Department of Oncology and Metabolism projects

Intercalated BSc Medical Sciences Research available projects

An oncology student in the lab

Projects: 

Comparison of breast reconstruction outcomes between Latissimus dorsi flap and implant based reconstruction: a matched analysis

Main Supervisor:

Professor lynda Wyld

l.wyld@sheffield.ac.uk

Second Supervisor:

Ms Jenna Morgan

j.morgan@sheffield.ac.uk

Type of Project:

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

Aims and Objectives:

To determine the long term physical, cosmetic and psychological outcomes of breast reconstruction using 2 different techniques using propensity score matched analysis

Research Methodology:

The project will involve collecting data on 2 cohorts of patients who have had either LD flap based reconstruction or implant /ADM reconstruction since 2002. Data will be extracted on the type of surgery, the acute and longer term complications and the risk factors for these. Women will be contacted and sent a quality of life questionnaire that looks at cosmetic satisfaction as well as psychological satisfaction. In addition, women will be interviewed about their perceptions, satisfaction, regrets etc about their surgery. The work will lead to a mixed methods synthesis regarding the different types of surgery and include both statistical analysis of data, questionnaire analysis and analysis of qualitative interviews (N=20).

Expected Outcome:       

The candidate will generate 3 types of data relating to the physical outcomes of both types of surgery, the psychological and cosmetic impacts of the surgery and the patients subjective opinions of the surgery. The candidate will be supported to present the data at an international conference and write the project up for publication in a surgical journal

Additional Training:

Data collection, data analysis using SPSS statistics package, quality of life analysis, interviewing training and experience, interview analysis, academic writing, literature review methods, presenting and publishing skills. The candidate will also be encouraged to attend breast clinics and breast theatres to see this type of surgery being performed

Ethical Approval:

Original research involving human tissues/human participants and/or patient details and information - UREC or NHS REC ethics approval needed

Antisense therapy of Cushing's disease

Main Supervisor:

Dr Helen Kemp

e.h.kemp@sheffield.ac.uk

Second Supervisor:

Professor John Newell-Price

j.newellprice@sheffield.ac.uk

Type of Project:

Lab/Bench Project - primarily working in a lab environment

Aims and Objectives:

Cushing’s disease (CD) is a rare but devastating condition, caused by hypersecretion of adrenocorticotropic hormone (ACTH) from a corticotroph adenoma in the anterior pituitary. CD is associated with a five-fold excess mortality and clinical features including hypertension, diabetes mellitus, osteoporosis, and depression. First-line treatment is transsphenoidal surgery, but this is effective in only 65% of cases and the relapse rate is high. Other treatment options are limited.

Antisense therapy is a technique for inducing post-transcriptional gene silencing by the use of antisense oligonucleotides (ASOs), which target specific sequences on mRNAs leading to RNase-H degradation or steric blocking of ribosomal machinery.

The aim of the project will be to use an in vitro cell system (At-T20 cells that over-express ACTH) to develop and test ASOs against POMC (gene encoding ACTH) that could be an effective treatment for CD by silencing POMC expression and thus decreasing the secretion of ACTH.

Research Methodology:

Lab techniques - antisense oligonucleotide design; cell culture; transfection of mammalian cells; PCR; ELISA; agarose gel electrophoresis; flow cytometry; statistical analyses.

Expected Outcome:       

Using the AtT-20 cell system, the ASOs would be expected to decrease secretion of ACTH when compared with untreated cells or cells treated with ASOs unrelated to POMC (the gene encoding ACTH).

Additional Training:

Training in above laboratory techniques; use of GraphPad Prism for graphical display of results; use of DNA sequence analysis software; use of DNA databases; presentations at lab meetings; presentation of results at the Medical School Research Day; potentially presentation of results at a scientific conference.

