ORCID Profile
0000-0001-9209-454X
Current Organisations
University of Oxford
,
Aston University
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Publisher: Wiley
Date: 14-01-2022
DOI: 10.1002/JCSM.12802
Abstract: Skeletal muscle wasting and dysfunction are common characteristics noted in people who suffer from chronic kidney disease (CKD). The mechanisms by which this occurs are complex, and although progress has been made, the key underpinning mechanisms are not yet fully elucidated. With work to date primarily conducted in nephrectomy‐based animal models, translational capacity to our patient population has been challenging. This could be overcome if rationale developing work could be conducted in human based models with greater translational capacity. This could be achieved using cells derived from patient biopsies, if they retain phenotypic traits noted in vivo . Here, we performed a systematic characterization of CKD derived muscle cells (CKD n = 10 age: 54.40 ± 15.53 years eGFR: 22.25 ± 13.22 ml/min/1.73 m 2 ) in comparison with matched controls (CON n = 10 age: 58.66 ± 14.74 years eGFR: 85.81 ± 8.09 ml/min/1.73 m 2 ). Harvested human derived muscle cells (HDMCs) were taken through proliferative and differentiation phases and investigated in the context of myogenic progression, inflammation, protein synthesis, and protein breakdown. Follow up investigations exposed HDMC myotubes from each donor type to 0, 0.4, and 100 nM of IGF‐1 in order to investigate any differences in anabolic resistance. Harvested human derived muscle cells isolated from CKD patients displayed higher rates of protein degradation ( P = 0.044) alongside elevated expression of both TRIM63 (2.28‐fold higher, P = 0.054) and fbox32 (6.4‐fold higher, P 0.001) in comparison with CONs. No differences were noted in rates of protein synthesis under basal conditions ( P 0.05) however, CKD derived cells displayed a significant degree of anabolic resistance in response to IGF‐1 stimulation (both doses) in comparison with matched CONs (0.4 nm: P 0.001 100 nM: P 0.001). In summary, we report for the first time that HDMCs isolated from people suffering from CKD display key hallmarks of the well documented in vivo phenotype. Not only do these findings provide further mechanistic insight into CKD specific cachexia, but they also demonstrate this is a reliable and suitable model in which to perform targeted experiments to begin to develop novel therapeutic strategies targeting the CKD associated decline in skeletal muscle mass and function.
Publisher: Informa UK Limited
Date: 07-2009
Publisher: MDPI AG
Date: 27-04-2022
DOI: 10.3390/NU14091817
Abstract: This systematic review and meta-analysis provides a synthesis of the available evidence for the effects of interventions on outcome measures associated with sarcopenia in end-stage kidney disease (ESKD). Thirteen databases were searched, supplemented with internet and hand searching. Randomised controlled trials of non-pharmacological or pharmacological interventions in adults with ESKD were eligible. Trials were restricted to those which had reported measures of sarcopenia. Primary outcome measures were hand grip strength and sit-to-stand tests. Sixty-four trials were eligible (with nineteen being included in meta-analyses). Synthesised data indicated that intradialytic exercise increased hand grip strength (standardised mean difference, 0.58 0.24 to 0.91 p = 0.0007 I2 = 40%), and sit-to-stand (STS) 60 score (mean difference, 3.74 repetitions 2.35 to 5.14 p 0.001 I2 = 0%). Intradialytic exercise alone, and protein supplementation alone, resulted in no statistically significant change in STS5 (−0.78 s −1.86 to 0.30 p = 0.16 I2 = 0%), and STS30 (MD, 0.97 repetitions −0.16 to 2.10 p = 0.09 I2 = 0%) performance, respectively. For secondary outcomes, L-carnitine and nandrolone-decanoate resulted in significant increases in muscle quantity in the dialysis population. Intradialytic exercise modifies measures of sarcopenia in the haemodialysis population however, the majority of trials were low in quality. There is limited evidence for efficacious interventions in the peritoneal dialysis and transplant recipient populations.
Publisher: BMJ
Date: 10-2021
DOI: 10.1136/BMJOPEN-2020-046945
Abstract: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients (KTRs). CVD risk scores underestimate risk in this population as CVD is driven by clustering of traditional and non-traditional risk factors, which lead to prognostic pathological changes in cardiovascular structure and function. While exercise may mitigate CVD in this population, evidence is limited, and physical activity levels and patient activation towards exercise and self-management are low. This pilot study will assess the feasibility of delivering a structured, home-based exercise intervention in a population of KTRs at increased cardiometabolic risk and evaluate the putative effects on cardiovascular structural and functional changes, cardiorespiratory fitness, quality of life, patient activation, healthcare utilisation and engagement with the prescribed exercise programme. Fifty KTRs will be randomised 1:1 to: (1) the intervention a 12week, home-based combined resistance and aerobic exercise intervention or (2) the control usual care. Intervention participants will have one introductory session for instruction and practice of the recommended exercises prior to receiving an exercise diary, dumbbells, resistance bands and access to instructional videos. The study will evaluate the feasibility of recruitment, randomisation, retention, assessment procedures and the intervention implementation. Outcomes, to be assessed prior to randomisation and postintervention, include: cardiac structure and function with stress perfusion cardiac MRI, cardiorespiratory fitness, physical function, blood biomarkers of cardiometabolic health, quality of life and patient activation. These data will be used to inform the power calculations for future definitive trials. The protocol was reviewed and given favourable opinion by the East Midlands-Nottingham 2 Research Ethics Committee (reference: 19/EM/0209 14 October 2019). Results will be published in peer-reviewed academic journals and will be disseminated to the patient and public community via social media, newsletter articles and presentations at conferences. NCT04123951 .
Publisher: Emerald
Date: 20-04-2010
DOI: 10.1108/14637151011035606
Abstract: The purpose of this paper is to help managers to successfully plan, implement, and operate enterprise resource planning (ERP) projects using a risk management framework. This paper adopted a combined literature review and case study method. Using literature review, the paper first identified major issues of managing ERP projects and develops a risk management framework for managing those issues. The proposed risk management framework was then applied to a ERP implementation project of a UK‐based energy services group and its effectiveness for managing ERP projects implementation had been demonstrated. Additionally, the risk factors as identified from the case application are compared with the risk factors from the previous researches so as to suggest mitigating measures. All the risk factors are categorized into planning, implementation and operations phases along with project processes, organizational transformation and information technology (IT) perspectives. Project implementation phase is the most vulnerable to failure. The case study results reveal that the effect of other projects on on‐going ERP project, management of overall IT architecture and non‐availability of resources for organizational transformation are most critical from likelihood and impact perspectives. Managing risk across various phases of project and equal emphasize to effective project management, organizational transformation and IT adoption are the key to success in ERP implementation. The risk factors, which were identified using literature review and the case study, have great significance as mitigating measures of those risks may result successful implementation of ERP projects in the industry. Additionally, proposed risk management framework could be customized to implement ERP projects elsewhere. ERP projects are risky as they are capital intensive, technically complex, and call for organizational transformation. There are both success and failure stories. However, both researchers and practitioners agree, that if it can be implemented and operated successfully and benefits should be achievable. Although there are many studies on ERP implementation, little has been discussed on managing risks of ERP projects. Therefore, this paper bridges the gap.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Kate A Robinson.