MRI-based brain volumetry in chronic whiplash patients: no evidence for traumatic brain injury

INTRODUCTION: Cognitive complaints, such as poor concentration and memory deficits, are frequent after whiplash injury and play an important role in disability. The origin of these complaints is discussed controversially. Some authors postulate brain lesions as a consequence of whiplash injuries. Potential diffuse axonal injury (DAI) with subsequent atrophy of the brain and ventricular expansion is of particular interest as focal brain lesions have not been documented so far in whiplash injury. OBJECTIVE: To investigate whether traumatic brain injury can be identified using a magnetic resonance (MR)-based quantitative analysis of normalized ventricle-brain ratios (VBR) in chronic whiplash patients with subjective cognitive impairment that cannot be objectively confirmed by neuropsychological testing. MATERIALS AND METHODS: MR examination was performed in 21 patients with whiplash injury and symptom persistence for 9 months on average and in 18 matched healthy controls. Conventional MR imaging (MRI) was used to assess the volumes of grey and white matter and of ventricles. The normalized VBR was calculated. RESULTS: The values of normalized VBR did not differ in whiplash patients when compared with that in healthy controls (F = 0.216, P = 0.645). CONCLUSIONS: This study does not support loss of brain tissue following whiplash injury as measured by VBR. On this basis, traumatic brain injury with subsequent DAI does not seem to be the underlying mechanism for persistent concentration and memory deficits that are subjectively reported but not objectively verifiable as neuropsychological deficits.

Non-invasive gene-expression-based detection of well-developed collateral function in individuals with and without coronary artery disease

BACKGROUND: In patients with coronary artery disease (CAD), a well grown collateral circulation has been shown to be important. The aim of this prospective study using peripheral blood monocytes was to identify marker genes for an extensively grown coronary collateral circulation. METHODS: Collateral flow index (CFI) was obtained invasively by angioplasty pressure sensor guidewire in 160 individuals (110 patients with CAD, and 50 individuals without CAD). RNA was extracted from monocytes followed by microarray-based gene-expression analysis. 76 selected genes were analysed by real-time polymerase chain reaction (PCR). A receiver operating characteristics analysis based on differential gene expression was then performed to separate individuals with poor (CFI<0.21) and well-developed collaterals (CFI>or=0.21) Thereafter, the influence of the chemokine MCP-1 on the expression of six selected genes was tested by PCR. RESULTS: The expression of 203 genes significantly correlated with CFI (p = 0.000002-0.00267) in patients with CAD and 56 genes in individuals without CAD (p = 00079-0.0430). Biological pathway analysis revealed 76 of those genes belonging to four different pathways: angiogenesis, integrin-, platelet-derived growth factor-, and transforming growth factor beta-signalling. Three genes in each subgroup differentiated with high specificity among individuals with low and high CFI (>or=0.21). Two out of these genes showed pronounced differential expression between the two groups after cell stimulation with MCP-1. CONCLUSIONS: Genetic factors play a role in the formation and the preformation of the coronary collateral circulation. Gene expression analysis in peripheral blood monocytes can be used for non-invasive differentiation between individuals with poorly and with well grown collaterals. MCP-1 can influence the arteriogenic potential of monocytes.

Future value based single assignment program representations and optimizations

An optimizing compiler internal representation fundamentally affects the clarity, efficiency and feasibility of optimization algorithms employed by the compiler. Static Single Assignment (SSA) as a state-of-the-art program representation has great advantages though still can be improved. This dissertation explores the domain of single assignment beyond SSA, and presents two novel program representations: Future Gated Single Assignment (FGSA) and Recursive Future Predicated Form (RFPF). Both FGSA and RFPF embed control flow and data flow information, enabling efficient traversal program information and thus leading to better and simpler optimizations. We introduce future value concept, the designing base of both FGSA and RFPF, which permits a consumer instruction to be encountered before the producer of its source operand(s) in a control flow setting. We show that FGSA is efficiently computable by using a series T1/T2/TR transformation, yielding an expected linear time algorithm for combining together the construction of the pruned single assignment form and live analysis for both reducible and irreducible graphs. As a result, the approach results in an average reduction of 7.7%, with a maximum of 67% in the number of gating functions compared to the pruned SSA form on the SPEC2000 benchmark suite. We present a solid and near optimal framework to perform inverse transformation from single assignment programs. We demonstrate the importance of unrestricted code motion and present RFPF. We develop algorithms which enable instruction movement in acyclic, as well as cyclic regions, and show the ease to perform optimizations such as Partial Redundancy Elimination on RFPF.