Ethical Approval:

Non-human tissue - no ethics approval required

Production and Characterisation of Long Acting PTH fusion for treatment of Hypoparathyroidism (HypoPT)

Main Supervisor:

Professor Richard Ross

r.j.ross@sheffield.ac.uk

Second Supervisor:

Dr Ian Wilkinson

i.wilkinson@sheffield.ac.uk

Other Supervisor(s):

Sue Justice

Type of Project:

Lab/Bench Project - primarily working in a lab environment

Aims and Objectives:

To produce a long acting PTH fusion for use in the treatment of hypoparathyroidism. To test the in vitro bioactivity of these fusion molecules with a view to taking forward into in vivo studies and future development for HypoPT treatment

Research Methodology:

The student will work on a novel piece of research to develop a potential treatment for hypoparathyroidism and will learn a series of specific skills throughout the project

  1. Grow & Express PTH fusion molecules in a mammalian cell system
  2. Purify PTH fusion molecules using a combination of anion exchange and affinity chromatography.
  3. Assess purity using SDS-PAGE and western blotting
  4. Test bioactivity using a suitable in vitro bioassay measuring cAMP levels
  5. Develop the ability to interpret data and analyse results using a number of data handling packages.
  6. Develop ability to write up results and conclusions to form part of a final report

Expected Outcome:       

PTH fusion molecules will retain biological activity and the have the potential to be further developed as a treatment for HypoPT

Additional Training:

Students will receive training in:

  • SDS-PAGE & Western blotting
  • In vitro cell based bioassays
  • Protein purification
  • Mammalian Cell culture technique
  • Teaching in use of various data analysis & handling packages including Lasergene, GraphPad prism and Excel
  • Effective report writing and presentation skills

Ethical Approval:

Non-human tissue - no ethics approval required

The Cavendish Hip Fellowship: KIF26B is a therapeutic target in heterotopic ossification

Main Supervisor:

Professor Mark Wilkinson

j.m.wilkinson@sheffield.ac.uk

Second Supervisor:

Professor Endre Kiss-Toth

e.kiss-toth@sheffield.ac.uk

Type of Project:

Lab/Bench Project - primarily working in a lab environment

Aims and Objectives:

This project is supported by the Cavendish Hip Foundation and comes funded with a student stipend and experimental costs for the year. The project would suit a student interested in analysis methods and laboratory based work, and who might be interested in a career in orthopaedics.

Aim 1. Determine the requirement for KIF26B activation in HO

Aim 2. Determine which signalling pathways KIF26B operates through downstream of BMP2 specifically in HO and identify potential therapeutic targets.

Research Methodology:

We have recently shown that KIF26B is an important molecule in heterotopic bone formation, a common complication of trauma and joint replacement. Here the student will be taught to use a variety of techniques, including cell culture, over-expression and knock-out constructs, PCR, CRISPR-Cas9 technology, and immunostaining to address the aims outlined above. In Aim 1 the student will use KIF26B overexpression constructs to determine whether its expression alone is sufficient to induce HO, or whether other stimuli are needed. Next the student will use various sub-domains of KIF26B to determine which is its active part. Finally, in Aim 2 the student will determine through which pathways KIF26B exerts its effect using Western blotting and a variety of specific pathway inhibitors.

Expected Outcome:       

The expected findings for Aim 1will be that KIF26B potentiates mineralisation but requires BMP2 stimulation ± osteogenic media for induction of HO and that KIF26B co-localises with the BMP2 receptor.

The expected findings for Aim 2 will be that specific BMP2 and/or canonical Wnt pathway effectors during HO formation will be modulated by KIF26B signals. We also expect that pharmacological inhibition of KIF26B-dependent pathways will prevent mineralisation, confirming the concept that KIF26B signalling is an intervention target in HO.

Additional Training:

In addition to the project-specific techniques outlined above that the student will learn on the project, they will learn general laboratory skills, data handling and record-keeping. Through regular weekly meetings with their supervisors the student will receive specific teaching in statistical analysis packages such as SPSS, and also graphical packages including Prism. They will actively participate in the departments seminar series and in the groups weekly lab meetings, presenting the findings of their work. The student will also be encouraged to present their work at national and international meetings and prepare the work for publication in peer-reviewed journals.

Ethical Approval:

Non-human tissue - no ethics approval required

Evaluation of pregnancy risk assessment prior to in utero transfers for women at risk of premature birth

Main Supervisor:

Professor Dilichukwu Anumba

d.o.c.anumba@sheffield.ac.uk

Second Supervisor:

Dr Victoria Stern

v.stern@sheffield.ac.uk

Type of Project:

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

Aims and Objectives:

To systematically review the literature regarding modalities and approaches to pregnancy risk assessment prior to in utero transfers to improve birth outcomes. To evaluate the practices and accuracy of prenatal risk assessment and indications for in utero transfers in the Yorkshire and Humber Strategic Health Authority (YHSHA) by interrogating the YHSHA EMBRACE in utero transfer database. To determine service improvements for better risk assessment to optimise in utero transfers within the region, thereby saving costs and improving birth outcomes.

