10 Challenges 4 Solutions 1 Shared Set of Values

Group 1: Re-engineering governance models for effective partnershipsBreakout sessions #1: Challenges and new paradigms under focuspublished_or_final_versio

Leadership and Management and the challenges facing the Modern University: Reflections, Challenges and Values

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The Future University and International Collaboration

Keynote SpeechConference Theme: Connecting Asia - preparing higher education to meet the demands of the 21st centurypublished_or_final_versio

From Glam to Gaga – Reflections on the changing management culture in UK Universities

I began my career in the late seventies when Glam Rock was beginning to give way to Punk and life was simpler, resources plentiful, letter writing an art and administrators knew and remained in their place. As the New Romantics of the early eighties gave way to the Dance Music of the nineties so traditional administrative values were eclipsed by a new managerial culture in which Universities sought to import the values of post Thatcher capitalism. With the advent of reality TV shows and the inexorable rise of The X Factor the new Century saw the boardroom give way to a form of popular accountability with its focus on transparency, value for money, freedom of information and a fear of failure. And now in 2010 as administrations, and indeed universities, face an uncertain future I pose the question will it be Lady Gaga or Susan Boyle?published_or_final_versio

Structure of Spherulites in Insulin, β-Lactoglobulin, and Amyloid β

Under denaturing conditions such as low pH and elevated temperatures, proteins in vitro can misfold and aggregate to form long rigid rods called amyloid fibrils; further self-assembly can lead to larger structures termed spherulites. Both of these aggregates resemble amyloid tangles and plaques associated with Alzheimer’s disease in vivo. The ability to form such aggregates in a multitude of different proteins suggests that it is a generic ability in their mechanism to form. Little is known about the structure of these large spherulites ranging from 5 to 100 microns and whether they can reproducibly form in amyloid β (1-40) (Aβ40), a 40-amino acid residue peptide, which is one of the major components of Alzheimer’s amyloid deposits. Here, we show that spherulites can readily form in Aβ40 under certain monomerization and denaturing conditions. Using polarized and nonpolarized Raman spectroscopy, we analyzed the secondary structure of spherulites formed from three different proteins: insulin, β-lactoglobulin (BLG), and Aβ40. Visually, these spherulites have a characteristic “Maltese Cross” structure under crossed polarizers through an optical microscope. However, our results indicate that insulin and Aβ40 spherulites have similar core structures consisting mostly of random coils with radiating fibrils, whereas BLG mostly contains β-sheets and fibrils that are likely to be spiraling from the core to the edge

Penetrance and expressivity of mitochondrial variants in a large clinically unselected population

\ua9 The Author(s) 2023. Published by Oxford University Press. Whole genome sequencing (WGS) from large clinically unselected cohorts provides a unique opportunity to assess the penetrance and expressivity of rare and/or known pathogenic mitochondrial variants in population. Using WGS from 179 862 clinically unselected individuals from the UK Biobank, we performed extensive single and rare variant aggregation association analyses of 15 881 mtDNA variants and 73 known pathogenic variants with 15 mitochondrial disease-relevant phenotypes. We identified 12 homoplasmic and one heteroplasmic variant (m.3243A>G) with genome-wide significant associations in our clinically unselected cohort. Heteroplasmic m.3243A>G (MAF = 0.0002, a known pathogenic variant) was associated with diabetes, deafness and heart failure and 12 homoplasmic variants increased aspartate aminotransferase levels including three low-frequency variants (MAF ~0.002 and beta~0.3 SD). Most pathogenic mitochondrial disease variants (n = 66/74) were rare in the population (<1:9000). Aggregated or single variant analysis of pathogenic variants showed low penetrance in unselected settings for the relevant phenotypes, except m.3243A>G. Multi-system disease risk and penetrance of diabetes, deafness and heart failure greatly increased with m.3243A>G level ≥ 10%. The odds ratio of these traits increased from 5.61, 12.3 and 10.1 to 25.1, 55.0 and 39.5, respectively. Diabetes risk with m.3243A>G was further influenced by type 2 diabetes genetic risk. Our study of mitochondrial variation in a large-unselected population identified novel associations and demonstrated that pathogenic mitochondrial variants have lower penetrance in clinically unselected settings. m.3243A>G was an exception at higher heteroplasmy showing a significant impact on health making it a good candidate for incidental reporting

Pneumatic compression devices for in-home management of lymphedema: two case reports

