Higashi Osaka City, Japan

Aquatic and Land Exercises for Chronic Low Back Pain

Single-Cell Sequencing Analysis of Radiation Pneumonitis Signals In Patients Treated For Cancer With Radiotherapy

Lung cancer is the third most common cancer in the UK with around 48,500 people diagnosed with the condition each year. Unfortunately, despite significant progress in treatment options and their delivery, improvements in survival remain elusive. Radiotherapy (RT) is a cornerstone of both radical and palliative treatment in non-small cell lung cancer (NSCLC). Radiation pneumonitis (RP) is the key dose-limiting constraint and a morbid, potentially even life-threatening, toxicity associated with RT to the thorax. Newer combinations of chemo-radiotherapy and adjuvant immunotherapy demonstrate improved survival but are associated with higher risk of RP. Current management of RP is very limited consisting of supportive measures and steroids; the latter of which are often ineffective and come with their own risks. The typical triad of symptoms (exertional dyspnoea, a non-productive cough and hypoxia) can be directly fatal for some whilst for others represent a devastating and permanent decline in their lung function and quality of life. Although modest understanding of the patient and treatment related risk factors for RP development have been identified the underlying mechanisms remain poorly understood and has been challenging to investigate. A cascade of inflammatory changes with hypoxia lead to endovascular damage, cytokine release and ultimately endothelial cell death and irreversible fibrosis. Single-cell RNA sequencing (scRNA-seq) is a relatively novel technique that allows access to an understanding of this process. It can allow the identification of what genetics, cell types and functional heterogeneity are up/down-regulated in association with irradiated lung tissue in humans. It is known that Stereotactic-Ablative Radiotherapy (SABR) is a well-tolerated highly conformal form of RT. It has been safely delivered to patients before radical surgery without significant toxicity or increase in complication rate. If a targetable mechanism behind this condition could be identified it has the potential to change the landscape of lung cancer RT management and in doing so save lives. A literature search revealed no investigation like this has been conducted in humans. A Chinese study has been done in murine models and demonstrated several signals which, if demonstrated in humans, could be of interest. SPITFIRE proposes to obtain inflamed lung tissue from patients who have developed pneumonitis following radiation for their lung cancer to find these answers. 1.2 RATIONALE FOR STUDY Both patients who have potentially been cured of their lung cancer and those being treated to alleviate symptoms in their last months-to-years of life are diagnosed with RP. Potentially treatable disease can be refused due to an unacceptable combination of risk factors for developing RP. Hospitalisation for RP is common and yet often frustratingly unhelpful. RP is a major contributor to patient morbidity, mortality and healthcare cost. Although clearly a constant concern in lung cancer any radiation delivered through the chest (including oesophageal, breast and pulmonary metastatic RT) carries a risk of RP. Pulmonary fibrosis treatment is starting to improve with novel agents such as Nintedanib and Pirfenidone demonstrating some promise. There is likely, though yet unproven, crossover between the molecular and genetic processes involved in these conditions. Should a better understanding of the mechanisms behind RP reveal a targetable signal, and subsequent treatment, it has the potential to completely change not only the management of this toxicity but that of thoracic malignancies. Obtaining tissue from human lung affected by RP is a challenge. These patients are often too unstable to safely proceed with such intervention. There is, however, a population of patients who have clinical and radiological features diagnostic of the condition but maintain oxygen saturations (SpO2) adequate to proceed to bronchoscopy. Some of these patients will be referred for a bronchoscopy to exclude super-added infection. As part of this process they may be enrolled in the ELFMAN (Edinburgh Lung Fibrosis Molecular Endotyping) Study - to better characterise suspected inflammatory and fibrotic interstitial lung disease, as it may have shared molecular pathways to interstitial pneumonias including idiopathic pulmonary fibrosis (IPF). Standard bronchoscopy may not reach the effect area of lung but deep bronchial brushings obtains a good cellular yield which should be adequate for scRNA-seq whilst minimising risk to the patient. This study proposes to utilise a brushing from these patients to process using a novel laboratory technique to help identify the cellular processes that may be involved in radiation pneumonitis.

A Study of GSK5764227 in Participants With Advanced Solid Tumors

A Study of MOv18 IgE in Folate Receptor Alpha-expressing Platinum Resistant Ovarian Cancer

EPS101-10-02 is a two-part, Phase Ib, open-label, dose escalation and expansion trial in patients with platinum resistant ovarian cancer whose disease has progressed after no more than 4 lines of standard therapy. In total, the trial will enrol approximately 45 patients. All enrolled patients will have biopsy accessible, measurable disease with a confirmed FRα expression of 5% or higher. MOv18 IgE will be administered to approximately 30 patients in Part 1 and up to a further 15 in Part 2. Patients will receive treatment on Days 1, 8 and 15 of a 21-day cycle and may continue treatment until radiological disease progression or unacceptable toxicity despite optimal medical management or dose or schedule modification, or withdrawal of consent. The starting dose of MOv18 IgE is 3 mg. Patient screening will occur during the 28 days prior to the first administration of MOv18 IgE. All patients will undergo PK, PD and safety assessments, as well as disease response (tumour) assessments to determine the potential clinical benefit of MOv18 IgE. In all instances, patients will be followed up for overall survival (OS) for a maximum of 270 days after their last dose of trial treatment, or until withdrawal of consent, lost to follow-up, death, or the overall end of trial, whichever is earliest. In Part 1, MOv18 IgE will be administered at increasing dose levels in different patient cohorts of approximately 6 patients, until selection of the Part 2 dose. The dose of MOv18 IgE administered in Part 1 will be escalated following a Bayesian logistic regression model - Escalation with overdose control (BLRM-EWOC) trial design. After determination of the Part 2 dose, up to 15 additional patients will be enrolled and treated with MOv18 IgE at that dose to further assess anti-tumour activity of MOv18 IgE and obtain additional information on its safety, PK and PD.

EMITT-1 (ERAP Mediated Immunopeptidome Targeting Trial - 1)

GRWD5769 is as a potential new treatment for advanced or metastatic solid malignancies. GRWD5769 works by stopping an enzyme in the body, called endoplasmic reticulum aminopeptidase 1 (ERAP1), from working. ERAP1 is part of how the body recognizes the presence of a cancer tumour and helps trigger the immune system to fight the cancer. However, in patients with cancer, the immune system cells can become exhausted and no longer work effectively. By blocking ERAP1 it makes the tumour look different to the immune system and so the immune system starts fighting the cancer again. GRWD5769 has the potential of producing clinically meaningful improvements in monotherapy and in combination with therapy like cemiplimab (Libtayo®) by enhancing the antitumour immune response. Who can participate? Patients with advanced or metastatic solid malignancy aged 18 years or older. What does the study involve? This study consists of Module 1 (Parts A to D), which will look at the effects of GRWD5769 when given alone and Module 2 (Parts A to C) which will look at the effects of GRWD5769 when given in combination with another anticancer drug called Libtayo® (cemiplimab).

Development and Validation of a New Paediatric Inflammatory Bowel Disease NUTrition Risk Score (PIBD-NUTS)

MEMRI and Kidney Disease

Examining Scottish Chiropractic Professional Identity Using Chiropractic Professional Identity Scales

Research Question(s) Using the CPIES and CPISOS, does the strength of chiropractic professional identity (CPI) vary across Scottish chiropractors? For the CPIES and CPISOS, are there any influences on CPI across age, gender, ethnicity, or pre-professional educational variables? Rationale and Significance of the Study By aiming to understand CPI and its drivers, the investigators may be able to strengthen and develop chiropractors' professional identity without homogenisation. A strong professional identity facilitates the taking up of professional responsibilities, promotes a sense of belonging and professional socialisation, increases competence, fosters greater belonging, stability, and esteem, and promotes enhanced decision-making and confidence. These have been shown to enhance trust and patient safety and ultimately lead to better practice and patient outcomes. By better understanding CPI, and through the use of the Chiropractic Professional Identity Embodiment Scale (CPIES) and the Subtype Orientation Scale (CPISOS), the investigators may be able to identify potential divisions or areas of friction in chiropractic curriculum and to better support the profession. Chiropractic research has shown that burnout and professional dissatisfaction may be a consequence of poor professional identity. In a sample of chiropractors, the CPIES and CPISOS may help to identify areas of professional identity that could be strengthened, and that may ultimately improve professional satisfaction and success. This project will also allow us to collect demographic data of Scottish chiropractors, which may also assist in understanding the profession in greater detail and depth. Literature/Past Research Review Simply belonging to a profession does not alone determine one's professional identity; rather, variation exists in beliefs relating to one's occupation. 11 While chiropractic is an established health profession, there is a lack of clarity about the role of chiropractic in healthcare. There is disagreement on what characterises the chiropractic profession, its philosophy, and scope of practice. Chiropractors themselves have reported being challenged at times by the unclear public identity of the profession brought about by contrasting practice styles. Studies exist on chiropractors' attitudes and beliefs on professional identity. In North America, New Zealand, and Australia, pre-chiropractic education and the geographic region have been shown to be associated with differences in professional identity. In North America, chiropractic students report a preference for participating in mainstream health care and a desire to hold to traditional chiropractic theories and practices, being elements of various domains of chiropractic professional identity. Professional identity has been said to begin with formal education and has been researched with undergraduate chiropractic students. Common themes of an interplay between professional association membership status, pre-chiropractic education, and institutional philosophy have been cited as being determining factors in identity construction. Limitations of these current studies exist, the main being that the surveys employed in the research were not psychometrically validated. Additionally, the surveys differed in each study, making generalisability and comparisons difficult. These issues may be remedied through the use of a consistent psychometrically robust scale such as the CPIES. The CPIES was derived through mixed methods research using a qualitative phase that used one-to-one cognitive interviews of 15 expert key informants to inform and develop a pool of 92-candidate items across six known CPI domains. These items were then tested on 231-participants (New Zealand chiropractors and chiropractic students) for psychometric robustness. The final CPIES comprised 22-items and was found to be a valid and reliable measure of CPI. It has been identified that further research is needed to improve the understanding of measurement properties of tools used in research and to aid their selection and use. 25, and this research aims to begin to fill some of these gaps in knowledge. Primary research question: Using the Chiropractic Professional Identity Embodiment Scale (CPIES) and Subtype Orientation Scale (CPISOS), does the strength of chiropractic professional identity (CPI) vary across Scottish chiropractors? Secondary research question: For the Chiropractic Professional Identity Embodiment Scale (CPIES) and Subtype Orientation Scale (CPISOS), are there any influences on chiropractic professional identity (CPI) across age, gender, ethnicity, or pre-professional educational variables? Design of the Study Study design and setting This research is quantitative descriptive study to analyse CPIES and CPISOS questionnaire data across Scottish chiropractors and chiropractic students. The study will be conducted primarily at the Scotland College of Chiropractic. The lead investigator for the project is Dr Alice Cade. Participants All practising Scottish chiropractors and currently enrolled chiropractic students will be invited to take part in this study. Potential participants will not be eligible if they are practising outside of Scotland or enrolled to study chiropractic in an institute outside of Scotland. Procedure Participants will be asked to review the purpose of this study and the participant selection criteria, indicate their agreement to participate, and complete an online web-based survey to rate their beliefs towards 22-CPIES and 21-CPISOS statements and one CPI self-categorisation question on a 5-point Likert scale. The survey is anticipated to take 10 minutes to complete. Data will be anonymous and collected on a platform such as Qualtrics to be analysed by R software. The sample size was based on calculations recommended by Bartlett (2001), where the alpha level a priori at .05, and based on a five-point scale, the level of acceptable error at 3%, and estimated the standard deviation of the scale was 1.25. As the sample size calculated exceeded 5% of the possible population, the available sample size was corrected using Cochran's (1977) formula, resulting in a recommended sample size of 78. There are approximately 90 practising chiropractors and 26 students enrolled at the Scotland College of Chiropractic, and the investigators hope to gain a response from over half of these potential participants, which previous studies have found achievable. Statistical analyses Primary outcomes: A unidimensional score and six sub-scale numerical scores from the Chiropractic Professional Identity Embodiment Scale (CPIES). Secondary outcomes: A unidimensional measurement of chiropractic practitioner subtypes numerical score from the Chiropractic Professional Identity Subtype Orientation Scale (CPISOS). A numerical score from the self-categorisation of chiropractors' professional identity along a philosophical continuum scale. Demographical details will be analysed through descriptive statistics. Pragmatic use of additional statistical analyses between year groups for the CPIES and CPISOS will be used, and various correlations will be investigated for subscale and sum scores. Location The data will be collected online, and the research will be hosted by the Scotland College of Chiropractic.

