Adults

The research activities of phase 1 and 2 will include purposively recruiting participants for focus group discussion and in-depth interviews. The implementation team will help us identify the key stakeholders in the communities. While the consent form for key stakeholder will be used for all other participants of phase 1 and 2, the consent for phase 1, 2 and 3 for young adults will be covered under 1) consent for parents, if age of participants in intervention is less than 18 and 2) participant consent if they are above 18. Phase 3 of research will follow different process. Phase 3 for children to participate in the study, who are of age less than 18, the parents will be contacted for consent, first a set of screening questions will be asked to determine the eligibility of the participant for the study, once found eligible, a baseline interview will be conducted for collecting non-identifiable socio-demographic, data of the family. The informed consent is sought at this point. The participant will undergo the interviews for the validated questionnaires at 3 time points. Once before the intervention starts, once after 12 months of intervention and once after 18 months of intervention. The consent form for parents to seek permission for participation of the these participants covers all the three phases of the study. Screening and recruitment process: The screening will be a verbal process where the participants will be assessed whether they are eligible for participation. The baseline interview to collect data of the non-identifiable socio-demographic data. The data points to be collected are; 1) details about the land ownership, 2)cattle ownership, 3) type of house, 4) nature of family income, 5) source of water, 6)electricity, 7) material possessions at 'your' (participant's) home (TV, two-wheeler, mobile phone).These details will be used for understanding the socio-economic differences among the participants. Those who qualify to take part in this research study will attend two or more, one and half hour sessions every week, for the duration of one year. They will be assigned a code (name/village/household information will not appear in any document) and placed in one of the 'One-all' groups. Each of the 'One-all' groups will have approximately 20 participants (which will undergo organized sessions and ultimate frisbee game for the duration of the study). The following questionnaires will be administered to the participants as part of evaluation: 1. Connor-Davidson resilience scale (CD- RISC) to measure participant's capacity to bounce back from adversities. 2. The Child Youth Resilience Measure (CYRM) - to measure participant's capacity to bounce back from adversities. 3. GHQ12, a validated measure of participant's mental well-being. 4. Schwarzer's General Self-Efficacy Scale (GSE), to measure participant's self-efficacy. Questionnaires 1-4 will be administered at 3 time points: First time point is the baseline (before the first One-all session); second time point will be at the end of 12 months of receiving one-all sessions and third time point will be after 18 months of receiving One-all sessions as Endline.The participant will undergo intervention provided by the One-all implementation team. Implementation team will visit the communities for enrolling the participants for the intervention. This team will pass on the list of participants who have enrolled for the intervention to the research team. One-all programme delivery by implementation team (separate from research) The three-year curriculum is structured as a series of chapters followed by a year-end event usually a workshop or a tournament. Each chapter begins with an introduction that outlines the major content of the chapter, with topics and their objectives. Lesson plans have been created by the One All curriculum development team for each of these topics. Each session is designed to take maximum of one and half hours. The suggested time is considered the components. However, the lessons can always be expanded on a given day, or spread out over one or more days, for deeper and more graduated learning as time permits. Each session has the following 4 parts: 1. Warm up: provides the opportunity to prepare the children to become familiar with the learning topic for the day through a fun activity that is related to the topic. 2. Drills: are sporting activities that are more physically involved, but also connected to the application of the learning topic. 3. Game: is a mixed-gender "ultimate frisbee" match with modified rules to emphasize the application of the learning topic. 4. Spirit circle: Group discussion that is used to reflect and share the learning of the day. It also guides children in making thoughtful connections that anchor the learning. The implementation team will keep the records pertaining to attendance and the reflections of the sessions in detail. The research team will use these records. No medical records will be accessed through the course of the study.

