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Inclusion Criteria: * Age 18 to 70 years old * Comfortable speaking and writing in English * Chronic pain present daily for at least 3 months * Currently experiencing depression * Able to comply with the study protocol and communicate with study personnel about adverse events and other clinically important information Exclusion Criteria: * Pregnant or breastfeeding * One or more health conditions that makes study unsafe or unfeasible, determined by study physicians * Regular use of medications that may have problematic interactions with the study drugs * Participating in another clinical trial which may conflict with this one

Inclusion Criteria: * Age 18 or older * Able to read and effectively communicate in English at the United States sites or able to read and effectively communicate in English or French at the Canadian site. * Meets criteria for chronic insomnia * Body Mass Index (BMI) 18.5 kg/m2 and higher Exclusion Criteria: * Age \< 18 * Unable to read and effectively communicate in English at the United States sites or able to read and effectively communicate in English or French at the Canadian site. * Unwilling to share email address/cell phone number to accept survey links. * Life time diagnosis of psychotic or bipolar disorder * History of severe apnea or an Apnea Hypopnea Index (AHI) ≥15 that is not currently treated with Positive Airway Pressure (PAP) therapy, an oral device or an implanted device, or was not treated with surgery or weight loss. * Started new or changed treatment for sleep apnea in the past three months * Does not meet criteria for chronic insomnia * Meets criteria for narcolepsy or hypersomnia disorder * Meets criteria for circadian rhythm disorder (including night shift work) * Unstable medical conditions that would make participation unsafe or unfeasible * Falls resulting in hospitalization, significant injury or fracture within past 12 months * 2 hospitalizations or emergency room visits within past 12 months for chronic conditions * Active chemotherapy or radiation therapy for cancer * Lifetime diagnoses/treatment of chronic renal failure, hepatic insufficiency, chronic heart failure * Does not agree to refrain from other treatments for insomnia beyond what is offered in this study * BMI less than 18.5 * Substance abuse or dependence in the past 12 months * Current use of prescription or over the counter medications taken for sleep greater than 2 times per week * Current use of systemic corticosteroids or opiate medications * Current pregnancy or breastfeeding; plans to get pregnant or unwillingness to use birth control for the length of the study * Current use of medications contraindicated with trazodone * Sleep apnea or periodic leg movement disorder as determined by sleep study * Blood Pressure levels defined as seated SBP greater than 180 or DBP greater than 110 mmHg * EKG corrected QT interval greater than or equal to 500 ms

Inclusion Criteria: * Have Type 2 Diabetes (T2D) * Have HbA1c ≥7.0% (53 millimoles per mole (mmol/mol)) to ≤10.5% (91 mmol/mol) * Have moderate or severe renal impairment * Have been on the following stable diabetes treatment during 90 days prior to screening * basal insulin (≥20 International Units (IU)/day) with or without * metformin and/or SGLT2 inhibitor * Are of stable weight for at least 90 days prior to screening * Have a Body Mass Index (BMI) ≥23.0 kilograms per meter squared (kg/m2) Exclusion Criteria: * Have Type 1 Diabetes (T1D) * Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening * Have a history of severe hypoglycemia or hypoglycemia unawareness within the last 6 months prior to screening * Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema * Have a history of unstable or rapidly progressing renal disease * Have a prior or planned surgical treatment for obesity * Have New York Heart Association Functional Classification III or IV congestive heart failure * Have had acute myocardial infarction, stroke, or were hospitalized for congestive heart failure within 90 days prior to screening * Have a known clinically significant gastric emptying abnormality * Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years * Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) syndrome Type 2. * Have any lifetime history of a suicide attempt * Had chronic or acute pancreatitis * Have taken prescribed or over-the-counter medication, or alternative remedies, intended to promote body weight reduction within 90 days prior to screening

Inclusion criterias 1. Definite diagnosis of aSAH: presence of SAH symptoms confirmed by CT, with rupture of an intracranial aneurysm identified by CTA or DSA. The ruptured aneurysm is scheduled for definitive treatment (clipping or endovascular therapy) within 72 hours of onset. 2. Age ≥ 18 years. 3. Symptom onset within 72 hours. 4. Hunt-Hess grade 2-4 and modified Fisher grade 2-4 on CT imaging. 5. Written informed consent obtained from the participant or legal representative. Exclusion criteria included 1. Pregnancy or lactation; 2. Bilateral fixed dilated pupils on admission; 3. Malignancy, bleeding disorders, or other severe systemic comorbidities, including chronic obstructive pulmonary disease, multiple organ dysfunction, severe diabetes, heart failure, or chronic kidney disease; 4. Pre-existing neurological disability due to previous brain disease or neurosurgery, defined as a premorbid modified Rankin Scale (mRS) score ≥3; 5. Significant structural abnormalities on neuroimaging, such as extensive encephalomalacia or marked mass effect; 6. Subarachnoid haemorrhage caused by non-aneurysmal aetiologies; 7. Moyamoya disease associated aneurysmal rupture; 8. Other underlying diseases expected to substantially affect prognosis; 9. Active request for ICP monitoring by the patient or family; 10. Any other condition considered unsuitable for enrolment by two investigators; 11. Concurrent participation in another clinical trial.

Inclusion Criteria: * Age ≥18 years * Female biological sex * Newly diagnosed, previously untreated, histologically confirmed early triple-negative breast cancer * Plan to initiate preoperative anti-PD-1 immunotherapy using pembrolizumab * Overweight or obesity, defined as a body mass index \>=25 kg/m2 * Ability to provide written informed consent * Allow the collection and storage of biospecimens and data for future use Exclusion Criteria: * Active autoimmune disease * Concomitant conditions that require the use of antibiotics (e.g., chronic sinusitis) * Digestive disease disorders (e.g., irritable bowel syndrome, Crohn's disease) * Currently pregnant, breastfeeding, or planning to become pregnant within the next 24 weeks * Recent (within 90 days) use of glucocorticoids for more than 10 consecutive days * Any other cardiovascular, pulmonary, orthopedic, neurologic, psychiatric, or other condition that, in the investigator's opinion, would preclude participation or successful compliance with the protocol * Any other situation that, in the opinion of the investigator, would negatively impact subject safety or successful compliance with the protocol

Inclusion Criteria: 1. Histological proven invasive breast cancer 2. Breast conserving surgery with no axillary dissection 3. Tumor dimension no more then 5 cm and no more than 2 positive sentinel node 5\) Negative surgical margin (no tumor cell on ink) 6) Performance Status (PS) \<2 7) Age \>18 8) Written informed consent Exclusion Criteria: 1. Previous thoracic RT 2. Mixed connective disorders 3. Distant metastases 4. Severe lung or cardiac diseases 5. Neoadjuvant systemic therapies 6. Axillary dissection 7. No surgical axillary investigation 8. Mastectomy 9. Axillary micrometastasis or isolated tumor cell

Inclusion Criteria: * The patient will meet all the following criteria to be considered eligible for the study: * Aged 18 years or over. * All patients who have attended full asthma workups from November 2021 till date * Willing and able to consent to use their data in this study (opt-out form or e-consent). * Patients referred to the Portsmouth asthma service for diagnosis and further management of presumed asthma. Comorbidities are common in asthma, thus patients with co-existing conditions such as obesity, bronchiectasis or COPD will be included. Exclusion Criteria: * The participant may not enter the study if either of the following apply: * Unable to comprehend the study and provide informed consent, e.g., insufficient command of English in the absence of someone who can adequately interpret. * Patients with other primary respiratory conditions, such as ILD.

