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Inclusion Criteria: 1. Signed or Verbal Informed Consent as required by IRB (if applicable). 2. Adult (age ≥ 18). 3. Monitored on the Accuryn® Monitoring System during their procedure and ICU stay (for retrospective enrollment). 4. Patient is undergoing cardiac surgical intervention(s). Exclusion Criteria: 1. Known history of advanced chronic kidney disease defined by an estimated glomerular filtration rate (eGFR) \<20 mL/min/1.73m2 within 30 days prior to procedure. 2. The patient is unsuitable for the study, in the opinion of the investigator. This may include vulnerable patient populations such as pregnant women, prisoners ,or those detained in a penal institution.

Inclusion Criteria: * Participant understands study procedures and is willing to participate in the study as indicated by the participant's signature * Provision of written, informed consent prior to any study specific procedures * Males and females with a clinical diagnosis of eosinophilic asthma (based on FENO ≥40ppb, blood eosinophilia≥ 200 cells/μl at screening) aged 18 to 70 years, inclusively, at the time of Visit 1 (enrolment), under the care of a respirologist * FEV1 ≥35 and ≤80% predicted * Participant is a current non-smoker and non-vaper, having not smoked tobacco or cannabis, pipe or cigar or vaped any product for at least 12 months prior to the study with a tobacco smoking history of no more than 1 pack-year (i.e. 1 pack per day for 1 year). * Women of childbearing potential (after menarche) must use a highly effective form of birth control (confirmed by the investigator or designee) * A highly effective form of birth control includes true sexual abstinence, a vasectomized sexual partner, Implanon®, female sterilization by tubal occlusion, any effective intrauterine device (IUD)/levonorgestrel intrauterine system (IUS), Depo-ProveraTM injections, oral contraceptive and Erva PatchTM or NuvaringTM * Women of childbearing potential (after menarche) must agree to use a highly effective form of birth control, as defined above, from enrolment, throughout the study duration, and 8 weeks after last dose of study drug, with negative pregnancy test result at Visit 1 * Male participants who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of the study drug until 8 weeks after last dose * Participant has documented treatment with a stable dose of low to medium dose inhaled corticosteroids (defined as \>250 and ≤500 mcg fluticasone proprionate/day or equivalent or, \>400 to ≤800 mcg Budesonide/day for at least 6 months prior to enrolment * long-acting β2-agonist (LABA) for at least 6 months prior to enrolment * Participant has blood eosinophils ≥ 200 cells/μl or FENO ≥25ppb at Visit 1 for all participants except for those with previous biologic therapy without washout who will be required to washout prior to screening. * Participant has ACQ-6 ≥ 1.5 at visit 1 * Participant has a history of poorly controlled asthma (i.e. ≥ 2 exacerbations in past 24 months) Exclusion Criteria: * Participant is, in the opinion of the investigator, mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand written material * Participant has clinically important pulmonary disease other than asthma (e.g. active lung infection, chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha-1 antitrypsin deficiency and primary ciliary dyskinesia) or been diagnosed with pulmonary or systemic disease other than asthma that is associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome), except for those atopic conditions that can be associated with asthma (e.g. allergic rhinitis, sinusitis with or without polyposis, eczema, and eosinophilic esophagitis) * Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Qualified Investigator and/or could affect the safety of the participant throughout the study, influence the findings of the study or their interpretations, or impede the participant's ability to complete the entire duration of the study, as assessed by the Qualified Investigator. * Known history of allergy or reaction to the study drug formulation * Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date of informed consent * Clinically significant asthma exacerbation, defined as a change from baseline deemed clinically relevant in the opinion of the Qualified investigator, including those requiring the use of OCS, or an increase in maintenance dosage of OCS within 30 days prior to the date of informed consent. Participants with an exacerbation after providing informed consent but prior to treatment start will be excluded from the study * Receipt of immunoglobulin or blood products within 30 days prior to the date of informed consent * Receipt of live attenuated vaccines 30 days prior to the date of enrolment * Previously randomized in any FF/UMEC/VI 200/62.5/25ug study * Planned surgical procedure during the conduct of the study * Concurrent enrolment in another clinical trial * Participant has history of alcohol or drug abuse within 12 months prior to the date of informed consent * Participant is a female who is ≤8 weeks post-partum or breast feeding an infant * Participant is pregnant, or intends to become pregnant during the time course of the study * Participant is unable to perform MRI breath-hold maneuver * Participant is unable to perform spirometry maneuver * Participant is hospitalized or has had a major surgical procedure, major trauma requiring medical attention, or significant illness requiring medical attention within 4 weeks of Visit 1 * Participant has a blood pressure of \>150 mmHg systolic or \>95 mmHg diastolic on more than 2 measurements done \>5 minutes apart at Visit 1 * In the opinion of the investigator, participant suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia * Participant has implanted mechanically, electrically or magnetically activated device or any metal in their body, which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) - at the discretion of the MRI Technologist.

Inclusion Criteria: * Patients aged 18 years or older with T1-3 invasive breast cancer; * Clinically node-positive breast cancer, defined as positive on preoperative axillary palpation, ultrasound examination, and computed tomography scan with contrast; * Patients who underwent mastectomy with a positive sentinel lymph node (SLN); * Patients who underwent breast-conserving surgery containing more than two positive SLNs. Exclusion Criteria: * Neoadjuvant chemotherapy; * Previous history of breast cancer.

Inclusion Criteria: * Asthma patients with age ≥18. Asthma is defined as those with a consistent history and prior documented evidence of variable airflow obstruction. * Subjects on steps 4 and 5 of GINA asthma therapy Exclusion Criteria: * Patients with respiratory diseases with other known respiratory diseases including chronic obstructive pulmonary disease, bronchiectasis, tuberculosis (TB)-destroyed lung parenchyma, history of lung resection and lung cancer * Individuals older than 40 years with a smoking history of more than 10 pack-years * Pregnant women

Inclusion Criteria: 1. Patient ≥ 40 years old 2. Histological diagnosis of ductal carcinoma in situ without infiltrating contingent 3. Clinical T0N0 4. Estrogen receptor positive (OR+) regardless of progesterone receptor (PR) status 5. Indication for mastectomy 6. DCIS visible on MRI performed with clip sequence 7. Effective contraceptive method for women of childbearing age who are sexually active and who have reported sexual activity. 8. Informing the patient and obtaining free, informed and written consent signed by the patient and the investigator. 9. Affiliated patient or beneficiary of the social security system. Exclusion Criteria: 1. Invasive breast carcinoma 2. Lobular carcinoma in situ 3. pN+ patient 4. Indication for conservative surgery 5. Contraindications to anastrozole or tamoxifen 6. Concomitant treatments that may interact and reduce the efficacy of tamoxifen by interaction with cytochrome CYP2D6. 7. Histologically proven multifocal lesion 8. Contraindication to breast MRI (pace maker, heart valve, metallic implant, neuronal or peripheral stimulator, severe claustrophobia, ...) 9. History of homolateral breast cancer 10. Ongoing contralateral breast cancer 11. Known mutation BRCA1 BRCA2 12. Other cancer in progress at inclusion 13. Pregnant woman, or breastfeeding, 14. Persons deprived of liberty or under guardianship or trusteeship, 15. Impossibility to undergo the medical follow-up of the trial for geographical, social, psychic or psychiatric reasons.

Inclusion Criteria: * Singleton pregnancy * English speaking * less than 20 weeks' gestation at enrollment * Blood pressure \< 140/90 * Moderate to high risk for hypertensive disorders of pregnancy Exclusion Criteria: * Multiple gestations * current severe depression or psychosis * ongoing mind-body practice (e.g., yoga, meditation, mindfulness =\> once a week).

Inclusion Criteria: * Patients with type 2 diabetes at or above 35 years of age * Diagnosis of diabetes mellitus was based on prior documentation or treatment with anti-hyperglycemic medication or diagnosed according to the WHO criteria (random plasma glucose \>11.1 mmol/L or fasting glucose \>7.0 mmol/L or HbA1C ≥6.5%). * written informed consent. Exclusion Criteria: * type 1 diabetes, MODY or secondary diabetes * conditions or treatments that in the judgement of the Investigator could affect the study evaluation * inability to understand written Swedish * connection with the study team, funders, authorities, universities or other public or private bodies in such a way that specific interests in the study outcomes could be suspected.

Inclusion Criteria: * Disease Characteristics - Breast, Prostate, and Lung Cancer * Part 1A (Monotherapy Dose Escalation) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer, CRPC, or NSCLC that is intolerant or resistant to standard therapy or for which no standard therapy is available. * Part 1B, Part 1C, Part 1D and Part 1E (Combination Dose Escalation) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of treatment with an endocrine therapy and CDK4/6 inhibitor in the advanced or metastatic setting. * Part 2A (ER+HER2- breast cancer 2L+, monotherapy) Histological or cytological diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after at least 1 prior line of CDK4/6 inhibitor and 1 line of endocrine therapy. * Part 2B (ER+HER2- breast cancer 2-4L, combination with fulvestrant) Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy.. Participants must not have received more than 3 prior lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have but are not required to have prior treatment with fulvestrant. * Part 2D (ER+HER2- breast cancer 2-4L, combination with PF-07220060 (CDK4i) and fulvestrant): Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy. * Participants must have not received more than 3 lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have but are not required to have prior treatment with fulvestrant. * Part 2E (ER+HER2- breast cancer 2-4L, combination with vepdegestrant): Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy; Participants must have not received more than 3 lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have received fulvestrant * Participants with ER+HER2- advanced or metastatic breast cancer must have documentation of ER-positive tumor (≥1% positive stained cells) based on most recent tumor biopsy utilizing an assay consistent with local standards. * Participants with ER+HER2- advanced or metastatic breast cancer must have documentation of HER2-negative tumor: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH/DISH) defined as a HER2/CEP17 ratio \<2 or for single probe assessment a HER2 copy number \<4. * Female participants with ER+HER2- advanced or metastatic breast cancer considered to be of childbearing potential (or have tubal ligations only) must be willing to undergo medically induced menopause by treatment with the approved LHRH agonist such as goserelin, leuprolide or equivalent agents to induce chemical menopause. * Female participants with ER+HER2- advanced or metastatic breast cancer of nonchildbearing potential must meet at least 1 criteria of achieving postmenopausal status. * Participants must have at least 1 measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated. * Eastern Cooperative Oncology Group (ECOG) Performance Status PS 0 or 1 * Female or male patients aged ≥ 18 years (Japan ≥ 20 years) (South Korea ≥ 19 years). * Adequate renal, liver, and bone marrow function. * Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for adverse events (AEs) not constituting a safety risk by investigator judgment. Exclusion Criteria: * Unmanageable ascites (limited medical treatment to control ascites is permitted, but all participants with ascites require review by sponsor's medical monitor). * Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ. * Major surgery, radiation therapy, or systemic anti-cancer therapy within 3 weeks prior to study entry. * Prior irradiation to \>25% of the bone marrow. * ECG clinically relevant abnormalities (eg, QTc \>470 msec, complete LBBB, second/third degree AV block, ST elevation or EKG changes suggesting myocardial infarction or active myocardia ischemia). * Therapeutic anticoagulation. However, low molecular weight heparin is allowed. Vitamin K antagonists or factor Xa inhibitors may be allowed following discussion with the Sponsor. * Known or suspected hypersensitivity or severe allergy to active ingredient/excipients of PF-07248144. * Active inflammatory GI disease, refractory and unresolved chronic diarrhea or previous gastric resection, lap band surgery or other GI conditions and surgeries that may significantly alter the absorption of PF-07248144 tablets. Gastroesophageal reflux disease under treatment is allowed. * Pregnant or breastfeeding female participants.

