Change management - practising what we teach: successfully engaging international students in the teaching, learning & assessment process

In this article we review processes of change in a module whose subject matter is change management. The module attracts mainly international students, and has suffered from uneven student engagement and performance. We will recount how a Teaching Enhancement and Student Success (TESS) project was used to inform our attempts to improve engagement and performance. Bearing in mind the origins of action research as part of Kurt Lewin‟s approach to planned change, we will use the four different elements of Lewin‟s work to reflect on the challenges we have been grappling with. The article will highlight different approaches to action research, which are linked to different aspirations as to the scope of change

Deposition of organic thin films by plasma and photochemical techniques

The work detailed in this thesis concerns organic thin films synthesised either using R.F. inductively coupled plasmas excited in unsaturated monomers containing either fluorine or a nitrile group, or else irradiating the said monomers in vacuo using ultraviolet light. The effect of the following parameters on the composition and structure of the resultant films was determined using ESCA/XPS : a) power input to the R.F. plasma system, b) photon flux during UV irradiation, c) monomer type (including structural isomerism), and d) monomer flow rate. Relative system deposition rates were rationalised in terms of Yasuda's parameter, W/FM, which was found to hold true qualitatively, if not quantitatively. Introduction of halogen vapour to the plasma system in the presence of nitrile monomers physically decreased the glow volume. Analysis by ESCA and UV absorption spectroscopy revealed the presence of ionic halogen species in the resultant films. An overall decrease in deposition rate of the system was also observed. A similar result for the latter was seen for UV irradiation in the presence of iodine. The results were rationalised by assigning a free radical mechanism for both plasma and photochemical film deposition which is inhibited by halogens. Films formed by irradiation at &gt;200 nm were found to have differing chemical compositions compared to those obtained in the vacuum ultraviolet (<200 nm). This result was attributed to the differing photochemistries occurring in the two wavelength regions. Reference to the gas-phase photochemical literature enabled identification of the likely intermediates and term states involved, including 1,1 and 1,2 molecular elimination from ethylenic monomers in the vacuum UV to give the respective ethynes, together with secondary photolysis products. Consequently a mechanism for surface photopolymerisation was outlined which was compared with that proposed for plasma polymerisation, both of which involve vibrationally excited ground states for the monomers studied

What is a sustainable level of CO2 emissions from transport activity in the UK in 2050?

The paper reports on the development of UK transport targets for CO2 emissions for 2050. Five key studies containing future carbon emissions scenarios for the UK were used to establish targets for overall reductions in emissions to achieve stabilisation at 550 ppm and 450 ppm of atmospheric CO2. Two approaches were used to consider the proportion of total emissions that would be attributable to transport in the future: 26% of total emissions as now and an increase to 41% of total emissions in line with forecasts. The overall targets and expected contributions from transport were used to derive target emissions for the transport sector to be achieved by 2050, which ranged from 8.2 MtC to 25.8 MtC. Even the weakest of these targets represents a considerable reduction from current emissions levels

TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits

Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3 x 10(-21)), A928V (rs35018800, OR = 0.53, P = 1.2 x 10(-9)), and I684S (rs12720356, OR = 0.86, P = 4.6 x 10(-7)). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6 x 10(-18)), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; P(omnibus) = 0.005). Finally, in a phenome-wide association study (PheWAS) assessing \u3e500 phenotypes using electronic medical records (EMR) in \u3e29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases

A Phase 2a cohort expansion study to assess the safety, tolerability, and preliminary efficacy of CXD101 in patients with advanced solid-organ cancer expressing HR23B or lymphoma.

BACKGROUND: This Phase 2a dose expansion study was performed to assess the safety, tolerability and preliminary efficacy of the maximum tolerated dose of the oral histone de-acetylase (HDAC) inhibitor CXD101 in patients with relapsed / refractory lymphoma or advanced solid organ cancers and to assess HR23B protein expression by immunohistochemistry as a biomarker of HDAC inhibitor sensitivity. METHODS: Patients with advanced solid-organ cancers with high HR23B expression or lymphomas received CXD101 at the recommended phase 2 dose (RP2D). Key exclusions: corrected QT > 450 ms, neutrophils  1. Baseline HR23B expression was assessed by immunohistochemistry. RESULTS: Fifty-one patients enrolled between March 2014 and September 2019, 47 received CXD101 (19 solid-organ cancer, 28 lymphoma). Thirty-four patients received ≥80% RP2D. Baseline characteristics: median age 57.4 years, median prior lines 3, male sex 57%. The most common grade 3-4 adverse events were neutropenia (32%), thrombocytopenia (17%), anaemia (13%), and fatigue (9%) with no deaths on CXD101. No responses were seen in solid-organ cancers, with disease stabilisation in 36% or patients; the overall response rate in lymphoma was 17% with disease stabilisation in 52% of patients. Median progression-free survival was 1.2 months (95% confidence interval (CI) 1.2-5.4) in solid-organ cancers and 2.6 months (95%CI 1.2-5.6) in lymphomas. HR23B status did not predict response. CONCLUSIONS: CXD101 showed acceptable tolerability with efficacy seen in Hodgkin lymphoma, T-cell lymphoma and follicular lymphoma. Further studies assessing combination approaches are warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01977638 . Registered 07 November 2013