Research Methodology:

You will drive the entire project with close supervision of Professor Anumba and his research team which focusses on the prevention and management of preterm birth in the UK and Globally. You will be encouraged to learn to systematically review and critically appraise literature, drawing out themes and key strengths and weaknesses, and identifying gaps in literature worthy of future research. You will be able to contribute to service quality improvement by evaluating a regional service across the specialties of Obstetrics and Paediatrics (Neonatology) . Finally you will have an opportunity to contribute to recommending service improvements with considerable potential for national scale up.

Expected Outcome:       

The key outcome is the identification of best practice for assessing the risk of imminent preterm birth and ensuring that women who need not be transferred to another facility are not transferred, and that women who need such transfers are correctly identified for in utero transfer in order to improve birth outcomes. Our findings could inform the development of improved national guidance for in utero transfers of pregnant women at high risk of very premature deliveries to units with the most appropriate facilities.

Additional Training:

You will be provided training in systematic review, data synthesis and analysis and guidelines development

Ethical Approval:

Service Evaluation - NHS Service Evaluation number required - UoS Ethics will additionally be required

A clinical paediatric normative data study using a novel non-invasive Short Synacthen Test.

 

Main Supervisor:

Dr Charlotte Elder

c.j.elder@sheffield.ac.uk

Second Supervisor:

Dr Neil Wright

n.p.wright@sheffield.ac.uk

Type of Project:

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

Aims and Objectives:

To establish, by use of the validated non-invasive Short Synacthen Test (SST), normative data for adrenal function in the paediatric population

Research Methodology:

Approximately 100 healthy children of both sexes, aged between 6 months and 15 years without exclusion criteria will be recruited, using previously successful recruitment strategies.

Children will undergo screening for eligibility.

Children, with accompanying parent/guardian, will either attend the CCRF at SCH for their non-invasive SST or be trained to undertake the test at home.

The test will involve salivary collection the day before the test, 30 minutes after waking on the day of the test and then at baseline, and 3-5 time points after administering the nasal synacthen.

Saliva will be collected for cortisol and cortisone measurements which will be carried out in a lab in Wythenshawe.

Expected Outcome:       

The salivary samples the day before will be used to validate adult data recently published that two samples enables day curves for cortisol to be constructed (JCEM 2018). The 30 minute awakening salivary samples will be used to study ACR (awakening cortisol response) as a screen for adrenal insufficiency in the healthy paediatric population. The salivary samples taken before and during the non-invasive SST will enable normative data on the paediatric response to nasal synacthen to be collected and derived.

Additional Training:

Critical appraisal

Literature searching

Relevant statistics

Use of GraphPad

Ethical Approval:

Original research involving human tissues/human participants and/or patient details and information - UREC or NHS REC ethics approval obtained already.

Computational AnalySiS of functionAl Neuroimaging and Drug Response in pAinful Diabetic Neuropathy (CASSANDRA-DN)

Main Supervisor:

Dr Selvarajah Dinesh

d.selvarajah@sheffield.ac.uk

Second Supervisor:

Professor Solomon Tesfaye

solomon.tesfaye@nhs.net

Other Supervisor(s):

Dr Kevin Teh

Type of Project:

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

Aims and Objectives:

To develop a magnetic resonance neuroimaging based model that characterises patients with painful diabetic neuropathy

Research Methodology:

One in 16 people in the UK has diabetes and a third of these will develop painful nerve damage. This can cause severe pain in the feet and legs. Unfortunately, current medications provide only partial benefit in some, with many enduring inadequate pain relief. Part of the problem is that a ‘one-size fits all’, ‘trial and error’ approach is used hoping to achieve meaningful pain relief. At best, we achieve partial pain relief in only one in three patients. Hence, a new, more personalised approach is needed where the right treatment is given to the right patient first time. Over the last 10 years, we have performed specialised brain imaging studies using magnetic resonance imaging (MRI) in patients with painful diabetic nerve damage and identified a number of MRI measures that can be used to help personalise treatment decisions. The main objective of this project is to determine if and how brain MRI can be used to predict the treatment response of an individual patient. In this clinical project, the successful candidate will recruit patients for the study, perform clinical assessments during study visits and analyse MR datasets.