Inclusion Criteria: * Ability to confirm voluntary participation and agree to all trial purposes by signing and dating the informed consent forms; * Participants of both sexes, with age greater than or equal to 18 years and less than or equal to 85 years; * Participants presenting the diagnosis of type II diabetes mellitus, and who did not reach the therapeutic goals of HbA1c with previous dietary, physical exercise guidance and previous therapies at a stable dose in the last 3 months; * HbA1c ≥ 7,5% and ≤ 10,5% and fasting blood glucose \> 100 mg/dL at the screening visit; * Participants with high or very high cardiovascular risk according to the Brazilian guideline on the prevention of cardiovascular diseases in patients with diabetes (2017), which have not reached the goal of LDL-c ≤ 70 mg/dL or ≤ 50 mg/dL, respectively, with lifestyle changes, who are or aren't using low or moderate potency statins; * BMI (body mass index) \> 19 Kg/m2 and ≤ 45 Kg/m2. Exclusion Criteria: * Any clinical and laboratory findings that, in the judgment of the investigator, may interfere with the safety of research participants; * History of alcohol abuse or illicit drug use; * Participation in a clinical trial in the year prior to this study; * Pregnancy or risk of pregnancy and lactating patients; * Known hypersensitivity to the formula components used during the clinical trial; * Type 1 diabetes mellitus; * Fasting blood glucose \> 300 mg/dL; * Risk factors for volume depletion; * Participants with total cholesterol \> 500 mg/dL or triglycerides \> 500 mg/dL; * Impaired renal function and end-stage renal disease; * Participants with known heart failure, class III to IV (New York Heart Association); * Impaired hepatic function; * Medical history of pancreatic diseases that may suggest insulin deficiency; * Participants who had any cardiovascular event (acute myocardial infarction, acute coronary syndrome, recent onset stable angina, stroke, unstable congestive heart failure requiring treatment change), underwent revascularization or vascular surgery in the 6 months prior to screening; * Bariatric surgery in the last two years and/ or other gastrointestinal surgeries that can cause chronic malabsorption syndrome; * Condition that, in the investigator's judgment, may favor clinically significant changes in CPK levels; * Current medical history of cancer and/ or cancer treatment in the last 5 years; * Participants with known uncontrolled hypothyroidism or TSH levels \> 5 mIU/L; * History of known muscle disease or prior statin intolerance; * Participants using SGLT2 inhibitors, sulfonylureas and/or insulin therapy or PCSK9 inhibitors; * Participants who used other medications with prominent action in the control of serum triglyceride and cholesterol levels in the last 4 weeks or who are using low or moderate-intensity statins that cannot be replaced by rosuvastatin 20 mg; * Participants using medications that may interfere with triglyceride and cholesterol metabolism started less than 4 weeks ago or with dose adjustment in the last 4 weeks prior to the screening visit; * Treatment with anti-obesity drugs for less than 2 months or with dose change in the last 2 months.

Inclusion Criteria: 1. The patient should have signed and dated the informed consent form (ICF). The enrollment of patients who have died is allowed. 2. Women aged ≥ 18 years. 3. Patients in one of the following situations: * Patients with breast cancer diagnosis during pregnancy, breastfeeding or within the year after delivery. * Patients with breast cancer who become pregnant after treatment. * Patients with breast cancer who were subjected to any fertility preservation method prior to the start of breast cancer treatment. 4. The patients referred to in the previous section and the patients who meet these characteristics prospectively could be enrolled retrospectively upon registry opening. 5. All cases diagnosed at the same site may be included. In order to prevent duplications, in case the patient followed her treatment and follow-up at another site, she will be enrolled as per the site where the diagnosis was made, requesting information of the treatment and progression, when possible. 6. Availability of clinical, epidemiological and progress data. Exclusion Criteria: Patients who do not wish to participate in the study for any reason could not be included in the study.

