Towards a Standard Approach for Wear Testing of Wheel and Rail Materials

Examination of the literature for wear testing methodologies for wheel and rail material reveals that while only a few different techniques have been used there is a wide variety in exactly how the tests have been conducted and the resulting data reported. This makes comparison of the data very difficult. This work, carried out as part of the International Collaborative Research Initiative (ICRI) which is aiming to bring together wheel/rail interface researchers from across the world to collate data and knowledge to try to solve some of the common problems that are faced, has examined the different approaches used and attempted to pull together all the good practice used into a test specification for future twin disc testing for wheel and rail materials. Adoption of the method will allow data to be compared reliably and eventually enable data to be compiled into wear maps to use as input, for example, to multi-body dynamics simulation wear prediction tools

Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol

Large changes in Great Britain’s vegetation and agricultural land-use predicted under unmitigated climate change

This is the author accepted manuscript. The final version is available from IOP Publishing via the DOI in this recordData availability: The parameter values used for JULES is available from the suite u-ao645 and branch ‘full_UK’ on the Rosie repository: https://code.metoffice.gov.uk/trac/roses-u (registration required). The data that support the findings of this study are openly available at DOI.The impact of climate change on vegetation including agricultural production has been the focus of many studies. Climate change is expected to have heterogeneous effects across locations globally, and the diversity of land uses characterising Great Britain (GB) presents a unique opportunity to test methods for assessing climate change effects and impacts. GB is a relatively cool and damp country, hence, the warmer and generally drier growing season conditions projected for the future are expected to increase arable production. Here we use state-of-the-art, kilometre-scale climate change scenarios to drive a land surface model (JULES; Joint UK Land Environment Simulator) and an ECOnometric AGricultural land use model (ECO-AG). Under unmitigated climate change, by the end of the century, the growing season in GB is projected to get >5°C warmer and 140 mm drier on average. Rising levels of atmospheric CO2 are predicted to counteract the generally negative impacts of climate change on vegetation productivity in JULES. Given sufficient precipitation, warming favours higher value arable production over grassland agriculture, causing a predicted westward expansion of arable farming in ECO-AG. However, drying in the East and Southeast, without any CO2 fertilisation effect, is severe enough to cause a predicted reversion from arable to grassland farming. Irrigation, if implemented, could maintain this land in arable production. However, the predicted irrigation demand of ~200 mm (per growing season) in many locations is comparable to annual predicted runoff, potentially demanding large-scale redistribution of water between seasons and/or across the country. The strength of the CO2 fertilisation effect emerges as a crucial uncertainty in projecting the impact of climate change on GB vegetation, especially farming land-use decisions.Natural Environment Research Council (NERC)Joint UK BEIS/Defra Met Office Hadley Centre Climate Programm

Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extremity osteosarcoma treated with doxorubicin and cisplatin: a report from the European Osteosarcoma Intergroup.

Chemotherapy-induced toxicity is an independent prognostic indicator in several cancers. We aimed to determine whether toxicity was related to survival and histological response in high-grade localised extremity osteosarcoma. We undertook a retrospective analysis of patients treated within three consecutive randomised controlled trials (RCTs) of the European Osteosarcoma Intergroup

Effect of smoking on physical and cognitive capability in later life: a multicohort study using observational and genetic approaches

Objectives: The observed associations between smoking and functional measures at older ages are vulnerable to bias and confounding. Mendelian randomisation (MR) uses genotype as an instrumental variable to estimate unconfounded causal associations. We conducted a meta-analysis of the observational associations and implemented an MR approach using the smoking-related single nucleotide polymorphism rs16969968 to explore their causal nature. Setting: 9 British cohorts belonging to the HALCyon collaboration. Participants: Individual participant data on N=26 692 individuals of European ancestry (N from earliest phase analysed per study) of mean ages 50-79 years were available for inclusion in observational meta-analyses of the primary outcomes. Primary outcomes: Physical capability, cognitive capability and cognitive decline. The smoking exposures were cigarettes per day, current versus ex-smoker, current versus never smoker and ever versus never smoker. Results: In observational analyses current and ever smoking were generally associated with poorer physical and cognitive capability. For example, current smokers had a general fluid cognition score which was 0.17 z-score units (95% CI -0.221 to -0.124) lower than ex-smokers in cross-sectional analyses. Current smokers had a walk speed which was 0.25 z-score units lower than never smokers (95% CI -0.338 to -0.170). An MR instrumental variable approach for current versus ex-smoker and number of cigarettes smoked per day produced CIs which neither confirmed nor refuted the observational estimates. The number of genetic associations stratified by smoking status were consistent with type I error. Conclusions: Our observational analysis supports the hypothesis that smoking is detrimental to physical and cognitive capability. Further studies are needed for a suitably powered MR approach

Distinct Binding and Immunogenic Properties of the Gonococcal Homologue of Meningococcal Factor H Binding Protein

Neisseria meningitidis is a leading cause of sepsis and meningitis. The bacterium recruits factor H (fH), a negative regulator of the complement system, to its surface via fH binding protein (fHbp), providing a mechanism to avoid complement-mediated killing. fHbp is an important antigen that elicits protective immunity against the meningococcus and has been divided into three different variant groups, V1, V2 and V3, or families A and B. However, immunisation with fHbp V1 does not result in cross-protection against V2 and V3 and vice versa. Furthermore, high affinity binding of fH could impair immune responses against fHbp. Here, we investigate a homologue of fHbp in Neisseria gonorrhoeae, designated as Gonococcal homologue of fHbp (Ghfp) which we show is a promising vaccine candidate for N. meningitidis. We demonstrate that Gfhp is not expressed on the surface of the gonococcus and, despite its high level of identity with fHbp, does not bind fH. Substitution of only two amino acids in Ghfp is sufficient to confer fH binding, while the corresponding residues in V3 fHbp are essential for high affinity fH binding. Furthermore, immune responses against Ghfp recognise V1, V2 and V3 fHbps expressed by a range of clinical isolates, and have serum bactericidal activity against N. meningitidis expressing fHbps from all variant groups