The purpose of this study is to evaluate the efficacy and safety of ibuzatrelvir with and without remdesivir compared with remdesivir alone for the treatment of symptomatic COVID-19 in adult participants who are severely immunocompromised. This study is being done to learn how the study drug, called ibuzatrelvir, works in treating people with COVID-19 who have a severely compromised immune system. Ibuzatrelvir stops the virus that causes COVID-19 from multiplying in cells and spreading around the body. It may help people to get better and stay out of the hospital.

This study systematically evaluates the efficacy of a highly promising neuromodulation strategy - continuous theta burst (cTBS) transcranial magnetic stimulation - as a tool to change alcohol use behavior (Aim 1) and neurobehavioral concomitants of that behavior (Aim 2) in non-treatment seeking individuals with alcohol use disorder (AUD). In addition, we can begin to test prediction of individual treatment response based on an electrocortical signature of sign tracking (exploratory aim). This study is a double-blind, active sham-controlled study in community dwelling, non-treatment seeking individuals who meet DSM 5 criteria for AUD. Participants will be randomized to one of three groups: cTBS to ventromedial prefrontal cortex, cTBS to pre-supplementary motor area, or sham stimulation (10 sessions in one day). Participants will undergo comprehensive outcomes assessment, with measures including pre- and immediately post-cTBS clinical assessments (e.g., interview, Timeline Follow-back), alcohol craving tests, structural and fMRI, MRS, and EEG/ERP during salience- and cognitive flexibility-related tasks. To test alcohol craving and also use in alcohol-available settings, participants will complete a bar-lab session post-cTBS only (to avoid potential habituation to alcohol cues within the laboratory setting). Finally at 1-week post-treatment participants will complete craving and Timeline Follow-back measures remotely via REDCap.

Feeding requires babies to coordinate sucking and swallowing, which depends on healthy brain development. Some newborns who experience brain injury or serious illness cannot safely practice feeding by mouth, which disrupts the development of these important brain circuits. As a result, many of these infants require a feeding tube placed in the stomach (called a G-tube) when they leave the hospital. Unfortunately, long-term feeding tube dependence is linked to poorer growth, delayed development, and breathing problems. Despite how common and serious these feeding difficulties are, there are currently no effective therapies for infants with the most severe swallowing problems. This study will test a non-invasive therapy called transcutaneous auricular vagus nerve stimulation (taVNS), which gently stimulates a nerve in the ear that connects to the brain. When paired with structured oral motor exercises, this approach may help strengthen the brain circuits needed for feeding. We will study 12 infants with severe feeding impairments to evaluate whether this therapy is safe, feasible, and shows early signs of benefit. This project will provide early evidence about whether a targeted brain-based therapy can improve feeding outcomes during a key window of early development.

This study is for family members and informal caregivers who support an adult with mild cognitive impairment or early Alzheimer's disease. Researchers are testing a 10‑week, online program designed to help caregivers feel supported and better manage caregiving‑related stress. The program includes education about dementia and future planning, brief relaxation exercises, and opportunities to connect with other caregivers by sharing experiences in a supportive setting. Participants will be randomly assigned to receive one or more parts of the program, which helps researchers understand which types of support are most helpful. All study activities can be completed from home. Findings from this study will be used to improve and expand support programs for families impacted by dementia.

This study is being conducted to evaluate the drug AZD0292, including how safe it is, how long it stays in the blood, and if it may help in reducing the number of exacerbations in people with Pseudomonas aeruginosa in their lungs. These patients have more frequent lung exacerbations and reduced quality of life. Pseudomonas aeruginosa is a bacteria that can make the symptoms of bronchiectasis worse. The study drug (AZD0292) works by attaching to Pseudomonas aeruginosa, thereby reducing its effects on the lungs and improving symptoms.
This study aims not only to test AZD0292 but is also being done to better understand bronchiectasis disease and its associated health problems.
Study drug (AZD0292) or placebo, will be given to participants as an intravenous (IV) infusion. The study is double-blinded.
About 435 participants with bronchiectasis 12 years of age and older, weighing at least 35kg will take part in this study. This study will be conducted globally in approximately 25 countries.

Individuals with obesity and a history of heart failure (condition where heart does not effectively pump) with a preserved or mildly reduced ejection fraction (measure of the heart's pumping ability) will be eligible for participation. Study participants will have a 50:50 chance to be randomly assigned to either the treatment (NNC0487-0111) or control (placebo) group. NNC0487-011 and placebo will be delivered in an injectable pen device for a subcutaneous, once weekly injection. Placebo means there is no active study treatment) Study participation will last approximately three years and begin with a screening period to ensure correct patient selection. After the screening period, research clinic visits will occur every 4 weeks initially and then every 12 weeks. Some visits may be completed virtually through telehealth or by phone. Study procedures include but are not limited to: blood draws, questionnaires, self injection of study medication, medical history review, vital signs, and electrocardiogram (test that records the heart's electrical activity) The study's primary objective is to demonstrate that study drug vs. once weekly placebo, with standard of care, reduces the risk of a composite heart failure outcome consisting of cardiovascular death, heart failure hospitalization, or urgent heart failure visit in patients with heart failure with a preserved or mildly reduced ejection fraction and obesity.

