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Investigating the impact of ethnicity on disease outcomes in FSHD

We aim to help determine if there is any difference between the experiences of non-white individuals with facioscapulohumeral muscular dystrophy (FSHD) in the UK, as compared with white individuals.

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Supervisors

• Dr Channa Hewamadduma (chewamadduma1@sheffield.ac.uk)
• Mr Jon Street (jon.street@sheffield.ac.uk)

Objectives

• To identify the key issues experienced by members of the BAME community in the UK with FSHD in the UK
• To identify any differences in disease severity reported by white and non-white individuals with FSHD in the UK
• To identify differences in quality of life measures of white and non-white individuals with FSHD in the UK

Methodology

The UK FSHD Registry has over 900 participants. Participants are sent questionnaires to complete each year, including information about their usual levels of mobility, arm function, pain, quality of life and demographic information.

We intend to use data supplied by the registry to analyse the quality of life (as measured by SF-36), disease severity (as measured by reported mobility and arm restrictions), and pain (as measured with the McGill pain questionnaire) of individuals on the registry who identify as non-white.

Expected outcome

Population studies in Iran, Japan, China and South Korea have presented evidence of reduced disease penetrance in these populations. Therefore, we expect to uncover differences in both disease severity and lived experience of BAME individuals living with FSHD as compared with white individuals living with the disease.

Type of project

Medical Humanities

Additional training

Students will be supported in analysing and interpreting quality of life data from SF-36 using SF-6D methodology. These methods apply to many other conditions where quality-of-life measures are used in medical research.

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 Remote Ischaemic Conditioning for secondary stroke prevention (RIC-prevent)

We aim to recruit 34 patients with minor stroke or TIA in a 1:1 randomised manner to undertake either true Remote Ischaemic Conditioning (RIC) or fake RIC for eight weeks.

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Supervisors

• Dr Ali Ali (ali.ali@sheffield.ac.uk)
• Dr Sheharyar Baig (sheharyar.baig@nhs.net)

Aim and objectives

and evaluate the following primary outcomes:

• Safety (adverse event profiles)
• Feasibility and compliance – treatment log of the number of completed treatments
• Tolerability – Likert scales of comfort

Methodology

Eligible patients will be randomised (1:1) to either RIC (BP cuff inflation around the upper arm at 200 mmHg for 5 minutes followed by 5 minutes of deflation), or sham (inflation pressure 20 mmHg), repeated 4 times, daily for eight weeks.

Patients must complete training on the intervention delivered by the MSc student and supervised by clinicians (AA).

Weekly telephone calls will ensure treatment log completion (assessing feasibility, compliance and tolerability) and detection of adverse events (safety). Secondary outcomes (BP, HR, functional measures, EQ-5D) will be measured at baseline and eight weeks.

Expected outcomes

Primary outcomes will be reported in descriptive terms. Secondary outcome measures will be reported descriptively and statistical tests for between-group differences will occur according to data distribution (parametric statistics for normally distributed data and non-parametric statistics for non-normally distributed data).

Type of project

Clinical project - based in the clinical environment with patients/including service evaluation

Additional training

Students will receive training in the delivery of the intervention, on how to take blood samples and prepare serum and plasma for storage, outcome measure assessment and undertaking a clinical study.

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Can we develop CognoSpeak for people with MND and stroke? 

The Stroop task is a widely used neuropsychological test for assessing executive function. Traditionally administered as a manual paper-based task, the Stroop task measures a person's ability to suppress their automatic response when asked to name the ink colour of a word when the word itself represents an incongruent colour. With the increasing use of digital tools in cognitive assessments, it is essential to validate digital versions of established tasks to ensure their reliability and accuracy in measuring cognitive function. 

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Supervisors

• Dr Dan Blackburn (d.blackburn@sheffield.ac.uk)
• Dr Ronan O'Malley (r.omalley@sheffield.ac.uk)

Objectives

• To compare performance on the digital Stroop task with the traditional paper-based Stroop task in terms of reaction time and accuracy in healthy controls.
• To assess the reliability of the digital Stroop task by evaluating internal consistency and test-retest reliability.
• To evaluate the user experience of the digital Stroop task using a standardised questionnaire.

Hypothesis: The digital version of the Stroop task will demonstrate comparable validity, reliability, and performance metrics (reaction times and error rates) to the traditional Stroop task when administered to healthy participants.

Methodology

A sample of 40 healthy adults will be recruited. Participants will complete both a traditional paper-based Stroop task and the digital version in a counterbalanced order. The traditional task will include three conditions: color naming, word reading, and the incongruent color-word condition, while the digital task will mirror these conditions using a computer interface.

We will seek to recruit 20 stroke survivors and 20 people with MND Measures

Primary Outcome: Reaction times and accuracy for congruent and incongruent trials in both versions of the task.

Secondary Outcomes: Internal consistency and test-retest reliability of the digital task (using a subset of participants tested again after one week).

Subjective Measures: Usability will be assessed using a usability scale or questionnaire.

