Circulating endothelial cell-derived extracellular vesicles mediate the acute phase response and sickness behaviour associated with CNS inflammation.

Brain injury elicits a systemic acute-phase response (APR), which is responsible for co-ordinating the peripheral immunological response to injury. To date, the mechanisms responsible for signalling the presence of injury or disease to selectively activate responses in distant organs were unclear. Circulating endogenous extracellular vesicles (EVs) are increased after brain injury and have the potential to carry targeted injury signals around the body. Here, we examined the potential of EVs, isolated from rats after focal inflammatory brain lesions using IL-1β, to activate a systemic APR in recipient naïve rats, as well as the behavioural consequences of EV transfer. Focal brain lesions increased EV release, and, following isolation and transfer, the EVs were sequestered by the liver where they initiated an APR. Transfer of blood-borne EVs from brain-injured animals was also enough to suppress exploratory behaviours in recipient naïve animals. EVs derived from brain endothelial cell cultures treated with IL-1β also activated an APR and altered behaviour in recipient animals. These experiments reveal that inflammation-induced circulating EVs derived from endothelial cells are able to initiate the APR to brain injury and are sufficient to generate the associated sickness behaviours, and are the first demonstration that EVs are capable of modifying behavioural responses

Immigrants in the labour market and beyond

I investigate the labour market performance of immigrants in the UK. In particular, I aim to advance understanding of the international transferability of qualifications, skills, and experience. I also discuss the roles of differential self-selection and labour market discrimination, and consider immigrant uptake of the native national identity. First, I examine the incidence and wage associations of over-education among migrants to the UK from the ‘A8’ EU accession countries of Central and Eastern Europe. I find that A8 immigrants face a substantially higher risk of over-education in the UK than other recent EU immigrants, and that this additional risk remains after taking account of observed characteristics. I argue that this result is driven by unobserved differences between the groups, arising from distinct self-selection processes associated with the institutional context of the EU accession. Second, I examine how qualifications and the origin of schooling and experience can help us to understand immigrant earnings, and, in particular, the difference between the wages paid to immigrants and natives with apparently similar human capital profiles. I show that accounting for the level of qualification held by immigrants, as well as the source and duration of schooling, causes conditional wage estimates to converge substantially with those of natives. Finally, I examine how variation in the original motives for migration can help us understand the labour market performance of immigrants, and their propensity to adopt the native national identity. On employment and wages, I find that those who originally came as work or student immigrants are the most successful, while family immigrants do less well, and refugees fare the worst. On national identity, I find that those who originally came as refugees and family immigrants are the most likely to identify as British, while work and student immigrants are the least

MINLO: Multi-scale improved NLO

In the present work we consider the assignment of the factorization and renormalization scales in hadron collider processes with associated jet production, at next-to-leading order (NLO) in perturbation theory. We propose a simple, definite prescription to this end, including Sudakov form factors to consistently account for the distinct kinematic scales occuring in such collisions. The scheme yields results that are accurate at NLO and, for a large class of observables, it resums to all orders the large logarithms that arise from kinematic configurations involving disparate scales. In practical terms the method is most simply understood as an NLO extension of the matrix element reweighting procedure employed in tree level matrix element-parton shower merging algorithms. By way of a proof-of-concept, we apply the method to Higgs and Z boson production in association with up to two jets.Comment: 27 pages, 17 figure

Neutron diffraction study of the magnetic order in NdMn2Ge1.6Si0.4

Here we report a detailed investigation of NdMn 2 Ge 1.6 Si 0.4 ; this forms part of our investigation of the magnetic order across the NdMn 2 Ge 2− x Si x (x = 0–2.0) series by magnetometry, x-ray diffraction and neutron diffraction over the temperature range 6–465 K. On decreasing the temperature from 465 K, NdMn 2 Ge 1.6 Si 0.4 exhibits four magnetic transitions: (i) from paramagnetism to intralayer antiferromagnetism AFl at T Intra N ~ 430 K; (ii) AFl to canted ferromagnetism Fmc at T Inter C ~ 330 K; (iii) Fmc to conical magnetic ordering of the Mn sublattice Fmi at T cc ~ 178 K and (iv) Fmi(Mn) to Fmi(Mn)+F(Nd) at T Nd C ~ 72 K. (c) 2011 IOP Publishing LT

Sample size calculations for cluster randomised controlled trials with a fixed number of clusters

Background\ud Cluster randomised controlled trials (CRCTs) are frequently used in health service evaluation. Assuming an average cluster size, required sample sizes are readily computed for both binary and continuous outcomes, by estimating a design effect or inflation factor. However, where the number of clusters are fixed in advance, but where it is possible to increase the number of individuals within each cluster, as is frequently the case in health service evaluation, sample size formulae have been less well studied. \ud \ud Methods\ud We systematically outline sample size formulae (including required number of randomisation units, detectable difference and power) for CRCTs with a fixed number of clusters, to provide a concise summary for both binary and continuous outcomes. Extensions to the case of unequal cluster sizes are provided. \ud \ud Results\ud For trials with a fixed number of equal sized clusters (k), the trial will be feasible provided the number of clusters is greater than the product of the number of individuals required under individual randomisation ($n_i$) and the estimated intra-cluster correlation ($\rho$). So, a simple rule is that the number of clusters ($\kappa$) will be sufficient provided: \ud \ud $\kappa$ > $n_i$ x $\rho$\ud \ud Where this is not the case, investigators can determine the maximum available power to detect the pre-specified difference, or the minimum detectable difference under the pre-specified value for power. \ud \ud Conclusions\ud Designing a CRCT with a fixed number of clusters might mean that the study will not be feasible, leading to the notion of a minimum detectable difference (or a maximum achievable power), irrespective of how many individuals are included within each cluster. \ud \u