Does Stress Change EEG Measures in Students: A Feasibility Study

The study's primary aim is to assess the feasibility of a more extensive future study. The investigators also hypothesise that as the semester progresses, participants will exhibit changes in their EEG outcomes that may be related to longitudinal or direct stressors. Study design and setting This study will be an observational study with a stress-related questionnaire (Depression, Anxiety, and Stress Scale - 21 (DASS-21)) over three time-points. Participants The investigators aim to recruit 10 participants and assess them three times over the course of their semester, early, middle, and late semester, with at least a four-week gap between each data collection. The investigators aim to recruit only healthy Scottish chiropractic students with no prior diagnosed mental disorder and who are capable of understanding the study procedure. Procedure Following screening for eligibility and consent, i.e., visit one (baseline), participants will be asked to answer a questionnaire and undergo EEG measurement and Montreal imaging stress task (MIST). The same EEG and questionnaire procedure will be performed in the remaining two data collection sessions. Each EEG recording session, with the participant seated, will consist of a two-minute resting state with the eyes closed for a baseline relaxation level among the participants. A following two-minute eyes-open phase will take place. After which, participants will be asked to perform the experimental phase of the MIST task, a following two-minute recording phase will be with the eyes open, and a final two-minute resting phase with eyes closed will conclude the task. The investigators aim to conclude the data collection around 16 weeks after the initial participant is recruited.

Visual Frailty in Ageing

This is a mixed methods observational cross-sectional study that will consist of designing a tool to measure visual frailty and piloting it in a cohort of participants in the ageing population. The study will be implemented over a period of three years: literature review to define visual frailty and designing of the tool in the first year, recruitment of participants and performing a pilot and a validation study in the second year and thesis write-up in the final year. Participants aged 60 and above with a known diagnosis of advanced Age-related Macular Degeneration (AMD) will be recruited from Princess Alexandra Eye Pavilion (PAEP) macular clinic, Anne Rowling Clinic which is hosting the NHS Low Visual Aid Clinic, or any other NHS Lothian facility treating patients with Age-related Macular Degeneration (AMD). The visual frailty index will consist of results from visual acuity, reading performance, functional status, mental health and co-morbidities. This tool will be piloted in a cohort of 20 patients with advanced AMD. The internal consistency of the tool will be determined at this phase of the project. In addition to visual frailty, physical frailty will also be assessed in this cohort to enable analysis and establishment of the relationship between the two. The patients with AMD and their relatives/carers will be invited to participate in remote data collection about their perspectives on visual frailty. Best corrected distance and near visual acuity will be assessed and recorded. Reading performance will consist of reading speed and reading acuity which will be automatically measured using Digital Radner that will be acquired and installed before the implementation of the study. Functional status will be assessed using Lawton and Brody Instrumental Activities of Daily Living (IADL) Scale. Mental health will consist of depression, anxiety, and cognitive impairment that will be assessed using General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Six-item Cognitive Impairment Test (6-CIT) respectively. All these are validated tools. Physical frailty will be assessed using the FRAIL scale which relies on functions of fatigue, resistance, ambulation, illnesses and loss of weight. Information about co-morbidities will be retrieved from the patients' health record through National Health Service (NHS) Lothian. The data to be collected remotely from both the patients and their relatives/carers will be done through a phone call which will be scheduled during the hospital appointment. These calls will be recorded for analysis. They will then be transcribed verbatim, coded, and themes will be generated during the analysis. In addition to defining and designing a tool to measure visual frailty, expert input will be sought from optometrists and ophthalmologists about this topic using an online survey.