Criteria for Inclusion of Subjects: Hand and forearm amputees: 1. Male or female, age 18 and older, of any race or ethnicity 2. Able and willing to sign Consent 3. Able and willing to participate in all study activities including implantation, testing and explantation of the study device. 4. Able to communicate effectively in English without an interpreter After preliminary screening subjects will be assessed for the following inclusion criteria: 1. Patient has an existing myoelectric hand prosthesis and demonstrates proficiency during daily use 2. Overall and phantom pain are well-controlled and not incapacitating Criteria for Exclusion of Subjects: 1. If MR neurogram and EMG/NCS study show nerve or muscle dysfunction/injury at a higher level than anticipated based on the appearance of the physical amputation stump, the subject may be excluded from the study due to adverse neuromuscular anatomy which would preclude use of the proposed experimental electrode implants. The radiographs will be used to confirm suitability of the amputation stump configuration. If the bony anatomy of the amputation stump is found to be unsuitable, the patient may be excluded from the study. 2. Subjects who have a history of cardiac arrhythmia will be excluded from the study.

• Age 1-40 years
• Histologically confirmed malignant extra-cranial solid tumor or demoid fibromatosis
• The subject's tumor must have relapsed after or failed to respond to frontline therapy and there must be no other known curative therapies available. Patients with desmoid fibromatosis must have relapsed after or failed to respond to at least one prior line of therapy, and in the opinion of the treating physician surgical resection of the tumor must not be possible without an amputation or other surgery predicted to result in an unacceptable functional deficit.
• Subject must have a life expectancy of > 8 weeks
• Karnofsky performance status > 50% for patients >16 years of age, or Lansky performance status > 50% for patients < 16 years of age.
• The subject must have at least 1 measurable target lesion >10mm in longest dimension that is in an anatomic location treatable by MR-HIFU. Note that for this study, lesions in bone WILL be considered measurable provided they meet the other criteria by RECIST and are confirmed to be metabolically active on baseline studies by either MIBG uptake (for neuroblastomas) or PET avidity. Target lesions should be located so that they can be adequately heated by a hyperthermia treatment cell with a diameter of up to 58 mm, centered at a depth of 35 to 80 mm from the skin. There should be no staples, implants, extensive scarring, or other highly ultrasound absorbing or reflecting tissue in the expected beam path. For the first 5 patients enrolled on this study only, the lesion must be located in the extremities or pelvis to be considered treatable by MR-HIFU.
• The subject must have recovered from the acute toxic effects of all prior therapy with the exception of alopecia. The following time must have elapsed from the last dose of the following medications to study enrollment:
• myelosuppressive chemotherapy 14 days
• hematopoetic growth factors 7 days (14 days for Neulasta)
• biologic agent 7 days
• monoclonal antibody 3 half-lives
• immunotherapy (ie tumor vaccines) 42 days
• palliative small port XRT 14 days
• substantial bone marrow XRT 6 weeks
• stem cell transplant or infusion without TBI 12 weeks
• total body irradiation (TBI) 24 weeks
• Adequate organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,000/mcL
• platelets ≥ 75,000/mcl (without transfusion for 7 days)
• hemoglobin > 8g/dL (may receive transfusions)
• total bilirubin < 1.5 mg/dL
• ALT(SPGT) < 225 U/L (45 U/L defined as ULN)
• creatinine clearance or radioisotope GFR > 70 mL/min/1.73m2 OR a serum creatinine (mg/dL) less than or equal to the following:
• Age (yrs)-----Male (mg/dL)-----Female (mg/dL)
• 1-1.99----------0.6------------------0.6
• 2-5.99----------0.8------------------0.8
• 6-9.99----------1--------------------1
• 10-12.99------1.2------------------1.2
• 13-15.99------1.5------------------1.4
• >16-------------1.7------------------1.4
• Adequate cardiac function defined as an ejection fraction > 50% or shortening fraction > 27%
• Cumulative lifetime anthracycline dose of < 450mg/m2
• Females and males of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A male of child-bearing potential is any male (regardless of sexual orientation, having undergone a vasectomy, or remaining celibate by choice) who has attained Tanner stage III or greater sexual development. A female of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has undergone menarche OR is > 13 years of age
• Females of child-bearing potential must have a negative serum pregnancy test within 7 days of treatment.
• Signed written informed consent must be obtained prior to any study procedures.
• Subjects may not be receiving any other investigational agents or anticancer therapies.
• Subjects with known active brain metastases will be excluded from this clinical trial. Patients with brain metastases that have been treated and stable for > 30 days following treatment will be eligible.
• Subjects who have received prior Doxil and progressed on this therapy are not eligible, but subjects may have received prior doxorubicin.
• Subjects with a history of tumor progression within 30 days of anthracycline administration are not eligible. However, subjects who have previously received an anthracycline and subsequently relapse greater than 30 days after their most recent prior dose of anthracycline will be eligible.
• History of allergic reactions attributed to doxorubicin or Doxil
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Subjects with a contraindication to MR-HIFU
• Subjects with conditions that carry high anesthetic risk in the opinion of the treating anesthesiologist are not eligible (i.e. subjects with significant airway compression by tumor or craniofacial abnormalities)

• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment

• Feasibility Phase: Patients must be < 21 years of age at the time of enrollment; please note: the feasibility phase is complete, effective with amendment #1
• Efficacy Phase: Patients must be =< 40 years of age at the time of enrollment
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study based upon stage, group, and age, as below
• RMS types included under embryonal rhabdomyosarcoma (ERMS) include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2013 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant); classification of alveolar rhabdomyosarcoma (ARMS) in the 2013 WHO classification is the same as in the ICR and includes classic and solid variants
• ERMS
• Stage 1, group III (non-orbit)
• Stage 3, group I/II
• Stage 2/3, group III
• Stage 4, group IV, < 10 years old
• ARMS:
• Stages 1-3, groups I-III
• Specimen Submission: Patients must have sufficient tissue available for the required biology study
• Lansky performance status score >= 50 for patients =< 16 years of age; Karnofsky performance status score >= 50 for patients > 16 years of age
• Peripheral absolute neutrophil count (ANC) >= 750/uL
• Platelet count >= 75,000/uL
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• 1 month to < 6 months old: 0.4 mg/dl (male), 0.4 mg/dl (female)
• 6 months to < 1 year old: 0.5 mg/dl (male), 0.5 mg/dl (female)
• 1 to < 2 years old: 0.6 mg/dl (male), 0.6 mg/dl (female)
• 2 to < 6 years old: 0.8 mg/dl (male), 0.8 mg/dl (female)
• 6 to < 10 years old: 1 mg/dl (male), 1 mg/dl (female)
• 10 to < 13 years old: 1.2 mg/dl (male), 1.2 mg/dl (female)
• 13 to < 16 years old: 1.5 mg/dl (male), 1.4 mg/dl (female)
• >= 16 years old: 1.7 mg/dl (male), 1.4 mg/dl (female)
• Patients with an elevated serum creatinine due to obstructive hydronephrosis secondary to tumor are still eligible; however, patients with urinary tract obstruction by tumor must have unimpeded urinary flow established via diversion (i.e. percutaneous nephrostomies or ureteric stents) of the urinary tract
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• All patients and/or their parents or legal guardians must sign a written informed consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
• Patients who have previously received temsirolimus, another mTOR inhibitor, or any other investigational agent
• Patients who have received any chemotherapy (excluding steroids) and/or RT prior to this enrollment
• Patients with uncontrolled hyperglycemia
• Patients with uncontrolled hyperlipidemia
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for at least 3 months after treatment is completed
• Female patients who are pregnant are not eligible; Note: a pregnancy test is required for female patients of childbearing potential prior to study entry
• Lactating females who plan to breastfeed their infants are not eligible