Expected Outcome:       

Primary Aim: We will examine the ability of our MRI model to classify patients with painful neuropathy based on its accuracy, precision, recall and area under the ROC curve. The MRI model will also be verified using the quality assurance procedures and with an external validation dataset.

Additional Training:

Training in machine learning and artificial intelligence methodologies

MR image data analyses

Ethical Approval:

Original research involving human tissues/human participants and/or patient details and information - UREC or NHS REC ethics approval obtained already.

Variation in consent for general surgical procedures

Main Supervisor:

Miss Jenna Morgan

j.morgan@sheffield.ac.uk

Second Supervisor:

Professor Lynda Wyld

l.wyld@sheffield.ac.uk

Type of Project:

Qualitative Project/non-lab based - primarily using qualitative methods

Aims and Objectives:

  1. Identify the variation in consent for two common general surgical procedures
  2. Explore the understanding of consent amongst general surgeons
  3. Examine the individual's training in consent amongst general surgeons

Research Methodology:

The project will be a mixed methods project using semi-structured qualitative interviews, analysed via the framework method in NVivo, and questionnaire methodology, analysed using descriptive statistics within SPSS.

Expected Outcome:       

Student will examine the differences in consent forms between surgeons based on a standard patient vignette and will interview trainees in surgery to identify how they have learnt to take consent, what training they have had and what they understand by informed consent. I expect there to be a great deal of variation as, anecdotally, consent is taken differently across the region and I feel this could be standardised and taught better.

Additional Training:

Student will be taught how to perform and analyse semi-structured qualitative interviews in NVivo.

Ethical Approval:

Original research involving human tissues/human participants and/or patient details and information - UREC or NHS REC ethics approval needed.

What do we need to know about patients having emergency surgery?

Main Supervisor:

Mr Matthew Lee

m.j.lee@sheffield.ac.uk

Second Supervisor:

Mr Peter Coe

petecoe@doctors.net.uk

Type of Project:

Qualitative Project/non-lab based - primarily using qualitative methods

Aims and Objectives:

Emergency surgery is a relative research desert, and advances in the field are limited by low quality research. One of the problems is that studies do not report the characteristics of included patients very well. This means that it is difficult to understand whether the study maps to the patient population we care for. We have undertaken a review of patient descriptors described in the literature and generate a longlist. We would like to reduce this to a shorter list that we can encourage other researchers to use in the future to help us generate 'better' research.

The aim of this study is to reduce a longlist of items into key domains or concepts relevant to reporting in studies of treatment of perforated peptic ulcer

Objectives:

Convert current long list of items into a questionnaire form

To assess the face validity of the long list with experts in the clinical field

To undertake a survey of clincians to identify which items in the long list they would like to know

To reduce this long list to key domains using factor analysis methodology and to further reduce items to key variables

To agree what items in these key domains should be reported in future studies

Research Methodology:

The student will be supported in questionnaire design for this project, as well as consensus techniques. They will be given access to an expert group of clinicians and will measure face validity of the questionnaire, adding any missing items.

The student will deliver an online questionnaire to clinicians using social media.

Student will analyse this data using factor analysis approaches (will be taught this) and using cut offs for the consensus technique.

Expected Outcome:       

You will be trained in survey design and some specialist statistical techniques, as well as consensus techniques.

We anticipate that this work will generate at least one presentation at a national or international meeting as well as a peer reviewed journal.

This reflects relatively novel methodology, and may also lead to a methods paper being prepared.

Additional Training:

We will provide training in survey design and analysis.

We will train you in the additional statistical techniques required.

We will encourage you to attend departmental teaching/journal clubs at the Northern General Hospital and in the local area.

We will teach you about the history of the condition and current treatment options. We will encourage you to attend the surgical admissions unit at the Northern General to understand how patients are managed. This will help you to understand the clinical problem.

Ethical Approval:

Original research involving human tissues/human participants and/or patient details and information - UREC or NHS REC ethics approval needed.

Fracture risk assessment and bone health in men starting ADT treatment for prostate cancer

Main Supervisor:

Professor Janet Brown

j.e.brown@sheffield.ac.uk

Second Supervisor:

Dr Jennie Walsh

Other Supervisor(s):

Mr Derek Rosario, Consultant Urologist

Type of Project:

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

Aims and Objectives:

Prostate cancer (PC) is set to become the most common cancer in men. One of our main approaches to treatment, Androgen Deprivation Therapy (ADT), is effective against the cancer by reducing testosterone hormone levels, but has side effects, including weakening the skeleton, causing bone loss, which can result in osteoporosis and debilitating fragility fractures. Treatments to prevent bone loss (antiresorptive agents) are available, but we need to determine which patients are at the most risk of fracture and will therefore benefit most from bone antiresorptive therapy. Sheffield is a world leader in bone health and we have just completed the UK National Guidelines for bone health in prostate cancer. This project, which follows on from these guidelines, will involve direct contact with patients in a clinical project using an assessment tool called FRAX, which was developed in Sheffield, to assess the fracture risk in men starting ADT.

Aim: To determine whether the bone health of men who start hormone therapy for prostate cancer is managed in accordance with guidelines, and to investigate the feasibility of undertaking routine fracture risk assessment in standard clinical practice.

Objectives: To attend outpatient urology clinics to identify patients who have been diagnosed with prostate cancer who are starting ADT hormone therapy, and determine the fracture risk in these patients using the validated fracture risk assessment tool, FRAX. The project will include Identification of patients who require further evaluation by DXA scan (to measure bone density), review of scan results, and determining whether patients subsequently receive appropriate intervention.

Research Methodology:

Students will initially undertake a literature review and be introduced to key clinical staff. The student will initially be based in urology clinics, and will work alongside clinicians and uro-oncology specialist nurses to identify patients starting ADT for prostate cancer, as well as gaining experience in oncology clinics in Weston Park Hospital. They will collect basic clinical data and fracture risk factor information.Depending on the number of men referred, this data will include 100-150 patients. When there is a significant risk of fracture, patients will be referred via usual clinical pathways to the metabolic bone unit at the NGH (for blood tests and a DXA scan). The student will follow the patients up and review blood test and DXA results, and whether anti-resorptive therapy was started.

Expected Outcome:       

This project is expected to lead to both a poster presentation (s) and publication in a peer reviewed journal. Students will gain experience in gathering clinical data from patient notes and clinic visits, in undertaking and interpreting fracture risk assessment, gain a better understanding of clinical pathways, and will gain a solid grounding in the clinical techniques used to assess bone health, as well as gaining experience in working in the cancer field.

Additional Training:

The student will need access to and training to use the Trust results server and have access to medical records. They will receive training in fracture risk assessment techniques. They will also have the opportunity to observe DXA scans, and learn how the results are interpreted, including assessment of vertebral fractures. They will be able to attend relevant teaching sessions at the metabolic bone centre at NGH, and the academic urology department.

Ethical Approval:

Service Evaluation - NHS Service Evaluation number required - UoS Ethics will additionally be required, Not known – please contact Fran Oldale in the first instance.

Optimising the Imaging of Suspected Scaphoid Fracture in Children

Main Supervisor:

Dr Amaka Offiah

a.offiah@sheffield.ac.uk

Second Supervisor:

Dr Iwan Roberts

Type of Project:

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

Aims and Objectives:

To ascertain the most effective imaging protocol for suspected scaphoid fracture in children
  • Determine time to diagnosis for each patient and compare this with the imaging strategy used
  • Conduct a patient/carer satisfaction survey in children suspected to have a scaphoid fracture
To recommend an imaging protocol for suspected scaphoid fracture in children

Research Methodology:

Retrospective review of Emergency Department notes, radiographic images and imaging outcome of 200 children presenting with suspected scaphoid fracture, documenting
  • Demographic details
  • Date of initial radiographic imaging and outcome
  • Date, modality and outcome of subsequent imaging (radiographs/MRI/CT/US)
Prospective recruitment and follow-up of 50 children presenting to the ED with suspected scaphoid fracture documenting the features/findings listed in Point 1 above Patient quality of life survey of those recruited in Point 2 above. This will involve the student interacting with children and parents as they attend the ED and enrolling them to complete the questionnaire on 3 occasions; Day 1, Day 10 and Month 3 following their injury