Inclusion Criteria: 1. Meet the DSM-5 criteria for unipolar MDD with a current major depressive episode (MDE) without psychotic features, with ≤ 2 failed treatment trials (non-treatment-resistant depression), as determined by a physician and validated by a MINI done by a trained research assistant 2. No change in the medication regimen or other forms of treatments (e.g., psychotherapy) for at least 4 weeks (28 days) prior to beginning the study, during the 20-session treatment period, and the 4-week post-treatment observation period. This will be established through self-report, in combination with the Antidepressant Treatment History Form (ATHF) form filled out by the participant. 3. Men and non-pregnant women aged \> 18 years Exclusion Criteria: * 1\. Paralysis of facial nerves 2\. Metallic implants or metal braces near the potential sites of electrical stimulation and any type of implanted electronic device 3\. Current fibromyalgia or currently receiving or have received repetitive transcranial magnetic stimulation (rTMS) within the last month (28 days) before screening 4\. Past or current symptoms of mania, hypomania, mixed episodes, psychotic disorders, active substance abuse, or dependence (excluding nicotine and caffeine) which will be confirmed on the MINI done by a trained research assistant 5\. Current suicidal intent or plan as demonstrated by a score of ≥ 2 on MADRS item 10

Inclusion Criteria: 1. Subjects willing and able to provide voluntary informed consent and to follow protocol requirements. 2. Male or females aged ≥18 years. 3. Subjects with chronic open-angle glaucoma or ocular hypertension in both eyes 4. Subjects requiring treatment of both eyes and able to discontinue the use of all ocular hypotensive medication(s) or switch ocular hypotensive medications and undergo appropriate washout period. 5. Adequate washout period prior to baseline of any ocular hypotensive medications as (to minimize potential risk to subjects due to intraocular pressure (IOP) elevations during the washout period, the Investigator may choose to substitute a parasympathomimetic or carbonic anhydrase inhibitor in place of a sympathomimetic, alpha-agonist, beta-adrenergic blocking agent, or prostaglandin; however, all the subjects must have discontinued their ocular hypotensive medications for the minimum washout period . 6. Baseline (Day 0/hour 0) IOP ≥22 mm Hg and \<28 mm Hg in each eye, with difference between the IOP in left and right eyes not being more than 5 mm Hg 7. Subjects' IOP is likely to be controlled with monotherapy as per the Investigator's discretion. 8. Baseline best corrected visual acuity equivalent to Snellen acuity of 20/100 or better in each eye, using a logarithmic visual acuity chart for testing at 10 feet (3 meters). 9. Women of childbearing potential (defined as women physiologically capable of becoming pregnant unless they are using an effective method of contraception during the dosing of the study drug) practicing any of the following acceptable methods of contraception: 1. Oral or parenteral (injection, patch, or implant) hormonal contraception which has been continuously used for at least 1 month prior to first dose of study medication. 2. Intrauterine device (IUD) or intrauterine system (IUS) 3. Double barrier method of contraception (condom and occlusive cap or condom and spermicidal agent) 4. Male sterilization (at least 6 months prior to screening, should be the sole male partner for that subject) 5. Female sterilization (surgical bilateral oophorectomy) or tubal ligation at least 6 weeks prior to study participation 6. Total abstinence; partial abstinence is not acceptable 10. No history of addiction to any recreational drug or drug dependence or alcohol addiction Exclusion Criteria: 1. Female who are pregnant, lactating or planning a pregnancy. 2. Subjects recently diagnosed with open-angle glaucoma or ocular hypertension and who are treatment naive. 3. Contraindication or known hypersensitivity to Bimatoprost, related class of drugs, or any of the excipients of formulation. 4. Current or history of severe hepatic or renal impairment. 5. Current or history within 2 months prior to baseline of any other significant ocular disease, e.g., corneal edema, uveitis, ocular infection, or ocular trauma in either eye (Note: stable myopia, strabismus, and cataracts as per the Investigator's discretion will be allowed provided that the other inclusion/exclusion criteria are met). 6. Current corneal abnormalities that would prevent accurate IOP readings with Goldmann applanation tonometer. 7. Functionally significant visual field loss in the Investigators' opinion. 8. Subject with corneal grafts. 9. Subject has contraindication to pupil dilation. 10. Use at any time prior to baseline of an intraocular corticosteroid implant. 11. Use of contact lens within 1 week prior to baseline. 12. Use within 2 weeks prior to baseline of 1) a topical ophthalmic corticosteroid or 2) a topical corticosteroid. 13. Use within 1 month prior to baseline of 1) a systemic corticosteroid or 2) high-dose salicylate therapy defined as 325 mg/day and taken on 3 consecutive days. 14. Use within 6 months prior to baseline of intravitreal or subtenon injection of an ophthalmic corticosteroid. 15. Underwent within 6 months prior to baseline any other intraocular surgery (e.g., cataract surgery). 16. Underwent within 12 months prior to baseline any refractive surgery, filtering surgery, or laser surgery for IOP reduction (e.g., laser trabeculoplasty). 17. Amblyopia - only one sighted eye. 18. Subjects with a history of IOP previously uncontrolled on bimatoprost monotherapy. 19. Significant ocular surface findings (e.g., hyperemia or irritation, mild or greater) in either eye found on gross macroscopic or slit lamp examination. 20. Severe retinal disease or other severe ocular pathology, such as glaucomatous damage with a cup/disk ratio greater than 0.8 (not including physiological cupping in the Investigators' opinion) or split fixation. 21. Chronic use of any systemic medication that may affect IOP with less than 3 months stable dosing regimen (i.e., sympathomimetic agents, beta-adrenergic blocking agents, alpha-agonists, alpha-adrenergic blocking agents, calcium channel blockers, angiotensin-converting enzyme inhibitors, etc.) 22. Central Corneal thickness (CCT) \<450 microns or \>650 microns. 23. Known history or presence of any uncontrolled systemic disease (e.g., cardiovascular disease, hypertension, diabetes mellitus, hepatic impairment, etc.) 24. History of recurrent ocular seasonal allergies within the past 2 years. 25. Any other medical condition or serious intercurrent illness that, in the Investigator's opinion, may make it undesirable for the subject to participate in the study and would limit adherence to the study requirements. 26. Participation in any clinical study within 30 days before the first dose of the study drug. 27. Subjects with known history of positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) infection. 28. Subjects with positive urine pregnancy test.

