Every student counts: promoting numeracy and enhancing employability

This three-year project investigated factors that influence the development of undergraduates’ numeracy skills, with a view to identifying ways to improve them and thereby enhance student employability. Its aims and objectives were to ascertain: the generic numeracy skills in which employers expect their graduate recruits to be competent and the extent to which employers are using numeracy tests as part of graduate recruitment processes; the numeracy skills developed within a diversity of academic disciplines; the prevalence of factors that influence undergraduates’ development of their numeracy skills; how the development of numeracy skills might be better supported within undergraduate curricula; and the extra-curricular support necessary to enhance undergraduates’ numeracy skills

The Psychosocial Impact of Neurobehavioral Disability

Neurobehavioural disability (NBD) comprises elements of executive and attentional dysfunction, poor insight, problems of awareness and social judgement, labile mood, altered emotional expression, and poor impulse control, any or all of which can have a serious impact upon a person’s decision-making and capacity for social independence. The aim of this narrative review is to explore some of the more intrusive forms of NBD that act as obstacles to psychosocial outcome to act as a frame of reference for developing effective rehabilitation interventions. Special consideration is given to the psychosocial impact of three core forms of NBD: a failure of social cognition, aggressive behaviour, and problems of drive/motivation. Consideration is also given to the developmental implications of sustaining a brain injury in childhood or adolescence, including its impact on maturational and social development and subsequent effects on long-term psychosocial behaviour

Uncertainty quantification and weak approximation of an elliptic inverse problem

We consider the inverse problem of determining the permeability from the pressure in a Darcy model of flow in a porous medium. Mathematically the problem is to find the diffusion coefficient for a linear uniformly elliptic partial differential equation in divergence form, in a bounded domain in dimension $d \le 3$, from measurements of the solution in the interior. We adopt a Bayesian approach to the problem. We place a prior random field measure on the log permeability, specified through the Karhunen-Lo\`eve expansion of its draws. We consider Gaussian measures constructed this way, and study the regularity of functions drawn from them. We also study the Lipschitz properties of the observation operator mapping the log permeability to the observations. Combining these regularity and continuity estimates, we show that the posterior measure is well-defined on a suitable Banach space. Furthermore the posterior measure is shown to be Lipschitz with respect to the data in the Hellinger metric, giving rise to a form of well-posedness of the inverse problem. Determining the posterior measure, given the data, solves the problem of uncertainty quantification for this inverse problem. In practice the posterior measure must be approximated in a finite dimensional space. We quantify the errors incurred by employing a truncated Karhunen-Lo\`eve expansion to represent this meausure. In particular we study weak convergence of a general class of locally Lipschitz functions of the log permeability, and apply this general theory to estimate errors in the posterior mean of the pressure and the pressure covariance, under refinement of the finite dimensional Karhunen-Lo\`eve truncation.Comment: 19 pages, 0 figures, submitted to SIAM Journal on Numerical Analysi

Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis

OBJECTIVE: To determine whether rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, or carriage of shared epitope (SE) and PTPN22 genetic susceptibility variants predict response to therapy in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) agents. METHODS: UK-wide multicentre collaborations were established to recruit a large cohort of patients treated with anti-TNF drugs for RA. Serum RF, anti-CCP antibody and SE status were determined using commercially available kits. PTPN22 R620W genotyping was performed by Sequenom MassArray. Linear regression analyses were performed to investigate the role of these four factors in predicting response to treatment by 6 months, defined as the absolute change in 28-joint Disease Activity Score (DAS28). RESULTS: Of the 642 patients analysed, 46% received infliximab, 43% etanercept and 11% adalimumab. In all, 89% and 82% of patients were RF and anti-CCP positive, respectively. Patients that were RF negative had a 0.48 (95% CI 0.08 to 0.87) greater mean improvement in DAS28 compared to patients that were RF positive. A better response was also seen among patients that were anti-CCP negative. No association was demonstrated between drug response and SE or PTPN22 620W carriage. CONCLUSION: The presence of RF or anti-CCP antibodies was associated with a reduced response to anti-TNF drugs. However, these antibodies only account for a small proportion of the variance in treatment response. It is likely that genetic factors will contribute to treatment response, but these do not include the well established RA susceptibility loci, SE and PTPN22

Clostridium perfringens epsilon toxin mutant Y30A-Y196A as a recombinant vaccine candidate against enterotoxemia

Epsilon toxin (Etx) is a β-pore-forming toxin produced by Clostridium perfringens toxinotypes B and D and plays a key role in the pathogenesis of enterotoxemia, a severe, often fatal disease of ruminants that causes significant economic losses to the farming industry worldwide. This study aimed to determine the potential of a site-directed mutant of Etx (Y30A-Y196A) to be exploited as a recombinant vaccine against enterotoxemia. Replacement of Y30 and Y196 with alanine generated a stable variant of Etx with significantly reduced cell binding and cytotoxic activities in MDCK.2 cells relative to wild type toxin (>430-fold increase in CT50) and Y30A-Y196A was inactive in mice after intraperitoneal administration of trypsin activated toxin at 1000× the expected LD50 dose of trypsin activated wild type toxin. Moreover, polyclonal antibody raised in rabbits against Y30A-Y196A provided protection against wild type toxin in an in vitro neutralisation assay. These data suggest that Y30A-Y196A mutant could form the basis of an improved recombinant vaccine against enterotoxemia

Worldwide insect declines: An important message, but interpret with caution.

A recent paper claiming evidence of global insect declines achieved huge media attention, including claims of "insectaggedon" and a "collapse of nature." Here, we argue that while many insects are declining in many places around the world, the study has important limitations that should be highlighted. We emphasise the robust evidence of large and rapid insect declines present in the literature, while also highlighting the limitations of the original study

Assessing walking posture with geometric morphometrics: Effects of rearing environment in pigs

International audienceRearing social animals like pigs in isolation from conspecifics can have consequences on behaviour and physiology. The aim of this experiment was to determine whether rearing conditions affect body postures. We adapted a method for quantitative evaluation of postures based on geometric morphometrics, developed in horses, for pigs and applied it in different conditions. Forty eight 75-day old females were reared either alone in 2.25 m2 pens (IH, N = 24 animals and 4 groups) or in groups of four in 4.64 m2 pens (GH, N = 24) for two weeks. They were habituated to human handling (stroking, speaking) and marking on their backs every day, and tested individually once a day for 10 min in a corridor outside the home pen during the two subsequent weeks. We observed their behaviour and posture during the first exposure to the test (novelty), and the fourth and fifth (after habituation). On the sixth and seventh tests, a familiar stockperson was present in the corridor (human presence). Before each test, the animals were marked with seven landmarks along their length, corresponding to anatomical points and easily located. An experimenter took pictures of the animals walking along the corridor, and these pictures were transferred to tps software for analysis. GH animals were more often active in the rearing pen than IH (median (IQ) 15% of observations [12-20%] versus 2% [0-13%]; P < 0.05). All animals except one IH initiated contact with the handler during the last sessions of handling (Fisher's exact test, ns). Principal Component Analyses revealed significant effects of rearing and testing conditions on pigs’ behaviour and posture. Novelty led to fewer vocalisations and more exploration for IH than GH animals (P < 0.05), but there were no differences between treatments after habituation to the testing situation. The backs of IH animals were more rounded than those of GH (P < 0.05; dimension 1 of PCA), independently of the test condition. Human presence had no effect on posture. In conclusion, the method based on geometric morphometrics that we developed to study pig posture detected variations in walking posture in pigs associated with rearing conditions. Postures might reflect affective states in pigs, as shown in other species, but further studies are needed to verify thi

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes