Low serum alpha-tocopherol and selenium are associated with accelerated apoptosis in severe sepsis

During sepsis, a severe systemic disorder, micronutrients often are decreased. Apoptosis is regarded as an important mechanism in the development of often significant immunosuppression in the course of the disease. This study aimed to investigate alpha-tocopherol and selenium in reference to apoptosis in patients with sepsis. 16 patients were enrolled as soon as they fulfilled the criteria of severe sepsis. 10 intensive care patients without sepsis and 11 healthy volunteers served as controls. alpha-Tocopherol, selenium and nucleosomes were measured in serum. Phosphatidylserine externalization and Bcl-2 expression were analyzed in T-cells by flow cytometry. Serum alpha-tocopherol and selenium were decreased in severe sepsis but not in non-septic critically ill patients (p < 0.05). Conversely, markers of apoptosis were increased in sepsis but not in critically ill control patients: Nucleosomes were found to be elevated 3 fold in serum (p < 0.05) and phosphatidylserine was externalized on an expanded subpopulation of T-cells (p < 0.05) while Bcl-2 was expressed at lower levels (p < 0.05). The decrease of micronutrients correlated with markers of accelerated apoptosis. Accelerated apoptosis in sepsis is associated with low alpha-tocopherol and selenium. The results support the investigation of micronutrient supplementation strategies in severe sepsis.

Potential for hardware-based techniques for reuse distance analysis

Reuse distance analysis, the prediction of how many distinct memory addresses will be accessed between two accesses to a given address, has been established as a useful technique in profile-based compiler optimization, but the cost of collecting the memory reuse profile has been prohibitive for some applications. In this report, we propose using the hardware monitoring facilities available in existing CPUs to gather an approximate reuse distance profile. The difficulties associated with this monitoring technique are discussed, most importantly that there is no obvious link between the reuse profile produced by hardware monitoring and the actual reuse behavior. Potential applications which would be made viable by a reliable hardware-based reuse distance analysis are identified.

Development of Hardware-In-the-Loop Simulation System for Hybrid Electric Vehicle Study

The development of embedded control systems for a Hybrid Electric Vehicle (HEV) is a challenging task due to the multidisciplinary nature of HEV powertrain and its complex structures. Hardware-In-the-Loop (HIL) simulation provides an open and convenient environment for the modeling, prototyping, testing and analyzing HEV control systems. This thesis focuses on the development of such a HIL system for the hybrid electric vehicle study. The hardware architecture of the HIL system, including dSPACE eDrive HIL simulator, MicroAutoBox II and MotoTron Engine Control Module (ECM), is introduced. Software used in the system includes dSPACE Real-Time Interface (RTI) blockset, Automotive Simulation Models (ASM), Matlab/Simulink/Stateflow, Real-time Workshop, ControlDesk Next Generation, ModelDesk and MotoHawk/MotoTune. A case study of the development of control systems for a single shaft parallel hybrid electric vehicle is presented to summarize the functionality of this HIL system.

Accelerated hypertrophic chondrocyte kinetics in GDF-7 deficient murine tibial growth plates

The Growth/Differentiation Factors (GDFs) are a subgroup of the Bone Morphogenetic Proteins (BMPs) well known for their role in joint formation and chondrogenesis. Mice deficient in one of these signaling molecules, GDF-5, have recently been shown to exhibit a decreased rate of endochondral bone growth in the proximal tibia due to a significantly longer hypertrophic phase duration. GDF-7 is a related family member, which exhibits a high degree of sequence identity with GDF-5. The purpose of the present study was to determine whether GDF-7 deficiency also alters the endochondral bone growth rate in mice and, if so, how this is achieved. Stereologic and cell kinetic parameters in proximal tibial growth plates from 5-week-old female GDF-7 -/- mice and wild type control littermates were examined. GDF-7 deficiency resulted in a statistically significant increase in growth rate (+26%; p = 0.0084) and rate of cell loss at the chondrosseous junction (+25%; p = 0.0217). Cells from GDF-7 deficient mice also exhibited a significantly shorter hypertrophic phase duration compared to wild type controls (-27%; p = 0.0326). These data demonstrate that, in the absence of GDF-7, the rate of endochondral bone growth is affected through the modulation of hypertrophic phase duration in growth plate chondrocytes. These findings further support a growing body of evidence implicating the GDFs in the formation, maturation, and maintenance of healthy cartilage.

Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C

BACKGROUND/AIMS: While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of this study was to assess independent predictors for fibrosis progression. METHODS: We identified 1189 patients from the Swiss Hepatitis C Cohort database with at least one biopsy prior to antiviral treatment and assessable date of infection. Stage-constant fibrosis progression rate was assessed using the ratio of fibrosis Metavir score to duration of infection. Stage-specific fibrosis progression rates were obtained using a Markov model. Risk factors were assessed by univariate and multivariate regression models. RESULTS: Independent risk factors for accelerated stage-constant fibrosis progression (>0.083 fibrosis units/year) included male sex (OR=1.60, [95% CI 1.21-2.12], P<0.001), age at infection (OR=1.08, [1.06-1.09], P<0.001), histological activity (OR=2.03, [1.54-2.68], P<0.001) and genotype 3 (OR=1.89, [1.37-2.61], P<0.001). Slower progression rates were observed in patients infected by blood transfusion (P=0.02) and invasive procedures or needle stick (P=0.03), compared to those infected by intravenous drug use. Maximum likelihood estimates (95% CI) of stage-specific progression rates (fibrosis units/year) for genotype 3 versus the other genotypes were: F0-->F1: 0.126 (0.106-0.145) versus 0.091 (0.083-0.100), F1-->F2: 0.099 (0.080-0.117) versus 0.065 (0.058-0.073), F2-->F3: 0.077 (0.058-0.096) versus 0.068 (0.057-0.080) and F3-->F4: 0.171 (0.106-0.236) versus 0.112 (0.083-0.142, overall P<0.001). CONCLUSIONS: This study shows a significant association of genotype 3 with accelerated fibrosis using both stage-constant and stage-specific estimates of fibrosis progression rates. This observation may have important consequences for the management of patients infected with this genotype.

Hierarchical Markov Random Fields Applied to Model Soft Tissue Deformations on Graphics Hardware

Many methodologies dealing with prediction or simulation of soft tissue deformations on medical image data require preprocessing of the data in order to produce a different shape representation that complies with standard methodologies, such as mass–spring networks, finite element method s (FEM). On the other hand, methodologies working directly on the image space normally do not take into account mechanical behavior of tissues and tend to lack physics foundations driving soft tissue deformations. This chapter presents a method to simulate soft tissue deformations based on coupled concepts from image analysis and mechanics theory. The proposed methodology is based on a robust stochastic approach that takes into account material properties retrieved directly from the image, concepts from continuum mechanics and FEM. The optimization framework is solved within a hierarchical Markov random field (HMRF) which is implemented on the graphics processor unit (GPU See Graphics processing unit ).

Interactive Ray Tracing for Virtual TV Studio Applications

In the last years, the well known ray tracing algorithm gained new popularity with the introduction of interactive ray tracing methods. The high modularity and the ability to produce highly realistic images make ray tracing an attractive alternative to raster graphics hardware. Interactive ray tracing also proved its potential in the field of Mixed Reality rendering and provides novel methods for seamless integration of real and virtual content. Actor insertion methods, a subdomain of Mixed Reality and closely related to virtual television studio techniques, can use ray tracing for achieving high output quality in conjunction with appropriate visual cues like shadows and reflections at interactive frame rates. In this paper, we show how interactive ray tracing techniques can provide new ways of implementing virtual studio applications.

Precise Near-to-Head Acoustics with Binaural Synthesis

For enhanced immersion into a virtual scene more than just the visual sense should be addressed by a Virtual Reality system. Additional auditory stimulation appears to have much potential, as it realizes a multisensory system. This is especially useful when the user does not have to wear any additional hardware, e.g., headphones. Creating a virtual sound scene with spatially distributed sources requires a technique for adding spatial cues to audio signals and an appropriate reproduction. In this paper we present a real-time audio rendering system that combines dynamic crosstalk cancellation and multi-track binaural synthesis for virtual acoustical imaging. This provides the possibility of simulating spatially distributed sources and, in addition to that, near-to-head sources for a freely moving listener in room-mounted virtual environments without using any headphones. A special focus will be put on near-to-head acoustics, and requirements in respect of the head-related transfer function databases are discussed.