• Age: ≥12 months to <18 years old at the time of informed consent
• Diagnosis: Histologically confirmed rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) (Grade 2 or 3), or Ewing sarcoma (EWS) which is relapsed or refractory (failed front line therapy)
• The presence of measurable disease meeting the following criteria:
• At least 1 lesion of ≥1.0 centimeter (cm) in the longest diameter for a non-lymph node or ≥1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI).
• Lesions that have had radiotherapy must show subsequent radiographic evidence of increase in size by at least 20% to be deemed a target lesion.
• Therapeutic options: Participant's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
• Performance level: Performance score ≥50%. Karnofsky (for participants >16 years of age) or Lansky (for participants ≤16 years of age)
• Participants must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to study drug administration. If, after the required time frame, the numerical eligibility criteria are met, eg, blood count criteria, the participant is considered to have recovered adequately:
• Cytotoxic chemotherapy or other chemotherapy known to be myelosuppressive: ≥21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea).
• Anticancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count [ANC] counts): ≥7 days after the last dose of agent.
• Antibodies: 3 half-lives must have elapsed from infusion of last dose of antibody (including checkpoint inhibitors), and toxicity related to prior antibody therapy must be recovered to Grade ≤1.
• Hematopoietic growth factors: ≥14 days after the last dose of a long-acting growth factor (eg, Neulasta) or 7 days for a short-acting growth factor. For agents that have known adverse events (AEs) occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur.
• Interleukins, interferons, and cytokines (other than hematopoietic growth factors): ≥21 days after the completion of interleukins, interferons, or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation [TBI]): ≥84 days
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion or boost infusion: ≥84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: ≥42 days
• Cellular therapy: ≥42 days after the completion of any type of cellular therapy (eg, modified T-cells, natural killer cells, dendritic cells, etc)
• Radiation therapy (XRT)/External Beam Irradiation including Protons: ≥14 days after local XRT, ≥150 days after TBI, craniospinal XRT or if radiation to ≥50% of the pelvis, ≥42 days if other substantial BM radiation
• Radiopharmaceutical therapy (eg, radiolabeled antibody, 131I-metaiodobenzylguanidine): ≥42 days after systemically administered radiopharmaceutical therapy.
• Adequate bone marrow function, defined as:
• ANC ≥1.0 × 10^9/Liter (L)
• Platelet count ≥100 × 10^9/L (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to study drug administration)
• Hemoglobin at least 8.0 grams per deciliter (g/dL) at Baseline (blood transfusions are allowed during the screening period to correct hemoglobin values less than 8.0 g/dL) As blood transfusions are permitted to meet the hemoglobin criteria, participants requiring transfusion must not be known to be refractory to red blood cell or platelet transfusions.
• Adequate renal function, defined as:
• A serum creatinine based on age/gender, derived from the Schwartz formula for estimating glomerular filtration rate (GFR)
• Or creatinine clearance or radioisotope GFR ≥50 milliliters per minute (mL/min)/1.73 meters squared (m^2) based on a 12 or 24 hour urine creatinine collection
• Adequate liver function, defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤1.5 × upper limit of normal (ULN) for age
• Alanine aminotransferase (ALT) ≤110 units per Liter (U/L). For the purpose of this study, the ULN for ALT is 45 U/L
• Serum albumin ≥2 g/dL
• Informed consent: All participants and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. Participants must be willing to comply with all aspects of the protocol.
• Pregnancy, breastfeeding, contraception: Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic [β-hCG] or human chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 International Units per Liter [IU/L] or equivalent units of β-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
• Females of childbearing potential (all post pubertal females will be considered to be of childbearing potential unless they have early menopause [amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause] or have been sterilized surgically [ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing]) who:
• Do not agree to use a highly effective method of contraception for the entire study period and for 6 months after study drug discontinuation, ie:
• Total abstinence (if it is their preferred and usual lifestyle);
• An intrauterine device (IUD) or intrauterine system (IUS);
• A contraceptive implant;
• An oral contraceptive (must be on a stable dose of the same oral hormonal contraceptive product for at least 4 weeks before dosing with study drug and for the duration of the study and for 6 months after study drug discontinuation); or
• Do not have a vasectomized partner with confirmed azoospermia. For sites outside of the European Union (EU), it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, or the participant has changed oral hormonal contraceptive product/dose within 4 weeks prior to study drug administration, then the participant must agree to use a medically acceptable method of contraception, ie, double barrier methods of contraception such as condoms plus diaphragm or cervical/vault cap with spermicide.
• Males who have not had a successful vasectomy (confirmed azoospermia) or if they and their female partners do not meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period or for 28 days after study drug discontinuation). No sperm donation is allowed during the study period or for 28 days after study drug discontinuation.
•Concomitant medications:
• Corticosteroids: Participants receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to study drug administration (except when indicated for Central Nervous System [CNS] metastases, then participants must not have received corticosteroids for at least 28 days)
• Anticancer Agents: participants who are currently receiving other anticancer agents
• Anti-GVHD agents posttransplant
• Participants who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant
• Received prior therapy with eribulin mesylate
• Any other malignancy that required treatment (except for non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ), within 2 years prior to study drug administration
• Has hypersensitivity to eribulin or any of the excipients
• Has a prior history of viral hepatitis (B or C) as demonstrated by positive serology (presence of antigens) or have an uncontrolled infection requiring treatment. Participants with a known prior history of hepatitis B or C may be eligible pending agreement with the sponsor.
• Has > Grade 1 peripheral sensory neuropathy or > Grade 1 peripheral motor neuropathy graded according to the Modified ("Balis") Pediatric Scale of Peripheral Neuropathies
• Has cardiac pathology: Participants with known congestive heart failure, symptomatic or left ventricular (LV) ejection fraction <50% or shortening fraction <27% and participants with congenital long QT syndrome, bradyarrhythmias, or QTc >480 msec on at least 2 separate electrocardiograms (ECGs).
• Has CNS Disease: Participants with brain or subdural metastases are not eligible unless the metastases are asymptomatic and do not require treatment or have been adequately treated by local therapy (eg, surgery or radiotherapy) and have discontinued the use of corticosteroids for this indication for at least 4 weeks prior to study drug administration. Confirmation of radiographic stability must be done by comparing the brain scan (CT or MRI) performed during the Screening Period, using the same imaging modality, to a brain scan performed earlier (and following local therapy where applicable). Participants must be clinically stable. It is not the intention of this protocol to treat participants with active brain metastases. Note: CNS imaging is required to confirm eligibility for participants with a known history of CNS disease.
• Have had or are planning to have the following invasive procedures:
• Major surgical procedure or significant traumatic injury within 28 days prior to study drug administration
• Laparoscopic procedure or open biopsy within 7 days prior to study drug administration
• Central line placement or subcutaneous port placement is not considered major surgery but must be placed at least 2 days prior to study drug administration
• Core biopsy, including bone marrow biopsy, within 2 days prior to study drug administration
• Fine needle aspirate within 3 days prior to study drug administration
• Has any serious concomitant illness that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
• Participants with known human immunodeficiency virus (HIV); due to lack of available safety data for eribulin therapy in HIV-infected participants

Inclusion Criteria for Patients:
• African-American or White
• age 65 or greater
• English-speaking
• residing in non-institutional setting
• cognitively able to participate in advance care planning
• Serious or chronic illness including: metastatic cancer; end stage renal disease; advanced liver disease, heart disease or lung disease; amyotrophic lateral sclerosis, severe Parkinson's disease; 2 or more unplanned hospitalizations in the last year; requiring assistance with any basic activity of daily living
• Serious illness based on the following: Clinician answers "no" to the surprise question: "Would you be surprised if this person died in the next 12 months?" Exclusion Criteria for Patients:
• residence in nursing home or assisted living facility
• diagnosis of dementia or unable to consent
• documented advance care plan (living will, health care proxy, MOST form, provider note)
• current or prior use of hospice
• current or prior use of non-hospice palliative care except inpatient palliative care consultation

Key Inclusion Criteria
• Patients ≥6 months and up to 60 months (1800 days) of age at time of dosing following diagnostic confirmation during screening period by genotype who demonstrate the ability to sit unassisted for 10 or more seconds but cannot stand or walk
• Diagnostic confirmation by genotype includes lab documentation of homozygous absence of SMN1 exon 7; with exactly three copies of SMN2
• Negative gene testing for SMN2 gene modifier mutation (c.859G>C)
• Onset of clinical signs and symptoms consistent with spinal muscular atrophy (SMA) at < 12 months of age
• Able to sit independently and not standing or walking independently. Definition of sitting independently is defined by the World Health Organization Multicentre Growth Reference Study (WHO-MGRS) criteria of being able to sit up unsupported with head erect for at least 10 seconds. Child should not use arms or hands to balance body or support position (Wijnhoven 2004)
• Be up-to-date on childhood vaccines. Seasonal vaccinations that include palivizumab prophylaxis (also known as Synagis) to prevent respiratory syncytial virus (RSV) infections are also recommended in accordance with American Academy of Pediatrics (AAP 2009) Key Exclusion Criteria
• Current or historical ability to stand or walk independently
• Contraindications for spinal tap procedure or administration of intrathecal therapy or presence of an implanted shunt for the drainage of CSF or an implanted central venous (CNS) catheter
• Severe contractures as determined by designated Physical Therapist(s) at screening that interfere with either the ability to attain/demonstrate functional measures or interferes with ability to receive intrathecal (IT) dosing
• Severe scoliosis (defined as ≥ 50° curvature of spine) evident on X-ray examination
• Previous, planned or expected scoliosis repair surgery/procedure within 1 year of dose administration
• Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening while the patient is awake, or for high altitudes > 1000 m, oxygen saturation < 92% while the patient is awake
• Pulse oximetry saturation must not decrease ≥ four (4) percentage points between screening and highest value on day of dosing
• Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two (2) weeks prior to dosing
• Medical necessity for a gastric feeding tube, where the majority of feedings are given by non-oral methods (i.e., nasogastric tube or nasojejunal tube) or patients whose weight-for-age falls below the 3rd percentile based on WHO Child Growth Standards (Onis 2006). Placement of a permanent gastrostomy prior to screening is not an exclusion
• Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two (2) weeks prior to dosing
• Medical necessity for a gastric feeding tube, where the majority of feedings are given by non-oral methods or patients whose weight-for-age falls below the 3rd percentile based on WHO Child Growth Standards (Onis 2006). Placement of a permanent gastrostomy prior to screening is not an exclusion
• Active viral infection (includes human immunodeficiency virus (HIV) or serology positive for hepatitis B or C, or Zika virus)
• Serious non-respiratory tract illness requiring systemic treatment and/or hospitalization within two (2) weeks prior to study entry
• Respiratory infection requiring medical attention, medical intervention or increase in supportive care of any manner within four (4) weeks prior to study entry
• Severe non-pulmonary/respiratory tract infection within four (4) weeks before study dosing or concomitant illness that in the opinion of the Principal Investigator (PI) creates unnecessary risks for gene transfer such as:
• Major renal or hepatic impairment
• Known seizure disorder
• Diabetes mellitus
• Idiopathic hypocalciuria
• Symptomatic cardiomyopathy
• History of bacterial meningitis or brain or spinal cord disease, including tumors, or abnormalities by magnetic resonance imaging (MRI) or computerized tomography (CT) that would interfere with the lumbar puncture (LP) procedures or CSF circulation
• Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
• Known allergy or hypersensitivity to iodine or iodine-containing products
• Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months of study dosing
• Inability to withhold use of laxatives or diuretics in the 24 hours prior to dose administration
• Anti-AAV9 antibody titers >1:50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay
• Should a potential patient demonstrate anti AAV9 antibody titer > 1:50, he or she may receive retesting within 30 days of the screening period and will be eligible to participate if the anti AAV9 antibody titer upon retesting is ≤ 1:50
• Abnormal laboratory values considered to be clinically significant (INR >1.4), GGT >3XULN, Bilirubin ≥3.0 mg/dL, Creatinine ≥1.0 mg/dL, Hgb <8 or >18 g/Dl; WBC >20,000 per cmm) prior to study dosing
• Participation in recent SMA treatment clinical trial or receipt of an investigational or approved compound product or therapy received with the intent to treat SMA at any time prior to screening for this study
• Oral beta agonists must be discontinued 30 days prior to dosing.
• Inhaled albuterol specifically prescribed for the purposes of respiratory (bronchodilator) management is acceptable and not a contraindication at any time prior to screening for this study
• Expectation of major surgical procedures during the 1-year study assessment period

