Injury severity and serum amyloid A correlate with plasma oxidation-reduction potential in multi-trauma patients: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>In critical injury, the occurrence of increased oxidative stress or a reduced antioxidant status has been observed. The purpose of this study was to correlate the degree of oxidative stress, by measuring the oxidation-reduction potential (ORP) of plasma in the critically injured, with injury severity and serum amyloid A (SAA) levels.</p> <p>Methods</p> <p>A total of 140 subjects were included in this retrospective study comprising 3 groups: healthy volunteers (N = 21), mild to moderate trauma (ISS < 16, N = 41), and severe trauma (ISS ≥ 16, N = 78). For the trauma groups, plasma was collected on an almost daily basis during the course of hospitalization. ORP analysis was performed using a microelectrode, and ORP maxima were recorded for the trauma groups. SAA, a sensitive marker of inflammation in critical injury, was measured by liquid chromatography/mass spectrometry.</p> <p>Results</p> <p>ORP maxima were reached on day 3 (± 0.4 SEM) and day 5 (± 0.5 SEM) for the ISS < 16 and ISS ≥ 16 groups, respectively. ORP maxima were significantly higher in the ISS < 16 (-14.5 mV ± 2.5 SEM) and ISS ≥ 16 groups (-1.1 mV ± 2.3 SEM) compared to controls (-34.2 mV ± 2.6 SEM). Also, ORP maxima were significantly different between the trauma groups. SAA was significantly elevated in the ISS ≥ 16 group on the ORP maxima day compared to controls and the ISS < 16 group.</p> <p>Conclusion</p> <p>The results suggest the presence of an oxidative environment in the plasma of the critically injured as measured by ORP. More importantly, ORP can differentiate the degree of oxidative stress based on the severity of the trauma and degree of inflammation.</p

Extended Friedberg Lee hidden symmetries, quark masses and CP-violation with four generations

Motivated in part by the several observed anomalies involving CP asymmetries of B and B_s decays, we consider the Standard Model with a 4th sequential family (SM4) which seems to offer a rather simple resolution. We initially assume T-invariance by taking the up and down-quark 4x4 mass matrix to be real. Following Friedberg and Lee (FL), we then impose a "hidden" symmetry on the unobserved ("hidden") up and down-quark SU(2) states. The hidden symmetry for four generations ensures the existence of two zero-mass eigenstates, which we take to be the (u,c) and (d,s) states in the up and down-quark sectors, respectively. Then, we simultaneously break T-invariance and the hidden symmetry by introducing two phase factors in each sector. This breaking mechanism generates the small quark masses m_u, m_c and m_d, m_s which, along with the orientation of the hidden symmetry, determine the size of CP-violation in the SM4. For illustration we choose a specific physical picture for the hidden symmetry and the breaking mechanism that reproduces the observed quark masses, mixing angles and CP-violation, and at the same time allows us to further obtain very interesting relations/predictions for the mixing angles of t and t'. For example, with this choice we get V_{td} ~ (V_{cb}/V_{cd} - V_{ts}/V_{us}) + O(\lambda^2) and V_{t'b} ~ V_{t'd}x(V_{cb}/V_{cd}), V_{tb'} ~ V_{t'd}x(V_{ts}/V_{us}), implying that V_{t'd} > V_{t'b},V_{tb'}. We furthermore find that the Cabibbo angle is related to the orientation of the hidden symmetry and that the key CP-violating quantity of our model at high-energies, J_{SM4} = Im[V_{tb} V_{t'b}^* V_{t'b'} V_{tb'}^*], which is the high-energy analogue of the Jarlskog invariant of the SM, is proportional to the light-quark masses and the measured CKM angles.Comment: 19 page

Phthalate esters used as plasticizers in packed red blood cell storage bags may lead to progressive toxin exposure and the release of pro-inflammatory cytokines