Expected Outcome:       

Recommendation of the most appropriate imaging strategy for suspected scaphoid fracture in children At least one local oral presentation Abstract submitted for potential poster/oral presentation at at least one national and one international conference Paper submitted for potential publication in a peer-reviewed journal

Additional Training:

Learn to interpret wrist images performed for suspected scaphoid fracture (most commonly radiographs and MRI, but CT and possibly ultrasound also) Opportunity to attend clinical radiology meetings at Sheffield Children's Hospital thus gaining experience in radiographic interpretation One-on-one teaching sessions with the main supervisor with the opportunity to be shown imaging examples of common exam conditions

Ethical Approval:

Original research involving human tissues/human participants and/or patient details and information - UREC or NHS REC ethics approval needed.

A pilot study to evaluate changes in the vaginal pressure profile during pregnancy and postpartum, using a novel intra-vaginal pressure sensing device (IVPSD).

Main Supervisor:

Dr Swati Jha

S.Jha@sheffield.ac.uk

Second Supervisor:

Dr Emma Ferriman

emma.ferriman@nhs.net

Type of Project:

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

Aims and Objectives:

To determine changes in the vaginal pressure profile during the first, second and third trimester of pregnancy as well as the postnatal period using the intra-vaginal pressure sensor device (IVPSD/FemFit).

Research Methodology:

40 Pregnant women who are medically fit and well in their first pregnancy will be included. They will be recruited when they attend for their booking visit. Consenting women will have their resting pelvic floor muscle pressure profile (standing/lying) measured during the first, second, third trimester and postnatal period (3 months postnatally) to determine the changes using the IVPSD. This will be done during maximal pelvic floor contraction for 5 seconds on 3 occasions and during coughing on 3 occasions. Patients will be sent an electronic Quality of Life questionnaire (ePAQ) during their first trimester and postnatal visits to assess their pelvic floor symptoms.

Expected Outcome:       

The differences in intravaginal pressure profiles throughout pregnancy and the postnatal period will be compared. The sequential change in the intravaginal pressure profiles for each trimester will be estimated. Patient symptoms will be assessed using the ePAQ. As some women will undergo a CS or an instrumental delivery we will also be able to see the difference in impact between Normal vaginal delivery , instrumental delivery and CS on the pelvic floor.

Additional Training:

Sample size calculation

Introduction to Qualitative research

Systematic reviews

Ethical Approval:

Original research involving human tissues/human participants and/or patient details and information - UREC or NHS REC ethics approval needed.

Improving health care for children and young people with congenital adrenal hyperplasia (CAH)

Main Supervisor:

Dr Nils Peter Krone

n.krone@sheffield.ac.uk

Second Supervisor:

Dr Irina Bacila

Type of Project:

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

Aims and Objectives:

CAH is one of the most challenging conditions in paediatric endocrinology with patients having a significant risk of co-morbidities and early mortality. Thus, this clinical research project aims to improve the health care delivery in children and young people with CAH.

This aim will be addressed by two key objectives:

  1. To establish the current clinical management of patients with CAH in the UK.
  2. To implement a novel non-invasive test for monitoring quality of steroid hormone replacement.

Research Methodology:

The student will be a member of a clinical and translational research team operating at the national and international forefront in the field, and will work within an existing national research collaboration.

In the first part collect, longitudinal retrospective data on clinical care provision from participating UK centres will be collected using the international congenital adrenal hyperplasia (I-CAH) registry. Data will be extracted from the I-CAH registry with support from I-CAH registry staff and analysed by the student under guidance of the supervisory team. This work will provide key skills around data management and data analysis as well as collaborative work within a multicentre research team.

The second part of the project will involve direct patient contact to recruit patients with CAH into a research study to establish a novel test for non-invasive therapy monitoring using steroid measurement form saliva. The student will be involved in recruiting patients, conducting research visits, sample and data collection as well as data analysis. Within this part of the project, the student has the opportunity to acquire skills essential to every clinical researcher such as study design, practical delivery of a clinical study and statistically analysis as well as interpretation of clinical and biochemical data.