• Histologically confirmed diagnosis of a locally advanced (not amenable to curative therapy such as surgical resection) metastatic cancer of the following histologies: melanoma (MEL), Merkel cell carcinoma (MCC), triple-negative breast cancer (TNBC), ovarian carcinoma, renal cell carcinoma (RCC), colorectal cancer, urothelial carcinoma, or sarcoma.
• Life expectancy > 12 weeks as determined by the Investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Measurable disease per RECIST 1.1.
• Patients enrolled in Cohorts 1-5, Cohort A, Cohort B and Phase 2 Doublet must be refractory to all therapies known to confer clinical benefit to their disease.
• Fresh tumor tissue available for cellular characterization and programmed cell death protein 1 (PD-L1) status.
• Injected lesions (up to two) must be between 20 mm and 90 mm in diameter for IT injection; lesions must be accessible for baseline and on-treatment biopsies.
• Demonstrated adequate organ function within 14 days of Cycle 1 Day 1 (C1D1).
• Use of an investigational agent or an investigational device within 21 days before administration of first dose of study drug(s).
• Patients treated with prior interleukin-2 (IL-2).
• Patients who have been previously treated with a toll-like receptor (TLR) agonist (excluding topical agents) and patients who have received experimental cancer vaccines.
• Patients who have received systemic interferon (IFN)α within the previous 6 months prior to enrollment to the study.
• Other active malignancy, except non-melanomic skin cancer
• Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
• Prior surgery or radiotherapy within 14 days of initiating study drug(s). Patients must have recovered from all radiation-related toxicities, not required corticosteroids and have not had radiation pneumonitis.
• Prolonged Fridericia's corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening.
• History of unstable or deteriorating cardiac disease within the previous 6 months prior to screening including but not limited to the following:
• Unstable angina or myocardial infarction.
• Congestive heart failure (NYHA Class III or IV).
• Uncontrolled clinically significant arrhythmias.
• Need for > 2 antihypertensive medications for management of hypertension (including diuretics).
• Patients with a history of any retinal disorders (e.g., retinal detachment, diabetic retinopathy, retinal hemorrhage, macular degeneration).

1. Subjects 21 to 90 years old 2. Subjects must have generalized MG, defined as MGFA clinical classification grades 2 (mild), 3 (moderate), or 4 (severe, but not intubated) at the time of screening/randomization. 3. Elevated AChR antibody titer 4. Subject's signs and symptoms should not be better explained by another disease process. 5. Subjects must be on a stable standard immunosuppressive regimen: 1. Prednisone only: Prednisone dose must be at least 15mg/day (or the equivalent on alternate days), and the dose of prednisone must have been stable for at least 4 weeks (28 days) prior to the baseline visit. 2. Prednisone plus another immunosuppressive therapy (IST). Immunosuppressive therapies other than prednisone, specifically azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus or methotrexate, are permitted, but the dose must have been stable for at least 6 months prior to the baseline visit. (Note: The prednisone dose must be stable as defined in the prednisone only group. The IST dose must remain stable throughout the course of the study). 6. Subjects must be willing to complete the study and return for follow-up visits. 7. No history of thymoma, tumor, infection, or interstitial lung disease on chest CT, MRI, or chest x-ray. Note: Chest x-ray will be completed at screening to look of interstitial lung disease. A chest CT or MRI to evaluate for thymoma must be completed as part of prescreening. 8. Able and willing to give written informed consent and comply with the requirements of the study protocol. 9. Subjects must be able to give written informed consent before participating in this study. A copy of the signed consent must be kept in the subject's medical record. 10. Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment. 1. A history of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue. 2. Other major chronic or debilitating illnesses within six months prior to study entry. 3. Female subjects who are premenopausal and are: 1. pregnant on the basis of a serum pregnancy test, 2. breast-feeding, or 3. not using an effective method of double barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) or birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures). 4. Altered levels of consciousness, dementia, or abnormal mental status. 5. Thymectomy in the previous six months. 6. Subjects who have been medicated with immunosuppressive drugs not listed in inclusion #5 within the last 8 weeks (56 days) prior to the baseline visit 7. Subjects who have been medicated with an immunosuppressive agent such as azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus or methotrexate, that is withdrawn within 8 weeks (56 days) of the Baseline Visit. 8. Subjects who have received IVIg or PLEX treatment within the last 4 weeks (28 days) prior to the baseline visit. 9. Unstable dose or a stable dose of > 480 mg/day of pyridostigmine in 2 weeks prior to screening visit. 10. Daily use of non-steroidal anti-inflammatory drugs (NSAIDs). 11. History of renal or hepatic insufficiency or elevated liver enzymes (AST or ALT >2.5 x Upper Limit of Normal). 12. History of bone marrow hypoplasia, leucopenia, thrombocytopenia, significant anemia, clinical or laboratory evidence of immunodeficiency syndromes. 13. Forced Vital Capacity (FVC) <50% of percent predicted. General Safety & Laboratory Exclusion Criteria 14. ANC < 1.5 x 103 cells/microliter 15. Hemoglobin: < 8.0 gm/dL 16. Platelets: < 100,000/mm 17. Positive Hepatitis B or C serology (Hep B surface antigen and Hep C antibody) 18. History of positive HIV (HIV conducted during screening if applicable) 19. Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer) 20. Receipt of a live vaccine within 4 weeks prior to randomization 21. Previous treatment with rituximab (MabThera® / Rituxan®) 22. Previous treatment with natalizumab (Tysabri®) 23. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies 24. History of recurrent significant infection or history of recurrent bacterial infections 25. Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening 26. Unstable steroid dose in the past 4 weeks (28 days) 27. Lack of peripheral venous access 28. History of drug, alcohol, or chemical abuse within 6 months prior to screening 29. Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or prostate. 30. History of psychiatric disorder that would interfere with normal participation in this protocol 31. Significant cardiac or pulmonary disease (including obstructive pulmonary disease) 32. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications 33. Subjects that do not record daily prednisone doses for at least 28 days before the Baseline Visit, or subjects whose prednisone dose varies by ≥6mg/day on average. 34. Prednisone dose of more than 100 mg/day (or 200 mg over a two day period).

• Adults aged 18 years or older
• Individuals undergoing surgery of the medial foot, medial ankle, or medial leg for which the anesthetic plan includes an adductor canal nerve block 1. Any known deficit of the ipsilateral lumbar nerve roots, ipsilateral lumbar plexus, ipsilateral femoral nerve, obturator nerve or saphenous nerve including diabetic peripheral neuropathy 2. Any local disorder of the skin or otherwise where blockade is to be performed 3. Body mass index >50 4. ASA classification greater than 3 5. Allergy to amide local anesthetic medications 6. Pregnancy 7. Incarceration 8. Inability to understand study procedures including inability to understand the English language

Key
• Advanced solid tumor for which, in the opinion of the Investigator, no other standard therapy offers greater benefit.
• A solid tumor diagnosis in the setting of: 1. a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor 2. a documented NTRK fusion unresponsive to a prior TRK inhibitor 3. a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
• NTRK gene fusions will be identified via a CLIA certified (or equivalent) laboratory. Exception: Patients with Infantile Fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) may be enrolled based on ETV6+ FISH test without identifying NTRK3
• Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3 (age ≥16) or Lansky Performance Score (LPS) ≥40% (age<16). If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Status (KPS) (age ≥16) or LPS (age<16) ≥ 50%
• Life expectancy > 4 weeks
• Adequate hematologic, hepatic and renal function.
• Patients with stable CNS primary tumor, brain metastases, or treated spinal cord compression are eligible if neurological symptoms and steroid use (if applicable) have been stable for 7 days prior to the first dose of LOXO-195
• Ability to receive study drug orally or by enteral administration Key
• Required treatment with certain strong CYP3A4 inhibitors or inducers.
• Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of LOXO-195 or prolongation of the QT interval corrected (QTcF) > 480 msec within the past 6 months
• Major surgery within 7 days of enrollment
• Uncontrolled systemic bacterial, fungal or viral infection
• Pregnancy or lactation.
• Known hypersensitivity to any of the components of LOXO-195 or Ora-Sweet® SF and OraOlus, for patients receiving liquid suspension