Inclusion Criteria: The subject must be a breast cancer survivor, at least 3 years beyond completion of cancer therapy, free of clinical disease, and eligible for surgical intervention. Participants who are not able to safely undergo general anesthesia and/or perioperative care for VLNT are excluded. * Ages 18 to 75 years (inclusive) * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2 * Life expectancy \> 2 years * Acquired (secondary) upper limb lymphedema secondary to breast cancer treatment * The participant must be eligible for surgical intervention * Swelling of 1 limb that is not completely reversed by elevation or compression * Stage I-II lymphedema at screening, based on the International Society of Lymphology (ISL) staging system * Participants must have no evidence of disease (NED), have completed breast cancer therapy 3 years prior to enrollment; use of endocrine therapy is allowed. * Completion of a full course of complete decongestive therapy (CDT), according to ISL guidelines at least 12 weeks prior to screening, including use of compression garments for at least 12 weeks without change in regimen * Willingness to comply with recommended regimen of self care, with consistent use of compression garments from screening through the entire study duration (through the safety follow up visit), excluding the first 3 weeks postoperatively where patients are required to not wear compression. Self bandaging, use of nighttime compression garments, and intermittent pneumatic compression devices are allowed, but the procedures and regimens are expected to remain consistent from screening though the entire study duration. * Consistent use of an appropriately sized compression garment for daytime use. * Limb volume (LV) in the affected limb and unaffected limb must be at least 10% of each other. * Evidence of abnormal bioimpedance ratio, if feasible, based upon unilateral disease: L Dex \> 10 units. * Willingness and ability to comply with all study procedures, including measurement of skin biopsy, and preoperative and postoperative imaging studies. * Willingness and ability to understand, and to sign a written informed consent form document Exclusion Criteria: * Edema arising from increased capillary filtration will be excluded (venous incompetence). * Inability to safely undergo general anesthesia and/or perioperative care related to vascularized lymph node transfer * Concurrent participation in a clinical trial of any other investigational drug or therapy, regardless of indication, within 1 month before screening or 5 times the drug's half life, whichever is longer * Recent initiation (≤ 12 weeks) of CDPT for lymphedema * Other medical condition that could lead to acute limb edema, such as (but not limited to) acute venous thrombosis or heart failure * Other medical condition that could result in symptoms overlapping those of lymphedema in the affected limb (eg, pain, swelling, decreased range of motion) * History of clotting disorder (hypercoagulable state) * Chronic (persistent) infection in the affected limb * Infection of the lymphedema limb within 1 month prior to screening * Currently receiving chemotherapy or radiation therapy * Current evidence, or a history of malignancy within the past 3 years (except for non melanoma skin cancer or cervical cancer in situ treated with curative intent). If the participant has undergone cancer treatment, this must have been completed \> 3 years prior to enrollment. * Significant or chronic renal insufficiency (defined as serum creatinine \> 2.5 mg/dL or an estimated glomerular filtration rate \[eGFR\] \< 30 mL/min at screening) or requires dialytic support * Hepatic dysfunction, defined as alanine transaminase (ALT) or aspartate transaminase (AST) levels \> 3 × upper limit of the normal range (ULN) and/or bilirubin level \> 2 × ULN at screening * Absolute neutrophil count \< 1500 mm3 at screening * Hemoglobin concentration \< 9 g/dL at screening * Body Mass Index (BMI) \>35 * Known sensitivity to porcine products * Anaphylaxis to iodine * Pregnancy or nursing * Substance abuse (such as alcohol or drug abuse) within 6 months prior to screening * Any reason (in addition to those listed above) that, in the opinion of the investigator, precludes full participation in the study.

Inclusion Criteria: * Female subjects aged over 20 years old * Subject with confirmed diagnosis of primary invasive breast cancer and is planning to receive treatments for breast cancer. However, subjects with breast cancer recurrence at screening will be enrolled if meet both the following conditions: 1. Subjects had received surgery for primary breast cancer within 3 years prior to screening \[i.e. recurrence within 3 years after surgery (mastectomy or BCS)\]; 2. Subjects diagnosed with stage IV breast cancer beyond 3 years after surgery (mastectomy or BCS) or who had received or are currently receiving treatments for breast cancer. And subjects with primary tumor FFPE tissues available and pass the RNA quality check. * Eastern Cooperative Oncology Group (ECOG) Performance score ≤ 3 * Life expectancy ≥ 3 months * Subject agrees to provide the written informed consent. If a subject has breast cancer recurrence within 3 years prior to screening, she will be eligible if she agrees to provide the paired FFPE tissues (primary and recurrent tumors) Exclusion Criteria: * Subjects will be excluded if they had primary cancer other than breast cancer within 5 years prior to screening

Inclusion Criteria: i1. Age 18 - 55; i2. Ability to read and speak in fluent English; i3. Current status as inpatient on the Forensic Treatment Unit. Exclusion Criteria: e1. Intellectual disability; e2. TBI with loss of consciousness followed by known severe neurological sequelae requiring hospitalisation and rehabilitation.

Inclusion Criteria: * Chronic migraine according to ICHD-3 * Episodic migraine without aura or with aura according to ICHD-3 * Unsuccessful treatment with 3 or more established prophylactic drugs * Medicine costs are covered by health insurance * Healthy controls must be free from any diagnosed chronic disease or acute infection requiring medication Exclusion Criteria: * Pregnancy and lactation * Neurosurgical interventions performed within the last 12 months * Coronary bypass surgery or revascularization procedures performed within the last 12 months * History of transient ischemic attacks (TIA), stroke, stable or unstable angina pectoris, myocardial infarction or uncontrolled hypertension * Known hypersensitivity to therapy with an anti-CGRP Antibodies * History of a disorder (other than migraine) that may affect the results of autonomic tests * Healthy controls must have no personal or family history of migraine