Expected Outcome:       

The first part of the project will provide insights into the current state of care delivery. From our recent cross-sectional nationwide study including 120 patients with CAH in the UK, we have provided evidence for significant differences of healthcare delivery in different centres across the UK. The first part of the project will provide more detailed evidence on such differences in a longitudinal way and will enable us to assess the impact of such differences on health outcomes. Thus, this will form the basis for nationwide health policies to improve standardised health care provision in individuals with CAH.

The second part of the project will establish a novel non-invasive test for therapy monitoring replacing the need for 3-monthly blood tests in children and young people with CAH. Replacing traumatising blood test is highly desirable and will significantly improve quality of life in patients with CAH.

Additional Training:

The student will be able to acquire a multitude of skills highly relevant to clinical practice and clinical research, which can be widely used in the future. This will include the understanding of study design and practical deliver as well collaborative multicentre work, which is essential for answering clinical question successfully in the 21st century. In addition, the student will be trained in statistical analysis and interpretation of data. This will not only support the research, but also equip the student with future skills, which will help to critically appraise clinical data and studies.

Ethical Approval:

Secondary data or tissue samples - UREC or NHS REC ethics approval already received for the intended research project, Original research involving human tissues/human participants and/or patient details and information - UREC or NHS REC ethics approval

Impact of cardiac dose on survival of thoracic cancer patients following radical radiotherapy

Main Supervisor:

Dr Bilal Tahir

b.tahir@sheffield.ac.uk

Second Supervisor:

Professor Matthew Hatton

Type of Project:

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

Aims and Objectives:

The RTOG 0617 trial identified cardiac radiation dose metrics as independent predictors of survival for locally advanced non-small cell lung cancer (NSCLC) patients following chemoradiotherapy of conventional and dose escalated regimes. Alternative radiotherapy dose schedules such as continuous hyperfractionated accelerated radiotherapy (CHART) are widespread in the UK for NSCLC and their effects on cardiac related survival are yet to be fully characterised. Likewise, the effect of cardiac dose on radiotherapy for other thoracic malignancies which receive significant cardiac doses such as small cell lung cancer (SCLC) and oesophageal cancer are yet to be studied.

The aim of this single-centre retrospective study is to analyse the impact of cardiac dose on overall survival of thoracic cancer patients radically treated with radiotherapy dose schedules widely used in the UK.

Research Methodology:

The student will review the records of NSCLC, SCLC and oesophageal cancer patients treated at our institution with radical radiotherapy between 2005 to 2017. Patient demographics, tumour characteristics, survival and dosimetric data will be collated. The heart will be delineated using commercial treatment planning software for a select cohort of these patients who were treated prior to the introduction of routine cardiac contouring. This will facilitate extraction of cardiac dosimetric parameters such as heart mean dose. The impact of these cardiac dose metrics on survival will be assessed using multivariate survival analysis via Cox regression.

Expected Outcome:       

We hypothesise that cardiac dosimetric parameters are independent predictors of survival following UK-based radiotherapy dose schedules for all three thoracic malignancies to be studied. Consequently, the results of this study may provide evidence of the need to minimise cardiac dose in thoracic radiotherapy, thus improving patient outcomes. It is also expected that the work will lead to conference proceedings at major national and international conferences and publication in reputable radiation oncology journals.

Additional Training:

Students will be trained in retrieving clinical prognostic information from patient notes and electronic records and contouring of thoracic structures including the heart using a commercial radiotherapy treatment planning system. Likewise, students will receive training in performing advanced statistical analysis including survival analysis (Kaplan-Meier and Cox regression) using SPSS software.

Ethical Approval:

Service Evaluation - NHS Service Evaluation number obtained - UoS Ethics will additionally be required.

Delays in diagnosing Primary Bone Cancer in the primary care setting - how can we improve awareness and improve patient outcomes?

Main Supervisor:

Professor Alison Gartland

A.gartland@shef.ac.uk

Second Supervisor:

Dr Joanne Thompson

j.thompson1@sheffield.ac.uk

Other Supervisor(s):

Additional supervisory input from Bone Cancer Research Trust Awareness Executive.