• Patients are eligible under ONE of the following criteria:
• Patients must have histologically confirmed rare cancer and must be able to submit specimens; NOTE: Subsequent to site's Institutional Review Board (IRB) approval of revision 3, patients are NOT required to participate in EAY131 "National Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH)" to register to this study
• FOR PATIENTS ENROLLED IN EAY131 "NCI-MATCH" PRIOR TO EAY131 ADDENDUM 10 ONLY: Patients must have histologically confirmed rare cancer that did not have a match to a molecularly-guided therapy on EAY131 "NCI-MATCH" protocol or who are off protocol treatment on EAY131, "NCI-MATCH" and have no further molecularly-matched treatment recommendations per EAY131, "NCI-MATCH" or who are otherwise unable to receive EAY131, "NCI-MATCH" therapy
• Patients that do not qualify for one of the histologic cohorts may be considered for registration in the "Not Otherwise Categorized" Rare Tumors cohort with confirmation of at least one of the study chairs via email
• Patients that are determined to have a rare cancer with unknown primary site are eligible under cohort #32 (tumor of unknown primary [cancer of unknown primary; CuP]), provided that there is histologic documentation of metastatic malignancy with no discernible primary site identified from histopathologic review, physical exam and associated cross-sectional imaging of the chest, abdomen, and pelvis
• Patients must have progressed following at least one line of standard systemic therapy and there must not be other approved/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolonged survival due to medical issues will be eligible, if other eligibility criteria are met; OR
• Patients for whose disease no standard treatment exists that has been shown to prolong overall survival
• Patients must have a diagnostic quality computed tomography (CT) scan or magnetic resonance imaging (MRI), performed within 28 days prior to registration, which demonstrates measurable disease, as defined in RECIST v. 1.1; all disease must be assessed and documented on the S1609 Baseline Tumor Assessment Form
• No other prior malignancy is allowed except for the following:
• Adequately managed stage I or II cancer from which the patient is currently in complete remission
• Any other cancer from which the patient has been disease free for one year
• Adequately managed stage I or II follicular thyroid or prostate cancer is also eligible, wherein patient is not required to be in complete remission
• Patients may have received prior anti-CTLA4 or other anti-PD-1/anti-PD-L1 therapy, not both, provided that it is completed >= 4 weeks prior to registration
• Patients who had prior grade 3 or higher immune-related adverse event (e.g. pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.) are not eligible
• Patients with clinically controlled thyroiditis or pituitary disorders on stable replacement therapy are eligible
• Patients are not eligible if they have had or are planned for solid organ transplant; patients who have received allogeneic hematopoietic stem cell transplant are eligible if:
• The transplant occurred at least 90 days prior to registration,
• Patient has no prior acute graft versus host disease (GVHD), and
• Within 48 hours of registration, patient demonstrates at least 90% engraftment, defined as: absolute neutrophil count (ANC) >= 500 mcl, measured over 3 consecutive days or 1 day with an ANC >= 1,000 mcl, or platelets >= 50,000 mcl measured, wherein the patient did not receive any platelet transfusions within 7 days prior to laboratory assessment
• Patients with autoimmune disease who are otherwise eligible must not have received steroid and immunosuppressive therapy within 28 days prior to registration
• Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 28 days prior to registration and have stable disease at time of registration; metastatic brain parenchymal disease must have been treated and patient must be off steroids for 7 days prior to registration; patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registration
• Patients must not currently be receiving any other investigational agents or any other systemic anti-cancer therapy (including radiation, excluding RANKL inhibitors and bisphosphonates); in event patient recently received any other systemic anti-cancer therapy, patient must be off therapy at least 7 days prior to registration and any therapy-induced toxicity must have recovered to =< grade 1, except alopecia and =< grade 2 neuropathy which are allowed; any planned radiation therapy must be completed before enrollment onto S1609
• Patients must not have prior history of allergy or known hypersensitivity to nivolumab or ipilimumab
• Patients must have a Zubrod performance status of 0-2
• Within 28 days prior to registration: ANC >= 1,000/mcL
• Within 28 days prior to registration: Platelets >= 75,000/mcL
• Within 28 days prior to registration: Hemoglobin >= 8 g/dL
• Within 28 days prior to registration: Total bilirubin =< 2.0 x institutional upper limit of normal (IULN) or for documented/suspected Gilbert's disease, total bilirubin =< 3.0 x IULN
• Within 28 days prior to registration: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 3 x IULN
• Within 28 days prior to registration: Serum creatinine =< 2.0 x IULN
• Within 28 days prior to registration: Creatinine clearance (CrCl) >= 50 mL/min., as estimated by the Cockcroft and Gault formula; estimated creatinine clearance is based on actual body weight
• Patients must have adequate thyroid function, as evidenced by either thyroid-stimulating hormone (TSH) or, free thyroxine (T4) serum tests demonstrating values within the normal range, within 28 days prior to registration; Note: TSH, with reflex T4 is allowable if per institutional standard; otherwise, both TSH and free-T4 must be obtained
• Patients must have adequate adrenal axis function, as evidenced by adrenocorticotropic hormone (ACTH) values within the institutional normal ranges OR cortisol levels within institutional normal ranges (ante meridiem [AM] cortisol preferred), within 28 days prior to registration
• Females of childbearing potential must have negative serum or urine pregnancy test 7 days prior to registration and agree to use birth control throughout study and for 23 weeks after completion of protocol therapy; patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
• Men of reproductive potential must have agreed to use birth control throughout the study and for 31 weeks after completion of protocol therapy; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (vasectomy); however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he is responsible for beginning contraceptive measures
• Patients must not have known active hepatitis B virus (HBV) or hepatitis virus (HCV) infection at time of registration; patients with HBV or HCV that have an undetectable viral load, or in the opinion of the treating investigator is well-controlled, are eligible
• Patients who are known to be human immunodeficiency virus (HIV)-positive at registration are eligible at the time of registration: 1. Cluster of differentiation (CD)4+ cell count greater or equal to 250 cells/mm^3 2. If patient is on antiretroviral therapy, there must be minimal interactions or overlapping toxicity of the antiretroviral therapy with the experimental cancer treatment; once daily combinations that use pharmacologic boosters may not be used 3. No history of non-malignancy acquired immunodeficiency syndrome (AIDS)-defining conditions other than historical low CD4+ cell counts
• Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, immunosuppressive drugs, or corticosteroids with doses higher than prednisone 10mg or equivalent); 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; autoimmune diseases include but are not limited to autoimmune hepatitis, inflammatory bowel disease (including ulcerative colitis and Chron's disease), as well as symptomatic disease (e.g. rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis or glomerulonephritis); vitiligo, alopecia, hypothyroidism on stable doses of thyroid replacement therapy, psoriasis not requiring systemic therapy within the past 2 years is permitted; short-term steroid premedication for contrast allergy is permitted
• Patients must not have any uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4 grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= grade 3)
• Note: Patients with history of CHF or patients who are deemed at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs should have an electrocardiogram (EKG) and echocardiogram (ECHO), as clinically indicated, at baseline and at the start of each cycle; patients who have evidence at baseline (or subsequently) of CHF, myocardial infarction (MI), cardiomyopathy, or myositis cardiac evaluation (NYHA I/II) should have additional consult by a cardiologist, including review of EKG, creatine phosphokinase (CPK), troponin, echocardiogram, as clinically indicated
• Patients must have amylase or lipase within =< 1.5 x IULN without symptoms of pancreatitis at registration, within 28 days prior to registration
• Patients must not have symptomatic interstitial lung disease or pneumonitis
• Patients must have fully recovered from any adverse effects of major surgery (to =< grade 1) at least 14 days prior to registration

• Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site
• For the purpose of this study metastatic disease is defined as one or more of the following:
• Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor; skip lesions in the same bone as the primary tumor do not constitute metastatic disease; skip lesions in an adjacent bone are considered bone metastases; if there is any doubt whether lesions are metastatic, a biopsy of those lesions should be performed
• Contralateral pleural effusion and/or contralateral pleural nodules
• Distant lymph node involvement
• Patients with pulmonary nodules are considered to have metastatic disease if the patient has:
• Solitary nodule >= 0.5 cm or multiple nodules of >= 0.3 cm unless lesion is biopsied and negative for tumor
• Patients with solitary nodule < 0.5 cm or multiple nodules < 0.3 cm are not considered to have lung metastasis unless biopsy documents tumor
• Bone marrow metastatic disease is based on morphologic evidence of Ewing sarcoma based on hematoxylin and eosin (H&E) stains; in the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse-transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study
• This study requires bilateral bone marrow biopsies at study entry; the suggested approach for patients with large pelvic tumors in which a posterior iliac crest bone marrow biopsy would track through the tumor is to instead undergo 2 marrow biopsies on the contralateral side (either 2 posterior biopsies or one posterior and one anterior biopsy)
• Bone metastasis: This study utilizes whole body FDG-PET scans to screen patients for bone metastases; areas suspicious for bone metastasis based on FDG-PET scans require confirmatory anatomic imaging with either MRI or computed tomography (CT) (whole body FDG-PET/CT or FDG-PET/magnetic resonance [MR] scan acceptable); whole body technetium bone scans may be performed at the discretion of the investigator and are not required; for patients without other sites of metastatic disease whose sole metastatic site to qualify for study entry is a single area suspicious for bone metastasis identified by FDG-PET, confirmatory biopsy or anatomic imaging evidence of an associated soft tissue mass at that site is required for study entry
• Patients must have adequate tumor tissue to meet the minimum requirement for submission
• Enrolling institutions are reminded that submission of pre-treatment serum, tumor tissue and whole blood is required
• Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age < 6 months: Maximum serum creatinine (mg/dL): 0.4 for males and females
• Age 6 months to < 1 year: Maximum serum creatinine (mg/dL): 0.5 for males and females
• Age 1 to < 2 years: Maximum serum creatinine (mg/dL): 0.6 for males and females
• Age 2 to < 6 years: Maximum serum creatinine (mg/dL): 0.8 for males and females
• Age 6 to < 10 years: Maximum serum creatinine (mg/dL): 1 for males and females
• Age 10 to < 13 years: Maximum serum creatinine (mg/dL): 1.2 for males and females
• Age 13 to < 16 years: Maximum serum creatinine (mg/dL): 1.5 for males and 1.4 for females
• Age >= 16 years: Maximum serum creatinine (mg/dL): 1.7 for males and 1.4 for females
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x upper limit of normal (ULN) for age (except for patients with liver metastasis who may enroll if ALT < 5 times ULN for age)
• Shortening fraction of >= 27% or
• Ejection fraction of >= 50%
• Patients must have a normal blood sugar level for age to participate; if an initial random draw (ie. non-fasting) blood glucose value is out of range, it is acceptable to repeat this test as a fasting draw
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Patients with regional node involvement as their only site of disease beyond the primary tumor will not be eligible
• Patients whose primary tumors arise in the intra-dural soft tissue (eg. brain and spinal cord) are not eligible
• Patients who have received prior chemotherapy or radiation therapy are not eligible
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained; lactating females are not eligible unless they have agreed not to breastfeed their infants for the duration of protocol therapy; sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of protocol therapy
• Patients with known pre-existing diabetes mellitus will be excluded from study
• Patients receiving chronic pharmacologic doses of corticosteroids are not eligible; for the purposes of eligibility, chronic exposure is defined as anticipated exposure of > 3 weeks, including the sum of both pre-enrollment and anticipated post-enrollment dosing; patients on acute corticosteroid therapy (=< 3 weeks of total planned exposure) must still meet the normal blood glucose requirement; patients receiving chronic inhaled corticosteroids or chronic physiologic replacement doses of corticosteroids are eligible

• Age ≤6 weeks (≤42 days) at time of dose
• Ability to tolerate thin liquids as demonstrated through a formal bedside swallowing test
• Compound muscle action potential (CMAP) ≥2mV at Baseline; centralized review of CMAP data will be conducted
• Gestational age of 35 to 42 weeks Patients with 2 copies of SMN2 (n ≥15)
• Patients with pre-symptomatic SMA Type 1 as determined by the following features: − 2 copies of SMN2 Patients with 3 copies of SMN2 (n ≥12)
• Patients with pre-symptomatic SMA Type 2 as determined by the following features: − 3 copies of SMN2 Patients with 4 copies of SMN2 (n ≥17)
• Patients with pre-symptomatic SMA Type 3 as determined by the following features:
• 4 copies of SMN2
• Weight at screening visit <2 kg
• Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support) at the screening visit or for altitudes >1000 m, oxygen saturation <92% awake or asleep without any supplemental oxygen or respiratory support at the screening visit
• Any clinical signs or symptoms at screening or immediately prior to dosing that are, in the opinion of the Investigator, strongly suggestive of SMA (e.g., tongue fasciculation, hypotonia, areflexia)
• Tracheostomy or current prophylactic use or requirement of noninvasive ventilatory support at any time and for any duration prior to screening or during the screening period
• Patients with signs of aspiration/inability to tolerate nonthickened liquids based on a formal swallowing test performed as part of screening or patients receiving any non-oral feeding method
• Clinically significant abnormalities in hematology or clinical chemistry parameters as determined by investigator or medical monitor
• Treatment with an investigational or commercial product, including nusinersen, given for the treatment of SMA. This includes any history of gene therapy, prior antisense oligonucleotide treatment, or cell transplantation.
• Patients whose weight-for-age is below the third percentile based on World Health Organization (WHO) Child Growth Standards [25]

1. Age (at the time of consent/assent): ≥6 months to ≤21 years
•Cohort 4 only: ≥10 years to ≤21 years 2. Performance Status:
• If <12 years of age: Lanksy Performance Status >50%
• If ≥12 years of age: Karnofsky Performance Status >50% 3. Has a life expectancy of >3 months 4. Has relapsed or refractory disease and no standard treatment options as determined by locally or regionally available standards of care and treating physician's discretion 5. Is ineligible or inappropriate for other treatment regimens known to have effective potential 6. Has a documented local diagnostic pathology of original biopsy confirmed by a Clinical Laboratory Improvement Amendments (CLIA)/College of American Pathologists (CAP) or equivalent laboratory certification 7. Has completed a prior therapy (ies) according to the criteria below:
• Other investigational study agent (any medicinal product that is not approved in the country of treatment for any indication, adult or pediatric) (At least 30 days or five half-lives, whichever is longer, since last dose prior to the first dose of tazemetostat)
• Chemotherapy: cytotoxic (At least 21 days since last dose of chemotherapy prior to first dose of tazemetostat)
• Chemotherapy: nitrosoureas (At least 6 weeks since last dose of nitrosoureas prior to first dose of tazemetostat)
• Chemotherapy: non-cytotoxic (e.g., small molecule inhibitor) (At least 14 days since last dose of non-cytotoxic chemotherapy prior to first dose of tazemetostat)
• Monoclonal antibody (ies) (At least 3 half-lives since the last dose of any monoclonal antibody prior to first dose of tazemetostat)
• Immunotherapy (e.g., tumor vaccine) At least 6 weeks since last dose of immunotherapy agent(s) prior to first dose of tazemetostat)
• Radiotherapy (RT) (At least 14 days from last local site RT prior to first dose of tazemetostat/At least 21 days from stereotactic radiosurgery prior to first dose of tazemetostat/At least 12 weeks from craniospinal, ≥ 50% radiation of pelvis, or total body irradiation prior to first dose of tazemetostat)
• Hematopoietic growth factor (At least 14 days from last dose of hematopoietic growth factor prior to first dose of tazemetostat)
• Hematopoietic cell transplantation (At least 60 days from infusion of hematopoietic cells prior to first dose of tazemetostat) 8. Has adequate hematologic (bone marrow and coagulation factors), renal and hepatic function as defined by criteria below:
• Hematologic (BM Function):
• Hemoglobin ≥ 8 g/dL
• Platelets ≥100,000/mm^3 (≥100 x 10^9/L)
• ANC ≥1,000/mm^3 (≥1.0 x 10^9/L)
• Hematologic (Coagulation Factors):
• PT ≤1.5 ULN
• PTT ≤1.5 ULN
• Fibrinogen ≥0.75 LLN
• Renal Function (creatinine clearance or serum creatinine):
• Calculated creatinine clearance ≥60 mL/min/1.73m^2
• Serum creatinine 6 months to 1 year: male 0.6 mg/dL (53 µmol/L) female 0.5 mg/dL (44 µmol/L)
• Serum creatinine 1 to < 2 years: male 0.6 mg/dL (53 µmol/L) female 0.6 mg/dL (53 µmol/L)
• Serum creatinine 2 to < 6 years: male 0.8 mg/dL (71 µmol/L) female 0.8 mg/dL (71 µmol/L)
• Serum creatinine 6 to <10 years: male 1 mg/dL (88 µmol/L) female 1 mg/dL (88 µmol/L)
• Serum creatinine 10 to <13 years: male 1.2 mg/dL (106 µmol/L) female 1.2 mg/dL (106 µmol/L)
• Serum creatinine 13 to <16 years: male 1.5 mg/dL (133 µmol/L) female 1.4 mg/dL (125 µmol/L)
• Serum creatinine ≥16 years: male 1.7 mg/dL (150 µmol/L) female 1.4 mg/dL (125 µmol/L)
• Hepatic Function:
• Total bilirubin <1.5 x ULN
• ALT or AST <3 x ULN 9. For subjects with CNS involvement: Subjects must have deficits that are stable for a minimum of 14 days prior to enrollment, or seizures that are stable, not increasing in frequency or severity and controlled on current anti-seizure medication(s) for a minimum of 7 days prior to enrollment NOTE: Subjects with leptomeningeal disease or brian tumors with positive cerebral spinal fluid cytology are eligible for this study. Subjects may receive glucocorticoids (at stable or tapering dose) to control CNS symptoms prior to enrollment; however, subjects should receive a stable or tapering dose for at least 7 days prior to enrollment. 10. Has a shortening fraction of >27% or an ejection fraction of ≥50% by echocardiogram or multi-gated acquisition scan 11. Has a QT interval corrected by Fridericia's formula (QTcF) ≤450 msec 12. Is able to swallow and retain orally administered medication and does not have any uncontrolled gastrointestinal (GI) condition such as nausea, vomiting, or diarrhea, or any clinically significant GI abnormalities that may alter absorption such as malabsorption syndromes, hereditary fructose intolerance, glucose-galactose malabsorption, sucrose-isomaltase insufficiency, or major resection of stomach and/or bowels 13. Has sufficient tumor tissue (slides or blocks) available for central confirmatory testing of immunohistochemistry and/or cytogenetics/fluorescence in situ hybridization (FISH) and/or deoxyribonucleic acid mutation analysis (required for study entry but enrollment based on local results) For Dose Escalation Only: 1. Has evaluable disease as defined as lesions that can be accurately measured at least in one dimension by radiographic examination or physical examination and other lesions such as bone lesions, leptomeningeal disease, ascites, hepatosplenomegaly from disease. 2. Has one of the following histologically confirmed tumors: (NOTE: Evidence of diagnostic pathology of original biopsy confirmed by a CLIA/CAP certified laboratory must be available)
• Rhabdoid tumor:
• ATRT
• MRT
• RTK
• Selected tumors with rhabdoid features
• NI1-negative tumor:
• Epithelioid sarcoma
• Epithelioid malignant peripheral nerve sheath tumor
• Extraskeletal myxoid chondrosarcoma
• Myoepithelial carcinoma
• Renal medullary carcinoma
• Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor approval
• Synovial sarcoma with SS18-SSX rearrangement 3. For subjects with ATRT, MRT, RTK, or selected tumors with rhabdoid features only, the following test results must be available: Morphology and immunophenotypic panel consistent with rhabdoid tumor and loss of INI1 or SMARCA4 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 or SMARCA4 loss/mutation when INI1 or SMARCA4 IHC is equivocal or unavailable 4. For subjects with INI1 negative tumor only, the following test results must be available: Morphology and immunophenotypic panel consistent with INI1-negative tumors, and loss of INI1 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 loss/mutation when INI1 IHC is equivocal or unavailable 5. For subjects with synovial sarcoma only, the following test results must be available: Morphology consistent with synovial sarcoma, and cytogenetics or FISH and/or molecular confirmation (e.g., DNA sequencing) of SS18 rearrangement t(X;18)(p11;q11) For Dose Expansion Only: 1. Has measurable disease 2. Has one of the following histologically confirmed tumors:
• Cohort 1
•ATRT
• Cohort 2
•MRT/RTK/selected tumors with rhabdoid features
• Cohort 3
•INI-negative tumors:
• Epithelioid sarcoma
• Epithelioid malignant peripheral nerve sheath tumor
• Extraskeletal myxoid chondrosarcoma
• Myoepithelial carcinoma
• Renal medullary carcinoma
• Chordoma (poorly differentiated or de-differentiated)
• Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor approval
• Cohort 4
•Tumor types eligible for Cohorts 1 through 3 or synovial sarcoma with SS18-SSX rearrangement 3. For subjects with ATRT/MRT/RTK only
•Has the following test results available: Morphology and immunophenotypic panel consistent with rhabdoid tumor, and loss of INI1 or SMARCA4 confirmed by IHC, or molecular confirmation of tumor bi-allelic INI1 or SMARCA4 loss/mutation when INI1 or SMARCA4 IHC is equivocal or unavailable 4. For subjects with INI1-negative tumors only
•have the following test results available:
• Morphology and immunophenotypic panel consistent with INI1-negative tumors, and
• Loss of INI1 confirmed by IHC, or
• Molecular confirmation of tumor bi-allelic INI1 loss/mutation when INI1 IHC is equivocal or unavailable 5. For subjects with synovial sarcoma with SS18-SSX rearrangement (in Cohort 4 only) - have the following test results available:
• Morphology consistent with synovial sarcoma, and
• Cytogenetics or FISH and/or molecular confirmation (e.g., deoxyribonucleic acid [DNA] sequencing) of SS18 rearrangement t(X;18)(p11;q11) 6. For subjects to be enrolled in Cohort 4: Able to swallow and retain orally administered tablets 1. Has had prior exposure to tazemetostat or other inhibitor(s) of EZH2 2. Is being actively treated for another concurrent malignancy or is less than five years from completion of treatment for another malignancy 3. Has participated in another interventional clinical study and received investigational drug within 30 days or 5 half-lives, whichever is longer, prior to the planned first dose of tazemetostat 4. Has had major surgery within 2 weeks prior to enrollment 5. Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study 6. Has clinically active heart disease including prolonged corrected QT interval 7. Is currently taking any prohibited medication(s) 8. Has an active infection requiring systemic treatment 9. Is immunocompromised (i.e. congenital immunodeficiencies), including subjects known history of infection with human immunodeficiency virus 10. Has known history of chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (detectable HCV RNA) 11. Has had a symptomatic venous thrombosis within the 14 days prior to study enrollment - NOTE: Subjects with a history of a deep vein thrombosis 14 days prior to study enrollment who are on anticoagulation therapy with low molecular weight heparin are eligible for this study 12. For subjects with CNS involvement (primary tumor or metastatic disease): Have any active bleeding, or new intratumoral hemorrhage of more than punctate size on Screening MRI obtained within 14 days of starting study drug,or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents

• Has a genetic diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51 skipping treatment
• Has been on a stable dose of oral corticosteroids for at least 12 weeks prior to study drug administration with continued dosing of oral corticosteroids while participating in the study*, or has not received corticosteroids for at least 12 weeks prior to study drug administration and will not initiate dosing of oral corticosteroids while participating in the study
• Has a left ventricular ejection fraction (LVEF) less than (<) 40 percent (%) based on an echocardiogram (ECHO) performed within 3 months prior to Screening or at the Screening visit
• Has a QT interval corrected with Fridericia's method (QTcF) >= 450 millisecond (msec) on the Screening electrocardiogram (ECG)
• Initiation or change of dosing (except for modifications to accommodate changes in weight) within 12 weeks prior to Screening and while participating in the study for any of the following: angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blocking agents (ARBs), beta-blockers, or potassium
• Requires antiarrhythmic and/or diuretic therapy for heart failure
• Forced vital capacity (FVC) <40% of predicted value within 3 months of Screening or at the Screening visit
• Known kidney disease or had an acute kidney injury within 6 months prior to Screening
• Treatment with eteplirsen or drisapersen within 6 months prior to Screening, or any experimental gene therapy for the treatment of DMD at any time
• Use of any herbal medication/supplement containing aristolochic acid Other inclusion/exclusion criteria apply. *The dose of steroids must remain constant except for modifications to accommodate changes in weight.

• Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement
•Note: Patients diagnosed with anaplastic large cell lymphoma (ALCL) harboring a gene rearrangement of interest may be eligible provided they meet all other inclusion/exclusion criteria
• For patients enrolled via local molecular testing, an archival or fresh tumor tissue (unless medically contraindicated) is required to be submitted for independent central molecular testing at Ignyta's CLIA laboratory post-enrollment
• Measurable or evaluable disease
• Patients with CNS involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously-treated and controlled, are allowed
• Prior anticancer therapy is allowed (excluding approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements)
•Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are prohibited.
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed after prior chemotherapy or small molecule targeted therapy
• At least 4 weeks must have elapsed since completion of antibody-directed therapy
• Prior radiotherapy is allowed if more than 14 days have elapsed since the end of treatment
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and minimum life expectancy of 4 weeks
• Adequate organ function as defined per protocol
• Ability to swallow entrectinib intact
• Other protocol specified criteria
• Current participation in another therapeutic clinical trial
• Prior treatment with approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements
•Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are prohibited.
• History of other previous cancer that would interfere with the determination of safety or efficacy
• Incomplete recovery from any surgery
• History of non-pharmacologically induced prolonged QTc interval
• History of additional risk factors for torsade de pointes
• Peripheral neuropathy Grade ≥ 2
• Known active infections
• Active gastrointestinal disease or other malabsorption syndromes
• Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis
• Other protocol specified criteria