Inclusion Criteria: 1. Male and female patients aged 18 -75 years. 2. Patients with diagnosis of PAH of the following types according to 2022 ERS/ESC guidelines: idiopathic, hereditary, drug and toxin-induced PAH or associated to connective tissues disease. 3. Patients who are stable and treated with standard medications for PAH on monotherapy or with combinations of drugs, including calcium channel blockers, phosphodiesterase type 5 inhibitors (PDE5i), endothelin receptor antagonists (ERA), prostacyclin analogues or selexipag or with stable dose of diuretics who had no treatment modification for at least 6 weeks before randomization. 4. Patients with an intermediate-low and intermediate-high risk score according to 2022 ERS/ESC guidelines. 5. Patients with severe deficiency of vitamin D, defined herein as plasma or serum 25(OH)vitamin D levels equal to or lower than 12 ng/ml 6. Patients who can understand and follow instructions, and who are able to participate in the study for the entire study. 7. Patients must have given their written informed consent to participate in the study after having received adequate previous information and before any study-specific procedures. Exclusion Criteria: 1. Participation in another interventional clinical study within 30 days before screening. 2. Previous randomisation to treatment during this study (no re-randomisation). 3. Pregnant women or breastfeeding women, or women with childbearing potential not using a effective contraception method throughout the study. 4. Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate in or complete this study, in the opinion of the investigator. 5. Patients with substance abuse (eg, alcohol or drug abuse) within the previous 3 months before and at randomisation. 6. Patients with underlying medical disorders with an anticipated life expectancy \<2 years. 7. Patients with a history of severe allergies or multiple drug allergies or with hypersensitivity to the investigational drug or any of the excipients. 8. Patients unable to perform a valid 6MWD test (eg, orthopaedic disease or peripheral artery occlusive disease that affects the patient's ability to walk). 9. Excluded medication/treatment: active treatment with digoxin.