Characterization of thermal and mechanical properties of polypropylene-based composites for fuel cell bipolar plates and development of educational tools in hydrogen and fuel cell technologies

In this project we developed conductive thermoplastic resins by adding varying amounts of three different carbon fillers: carbon black (CB), synthetic graphite (SG) and multi-walled carbon nanotubes (CNT) to a polypropylene matrix for application as fuel cell bipolar plates. This component of fuel cells provides mechanical support to the stack, circulates the gases that participate in the electrochemical reaction within the fuel cell and allows for removal of the excess heat from the system. The materials fabricated in this work were tested to determine their mechanical and thermal properties. These materials were produced by adding varying amounts of single carbon fillers to a polypropylene matrix (2.5 to 15 wt.% Ketjenblack EC-600 JD carbon black, 10 to 80 wt.% Asbury Carbon's Thermocarb TC-300 synthetic graphite, and 2.5 to 15 wt.% of Hyperion Catalysis International's FIBRILTM multi-walled carbon nanotubes) In addition, composite materials containing combinations of these three fillers were produced. The thermal conductivity results showed an increase in both through-plane and in-plane thermal conductivities, with the largest increase observed for synthetic graphite. The Department of Energy (DOE) had previously set a thermal conductivity goal of 20 W/m·K, which was surpassed by formulations containing 75 wt.% and 80 wt.% SG, yielding in-plane thermal conductivity values of 24.4 W/m·K and 33.6 W/m·K, respectively. In addition, composites containing 2.5 wt.% CB, 65 wt.% SG, and 6 wt.% CNT in PP had an in–plane thermal conductivity of 37 W/m·K. Flexural and tensile tests were conducted. All composite formulations exceeded the flexural strength target of 25 MPa set by DOE. The tensile and flexural modulus of the composites increased with higher concentration of carbon fillers. Carbon black and synthetic graphite caused a decrease in the tensile and flexural strengths of the composites. However, carbon nanotubes increased the composite tensile and flexural strengths. Mathematical models were applied to estimate through-plane and in-plane thermal conductivities of single and multiple filler formulations, and tensile modulus of single-filler formulations. For thermal conductivity, Nielsen's model yielded accurate thermal conductivity values when compared to experimental results obtained through the Flash method. For prediction of tensile modulus Nielsen's model yielded the smallest error between the predicted and experimental values. The second part of this project consisted of the development of a curriculum in Fuel Cell and Hydrogen Technologies to address different educational barriers identified by the Department of Energy. By the creation of new courses and enterprise programs in the areas of fuel cells and the use of hydrogen as an energy carrier, we introduced engineering students to the new technologies, policies and challenges present with this alternative energy. Feedback provided by students participating in these courses and enterprise programs indicate positive acceptance of the different educational tools. Results obtained from a survey applied to students after participating in these courses showed an increase in the knowledge and awareness of energy fundamentals, which indicates the modules developed in this project are effective in introducing students to alternative energy sources.