This study is enrolling subjects with heart failure and a preserved fraction meaning the heart is too stiff to fill properly to meet the body's needs. This study is researching an investigational device (study device) called the Alleviant ALV1 System. Investigational means it has not been approved for commercial use by the Food and Drug Administration. (FDA) This study will test the safety and effectiveness of the Alleviant ALV1 System. The Alleviant ALV1 System is intended to create a shunt (an opening) in the heart to allow for proper blood flow through the heart which may improve your symptoms. No device is left in your heart it is just used to create the shunt. This is a randomized study which means subjects are assigned by chance to either have the study device create this shunt or not have the study device create the shunt. Randomization is 50/50 meaning there is a 50% chance to have the study device create a shunt and a 50% chance the study device will not be used. Using the study device to create the shunt is performed during a right heart catheterization (RHC) so all subjects will undergo the RHC but only 50% will have the shunt. Neither the subjects nor the study doctor will know which group subjects are randomized to but other study staff will know in the event this information is needed. All subjects will stay overnight in the hospital after the procedure. Other study related procedures include echocardiograms - ultrasound test of the heart, electrocardiograms (ECG) - a tracing of the heart's electrical activity, blood work, questionnaires, 6 minute hall walk test, and assessments of heart failure status. Risks include risks related to the study device including blood vessel damage from placing the device in the vein to get to the heart, risks from the right heart catheterization such as bleeding or bruising, abnormal heart beats, and risks related to study related procedures. There may be risks that are not known at this time. Participation in this study is expected to last about 60 months and include approximately 15 in person visits and 3 telephone calls.

This study is designed to evaluate a new therapy formulation for Alpha-1 Antitrypsin Deficiency (AATD). AATD is an inherited condition in which a person has low blood levels of a protein known as alpha-1 protease inhibitor (called Alpha1-PI). AATD causes an increased risk of chronic obstructive pulmonary disease (COPD) in the form of emphysema (long term lung disease) and, less frequently, other diseases.

This study is being conducted to evaluate the safety and tolerability of 2 different doses of Alpha-1 drugs (Alpha-1 15% and Liquid Alpha1-PI) in participants with AATD. Participants will be placed into one of two groups. Each group will receive both drugs, but different doses of each, at different points in the treatment period (8 Weekly IV infusions of Liquid Alpha1-PI 60 mg/kg followed by 8 Weekly SC (subcutaneous) infusions Alpha1-PI 90 mg/kg OR 8 Weekly IV infusions of Liquid Alpha1-PI 120 mg/kg followed by 8 Weekly SC (subcutaneous) infusions Alpha1-PI 180 mg/kg).

This is an "open label" study, meaning participants and the study staff know which dose of study drug participants receive. The study will last up to 161 days (23 weeks). Many visits are able to be conducted through home health care, lessening the need to come into the clinic.

Alpha-1 15% is an investigational product, meaning it is not approved by the U.S. Food and Drug Administration (FDA). The other drug in this study is Liquid Alpha1-PI (licensed as Prolastin®-C Liquid) and is an FDA approved treatment for adults with emphysema due to AATD. However, it is only approved for the recommended dose of 60 mg/kg. This study includes both the FDA approved 60mg/kg of Liquid Alpha1-PI and an experimental dose of 120 mg/kg that is not FDA approved. Alpha-1 15% is given as an injection under the skin and Liquid Alpha1-PI is given as an infusion into the veins.

This study is enrolling patients with uncontrolled high blood pressure. This study will see if a medication called Zilebesiran can help lower blood pressure. Zilebesiran is an investigational medication meaning it is not approved for commercial use by the Food and Drug Administration (FDA) but it is approved for use in this study. This is a randomized study meaning if you are eligible, you will be assigned by chance, like the flip of a coin to receive Zilebesiran or placebo. Placebo will look like the study medication but will not contain any active ingredients. You and the study team will not know if you are taking Zilebesiran or placebo, both of which are given as an injection under the skin every six months. This study will last between 2.5 and 5 years and include 10-14 visits. Study related procedures include physical exams, medical history including medications, vital signs, blood and urine collection. and electrocardiogram (ECG - a recording of your heart's electrical activity)

The purpose of this research study is to evaluate the safety and effectiveness of a
physician-modified endograft (tubular medical device used to reinforce weakened or damaged blood vessels) for repairing serious diseases of the aorta (largest artery in the human body, responsible for blood from the heart to the rest of the body). This device is considered investigational, and this research study received an Investigational Device Exemption (IDE) from the FDA.