Radiotherapy for cancer has been a forerunner of personalized medicine, developing individualized treatments based on patient-specific anatomical information. Despite many advances in radiotherapy over the past decade, which have effectively enhanced local or loco-regional tumor control for many patients, there remains substantial room for improvement. The challenges for radiotherapy to further widen the therapeutic window in the era of precision medicine are mainly two-fold: (a) further improve radiation dose conformity to the defined target volume, and (b) adapt novel biological strategies for personalized treatment. Four-dimensional (4D) imaging and deformable image registration (DIR) are key tools in modern radiotherapy, playing critical roles in many recent advances, including 4D radiotherapy, adaptive radiotherapy, and treatment assessment. However, current 4D imaging and DIR technologies are facing significant challenges as the requirement for precision increases. The current standard of 4D imaging in radiotherapy is 4D-CT. However, it has two major limitations preventing it from precision radiotherapy applications: (a) low soft-tissue contrast. 4D-CT is therefore not ideal for abdominal applications; (b) motion artifacts caused by irregular breathing. 4D-CT motion artifacts have been shown to cause errors in various radiotherapy applications, including motion measurement, target volume delineation, dose calculation, DIR, and lung ventilation calculation. 4D-MRI is an emerging 4D imaging technology for radiotherapy. It has superior soft-tissue contrast to 4D-CT and is therefore superb for abdominal imaging. Despite many recent advances in 4D-MRI, current 4D-MRI implementations have inadequate image quality for precision radiotherapy application due to at least one of the following deficiencies: low temporal and/or spatial resolutions, long image acquisition time, and suboptimal contrast in the lungs. Resulting 4D-MRI images lack sufficient anatomical details for clinical applications, which can adversely affect the performance of DIR. Current DIR techniques focus on morphological similarity but not on the physiological plausibility of the deformation. Studies have shown that an increased morphological similarity of the aligned data does not always imply increased registration accuracy. Therefore, more sophisticated approaches are desirable. The investigators will take a systematic approach to address the aforementioned limitations of 4D imaging and deformable image registration (DIR) based on the development and cross-fertilization of two major techniques: ultra-quality 4D-MRI and physiological-based hybrid DIR. There are two parts of this research, comprising three main objectives: Part 1. Technical development in healthy subjects: The investigators will extend their existing pulse sequence strategy for ultra-quality 3D MRI to enable ultra-quality 4D-MRI. Compared to 4D-CT and current 4D-MRI techniques, the proposed ultra-quality 4D-MRI technique offers the following advantages: (a) high spatial resolution (1.5 mm isotropic) with rich image features (e.g. vessel trees) in the whole torso; (b) high temporal pseudo-resolution (\>20 phases/cycle); and (c) (nearly) free of motion artifacts. • Objective 1: Develop an MRI pulse sequence and image reconstruction pipeline that generates images meeting these three design goals. Part 2. Evaluation of 4D-MRI in a patient study: 4D-MRI will be compared with existing DIR and 4D-CT methods. There will be two classes of comparisons, each formulated as a separate objective: * Objective 2: Compare motion modelling based on 4D-MRI with deformable image registration (DIR) in healthy volunteers and cancer patients. An improved motion modeling method will be developed that is tailored for the ultra-quality 4D-MRI applications. The investigators hypothesize that a new motion modeling method based on 4D-MRI will outperform current DIR algorithms for respiratory motion estimation. This hypothesis will be tested by comparing the new method to five DIR algorithms which include a mix of commercial software and publicly available algorithms. * Objective 3: Compare 4D-MRI with 4D-CT in lung and liver cancer patients. The overall hypothesis of this objective is that the ultra-quality 4D-MRI provides better image quality than 4D-CT for motion management of radiotherapy in the lungs and the liver, especially in patients with irregular breathing.

GenSci134 was tested in 7 predetermined dose groups with placebo and positive drug controls to explore the dosage, and to assess its safety, tolerability, pharmacokinetic (PK) characteristics, pharmacodynamic (PD) characteristics, immunogenicity, and exploratory endpoints in 64 healthy adult male subjects

The purpose of the study is to evaluate the safety of SPH9788 tablets in healthy subjects.

The proportion of older adults is on the rise in Canada, with the fastest growth recorded among those seventy years of age or older. The prevalence of cardiovascular risk factors (CVRF) such as diabetes, hypertension, and high cholesterol increases drastically with age. Individuals with CVRF often show impaired cognition, such as attention and memory deficits. In healthy older adults, exercise training and cognitive stimulation can help enhance cognitive performances. More precisely, combined intervention, including physical and cognitive training, has shown beneficial effects on cognition in older adults without cognitive impairment and with mild cognitive impairment. However, the effect of such programs on cognition in individuals with CVRF is not well documented. This project compares the effect of a physical exercise program, including aerobic and resistance training, alone or combined with cognitive training on cognitive performances and brain imaging outcomes in individuals with CVRF and healthy controls.

The objectives of the study are to investigate the feasibility and pilot-test the benefits of the computer-based E-MinD Life (Semantic) program to promote everyday performance in healthy older adults, older adults with memory complaints, mild cognitive impairment (MCI) and mild dementia in Hong Kong using a randomised control trial. Three groups of participants will be recruited: (1) 15 healthy older adults, (2) 15 older adults aged over 65 years with memory complaints, or older adults aged over 65 years, meeting the diagnostic criteria for MCI with a Clinical Dementia Rating score of 0 or having mild dementia with a Clinical Dementia Rating score of 1. All participants will have no depression and other clinical conditions that may affect their cognition. Their scores on the Montreal Cognitive Assessment will be recorded. Their carers or family members are invited to participate.