Inclusion Criteria: * Women over 18 years * Meets the diagnostic criteria for depressive disorder with peripartum onset (PPD) (APA, 2013) and has already given birth * EPDS score over 10 * Have given their consent to take part in the study * Be affiliated to a social security system * Have an adequate knowledge of written, understood and spoken French (French mother tongue or primary education in the French education system) All women with PPD, whether breastfeeding or not, can be included in the study. Baby care can be organised if mothers are unable to have their babies looked after. This service is provided by nurses from the UPPE in the unit's reception room, which has all the equipment needed to care for infants. Mothers meet the nurses before the group and tell them what they expect, and the nurses give them feedback when they come to collect their baby. Exclusion Criteria: * \- Be the subject of a protection measure * Being a minor * Meets the diagnostic criteria for schizophrenia spectrum disorders (brief psychotic disorder; schizophrenic disorder; schizoaffective disorder; delusional disorder; brief psychotic disorder with peripartum onset) * Meet the criteria for substance abuse or dependence (alcohol, drugs) * With insufficient command of the French language * People with a deceased child * People who do not meet the diagnostic criteria for depressive disorder with peripartum onset (APA, 2013) * People who do not agree to take part in the study

Inclusion Criteria: * Patients seen at the Emergency Department Post-Discharge Clinic * \>=18 years * Blood pressure \>=130/80 mmHg and \<=160/100 mmHg * English speakers * Have a smartphone Exclusion Criteria: * Patients with blood pressure \>=160 mmHg

Inclusion Criteria: * Youth must be on the wait-list for mental health services at St. Joseph's Care Group or Thunder Bay Counselling Centre and be between 12-17 years old. * Eligible youth will also need to be available to attend a virtual or in-person orientation session. * In order to download the JoyPop app, participants will need access to an iOS device (e.g., iPhone, iPad). Refurbished iPhones containing just the JoyPop app will be provided to participants to use for the duration of the trial if they do not have access to their own.

Inclusion Criteria: To be eligible for the MOMI PODS RCT, individuals will be required to be pregnant, with a current diagnosis or history of one or more of the following reflected in the medical record or by self-report - chronic hypertension (with or without super-imposed preeclampsia); gestational hypertension; preeclampsia; eclampsia; hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome; type 1 diabetes mellitus; type 2 diabetes mellitus; gestational diabetes mellitus (GDM); a depressive disorder (e.g., major depressive disorder, persistent depressive disorder) or anxiety disorder (e.g., generalized anxiety disorder, panic disorder).43-48 Inclusion criteria will also include a singleton pregnancy and medical record documentation or self-report of private or government-sponsored health insurance at the time of enrollment. Exclusion Criteria: Exclusion criteria will include the presence of a pre-existing, community driven MOMI PODS referral and enrollment into the program, maternal history of a seizure disorder, medical record documentation or self-report of a major complication of the infant that would be expected to preclude them from receiving or significantly delay their ability to receive outpatient pediatric care during the first year of life. Examples include but are not limited to anencephaly, myelomeningocele, esophageal atresia, gastroschisis, hypoplastic left heart syndrome, transposition of the great arteries, or tetralogy of Fallot. Exclusion criteria will also include the presence of a major genetic disorder among the infant that would be expected to preclude them from receiving or significantly delay their ability to receive outpatient pediatric care during the first year of life. Examples include but are not limited to trisomy 13, or trisomy 18 (trisomy 21 is not an exclusion criteria).

Inclusion Criteria: * All participants aged 40 or above * With hypertension and diabetes * Residents of specific study areas * Willing to participate Exclusion Criteria: * Adults aged less than 40 years * Children * Pregnant women * Severely ill * Having severe disabilities both physical and mental)

