Identification of vehicle related risk factors, deliverable 6.1 of the H2020 project SafetyCube

The present Deliverable (D6.1) describes the identification and evaluation of vehicle related risk factors. It outlines the results of Task 6.1 of Work Package 6 (WP6) of SafetyCube, which aimed to identify and evaluate vehicle related risk factors and related road safety problems by (i) presenting a taxonomy of vehicle related risks, (ii) identifying “hot topics” of concern for relevant stakeholders and (iii) evaluating the relative importance for road safety outcomes (crash risk, crash frequency and severity etc.) within the scientific literature for each identified risk factor. To reach this objective, Task 6.1 has initially exploited current knowledge (e.g. existing studies) and existing accident data (macroscopic and in-depth) in order to quantify scenarios (defined in Work Package 8) related to the vehicle element. This information will help further on in WP6 to identify countermeasures for addressing these risk factors and finally to undertake an assessment of the effects of these countermeasures (...continues)

Description of data-sources used in SafetyCube. Deliverable 3.1 of the H2020 project SafetyCube

Safety CaUsation, Benefits and Efficiency (SafetyCube) is a European Commission supported Horizon 2020 project with the objective of developing an innovative road safety Decision Support System (DSS) that will enable policy-makers and stakeholders to select and implement the most appropriate strategies, measures and cost-effective approaches to reduce casualties of all road user types and all severities. This deliverable describes the available data in the form of an inventory of databases that can be used for analyses within the project. Two general types of data are available: one describing the involvement of different components for the road safety (vehicles, infrastructure, and the road user) and one describing the injury outcomes of a crash. These two database categories are available to the partners of SafetyCube and gathered in two excel tables. One table contains traffic databases (accident and naturalistic driving studies) and the second table contains injury databases. The tables contain information on 58 and 35 variables, respectively. The key information describing the databases that was needed for the inventory were items such as: Type of data collected (crashes, injuries, etc.) Documentation of the variables Sampling criteria for the data collected SafetyCube partners with access to the data Extent of data access (raw data vs. summary tables) The tables contain 36 traffic accident databases, five naturalistic driving studies or field-tests and 22 injury databases where of four were coded in both sheets

Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a complex genetic background, hampering identification of underlying genetic risk factors. We hypothesized that combining linkage analysis and whole-exome sequencing (WES) in multi-generation pedigrees with multiple affected individuals can point toward novel ADHD genes. Three families with multiple ADHD-affected members (Ntotal = 70) and apparent dominant inheritance pattern were included in this study. Genotyping was performed in 37 family members, and WES was additionally carried out in 10 of those. Linkage analysis was performed using multi-point analysis in Superlink Online SNP 1.1. From prioritized linkage regions with a LOD score ≥ 2, a total of 24 genes harboring rare variants were selected. Those genes were taken forward and were jointly analyzed in gene-set analyses of exome-chip data using the MAGMA software in an independent sample of patients with persistent ADHD and healthy controls (N = 9365). The gene-set including all 24 genes together, and particularly the gene-set from one of the three families (12 genes), were significantly associated with persistent ADHD in this sample. Among the latter, gene-wide analysis for the AAED1 gene reached significance. A rare variant (rs151326868) within AAED1 segregated with ADHD in one of the families. The analytic strategy followed here is an effective approach for identifying novel ADHD risk genes. Additionally, this study suggests that both rare and more frequent variants in multiple genes act together in contributing to ADHD risk, even in individual multi-case families

Identification of road user related risk factors, deliverable 4.1 of the H2020 project SafetyCube.

Safety CaUsation, Benefits and Efficiency (SafetyCube) is a European Commission supported Horizon 2020 project with the objective of developing an innovative road safety Decision Support System (DSS). The DSS will enable policy-makers and stakeholders to select and implement the most appropriate strategies, measures, and cost-effective approaches to reduce casualties of all road user types and all severities. This document is the first deliverable (4.1) of work package 4 which is dedicated to identifying and assessing human related risk factors and corresponding countermeasures as well as their effect on road safety. The focus of deliverable 4.1 is on identification and assessment of risk factors and describes the corresponding operational procedure and corresponding outcomes. The following steps have been carried out: Identification of human related risk factors – creation of a taxonomy Consultation of relevant stakeholders and policy papers for identification of topic with high priority (‘hot topics’) Systematic literature search and selection of relevant studies on identified risk factors •Coding of studies •Analysis of risk factors on basis of coded studies •Synopses of risk factors, including accident scenarios The core output of this task are synopses of risk factors which will be available through the DSS. Within the synopses, each risk factor was analysed systematically on basis of scientific studies and is further assigned to one of four levels of risk (marked with a colour code). Essential information of the more than 180 included studies were coded and will also be available in the database of the DSS. Furthermore, the synopses contain theoretical background on the risk factor and are prepared in different sections with different levels of detail for an academic as well as a non-academic audience. These sections are readable independently. It is important to note that the relationship between road safety and road user related risk factors is a difficult task. For some risk factors the available studies focused more on conditions of the behaviour (in which situations the behaviour is shown or which groups are more likely to show this behaviour) rather than the risk factor itself. Therefore, it cannot be concluded that those risk factors that have not often been studied or have to rely more indirect and arguably weaker methodologies, e.g. self-reports , do not increase the chance of a crash occurring. The following analysed risk factors were assessed as ‘risky’, ‘probably risky’ or ‘unclear’. No risk factors were identified as ‘probably not risky’. Risky Probably risky Unclear • Influenced driving – alcohol • Influenced Driving – drugs (legal & illegal) • Speeding and inappropriate speed • Traffic rule violations – red light running • Distraction – cell phone use (hand held) • Distraction – cell phone use (hands free) • Distraction – cell phone use (texting) • Fatigue – sleep disorders – sleep apnea • Risk taking – overtaking • Risk taking – close following behaviour • Insufficient knowledge and skills • Functional impairment – cognitive impairment • Functional impairment – vision loss • Diseases and disorders – diabetes • Personal factors – sensation seeking • Personal factors – ADHD • Emotions – anger, aggression • Fatigue – Not enough sleep/driving while tired • Distraction – conversation with passengers • Distraction – outside of vehicle • Distraction – cognitive overload and inattention • Functional impairment – hearing loss (few studies) • Observation errors (few studies) • Distraction – music – entertainment systems (many studies, mixed results) • Distraction – operating devices (many studies, mixed results) The next step in SafetyCube’s WP4 is to identify and assess the effectiveness of measures and to establish a link to the identified risk factors. The work of this first task indicates a set of risk factors that should be centre of attention when identifying corresponding road safety measures (category ‘risky’)

Identification and safety effects of road user related measures. Deliverable 4.2 of the H2020 project SafetyCube

Safety CaUsation, Benefits and Efficiency (SafetyCube) is a European Commission supported Horizon 2020 project with the objective of developing an innovative road safety Decision Support System (DSS). The DSS will enable policy-makers and stakeholders to select and implement the most appropriate strategies, measures, and cost-effective approaches to reduce casualties of all road user types and all severities. This document is the second deliverable (4.2) of work package 4, which is dedicated to identifying and assessing road safety measures related to road users in terms of their effectiveness. The focus of deliverable 4.2 is on the identification and assessment of countermeasures and describes the corresponding operational procedure and outcomes. Measures which intend to increase road safety of all kind of road user groups have been considered [...continues]

