Investigation of the chemical vicinity of crystal defects in ion-irradiated Mg and AZ31 with coincident Doppler broadening spectroscopy

Crystal defects in magnesium and magnesium based alloys like AZ31 are of major importance for the understanding of their macroscopic properties. We have investigated defects and their chemical surrounding in Mg and AZ31 on an atomic scale with Doppler broadening spectroscopy of the positron annihilation radiation. In these Doppler spectra the chemical information and the defect contribution have to be thoroughly separated. For this reason samples of annealed Mg were irradiated with Mg-ions in order to create exclusively defects. In addition Al- and Zn-ion irradiation on Mg-samples was performed in order to create samples with defects and impurity atoms. The ion irradiated area on the samples was investigated with laterally and depth resolved positron Doppler broadening spectroscopy (DBS) and compared with preceding SRIM-simulations of the vacancy distribution, which are in excellent agreement. The investigation of the chemical vicinity of crystal defects in AZ31 was performed with coincident Doppler broadening spectroscopy (CDBS) by comparing Mg-ion irradiated AZ31 with Mg-ion irradiated Mg. No formation of solute-vacancy complexes was found due to the ion irradiation, despite the high defect mobility.Comment: Submitted to Physical Review B on March 20 20076. Revised version submitted on September 28 2007. Accepted on October 19 200

Future circular collider injection and extraction kicker topologies and solid state generators

A 100 TeV center-of-mass energy frontier proton collider, in a new tunnel of 80–100 km circumference, is a central part of CERN’s Future Circular Colliders (FCC) design study. The designs of the injection and extraction systems of the FCC are initially based upon the parameters of the injection and extraction systems of the Large Hadron Collider and a preliminary study of the FCC beam optics and lattice. The injection and, in particular, the extraction systems of the FCC have to be highly reliable. In order to achieve high reliability, solid state switches will be used for the generators of the injection and extraction systems. This paper discusses topologies of these kicker systems, which are presently under consideration

Identification of infrastructure related risk factors, Deliverable 5.1 of the H2020 project SafetyCube

The present Deliverable (D5.1) describes the identification and evaluation of infrastructure related risk factors. It outlines the results of Task 5.1 of WP5 of SafetyCube, which aimed to identify and evaluate infrastructure related risk factors and related road safety problems by (i) presenting a taxonomy of infrastructure 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 help achieve this, Task 5.1 has initially exploited current knowledge (e.g. existing studies) and, where possible, existing accident data (macroscopic and in-depth) in order to identify and rank risk factors related to the road infrastructure. This information will help further on in WP5 to identify countermeasures for addressing these risk factors and finally to undertake an assessment of the effects of these countermeasures. In order to develop a comprehensive taxonomy of road infrastructure-related risks, an overview of infrastructure safety across Europe was undertaken to identify the main types of road infrastructure-related risks, using key resources and publications such as the European Road Safety Observatory (ERSO), The Handbook of Road Safety Measures (Elvik et al., 2009), the iRAP toolkit and the SWOV factsheets, to name a few. The taxonomy developed contained 59 specific risk factors within 16 general risk factors, all within 10 infrastructure elements. In addition to this, stakeholder consultations in the form of a series of workshops were undertaken to prioritise risk factors (‘hot topics’) based on the feedback from the stakeholders on which risk factors they considered to be the most important or most relevant in terms of road infrastructure safety. The stakeholders who attended the workshops had a wide range of backgrounds (e.g. government, industry, research, relevant consumer organisations etc.) and a wide range of interests and knowledge. The identified ‘hot topics’ were ranked in terms of importance (i.e. which would have the greatest effect on road safety). SafetyCube analysis will put the greatest emphasis on these topics (e.g. pedestrian/cyclist safety, crossings, visibility, removing obstacles). To evaluate the scientific literature, a methodology was developed in Work Package 3 of the SafetyCube project. WP5 has applied this methodology to road infrastructure risk factors. This uniformed approach facilitated systematic searching of the scientific literature and consistent evaluation of the evidence for each risk factor. The method included a literature search strategy, a ‘coding template’ to record key data and metadata from individual studies, and guidelines for summarising the findings (Martensen et al, 2016b). The main databases used in the WP5 literature search were Scopus and TRID, with some risk factors utilising additional database searches (e.g. Google Scholar, Science Direct). Studies using crash data were considered highest priority. Where a high number of studies were found, further selection criteria were applied to ensure the best quality studies were included in the analysis (e.g. key meta-analyses, recent studies, country origin, importance). Once the most relevant studies were identified for a risk factor, each study was coded within a template developed in WP3. Information coded for each study included road system element, basic study information, road user group information, study design, measures of exposure, measures of outcomes and types of effects. The information in the coded templates will be included in the relational database developed to serve as the main source (‘back end’) of the Decision Support System (DSS) being developed for SafetyCube. Each risk factor was assigned a secondary coding partner who would carry out the control procedure and would discuss with the primary coding partner any coding issues they had found. Once all studies were coded for a risk factor, a synopsis was created, synthesising the coded studies and outlining the main findings in the form of meta-analyses (where possible) or another type of comprehensive synthesis (e.g. vote-count analysis). Each synopsis consists of three sections: a 2 page summary (including abstract, overview of effects and analysis methods); a scientific overview (short literature synthesis, overview of studies, analysis methods and analysis of the effects) and finally supporting documents (e.g. details of literature search and comparison of available studies in detail, if relevant). To enrich the background information in the synopses, in-depth accident investigation data from a number of sources across Europe (i.e. GIDAS, CARE/CADaS) was sourced. Not all risk factors could be enhanced with this data, but where it was possible, the aim was to provide further information on the type of crash scenarios typically found in collisions where specific infrastructure-related risk factors are present. If present, this data was included in the synopsis for the specific risk factor. After undertaking the literature search and coding of the studies, it was found that for some risk factors, not enough detailed studies could be found to allow a synopsis to be written. Therefore, the revised number of specific risk factors that did have a synopsis written was 37, within 7 infrastructure elements. Nevertheless, the coded studies on the remaining risk factors will be included in the database to be accessible by the interested DSS users. At the start of each synopsis, the risk factor is assigned a colour code, which indicates how important this risk factor is in terms of the amount of evidence demonstrating its impact on road safety in terms of increasing crash risk or severity. The code can either be Red (very clear increased risk), Yellow (probably risky), Grey (unclear results) or Green (probably not risky). In total, eight risk factors were given a Red code (e.g. traffic volume, traffic composition, road surface deficiencies, shoulder deficiencies, workzone length, low curve radius), twenty were given a Yellow code (e.g. secondary crashes, risks associated with road type, narrow lane or median, roadside deficiencies, type of junction, design and visibility at junctions) seven were given a Grey code (e.g. congestion, frost and snow, densely spaced junctions etc.). The specific risk factors given the red code were found to be distributed across a range of infrastructure elements, demonstrating that the greatest risk is spread across several aspects of infrastructure design and traffic control. However, four ‘hot topics’ were rated as being risky, which were ‘small work-zone length’, ‘low curve radius’, ‘absence of shoulder’ and ‘narrow shoulder’. Some limitations were identified. Firstly, because of the method used to attribute colour code, it is in theory possible for a risk factor with a Yellow colour code to have a greater overall magnitude of impact on road safety than a risk factor coded Red. This would occur if studies reported a large impact of a risk factor but without sufficient consistency to allocate a red colour code. Road safety benefits should be expected from implementing measures to mitigate Yellow as well as Red coded infrastructure risks. Secondly, findings may have been limited by both the implemented literature search strategy and the quality of the studies identified, but this was to ensure the studies included were of sufficiently high quality to inform understanding of the risk factor. Finally, due to difficulties of finding relevant studies, it was not possible to evaluate the effects on road safety of all topics listed in the taxonomy. The next task of WP5 is to begin identifying measures that will counter the identified risk factors. Priority will be placed on investigating measures aimed to mitigate the risk factors identified as Red. The priority of risk factors in the Yellow category will depend on why they were assigned to this category and whether or not they are a hot topic

The Reproducibility of Blood Acid Base Responses in Male Collegiate Athletes Following Individualised Doses of Sodium Bicarbonate: A Randomised Controlled Crossover Study