Inclusion Criteria: * Patients newly diagnosed with histologically verified breast cancer and scheduled for neoadjuvant chemotherapy * Female gender * Aged ≥ 18 years old * Signed informed consent Exclusion Criteria: * Patients ineligible for or who have declined to receive neoadjuvant chemotherapy * Contraindications to magnetic resonance imaging (MRI) * Physical or cognitive disabilities preventing exercise or physical testing * Inability to read and understand Danish * Based on clinical judgement, the physician assesses that the patient is not suitable for inclusion

Inclusion Criteria: Healthy Volunteers: * Subject has no diagnosed pulmonary conditions * Ability to read and understand English or Spanish Subjects with Lung Disease: * Subject has a diagnosis of pulmonary dysfunction made by a physician * No acute worsening of pulmonary function in the past 30 days * Ability to read and understand English or Spanish Exclusion Criteria: * MRI is contraindicated based on responses to MRI screening questionnaire * Subject is pregnant or lactating * Subject does not fit into 129Xe vest coil used for MRI * Subject cannot hold his/her breath for 15-16 seconds * Subject deemed unlikely to be able to comply with instructions during imaging * Oxygen saturation \<88% on room air or with supplemental oxygen * Cognitive deficits that preclude ability to provide consent * Institutionalization

Client Participants (anticipated enrollment: 288) Inclusion Criteria: Referral to study (stage 1): 1. Age ≥ 60 years. 2. Attends one of 18 participating Seattle, NYC, or Tampa area senior centers. 3. Patient Health Questionnaire (PHQ-9) score of ≥10 via routine screening. Research assessment (stage 2): 1. Clinically-assessed HAM-D\>14 2. Mini-Mental Status Exam (MMSE) ≥ 24 OR modified Telephone Interview for Cognitive Status (mTICS) ≥ 19 3. Off antidepressants or on a stable dose for 12 weeks. 4. Capacity to provide written consent for both research assessment and the BA intervention. Client Participants Exclusion Criteria: 1. Current active suicidal ideation. 2. Presence of psychiatric diagnoses other than unipolar, non-psychotic major depression or generalized anxiety disorder by SCID-V (Structure Clinical Interview for DSM-V). 3. Severe or life-threatening medical illness (e.g., end stage organ failure). 4. Inability to speak English or Spanish Volunteer Participants (anticipated enrollment: 36) Inclusion Criteria 1. Age ≥ 60 years. 2. Attends one of the participating Seattle, NYC, or Tampa-area senior centers. Volunteer Participants Exclusion Criteria 1. Current major depressive disorder, alcohol or substance abuse, or manic, hypomanic, or psychotic symptoms (SCID-V); 2. Mini-Mental Status Exam (MMSE) ≥ 24 OR modified Telephone Interview for Cognitive Status (mTICS) ≥ 19; 3. Inability to speak and read English or Spanish Clinician Participants (anticipated enrollment: 36) Inclusion Criteria 1. Master's degree in social work, counseling, marriage/family, or other clinical mental health degree 2. English or Spanish Speaking 3. Capacity to provide consent for all study procedures 4. Willing to audio record study sessions for supervision and evaluation Clinician Participants Exclusion Criteria 1. Non-English or Non-Spanish speaking 2. Does not hold a Master's degree in social work, counseling, marriage/family, or other clinical mental health degree 3. Unable to provide consent 4. Unwilling to audio record study sessions for supervision and evaluation

Inclusion Criteria: * Suffering from chronic hepatitis induced cirrhosis * Informed consent available Exclusion Criteria: * Medical * Child-Pugh Class C * Uncorrected platelet count \<50,000 * INR \> 1.5 (natural) * Anatomical * Previous transjugular intrahepatic or surgical portosystemic shunt * Portal vein thrombosis * Anatomic alterations of the hepatic vasculature that prevent access to the portal vein or intrahepatic portion of the hepatic veins (identified at screening and/or during the endoscopic procedure). * Previous history of spontaneous bacterial peritonitis within the previous three months * Portopulmonary hypertension * Cardiac decompensation * Endoscopically Confirmed Exclusion Criteria * Evidence of active GI bleeding (identified at screening and/or during the endoscopic procedure) * If the volume of ascites in the path of the needle prevents apposition of the gastrointestinal tract and liver. * Presence of gastric or duodenal ulcers, dieulafoy's lesion or cancers.