Inclusion Criteria: 1. Must be able to sign the informed consent form (ICF). Participants will demonstrate capacity to provide informed consent by demonstrated understanding of the protocol and what their involvement in the study requires from them. 2. Be 18-55 years of age at screening. 3. At least moderate Major Depressive Disorder (MDD; single or recurrent episode as informed by Diagnostic and Statistical Manual Version 5 (DSM-V); if single episode, duration of ≥ 3 months and ≤ 3 years) based on clinical assessment and a structured clinical interview, the Mini International Neuropsychiatric Interview Version 7.02 (MINI).43 4. Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS)44 score ≥ 18 at Screening and at Baseline. 5. Failure to respond to an adequate dose and duration of 1, 2, 3, or 4 pharmacological treatments for the current episode as determined through the Massachusetts General Hospital Antidepressant Treatment History Response Questionnaire (MGH-ATRQ)45 and using the supplementary advice on additional antidepressants not included in MGH-ATRQ. Augmentation with an add-on treatment counts as a second treatment, provided it is approved for the adjunctive treatment of MDD. 6. McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) \< 7 at Screening. 7. Participants will also have to successfully undergo a taper off of all psychotropic medications under the supervision of a study psychiatrist and in coordination with their treatment team, which will be completed at least 2 weeks prior to Baseline Scan. Please see below regarding details about discontinuation of antidepressants. 8. A score \> 40 on the Wechsler Test of Adult Reading.46 9. Be right-handed as determined by the Edinburgh Handedness Inventory.48 10. Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits. 11. Have ongoing established mental health care. Exclusion Criteria: Patients meeting any of the following criteria are to be excluded from the study: 1. Current, past history, or family history, of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, or any serious psychiatric comorbidity as assessed by medical history and a structured clinical interview (version 7.0.2 MINI). 2. Positive Magnetic Resonance screen (e.g., metal implant, claustrophobia, etc). 3. Prior electroconvulsive therapy and/or ketamine for current episode. 4. Current cognitive behavioral therapy (CBT) that will not remain stable for the duration of the study. CBT cannot be initiated within 21 days of Baseline. 5. Current (within the last year) alcohol or substance abuse as informed by DSM-5 at Screening. 6. Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS)49 within the past year, at Screening or at Baseline, or; (2) suicidal behaviors within the past year, or; (3) clinical assessment of significant suicidal risk during clinical interview. 7. Significant homicide risk as defined by clinical interview. 8. Depression secondary to other severe medical conditions. 9. Currently taking benzodiazepines daily. 10. Other personal circumstances and behavior judged to be incompatible with establishment of rapport or safe exposure to psilocybin, as well as exposure to psilocybin or other psychedelics within one year of screening. 11. Women who are pregnant, nursing, or planning a pregnancy. Participants who are sexually active must agree to use a highly effective contraceptive method throughout their participation in the study. Women of childbearing potential must have a negative urine pregnancy test at Screening and Day Before Psilocybin. 12. Cardiovascular conditions: recent stroke (\< 1 year from signing of consent), recent myocardial infarction (\< 1 year from signing of ICF), hypertension (blood pressure \> 140/90 mmHg) or corrected QT interval \> 450 msec) or clinically significant arrhythmia within 1 year of signing the ICF, current anticoagulant therapy, aneurysmal disease. 13. Uncontrolled insulin dependent diabetes. 14. Seizure disorder. 15. Positive urine drug screen for illicit drugs or drugs of abuse (to include but not limited to opiates, phenylcyclohexyl piperidine(PCP), cocaine, amphetamines, methamphetamines, benzodiazepines, barbiturates, and cannabis) at Screening and Day Before Psilocybin. Any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator's discretion. 16. Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention which, according to the screening clinician, is deemed associated with significant injury to or malfunction of the CNS, or history of significant head trauma within the past 2 years. 17. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation. 18. Current enrollment in any investigational drug or device study or participation in such within 6 months of Screening. 19. Current enrollment in an interventional study for depression or participation in such within 6 months of Screening Visit. 20. Non-native speakers of English.

