Oxford

Patients entering the study will attend for implantation of a pacemaker device and be randomised to either right ventricular pacing or physiological pacing. Patients at sites participating in echo sub-study will be informed of and given opportunity to consent to echo sub-study, this will be optional to them, even if they have consented to the main study.

This is a randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of elenestinib (BLU-263) + symptom directed therapy (SDT) with placebo + SDT in participants with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by SDT. Parts 1 and 2 will enroll participants with ISM. Participants enrolled in Part 2 will roll over onto Part 3 to receive treatment with elenestinib in an open-label fashion following completion of the earlier Part. Part K will enroll participants with ISM who have previously received an approved selective KIT inhibitor. The study also includes pharmacokinetic (PK) groups that will enroll participants with ISM.

Antidepressants typically decrease amygdala response to negative stimuli while enhancing response to positive stimuli, but it is unclear at a mechanistic level how increasing serotonin would have this opposing effect. One hypothesis is that although positive and negative cues activate the same area at a global level, more detailed characterisation may reveal key differences in processing in terms of localisation or response function. Until now, due to methodological restriction, the amygdala has been mostly studied as a single structure. It is however known that it consists of a number of subfields, which are likely to play distinct roles in emotional processing. In this study the investigators will make use of 7T fMRI scanning to study the effects of a single dose (20 mg) of citalopram (selective serotonin reuptake inhibitor, SSRI) on these subfields during emotional face processing, allowing greater precision to identify underlying neural mechanisms underpinning psychological effects.

Clinical history, imaging data, biological samples and information derived from are the main items to be captured to the SwissNeuroFoundation AneurysmDataBase. No limits are set on the number of healthy volunteers and patient cases for whom data can be entered to the SwissNeuroFoundation AneurysmDataBase. Participants will be recruited from the following sources: * Patients arriving at partner clinical centers either as newly diagnosed (incidental cases) or already known for the disease (prevalent cases) * Healthy volunteers answering a call, randomly selected subjects from a known population that consent to participate or non genetically linked family members of patients that consent to participate * Family members of patients identified as having a familial history of intracranial aneurysm (IA). Points of consent: The specific items on which participants are asked to consent: * to having been verbally informed of the aims of the project * to having read the information sheet about the project, been able to ask questions about the project, and to having received satisfactory answers and enough time to make the decision. * to having been informed that any damage that could be directly caused by the participation to the project is covered by insurance. * that hospital care providers working on behalf of the project and representatives of the local authorities and ethics commission may access in a strictly confidential term raw data for quality check. * to having been informed that participation can be withdrawn anytime without justification and will result in a medical assessment for own security. There will be no impact on future care resulting from withdrawal. * to be free to refuse answering questions without requiring any justification and it will have no impact on future care. * to understand that data may be used in a non-identifying form for publication. * to understand that data provided may form part of future commercial applications, and will not benefit financially from this. * to understand and agree that coded data may be used for further cerebrovascular-related research. * that they understand that coded data about them or biological samples may be transferred outside the European Union. The specific items on which participants are asked to agree or disagree: * that they agree to provide access to health records, to provide a link from them to the SwissNeuroFoundation AneurysmDataBase, and to complete a questionnaire on their clinical history. * give agreement to provide image data to SwissNeuroFoundation AneurysmDataBase. * give agreement to provide blood samples to SwissNeuroFoundation AneurysmDataBase. * give agreement to use biological samples resulting from therapeutical intervention. * give agreement to use saliva and stool samples to SwissNeuroFoundation AneurysmDataBase. * give agreement to be re-contacted by SwissNeuroFoundation AneurysmDataBase for further consent or to request further information. * give agreement to inform the General Practitioner about the participation to the project. * give agreement to contact the General Practitioner to request information on participant whereabouts or limited relevant medical information, if direct contact was unsuccessful during 3 months. * request to be informed by the clinician in charge about observations resulting from the project that may have a significant impact on the participant health. * request the General Practitioner of the participant to be informed about observations resulting from the project that may have a significant impact on the participant health. Separate specific points of consent relative to biological samples and genetics: * having read the genetic testing information sheet, been able to ask questions about genetic testing, and understanding why the research is being done and any risks involved * give agreement to provide blood samples to SwissNeuroFoundation AneurysmDataBase * understanding that genetic data arising from samples may form part of future commercial applications, and that they will not benefit financially from this. * understanding that they are free to withdraw at any time and may ask for their sample to be destroyed then, or at any other time. * agree that blood samples be stored and used for genetic analysis. * agree that blood, aneurysm dome, cerebrospinal fluid (CSF) and microdialysis samples be stored and used for further cerebrovascular-related research. * agreement that blood samples may be transferred with coded labels to other Universities in the World. For the purpose of the AneurysmDataBase: Clinical Information consists of: * Demographic information (Pseudonym, Age, Gender, Size, Weight, work and sport activities, habits: smoking, alcool consumption). * Personal medical history (Previous strokes, previous epilepsy, previous medication) * Family tree denoting known or likely diagnosed IA or subarachnoid hemorrhage (SAH) events. * Signs and symptoms (date of ictus, date of diagnosis, mRankin score, Glasgow Coma Scale (GCS), NIH Stroke Scale (NIHSS),Mini Mental State Exam (MMSE), World Federation of Neurosurgeons Scale WFNS, Cranial nerve deficits) * Identified epidemiology factors according to check list. * Imaging analysis (Presence of SAH, Fisher grade, size of ventricles, size of basal cisterns, volume of hematoma and location, number of aneurysms, location of aneurysms, size of aneurysms, shape of aneurysm) * Treatment and outcome information (treatment method, success) * Follow-up and outcome information (Quality of life assessment, MMSE, mRankin, NIHSS, Cranial nerve deficits, aneurysms status: stable, growth, treated, partially treated) Imaging Data consist of: * Pseudonymised DICOM files of: * MRI angiography (MRA) * Computed Tomography Angiography (CTA) * 3D reconstruction of Digital Rotation Angiography (3D-DRA) Samples consist of: * Blood in DNA saving solution * Blood in RNA saving solution * Blood in EDTA * CSF * Aneurysm dome * Saliva * Stool * Other biological sample to be specified

Researchers want to know if the study treatment called MK-2214 works to slow certain changes in the brains of people with Alzheimer's disease (AD). AD is a type of dementia that can cause loss of memory, communication (such as speech), and decision-making skills. It can limit a person's ability to do daily tasks. MK-2214 is a study treatment designed to slow down AD. The goals of the study are to learn: * If MK-2214 slows the spread of tau in the brain compared to placebo. Tau is a protein that accumulates in AD \& damages brain cells. A placebo looks like the study treatment but has no study treatment in it. Using a placebo helps researchers better understand the effects of a study treatment. * About the safety of MK-2214 and if people tolerate it

Researchers are looking for other ways to prevent severe illness from COVID-19. COVID-19 is a virus that most often causes mild flu or cold-like symptoms. However, people with certain health conditions or other factors have a high risk (chance) of getting severely ill from COVID-19, which can require a hospital stay or lead to death. Some people who are high risk for severe illness may be unable to take certain treatments for COVID-19 because they are not available to them, or they take other medicines that may react with a treatment and cause an unwanted effect. Molnupiravir (MK-4482) is a study medicine designed to stop the COVID-19 virus from copying itself in the body (multiplying). The goal of this study is to learn if molnupiravir prevents severe illness from COVID-19 more than placebo in people who are high risk.

Researchers are looking for ways to treat germinal center B-cell-like diffuse large B-cell lymphoma (GCB DLBCL). DLBCL is a fast-growing blood cancer that affects B-cells. GCB is a type of DLBCL that affects young B-cells that are still maturing. The goal of this study is to learn if more people who receive zilovertamab vedotin (MK-2140) and R-CHP have the cancer respond (go away) than those who receive polatuzumab vedotin and R-CHP.

The purpose of this Phase 2 study is to evaluate the safety, tolerability, pharmacometrics, and efficacy of DNTH103 in participants with multifocal motor neuropathy (MMN).

An open-label, controlled, multi-site, interventional, 2-arm, Phase II/III trial of BNT113 in combination with pembrolizumab vs pembrolizumab monotherapy as first line treatment in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing programmed cell death ligand-1 (PD-L1) with combined positive score (CPS) ≥1. This trial has two parts. Part A, is an initial non-randomized Safety Run-In Phase to confirm the safety and tolerability at the selected dose range level of BNT113 in combination with pembrolizumab. Part B, is a randomized part to generate pivotal efficacy and safety data of BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy in the first line setting in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing PD-L1 with CPS ≥1. Patients included in the Safety Run-In Phase of the trial (Part A) will not be randomized to Part B and will continue on-trial treatment (BNT113 plus pembrolizumab) within Part A. For Part B, an optional pre-screening phase is available for all patients where patients' tumor samples may be submitted for central HPV16 DNA and central PD-L1 expression testing prior to screening into the main trial. Patients will be treated with BNT113 in combination with pembrolizumab or with pembrolizumab monotherapy for approximately up to 24 months.

The purpose of this study is to assess the efficacy and safety of trontinemab in participants with early symptomatic Alzheimer's disease (AD) (mild cognitive impairment \[MCI\] to mild dementia due to AD).