Type of Project:

Qualitative Project/non-lab based - primarily using qualitative methods

Aims and Objectives:

Primary bone cancer, also referred to as a bone sarcoma, is very rare and makes up approximately 0.2% of all cancers diagnosed in the UK. Awareness of primary bone cancer amongst healthcare professionals is relatively poor, meaning that diagnosis is often delayed. Patients are thus often referred to specialist sarcoma centres with advanced disease, meaning that survival rates are drastically reduced. For example, Osteosarcoma is an aggressive bone cancer that mainly affects children and adolescents with a 5-year survival of ~70% but that is reduced to ~20% with metastasis. Time to diagnosis is often protracted and a very stressful time for patients, which can have a negative impact on the rest of their treatment.

In their 2017-2022 strategy, the Bone Cancer Research Trust committed to a number of key activities to improve awareness of primary bone cancer amongst key healthcare professionals, including GPs, Physiotherapists and Radiologists, with the ultimate aim of improving the speed of diagnosis and outcomes for primary bone cancer patients. Raising awareness of this rare group of cancers, amongst both professionals and the public is of paramount importance if improvements in time to diagnosis are to be made.

The aims and objectives of this project is to review the current provision of primary bone cancer(PBC) diagnosis/awareness in the medical course curriculum as well as GP and other primary health care professional training/CPD and identify barriers to engagement. As well as engaging primary health care professionals, this project will also include conducting focus groups and/or individual interviews with a range of participants recruited by BCRT who are survivors of bone cancer to understand the patient experience of the diagnosis pathway.

Engagement with GP networks to explore the barriers with accessing PBC training will be done via focus groups and questionnaires. Similarly, the research will also include conducting focus groups and/or individual interviews with a range of participants recruited by BCRT who are survivors of bone cancer. The student will also work closely with the Bone Cancer Research Trust Awareness Executive to inform their awareness strategy amongst primary health care professionals and also the general public.

Research Methodology:

Students will be responsible for reviewing the current provision of primary bone cancer(PBC) diagnosis/awareness in the medical course curriculum as well as GP and other primary health care professional training/CPD provision. Engagement with GP networks to explore the barriers with accessing PBC training will be done via focus groups and questionnaires. The student will also work closely with the Bone Cancer Research Trust Awareness Executive to inform their awareness strategy amongst primary health care professionals and also the general public. In addition, the research will also include conducting focus groups and/or individual interviews with a range of participants recruited by BCRT who are survivors of bone cancer to explore their experience of the diagnosis pathway.

Expected Outcome:       

To identify the barriers GPs and other primary health care professionals face in accessing training in PBC.

To increase awareness of PBC in primary healthcare professionals.

To understand the impact of the diagnosis pathway has on patient experince and outcomes

The student will gain experience in conducting and analysing qualitative data as well as disseminate the findings to BCRT in a report/presentation and also via medical education/academic publication.

Additional Training:

Training/experience in qualitative methodology will be provided.

This research will also include conducting focus groups and/or individual interviews with a range of participants.

Training/experience in conducting and analysing qualitative data

Ethical Approval:

Study in Trust involving NHS staff working methods only – no NHS ethics approval required (although this should still be agreed by the relevant Trust R&D department). However as a medical student is completing the study, please contact Fran Oldale about putting the study through UREC.

The DNA damage response in Neuroblastoma

Main Supervisor:

Dr bryant helen

h.bryant@sheffield.ac.uk

Second Supervisor:

Ruth Thompson

Other Supervisor(s):

Dr Dan Yeomason, Dr David King

Type of Project:

Lab/Bench Project - primarily working in a lab environment

Aims and Objectives:

Characterise the DNA damage response in Neuroblastoma cell lines

Test DNA damage response inhbitors in Neuroblastoma cell lines

Research Methodology:

Tissue culture, RT-PCR, western blotting and immunohistochemistry

Expected Outcome:       

The student will contribute origional research to teh larger area of research in our lab. Specificalay they will identfy differences in the DDR between normal and Neuroblastoma cells. This will contribute to at least one research paper and a poster/oral presentation at a meeting

Additional Training:

The student will be trained in all the techniques above.

Ethical Approval:

Non-human tissue - no ethics approval required.

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