The two patients in this case series had experienced long-term difficulty controlling lymphedema at home. Both patients had used numerous home therapies, including older-generation intermittent pneumatic compression devices, without success. The Flexitouch® system, an advanced pneumatic device, was prescribed to assist them with in-home efforts by providing therapy to their affected limbs in addition to the lower trunk area for the patient with lymphedema of the lower extremity; and the trunk, chest wall, and shoulder areas for the patient with lymphedema of the upper extremity. Both patients achieved successful home maintenance of lymphedema, as judged by limb volume, clinical observations, and subjective patient impressions, after incorporating the Flexitouch® system. Neither patient experienced the deleterious effects (worsening genital edema; fibrotic cuff development) that they had experienced with the older-generation intermittent pneumatic compression devices they had previously used. Incorporating the Flexitouch® system as part of maintenance may improve success for lymphedema patients who have previously struggled with in-home management

Penetrance and expressivity of mitochondrial variants in a large clinically unselected population

This is the final version. Available on open access from Oxford University Press via the DOI in this recordData availability: The data supporting the findings of this study are available within the article and its Supplementary Data files. Additional information for reproducing the results described in the article is available upon reasonable request and subject to a data use agreement. The UK Biobank dataset is available from https://biobank.ctsu.ox.ac.ukBACKGROUND: Whole genome sequencing (WGS) from large clinically unselected cohorts provides a unique opportunity to assess the penetrance and expressivity of rare and/or known pathogenic mitochondrial variants in population. METHOD: Using WGS from 179 862 clinically unselected individuals from the UK Biobank, we performed extensive single and rare variant aggregation association analyses of 15 881 mtDNA variants and 73 known pathogenic variants with 15 mitochondrial disease-relevant phenotypes. RESULTS: We identified 12 homoplasmic and one heteroplasmic variant (m.3243A>G) with genome-wide significant associations in our clinically unselected cohort. Heteroplasmic m.3243A>G (MAF = 0.0002, a known pathogenic variant) was associated with diabetes, deafness and heart failure and 12 homoplasmic variants increased aspartate aminotransferase levels including three low-frequency variants (MAF ~0.002 and beta~0.3 SD). Most pathogenic mitochondrial disease variants (n = 66/74) were rare in the population (G. Multi-system disease risk and penetrance of diabetes, deafness and heart failure greatly increased with m.3243A>G level ≥ 10%. The odds ratio of these traits increased from 5.61, 12.3 and 10.1 to 25.1, 55.0 and 39.5 respectively. Diabetes risk with m.3243A>G was further influenced by type 2 diabetes genetic risk. CONCLUSION: Our study of mitochondrial variation in a large-unselected population identified novel associations and demonstrated that pathogenic mitochondrial variants have lower penetrance in clinically unselected settings. m.3243A>G was an exception at higher heteroplasmy showing a significant impact on health making it a good candidate for incidental reporting.Diabetes UKMedical Research Council (MRC)Wellcome TrustNational Institute for Health and Care Research (NIHR

Sendaway capillary NT-proBNP in pulmonary hypertension

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of cardiac ventricular wall stress that is incorporated into pulmonary hypertension (PH) risk stratification models. Sendaway sampling may enable patients to perform NT-proBNP tests remotely. This UK-wide study aimed to assess the agreement of sendaway NT-proBNP with standard venous NT-proBNP and to assess the effect of delayed processing. METHODS: Reference venous NT-proBNP was collected from PH patients. Samples for capillary and venous sendaway tests were collected contemporaneously, mailed to a reference laboratory and processed at 3 and 7 days using a Roche Cobas e411 device. Differences in paired measurements were analysed with Passing-Bablok regression, percentage difference plots and the % difference in risk strata. RESULTS: 113 patients were included in the study. 13% of day 3 capillary samples were insufficient. Day 3 capillary samples were not equivalent to reference samples (Passing Bablok analysis slope of 0.91 (95% CI 0.88 to 0.93) and intercept of 6.0 (95% CI 0.2 to 15.9)). The relative median difference was -7% and there were acceptable limits of agreement. Day 3 capillary NT-proBNP accurately risk stratified patients in 93.5% of cases. By comparison, day 3 venous results accurately risk stratified patients in 90.1% of cases and were equivalent by Passing-Bablok regression. Delayed sampling of sendaway tests led to an unacceptable level of agreement and systematically underestimated NT-proBNP. CONCLUSIONS: Sendaway NT-proBNP sampling may provide an objective measure of right ventricular strain for virtual PH clinics. Results must be interpreted with caution in cases of delayed sampling