Phthalate esters (PE's) are plasticizers used to soften PVC-based medical devices. PE's are the most abundant man-made pollutants and increase the risk of developing an allergic respiratory disease or a malignancy. The leaching of PE's in donated packed red blood cells (PRBC) during storage was assessed. PRBC transfusion bags containing CPD/AS-1 (ADSOL) buffer were analyzed. Samples were collected on storage day 1 and day 42. Two PE's, di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP), were measured by liquid chromatography coupled to mass spectrometry (LCMS). Interleukin-8 (IL-8) was measured by standard ELISA techniques. DEHP significantly increased from 34.3 µM (±20.0 SD) on day 1 to 433.2 µM (±131.2 SD) on day 42, a 12.6-fold increase. Similarly, MEHP significantly increased from 3.7 µM (±2.8 SD) on day 1 to 74.0 µM (±19.1 SD) on day 42, a 20.2-fold increase. Also, DEHP and MEHP increased the release of IL-8 from human umbilical vein endothelial cells (HUVEC). The transfusion of older units of PRBC could lead to an accumulation of PE's possibly resulting in inflammation and other effects. This accumulation could be exacerbated due to the decreased metabolism of PE's since trauma patients have a lower esterase activity, the enzymes responsible for metabolizing PE's. The effect of oxidative stress caused by PE's is discussed as a potential mechanism for increases in inflammation caused by older units of PRBC

Accelerating Bayesian hierarchical clustering of time series data with a randomised algorithm

We live in an era of abundant data. This has necessitated the development of new and innovative statistical algorithms to get the most from experimental data. For example, faster algorithms make practical the analysis of larger genomic data sets, allowing us to extend the utility of cutting-edge statistical methods. We present a randomised algorithm that accelerates the clustering of time series data using the Bayesian Hierarchical Clustering (BHC) statistical method. BHC is a general method for clustering any discretely sampled time series data. In this paper we focus on a particular application to microarray gene expression data. We define and analyse the randomised algorithm, before presenting results on both synthetic and real biological data sets. We show that the randomised algorithm leads to substantial gains in speed with minimal loss in clustering quality. The randomised time series BHC algorithm is available as part of the R package BHC, which is available for download from Bioconductor (version 2.10 and above) via http://bioconductor.org/packages/2.10/bioc/html/BHC.html. We have also made available a set of R scripts which can be used to reproduce the analyses carried out in this paper. These are available from the following URL. https://sites.google.com/site/randomisedbhc/

Identifying dynamical modules from genetic regulatory systems: applications to the segment polarity network

BACKGROUND It is widely accepted that genetic regulatory systems are 'modular', in that the whole system is made up of smaller 'subsystems' corresponding to specific biological functions. Most attempts to identify modules in genetic regulatory systems have relied on the topology of the underlying network. However, it is the temporal activity (dynamics) of genes and proteins that corresponds to biological functions, and hence it is dynamics that we focus on here for identifying subsystems. RESULTS Using Boolean network models as an exemplar, we present a new technique to identify subsystems, based on their dynamical properties. The main part of the method depends only on the stable dynamics (attractors) of the system, thus requiring no prior knowledge of the underlying network. However, knowledge of the logical relationships between the network components can be used to describe how each subsystem is regulated. To demonstrate its applicability to genetic regulatory systems, we apply the method to a model of the Drosophila segment polarity network, providing a detailed breakdown of the system. CONCLUSION We have designed a technique for decomposing any set of discrete-state, discrete-time attractors into subsystems. Having a suitable mathematical model also allows us to describe how each subsystem is regulated and how robust each subsystem is against perturbations. However, since the subsystems are found directly from the attractors, a mathematical model or underlying network topology is not necessarily required to identify them, potentially allowing the method to be applied directly to experimental expression data

Retention of Re in metakaolin based geopolymer in the presence of an organic reductant – an experimental study