• Upper age limit of =< 18 years of age for medullary thyroid carcinoma (MTC), renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC)
• Patients must have a body surface area >= 0.35 m^2
• Patients must have recurrent or refractory disease, or newly diagnosed disease with no known curative therapy or therapy proven to prolong survival with an acceptable quality of life; patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse:
• Ewing sarcoma
• Rhabdomyosarcoma (RMS)
• Non-rhabdomyosarcoma soft tissue sarcomas (STS) including microphthalmia transcription factor associated STS (alveolar soft part sarcoma [ASPS] and clear cell sarcoma [CCS])
• Osteosarcoma
• Wilms tumor
• Rare tumors
• Medullary thyroid carcinoma (MTC)
• Renal cell carcinoma (RCC)
• Hepatocellular carcinoma (HCC)
• Hepatoblastoma
• Adrenocortical carcinoma
• Pediatric solid tumors (including central nervous system [CNS] tumors) with known molecular alterations in the targets of XL184 (i.e., MET amplification, overexpression, activating mutation, MET translocation, MET exon skipping mutations, activating RET mutations, RET rearrangement, overexpression or activation of AXL); documentation of the alteration from a Clinical Laboratory Improvement Act (CLIA) certified laboratory will be required
• Note: Documentation of any known tumor molecular alterations and RET mutation status for patients with MTC (germline) must be uploaded via the RAVE system
• Patients must have radiographically measurable disease; measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)
• Note: The following do NOT qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans)
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement parameters noted above
• Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
• At least 7 days must have elapsed since the completion of therapy with a growth factor. At least 14 days must have elapsed after receiving pegfilgrastim
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of M-Iodobenzylguanidine (MIBG); >= 3 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total-body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given
• Subjects should not have any clinically relevant ongoing complications from prior radiation therapy (i.e., radiation esophagitis or other inflammation of the viscera)
• No evidence of active graft versus (vs.) host disease and >= 2 months must have elapsed since transplant
• Not previously received XL184 or another MET/HGF inhibitor (tivantinib or crizotinib); there are no limits on number of prior therapeutic regimens; patients who have been treated with prior VEGF pathway, or RET inhibitors (except XL184) may be eligible
• Peripheral absolute neutrophil count (ANC) >= 1000/uL for patients with solid tumors without bone marrow involvement
• Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment) for patients with solid tumors without bone marrow involvement
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) for patients with solid tumors without bone marrow involvement
• Peripheral absolute neutrophil count (ANC) >= 750/uL for patients with solid tumors and known bone marrow metastatic disease
• Platelet count >= 50,000/uL for patients with solid tumors and known bone marrow metastatic disease
• Hemoglobin >= 8.0 g/dL for patients with solid tumors and known bone marrow metastatic disease
• Transfusions are permitted to meet both the platelet and hemoglobin criteria; patients must not be known to be refractory to red blood cell or platelet transfusions
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• 2 to < 6 years of age
• Male and female: 0.8 (maximum serum creatinine [mg/dL])
• 6 to < 10 years of age
• Male and female: 1 (maximum serum creatinine [mg/dL])
• 10 to < 13 years of age
• Male and female: 1.2 (maximum serum creatinine [mg/dL])
• 13 to < 16 years of age
• Male 1.5 (maximum serum creatinine [mg/dL])
• Female: 1.4 (maximum serum creatinine [mg/dL])
• >= 16 years of age
• Male: 1.7 (maximum serum creatinine [mg/dL])
• Female: 1.4 (maximum serum creatinine [mg/dL])
• Urine protein: =< 30 mg/dl in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour (h) urine sample
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3 x ULN) (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2.8 g/dL
• No history of congenital prolonged corrected QT (QTc) syndrome, New York Heart Association (NYHA) class III or IV congestive heart failure (CHF)
• No clinically significant cardiac arrhythmias, stroke or myocardial infarction within 6 months prior to enrollment
• QTc =< 480 msec; Note: Patients with grade 1 prolonged QTc (450- 480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications)
• Patients with a known seizure disorder who are receiving non-enzyme inducing anticonvulsants and have well-controlled seizures may be enrolled
• CNS toxicity =< grade 2 with the exception of decreased tendon reflex (DTR); any grade of DTR is eligible
• A blood pressure (BP) =< the 95th percentile for age, height, and gender for pediatric patients < 18 years old and =< 140/90 mmHg for patients >= 18 years old; patients should not be receiving medication for treatment of hypertension (except patients with Wilms tumor and RCC who may be eligible if on stable doses of no more than one anti-hypertensive medication with a baseline BP =< ULN for pediatric patients and =< 140/90 for adult patients); please note that 3 serial blood pressures should be obtained and averaged to determine baseline BP
• International normalized ratio (INR) =< 1.5
• Serum amylase =< 1.5 ULN
• Serum lipase =< 1.5 ULN
• Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use two methods of birth control- a medically accepted barrier method of contraceptive method (e.g., male or female condom) and a second effective method of birth control-during protocol therapy and for at least 4 months after the last dose of XL184; abstinence is an acceptable method of birth control
• Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim)
• Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Previous treatment with XL184 (cabozantinib) or another MET/HGF inhibitor (tivantinib, crizotinib)
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial
• Patients must not be receiving any of the following potent CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort
• Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin, and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel) are prohibited
• Note: Low-dose aspirin for cardioprotection (per local applicable guidelines) and low dose, low molecular weight heparins (LMWH) are permitted; anticoagulation with therapeutic doses of LMWH is allowed in subjects without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no complications from a thromboembolic event or the anticoagulation regimen
• Patients must not have received enzyme-inducing anticonvulsants within 14 days prior to enrollment
• Patients who are receiving drugs that prolong QTc are not eligible
• Patients who are unable to swallow intact tablets are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Patients with active bleeding are not eligible; specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment; patients with evidence of an acute intracranial or intratumoral hemorrhage on CT or MRI are not eligible (patients with evidence of resolving hemorrhage will be eligible); in patients with CNS tumors, an MRI with ECHO gradient sequences would be required to exclude presence of petechial hemorrhages
• Patients who have had or are planning to have the following invasive procedures are not eligible:
• Major surgical procedure, laparoscopic procedure, or open biopsy within 28 days prior to enrollment
• Central line placement or subcutaneous port placement is not considered major surgery but must be placed at least 3 days prior to enrollment for external lines (e.g., Hickman or Broviac catheter, peripherally inserted central catheter [PICC]) and at least 7 days prior to enrollment for a subcutaneous port
• Core biopsy within 7 days prior to enrollment
• Fine needle aspirate within 7 days prior to enrollment
• Surgical or other wounds must be adequately healed prior to enrollment
• NOTE: For purposes of this study, bone marrow aspirate and biopsy are not considered surgical procedures and therefore are permitted within 14 days prior to start of protocol therapy
• Patients who have had significant traumatic injury within 28 days prior to enrollment are not eligible
• Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of the study drug are not eligible

• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g. langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); please note: Patients with Hodgkin lymphoma are not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have an formalin-fixed paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized acid-based decalcification methods are not generally suitable for MATCH study testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol. Patients must be enrolled onto a subprotocol within 12 weeks (84 days) of treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease; patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required:
• Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be myelosuppressive: for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the last dose of agent; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation; note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase (SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in females who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols

1. All open tibia fractures meeting at least one of 1 the following criteria:
• Diaphyseal or metaphyseal Type IIIB (Gustilo IIIB Fractures are open fractures that require either a rotational or free flap for coverage of a soft tissue defect).
• Diaphyseal or metaphyseal Type IIIA where extensive contamination or muscle damage (e.g. all military injuries from IED) precludes nail/plate placement at first debridement.
• Diaphyseal or metaphyseal Type IIIA, where injury would have been classified as a IIIB, but because enough muscle was removed, the skin could be closed.
• Diaphyseal or metaphyseal Type IIIA, where after debridement, bone gap is greater than 1cm.
• Diaphyseal or metaphyseal Type IIIA, where fasciotomies were performed for impending or diagnosed compartment syndrome, and wounds could not be closed primarily (i.e. needs skin grafting). 2. Ages 18
•64 years inclusive 3. Study fracture is suitable for limb salvage using either a modern ring external fixator or internal fixation (internal fixation =locked intramedullary nail or plate). Inclusion notes: 1. Patients may have co-existing non-tibial infection, with or without antibiotic treatment. 2. Patients may have risk factors for infection including diabetes, immunosuppression from steroids or other medications, HIV, or other infections. 3. Patients may have a traumatic brain injury. 4. Patients may be treated initially with a temporary external fixator prior to randomization. 5. Patients may be treated initially at an outside institution prior to transfer to the study institution, as long as the definitive fixation was not performed prior to entrance into the study. 6. Patients with bilateral injuries that meet inclusion criteria may be included, but only the limb rated as "more severe" by the treating surgeon will be enrolled in the study. 7. Fractures may have a gap after debridement of any size, including no gap. 1. Patients presenting with a traumatic amputation of the tibia 2. Patients already received definitive fixation with an IM nail, plate or ring fixator prior to study enrollment 3. Tibia already infected as diagnosed by a surgeon and currently receiving treatment for it 4. Patient speaks neither English nor Spanish 5. Patient is a prisoner 6. Patient has been diagnosed with a severe psychiatric condition 7. Patient is intellectually challenged without adequate family support 8. Patient lives outside the catchment area 9. Non-ambulatory patient due to an associated complete spinal cord injury 10. Non-ambulatory before the injury due to a pre-existing condition. 11. Complex pilon and plateau fractures. The study tibia fracture may have extension into the joint surface, but should primarily be a metaphyseal or diaphyseal fracture and not have an ipsilateral tibial plateau or pilon fracture.Contralateral tibial plateau and pilon fractures are allowed

• STRATUM I AND STRATUM II: LEUKEMIA AND LYMPHOMA SURVIVORS
• Previously enrolled leukemia and lymphoma survivors, randomized to + or
•DRZ on P9404, P9425, P9426, or DFCI 95-01 (high-risk patients only)
• STRATUM I: Alive and in continuous first complete remission from their original cancer (leukemia/lymphoblastic lymphoma [P9404, high-risk DFCI 95-01] or Hodgkin lymphoma [P9425/P9426])
• STRATUM I: Did not have progressive disease or induction failure requiring off-protocol therapy including hematopoietic cell transplantation
• STRATUM I: Must not have been diagnosed with any subsequent malignancy that required additional cardiotoxic therapies (i.e., radiotherapy to the chest [also includes fields directed towards the neck, upper abdomen, or spine], or additional anthracyclines or anthraquinones); patients with history of subsequent malignancy that did not require such therapies remain eligible
• STRATUM I: All patients and/or their parents or legal guardians must sign a written informed consent
• STRATUM II: Among leukemia and lymphoma patients randomized to + or
•DRZ on P9404, P9425, P9426, and DFCI 95-01 (high risk patients only) who have relapsed or have experienced a subsequent malignancy that precludes eligibility since their original diagnosis, the study committee will review the available data (both from Children's Oncology Group's [COG?s] Statistics and Data Center [SDC] and the participating institution) to determine if individual patients are to be selected for Stratum 2; in recognition that local institutions sometimes have more updated relapse/subsequent cancer data than SDC, in cases where local data is more updated, local data will be used preferentially; the study will petition the Institutional Review Board (IRB) specifically for a waiver of consent to include any relapse and subsequent cancer data obtained from existing records for analysis of the secondary aims; patients selected for Stratum 2 will be those for whom late relapse or subsequent cancer is reported but who lack clear confirmation in existing records (either at SDC or at the local institution)
• STRATUM II: Alive, but have experienced relapse of their original cancer and/or have developed a subsequent cancer (other than non-melanomatous skin cancer) since their original diagnosis
• STRATUM II: All patients and/or their parents or legal guardians must sign a written informed consent
• STRATUM III: OSTEOSARCOMA SURVIVORS
• Previously enrolled osteosarcoma survivors treated on P9754 who are alive and able (themselves and/or parents/legal guardian) to provide written informed consent; note that relapse and subsequent malignancy are not exclusion criteria for P9754 survivors
• Comparison subjects for P9754 survivors will be eligible to be enrolled from any ALTE11C2 participating COG site (even if that institution did not participate on P9754), according to the following criteria:
• Newly diagnosed, previously untreated biopsy-proven moderate or high grade osteosarcoma without metastasis; patients with low grade osteosarcoma, parosteal or periosteal sarcoma are ineligible
• < 31 years of age at time of initial osteosarcoma diagnosis
• Diagnosis occurred between January 1, 1999 through December 31, 2002; duration of therapy can extend beyond 2002
• No evidence of poor or low cardiac function at time of initial osteosarcoma diagnosis; if reports from the time are available: shortening fraction >= 28% by echocardiogram and within the institutional normative range for age, or radionuclide angiogram ejection fraction >= 50%; if imaging reports from the time are no longer available, there must be no documentation within available medical records that suggest poor or low cardiac function at time of diagnosis
• Comparison subject must have institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) documenting lifetime receipt of 450 to 600 mg/m^2 of doxorubicin (doses within 10% are acceptable); this includes initial therapy as well as any subsequent therapy for relapse or second cancer, if relevant; as such, comparison subjects who have had osteosarcoma relapse or subsequent malignancies remain eligible so long as they meet all other eligibility criteria
• No anthracycline or anthraquinone aside from doxorubicin was ever given as part of initial or subsequent therapies
• No exposure to DRZ at any point in time
• All patients and/or their parents or legal guardians must sign a written informed consent
• For all participants, all institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

• Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial
• History of exposure to ataluren in a prior PTC study in nmDBMD at a trial site in the US
• Male sex
• Confirmed screening laboratory values within the specified ranges
• In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and the 6-week follow up period
• Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions
• Exposure to another investigational drug within 1 month prior to start of study treatment.
• Eligibility for another ataluren clinical trial that is actively enrolling study participants.
• Positive for Hepatitis B core antibody or Hepatitis C antibody at screening
• Known hypersensitivity to any of the ingredients or excipients of ataluren (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], magnesium stearate).
• Ongoing use of the following medications: a. Systemic aminoglycoside therapy
• Ongoing uncontrolled medical/surgical condition, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the patient or make it unlikely that follow-up would be completed.

• Shoulder pain with associated sleeping disturbance
• Between the ages of 18-89
• Present to the clinics in the Departments of Internal Medicine, Family Medicine, and Orthopedic Surgery at UTSW
• non-English speakers
• chronic pain or rheumatic disorders
• unstable psychopathology, cognitive impairment (including dementia)
• current or recent history (within 6 months) of substance abuse disorders
• recent history of surgery or fracture to the cervical spine, thoracic spine, ribs, or shoulders (within 6 months)
• metabolic bone disease (including osteoporosis)
• fusion or ankyloses
• osteomyelitis, pregnancy, vertebral basilar insufficiency, neoplastic disease, malignancy in the area of treatment
• actively treated for sleep disorders (including insomnia)
• uncontrolled congestive heart failure, COPD, hypertension, or other serious medical illness

• Cases with diagnosis of coronal
• Unaffected relatives of cases
• Unaffected controls including those who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease. These individuals will be recruited at some of the other collaborating institutions, but not at Mount Sinai. Individuals of any racial or ethnic group with the established or suspected clinical diagnosis of coronal, nonsyndromic craniosynostosis will be included in this study. Unaffected relatives, such as their biological parents and/or sibs, will also be included to contribute medical information and samples as negative controls for our study.
• Those who fit the criteria, but who choose not to participate
• Those who do not meet the criteria.
• Other than children, no vulnerable individuals will be recruited, such as intellectual impaired individuals or prisoners.

• Histologically or cytologically confirmed diagnosis of 1 of the following:
• Rhabdomyosarcoma
• Non-rhabdomyosarcoma soft tissue sarcoma
• Chordoma
• Desmoid fibromatosis
• Desmoplastic round cell tumors
• Undifferentiated embryonal sarcoma of the liver
• Unclassified soft tissue sarcoma that is too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called ?undifferentiated soft tissue sarcoma? or ?soft tissue sarcoma NOS?)
• Other soft tissue neoplasms, excluding benign tumors
• Must have pathological specimens of tumor-containing tissue or bone marrow (beyond that needed by the institution for diagnosis) available for study
• No malignant rhabdoid tumor, Ewing sarcoma/primitive neuroectodermal tumor, or osteogenic sarcoma of bone
• No osteogenic sarcoma

• Must have MGFA MG grades 2, 3, or 4 generalized MG, according to the MGFA classification system
• Elevated AChR or MuSK Ab
• Patient's signs and symptoms should not be better explained by another disease process
• IVIg maintenance dose of 0.2 to 2 gm/kg/4 weeks or equivalent dose administered every 2-4 weeks
• Stable IVIg for at least 3 cycles
• Able to complete the study and return for follow-up visits
• Able to give written informed consent before participating in the study
• History of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue
• Other major chronic or debilitating illnesses within six months prior to study entry
• Female patients who are premenopausal and are (a) pregnant, (b) breastfeeding, or (c) not using an effective method of double barrier birth control
• Altered levels of consciousness, dementia, or abnormal mental status
• Thymectomy in the previous three months
• History of renal insufficiency or liver disease
• Skin disease that would interfere with assessment of injection site reaction
• History of severe reactions to IVIg or SCIg
• Participation in a research study within the last 3 months
• Treatment with rituximab or other biologics within 12 months of study entry
• Unable to provide informed consent

• Female or male subjects aged 2 to 17 years inclusive
• Decision to prescribe abobotulinumtoxinA, to be made prior to and independently from the decision to enrol in the study
• Primary diagnosis of paediatric lower limb (PLL) spasticity and either: Previously untreated with BoNT (naïve to BoNT), or previously treated with a BoNT (i.e. non naïve to BoNT), and for those who were previously treated with BoNT-A, they should have responded to BoNT-A treatment according to the investigator's criteria
• For non naïve BoNT subjects, a minimum interval of 12 weeks since the last BoNT injection and in the presence of spasticity
• Known resistance to any BoNT or experienced serious safety issues with previous use of BoNT
• Concomitant treatment with other BoNT
• Known hypersensitivity to abobotulinumtoxinA or related compounds, or any component in the study drug formulation
• Subjects with any clinical (or subclinical) evidence of marked defective neuromuscular transmission (e.g. Lambert Eaton syndrome or myasthenia gravis) or persistent clinically significant neuromuscular disorders

• Suspected malignancy
• Age ≤ 26 years and being cared for at Children's Medical Center
• Ability to undergo standard of care diagnostic procedure, including biopsy or resection of the tumor, in the OR or IR at CMC
• Poorly controlled diabetes
• Any other medical condition that prevents administration of glucose

Inclusion Criteria for the registry:
• Diagnosis of transverse myelitis (TM) or acute flaccid myelitis (AFM)
• Patient is within 6 months of symptom onset
• Ability of patent or legal guardian is able to provide informed consent
• Ability of a child 10 or older able to provide assent
• Access to the internet Exclusion Criteria for the registry:
• Inability to provide appropriate consent or assent
• Diagnosis of multiple sclerosis, neuromyelitis optica, or neuromyelitis optica spectrum disorder Inclusion Criteria for clinical sub study:
• All inclusion for the registry study
• Ability to have clinic visits 3 months ,6 months and 12 months post symptom onset Exclusion Criteria for clinical sub study:
• All exclusion criteria for the registry study
• Inability to take part in clinical assessments

• The patient must be enrolled on a frontline COG therapeutic trial for treatment of a primary malignancy and is nearing completion of or has recently completed protocol treatment (within the past 180 days)*; or the patient must have been enrolled on a COG (or Legacy Group) therapeutic or non-therapeutic trial targeted for long-term follow-up by ALTE05N1
• Hodgkin lymphoma
• CCG 5942
• POG 9425
• POG 9426
• AHOD0031
• Brain tumor
• A9961
• Acute lymphoblastic leukemia
• POG 9404
• Osteosarcoma
• POG 9754
• Stem cell transplantation
• ASCT0631D
• Rhabdomyosarcoma
• IRS-III
• IRS-IV
• Note: For purposes of enrollment onto this study, completion of treatment is defined as the date protocol therapy was terminated as reported (or will be reported) on this patient?s last ?Reporting Period Worksheet/CRF? for their frontline therapeutic protocol; patients become eligible as they approach this date, and remain eligible for 180 days following the date that protocol therapy was terminated; early termination of protocol therapy per the decision of the patient, family and/or investigator does NOT preclude enrollment on this study
• Note: For purposes of eligibility for ALTE05N1, ?early termination of protocol therapy? means that the patient has finished protocol therapy and will not receive further treatment; patients whose therapy is terminated early due to toxicity or who opt out of an end-of-therapy randomization (e.g., randomization to continue with an experimental agent versus [vs.] no further treatment) are eligible because they will not be receiving further therapy; however, a patient who is removed from protocol therapy or opts to discontinue protocol participation early in the course of treatment (e.g., following Induction) is not eligible
• The patient must reside in the U.S. on the date of enrollment to ALTE05N1
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met