Multidimensional preventive home visit programs for community-dwelling older adults: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Multidimensional preventive home visit programs aim at maintaining health and autonomy of older adults and preventing disability and subsequent nursing home admission, but results of randomized controlled trials (RCTs) have been inconsistent. Our objective was to systematically review RCTs examining the effect of home visit programs on mortality, nursing home admissions, and functional status decline. METHODS: Data sources were MEDLINE, EMBASE, Cochrane CENTRAL database, and references. Studies were reviewed to identify RCTs that compared outcome data of older participants in preventive home visit programs with control group outcome data. Publications reporting 21 trials were included. Data on study population, intervention characteristics, outcomes, and trial quality were double-extracted. We conducted random effects meta-analyses. RESULTS: Pooled effects estimates revealed statistically nonsignificant favorable, and heterogeneous effects on mortality (odds ratio [OR] 0.92, 95% confidence interval [CI], 0.80-1.05), functional status decline (OR 0.89, 95% CI, 0.77-1.03), and nursing home admission (OR 0.86, 95% CI, 0.68-1.10). A beneficial effect on mortality was seen in younger study populations (OR 0.74, 95% CI, 0.58-0.94) but not in older populations (OR 1.14, 95% CI, 0.90-1.43). Functional decline was reduced in programs including a clinical examination in the initial assessment (OR 0.64, 95% CI, 0.48-0.87) but not in other trials (OR 1.00, 95% CI, 0.88-1.14). There was no single factor explaining the heterogenous effects of trials on nursing home admissions. CONCLUSION: Multidimensional preventive home visits have the potential to reduce disability burden among older adults when based on multidimensional assessment with clinical examination. Effects on nursing home admissions are heterogeneous and likely depend on multiple factors including population factors, program characteristics, and health care setting.

Landscape and forest structure at moose mortality sites on Isle Royale National Park. A LiDAR based assessment

Landscape structure and heterogeneity play a potentially important, but little understood role in predator-prey interactions and behaviourally-mediated habitat selection. For example, habitat complexity may either reduce or enhance the efficiency of a predator's efforts to search, track, capture, kill and consume prey. For prey, structural heterogeneity may affect predator detection, avoidance and defense, escape tactics, and the ability to exploit refuges. This study, investigates whether and how vegetation and topographic structure influence the spatial patterns and distribution of moose (Alces alces) mortality due to predation and malnutrition at the local and landscape levels on Isle Royale National Park. 230 locations where wolves (Canis lupus) killed moose during the winters between 2002 and 2010, and 182 moose starvation death sites for the period 1996-2010, were selected from the extensive Isle Royale Wolf-Moose Project carcass database. A variety of LiDAR-derived metrics were generated and used in an algorithm model (Random Forest) to identify, characterize, and classify three-dimensional variables significant to each of the mortality classes. Furthermore, spatial models to predict and assess the likelihood at the landscape scale of moose mortality were developed. This research found that the patterns of moose mortality by predation and malnutrition across the landscape are non-random, have a high degree of spatial variability, and that both mechanisms operate in contexts of comparable physiographic and vegetation structure. Wolf winter hunting locations on Isle Royale are more likely to be a result of its prey habitat selection, although they seem to prioritize the overall areas with higher moose density in the winter. Furthermore, the findings suggest that the distribution of moose mortality by predation is habitat-specific to moose, and not to wolves. In addition, moose sex, age, and health condition also affect mortality site selection, as revealed by subtle differences between sites in vegetation heights, vegetation density, and topography. Vegetation density in particular appears to differentiate mortality locations for distinct classes of moose. The results also emphasize the significance of fine-scale landscape and habitat features when addressing predator-prey interactions. These finer scale findings would be easily missed if analyses were limited to the broader landscape scale alone.

MARVIN: a medical research application framework based on open source software

This paper describes the open source framework MARVIN for rapid application development in the field of biomedical and clinical research. MARVIN applications consist of modules that can be plugged together in order to provide the functionality required for a specific experimental scenario. Application modules work on a common patient database that is used to store and organize medical data as well as derived data. MARVIN provides a flexible input/output system with support for many file formats including DICOM, various 2D image formats and surface mesh data. Furthermore, it implements an advanced visualization system and interfaces to a wide range of 3D tracking hardware. Since it uses only highly portable libraries, MARVIN applications run on Unix/Linux, Mac OS X and Microsoft Windows.

Hands-on time during cardiopulmonary resuscitation is affected by the process of teambuilding: A prospective randomised simulator-based trial

Background Cardiac arrests are handled by teams rather than by individual health-care workers. Recent investigations demonstrate that adherence to CPR guidelines can be less than optimal, that deviations from treatment algorithms are associated with lower survival rates, and that deficits in performance are associated with shortcomings in the process of team-building. The aim of this study was to explore and quantify the effects of ad-hoc team-building on the adherence to the algorithms of CPR among two types of physicians that play an important role as first responders during CPR: general practitioners and hospital physicians. Methods To unmask team-building this prospective randomised study compared the performance of preformed teams, i.e. teams that had undergone their process of team-building prior to the onset of a cardiac arrest, with that of teams that had to form ad-hoc during the cardiac arrest. 50 teams consisting of three general practitioners each and 50 teams consisting of three hospital physicians each, were randomised to two different versions of a simulated witnessed cardiac arrest: the arrest occurred either in the presence of only one physician while the remaining two physicians were summoned to help ("ad-hoc"), or it occurred in the presence of all three physicians ("preformed"). All scenarios were videotaped and performance was analysed post-hoc by two independent observers. Results Compared to preformed teams, ad-hoc forming teams had less hands-on time during the first 180 seconds of the arrest (93 ± 37 vs. 124 ± 33 sec, P < 0.0001), delayed their first defibrillation (67 ± 42 vs. 107 ± 46 sec, P < 0.0001), and made less leadership statements (15 ± 5 vs. 21 ± 6, P < 0.0001). Conclusion Hands-on time and time to defibrillation, two performance markers of CPR with a proven relevance for medical outcome, are negatively affected by shortcomings in the process of ad-hoc team-building and particularly deficits in leadership. Team-building has thus to be regarded as an additional task imposed on teams forming ad-hoc during CPR. All physicians should be aware that early structuring of the own team is a prerequisite for timely and effective execution of CPR.

Social Support Quality in Internet Based Information and Communication: From "Digital Divide" to "Voice Divide"

National and international studies demonstrate that the number of teenagers using the inter-net increases. But even though they actually do have access from different places to the in-formation and communication pool of the internet, there is evidence that the ways in which teenagers use the net - regarding the scope and frequency in which services are used as well as the preferences for different contents of these services - differ significantly in relation to socio-economic status, education, and gender. The results of the regarding empirical studies may be summarised as such: teenager with low (formal ) education especially use internet services embracing 'entertainment, play and fun' while higher educated teenagers (also) prefer intellectually more demanding and particularly services supplying a greater variety of communicative and informative activities. More generally, pedagogical and sociological studies investigating "digital divide" in a dif-ferentiated and sophisticated way - i.e. not only in terms of differences between those who do have access to the Internet and those who do not - suggest that the internet is no space beyond 'social reality' (e.g. DiMaggio & Hargittai 2001, 2003; Vogelgesang, 2002; Welling, 2003). Different modes of utilisation, that structure the internet as a social space are primarily a specific contextualisation of the latter - and thus, the opportunities and constraints in virtual world of the internet are not less than those in the 'real world' related to unequal distribu-tions of material, social and cultural resources as well as social embeddings of the actors involved. This fact of inequality is also true regarding the outcomes of using the internet. Empirical and theoretical results concerning forms and processes of networking and commu-nity building - i.e. sociability in the internet, as well as the social embeddings of the users which are mediated through the internet - suggest that net based communication and infor-mation processes may entail the resource 'social support'. Thus, with reference to social work and the task of compensating the reproduction of social disadvantages - whether they are medial or not - the ways in which teenagers get access to and utilize net based social sup-port are to be analysed.