Loci associated with N-glycosylation of human IgG are not associated with rheumatoid arthritis: a Mendelian randomisation study

Objectives: A recent study identified 16 genetic variants associated with N-glycosylation of human IgG. Several of the genomic regions where these single nucleotide polymorphisms (SNPs) reside have also been associated with autoimmune disease (AID) susceptibility, suggesting there may be pleiotropy (genetic sharing) between loci controlling both N-glycosylation and AIDs. We investigated this by testing variants associated with levels of IgG N-glycosylation for association with rheumatoid arthritis (RA) susceptibility using a Mendelian randomisation study, and testing a subset of these variants in a less well-powered study of treatment response and severity. Methods: SNPs showing association with IgG N-glycosylation were analysed for association with RA susceptibility in 14 361 RA cases and 43 923 controls. Five SNPs were tested for association with response to anti-tumour necrosis factor (TNF) therapy in 1081 RA patient samples and for association with radiological disease severity in 342 patients. Results: Only one SNP (rs9296009) associated with N-glycosylation showed an association (p=6.92×10–266) with RA susceptibility, although this was due to linkage disequilibrium with causal human leukocyte antigen (HLA) variants. Four regions of the genome harboured SNPs associated with both traits (shared loci); although statistical analysis indicated that the associations observed for the two traits are independent. No SNPs showed association with response to anti-TNF therapy. One SNP rs12342831 was modestly associated with Larsen score (p=0.05). Conclusions: In a large, well-powered cohort of RA patients, we show SNPs driving levels of N-glycosylation have no association with RA susceptibility, indicating colocalisation of associated SNPs are not necessarily indicative of a shared genetic background or a role for glycosylation in disease susceptibility

Achieving consensus on psychosocial and physical rehabilitation management for people living with kidney disease

From Crossref journal articles via Jisc Publications RouterHistory: epub 2023-05-19, issued 2023-05-19Article version: AMPublication status: PublishedPelagia Koufaki - ORCID: 0000-0002-1406-3729 https://orcid.org/0000-0002-1406-3729Background People living with chronic kidney disease (CKD) need to be able to live well with their condition. The provision of psychosocial interventions (psychological, psychiatric, and social care) and physical rehabilitation management is variable across England, as well as the rest of the United Kingdom. There is a need for clear recommendations for standards of psychosocial and physical rehabilitation care for people living with CKD, and guidance for the commissioning and measurement of these services. The NHS England Renal Services Transformation Programme (RSTP) supported a programme of work and modified Delphi process to address the management of psychosocial and physical rehabilitation care as part of a larger body of work to formulate a comprehensive commissioning toolkit for renal care services across England. We sought to achieve expert consensus regarding the psychosocial and physical rehabilitation management of people living with CKD in England and the rest of the UK. Method A Delphi consensus method was used to gather and refine expert opinions of senior members of the kidney multi-disciplinary team (MDT) and other key stakeholders in the UK. An agreement was sought on 16 statements reflecting aspects of psychosocial and physical rehabilitation management for people living with CKD. Results Twenty-six expert practitioners and other key stakeholders, including lived experience representatives, participated in the process. The consensus (&amp;gt;80% affirmative votes) amongst the respondents for all 16 statements was high. Nine recommendation statements were discussed and refined further to be included in the final iteration of the ‘Systems’ section of the NHS England RSTP commissioning toolkit. These priority recommendations reflect pragmatic solutions that can be implemented in renal care and include recommendations for a holistic well-being assessment for all people living with CKD who are approaching dialysis, or who are at listing for kidney transplantation, which includes the use of validated measurement tools to assess the need for further intervention in psychosocial and physical rehabilitation management. It is recommended that the scores from these measurement tools be included in the NHS England Renal Data Dashboard. There was also a recommendation for referral as appropriate to NHS Talking therapies, psychology, counselling or psychotherapy, social work or liaison psychiatry for those with identified psychosocial needs. The use of digital resources was recommended to be used in addition to face-to-face care to provide physical rehabilitation, and all healthcare professionals should be educated to recognise psychosocial and physical rehabilitation needs and refer/sign-post people with CKD to appropriate services. Conclusion There was high consensus amongst senior members of the kidney MDT and other key stakeholders, including those with lived experience, in the UK on all aspects of the psychosocial and physical rehabilitation management of people living with CKD. The results of this process will be used by NHS England to inform the ‘Systems’ section of the commissioning toolkit and data dashboard and to inform the National Standards of Care for people living with CKD.inpressinpres