Jiangsu, China

Impact of Chronic Pulmonary Aspergillosis (CPA) on Health Status and Well-being

APACE - Feasibility of Using Accelerometers to Measure Physical Activity in Cancer Patients on Early Phase Clinical Trials

Different Doses of BI-1607 in Combination with Pembrolizumab and Ipilimumab, in Participants with Unresectable or Metastatic Melanoma

Trial Participants: This trial will include an estimated number of 35 participants with melanoma cancer who have not been helped by standard treatments. The main purposes of this trial are : 1. To learn about the safety and tolerability of BI1607 when received in combination with ipilimumab and pembrolizumab, 2. To determine the best dose (quantity) of both BI-1607 and ipilimumab when combined with pembrolizumab, and 3. To see if this triple combination therapy of BI-1607/ipilimumab/ pembrolizumab is more effective. To investigate this, the researchers will study: - what medical problems can happen during the trial, whether there are changes in the participants' health, how many participants reduce their dose of treatment or stop treatment for a period during the trial, and how many participants have medical problems that cause them to stop their trial treatment early. - how many participants have dose-limiting toxicities (also called "DLTs", which are medical problems severe enough to stop the trial doctors from increasing a treatment dose in the next group of participants). 2. The researchers will also study the following additional questions in this trial: - how BI-1607 acts in the body when received with ipilimumab/pembrolizumab. - whether the triple combination at varying doses of BI-1607 and ipilimumab acts in the participants' bodies as expected and has a desired effect on certain proteins in the participants' immune systems. - the number of participants who produce "antibodies" against BI-1607 and tolerability. Antibodies are proteins which are part of the immune system that help fight an infection. However, the body can produce antibodies against a treatment, which can stop the treatment from working properly. - how many participants' tumors shrink after receiving BI-1607 in combination with ipilimumab/pembrolizumab, and how long do their tumors shrink before their melanoma get worse or they pass away. What is planned to happen during this trial: The participants are planned to be in this trial for a maximum of 25.5 months. This trial started end of 2024 and is planned to end in 2028. This trial will have 2 parts, called Phase 1 and Phase 2. In Phase 1, at least 15 participants will receive BI-1607 and ipilimumab once every three weeks over four treatment time points, i.e., 12 weeks. Pembrolizumab will be added to the combination treatment at the third and fourth treatment. If the participant continues in the trial thereafter, pembrolizumab will be administered alone every third week from the fifth week onwards, up to a total of 35 treatments or approximately 2 years. This phase 1 will likely contain 4 groups of participants receiving different dose levels of treatments. After the participants in the first dose group have received their first treatments, the Sponsor, in collaboration with researchers, decides if this dose is safe, and the dose will be increased in the next group of participants. In Phase 2, approximately 20 participants will receive BI-1607 at the selected dose that the Sponsor and researchers decide is safe during Phase 1. BI-1607 will be administered once every three weeks in combination with both ipilimumab and pembrolizumab over four treatment time points, i.e., 12 weeks. Thereafter, pembrolizumab will be administered alone every third week, up to a total of 35 treatments or approximately 2 years. In both phases, the treatments will be administered via an "IV infusion" in which an IV line is inserted into a vein usually in the arm. The treatments will be dosed in milligrams, also called "mg". The lowest dose of BI-1607 will be 350 mg, and the highest possible dose will be 700 mg. Ipilimumab will be given to participants at a dose of 1 mg/kg body weight or 3 mg/kg. The dose of pembrolizumab will be 200 mg. Throughout the trial, the researchers will check the participants' health and any medical problems, ask about any medications they are receiving, take blood, tumor, and urine samples, and scan their tumors. The researchers will do these tests to learn how safe BI-1607 is in combination with ipilimumab/pembrolizumab, how the drug acts in the body, and how the treatment affects the participants' tumors. Benefits of this trial: There is no guarantee that the participants will receive any benefit from participating in this trial. However, their participation may help other people who have melanoma receive better care in the future. Risks of this trial: Participant safety is the most important factor in clinical trials. However, it cannot be guaranteed that the participants will not have medical problems during this trial. The clinical researcher will determine if the participant should no longer take part in the study if the results show the treatment doses are not safe. The Sponsor, Ethics Committee, or Regulatory Authority may also decide to stop the study at any time for any reason.

A First-in-human Study to Learn About the Safety of BAY 3547926 and How Well it Works in Participants With Advanced Liver Cancer

A First-in-human Study to Learn How Safe BAY 3713372 is and How it Works in Participants With MTAP-deleted Solid Tumors

The Biomechanical Outcomes of Autologous Chondrocyte Implantation

Knee joint articular cartilage is a primary load-bearing surface that endures repetitive high impact loading during activities of daily living. Individuals of any age can injure the knee's articular cartilage. However, as cartilage has an innate limited capacity to regenerate, surgical interventions that adopt tissue engineering techniques are often necessary to repair cartilage and preserve the joint. Autologous chondrocyte implantation (ACI) is a surgical procedure that is offered to some patients with focal cartilage injuries of the knee. The first pilot study on the use of ACI in humans was published by Brittberg and colleagues in 1994. By 2010 35,000 ACI procedures had been performed worldwide. Patient-reported outcomes and survivorship of ACI have been well reported in current literature. However, objective biomechanical and functional outcomes of ACI patients are not well understood. This knowledge is essential for optimising treatment, because poor functional outcome is known to worsen quality of life. This is particularly true for patients of working age who wish to return to an active and independent lifestyle. The applicant recently conducted and published a systematic review on the functional outcome of ACI. The review identified only 19 eligible articles of 20 ACI cohorts. The data showed that the average range of motion (ROM) improved with clinical (>5˚) and statistical significance (p < 0.05) postoperatively: 130.5± 14.8˚ to 136.1±10.2º, however only 7 studies reported both pre- and post-operative RoM. Knee strength significantly improved within the first two postoperative years but remained poorer than control groups at final follow-up (n=11). The review also found no statistical differences between ACI and control groups in their ability to perform functional activities like the 6-minute walk and hop tests post-operatively (n = 8). Only two papers had published on the kinematics of gait post-operatively. Both papers reported the outcomes of the same cohort, stating that there were no significant differences in spatio-temporal parameters between ACI patients and controls post-operatively. However, kinematic differences were observed during two specific phases of the gait cycle. Differences were also reported in peak knee adduction and peak knee extension moments. The limited literature identified by this review highlighted the urgent need for research into the functional outcomes of joint preservation surgeries like ACI to optimise functional outcome.

Aftereffects of PES Preconditioned with RTMS on the Human Pharyngeal Motor Cortex

1 Study design This is a cross-over study with the order of experimental conditions randomized for each participant. The randomisation will be conducted using a randomisation program (Stats Direct, v2.7.8, StatsDirect Ltd, Altrincham, UK). Each condition will be given on separate days, at least one week apart. 2. Participants Healthy volunteers over the age of 18 will be recruited through adverts placed around Salford Royal Hospital, on a University of Manchester website which advertises for research volunteers and through a departmental database of volunteers who have expressed an interest in future research. 3. Informed consent A participant information sheet will be given to each participant. A researcher with up-to-date Good Clinical Practice (GCP) training will be responsible for obtaining consent from the participants. He/she will explain the study purpose and nature and experimental procedures verbally to the participants. The participants will be given sufficient time (at least 24 hours) to read and digest the written information and discuss with the researcher about the study. The researcher will ensure the participants are volunteering to participate, understand the purpose and nature, experimental procedures, benefits and risks of the study before obtaining written consent from them. The participants should understand that they have the rights to withdraw from the study anytime throughout the study. 4. Study Procedures Participants will undergo either active or sham preconditioned 1 Hz rTMS interventions with 30 min intervals before active or sham 5 Hz PES (Fig 1). Each session involved: 1. A baseline measurement of PMEP and TMEP. 2. Application of (active/sham) 1 Hz rTMS (preconditioning). 3. A resting interval (30 minutes). 4. Application of (active/sham) 5 Hz PES (conditioning). 5. Measurement of PMEP and TMEP at multiple time points (immediately, 15, 30, 45, and 60 minutes post-PES). 5. End of study The study will come to an end after the period of data collection and analysis by the end of August 2025. 6. Withdraw consent Participants are able to withdraw consent at any time they wish. This will be stressed to all participants by members of the research team. Should this happen, their data will be retained with permission from the subject and they will be removed from the study. As only healthy participants will be recruited for this study, no participant is expected to lose the capacity to consent during the course of the study. However, if for any reason a loss of capacity is suspected, the participant will be excluded from the study.

Investigating the Impacts of Early Life Experience on the Brain & Behaviour

Step 1: Telephone/Video screening call (20 minutes) The first part of this study is a brief telephone/video call during which you will: - Be asked questions to check whether you meet the study eligibility criteria. - Be asked questions about your medical history (including mental health) and use of psychiatric medication. Step 2: ONLINE PARTS OF THE STUDY (3 hours) Once you have completed the online consent form you will be emailed a link to the online parts of the study. - You will be asked to fill in three online questionnaires which take around 30 minutes each and collect information about your demographics (e.g., sex, job, ethnicity, income etc.,), medical history, mental health conditions (e.g., autism spectrum quotient (you may opt of this questionnaire), depression, anxiety, addiction, drug and alcohol use) and personality traits (e.g., impulsivity, attachment, neuroticism, extraversion). - You will be asked to complete online games which are designed to assess memory, impulsivity, attention, face recognition and social interaction. These short tasks (5 - 10 minutes each) are similar to simple "brain training" games you may have seen online. They will take around 1.5 hours to complete in total. Step 3: FACE-TO-FACE PARTS OF THE STUDY (2-hours) BRAIN SCAN (1.5 hours) - When you arrive, you will be asked to review this study information sheet and sign a paper consent form and other safety/screening forms required for the study. - You will then be asked to take part in a magnetic resonance imaging (MRI) brain scan. You will be asked to lie down in a strong magnetic field for an hour whilst a computer takes pictures of your brain, and you complete short cognitive tasks (3 x 10 minutes each) and a resting state brain scan (10 minutes). BLOOD TEST (30 minutes) We would also like to collect a blood sample from you, as this will help us understand how early life events can impact your white blood cells which are a key part of your immune system. Step 4: INTERVIEWS, QUESTIONNAIRES & MEMORY GAME (1.5 - 3 hours) You can choose to do the following parts of the study either when you visit the University of Manchester or during a remote session (Zoom/telephone). - The researcher will conduct interviews about your mental health history and your experience of friendships and relationships (up 2.5 hours). - You will be asked to complete a short, anonymised questionnaires about your experience of trauma and stress in your childhood including the Childhood Trauma Questionnaire and the Adverse Childhood Experiences questionnaire (15 minutes). - You will complete a short emotional memory game (on the researchers' laptop or via your computer if via Zoom) (5 minutes).

A Phase Ⅲ Study of Rilvegostomig in Combination With Fluoropyrimidine and Trastuzumab Deruxtecan as the First-line Treatment for HER2-positive Gastric Cancer

The purpose of this study is to assess the efficacy and safety of rilvegostomig in combination with fluoropyrimidine and T-DXd (Arm A) compared to trastuzumab, chemotherapy, and pembrolizumab (Arm B) in HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma participants whose tumors express PD L1 CPS ≥ 1. Rilvegostomig in combination with trastuzumab and chemotherapy will be evaluated in a separate arm (Arm C) to assess the contribution of each component in the experimental arm. This study will be conducted at up to 200-250 sites globally in approximately 25 countries.

Driving with Neuropathy

Each participant will attend the driving simulator laboratory within the Manchester Institute of Sport at the Manchester Metropolitan University. All participants will, after a practice drive on the simulator (Drive 1) undergo a baseline assessment of their driving (Drive 2). Participants with DPN who never pushed the accelerator pedal down more than 9 degrees in the baseline assessment drive (Drive 2) will be screened out and take no further part in the study (as they cannot further reduce their use of the accelerator pedal beyond 9 degrees; they already spend no time driving with the pedal in that range). Participants with DPN who did push the accelerator down more than 9 degrees in the baseline assessment drive (Drive 2) will at the end of that drive be randomly assigned to intervention or control group. The intervention group will experience an active visual feedback intervention during simulated driving which aims to modify their use of the accelerator pedal, specifically to reduce the % of time they spend driving with the accelerator pedal pushed down more than 9 degrees i.e., to moderate their use of the accelerator and so help them to drive safely. The control group will receive a minimal intervention with no visual feedback and the minimum simulated driving experience necessary for us to assess their driving. Intervention (DPN) The active intervention phase for the DPN group will consist of 6 visits to the simulator with a month between each visit. Control (DPN) The DPN control group who receive minimal intervention will have an initial visit (baseline assessment), a second visit timed to match visit 3 of the intervention group (the halfway point in the study), and a final visit timed to match visit 6 of the intervention group, to permit comparisons with the intervention group at the start, halfway point, and end of the study. At the first visit, the session will last up to 1 hour 45 minutes in total. There will be a number of different components to the protocol (see below). At the first visit, informed consent will be taken by a researcher at the Manchester Metropolitan University trained in Good Clinical Practice. Also, at first visit only, physiological measures to confirm the severity (or absence) of neuropathy will then be taken as described below; and demographic and other information will be obtained. This will be followed by driving simulator testing. In all subsequent visits, only simulated driving will be tested. In all visits, a blood glucose test will be performed prior to undertaking the driving simulator test, to confirm that participants are not close to the hypoglycaemic range (should be ≥4.5 mmol/l) or hyperglycaemic (<20 mmol/l) at the time of driving. Peripheral neuropathy testing [approximately 15 minutes]: All participants will undergo the neuropathy tests described at their first visit only. These tests are routine clinical tests performed for diabetes patients to test peripheral sensory perception. For participants who arrive with diagnosed diabetic peripheral neuropathy researchers would be conducting these tests to assess the severity of peripheral neuropathy. For participants who arrive with no diagnosed neuropathy, researchers would be conducting these tests to confirm the absence of neuropathy. Researchers will apply two common tests for neuropathy - the mNDS and VPT. The mNDS is a composite test of multiple sensory modalities testing temperature perception (ability to distinguish between a warm and cold object applied to the end of the big toe), pain perception (ability to distinguish between a sharp and blunt object applied to the end of the big toe), vibration detection (ability to distinguish between a tuning fork applied to the end of the big toe that is vibrating at 128Hz, and the same tuning fork applied without any vibration) and the presence of an Achilles tendon reflex. The VPT involves an instrument applied to the end of the big toe with the vibration incrementally increased until the person can first detect the vibration. Researchers will assign participants either to the no/low DPN group, or to the DPN group, based upon their prior clinical diagnosis confirmed by the results of these tests for neuropathy. Testing of proprioception [approximately 15 minutes]: Participants will undergo testing of proprioception at first visit only. Researchers measure this because loss of proprioception at the ankle is another sensory consequence of neuropathy, and ankle joint angle varies with accelerator position when driving. This measurement therefore permits further confirmation of the presence of neuropathy and a consequence that might be important for driving (in addition to the standard clinical tests described above). To assess proprioception at the ankle, researchers will use a machine called an isokinetic dynamometer (a CE marked device) that researchers have routinely used to test proprioception in people with diabetes, older adults and other populations. Participants will be positioned prone on the bed of the dynamometer with their knee in full extension and their right foot (because this is the foot used for applying the accelerator and brake) secured into the footplate of the dynamometer. To assess proprioception at the ankle, which is a useful proxy for the extent to which the person knows the position of their foot during driving, researchers will ask them to recreate certain joint positions. This will entail moving the participant's foot to a given ankle joint angle and then moving their foot away from this position and asking them to return their foot to the previous position as accurately as possible. Researchers will be able to record the ankle joint position and the 'error' in degrees between the intended and actual positions. Blood glucose test [approximately 10 minutes]: A blood glucose test will always be performed prior to undertaking the driving simulator test, to confirm that participants are not close to the hypoglycaemic range (should be ≥4.5 mmol/l) or hyperglycaemic (should be <20 mmol/l) at the time of driving. Participants should therefore have a blood glucose level within the range 4.5 to 20 mmol/l. If participants are outside of this blood glucose range, they will be invited back to the university for testing on another occasion. A capillary blood sample will be acquired from the finger by 'pricking' the finger and acquiring blood onto the testing strip of a blood glucose meter immediately after being taken. The sample will therefore not be stored and will be disposed of appropriately immediately after testing for the level of glucose. In the case where participants have continuous glucose monitors, researchers will take blood glucose readings from their device to avoid the need for any additional blood measures. Because people with diabetes may carry glucose testing meters with them and will be familiar with testing themselves regularly, they may prefer to test themselves - in this instance researchers will use the value they obtain. Demographic details and other information [approximately 20 minutes]: At first visit only, researchers will take routine anthropometric measures: height and body weight to adequately characterise our sample. Researchers will ask participants a series of questions to establish the demographic information about the sample researchers are studying such as their date of birth and ethnicity. Researchers will perform a Snellen test (sight test) to check their corrected visual acuity (ie while they wear any prescription spectacles) - this involves reading standard-sized letters from a piece of paper at a set distance. Researchers will ask about any current involvement in other research studies. Researchers will ask participants their time since diagnosis of diabetes and about any medication they are currently taking (for all groups, since this might affect driving performance). Researchers will ask a series of questions about driving such as the type of car the person currently drives (i.e., manual or automatic, estate-type car or saloon-type etc.) and how long they have held their UK driving licence for. Researchers will also ask participants some questions similar to those that a car insurance firm would ask when someone is taking out car insurance - specifically whether they have had any accidents in the last 5 years, if so whether it was judged to be their fault or not and whether they have any points on their driving licence. The reason researchers intend to ask these questions is so that they may relate this kind of specific information to driving performance in the simulator, or more specifically to use of the accelerator pedal. As with all other research data, this information will be pseudo-anonymised and only associated with a participant code. Before researchers ask all of these questions, they will make it very clear to participants that all of this information is confidential, is used only for the purpose of the research study and will not be shared with anyone outside of the research team. If participants do not wish to provide this information they will still be able to proceed with the remainder of the protocol. Driving simulator testing [27-39 minutes of driving]: While taking consent from the participant and therefore before the participant initiates the driving tests, researchers will have been very clear to explain that the purpose of these measurements of their simulated driving is for research purposes only and that they will not be used in any way to inform decisions on their fitness to drive. Researchers will also clarify that they will not be sharing their data with anyone outside of the research team. These research data will be stored on a password protected computer and as with all other research data will be stored using pseudorandomised participant codes. The assessment of driving will follow a well-established protocol built up from a number of previous studies in our laboratory using the identical simulator. The participant sits in a comfortable car seat in front of a bench on which there is a large, windscreen-sized flat screen display (viewing distance approx 1 metre) showing the view of the road ahead. The car seat is adjustable to achieve a comfortable driving position with hands on the steering wheel and feet on the pedals. Sensors within the steering wheel and accelerator pedal housing are invisible to the driver and measure the position of the steering wheel and accelerator pedal throughout the tests. There are no sensors attached to the participant; the aim is to monitor his or her driving imperceptibly so as not to cause any distraction. Once the participant is seated in a comfortable driving position, a standard instruction to 'drive safely, as you would in a real car on the road' together with other brief information on the absence of other vehicles, pedestrians or junctions along the route, will be read out. The driving simulation programme is then started, this is essentially a driving computer game which offers a number of routes along winding country roads. The DPN intervention group will be asked to complete the following 5 drives each time they visit: Drive 1. Practice (3 minutes). Drivers with neuropathy take a little longer than other drivers to get used to the feel of the simulator. They drive differently for the first 3 minutes as they learn the weighting of the pedals and steering wheel. This standardised practice drive, along a route similar to the one on which they will subsequently be tested, ensures that before beginning the evaluation and intervention part of the session they are familiar with the simulator and driving as well as they can. Drive 2. Assessment (6-9 minutes). This drive along a standard test route assesses their driving ability as they arrived at the simulator on the day. Since participants choose their own safe driving speed, time to complete the route varies (typically 7 minutes driving mainly at 30-35 mph). Researchers will impose an upper limit of 9 minutes' driving to avoid fatigue over the course of the session. At the end of this drive, in their first visit, drivers with DPN who never pushed the accelerator pedal beyond 9 degrees down (the trigger value for delivering visual feedback) will be told that their use of the accelerator pedal does not need modification by visual feedback training, and that they therefore will not continue to the intervention phase of the study but will stop at this point. At the end of this drive, in their first visit, drivers with DPN who did push the accelerator pedal beyond 9 degrees for some % of the drive time will at this point be randomly assigned to either the intervention group or the control group. Drivers assigned to the intervention group will receive an immediate analysis of their use of the accelerator pedal and their overall speed. Researchers will explain that changes in driving can develop gradually as a consequence of diabetic peripheral neuropathy, and that one of these is a tendency to sometimes skip over the mid-range of the accelerator pedal, so that the pedal is pushed down a long way, resulting in too strong accelerations that make it difficult to stay in control of the vehicle. Researchers will then demonstrate a simple visual feedback system consisting of an illuminated pedal warning symbol (in the style of a road speed limit sign, a white background with a red circular surround, containing an icon of a foot just off/above a pedal) at the right hand side of the simulated car windscreen, which will appear whenever the pedal is pushed down beyond its mid-range into a more extreme position, defined as more than 9 degrees down. In the simulator, maximum depression of the pedal is 20 degrees down, so 9 degrees represents 45% of maximum acceleration. The region beyond this point is infrequently used by drivers with no medical condition who have been told to drive safely, as they would in a real car on the road. The participant will be instructed that in the next drive whenever they push the accelerator pedal more than halfway down, the pedal warning symbol will appear, and they should ease back off the accelerator until it turns off (which will happen when the pedal is once again less than halfway down). Before driving, the participant will practise a few times pushing the accelerator down by different amounts with the visual feedback active to enable them to get a feel for the pedal position at which the warning symbol will appear. Researchers will then ask them to drive the same standard test route again with this visual feedback on their use of the accelerator activated (which will be Drive 3, see below). Repeated driving of the same test route allows us to assess a common driving task such as the daily commute, in which the journey is well known and practised. Drive 3. Driving with feedback and immediate prior instruction (6-9 minutes). The standard test route will be driven again, this time with the pedal warning symbol coming on to indicate whenever the accelerator pedal is pushed too far down (more than 9 degrees). At the end of this drive, an immediate analysis will be provided as before to identify whether there has been any change in driving behaviour away from that associated with diabetic peripheral neuropathy and towards that seen for drivers without this condition. Drive 4. Driving after feedback, without feedback (6-9 minutes). The same route will be driven again, but without feedback. This will identify whether any changes seen whilst feedback was being provided in Drive 3 persist after feedback is withdrawn. This will indicate whether driver training using feedback was only effective whilst the feedback was actually being given (so that it would be permanently required) or whether a brief period of training could induce a change that persisted beyond its duration (so that it could be episodic). Drive 5. Driving with feedback again but without immediate prior instruction (6-9 minutes). This final drive will assess the effectiveness of the warning symbol to modify driving when no immediately prior instruction has been given (but the meaning of the symbol is understood). Simulated driving time at each visit will therefore be 3 minutes + 4 x (6-9 minutes) yielding a total time of 27-39 minutes. Comparison of all these drives between monthly visits will reveal how the long-term benefits of visual feedback training are sustained. Researchers will ask participants in the DPN control group, and the no/low DPN group, to complete only the following driving tasks: Drive 1. Practice (3 minutes). Drivers with neuropathy take a little longer than other drivers to get used to the feel of the simulator. They drive differently for the first 3 minutes as they learn the weighting of the pedals and steering wheel. This standardised practice drive, along a route similar to the one on which they will subsequently be tested, ensures that before beginning the assessed drive along the standard test route they are familiar with the simulator and driving as well as they can. Drivers in the no/low neuropathy group will complete the same drive to permit comparison with drivers in the other groups. Drive 2. Assessment (6-9 minutes). This drive along a standard test route assesses their driving ability as they arrived at the simulator on the day. Since participants choose their own safe driving speed, time to complete the route varies (typically 7 minutes driving mainly at 30-35 mph). Researchers will impose an upper limit of 9 minutes' driving to maintain compatibility with Drive 2 as experienced by the DPN intervention group. At the end of this drive, no analysis will be provided of their use of the accelerator pedal, and no explanation given that changes in driving can develop as a consequence of diabetic peripheral neuropathy. There will be no further drives, and consequently no experience of the visual feedback training. These participants therefore receive the minimum experience on the driving simulator that will still enable us to assess their driving at that visit on that day. Post-driving participant feedback: After the driving session has finished in their last visit to the simulator only researchers will provide an opportunity for participant feedback on their experience to the research team. Researchers will encourage participants to share their thoughts about their experience and use their comments for our future guidance. Often, participants provide insights into their own approach to the task which are helpful for us to assess the current protocol, and to feed into the development of future experimental protocols. Researchers will ask the following questions: 1. Having completed the last driving session today do you have any comments about your experience of driving in the simulator in this study? 2. How did it feel to drive with the visual feedback turned on? 3. Do you have any suggestions for changes we could make to the simulated driving sessions, or other things we could do in the future? 4. Did you find anything about the task annoying or difficult? Anything we could improve? 5. Is there anything else you'd like to tell us? The DPN intervention group will be asked all of the above questions in their final visit. The DPN control group and the no/low DPN group will in their final visit be asked all of the questions except question 2 (as they did not drive with the visual feedback turned on). All DPN drivers will be given an information leaflet published by the DVLA which has information about driving with neuropathy. Researchers will also provide the details of the local driving mobility assessment centre, and advise that if they have any concerns about their driving they can contact this centre to arrange a professional driving assessment by an approved instructor.