IS711-based real-time PCR assay as a tool for detection of Brucella spp. in wild boars and comparison with bacterial isolation and serology

BACKGROUND: Control of brucellosis in livestock, wildlife and humans depends on the reliability of the methods used for detection and identification of bacteria. In the present study, we describe the evaluation of the recently established real-time PCR assay based on the Brucella-specific insertion sequence IS711 with blood samples from 199 wild boars (first group of animals) and tissue samples from 53 wild boars (second group of animals) collected in Switzerland. Results from IS711 real-time PCR were compared to those obtained by bacterial isolation, Rose Bengal Test (RBT), competitive ELISA (c-ELISA) and indirect ELISA (i-ELISA). RESULTS: In the first group of animals, IS711 real-time PCR detected infection in 11.1% (16/144) of wild boars that were serologically negative. Serological tests showed different sensitivities [RBT 15.6%, c-ELISA 7.5% and i-ELISA 5.5%] and only 2% of blood samples were positive with all three tests, which makes interpretation of the serological results very difficult. Regarding the second group of animals, the IS711 real-time PCR detected infection in 26% of animals, while Brucella spp. could be isolated from tissues of only 9.4% of the animals. CONCLUSION: The results presented here indicate that IS711 real-time PCR assay is a specific and sensitive tool for detection of Brucella spp. infections in wild boars. For this reason, we propose the employment of IS711 real-time PCR as a complementary tool in brucellosis screening programs and for confirmation of diagnosis in doubtful cases.

Microarray-based detection of 90 antibiotic resistance genes of gram-positive bacteria

A disposable microarray was developed for detection of up to 90 antibiotic resistance genes in gram-positive bacteria by hybridization. Each antibiotic resistance gene is represented by two specific oligonucleotides chosen from consensus sequences of gene families, except for nine genes for which only one specific oligonucleotide could be developed. A total of 137 oligonucleotides (26 to 33 nucleotides in length with similar physicochemical parameters) were spotted onto the microarray. The microarrays (ArrayTubes) were hybridized with 36 strains carrying specific antibiotic resistance genes that allowed testing of the sensitivity and specificity of 125 oligonucleotides. Among these were well-characterized multidrug-resistant strains of Enterococcus faecalis, Enterococcus faecium, and Lactococcus lactis and an avirulent strain of Bacillus anthracis harboring the broad-host-range resistance plasmid pRE25. Analysis of two multidrug-resistant field strains allowed the detection of 12 different antibiotic resistance genes in a Staphylococcus haemolyticus strain isolated from mastitis milk and 6 resistance genes in a Clostridium perfringens strain isolated from a calf. In both cases, the microarray genotyping corresponded to the phenotype of the strains. The ArrayTube platform presents the advantage of rapidly screening bacteria for the presence of antibiotic resistance genes known in gram-positive bacteria. This technology has a large potential for applications in basic research, food safety, and surveillance programs for antimicrobial resistance.

Non-ignorable loss to follow-up: correcting mortality estimates based on additional outcome ascertainment

Loss to follow-up (LTFU) is a common problem in many epidemiological studies. In antiretroviral treatment (ART) programs for patients with human immunodeficiency virus (HIV), mortality estimates can be biased if the LTFU mechanism is non-ignorable, that is, mortality differs between lost and retained patients. In this setting, routine procedures for handling missing data may lead to biased estimates. To appropriately deal with non-ignorable LTFU, explicit modeling of the missing data mechanism is needed. This can be based on additional outcome ascertainment for a sample of patients LTFU, for example, through linkage to national registries or through survey-based methods. In this paper, we demonstrate how this additional information can be used to construct estimators based on inverse probability weights (IPW) or multiple imputation. We use simulations to contrast the performance of the proposed estimators with methods widely used in HIV cohort research for dealing with missing data. The practical implications of our approach are illustrated using South African ART data, which are partially linkable to South African national vital registration data. Our results demonstrate that while IPWs and proper imputation procedures can be easily constructed from additional outcome ascertainment to obtain valid overall estimates, neglecting non-ignorable LTFU can result in substantial bias. We believe the proposed estimators are readily applicable to a growing number of studies where LTFU is appreciable, but additional outcome data are available through linkage or surveys of patients LTFU. Copyright © 2013 John Wiley & Sons, Ltd.

