Designing a road traffic model for the cross-sectoral analysis of future national infrastructure

This paper presents a UK national road traffic model developed as part of the ITRC MISTRAL - a large interdisciplinary project of the Infrastructure Transitions Research Consortium (ITRC). The proposed model includes passenger and freight vehicle flows on major UK roads and predicts future demand in the form of an inter-zonal origin-destination matrix, using and elasticity-based simulation approach. An important part of the model is the network assignment step during which predicted flows are assigned to the road network. This allows for the assessment of road capacity utilisation and facilitates the identification of "pinch points" where future infrastructure investments might be targeted. Several policy interventions are studied in the paper, including road expansion with additional lanes, new road development and vehicle electrification. The model also explicitly considers cross-sectoral interdependencies with other infrastructure networks, primarily with the energy sector where the transport sector is the largest consumer, the digital communications sector, water supply and waste management. In future extensions, the model will also be able to estimate the environmental footprint and assess the risk and resilience of the transport network. This model has the potential to inform policy makers about the long-term performance of UK road infrastructure, considering a range of possible future scenarios for population growth, technological innovation and climate change

The implications of ambitious decarbonisation of heat and road transport for Britain’s net zero carbon energy systems

Decarbonisation of heating and road transport are regarded as necessary but very challenging steps on the pathway to net zero carbon emissions. Assessing the most efficient routes to decarbonise these sectors requires an integrated view of energy and road transport systems. Here we describe how a national gas and electricity transmission network model was extended to represent multiple local energy systems and coupled with a national energy demand and road transport model. The integrated models were applied to assess a range of technologies and policies for heating and transport where the UK’s 2050 net zero carbon emissions target is met. Overall, annual primary energy use is projected to reduce by between 25% and 50% by 2050 compared to 2015, due to ambitious efficiency improvements within homes and vehicles. However, both annual and peak electricity demands in 2050 are more than double compared with 2015. Managed electric vehicle charging could save 14TWh/year in gas-fired power generation at peak times, and associated emissions, whilst vehicle-to-grid services could provide 10GW of electricity supply during peak hours. Together, managed vehicle charging, and vehicle-to-grid supplies could result in a 16% reduction in total annual energy costs. The provision of fast public charging facilities could reduce peak electricity demand by 17GW and save an estimated £650 million annually. Although using hydrogen for heating and transport spreads the hydrogen network costs between homeowners and motorists, it is still estimated to be more costly overall compared to an all-electric scenario. Bio-energy electricity generation plants with carbon capture and storage are required to drive overall energy system emissions to net zero, utilisation of which is lowest when heating is electrified, and road transport consists of a mix of electric and hydrogen fuel-cell vehicles. The analysis demonstrates the need for an integrated systems approach to energy and transport policies and for coordination between national and local governments

Farmers’ reasoning behind the uptake of agroforestry practices: evidence from multiple case-studies across Europe

Potential benefits and costs of agroforestry practices have been analysed by experts, but few studies have captured farmers’ perspectives on why agroforestry might be adopted on a European scale. This study provides answers to this question, through an analysis of 183 farmer interviews in 14 case study systems in eight European countries. The study systems included high natural and cultural value agroforestry systems, silvoarable systems, high value tree systems, and silvopasture systems, as well as systems where no agroforestry practices were occurring. A mixed method approach combining quantitative and qualitative approaches was taken throughout the interviews. Narrative thematic data analysis was performed. Data collection proceeded until no new themes emerged. Within a given case study, i.e. the different systems in different European regions, this sampling was performed both for farmers who practice agroforestry and farmers who did not. Results point to a great diversity of agroforestry practices, although many of the farmers are not aware of the term or concept of agroforestry, despite implementing the practice in their own farms. While only a few farmers mentioned eligibility for direct payments in the CAP as the main reason to remove trees from their land, to avoid the reduction of the funded area, the tradition in the family or the region, learning from others, and increasing the diversification of products play the most important role in adopting or not agroforestry systems