Quasi-Convolution Pyramidal Blurring

Efficient image blurring techniques based on the pyramid algorithm can be implemented on modern graphics hardware; thus, image blurring with arbitrary blur width is possible in real time even for large images. However, pyramidal blurring methods do not achieve the image quality provided by convolution filters; in particular, the shape of the corresponding filter kernel varies locally, which potentially results in objectionable rendering artifacts. In this work, a new analysis filter is designed that significantly reduces this variation for a particular pyramidal blurring technique. Moreover, the pyramidal blur algorithm is generalized to allow for a continuous variation of the blur width. Furthermore, an efficient implementation for programmable graphics hardware is presented. The proposed method is named “quasi-convolution pyramidal blurring” since the resulting effect is very close to image blurring based on a convolution filter for many applications.

Survey on haptic rendering of data sets: Exploration of scalar and vector fields

Complementary to automatic extraction processes, Virtual Reality technologies provide an adequate framework to integrate human perception in the exploration of large data sets. In such multisensory system, thanks to intuitive interactions, a user can take advantage of all his perceptual abilities in the exploration task. In this context the haptic perception, coupled to visual rendering, has been investigated for the last two decades, with significant achievements. In this paper, we present a survey related to exploitation of the haptic feedback in exploration of large data sets. For each haptic technique introduced, we describe its principles and its effectiveness.

Accelerated partial breast irradiation with interstitial brachytherapy as second conservative treatment for ipsilateral breast tumour recurrence: multicentric study of the GEC-ESTRO Breast Cancer Working Group

PURPOSE To analyse the clinical outcome after salvage lumpectomy and multi-catheter brachytherapy (MCB) for ipsilateral breast tumour recurrence (IBTR). MATERIAL AND METHODS Between 09/00 and 09/10, 217 patients presenting an IBTR underwent lumpectomy and MCB (low, pulsed, or high-dose rate). Survival rates without second local recurrence (2nd LR), distant metastasis (DM), and overall survival (OS) were analysed as well as late effects and cosmetic results. Univariate and multivariate analyses (MVA) based on IBTR data were performed to find prognostic factors for 2nd LR, DM, and OS. RESULTS Median follow-up after the IBTR was 3.9 years [range: 1.1-10.3]. Five and 10-year actuarial 2nd LR rates were 5.6% [range: 1.5-9.5] and 7.2% [range: 2.1-12.1], respectively. Five and 10-year actuarial DM rates were 9.6% [range: 5.7-15.2] and 19.1% [range: 7.8-28.3], respectively. Five and 10-year actuarial OS rates were 88.7% [range: 83.1-94.8] and 76.4% [range: 66.9-87.3], respectively. In MVA, histological grade was prognostic factor for 2nd LR (p=0.008) and OS (p=0.02); while tumour size was prognostic factor for DM (p=0.03). G3-4 complication rate was 11%. Excellent/good cosmetic result was achieved in 85%. CONCLUSION This study suggests that in case of IBTR, lumpectomy plus MCB is feasible and effective in preventing 2nd LR with an OS rate at least equivalent to those achieved with salvage mastectomy.

Comparing growth trajectories of risk behaviors from late adolescence through young adulthood: An accelerated design

Risk behaviors such as substance use or deviance are often limited to the early stages of the life course. Whereas the onset of risk behavior is well studied, less is currently known about the decline and timing of cessation of risk behaviors of different domains during young adulthood. Prevalence and longitudinal developmental patterning of alcohol use, drinking to the point of drunkenness, smoking, cannabis use, deviance, and HIV-related sexual risk behavior were compared in a Swiss community sample (N = 2,843). Using a longitudinal cohort-sequential approach to link multiple assessments with 3 waves of data for each individual, the studied period spanned the ages of 16 to 29 years. Although smoking had a higher prevalence, both smoking and drinking up to the point of drunkenness followed an inverted U-shaped curve. Alcohol consumption was also best described by a quadratic model, though largely stable at a high level through the late 20s. Sexual risk behavior increased slowly from age 16 to age 22 and then remained largely stable. In contrast, cannabis use and deviance linearly declined from age 16 to age 29. Young men were at higher risk for all behaviors than were young women, but apart from deviance, patterning over time was similar for both sexes. Results about the timing of increase and decline as well as differences between risk behaviors may inform tailored prevention programs during the transition from late adolescence to adulthood.

Third degree atrioventricular block and accelerated idioventricular rhythm associated with a heart base chemodectoma in a syncopal Rottweiler.

A 7-year-old male intact Rottweiler was presented with a 1-week history of lethargy, anorexia, vomiting and multiple syncopal events. The results of the clinical examination and electrocardiography were consistent with a third degree atrioventricular block and an intermittent accelerated idioventricular rhythm. Haematology, serum biochemistry, serology for Borrelia burgdorferi, blood culture, total T4, thoracic radiography and echocardiography did not reveal the cause of the arrhythmia. Response to medical treatment with isoproterenol was poor. Pacemaker placement was declined by the owners and the dog was euthanized at their request. Histopathological examination of the heart revealed a chemodectoma at the base of the heart. There was no neoplastic infiltration of the conduction tissue. Potential mechanisms explaining the association of the arrhythmias and the tumour, such as vagal stimulation and neuroendocrine factors are discussed.

Effectiveness of non-conventional methods for accelerated orthodontic tooth movement: a systematic review and meta-analysis.

OBJECTIVES To assess the available evidence on the effectiveness of accelerated orthodontic tooth movement through surgical and non-surgical approaches in orthodontic patients. METHODS Randomized controlled trials and controlled clinical trials were identified through electronic and hand searches (last update: March 2014). Orthognathic surgery, distraction osteogenesis, and pharmacological approaches were excluded. Risk of bias was assessed using the Cochrane risk of bias tool. RESULTS Eighteen trials involving 354 participants were included for qualitative and quantitative synthesis. Eight trials reported on low-intensity laser, one on photobiomodulation, one on pulsed electromagnetic fields, seven on corticotomy, and one on interseptal bone reduction. Two studies on corticotomy and two on low-intensity laser, which had low or unclear risk of bias, were mathematically combined using the random effects model. Higher canine retraction rate was evident with corticotomy during the first month of therapy (WMD=0.73; 95% CI: 0.28, 1.19, p<0.01) and with low-intensity laser (WMD=0.42mm/month; 95% CI: 0.26, 0.57, p<0.001) in a period longer than 3 months. The quality of evidence supporting the interventions is moderate for laser therapy and low for corticotomy intervention. CONCLUSIONS There is some evidence that low laser therapy and corticotomy are effective, whereas the evidence is weak for interseptal bone reduction and very weak for photobiomodulation and pulsed electromagnetic fields. Overall, the results should be interpreted with caution given the small number, quality, and heterogeneity of the included studies. Further research is required in this field with additional attention to application protocols, adverse effects, and cost-benefit analysis. CLINICAL SIGNIFICANCE From the qualitative and quantitative synthesis of the studies, it could be concluded that there is some evidence that low laser therapy and corticotomy are associated with accelerated orthodontic tooth movement, while further investigation is required before routine application.

Accelerated wound closure in vitro by fibroblasts from a subgroup of cleft lip/palate patients: role of transforming growth factor-α.

In a fraction of patients surgically treated for cleft lip/palate, excessive scarring disturbs maxillary growth and dento-alveolar development. Since certain genes are involved in craniofacial morphogenesis as well as tissue repair, a primary defect causing cleft lip/palate could lead to altered wound healing. We performed in vitro wound healing assays with primary lip fibroblasts from 16 cleft lip/palate patients. Nine foreskin fibroblast strains were included for comparison. Cells were grown to confluency and scratch wounds were applied; wound closure was monitored morphometrically over time. Wound closure rate showed highly significant differences between fibroblast strains. Statistically, fibroblast strains from the 25 individuals could be divided into three migratory groups, namely "fast", "intermediate", and "slow". Most cleft lip/palate fibroblasts were distributed between the "fast" (5 strains) and the "intermediate" group (10 strains). These phenotypes were stable over different cell passages from the same individual. Expression of genes involved in cleft lip/palate and wound repair was determined by quantitative PCR. Transforming growth factor-α mRNA was significantly up-regulated in the "fast" group. 5 ng/ml transforming growth factor-α added to the culture medium increased the wound closure rate of cleft lip/palate strains from the "intermediate" migratory group to the level of the "fast", but had no effect on the latter group. Conversely, antibody to transforming growth factor-α or a specific inhibitor of its receptor most effectively reduced the wound closure rate of "fast" cleft lip/palate strains. Thus, fibroblasts from a distinct subgroup of cleft lip/palate patients exhibit an increased migration rate into wounds in vitro, which is linked to higher transforming growth factor-α expression and attenuated by interfering with its signaling.