Experiences of first-generation scholars at a highly selective UK university

Targets set by the UK Office for Students require highly academically selective UK universities to enrol a greater percentage of students identified as least likely to participate in higher education. Such students are typically at a disadvantage in terms of levels of academic preparedness and economic, cultural and social capital. Drawing on 18 interviews with first generation students at Durham University, we identify five sites of pressure: developing a sense of belonging within the terms of an elite university culture; engagement in student social activities; financial worries; concerns about academic progress, and self-transformation. Based on these insights, we argue that support for first generation scholars will require that universities recognise and redress elitist cultures that discourage applications from prospective first-generation scholars ultimately ensuring those who do enrol have the best educational and all-round experience

Early reconstitution of effector memory CD4+ CMV-specific T cells protects against CMV reactivation following allogeneic SCT.

Reactivation of CMV is a common complication following allogeneic haematopoietic SCT and is associated with significant morbidity and mortality. The relative importance of the CD4+ and CD8+ components of the CMV-specific immune response in protection from reactivation is unclear. The CMV-specific CD4+ and CD8+ immune response was measured at serial time points in 32 patients following allogeneic HSCT. Intracellular cytokine staining following CMV lysate stimulation and HLA-peptide tetramers were used to determine CMV-specific CD4+ and CD8+ responses, respectively. A deficient CMV-specific CD4+ T-cell immune response within the first 30-50 days post transplant was associated with high risk of viral reactivation. Patients with combined impairment of the CD4+ and CD8+ immune response within the first 100 days were susceptible to late viral reactivation. The frequency of CMV-specific CD4+ T cells correlated with CMV-specific CD8+ T cells, comprising 10% of the whole T-cell repertoire. Early CMV-specific CD4+ T-cell reconstitution was dominated by effector memory cells with normal levels of IL-2 resuming 6 months following transplantation. In summary, both CD4 and CD8 CMV-specific immune reconstitution is required for protection from recurrent activation. Measurement of the magnitude of the CMV-specific CD4+ immune response is useful in managing viral reactivation following HSCT

Development of novel bioassays to detect soluble and aggregated Huntingtin proteins on three technology platforms

Huntington’s disease is caused by a CAG / polyglutamine repeat expansion. Mutated CAG repeats undergo somatic instability, resulting in tracts of several hundred CAGs in the brain; and genetic modifiers of Huntington’s disease have indicated that somatic instability is a major driver of age of onset and disease progression. As the CAG repeat expands, the likelihood that exon 1 does not splice to exon 2 increases, resulting in two transcripts that encode full-length huntingtin protein, as well as the highly pathogenic and aggregation-prone exon 1 huntingtin protein. Strategies that target the huntingtin gene or transcripts are a major focus of therapeutic development. It is essential that the levels of all isoforms of huntingtin protein can be tracked, to better understand the molecular pathogenesis, and to assess the impact of huntingtin protein-lowering approaches in preclinical studies and clinical trials. Huntingtin protein bioassays for soluble and aggregated forms of huntingtin protein are in widespread use on the homogeneous time-resolved fluorescence and Meso Scale Discovery platforms, but these do not distinguish between exon 1 huntingtin protein and full-length huntingtin protein. In addition, they are frequently used to quantify huntingtin protein levels in the context of highly expanded polyglutamine tracts, for which appropriate protein standards do not currently exist. Here, we set out to develop novel huntingtin protein bioassays to ensure that all soluble huntingtin protein isoforms could be distinguished. We utilized the zQ175 Huntington’s disease mouse model that has ∼190 CAGs, a CAG repeat size for which protein standards are not available. Initially, 30 combinations of six antibodies were tested on three technology platforms: homogeneous time-resolved fluorescence, amplified luminescent proximity homogeneous assay and Meso Scale Discovery, and a triage strategy was employed to select the best assays. We found that, without a polyglutamine-length-matched standard, the vast majority of soluble mutant huntingtin protein assays cannot be used for quantitative purposes, as the highly expanded polyglutamine tract decreased assay performance. The combination of our novel assays, with those already in existence, provides a tool-kit to track: total soluble mutant huntingtin protein, soluble exon 1 huntingtin protein, soluble mutant huntingtin protein (excluding the exon 1 huntingtin protein) and total soluble full-length huntingtin protein (mutant and wild type). Several novel aggregation assays were also developed that track with disease progression. These selected assays can be used to compare the levels of huntingtin protein isoforms in a wide variety of mouse models of Huntington’s disease and to determine how these change in response to genetic or therapeutic manipulations