Key Inclusion Criteria: * Participants with advanced solid tumors with documented evidence of a PI3KαH1047R mutation in tumor tissue and/or blood (ie, ctDNA). * Eastern Cooperative Oncology Group (ECOG) Performance status score of to 1. * Life expectancy \> 12 weeks for Part A and \> 6 months for Parts B, C, D, and E in the opinion of the Investigator. * Adequate organ and bone marrow function * Have adequate archival tumor tissue sample available or be approved by the Sponsor for enrollment if no tumor sample is available. * At least 1 measurable lesion based on RECIST version 1.1. Additional Cohort-specific key inclusion criteria: Part A * Participants with HR+/HER2- locally advanced, unresectable or metastatic breast cancer, must have received at least 1 prior line of hormonal therapy and at least 1 prior line of CDK4/6-inhibitor in the advanced or metastatic setting. * Participants with HER2+ locally advanced, unresectable or metastatic breast cancer, must have received prior taxane, trastuzumab, pertuzumab, and tucatinib. Prior trastuzumab deruxtecan is allowed but not required. * Participants with HER2-low breast cancer must have received prior trastuzumab deruxtecan. * Participants with colorectal cancer must have KRAS wild-type disease. Part B * Participants with locally advanced, unresectable or metastatic HR+/HER2- breast cancer must have received at least 1 prior line of hormonal therapy in the advanced or metastatic setting and at least 1 prior CDK4/6-inhibitor. * Participants with HER2-low breast cancer should have received prior trastuzumab deruxtecan Part C ● Participants with HR±/HER2+ locally advanced, unresectable or metastatic breast cancer must have received prior taxane, trastuzumab, and pertuzumab unless unavailable in the region or contraindicated. Prior trastuzumab deruxtecan is allowed but not required. Part D ● Participants must have HR+/HER2- locally advanced, unresectable or metastatic breast cancer Part E ● Participants must have HR+/HER2- locally advanced, unresectable or metastatic breast cancer. Key Exclusion Criteria: * Treatment with any investigational product or other anticancer therapy within 28 days or 5 half-lives, whichever is shorter, of the start of treatment * Participants with a known KRAS mutation. * Participants with a known deleterious mutation in phosphatase and tensin homolog (PTEN) or negative for PTEN protein expression by IHC. * Major surgery or wide-field radiation within 28 days or limited field palliative radiation within 7 days prior to the first dose of study drug. * Known active central nervous system metastasis, including leptomeningeal disease. * Uncontrolled Type 1 or Type 2 diabetes as defined by HbA1C ≥ 8%. * Concomitant active malignancy or previous malignancy within 2 years of the time of enrollment. * Impaired cardiovascular function or clinically significant cardiovascular disease, * History of symptomatic drug-induced pneumonitis. * Participants with active HIV, Hepatitis B, and Hepatitis C viral infections Additional Cohort-specific key exclusion criteria: Part C: * Grade 2 or higher diarrhea at study entry. * History of chronic liver disease. Part E: ● History of interstitial lung disease.