Development and validation of energy expenditure prediction models based on GT3X accelerometer data in 5- to 9-year-old children

Background: Accelerometry has been established as an objective method that can be used to assess physical activity behavior in large groups. The purpose of the current study was to provide a validated equation to translate accelerometer counts of the triaxial GT3X into energy expenditure in young children. Methods: Thirty-two children aged 5–9 years performed locomotor and play activities that are typical for their age group. Children wore a GT3X accelerometer and their energy expenditure was measured with indirect calorimetry. Twenty-one children were randomly selected to serve as development group. A cubic 2-regression model involving separate equations for locomotor and play activities was developed on the basis of model fit. It was then validated using data of the remaining children and compared with a linear 2-regression model and a linear 1-regression model. Results: All 3 regression models produced strong correlations between predicted and measured MET values. Agreement was acceptable for the cubic model and good for both linear regression approaches. Conclusions: The current linear 1-regression model provides valid estimates of energy expenditure for ActiGraph GT3X data for 5- to 9-year-old children and shows equal or better predictive validity than a cubic or a linear 2-regression model.

Development and validation of GT3X accelerometer cut-off points in 5- to 9-year-old children based on indirect calorimetry measurements

The ActiGraph accelerometer is commonly used to measure physical activity in children. Count cut-off points are needed when using accelerometer data to determine the time a person spent in moderate or vigorous physical activity. For the GT3X accelerometer no cut-off points for young children have been published yet. The aim of the current study was thus to develop and validate count cut-off points for young children. Thirty-two children aged 5 to 9 years performed four locomotor and four play activities. Activity classification into the light-, moderate- or vigorous-intensity category was based on energy expenditure measurements with indirect calorimetry. Vertical axis as well as vector magnitude cut-off points were determined through receiver operating characteristic curve analyses with the data of two thirds of the study group and validated with the data of the remaining third. The vertical axis cut-off points were 133 counts per 5 sec for moderate to vigorous physical activity (MVPA), 193 counts for vigorous activity (VPA) corresponding to a metabolic threshold of 5 MET and 233 for VPA corresponding to 6 MET. The vector magnitude cut-off points were 246 counts per 5 sec for MVPA, 316 counts for VPA - 5 MET and 381 counts for VPA - 6 MET. When validated, the current cut-off points generally showed high recognition rates for each category, high sensitivity and specificity values and moderate agreement in terms of the Kappa statistic. These results were similar for vertical axis and vector magnitude cut-off points. The current cut-off points adequately reflect MVPA and VPA in young children. Cut-off points based on vector magnitude counts did not appear to reflect the intensity categories better than cut-off points based on vertical axis counts alone.

Internet-Based Interventions for Social Anxiety Disorder - an Overview

Internet-based interventions hold specific advantages and disadvantages in the treatment of social anxiety disorder (SAD). The present review examines different approaches in the internet-based treatment of SAD and reviews their efficacy and effectiveness. 21 studies investigated the potential of guided and unguided internetbased cognitive-behavioral treatments (ICBT) for SAD, comprising a total of N = 1,801 socially anxious individuals. The large majority of these trials reported substantial reductions of social anxiety symptoms through ICBT programs. Within effect sizes were mostly large and comparisons to waitlist and more active control groups were positive. Treatment gains were stable from 3 months to 5 years after treatment termination. In conclusion, ICBT is effective in the reduction of social anxiety symptoms. At the same time, not all participants benefit from these treatments to a sufficient degree. Future research should focus on what makes these interventions work in which patient populations, and at the same time, examine ways to implement internet-based treatment in the routine care for socially anxious patients