This prospective, single-arm study is designed to understand the mechanisms that lead to a loss of response to influenza vaccine in older adults through the establishment of the FluVax3 cohort of healthy older adults. In this study, the investigators will perform comprehensive profiling of blood antibodies and immune cells over time, and associate specific age-related immune alterations with vaccine responder or non-responder status. This will allow the investigators to pinpoint biological pathways that can be targeted to enhance vaccine efficacy and that can also help the investigators progress towards developing a universal influenza vaccine. The results are expected to provide the foundation for new approaches to improve overall vaccine efficacy and protection in older adults, an outcome of significant public health relevance considering the vulnerability of this population. In this study, up to seventy-five (75) healthy adults aged 65 years and older who have not received influenza vaccination for the approaching influenza season will be enrolled in the study and vaccinated with influenza vaccines approved by the U.S Food and Drug Administration (FDA) and recommended by the Centers for Disease Control and Prevention (CDC) for individuals ≥65 years. All participants receive influenza vaccine during the 2022-23, 2023-24, and 2024-25 influenza seasons. Participants will receive Fluzone® Quadrivalent High-Dose vaccine during the 2022-23 flu season, FLUAD® Quadrivalent during the 2023-24 flu season and Flublok Quadrivalent in the 2024-2025 flu season. The study sample will be drawn from the population of healthy older participants in the catchment area of UConn Health in Farmington, CT. Study participation will involve six study visits around the flu vaccine each year and one final study visit for a total of nineteen study visits over three years. Blood samples will be collected at sixteen study visits for transcriptional, epigenetic and biological analyses pre- and post-vaccination. Nasal swab and stool samples will also be collected from participants at seven time-points across the study period. These microbiome samples will be stored and used in future research. The study is not designed to assess safety or tolerability of the influenza vaccines administered as part of this proposed study. This project will yield an unparalleled dataset from healthy older adults that will be used to identify fundamental mechanisms, cell populations, and pathways associated with durable protective antibody immune responses, and lack thereof, upon influenza vaccination. In sum, this study will reveal the mechanistic alterations that explain the heterogeneity in response to vaccines observed in older individuals. Understanding this heterogeneity opens the possibility of stratifying older adults for personalized vaccines. In addition, understanding the mechanistic overlap between the correlates of responsiveness to three different influenza vaccines will advance the ultimate development of a universal influenza vaccine, which is a key focus of NIAID's influenza research program. Finally, this study will generate a considerable amount of transcriptional and functional data related to the outputs of key innate immune and T/B-cell subsets involved in responses to influenza vaccines in older adults. These data will collectively become an important resource for future studies focused on the older adult immune system in health and disease.

The objective of this study is to evaluate the effect of multiple oral doses of vorasidenib on the single dose pharmacokinetics of the representative combined oral contraceptive, drospirenone (DRSP)/ethinyl estradiol (EE), in healthy female participants. The study includes a screening phase, two treatment periods in-house, and a follow-up period. During the first period, from Day 1 through Day 5, participants will take one dose of DRSP/EE. In the second treatment period, from Day 6 through Day 24, participants will take vorasidenib every day, and on Day 20, they will take DRSP/EE along with vorasidenib. The entire study, including screening and follow-up, will last up to 83 days. Participants may undergo blood tests, heart tests (electrocardiogram (ECG)), vital sign checks, and physical exams.

Adults with cerebral palsy (CP) often face challenges in accessing exercise programmes that are appropriate for their needs. Barriers such as limited mobility, a lack of tailored options, and restricted access to physiotherapy services can make participation difficult. Exercise is important for improving physical health, mental well-being, and overall quality of life. However, many adults with CP do not have regular opportunities to take part in structured physical activity. This study aims to investigate whether an online exercise programme can serve as an effective and accessible alternative. The main aim of the study is to assess the feasibility of delivering an online exercise programme for adults with CP. Key areas of focus will include demand, implementation, practicality, adaptability, acceptability, and potential benefits to physical, mental, and social well-being. A total of 60 adults with CP will be recruited and randomly assigned to one of two groups (30 participants per group). One group will complete an 8-week online exercise and education programme. The second group will receive the same educational materials during the study and will be provided with information about the home exercise programme after the 8-week intervention period. Data will be collected on attendance, completion rates, engagement with exercises, and any reported adverse events. Health-related surveys will be completed before and after the programme to assess any changes. In addition, a selected group of participants from the intervention group will take part in interviews to provide feedback on their experiences. Findings from this study may support the development of accessible, effective, and person-centred online exercise programmes for adults with CP. Results may help improve future programme design and contribute to better care and support for adults with CP in Ireland.

This is a phase I randomized, double-blind, placebo-controlled, single ascending dose (SAD) study. The study will consist of 4 planned cohorts (A1 to A4), each comprised of 8 healthy participants. Doses of ABCL575 are intended to escalate through cohorts A1 to A4.