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

TRAIL/Apo-2L has shown promise as an anti-glioma drug, based on investigations of TRAIL sensitivity in established glioma cell lines, but it is not known how accurately TRAIL signalling pathways of glioma cells in vivo are reproduced in these cell lines in vitro. To replicate as closely as possible the in vivo behaviour of malignant glioma cells, 17 early passage glioma cell lines and 5 freshly resected gliomas were exposed to TRAIL-based agents and/or chemotherapeutic drugs. Normal human hepatocytes and astrocytes and established glioma cell lines were also tested. Cross-linked TRAIL, but not soluble TRAIL, killed both normal cell types and cells from three tumours. Cells from only one glioma were killed by soluble TRAIL, although only inefficiently. High concentrations of cisplatin were lethal to glioma cells, hepatocytes and astrocytes. Isolated combinations of TRAIL and chemotherapy drugs were more toxic to particular gliomas than normal cells, but no combination was generally selective for glioma cells. This study highlights the widespread resistance of glioma cells to TRAIL-based agents, but suggests that a minority of high-grade glioma patients may benefit from particular combinations of TRAIL and chemotherapy drugs. In vitro sensitivity assays may help identify effective drug combinations for individual glioma patients

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

Background: Depression is common in individuals with diabetes. The present study is the first randomized controlled trial to test the efficacy of ω-3 ethyl-eicosapentaenoic acid (E-EPA) as adjuvant to antidepressant medication in the treatment of depression in adults with diabetes mellitus. Methods: In the VU University Medical Center, we conducted a 12-week, placebo-controlled, double-blind, parallel-group intervention study of E-EPA (1 g/day) versus placebo in 25 diabetes patients meeting DSM-IV criteria for major depressive disorder, who were already using antidepressant medication. The primary outcome was severity of depressive symptoms, assessed by the Montgomery Åsberg Depression Rating Scale (MADRS) at baseline and 12-week follow-up at two-weekly intervals. Blood samples were collected at baseline and at 12-week follow-up to determine EPA levels in erythrocyte membranes. Data were analyzed with ANOVA for repeated measures. Results: Thirteen participants were randomly assigned to E-EPA; 12 participants were given placebo. At 12-week follow-up, erythrocyte membranes from patients receiving E-EPA contained tripled levels of EPA, while no changes were noted in participants receiving placebo. In both groups, depressive symptoms significantly decreased over time (F = 21.14, p < 0.001), yet no significant differences were found between those treated with E-EPA versus placebo (F = 1.63, p = 0.17). Limitations: Although having sufficient study power, this study had a relatively small sample size. Small effects could not be detected, and dose-dependent effects could not be studied. Conclusions: No evidence was found for the efficacy of adding E-EPA to antidepressants in reducing depressive symptoms in diabetic patients with co-morbid depression. © 2009 Elsevier B.V. All rights reserved

Characterization of different fat depots in NAFLD using inflammation-associated proteome, lipidome and metabolome

Non-alcoholic fatty liver disease (NAFLD) is recognized as a liver manifestation of metabolic syndrome, accompanied with excessive fat accumulation in the liver and other vital organs. Ectopic fat accumulation was previously associated with negative effects at the systemic and local level in the human body. Thus, we aimed to identify and assess the predictive capability of novel potential metabolic biomarkers for ectopic fat depots in non-diabetic men with NAFLD, using the inflammation-associated proteome, lipidome and metabolome. Myocardial and hepatic triglycerides were measured with magnetic spectroscopy while function of left ventricle, pericardial and epicardial fat, subcutaneous and visceral adipose tissue were measured with magnetic resonance imaging. Measured ectopic fat depots were profiled and predicted using a Random Forest algorithm, and by estimating the Area Under the Receiver Operating Characteristic curves. We have identified distinct metabolic signatures of fat depots in the liver (TAG50:1, glutamate, diSM18:0 and CE20:3), pericardium (N-palmitoyl-sphinganine, HGF, diSM18:0, glutamate, and TNFSF14), epicardium (sphingomyelin, CE20:3, PC38:3 and TNFSF14), and myocardium (CE20:3, LAPTGF-beta 1, glutamate and glucose). Our analyses highlighted non-invasive biomarkers that accurately predict ectopic fat depots, and reflect their distinct metabolic signatures in subjects with NAFLD.Peer reviewe

Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus (SLE) - results from a nationwide cohort in Germany (GRAID)