Part 1 (Dose Escalation) Inclusion Criteria: * Monotherapy Cohorts: Participants with histologically or cytologically confirmed advanced or metastatic solid tumors potentially associated with CDK2 dependency including HR+/HER2- breast cancer, platinum refractory or resistant serous ovarian cancer (PROC), endometrial cancer, and others. Prior available standard-of-care systemic therapies for advanced or metastatic disease are required. The requirements for enrollment into a food effect evaluation cohort are the same as the monotherapy cohorts with the exception that participants with gastric cancer and gastroesophageal adenocarcinoma are excluded. * Combination Cohorts (BG-68501 with fulvestrant with or without BGB-43395): Enrollment is restricted to only participants with HR+/HER2- BC. In regions where approved and available, participants must have received one or more lines of treatment for advanced/metastatic disease as well as prior endocrine therapy and a CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting. If applicable, the requirements for enrollment into a food effect evaluation cohort are the same as the combination cohorts. Part 1 (Safety Expansion) and Part 2 (Dose Expansion) Inclusion Criteria: * Participants with advanced, non-resectable, or metastatic HR+/HER2- BC or PROC, including fallopian tube or primary peritoneal cancer. * PROC participants must have received: * ≥ 1 line of platinum-containing chemotherapy for advanced disease. * ≤ 4 prior therapeutic regimens in the advanced/metastatic setting. * HR+/HER2- BC: * Participants enrolled in regions where CDK4/6 inhibitors are approved and available must have received ≥ 1 line of therapy including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy or ADC treatments for advanced disease. General Inclusion Criteria: * Female participants with advanced or metastatic HR+/HER2- BC will be required to have ovarian function suppression using gonadotropin hormone-releasing hormone (GnRH) agonists (such as goserelin) or be postmenopausal. * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1. * Adequate organ function. * For dose escalation, participants with advanced solid tumors other than HR+/HER2- BC must have measurable disease per RECIST 1.1. Participants with HR+/HER2- BC with bone-only disease are eligible for dose escalation only. For safety expansion and dose expansion, all participants must have ≥1 measurable lesion per RECIST v 1.1. General Exclusion Criteria: * For all cohorts: Prior therapy selectively targeting CDK2 inhibition. * For triple combination cohorts: Prior therapy targeting CDK2 or selectively targeting CDK4. Prior CDK4/6 inhibitor therapy is permitted and required in local regions where it is approved and available. * Known leptomeningeal disease or uncontrolled, untreated brain metastasis. Participants with a history of treated central nervous system (CNS) metastases may be eligible if they meet additional criteria. * Any malignancy ≤ 3 years before the first dose of study treatment(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, treated papillary thyroid carcinoma, or carcinoma in situ of the cervix or breast). * Uncontrolled diabetes. * Infection requiring systemic antibacterial, antifungal, or antiviral therapy antiviral therapy ≤ 28 days before the first dose of study drug(s), or symptomatic COVID-19 infection. * Active hepatitis B infection or active hepatitis C infection. * Any major surgical procedure ≤ 28 days before the first dose of study treatment(s). * Prior allogeneic stem cell transplantation, or organ transplantation. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Key Inclusion Criteria: * Age ≥ 18 years * Have relapsed/refractory HER2-altered malignancy; for selected cohorts, prospective confirmation of HER2 alteration by central testing is required * Have progression of disease after the last systemic therapy, or be intolerant of last systemic therapy * Have radiographically measurable disease by RECIST v1.1 and/or RANO-BM * Eastern Cooperative Oncology Group (ECOG) performance score 0-1 * Have adequate baseline hematologic, liver and renal function * Have left ventricular ejection fraction (LVEF) ≥ 50% * Able to swallow oral medication Key Exclusion Criteria: * Clinically significant cardiac disease * Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: Participants with well-controlled HIV (e.g., CD4 \>350/mm3 and undetectable viral load) are eligible * Current active liver disease including hepatitis A, hepatitis B , or hepatitis C * Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate absorption * Uncontrolled diabetes * History of solid organ transplantation * History of Grade ≥2 CNS hemorrhage, or any CNS hemorrhage within 28 days before C1D1 * Prior history of non-infectious interstitial lung disease (ILD). (Exceptions: participants with prior grade 1 ILD that has completely resolved are eligible) * Participants requiring immediate local therapy for brain metastases

Inclusion Criteria: * Any infant/child/young person admitted to the RHC, Glasgow for an elective bronchoscopy or GI endoscopy. * Any infant/child attending for an emergency/elective orthopaedic operation without active respiratory or gastrointestinal conditions or receiving treatment for either condition. (Age range birth to 16 years for all groups recruited). * Any child attending respiratory department at RHC who can induce sputum and is having a blood sample taken, with latter part of standard of care. * Any infant/child/young person admitted to RHC for a clinical care appointment with Asthma/wheeze before commencement of biologics therapy (treatment group). * Any child admitted to RHC with asthma/wheeze not indicated for biologic therapy (asthma control group). Exclusion Criteria: * Use of antibiotics by the day of admission or have used antibiotics in the previous month (unless prophylactic antibiotics \> 1 month use). * Any person 17 years old and above. * Any child known to be infected with, or at high risk of having had exposure to HIV, hepatitis B or hepatitis C viruses * . Any child and/or parent/guardian who cannot understand the English language where consent would be unethical. * Any child with Asthma currently receiving Biologics therapy (unless recruited via bronchoscopy route).