Background: Current evidence suggests sodium bicarbonate (NaHCO3) should be ingested based upon the individualised alkalotic peak of either blood pH or bicarbonate (HCO3−) because of large inter-individual variations (10–180 min). If such a strategy is to be practical, the blood analyte response needs to be reproducible. Objective: This study aimed to evaluate the degree of reproducibility of both time to peak (TTP) and absolute change in blood pH, HCO3− and sodium (Na+) following acute NaHCO3 ingestion. Methods: Male participants (n = 15) with backgrounds in rugby, football or sprinting completed six randomised treatments entailing ingestion of two doses of 0.2 g·kg−1 body mass (BM) NaHCO3 (SBC2a and b), two doses of 0.3 g·kg−1 BM NaHCO3 (SBC3a and b) or two control treatments (CON1a and b) on separate days. Blood analysis included pH, HCO3− and Na+ prior to and at regular time points following NaHCO3 ingestion over a 3-h period. Results: HCO3− displayed greater reproducibility than pH in intraclass correlation coefficient (ICC) analysis for both TTP (HCO3− SBC2 r = 0.77, P = 0.003; SBC3 r = 0.94, P < 0.001; pH SBC2 r = 0.62, P = 0.044; SBC3 r = 0.71, P = 0.016) and absolute change (HCO3− SBC2 r = 0.89, P < 0.001; SBC3 r = 0.76, P = 0.008; pH SBC2 r = 0.84, P = 0.001; SBC3 r = 0.62, P = 0.041). Conclusion: Our results indicate that both TTP and absolute change in HCO3− is more reliable than pH. As such, these data provide support for an individualised NaHCO3 ingestion strategy to consistently elicit peak alkalosis before exercise. Future work should utilise an individualised NaHCO3 ingestion strategy based on HCO3− responses and evaluate effects on exercise performance

Inventory of assessed infrastructure risk factors and measures, Deliverable 5.4 of the H2020 project SafetyCube

Inventory of assessed infrastructure risk factors and measures, Deliverable 5.4 of the H2020 project SafetyCub

Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme

BACKGROUND: The relevance of angiogenesis inhibition in the treatment of glioblastoma multiforme (GBM) should be considered in the unique context of malignant brain tumours. Although patients benefit greatly from reduced cerebral oedema and intracranial pressure, this important clinical improvement on its own may not be considered as an anti-tumour effect. DISCUSSION: GBM can be roughly separated into an angiogenic component, and an invasive or migratory component. Although this latter component seems inert to anti-angiogenic therapy, it is of major importance for disease progression and survival. We reviewed all relevant literature. Published data support that clinical symptoms are tempered by anti-angiogenic treatment, but that tumour invasion continues. Unfortunately, current imaging modalities are affected by anti-angiogenic treatment too, making it even harder to define tumour margins. To illustrate this we present MRI, biopsy and autopsy specimens from bevacizumab-treated patients. Moreover, while treatment of other tumour types may be improved by combining chemotherapy with anti-angiogenic drugs, inhibiting angiogenesis in GBM may antagonise the efficacy of chemotherapeutic drugs by normalising the blood-brain barrier function. SUMMARY: Although angiogenesis inhibition is of considerable value for symptom reduction in GBM patients, lack of proof of a true anti-tumour effect raises concerns about the place of this type of therapy in the treatment of GBM

Frontally mediated inhibitory processing and white matter microstructure: age and alcoholism effects

RationaleThe NOGO P3 event-related potential is a sensitive marker of alcoholism, relates to EEG oscillation in the δ and θ frequency ranges, and reflects activation of an inhibitory processing network. Degradation of white matter tracts related to age or alcoholism should negatively affect the oscillatory activity within the network.ObjectiveThis study aims to evaluate the effect of alcoholism and age on δ and θ oscillations and the relationship between these oscillations and measures of white matter microstructural integrity.MethodsData from ten long-term alcoholics to 25 nonalcoholic controls were used to derive P3 from Fz, Cz, and Pz using a visual GO/NOGO protocol. Total power and across trial phase synchrony measures were calculated for δ and θ frequencies. DTI, 1.5 T, data formed the basis of quantitative fiber tracking in the left and right cingulate bundles and the genu and splenium of the corpus callosum. Fractional anisotropy and diffusivity (λL and λT) measures were calculated from each tract.ResultsNOGO P3 amplitude and δ power at Cz were smaller in alcoholics than controls. Lower δ total power was related to higher λT in the left and right cingulate bundles. GO P3 amplitude was lower and GO P3 latency was longer with advancing age, but none of the time-frequency analysis measures displayed significant age or diagnosis effects.ConclusionsThe relation of δ total power at CZ with λT in the cingulate bundles provides correlational evidence for a functional role of fronto-parietal white matter tracts in inhibitory processing

Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure

Background & Aims Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. Methods Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). Results There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. Conclusions These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. Impact and implications This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. Clinical trial number NCT03065699