XeNA: an automated ‘open-source’ 129Xe hyperpolarizer for clinical use

Here we provide a full report on the construction, components, and capabilities of our consortium’s “open-source” large-scale (~ 1 L/h) 129Xe hyperpolarizer for clinical, pre-clinical, and materials NMR/MRI (Nikolaou et al., Proc. Natl. Acad. Sci. USA, 110, 14150 (2013)). The ‘hyperpolarizer’ is automated and built mostly of off-the-shelf components; moreover, it is designed to be cost-effective and installed in both research laboratories and clinical settings with materials costing less than $125,000. The device runs in the xenon-rich regime (up to 1800 Torr Xe in 0.5 L) in either stopped-flow or single-batch mode—making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell 129Xe nuclear spin polarization values of ~ 30%–90% have been measured for Xe loadings of ~ 300–1600 Torr. Typical 129Xe polarization build-up and T1 relaxation time constants were ~ 8.5 min and ~ 1.9 h respectively under our spin-exchange optical pumping conditions; such ratios, combined with near-unity Rb electron spin polarizations enabled by the high resonant laser power (up to ~ 200 W), permit such high PXe values to be achieved despite the high in-cell Xe densities. Importantly, most of the polarization is maintained during efficient HP gas transfer to other containers, and ultra-long 129Xe relaxation times (up to nearly 6 h) were observed in Tedlar bags following transport to a clinical 3 T scanner for MR spectroscopy and imaging as a prelude to in vivo experiments. The device has received FDA IND approval for a clinical study of chronic obstructive pulmonary disease subjects. The primary focus of this paper is on the technical/engineering development of the polarizer, with the explicit goals of facilitating the adaptation of design features and operative modes into other laboratories, and of spurring the further advancement of HP-gas MR applications in biomedicine

The F0F1-ATP Synthase Complex Contains Novel Subunits and Is Essential for Procyclic Trypanosoma brucei

The mitochondrial F0F1 ATP synthase is an essential multi-subunit protein complex in the vast majority of eukaryotes but little is known about its composition and role in Trypanosoma brucei, an early diverged eukaryotic pathogen. We purified the F0F1 ATP synthase by a combination of affinity purification, immunoprecipitation and blue-native gel electrophoresis and characterized its composition and function. We identified 22 proteins of which five are related to F1 subunits, three to F0 subunits, and 14 which have no obvious homology to proteins outside the kinetoplastids. RNAi silencing of expression of the F1 α subunit or either of the two novel proteins showed that they are each essential for the viability of procyclic (insect stage) cells and are important for the structural integrity of the F0F1-ATP synthase complex. We also observed a dramatic decrease in ATP production by oxidative phosphorylation after silencing expression of each of these proteins while substrate phosphorylation was not severely affected. Our procyclic T. brucei cells were sensitive to the ATP synthase inhibitor oligomycin even in the presence of glucose contrary to earlier reports. Hence, the two novel proteins appear essential for the structural organization of the functional complex and regulation of mitochondrial energy generation in these organisms is more complicated than previously thought

Development of a Listeria monocytogenes EGDe partial proteome reference map and comparison with the protein profiles of food isolates

A partially annotated proteome reference map of the food pathogen Listeria monocytogenes was developed for exponentially growing cells under standardized, optimal conditions by using the sequenced strain EGDe (serotype 1/2a) as a model organism. The map was developed by using a reproducible total protein extraction and two-dimensional (2-D) polyacrylamide gel electrophoresis analysis procedure, and it contained 33 identified proteins representing the four main protein functional classes. In order to facilitate analysis of membrane proteins, a protein compartmentalization procedure was assessed. The method used provided partial fractionation of membrane and cytosolic proteins. The total protein 2-D profiles of three serotype 1/2a strains and one serotype 1/2b strain isolated from food were compared to the L. monocytogenes EGDe proteome. An average of 13% of the major protein spots in the food strain proteomes were not matched in the strain EGDe proteome. The variation was greater for the less intense spots, and on average 28% of these spots were not matched. Two of the proteins identified in L. monocytogenes EGDe were missing in one or more of the food isolates. These two proteins were proteins involved in the main glycolytic pathway and in metabolism of coenzymes and prosthetic groups. The two corresponding genes were found by PCR amplification to be present in the four food isolates. Our results show that the L. monocytogenes EGDe reference map is a valuable starting point for analyses of strains having various origins and could be useful for analyzing the proteomes of different isolates of this pathogen.Articl

Development of a <I>Listeria monocytogenes </I>EGDe partial proteome reference map and comparison with the protein profiles of food isolates

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