The goal of this research was to examine the change in redox sensitive contaminant retention and leaching behavior from a model geopolymer system, during oxidation and carbonation, in the presence of an organic reductant. The behavior of redox sensitive elements under variable environmental conditions is specifically important for understanding the leaching of radionuclides retained in geopolymeric materials (e.g. Tc) that are soluble when oxidized and insoluble under reducing conditions. An alkali-activated metakaolin geopolymer with high silica/alumina ratio was selected as a model material. Rhenium was selected as the model redox sensitive element, which exhibits a large valence (-3 to +7) and solubility range. Rhenium was introduced in its most oxidized form (VII) as Re2S7. Ascorbic acid was used as a reducing agent during geopolymer casting due to its high solubility and homogeneous distribution within the matrix. Cylindrical monoliths were cured for 90 days under an inert atmosphere (N2) and then aged for 60 days under 98% N2 + 2% CO2 or CO2 deficient air, at a constant relative humidity (68%). The samples were then subjected to EPA 1313 pH dependent leaching test and EPA 1315 monolith leaching test. Leachates were analyzed using DOC and ICP techniques. XRD and SEM – EDS imaging and analyses were used to characterizes the solids Results show that Re has precipitated as ReS2 (IV) in the matrix. The pH dependent leaching test show that Re was released homogenously throughout most of the pH range (3-12). However, the retention of the material aged under CO2 deficient air was three times lower, indicating that the main effect on leaching from this material is of the oxidation process. The natural pH values were 11.3 and 12 for the material aged under 2% CO2 and for material aged under CO2 deficient air respectively, indicating minor carbonation in the former, however, no carbonate minerals were detected in the matrix. Monolith leaching results show that the geopolymers aged under CO2 deficient air have retained significantly less Re (0.24% leaching) relative to the sample aged under 2% CO2 (0.07wt % leaching). -log(diffusivity) values were in the order of 15 and 16 for CO2 deficient air and 2% CO2 respectively. There is a clear positive correlation between the amount of Re and DOC released from the samples, where their amounts are significantly larger for the samples aged under CO2 deficient air, indicating that the main Re-release mechanism from these samples is related to chelation to organic species under oxidizing conditions

Salvage Fractionated Stereotactic Re-irradiation (FSRT) for Patients with Recurrent High Grade Gliomas Progressed after Bevacizumab Treatment

Purpose/Objectives: Bevacizumab failure is a major clinical problem in the manage- ment of high grade gliomas (HGG), with a median overall survival of less than 4 months (m). This study evaluated the efficacy of fractionated stereotactic re-irradiation (FSRT) for patients with HGG after progression on Bevacizumab. Materials/Methods: Retrospective review was conducted of patients treated with FSRT after progression on bevacizumab. A total of 36 patients were identified. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed. Results: Among the 36 patients, 31 patients had recurrent glioblastoma, and 5 patients had recurrent anaplastic astrocytoma. The median time from initial bevacizumab treatment to FSRT was 8.5 m (range 2.3 – 32.0 m). The median plan target volume for FSRT was 27.5 cc (range 1.95 – 165 cc). With a median follow up of 20.4 m, the overall survival of the patients since initial diagnosis was also 24.9 m. The median overall survival after initiation of bevacizumab was 13.4 months. The median overall survival from FSRT was 4.8 m. FSRT treatment was well tolerated with no Grade \u3e3 toxicity. Conclusions: Favorable outcomes were observed in patients with recurrent HGG who received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for selected patients with recurrent HGG amenable to FSRT, who had failed bevacizumab treatment

CP Nonconservation in ppˉ→tbˉXp\bar p\to t\bar b X at the Tevatron

The reaction $p\bar p\to t\bar bX$ is found to be rather rich in exhibiting several different types of CP asymmetries. The spin of the top quark plays an important role. Asymmetries are related to form factors arising from radiative corrections of the $tbW$ production vertex due to non-standard physics. As illustrations, effects are studied in two Higgs Doublet Models and in Supersymmetric Models; asymmetries up to a few percent may be possible.Comment: 14 pages, 3 figures. Note: replaced due to minor problems that appeared on some postscript previewers. No change in conten