The Emergence of Group Potency and Its Implications for Team Effectiveness

Much of the previous research on the emergence of team-level constructs has overlooked their inherently dynamic nature by relying on static, cross-sectional approaches. Although theoretical arguments regarding emergent states have underscored the importance of considering time, minimal work has examined the dynamics of emergent states. In the present research, we address this limitation by investigating the dynamic nature of group potency, a crucial emergent state, over time. Theory around the “better-than-average” effect (i.e., an individual’s tendency to think he/she is better than the average person) suggests that individuals may have elevated expectations of their group’s early potency, but may decrease over time as team members interact gain a more realistic perspective of their group’s potential. In addition, as members gain experience with each other, they will develop a shared understanding of their team’s attributes. The current study used latent growth and consensus emergence modeling to examine how potency changes over time, and its relation with team effectiveness. Further, in accordance with the input-process-output framework, we investigated how group potency mediated the relations between team-level compositions of conscientiousness and extraversion and team effectiveness. We collected data at three time points throughout an engineering design course from 337 first-year engineering students that comprised 77 project teams. Results indicated that group potency decreased over time in a linear trend, and that group consensus increased over time. We also found that teams’ initial potency was a significant predictor of team effectiveness, but that change in potency was not related to team effectiveness. Finally, we found that the indirect effect linking conscientiousness to effectiveness, through initial potency, was supported. Overall, the current study offers a unique understanding of the emergence of group potency, and facilitate a number theoretical and practical implications, which are discussed

EVerT: Cryotherapy versus salicylic acid for the treatment of verrucae - a randomised controlled trial

OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of cryotherapy using liquid nitrogen versus patient daily self-treatment with 50% salicylic acid for the treatment of verrucae (plantar warts). DESIGN: A multicentre, pragmatic, open, two-armed randomised controlled trial with an economic evaluation. Randomisation was simple, with the allocation sequence generated by a computer in a 1 : 1 ratio. SETTING: Podiatry clinics, university podiatry schools and primary care in England, Scotland and Ireland. PARTICIPANTS: Patients were eligible if they presented with a verruca which, in the opinion of the health-care professional, was suitable for treatment with both salicylic acid and cryotherapy, and were aged 12 years and over. INTERVENTIONS: Cryotherapy using liquid nitrogen delivered by a health-care professional compared with daily patient self-treatment with 50% salicylic acid (Verrugon, William Ransom & Son Plc, Hitchin, UK) for a maximum of 8 weeks. MAIN OUTCOME MEASURES: The primary outcome was complete clearance of all verrucae at 12 weeks. Secondary outcomes were complete clearance of all verrucae at 12 weeks, controlling for age, whether or not the verrucae had been previously treated and type of verrucae, with a second model to explore the effect of patient preferences, time to clearance of verrucae, clearance of verrucae at 6 months, number of verrucae at 12 weeks and patient satisfaction with the treatment RESULTS: In total, 240 eligible patients were recruited, with 117 patients allocated to the cryotherapy group and 123 to the salicylic acid group. There was no evidence of a difference in clearance rates between the treatment groups in the primary outcome [17/119 (14.3%) in the salicylic acid group vs 15/110 (13.6%) in the cryotherapy group; p = 0.89]. The results of the study did not change when controlled for age, whether or not the verrucae had been previously treated and type of verrucae, or when patient preferences were explored. There was no evidence of a difference in time to clearance of verrucae between the two groups [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.51 to 1.25; p = 0.33] or in the clearance of verrucae at 6 months (33.7% cryotherapy vs 30.5% salicylic acid). There was no evidence of a difference in the number of verrucae at 12 weeks between the two groups (incidence rate ratio 1.08, 95% CI 0.81 to 1.43; p = 0.62). Nineteen participants reported 28 adverse events, 14 in each group, with two treatment-related non-serious adverse events in the cryotherapy group. Cryotherapy was also associated with higher mean costs per additional healed patient (£101.17, 95% bias-corrected and accelerated CI £85.09 to £117.26). The probability of cryotherapy being cost-effective is 40% for a range of willingness-to-pay thresholds of £15,000-30,000 per patient healed. CONCLUSIONS: There is no evidence for a difference in terms of clearance of verrucae between cryotherapy and salicylic acid (at both 12 weeks and 6 months), number of verrucae at 12 weeks and time to clearance of verrucae. Cryotherapy was associated with higher mean costs per additional healed patient compared with salicylic acid. TRIAL REGISTRATION:Current Controlled Trials ISRCTN18994246. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 32. See the HTA programme website for further project information