Registration Stage Inclusion Criteria: 1. Women determined to be postmenopausal according to established local criteria. 2. Diagnosed operable invasive breast cancer with a clinical/radiological tumour size ≥1.0cm\* 3. Grade 2 or 3 tumours 4. Preoperative full assessment completed (including bilateral breast examination and imaging with mammogram +/- ultrasound/MRI as performed locally). 5. Tumour ER positive. ER positivity is defined as \>/=1% cells staining positive (or equivalent Allred Score of ER \>/=3 out of 8). 6. Tumour HER2 negative or HER2 status unknown. HER2 negativity will be defined as per the 2018 ASCO/CAP updated guidelines. Patients whose HER2 status is pending/unknown at the time of registration will be allowed to register to the trial. However, please note that only patients who are confirmed to be HER2 negative will be eligible to join the randomised part. 7. Received or planned to receive 10 days to 6 months of anastrozole or letrozole prior to surgery. 8. Written informed consent to enter the registration stage of the trial and to donation of fresh tissue. 9. The patient has given written informed consent prior to any study-specific procedures and is willing and able to make herself available for the duration of the study and amenable and able to follow study schedule during treatment and follow-up and for the use of routinely collected electronic health and related records. Registration Stage Exclusion Criteria: 1. Men and pre/perimenopausal women. 2. Intended or actual use of HRT or any other oestrogen-containing medication (including vaginal oestrogens) within 4 weeks prior to planned surgery). Note: patient with a Mirena coil in situ at the time of registration are not excluded. 3. Patients who commenced pre-surgical AI therapy \>6 months prior to surgery. 4. Prior endocrine therapy for breast cancer or breast cancer prevention. 5. Prior neoadjuvant chemotherapy for breast cancer. 6. Evidence of metastatic disease. 7. Locally advanced breast cancer not amenable to surgery. 8. Bilateral invasive breast cancer (excluding contralateral DCIS/LCIS). 9. Multiple unilateral tumours with different ER and/or HER2 status. Synchronous DCIS/LCIS, as well as multifocal disease with homogenous ER/HER2 status is allowed if at least one lesion is at least 1.0cm; the largest lesion should be used for sample collection and CRF completion. If ER/HER2 status of smaller foci is unknown at time of registration, patients can be registered; however, note that congruity of receptor status will need to be confirmed by the time of randomisation, unless smaller foci are \<10mm and receptor status is unknown. 10. Previous invasive breast cancer except for ipsilateral DCIS or LCIS treated \>5 years previously by locoregional therapy alone or contralateral DCIS/LCIS treated by locoregional therapy at any time. 11. Any invasive malignancy diagnosed within previous 5 years (other than non-melanoma skin cancer or cervical carcinoma in situ). 12. Any other medical condition likely to exclude the patient from subsequent randomisation stage. (See exclusion criteria: Eligibility for Randomisation). Randomisation Stage Inclusion Criteria: 1. Patient previously consented and registered for screening component of POETIC-A. 2. Tumour HER2 negative. HER2 negativity will be defined as per the 2018 ASCO/CAP updated guidelines 3. Centrally confirmed Ki67 \>/=8% following 2 weeks of AI. 4. Patient is expected by the time of treatment initiation to have undergone definitive surgery for the primary breast tumour with clear radial margins as judged by the multidisciplinary team, and will have completed any adjuvant chemotherapy or radiotherapy (if prescribed). 5. Surgical staging of the axilla must have been undertaken by sentinel node biopsy, axillary sampling or dissection. 6. The patient is randomised in time for treatment to start no later than three months after completion of non-endocrine therapy (defined as the final fraction of radiotherapy, Day 1 of the final cycle of chemotherapy or the date of the final surgical procedure). 7. The patient is able to swallow oral medications (excluding transient side effects from adjuvant non-endocrine treatment, if randomised before the end of this treatment). 8. The patient intends to take adjuvant endocrine therapy for at least 5 years. 9. The patient has given written informed consent prior to any study-specific procedures (for the randomised intervention part), is willing to donate tissue from diagnostic biopsy, and is willing and able to make herself available for the duration of the study and to follow study schedule during treatment and follow-up and for the use of routinely collected electronic health and related records. Randomisation Stage Exclusion Criteria: 1. Patient has received prior CDK4/6 inhibitor. 2. Patient is planned to receive adjuvant abemaciclib as standard of care. 3. Any patient with a history of VTE (for example, DVT of the leg or arm and/or PE) will be excluded. Patients with a history of venous catheter occlusion by thrombus that did NOT surround the catheter, and the lumen could be made patent by appropriate measures (for example, saline or thrombolytic agent), are not excluded. 4. The patient has a serious/or uncontrolled pre-existing medical condition(s) that, in the judgment of the investigator, is likely to preclude study treatment (such as severe renal impairment, \[for example, estimated creatinine clearance \<30 mL/min\], interstitial lung disease, severe dyspnoea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or pre-existing Crohn's disease or ulcerative colitis or a pre-existing chronic condition resulting in baseline Grade 2 diarrhoea). 5. The patient has a personal history of any of the following conditions: syncope of cardiovascular aetiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: patients with controlled atrial fibrillation diagnosed more than 30 days prior to randomisation are not excluded. 6. The patient has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to randomisation, or is currently enrolled in any other type of medical research (for example: medical device) judged by the Chief Investigator not to be scientifically or medically compatible with this study. 7. The patient has any known active systemic bacterial infections (that would be expected to require IV antibiotics at time of initiating study treatment), systemic fungal infection or detectable viral infection (such as known HIV positivity or with known active hepatitis B or C, e.g. hepatitis B surface antigen positive) which would be expected to preclude study treatment. Screening is not required for enrolment. 8. Evidence of metastatic disease or local recurrence. 9. Multiple unilateral tumours with different ER and/or HER2 status (DCIS/LCIS are permitted, and confirmation of congruent ER/HER2 status is not necessary for lesions less than 10mm). Week 1 Day 1 Inclusion Criteria: 1. Patient must have undergone definitive surgery for the primary breast tumour with clear radial margins as judged by the multidisciplinary team. 2. Adjuvant chemotherapy, if prescribed, must have been completed prior to Week 1 Day 1, and patients must have recovered (Common Terminology Criteria for Adverse Events, version 5 \[CTCAE v5\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Week 1 Day 1. A washout period of a minimum of 28 days from day 1 of the last cycle of treatment is required. 3. Adjuvant radiotherapy, if prescribed, must have been completed prior to Week 1 Day 1, and patients must have recovered (Grade \</=1) from the acute effects of radiotherapy. A washout period of at least 14 days i

Newly diagnosed advanced/metastatic breast cancer at diagnosis that progressed with documented evidence of progression after one line of endocrine therapy (with either an antiestrogen or an aromatase inhibitor) (AND/OR) Previously diagnosed and treated metastatic BC, for the first time being offered CDK4/6 inhibition with endocrine therapy ( can have progressed after endocrine therapy before) Male Breast cancer patients are eligible to participate on the trial. Inclusion Criteria: * Female ≥ 18 years of age pre and post-menopausal * Metastatic disease (≤ 5 sites of measurable disease by RECIST) * Eligible for treatment with CDK4/6 + aromatase inhibitors * Premenopausal status is defined as either: * Patient had last menstrual period within the last 12 months, OR * If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, OR * In case of therapy-induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range. * Patients who have undergone bilateral oophorectomy are eligible. * Post-menopausal status defined as either 1) at least 2 years without menstrual period or 2) patients older than 50 with serological evidence of post-menopausal status or 3) hysterectomized patients of any age with FSH confirmation of post-menopausal status. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Biopsy proven diagnosis of HR+HER2- metastatic breast cancer. ER expression is \>10% * Patient needs to be able to understand and demonstrate a willingness to sign a written informed consent document * Hematological WBC ≥ 2000/uL * Absolute neutrophil count (ANC) ≥1500/µL * Platelets ≥100 000/µL * Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Renal Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for the participant with creatinine levels \>1.5 × institutional ULN Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN * AST (SGOT) and ALT (SGPT) ≤2.5 × ULN * Coagulation International normalized ratio (INR) OR prothrombin time (PT) * Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the participant is receiving anticoagulant therapy if PT or aPTT is within the therapeutic range of intended use of anticoagulants Exclusion Criteria: * Active connective tissue disorders, such as lupus or scleroderma requiring flare therapy * Current use of systemic chemotherapy, endocrine therapy or HER2-neu targeted therapy * Any lesion \>5 cm in greatest diameter. * Inability to obtain histologic proof of metastatic breast cancer * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. * Has a known additional malignancy (second primary) that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. cervical cancer in situ) that have undergone potentially curative therapy are not excluded. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has an active infection requiring systemic therapy. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Patients with uncontrolled brain metastases