Expected outcomes

It is expected that performance on the digital Stroop task will be comparable to the traditional version, with no significant differences in reaction times or accuracy across the two formats. We also anticipate that the digital Stroop task will show good reliability, with high internal consistency and stable performance across repeated testing. Usability scores are expected to reflect a user-friendly design comparable to the traditional task.

The successful validation of the digital Stroop task will support its integration into a broader digital cognitive assessment tool designed for individuals with MND and stroke. This could enable remote monitoring of cognitive function in MND patients and stroke survivors. Additionally, the tools scalability could extend its utility to other neurodegenerative conditions or executive function assessments in clinical and research settings.

Type of project

Clinical project - based in the clinical environment with patients/including service evaluation

Additional training

• Interdisciplinary skills (in between engineering/computational and clinical (cognitive neurology).
• Co-design technology development with pwMCI (including those from ethnic minority groups) and clinicians will ensure accptability and scalability of tool.
• Working with an industrial partner will provide a bussiness approach to medical software development.
• Quantitative skills (computation, data analytics and informatics and developing digital and technology excellence as the student will experience web design and large scale data collection.

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Investigating the medication burden of people living with motor neuron disease (plwMND)

Hypothesis: the drug burden on people living with motor neuron disease (plwMND) is unnecessarily high placing patients at risk of harm through drug-drug interactions and incurring preventable costs for the NHS.

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Supervisors

• Dr Sarah Boddy (s.l.boddy@sheffield.ac.uk)
• Dr Rebecca Simpson (r.simpson@sheffield.ac.uk)

Objectives

• Identify the levels of polypharmacy in the UK population of plwMND
• Identify the extent of potential drug-drug interactions in plwMND
• Identify drugs taken by plwMND that may not be appropriate given the severely restricted lifespan and physical impairments associated with MND
• Report these findings in a clear and cohesive way that may facilitate better understanding of these problems in this patient group

Methodology

Comprehensive drug history data from ~480 participants were collected by 35 sites as part of a study on secretion management in plwMND.

The student will be required to

• clean this data into a standardised form
• report levels of polypharmacy in the study cohort
• identify potential drug-drug interactions that individuals may have been exposed to
• rank the level of potential risk in each instance
• identify potentially unnecessary drugs reported (eg those for mitigating long-term risks in participants with advanced MND)
• review background literature: polypharmacy risks and mitigation strategies (worldwide)

Expected outcomes

A pilot investigation revealed potential DDIs (some severe) in plwMND. Therefore, it is expected that low, medium and severe potential DDIs will be identified in these data. It is also known that plwMND often have co-morbidities and are prescribed multiple medications.

It is predicted that medications prescribed to reduce future risks, like the risk of stroke, will not have been revised in light of an MND diagnosis (life expectancy 2-5 years) meaning many individuals will be following unnecessary drug regimes.

Reporting the extent of these issues will be invaluable in planning strategies to reduce the drug burden of this vulnerable patient group.

Type of project

Clinical project - based in the clinical environment with patients/including service evaluation

Additional training

The student will be trained to clean and process clinical data for analysis. Training in using key tools for statistical analysis will be provided (SPSS and R) alongside relevant statistical methods. There will also be training in data visualisation methods to optimise the impact of reported findings. The student will also have the opportunity to shadow neurologists and other healthcare professionals involved in the care of plwMND.

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Axonal transport of mitochondria as a therapeutic target in ALS

Work from our group and others has shown that defective axonal transport of mitochondria is an early neuropathological feature in many neurodegenerative diseases, including mutant SOD1-related ALS. We have data showing that inhibition of conventional protein kinase C (cPKC) signaling can rescue defective axonal transport of mitochondria in models of mutant SOD1-related ALS, and preliminary data indicates that this involves the phosphorylation of TRAK1.

Our Aim is to establish how cPKC-mediated TRAK1 phosphorylation regulates mitochondrial transport and how this contributes to ALS. We hypothesise that cPKC-mediated phosphorylation of TRAK1 regulates axonal transport and is a potential therapeutic target. 

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Supervisors

• Professor Kurt De Vos (k.de_vos@sheffield.ac.uk)
• Dr Andrew Grierson (a.j.grierson@sheffield.ac.uk)
• Natalie Pye

Objectives

• To test phosphorylation resistant and mimicking TRAK1 mutants and confirm genuine PKC sites on immunoblot.
• To investigate the interaction of TRAK1 mutants with the Miro1/KIF5 transport complex by immunoprecipitation
• To investigate how TRAK1 mutants affect mitochondrial trafficking by immunofluorescence imaging in fixed and living cells

Methodology

• Pipetting
• Solutions and dilutions
• DNA techniques (plasmids)
• Cell culture
• Transfection
• Immunoblotting
• Immunofluorescence microscopy
• Immunoprecipitation
• Live microscopy of mitochondrial trafficking

Expected outcomes

We expect that increased phosphorylation of TRAK1 by PKC will reduce its binding to Miro1/KIF5 and disrupt transport of mitochondria. We expect this disruption of transport to affect neuronal function and so contribute to ALS.

Type of project

Lab/Bench Project - primarily working in a lab environment

Additional training

In this project you will learn the essential laboratory skills that are required for any bioscience researcher, and any other techniques we require.

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