ObjectiveThe objective of this article is to evaluate the safety and clinical outcome of rituximab treatment in systemic lupus erythematosus (SLE) patients refractory to standard of care therapy in a real-life setting in Germany. MethodsThe GRAID registry included patients with different autoimmune diseases who were given off-label treatment with rituximab. Data on safety and clinical response were collected retrospectively. In SLE patients, clinical parameters included tender and swollen joint counts, fatigue, myalgia, general wellbeing, Raynaud's and the SLEDAI index. Laboratory tests included dsDNA antibody titres, complement factors, hematologic parameters and proteinuria. Finally, the investigators rated their patients as non-, partial or complete responders based on clinical grounds. ResultsData from 85 SLE patients were collected, 69 female and 16 male, with a mean disease duration of 9.8 years. The mean follow-up period was 9.67.4 months, resulting in 66.8 patient years of observation. A complete response was reported in 37 patients (46.8%), partial response in 27 (34.2%), no response in 15 (19.0%). On average, major clinical as well as laboratory efficacy parameters improved substantially, with the SLEDAI decreasing significantly from 12.2 to 3.3 points. Concerning safety, one infusion reaction leading to discontinuation of treatment occurred. Infections were reported with a rate of 19.5 (including six severe infections) per 100 patient years. ConclusionWith the restrictions of a retrospective data collection, the results of this study confirm data of other registries, which suggest a favourable benefit-risk ratio of rituximab in patients with treatment-refractory SLE

Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus (SLE) - results from a nationwide cohort in Germany (GRAID)

ObjectiveThe objective of this article is to evaluate the safety and clinical outcome of rituximab treatment in systemic lupus erythematosus (SLE) patients refractory to standard of care therapy in a real-life setting in Germany. MethodsThe GRAID registry included patients with different autoimmune diseases who were given off-label treatment with rituximab. Data on safety and clinical response were collected retrospectively. In SLE patients, clinical parameters included tender and swollen joint counts, fatigue, myalgia, general wellbeing, Raynaud's and the SLEDAI index. Laboratory tests included dsDNA antibody titres, complement factors, hematologic parameters and proteinuria. Finally, the investigators rated their patients as non-, partial or complete responders based on clinical grounds. ResultsData from 85 SLE patients were collected, 69 female and 16 male, with a mean disease duration of 9.8 years. The mean follow-up period was 9.67.4 months, resulting in 66.8 patient years of observation. A complete response was reported in 37 patients (46.8%), partial response in 27 (34.2%), no response in 15 (19.0%). On average, major clinical as well as laboratory efficacy parameters improved substantially, with the SLEDAI decreasing significantly from 12.2 to 3.3 points. Concerning safety, one infusion reaction leading to discontinuation of treatment occurred. Infections were reported with a rate of 19.5 (including six severe infections) per 100 patient years. ConclusionWith the restrictions of a retrospective data collection, the results of this study confirm data of other registries, which suggest a favourable benefit-risk ratio of rituximab in patients with treatment-refractory SLE

Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome overwhelmingly progresses to ESRD. More than 30 monogenic genes have been identified to cause steroid-resistant nephrotic syndrome. We previously detected causative mutations using targeted panel sequencing in 30% of patients with steroid-resistant nephrotic syndrome. Panel sequencing has a number of limitations when compared with whole exome sequencing. We employed whole exome sequencing to detect monogenic causes of steroid-resistant nephrotic syndrome in an international cohort of 300 families. DESIGN, SETTING, PARTIIPANTS AND MEASUREMENTS: Three hundred thirty-five individuals with steroid-resistant nephrotic syndrome from 300 families were recruited from April of 1998 to June of 2016. Age of onset was restricted to <25 years of age. Exome data were evaluated for 33 known monogenic steroid-resistant nephrotic syndrome genes. RESULTS: In 74 of 300 families (25%), we identified a causative mutation in one of 20 genes known to cause steroid-resistant nephrotic syndrome. In 11 families (3.7%), we detected a mutation in a gene that causes a phenocopy of steroid-resistant nephrotic syndrome. This is consistent with our previously published identification of mutations using a panel approach. We detected a causative mutation in a known steroid-resistant nephrotic syndrome gene in 38% of consanguineous families and in 13% of nonconsanguineous families, and 48% of children with congenital nephrotic syndrome. A total of 68 different mutations were detected in 20 of 33 steroid-resistant nephrotic syndrome genes. Fifteen of these mutations were novel. NPHS1, PLCE1, NPHS2, and SMARCAL1 were the most common genes in which we detected a mutation. In another 28% of families, we detected mutations in one or more candidate genes for steroid-resistant nephrotic syndrome. CONCLUSIONS: Whole exome sequencing is a sensitive approach toward diagnosis of monogenic causes of steroid-resistant nephrotic syndrome. A molecular genetic diagnosis of steroid-resistant nephrotic syndrome may have important consequences for the management of treatment and kidney transplantation in steroid-resistant nephrotic syndrome