2.1 molecules and to generate PTH-rP-specific cytotoxic T cell (CTL) lines from healthy HLA-A2.1+ individual peripheral-blood-mononuclear-cells (PBMC). In this model, we investigated the in vitro possibility of generating an efficient PTH-rP specific CTL response by cyclical stimulations with IL-2 and PTR-4 peptide-pulsed autologous dendritic cells (DC), of HLA-A2.1+ tumour infiltrating lymphocytes (TIL) derived from a patient with metastatic prostate carcinoma. A T cell line generated in this way (called TM-PTR-4) had a CD3+, CD5+, CD4−, CD8+, CD45Ro+, CD56− immunophenotype and a HLA-A2.1 restricted cytotoxic activity to PTR-4-peptide pulsed CIR-A2 (HLA-A2.1+) target cells, PTH-rP+/HLA-A2.1+ CIR-A2 transfected with PTH-rP gene, prostate carcinoma LNCaP cells, and autologous metastatic prostate cancer cells (M-CaP). These lymphocytes were not cytotoxic to HLA-A2.1+ targets not producing PTH-rP, such as peptide-unpulsed CIR-A2 and colon carcinoma SW-1463, cell lines. Our results provide evidence that PTR-4 peptide-pulsed autologous DC may break the tolerance of human TIL against the autologous tumour by inducing a PTH-rP-specific CTL immune reaction. In conclusion PTR-4 peptide-pulsed autologous DC may be a promising approach for vaccine-therapy and antigen-specific CTL adoptive immunotherapy of hormone-resistant prostrate cancer. © 2001 Cancer Research Campaign http://www.bjcancer.co

Strongly magnetized pulsars: explosive events and evolution

Well before the radio discovery of pulsars offered the first observational confirmation for their existence (Hewish et al., 1968), it had been suggested that neutron stars might be endowed with very strong magnetic fields of $10^{10}$-$10^{14}$G (Hoyle et al., 1964; Pacini, 1967). It is because of their magnetic fields that these otherwise small ed inert, cooling dead stars emit radio pulses and shine in various part of the electromagnetic spectrum. But the presence of a strong magnetic field has more subtle and sometimes dramatic consequences: In the last decades of observations indeed, evidence mounted that it is likely the magnetic field that makes of an isolated neutron star what it is among the different observational manifestations in which they come. The contribution of the magnetic field to the energy budget of the neutron star can be comparable or even exceed the available kinetic energy. The most magnetised neutron stars in particular, the magnetars, exhibit an amazing assortment of explosive events, underlining the importance of their magnetic field in their lives. In this chapter we review the recent observational and theoretical achievements, which not only confirmed the importance of the magnetic field in the evolution of neutron stars, but also provide a promising unification scheme for the different observational manifestations in which they appear. We focus on the role of their magnetic field as an energy source behind their persistent emission, but also its critical role in explosive events.Comment: Review commissioned for publication in the White Book of "NewCompStar" European COST Action MP1304, 43 pages, 8 figure

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres