Brain Activation During Simple Vocal Behaviors

Summary: This study will examine the central regions and brain activation patterns associated with simple vocal behaviors under conditions of normal auditory feedback-when people hear themselves speak. Such feedback plays a major role in learning and maintaining human voice control. But voice control can be harmed by neurological injury or disease, reducing the ability of a person to orally communicate. Research has shown that auditory feedback is continuously monitored, brought about by both automatic and voluntary corrections in the amplitude (loudness) and frequency of (pitch) of the human voice. This study aims to determine which areas of the brain have activity dependent on the level of blood oxygen. It will provide new knowledge about basic vocal motor control and provide a basis for investigations into the integration of hearing and speaking in human vocal expression throughout life.~Participants 18 to 45 years of age with normal hearing and voice function and with a steady heart rate may be eligible for this study.~Participants will be evaluated by a speech-language specialist, regarding a history of voice health and measures of voice function. They will be tested on their ability to vary voice amplitude and frequency and tested on their hearing. Also, they will undergo an electrocardiogram to determine their heart rate.~For the study, participants will undergo an MRI scan. During the MRI scan, patients will lie still on a table that can slide in and out of a metal cylinder surrounded by a strong magnetic field. Scanning time varies from 20 minutes to 3 hours, with most scans between 45 and 90 minutes. Patients may be asked to lie still for up to 90 minutes at a time. As the scanner takes pictures, there will be loud knocking noises, and patients will wear headphones to muffle the sound. The headphones will also enable patients to hear their voice. The patient's head will be positioned with a coil of 25 to 30 cm diameter and supported by a headrest. A microphone will be placed about 2 cm from the patient's mouth for communication and collection of data. Also, an angled mirror will be attached to the head coil, so that the patient can look outside of the scanner. By way of a projection screen, the patient will receive a visual cue to vocalize, or use his or her voice.~Patients will be asked to repeatedly do some of the following vocalization tasks: (1) rest, (2) hum or sigh without voicing (exhale), (3) hum or sigh audibly, (4) hum audibly while increasing or decreasing voice frequency, and (5) hum audibly while increasing or decreasing voice amplitude. During the scan, patients will be able to communicate with the MRI staff at all times and may ask to be moved out of the machine at any time. Some scans may be done in a 3 Tesla scanner. It is the latest advance in MRI, with a stronger magnetic field than in the more common 1.5 Tesla scanner. Functional MRI is done while a person is performing tasks, such as moving a limb or speaking. The fMRI scan will take about 1 hour.
Inclusion criteria: inclusion criteria:

 Males and females of any race or ethnicity will be eligible to participate in this study.

 Volunteers must be between the ages of 18 and 45 with normal hearing and voice function. Participants will be further selected for having a steady heart rate. A history of voice training is not required, but participants must be able to produce grossly independent voice F0 and amplitude changes.

Exclusion criteria: :

 Contraindications to participation include: pregnancy, cardiac pacemaker or auto defibrillator, artificial heart valve, neural pacemaker, surgical metal clips in the brain, eye, or on blood vessels, cochlear implants, ocular implants or foreign bodies such as metal shavings or splinters, insulin pump, implanted drug infusion device, shrapnel, bullet or shot wound, and tattooed makeup. Participants will be screened with the NMR Center Safety Screening Questionnaire which also includes items such as intraventricular shunts, transdermal medication patches, wire sutures, bone/joint pins, screws, nails, or plates, and body piercings. Given that surgical staples, orthopedic pins, orthodontic braces and dental implants are no longer considered absolute contraindications in MRI, Dr. Saxon or Dr. Kearney will approve or disapprove participation in the study based on their judgment of the MR compatibility of these items, using published guides including those referenced above.

 Volunteers will be also excluded if they are found to be pregnant, report any tendency toward claustrophobia or are unable for any reason to lie still within an MR scanner.


Randomized, School-based Effectiveness Trial of the Adolescent Depression Awareness Program

Summary: The primary goal of the proposed research is to assess the effectiveness of the Adolescent Depression Awareness Program (ADAP), a school-based depression education program, in increasing depression literacy and treatment seeking in high school students. The ADAP intervention will be carried out in approximately 60 schools with over 15,000 students. The following are ADAP Implementation Sites: Baltimore Archdiocese High Schools; New Castle County, Delaware; Washtenaw County, Michigan; and York County, Pennsylvania.
Inclusion criteria: inclusion criteria:

 enrolled in one of the participating schools parental consent and student assent is required for the web-based survey

Exclusion criteria: :

 not enrolled in the participating schools

['Adolescent Depression Awareness Program (ADAP)']

['Adolescent - Emotional Problem', 'Depression', 'Prevention Harmful Effects']

Adolescent - Emotional Problem
Depression
Prevention Harmful Effects


Study of Live Attenuated ChimeriVax™-Japanese Encephalitis Vaccine

Summary: The purpose of this study is to assess the safety, tolerability, and immunogenicity of a new formulation of lyophilised ChimeriVax™-JE, given at three dose levels, compared with placebo.~Primary Objectives:~Safety:~To obtain safety and tolerability data for a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels, in healthy adult volunteers (18-49 years old).~Immunogenicity:~To obtain data on the antibody response to a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels, in healthy adult volunteers without prior Japanese encephalitis immunity.~To assess the durability of immune response up to 12 months following a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels.
Inclusion criteria: inclusion criteria :

 All aspects of the protocol explained and written informed consent obtained from the participant.

 Aged ≥18 to < 49 years.

 In good general health, without significant medical history, physical examination findings, or clinically significant abnormal laboratory results.

 Participant must be available for the study duration, including all planned follow-up visits.

 Participant must agree to take the following precautions to avoid insect bites for 7 days following vaccination by using N,N-diethyl-meta-toluamide (DEET)-containing insect repellent, where appropriate.

 For female participants: Negative pregnancy tests at Screening and Day 0, in conjunction with a menstrual and contraceptive history indicating a low probability of pregnancy in the opinion of the physician. Females of childbearing potential will be required to be correctly using an efficacious hormonal method of contraception or intrauterine device for at least 1 month before randomisation and during the on-study phase to Day 30. Barrier methods of contraception will not be considered acceptable for study entry. Female participants of child-bearing potential will sign an agreement that contraception will be correctly practised during the specified periods and will specify the method used. Female participants unable to become pregnant must have this documented (e.g., tubal ligation, hysterectomy or postmenopausal [at least one year since last menstrual period]).

Exclusion criteria:  :

 A history of vaccination or infection to Japanese encephalitis (JE) or yellow fever (YF) or other flaviviruses (including Japanese encephalitis, tick-borne encephalitis, St Louis encephalitis, West Nile virus, dengue fever, Murray Valley encephalitis). Previous vaccination will be determined by history (interview of subject).

 Previous or current military service.

 History of residence in or travel to flavivirus endemic areas in the tropics (Cape York region of Northern Queensland, India, Southeast Asia, Central America, Caribbean or South America) for periods of 4 weeks or more.

 Known or suspected immunodeficiency (e.g., human immunodeficiency virus [HIV] infection, primary immunodeficiency disorder, leukemia, lymphoma), use of immunosuppressive or antineoplastic drugs (corticosteroids > 10 mg prednisone, or equivalent, in the last three months or during the trial (up to Day 30).

 History of thymoma, thymic surgery (removal) or myasthenia gravis.

 Clinically significant abnormalities on laboratory assessment (i.e., meeting the mild, moderate or severe criteria described in the toxicity gradings for laboratory values).

 Anaphylaxis or other serious adverse reactions characterised by urticaria or angioedema to foods, hymenoptera (bee family) stings, or drugs (including vaccines).

 Transfusion of blood or treatment with any blood product, including intramuscular or intravenous serum globulin within six months of the Screening Visit or up to Day 30.

 Administration of another vaccine or antiviral within 30 days preceding the screening visit or up to Day 30 (these subjects will be rescheduled for vaccination at a later date).

 Physical examination indicating any clinically significant medical condition.

 Body temperature > 38.1°C (100.6°F) or acute illness within 3 days prior to inoculation (participant may be rescheduled).

 Intention to travel out of the area prior to the study visit on Day 30.

 Seropositive to hepatitis C virus or HIV or positive for Hepatitis B Surface Antigen.

 Lactation or intended pregnancy in female subjects.

 Excessive alcohol consumption, drug abuse, significant psychiatric illness.

 A known or suspected physiological or structural condition that compromises the integrity of the blood-brain barrier (e.g., significant hypertensive cerebrovascular disease, trauma, ischaemia, infection, inflammation of the brain).

 Intention to increase normal exercise routine, participate in contact sports or strenuous weight lifting or to initiate vigorous exercise from Screening until after Day 30.

['Live attenuated Japanese encephalitis virus', 'Live attenuated Japanese encephalitis virus', 'Live attenuated Japanese encephalitis virus', 'ChimeriVax™ diluent (Placebo)']


Autologous Redirected RNA Meso-CIR T Cells

Summary: To determine the safety and manufacturing feasibility of IV autologous chimeric immune receptor (CIR) T cells transfected with anti-mesothelin messenger RNA (mRNA) expressing a single chain antibody variable fragment linked to the intracellular CD 3 zeta T cell receptor domain and the 4-1BB costimulatory domain.
Inclusion criteria: inclusion criteria:

 Subjects must have histologically confirmed MPM (epithelial or biphasic).

 Subjects must have completed standard first line therapy with a platinum-based double regimen and had PD or they must have chosen not to pursue primary standard of care therapy.

 ECOG performance status 0 to 1.

 Age greater than 18 years

 Life expectancy > 4 months

 At least 2 weeks since prior and no other concurrent chemotherapy, radiotherapy, or immunotherapy (e.g., interferons, tumor necrosis factor, interleukins, or monoclonal antibodies). In addition, the patient must have fully recovered from any adverse events related to these agents.

 More than 4 weeks since prior and no other concurrent investigational agents.

 Subjects must have measurable disease as defined by accepted MPM measurement techniques (modified RECIST criteria).

 Blood coagulation parameters: PT such that international normalized ratio (INR) is < 1.5 (or an in-range INR, usually between 2 and 3, if a subject is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus) and a PTT < 1.2 times the upper limit of normal.

 Subjects must have adequate venous peripheral access for apheresis. Patients must also have adequate venous access for subsequent modified CIR T-cell administration which can be done through a central venous access (e.g. port of systemic chemotherapy).

 Short-term therapy for acute conditions not specifically related to MPM is allowed if such therapy does not include any immune modulating agents.

 Male and Female subjects agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device , abstinence) during the study and for 3 months following the last dose of the study cell infusion.

 Subject must understand and sign the study-specific informed consent .

 Satisfactory organ and bone marrow function as defined by :

 Absolute neutrophil count > 1,000/µl Platelets > 100,000/µl Hematocrit > 30 % AST(SGOT)/ALT(SGPT) < 3x the institutional normal upper limit Bilirubin < 2.0 mg/dL unless secondary to malignant bile duct obstruction Creatinine < 1.5x the institutional normal upper limit

Exclusion criteria: :

 Previously treated with any investigation therapy within 1 month prior to screening.

 Sacromatoid MPM histology which does not express mesothelin

 Prior invasive malignancies unless surgically and medically cured without evidence of recurrent disease for 5 years with the exception of non-melanoma skin cancer, prostate cancer with PSA level < 1.0.

 Prior hematologic malignancy with bone marrow transplantation or immune modifying therapy within the past 4 weeks with the exception of thyroid replacement.

 Use of immunosuppressive drugs with 4 weeks prior to study entry, or anticipated use of immunosuppressive agents.

 Any clinically -significant pericardial effusion, CHF (NY Heart Association Grade II-IV ), or cardiovascular condition.

 Any clinically -significant pleural effusion or ascites that cannot be drained with standard approaches or with pre-enrollment in dwelling drainage device placement.

 Forced vital capacity < 50% predicted, DLCO < 40% predicted.

 Underlying lung disease requiring supplemental oxygen therapy.

 Have a recognized immunodeficiency disease including cellular immunodeficiency, hypogammaglobulinemia, or dysgammaglobulinemia; patients who have acquired hereditary, congenital immunodeficiency.

 Viral infections: HIV, HCV, HBV.

 Pregnant women are excluded from this study because autologous transduced T cells, breastfeeding should be discontinued if the mother is treated.

 Feasibility assessment during screening demonstrates < 30% transfection of target lymphocytes, or < 5-fold expansion in modified CIR T-cells in response to CD3/CD28 costimulation.


An fMRI Study on Temporal Discounting in Bipolar Disorder

Summary: The investigators propose to explore the link between bipolar disorder, anxiety, and suicide by investigating intertemporal discounting in depressed, suicidal patients with bipolar I and II disorder who have various levels of anxiety. The investigators will determine the effect of anxiety on their intertemporal discounting (small rewards now compared to larger rewards later) in a decision-making paradigm and investigate the associated functional neuroanatomy using functional magnetic resonance imaging (fMRI).
Inclusion criteria: inclusion criteria:

 Meets DSM-IV criteria for BD I and II current depressive episode

 Able to give written informed consent

 Age > to 18 years and < 65 years

 Currently suicidal as defined by a MADRS suicide item score of > 3 or previous history of serious suicidal ideation that required hospitalization.

 All subjects need to have normal hearing and normal/corrected-to-normal vision.

Exclusion criteria: :

 Medical illness or non-psychiatric medical treatment that would likely interfere with study participation

 Neurologic disorder, previous ECT, or history of head trauma (i.e. known structural brain lesion potentially confounding MRI results)

 Substance abuse within the past 3 months or current substance dependence (confirmed by MINI)

 Left-handedness

 Contraindications to MRI (metallic implants, claustrophobia, etc.)

 Subjects who need urgent psychiatric care requiring hospitalization (evaluated by clinicians).

['Bipolar Disorder', 'Suicidal Ideation', 'Depression']

Bipolar Disorder
Suicidal Ideation
Depression


Effect of Lugol's Solution in the Patients With Graves' Disease

Summary: Context: Although some of endocrine surgeons administer Lugol's solution to decrease thyroid gland vascularity, there is still no agreement on its effectiveness.~Objective: The aims of this clinical trial are to evaluate thyroid blood flow and microvessel density in the patients with Graves' disease according to the Lugol's solution treatment preoperatively.~Design: Retrospective clinical trial. Setting: A tertiary referral center. Method: Thirty-six patients were randomly assigned to preoperative medication with Lugol's solution. Patients in group 1 (n=17) received Lugol's solution for 10 days before surgical intervention, whereas patients in group 2 (n=19) didn't receive it.~Main Outcome Measures: Blood flow through the thyroid arteries of patients with Graves' disease was measured by color flow Doppler ultrasonography. The microvessel density (MVD) was assessed immunohistochemically and Western blot analysis using the level of expression of CD-34 in thyroid tissue. The thyroid gland's weight and blood loss were measured in all patients.
Inclusion criteria: inclusion criteria:

 Graves disease

Exclusion criteria: :

 Anticoagulant usage,

 Previous thyroid operation,

 Refused to participate in this study.


Primary Transplant Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation

Summary: The purpose of this study is to see how well transfusions of T-cells work in treating CMV. T-cells are a type of white blood cell that helps protect the body from infection. A transfusion is the process by which blood from one person is transferred to the blood of another. In this case, the T-cells are made from the blood of donors who are immune to CMV. The T-cells are then grown and taught to attack the CMV virus in a lab.
Inclusion criteria: inclusion criteria:

 Each patient must satisfy at least one of the following criteria:

 The patient must have a clinically documented condition associated with CMV (e.g. interstitial pneumonia, hepatitis, retinitis, colitis) Or

 The patient must have microbiological evidence of CMV viremia or tissue invasion as attested by viral culture, or detection of levels of CMV DNA in the blood or body fluids consistent with CMV infection.

 Patient must also satisfy at least one of the following criteria:

 The patient's CMV infection is clinically progressing or CMV viremia is persistent or increasing (as evidenced by quantitation of CMV DNA in the blood) despite two weeks induction therapy with antiviral drugs.

 Or

 The patient has developed CMV viremia as attested by viral culture, or detection of levels of CMV DNA in blood or body fluids while receiving prophylactic doses of antiviral drugs to prevent CMV infection post transplant.

 Or c. The patient is unable to sustain treatment with antiviral drugs due to drug associated toxicities (e.g. myelosuppression [ANC< 1000μl/ml without GCSF support] or nephrotoxicity [corrected creatinine clearance ≤ 60 ml/min/1.73 m2 or serum creatinine > 2 mg/dl]) Patient has CMV specific T-cells from the donor of his/her HSCT available. CMV infections are life threatening, and may involve multiple organ systems such as the lungs, liver, gastrointestinal tract, hematopoietic and central nervous systems. Antiviral drugs used for treatment may also compromise renal and hematopoietic function. Therefore, dysfunctions of these organs will not affect eligibility for this protocol Patients must meet the following clinical criteria to receive CMVpp65-CTL infusions

 Stable blood pressure and circulation, not requiring pressor support

 Evidence of adequate cardiac function as demonstrated by EKG and/or echocardiography.

 A life expectancy of at least 3 weeks, even if requiring artificial ventilation.

 There are no age restrictions

Exclusion criteria: :

 Patients requiring high doses of glucocorticosteroids (≥ 0.3 mg/kg prednisone or its equivalent) 2. Patients who are moribund 3. Patients with other conditions not related to CMV infection (e.g. uncontrolled bacterial sepsis or invasive fungal infection) which are also life-threatening and which would preclude evaluation of the effects of a T-cell infusion.

 3.4. Patients who are pregnant 6.1.3 Donor inclusion criteria 6.1.3a Donors in Group 1 (Historical Donors) Donors in Group 1 (Section 5.1) would have already been determined to be eligible and will have donated blood or leukocytes to establish CMV-specific T-cells under IRB # 05-065, 07-055, 95-024, or 11-130. There are no additional eligibility requirements for these donors.

 6.1.3b Donors in Groups 2 & 3 (Prospective and Volunteer Donors)

 Transplant donors and healthy HLA typed volunteers who agree to provide T-cells for Third-party donation (section 5.1, Groups 2 and 3) will need to meet the following eligibility requirements prior to donation:

 Donors must satisfy the criteria specified in FDA 21 CFR 1271.

 Donors must be typed for HLA-A, B, C and DR

 Donors must have a hemoglobin value > 10g/dl

 Donors must be capable of undergoing, at least, a single standard 2 blood volume leukapheresis or a donation of one unit of whole blood

 6.1.4 Donor


Pain During Chest Tube Withdrawal: Evaluation Using Pan Monitor

Summary: Pain evaluation remains a clinical problem. Pain Monitor allows pain evaluation using the measurement of skin conductance.~Withdrawal of chest tube can be painful and the purpose of the study was to compare auto-evaluation of pain (visual analogic scale) and the index measured by the Pain Monitor.
Inclusion criteria: inclusion criteria:

 patients undergoing removal of a chest tube after lung surgery,

 patients able to indicate the pain score.

Exclusion criteria: :

 pregnancy, lactation ,

 insulin-dependent diabetes with dysautonomia,

 central or peripheral neurological disease, agitation,

 inability to understand the protocol,

 inability to use the Pain Monitor: skin abnormalities at the site of measurement, pacemaker or implantable defibrillator, condition affecting the sympathetic nervous system, tremor of the extremities,

 contra-indication to oral morphine ,

 respiratory failure, severe hepatic insufficiency, intracranial hypertension, epilepsy associations

 recent administration of neostigmine or of atropine.

['Chest drain withdrawal', 'Pain Monitor']


Trial to Reduce Falls Incidence Rate in Frail Elderly

Summary: Background: Approximately 750,000 elderly Dutch people fall at least once a year, which often results in physical injuries and a fear of falling, with high costs and far-reaching consequences on functionality, physical activity, quality of life and mental well-being. Falling is not only a burden for patients, it is also a burden for their caregivers. Recurrent falling is a complex problem. However, the pathophysiological background of falls, gait problems and dementia is largely unknown. The general pathophysiological hallmark of aging is a liability in homeostatic mechanisms of organs. This liability results in an impaired ability to adapt to stress and in increased biological variation in outcome measures within individuals. In this study the investigators aim at developing an intervention to reduce recurrent falling in frail elderly fallers.~Hypotheses: The investigators hypothesize that the intervention program will decrease the number of falls and fear of falling and increase mental well-being, physical activity and functional performance in frail elderly people with a history of recurrent falling. In addition, the burden on the caregivers will be reduced due to the intervention and will be cost-effective. Furthermore, the investigators hypothesize that patients with a high short-term intra-individual biological variability in gait and cognition variables have a higher risk of falling, worse gait performance and cognitive decline after long term follow-up.~Study Design: Randomized, controlled, single-blind trial.~Study Population: 160 patients referred to a geriatric outpatient clinic, who fell at least once in the last 6 months and their primary caregivers (N=160).~Intervention: A multifaceted fall prevention program for frail elders to reduce falls incidence rate, consisting of physical and cognitive components. Moreover, it includes a training program for caregivers in which they learn to support and give advice to the patients, aiming to decrease the burden on the caregivers.~Primary Outcome Measures: The fall incidence rate is the primary outcome measure. Total observation time of falls will be 6 months after the start of the intervention.~Secondary Outcome Measures: In the patients, the secondary outcome measures are fear of falling (FES), quality of life (MOS-20), depression and general anxiety, functional performance in activities of daily living, physical activity, mobility, gait parameters, body sway and biomarkers of endothelial function and frailty. For the caregiver, the secondary outcome measures are caregiver's burden, mood and quality of life. In addition, intraindividual variability of cognition, balance and gait in both patients and caregivers, will be assessed and cost-effectiveness of the intervention will also be determined.
Inclusion criteria: inclusion criteria:

 At least one fall in the last 6 months

 Living in their own home or in a home for the aged

 Availability of a primary caregiver caring for the patient at least once a week

 Ability to walk 15 meters independently (use of a walking aid is permitted)

 Life expectancy of more than 6 months, as judged by their geriatrician

Exclusion criteria: :

 Dyads of patients and caregivers in whom outcome assessment is highly unlikely to succeed, for example because they proved not to be able to register falls in the three months before randomization, will be excluded

 MMSE score of less than 15

 On the waiting list for a nursing home


Brain Anatomy in Dystonia

Summary: This study will use high-resolution magnetic resonance imaging (MRI) to look for subtle differences in brain anatomy between patients with focal hand dystonia (also called writer s cramp) and healthy normal volunteers. Patients with hand dystonia have prolonged muscle contractions that cause sustained twisting movements and abnormal postures. These abnormal movements often occur with activities such as writing, typing, playing certain musical instruments such as guitar or piano, or playing golf or darts.~Patients with focal hand dystonia and healthy volunteers will be enrolled in this study. Patients will be recruited from NINDS s database of patients with focal hand dystonia. Volunteers will be selected to match the patients in age, sex and handedness.~This study involves two visits to the NIH Clinical Center. The first visit is a screening visit, in which patients and volunteers will have a medical history, physical examination, neurological examination, and assessment of handedness. Women of childbearing age will be screened with a pregnancy test. Pregnant women are exclude from this study.~Those who join the study will return for a second visit for magnetic resonance imaging. MRI uses a magnetic field and radio waves to produce images of the brain. For the procedure, the participant lies still on a stretcher that is moved into the scanner (a narrow cylinder containing the magnet). Earplugs are worn to muffle loud noises caused by electrical switching of radio frequency circuits used in the scanning process. The scan will last about 45 to 60 minutes, at most. Some volunteers may be asked to return for a third visit to obtain a second MRI on a different scanner.
Inclusion criteria: inclusion criteria:

 HEALTHY VOLUNTEERS: Healthy volunteers who consented to participate in the study and matched for age, sex, handedness with the group of patients with primary focal hand dystonia.

 PATIENTS: Patient with primary focal dystonia from our dystonia patient database who consented to participate in the study. This criterion will be established by the preliminary screening in the Human Motor Control Outpatient Clinic.

Exclusion criteria: :

 The following subjects will be excluded:

 Healthy volunteers with cognitive complaints, abnormal neurological exam or history of past neurological disease.

 Dystonia patients with the presence of a second neurological disease or condition; abnormal neurological findings on exam that are not related to primary focal dystonia.

 Subjects with past or present neuropsychiatric illness, head trauma with loss of consciousness, epilepsy, cerebro-vascular disease, migraine, past and present history of alcohol abuse, medical conditions that may alter cerebral structure.

 Subjects with abnormal MRI findings at visual inspection (prominent normal variants such as mega cisterna or cavum septum pellucidum, signs of severe cortical or subcortical atrophy, brain tumors, vascular diseases, trauma or AVMs).

 Subjects with any metallic objects within them just prior to MR imaging (cardiac or neural pacemaker, aneurysm clips [metal clips on the wall of a large artery], metallic prostheses [including heart valves and cochlear implants] or shrapnel fragments. Welders and metal workers are also at risk for injury and may not take part in the study because of possible small metal fragments in the eye of which they may be unaware.

 Subjects not capable of giving an informed consent.

 Women who are pregnant

 Children


A School-Based Intervention to Reduce Lyme Disease

Summary: Our overall purpose of this study is evaluate whether a short in-class Lyme Disease education program based on social learning theory and the Health Belief Model can impact a child's knowledge, attitude, and preventive behavior.~1. Deliver an educational program in schools to promote personal protective practices, encourage early disease detection and modify residential habitats to reduce tick density.~3. Evaluate the program's efficacy by comparing the acceptability and practice of precautionary behavior, tick density in residential areas and rates of Lyme disease between groups using primary and surveillance data sources Evaluate the contribution of knowledge, attitudes, and parental involvement to children's adoption of prevention strategies.~Hypothesis~The community intervention will reduce the incidence of Lyme disease among children and families living in endemic areas by increasing the practice of precautionary behavior and reducing tick density in residential areas. Specifically, we hypothesize that:~The educational intervention will reduce the incidence of Lyme disease among children and families living in an endemic area.~The educational intervention will improve the childrens' self-confidence (behavioral self-efficacy), intention to perform, and actual practice of Lyme disease prevention behaviors.
Inclusion criteria: Inclusion:

 Child age 7-12 and their parents living in the selected endemic areas

 Exclusion:

 No exclusions
Exclusion criteria:

['Education', 'Control (pre and post surveys)']

Education
Control (pre and post surveys)


Pilot Study to Evaluate Individualized Choice of Antidepressants in Patients With Cancer

Summary: This is a pilot study to test the hypothesis that the antidepressants mirtazapine and citalopram are effective treatment for major depressive disorder (MDD) in cancer patients.
Inclusion criteria: inclusion criteria:

 Diagnosed with a malignancy

 Informed consent obtained and signed

 Greater than or equal to 18 years of age

 Life expectancy determined to be greater than or equal to 6 months

 Diagnosed with Major Depressive Disorder based on clinical examination and the DSM-IV-TR criteria

 PHQ-9 depression assessment completed by subject, with a score of 10 or greater

 Able to take whole or crushed tablets by mouth or by feeding tube

Exclusion criteria: :

 Unable to complete self-report instruments due to illiteracy, neurologic illness, visual problems, inability to speak or read English, or other causes

 Treatment with antidepressants or antipsychotics within the last 3 months

 Psychotic or manic behavior

 Active suicidal ideation or plan

 Current illicit substance abuse

 Severe renal impairment as defined by creatinine clearance of <15 milliliters/minute/1.73 meters squared (mL/min/m2)

 Severe hepatic impairment as defined by Aspartate Aminotransferase (AST) or alanine aminotransferase (ALT) >5x the upper limit of normal, or a total bilirubin > 3.0 milliliters/deciliter (mL/dL)

 History of congenital long QT syndrome

 Clinically significant congestive heart failure or bradyarrhythmias

 Treatment with a concomitant medication that is known to have a strong association with corrected QT interval (QTc) prolongation AND a QTc >460 for men or >470 for women. Applicable to the citalopram arm only

['Major Depressive Disorder', 'Neoplasms']


Prognosis of Failure Treatment of Amebic Liver Abscess

Summary: Amebic liver abscess is the most frequent extra-intestinal form of the amoebiasis; actually the factors for predicting failure in the medical treatment are not clear. We conducted trial for determining the clinical value of paraclinical factor in this issue.
Inclusion criteria: inclusion criteria:

 Clinical, ultrasonographic and serologic diagnosis (ELISA) of amebic liver abscess.

 Both genders

 Older 15 years

Exclusion criteria: :

 Clinically suspected piogenous liver abscess

 Positive hemoculture

 Negative ELISA for amoebic antigens

 Immunosupresion (HIV)

 Abdominal or biliary surgery antecedents

 Abdominal neoplasia antecedents


The Effects of Mindsets on the Brain's Response to Food Cues

Summary: Previous studies have shown that obese individuals exhibit greater reward-related brain activity in response to food cues than lean individuals and our group has shown that successful weight loss maintainers who were previously obese and now maintain a healthy weight have increased control-related activity when viewing food cues. These findings suggest key roles for both reward-related brain areas and inhibitory control regions in eating behavior. However, no studies to date have examined (a) whether the response to food cues (i.e., cue-reactivity) can be changed in obese individuals, (b) which strategies are most effective at altering brain response to food cues, or (c) the neural mechanisms that support such change.~Given the omnipresent environmental cues to eat and the association between heightened reward-responsivity and obesity, it is critical to investigate ways to potentially alter food cue-reactivity in the obese. The most widely employed approach for behavioral weight loss treatment is Cognitive Behavioral Therapy (CBT), which incorporates strategies to control and change cognitions (e.g., avoid desire to eat tempting foods by focusing on something else). This approach is sometimes described as change- focused because modifying negative thoughts is assumed to thereby change associated maladaptive emotions and behaviors. Alternatively, emerging evidence suggests Acceptance and Commitment Therapy (ACT), which teaches participants to recognize and accept their cravings as feelings that need not be acted upon, may also be effective in treating obesity. A third strategy often employed in smoking cessation and substance abuse treatment is to focus on the long-term consequences of behaviors, however this form of treatment is not typically used in behavioral weight loss therapy. Thus although each approach is potentially effective, these treatment approaches differ greatly in the cognitive strategies they employ.~The primary aim of the proposed research is to compare a cognitive strategy used in CBT ('CHANGE'), a cognitive strategy emphasized in ACT ('ACCEPT'), and a cognitive strategy used in smoking cessation ('LATER') relative to a control condition ('NOW'), in their effectiveness in altering reward and inhibitory control responses to food cues among obese individuals.
Inclusion criteria: inclusion criteria:

 MRI compatibility

 25-55 yrs old

 25-40 BMI

 weight stable

 right handed

Exclusion criteria: :

 MRI incompatibility

 left handed


Decoy Receptor 3 (DcR3) Polymorphisms in Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE)

Summary: Although SLE and RA are correlated with genetic predisposing factors such as human leukocyte antigen (HLA) class II, both diseases and other genetic factors might have contributed to the development of dysregulated lymphocyte activation and autoimmunity.~Decoy receptor 3 (DcR3)/TR6 is a secreted protein belonging to the tumor necrosis factor (TNF) receptor family. It binds to Fas ligand (FasL), LIGHT, and TL1A that are all TNF family members. It was noted that soluble or solid phase DcR3-Fc co-stimulated proliferation, lymphokine production and cytotoxicity of mouse and human T cells upon T-cell receptor (TCR) ligation. Recently, the investigators found that the serum level of soluble DcR3 was higher in SLE patients than in healthy control subjects (unpublished data). Taken together, the investigators propose that in autoimmune diseases, such as RA and SLE, activated T cells secrete more DcR3 than non-autoimmune controls, which may, in turn, costimulate T cells further and cause dysregulated lymphocyte activation. With the aim to establish the possible correlation between DcR3 genetic polymorphisms, DcR3 expressions, and autoimmune phenotypes, the investigators offer this proposal. They plan to investigate the single nucleotide polymorphisms (SNPs) in the DcR3 gene. The genetic polymorphisms on the DcR3/TR6 gene and circulating DcR3 level will be compared between RA, SLE and non-autoimmune control subjects.
Inclusion criteria: inclusion criteria:

 SLE, RA, or healthy
Exclusion criteria:

['Rheumatoid Arthritis', 'Systemic Lupus Erythematosus']

Rheumatoid Arthritis
Systemic Lupus Erythematosus

inclusion criteria:

 SLE, RA, or healthy


Phenytoin and Driving Safety: A Randomized, Controlled Cross-Over Study

Summary: Automobile driving is a crucial aspect of everyday life, yet vehicular crashes represent a serious public health problem. Patients with epilepsy are at elevated risk for automobile crashes, causing great personal suffering and financial costs to society. Most collisions involving epileptic drivers are not seizure related but may instead result from cognitive effects upon driving performance of epilepsy and antiepileptic drugs (AEDs). Several million American drivers take AEDs for treatment of medical conditions besides epilepsy and may also be at risk for cognitive impairments that can reduce driving performance. Empirical evidence of the effects of AEDs on driving performance would enable development of driving guidelines that could lower the risk of injurious motor vehicle collisions; however, this evidence is currently lacking. The broad goal of our project is to determine the specific effects of the most commonly utilized AED, phenytoin, by assessing driving performance and cognitive abilities in neurologically normal volunteers taking phenytoin in a randomized, double-blind, placebo-controlled, crossover study. Our proposed experiments will assess: (1) cognitive functions using standardized neuropsychological tests (of attention, perception, memory, and executive functions), (2) driving performance during phenytoin and placebo administration, and (3) the effects of phenytoin-related cognitive performance upon driving performance. To measure driving performance, we will use a state-of-the-art fixed-base interactive driving simulator that allows us to observe driver errors in an environment that is challenging yet safe for the driver and tester, under conditions of optimal stimulus and response control. The results of this study of 30 drivers treated with phenytoin and placebo will increase the understanding of the role of AED-related cognitive impairment on driving safety errors. A better understanding of the impact of AEDs upon driving performance is necessary to rationally develop interventions that could help prevent crashes by drivers treated with AEDs.
Inclusion criteria: inclusion criteria:

 Anticipating a 10-15% drop-out rate, we will induct 30 neurologically normal subjects (age 18 (21) -60) to obtain 25 evaluable subjects who are legally licensed to drive in their state of residence and have been actively driving under appropriate legal guidelines for at least 5 years (to minimize performance variations of novice drivers).

 Because this study is intended to determine the potential effects of phenytoin on driving performance, a relatively healthy cohort of patients must be chosen. Chronic medical or psychiatric conditions could cause significant alterations in driving performance independent of those caused by phenytoin, which would complicate interpretation of performance impairments.

Exclusion criteria: :

 Subjects who are younger than 18 or older than 60

 Have history of prior seizures, family history of epilepsy, or prior history of head injury

 Have a known history of prior drug or alcohol abuse or unwillingness to abstain from drug or alcohol use during the study period

 Have a past or current active neurological or psychiatric disorder that could impair cognitive or driving performance (i.e. baseline IQ < 90, dementia, mental retardation, stroke, severe head injury, schizophrenia, active clinical depression, progressive brain tumor).

 Subjects who have a chronic medical condition (i.e. diabetes mellitus, renal insufficiency, congestive heart failure, hepatic dysfunction, hematologic condition, HIV)

 Taking medications known to affect the central nervous system (i.e. baseline pre-study treatment with antiepileptic drug, anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, narcotics and tranquilizers)

 Regularly use over-the-counter cough suppressants, antihistamines, or sleep aids; or who ingest over 7 cups of daily coffee or currently smoke cigarettes.

 Subjects will be excluded if they cannot complete SIREN testing or neuropsychological instruments because of visual or hearing impairment (history or screening discovery of corrected visual acuity of less than 20/50) or other physical disability, or if they have a history of severe motion sickness as an adult-a marker for patients who develop simulator sickness and therefore cannot participate in SIREN testing.

['Cognitive Measures', 'Driving Simulator Performance']

Cognitive Measures
Driving Simulator Performance


Test of A Model of Representational Knowledge Stored in the Human Prefrontal Cortex

Summary: This study will examine the underlying mental processes that determine how people understand social behavior, remember information, and think. Language, planning, problem solving, reasoning, social behavior, and memory are the critical parts of cognition that make up daily life. This study will explore the association between performance on various experimental tasks and day-to-day functioning.~Healthy normal volunteers and patients with certain kinds of brain damage (primarily focal or degenerative lesions of the human prefrontal cortex) or psychiatric disorders may be eligible for this study. Candidates with central nervous system trauma, disease or dysfunction will be screened with a routine neurological examination and history.~Participants may be asked to complete written tests, sit in front of a computer monitor and press a key to indicate a decision about what appears on the screen (for example, whether a statement is accurate) and answer questions from a test examiner. A skin conductance response (SCR) test may be done along with some of the cognitive tests. SCR uses electrodes (pieces of metal attached to wires) placed on the fingers to measure the subject's emotional reaction to a test. Participants may also do an evoked response test, in which the subject watches words or scenes on a TV screen while his or her responses are recorded from electrodes placed on the scalp (similar to an electroencephalogram). The tests will be scheduled for an average of one session a week, with each session lasting from 30 minutes to 3 hours. Generally, 15 sessions will be scheduled over a 1-year period. Special arrangements will be made to accommodate participants from out-of-town.~Participants may have a magnetic resonance imaging (MRI) scan of the brain. This test uses radio waves and a strong magnetic field to picture structural and chemical changes in tissue. For the procedure, the subject lies on a table in a space enclosed by a metal cylinder (the scanner) for about 1 hour.~In addition, some study subjects will be invited to participate in a training study designed to improve their planning or social behavior. Participation requires coming to NIH daily over a 1- to 2-month period for 1 to 2 hours each visit.
Inclusion criteria: INCLUSION AND
Exclusion criteria: :

 Controls: Healthy normal controls matched to specific patient groups for age, education, gender, and race to be recruited by advertisement from the community or from among friends and relatives of the patient. Individuals with a neurological or psychiatric history or medical condition that would compromise our interpretation of the test results will not be included.

 Patients: Patients will be selected from referrals to the Cognitive Neuroscience Section, the NIH Clinical Center, and from referrals recruited through approved advertisement in appropriate media and medical journals.

 All patients must have a diagnosed CNS disorder with lesions localization (when suspected) verified by CT or MRI scanning available from the referring physician or completed at the NIH Clinical Center. Subjects without neurological, neuropsychological, and imaging evidence compatible with one of the recruited diagnoses will be excluded from the study as will subjects who cannot cooperate with neuropsychological testing (based on family report and the report of the referring healthcare professional).

 The bulk of the patients recruited for this protocol will have focal or degenerative lesions of the HPFC. We also will recruit patients with non-frontal lesions in order to determine the specificity of the deficit we observe in patients with HPFC lesions. These patients will undergo the same testing but are not expected to have marked cognitive deficits on tests of frontal lobe function.

 Patients with different basal ganglia disorders or limbic system lesions are included because their lesions involve differing subsets of subcortical structures that are thought to play an important role in the automatic activation of stored plans and social behavior. Another prediction from the SEC model is that patients with basal ganglia disorders will have deficits primarily on over-learned components of tasks that require visuomotor interaction (e.g., a visuomotor serial reaction time task) but have spared performance on higher level cognitive planning tasks that don't require simple visuomotor responses.

 The bulk of the patients will be patients with focal penetrating head injuries who will be seen here at the NIH as part of a newly funded study to be conducted primarily, but not solely, at the National Naval Medical Center. Patients with dementing disorders (e.g., frontotemporal dementia) are suitable for assessment of the structure of knowledge, and in particular, the systematic general breakdown of social and non-social SEC knowledge representation. Patients with focal lesions (e.g., dorsolateral frontal) will be studied to assess damage to specific sub-components of the structured event complex model. Occasionally, single cases will be intensively studied due to a unique behavioral presentation (see above for a lengthier description).

 A durable power of attorney will be appointed if the patient is unable to make decisions about any or all aspects of this protocol. In the past in our protocols, this has almost always been the spouse.

 The age range of the brain-damaged patients will be determined on entrance into the protocol. An equal number of left and right unilateral lesions will be sought for determination of laterality differences. Patients with lesions limited to (rather than simply including) the frontal lobe will also be especially sought.

 Minors (ages 6-17) are included in this protocol in order to examine 3 specific questions: (1) What is the distinction in retrievable SEC knowledge (e.g., plans or social rules) learned prior to adolescence from that subsequent to adolescence?; (2) Does learning and development of all aspects of social cognition require an intact prefrontal cortex?; and (3) Will some effects of early prefrontal cortex lesions only appear after the age of 14? The first question will be addressed by studying healthy normal children before the age of 14 on experimental social cognition and planning tasks slightly modified from those used with adults (see the six studies described above). The second question will be addressed by studying single cases and groups of children with prefrontal cortex lesions on social cognition tasks before and after the age of 14. The third question will be addressed by studying children with prefrontal cortex lesions incurred before the age of 14 both before and after the age of 14 on social cognition, meta-cognition, and planning tasks.

['Intracranial Central Nervous System Disorder', 'Mental Disorder', 'Healthy']


Nontypeable H. Influenzae in Healthy Adults

Summary: The purpose of this study is to learn more about the safety of Haemophilus (H.) influenzae, its ability to produce adverse reactions and to live in the nose and throat. The nose and throat of healthy adults will be populated with a specific type of H. influenzae Nontypeable Haemophilus influenzae (NTHi) 2019 Streptomycin Resistant (StrR) number 1. Researchers will study whether the germ settles in the nose and throat, whether it causes symptoms after it has been placed in the nose, how long the germs last in the nose and throat, and whether the body tries to produce a permanent defense to the germ. Volunteers will receive a lower dose (3,200 germs) or a higher dose (32,000 germs). Active participation will last about 28 days, including a 3 night hospital stay, additional follow-up visits, followed by a 6 month follow-up phone call. Study procedures will include blood samples, saliva samples, several nose washes and throat swabs.
Inclusion criteria: inclusion criteria:

 inclusion criteria for Inoculated Volunteers:

 Healthy 18-54 years old (male or female) with no chronic medical conditions with the exception of well-controlled hypertension

 Availability for study visits over the next 1 month

 Normal hemoglobin, white blood cell count, creatinine, alanine aminotransferase (ALT), platelet count

 Signed informed consent form

 In good health as determined by medical history and physical exam on the screening evaluation [including heart rate 55-100 beats per minute (bpm); blood pressure: systolic 90-140 mm Hg and diastolic 50-90 mm Hg]. If the subject is a well trained athlete by the judgment of the Principal Investigator (PI), heart rate of 40-100 bpm is acceptable.

 Negative urine pregnancy test for women of childbearing potential

 If the subject is female and of childbearing potential, she agrees to use acceptable contraception and not become pregnant for the duration of the study. (Acceptable contraception includes abstinence, implants, injectables, combined oral contraceptives, effective intrauterine devices, or a vasectomized partner)

 Negative human immunodeficiency virus (HIV) enzyme linked immunosorbent assay (ELISA) for HIV 1 and 2 or indeterminate Western blot or other assay confirming that the serostatus does not reflect HIV infection, negative hepatitis C and hepatitis B serology or other assay confirming that the serostatus does not reflect active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection

 Negative urine protein and glucose by dipstick

 Subjects must be willing to be housed in the clinical research unit for the first 3 nights of the inoculation period.

 inclusion criteria for Transmissibility Substudy:

 Healthy 18-54 years old (male or female) with no chronic medical conditions with the exception of well-controlled hypertension

 Normal hemoglobin, white blood cell count, creatinine, ALT, platelet count

 Negative HIV ELISA for HIV 1 and 2 or indeterminate Western blot or other assay confirming that the serostatus does not reflect HIV infection, negative hepatitis C and hepatitis B serology or other assay confirming that the serostatus does not reflect active HCV or HBV infection

 Negative urine protein and glucose by dipstick

 Availability for study visits over the next 1 month

 Signed informed consent form

 In good health as determined by medical history and physical exam on the screening evaluation (including heart rate 55-100 bpm; blood pressure: systolic 90-140 mm Hg and diastolic 50-90 mm Hg). If the subject is a well trained athlete by the judgment of the PI, heart rate of 40-100 bpm is acceptable.

 Negative urine pregnancy test for women of childbearing potential

 If the subject is female and of childbearing potential, she agrees to use acceptable contraception and not become pregnant for the duration of the study. (Acceptable contraception includes abstinence, implants, injectables, combined oral contraceptives, effective intrauterine devices, or a vasectomized partner)

 Subjects must be willing to spend 3-5 hours per day for 6 days in nonintimate contact with their paired inoculated contact.

Exclusion criteria: :


The Incidence of Nontuberculous Mycobacterial Pulmonary Infection in Bilateral Bronchiectasis and Bronchiolitis

Summary: Nontuberculous mycobacteria (NTM) are ubiquitous organisms in the environment and are now increasingly being recognized as significant causes of chronic pulmonary infection in immunocompetent individuals (1). The most frequently encountered NTM lung disease worldwide is caused by Mycobacterium avium-intracellular complex (MAC) (2-4).~In several studies with chest computed tomography (CT), researchers have demonstrated that the presence of bilateral multifocal bronchiolitis (well-defined small nodules and branching centrilobular nodules, or tree-in-bud pattern) and bronchiectasis distributed mainly in the right middle lobe and lingular segment are indicative of NTM pulmonary infection (7-11). Accordingly, it is believed that radiologic findings of bilateral bronchiolitis and bronchiectasis on chest CT scans specifically suggest NTM pulmonary infection (1). These CT findings, however, may not be specific for NTM pulmonary infection. CT patterns of bronchiectasis and bronchiolitis in the pulmonary infections caused by various NTM organisms have been reported, and these organisms include Mycobacterium kansasii, Mycobacterium xenopi, and rapidly growing mycobacteria such as Mycobacterium abscessus, Mycobacterium fortuitum, and Mycobacterium chelonae (12-14). In addition, not all patients with bronchiectasis and bronchiolitis have NTM pulmonary infection. Two recent studies showed that only about 50% of patients with such CT features have MAC pulmonary infection (9,15). To the best of our knowledge, however, there is no report about the incidence of NTM in patients with bronchiectasis or bronchiolitis in countries with low incidence of TB. Thus, the purpose of our study was to determine the frequency of NTM pulmonary infection in patients with bilateral bronchiectasis and bronchiolitis at chest CT and to investigate whether these CT findings are specifically indicative of MAC infection or other specific pathogen.
Inclusion criteria: inclusion criteria:

 All patients with bronchiectasis or bronchiolitis

Exclusion criteria: :

 All patients with severe lung disease other than bronchiectasis

 Active lung infection

 Active infection other site except the lung


Algorithm for Oliguria in Septic Shock

Summary: Acute Kidney Injury (AKI) develops in 88% to 30% of critically ill patients admitted to an intensive care unit and is a strong predictor of mortality.Therefore any management strategy that prevents progression of renal risk to injury or failure has the potential to improve outcomes in these patients.Conventional management of acute oliguria in shock has been to blindly 'push' fluids to improve renal perfusion or to give loop diuretics once fluid loading has been considered as accomplished. However both volume overload and 'blind' attempts at fluid removal can worsen renal injury and have been associated with higher mortality by venous overcongestion and inappropriate hypovolemia. It seems reasonable to assume that a bedside test to visualize volume status and renal perfusion may assist in improving outcomes in this cohort.The investigators developed a goal-directed ultrasonographic protocol to provide immediate hemodynamic information in acutely oliguric patients with shock as well as a management algorithm for guiding therapy. The investigators incorporated IVC diameter measurement, respiratory variation and response to a passive leg raise to assess whether further fluid boluses were required and a measurement of renal perfusion to determine whether diuretics or renal replacement therapy were indicated. The investigators aim to measure the effects of this management protocol on the rates of AKI in the study participants as compared to prior to the implementation of the protocol.The study design is a prospective, observational. Since this is a proof of concept study, the projected sample size is 40 patients. An interim analysis will be carried out after 20 patients are enrolled and a further 20 will be enrolled as necessary
Inclusion criteria: inclusion criteria:

 Critically ill, adult patients AND with acute oliguric renal failure AND within 6 hours of presentation

Exclusion criteria: :

 i. Patients with pre-existing chronic renal failure ii. Patients on renal replacement therapy/ Dialysis iii. Patients with poor sonographic windows


Trial Comparing Complication Rates Associated With Robot-assisted Thyroidectomy to External Thyroidectomy

Summary: The main objective is to compare 12 month complication rates between a new surgical method for thyroidectomy (robot-assisted endoscopic thyroidectomy via a sub-clavical approach) and open thyroidectomy.
Inclusion criteria: inclusion criteria:

 The patient must have given his/her informed and signed consent

 The patient must be insured or beneficiary of a health insurance plan

 The patient is available for 12 months of follow-up

 The patient is a candidate for total thyroidectomy because of a nodular pathology, a diffuse goiter, thyroiditis, or Basedow's disease

 Patient has calcitoninemia < 9 ng/pl

 Patient has normal calcemia

 Patient has PTH level between 5 ng/l and 75 ng/l

 The subject has a normal laryngeal mobility

Exclusion criteria: :

 The patient is participating in another study

 The patient is in an exclusion period determined by a previous study

 The patient is under judicial protection, under tutorship or curatorship

 The patient refuses to sign the consent

 It is impossible to correctly inform the patient

 The patient is pregnant

 The patient is breastfeeding

 The patient is not available for 12 months of follow-up

 Subject has a preoperative diagnosis of cancer on fine needle aspiration biopsy of the thyroid or cervical lymph node

 Lymph node metastasis strongly suspected clinically and/or sonographically

 The subject has an extension of substernal thyroid (diving goiter)

 Family history of medullary thyroid cancer

 The subject has a history of neck surgery

 Contraindication for general anesthesia

['Robot-assisted thyroidectomy', 'Open thyroidectomy']

Robot-assisted thyroidectomy
Open thyroidectomy

['Thyroid Nodule', 'Goiter', 'Thyroiditis', 'Graves Disease']

Thyroid Nodule
Goiter
Thyroiditis
Graves Disease


Safety and Efficacy Study of a Vaccine Against Enterotoxigenic Escherichia Coli (ETEC) to Prevent Moderate to Severe Diarrhea

Summary: This is a research study about an experimental (investigational) vaccine called ACE527. ACE527 is a vaccine that is being made to prevent disease from a germ called enterotoxigenic Escherichia coli (ETEC). This germ causes diarrhea, largely in children living in developing countries and in travelers to those countries. One purpose of this study is to see if the vaccine is safe and develops an immune response. Another purpose is to see if it prevents people from getting sick when exposed to the ETEC germ. This ETEC germ is also experimental (investigational).
Inclusion criteria: inclusion criteria:

 Male or female age ≥18 and ≤ 50 years.

 General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.

 Negative serum pregnancy test before first (visit V0) and before challenge (visit C0) for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female subjects unable to bear children must have this documented (e.g. tubal ligation or hysterectomy) or must have negative pregnancy tests.

 Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.

 Completion of a training session and demonstrated comprehension of the protocol procedures, knowledge of ETEC-associated illness, and by passing a written examination.

 Availability for the study duration, including all planned follow-up visits.

Exclusion criteria: :

 Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study. Some medical conditions which are adequately treated and stable would not preclude entry into the study. These conditions might include stable asthma controlled with inhalers or mild hypertension stably controlled with a single agent.

 Significant abnormalities in screening hematology, serum chemistry or urinalysis as determined by PI or PI in consultation with the MM and sponsor.

 Presence in the serum of HIV antibody, HBsAg, or HCV antibody.

 Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay).

 Evidence of current excessive alcohol consumption or drug dependence.

 Evidence of impaired immune function.

 BMI <19, >34

 Recent vaccination or receipt of an investigational product (within 30 days before vaccination).

 Intention to donate blood or blood products for one month following the completion of study participation (note: The Red Cross will not allow blood donations for 1 year following participation in an investigational research study).

 Any other criteria which, in the investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study

 Working as a food handler, in child-care or as a healthcare worker with direct patient contact.

 Have household contacts who are <2 years old or >80 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).

 Abnormal stool pattern (fewer than 3 per week or more than 3 per day).

 Regular use of laxatives, antacids, or other agents to lower stomach acidity.

 Use of any medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.

 Known allergy to two of the following antibiotics: quinolones, trimethoprim-sulfamethoxazole, and penicillin.

 Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within two years prior to dosing, OR planned travel to endemic countries during the length of the study.

 Vaccination for or ingestion of ETEC, cholera, or LT toxin within 3 years prior to dosing.

 Use of antibiotics during the 7 days before dosing or proton pump inhibitors, H2 blockers or antacids within 48 hours prior to dosing.

 History of diarrhea in the 7 days prior to vaccination (outpatient diarrhea is defined as ≥ 3 unformed loose stools in 24 hours).


Natural History of Isolated Deep Vein Thrombosis of the Calf

Summary: Whether isolated distal DVT (IDDVT), DVT confined to the calf, should be looked for and diagnosed to allow them to be treated with anticoagulants remains one of the still unsolved issues in vascular medicine, especially because of the insufficient data on clinical risks of untreated distal DVT. Management studies have shown that it is safe to withhold anticoagulation in outpatients with suspected DVT if compression ultrasonography (CUS) limited to the proximal deep veins yields normal results on presentation and on repeated examination after 5 to 7 days. This strategy is based on the premise that IDDVT do not need to be diagnosed and treated, what is necessary when they extend involving the proximal veins. There is no general agreement, however, on the assumption that the non-extending IDDVT do not need to be diagnosed and treated, and many authors recommend to perform a single CUS examination extended to the distal deep veins. All the available studies have treated with anticoagulants the diagnosed IDDVT and no adequate information is available on the risk of IDDVT left untreated.~The present study, performed in outpatients with suspected leg DVT, aims at assessing the clinical consequences of IDDVT diagnosed (by a complete US investigation) but not treated because the results of this investigation remain blind to both the patient and the treating doctor, whereas the diagnostic-therapeutic procedure remains the usual one, based on CUS investigation limited to diagnose proximal DVT, to be repeated after 5-7 days (or earlier) to exclude an extension to proximal veins of an IDDVT potentially present.
Inclusion criteria: inclusion criteria:

 suspected deep vein thrombosis of a leg

 intermediate/high pre-test clinical probability or high D-dimer levels

Exclusion criteria: :

 age < 18 years

 presence of proximal DVT

 suspected isolated iliac DVT

 symptoms/signs lasting from > 30 days

 presence of symptoms of pulmonary embolism

 pregnancy or puerperium

 full dose treatment with heparin or derivatives from > 1 day

 presence of superficial vein thrombosis

 limited life expectancy (< 6 months)

 geographically inaccessible location

 inability or refusal to give consent

 participation in other clinical studies

['Isolated Distal DVT', 'Proximal DVT', 'Pulmonary Embolism']

Isolated Distal DVT
Proximal DVT
Pulmonary Embolism


Prospective Study of Voice Therapy in Children: A Pilot Study

Summary: The purpose of this prospective study is to obtain preliminary data on changes in pre-post voice therapy outcomes in children diagnosed with vocal fold nodules, as a function of a series of cognitive operations. The primary outcome is voice-related quality of life (questionnaire). Secondary outcomes are standard acoustic and aerodynamic measures derived from sustained vowel and running speech samples.
Inclusion criteria: inclusion criteria:

 Diagnosis of vocal fold nodules.

 Age 4-11 yr.

 Informed Consent.

 English comprehension and production sufficient to participate in the protocol and in voice therapy.

 Considered behaviorally and cognitively appropriate by the ear, nose, and throat physician and speech-language pathologist for voice therapy.

 Parent and child willingness to participate in all aspects of the protocol and voice therapy.

Exclusion criteria: :

 Co-morbid medical conditions or medications that would mask or amplify the outcome of voice therapy, including (a) developmental or other neuromuscular conditions, (b) major illness, chronic or acute, with the exception of laryngopharyngeal reflux disease (LPR) or allergies and their treatments, which are common in both children and adults with voice disorders, thus their exclusion would severely restrict the participant pool and, moreover, threaten external validity.

 Hearing loss: > 20 dB hearing loss at 1000, 2000, 4000 Hz in at least one ear.

['Adventures in Voice: Pediatric Voice Therapy']


The Interaction Between Severe Acute Respiratory Distress Syndrome Viral Proteins and Monocytes

Summary: Severe acute respiratory syndrome (SARS) is a new threat to public health since November, 2002. The SARS is highly contagious and is believed to be transmitted by person-to-person through droplet and direct contact. The patients present with fever, chills, cough, myalgia, dyspnea, and diarrhea. The symptoms aggravate in the second week and nearly 40% of the patients develop respiratory failure that requires assisted ventilation. The mortality rate is reported as 6.5%-7%.~After several months, the world scientists found the etiology to be a new coronavirus not belonging to the previous coronavirus group I, II and III. The new virus is called SARS associated coronavirus (SARS-CoV).~Although the high morbidity and mortality of SARS occurred in adults, there was rare mortality reported in the children. The report from Hong Kong pointed out that the symptoms of SARS in younger children were milder and the clinical course was not as aggressive as in adults. Therefore, the aim of the project is to design the experiment to see the differences of immunological responses to SARS-CoV protein in healthy younger children, teenagers, and adults. The investigators hope that the result could explain the reason for milder disease in younger children and the immunological pathogenesis of SARS.
Inclusion criteria: inclusion criteria:

 Healthy adults, children and cord blood
Exclusion criteria:


The Effect of the Hydroxyethyl Starch on Kidney Injury in Pediatric Cardiac Surgery

Summary: The investigator will evaluate the influence of colloid administration on postoperative acute kidney injury in pediatric patients undergoing cardiac surgery under cardiopulmonary bypass.
Inclusion criteria: inclusion criteria:

 Children aged less than 7 years old

 American Society of Anesthesiology (ASA) physical status 1-3

Exclusion criteria: :

 Preoperative creatinine > 1.5mg/dl

 History of dialysis

 Liver function abnormality

 Diabetes Mellitus

 History of allergic reaction

 Coagulation abnormality


Efficacy and Safety of Garamycin® Sponge in Diabetic Patients With a Moderate or Severe Foot Ulcer Infection

Summary: The purpose of this study is to determine whether Garamycin Sponge (Gentamicin-Collagen sponge) in combination with antibiotics is safe and effective in treating moderate and severe diabetic foot infections.
Inclusion criteria: inclusion criteria:

 Is aged ≥ 18.

 Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria.

 Has an open foot wound with visible inflammation, namely at least 1 skin ulcer located on or below the malleolus that presents with the following clinical manifestations of a moderate or severe infection based on the Infectious Disease Society of America (IDSA).

 Has received appropriate surgical intervention to remove all necrotic and infected bone if diagnosed with osteomyelitis

 Meets certain minimal laboratory criteria.

Exclusion criteria: :

 Has an ulcer infection which, based upon the patient's known history of hypersensitivity cannot be appropriately treated with at least one of the empiric systemic antibiotic regimens per protocol.

 Has received > 48 hours of potentially effective antibiotic therapy and the wounds are clinically improving. If a patient has received an antibiotic within 72 hours, but is not improving or deep-tissue culture results indicate that the infecting pathogen is not susceptible to that antibiotic, the patient may be enrolled.

 Requires or is likely to require treatment with any concomitant topical product or wound therapy during the study period.

['Garamycin Sponge (Gentamicin-Collagen sponge)', 'Systemic Antibiotic']


Phone-Based Postpartum Continuing Care for Smoking Cessation

Summary: Smoking is a leading cause of death and other negative health outcomes. While a high percentage of women quit smoking during pregnancy, the majority relapse in the first 6 months postpartum. We propose developing and pilot testing a phone-based postpartum continuing care (PPCC) protocol based on existing evidence-based approaches to increase smoking cessation, reduce relapse, increase early re-intervention, and reduce infant exposure to environmental tobacco smoke in the postpartum period.
Inclusion criteria: inclusion criteria:

 first or second trimester of pregnancy

 age 18 or older

 self-reported tobacco use in the past 90 days or nicotine-dependence in the past year

Exclusion criteria: :

 intend to terminate their pregnancy

 intend to move out of the city within the next 12 months

 are unable to provide informed consent and participate in English

['Phone-based postpartum continuing care', 'Standard care']

Phone-based postpartum continuing care
Standard care


Optimal Treatment for Women With a Persisting Pregnancy of Unknown Location

Summary: This is a randomized controlled trial to compare three currently available management strategies for women with a persisting pregnancy of unknown location (PPUL), which makes them at-risk for ectopic pregnancy. We will recruit hemodynamically stable women with a confirmed PPUL to be randomized to one of three strategies: 1) Uterine evacuation followed by methotrexate (MTX) for some (those that have evidence of a non visualized ectopic pregnancy) 2) Empiric treatment with MTX for all 3) Expectant management. Randomization will be 1:1:1 into these three arms. After randomization, they will be followed and treated clinically as is indicated by the progression of their condition. Primary outcome measures: uneventful decline of hCG to 5 IU/mL.
Inclusion criteria: inclusion criteria:

 Female with a persisting pregnancy of unknown location:

 A pregnancy of unknown location is defined as a pregnancy in a woman with a positive pregnancy test but no definitive signs of pregnancy in the uterus or adnexa on ultrasound imaging. A definitive sign of gestation includes ultrasound visualization of a gestational sac with a yolk sac (with or without an embryo) in the uterus or in the adnexa. Ultrasound must be performed within 7 days prior to randomization.

 Persistence of hCG is defined as at least 2 serial hCG values (over 2-14 days), showing < 15% rise per day, or < 50% fall between the first and last value.

 Patient is hemodynamically stable, hemoglobin >10 mg/dL

 Greater than or 18 years of age

Exclusion criteria: :

 Hemodynamically unstable in need of acute treatment

 Most recent hCG > 5000 mIU/mL

 Patient obtaining care in relation to a recently completed pregnancy (delivery, spontaneous or elective abortion)

 Diagnosis of gestational trophoblastic disease

 Subject unwilling or unable to comply with study procedures

 Known hypersensitivity to MTX

 Presence of clinical contraindications for treatment with MTX

 Prior medical or surgical management of this gestation

 Subject unwilling to accept a blood transfusion

['Methotrexate', 'Uterine Evacuation', 'Expectant Management']

Methotrexate
Uterine Evacuation
Expectant Management

['Persistent Pregnancy of Unknown Location', 'Ectopic Pregnancy']


Clinical Trial Comparing Continuous Versus Intermittent Hemodialysis in ICU Patients

Summary: The mortality of acute renal failure (ARF) remains to be high (around 60-70%) despite manifold improvements in ICU care. At present, it is not clear if the method chosen for renal replacement therapy, i.e. intermittent haemodialysis (IHD) or continuous haemofiltration (CVVH), might impact on the outcome of these patients. For this purpose, a prospective randomised clinical study of the effect of continuous versus intermittent renal replacement therapy on the mortality and outcome of acute renal failure will be performed.
Inclusion criteria: inclusion criteria:

 all ICU patients requiring renal replacement therapy

Exclusion criteria: :

 patient denies informed consent

 patient not requiring intensive care therapy

 kidney transplanted patients

 chronic renal failure (serum creatinine > 3mg/dl)

['RRT for acute kidney failure using the CVVH method', 'RRT for acute kidney failure using the IHD (intermittent HD)']


A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)

Summary: Cytomegalovirus (CMV) is a common virus that usually presents with few if any side effects. When first infected, some people may have symptoms similar to mononucleosis (i.e., fatigue, weakness, fever, swollen glands). Most people in the United States are infected during childhood or as adults if they work around children. Pregnant women, who have not been infected with CMV in the past and become infected during pregnancy (i.e. a primary infection), may cause their babies to get infected with CMV. Babies that are infected may develop permanent disabilities including hearing loss and a small portion will die from the infection.~Currently it is not routine practice to screen pregnant women for CMV infection. Additionally, there is no agreement about how to evaluate and manage pregnant women infected with CMV for the first time. There is also no evidence that treatment is beneficial for the baby.~The purpose of this research study is to determine whether treating pregnant women who have a primary CMV infection with CMV antibodies will reduce the number of babies infected with CMV.
Inclusion criteria: inclusion criteria:

 Diagnosis of primary maternal CMV infection on the basis of one of the following:

 A positive CMV Immunoglobulin M (IgM) antibody and low-avidity maternal CMV Immunoglobulin G (IgG) antibody screen

 Evidence of maternal seroconversion with development of CMV IgG antibody following a prior negative CMV screen

 Gestational age at randomization no later than 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound; or no later than 27 weeks 6 days for women with a positive IgM, negative IgG initially screened before 23 weeks who are rescreened after 2-4 weeks and have evidence of IgG seroconversion.

 Singleton pregnancy. A twin pregnancy reduced to singleton (either spontaneously or therapeutically) before 14 weeks by project gestational age is acceptable.

Exclusion criteria: :

 Maternal CMV infection pre-dating pregnancy as defined by a high IgG avidity index or a positive IgG in the presence of a negative IgM.

 Known hypersensitivity to plasma or plasma derived products

 Planned termination of pregnancy

 Known major fetal anomalies or demise

 Maternal Immunoglobulin A (IgA) deficiency

 Planned use of immune globulin, ganciclovir, or valganciclovir

 Maternal renal disease (most recent pre-randomization serum creatinine ≥ 1.4 mg/dL; all women must have serum creatinine measured during the pregnancy and prior to randomization)

 Maternal immune impairment (e.g., HIV infection, organ transplant on anti-rejection medications)

 Findings on pre-randomization ultrasound suggestive of established fetal CMV infection (cerebral ventriculomegaly, microcephaly, cerebral or intra-abdominal calcifications, abnormalities of amniotic fluid volume, echogenic bowel or ascites). Abnormally low amniotic fluid volume is defined as no fluid prior to 14 weeks or maximum vertical pocket < 2 cm on or after 14 weeks gestation. Abnormally high amniotic fluid volume is defined as > 10 cm.

 Positive fetal CMV findings from culture (amniotic fluid) or PCR.

 Congenital infection with rubella, syphilis, varicella, parvovirus or toxoplasmosis diagnosed by serology and ultrasound or amniotic fluid testing.

 Intention of the patient or of the managing obstetricians for the delivery to be outside a Maternal-Fetal Medicine Units Network (MFMU) Network center

 Participation in another interventional study that influences fetal or neonatal death

 Unwilling or unable to commit to 2 year follow-up of the infant

['Congenital Cytomegalovirus Infection', 'Maternal Cytomegalovirus Infection']

Congenital Cytomegalovirus Infection
Maternal Cytomegalovirus Infection


Effects of Freeze Dried Strawberry Powder Supplementation on Vascular Function and Blood Markers of Cardiovascular Risk

Summary: The purpose of this study is to evaluate the effects of freeze dried strawberry powder on LDL cholesterol, central and peripheral blood pressure, indices of arterial stiffness, and other lipid and lipoprotein concentrations. The investigators hypothesize that the bioactive compounds in freeze dried strawberry powder may elicit beneficial effects on LDL cholesterol, as well as blood pressure and arterial health.
Inclusion criteria: inclusion criteria:

 Men and women 35-65 years of age

 BMI ≥ 25 and ≤ 39 kg/m^2

 LDL-C > 116 mg/dL

 Total Cholesterol below 273 mg/dL for men and below 284 mg/dL for women

 Triglycerides below 350 mg/d

 Non-smokers

 Blood pressure < 160/100 mmHg

Exclusion criteria: :

 History of acute or chronic inflammatory conditions or heart disease, kidney disease, liver disease, autoimmune disorders, or thyroid disease (unless controlled by medication and blood results within the previous 6 months are provided)

 History of diabetes mellitus (and/or a fasting glucose > 126 mg/dL at screening)

 Stage II hypertension (blood pressure ≥ 160/100 mmHg)

 Lactation, pregnancy, or desire to become pregnant during the study

 Unwillingness to discontinue nutritional supplements, herbs, or vitamins, unless approved by investigator

 Use of medications/supplements for elevated lipids, blood pressure, or glucose

 Chronic use of non-steroidal anti-inflammatory or immunosuppressant medication

 Conditions requiring the use of steroids

 Unwillingness to refrain from blood donation prior to and during the study

 Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator

 Allergy or sensitivity to strawberries or any ingredient in the study powders

['Low Dose Strawberry Powder', 'High Dose Strawberry Powder', 'Placebo Powder']

Low Dose Strawberry Powder
High Dose Strawberry Powder
Placebo Powder


Multi-center Prospective Randomized Control Trail of High Dose Aspirin in Acute Stage of Kawasaki Disease

Summary: Kawasaki disease (KD) is an acute multi-system vasculitis syndrome of unknown etiology occurring mostly in infants and children younger than 5 years of age. In developed countries, it is the leading cause of acquired heart disease in children. However, KD remains a mysterious disease.~Single high dose intravenous immunoglobulin (IVIG, 2gm/kg) and aspirin are standard treatment for KD. Aspirin have been prescribed in treatment of KD for decade even earlier than usage of IVIG. High dose aspirin mainly act as anti-inflammation, while low dose aspirin as anti-platelet. IVIG may play most of the role of anti-inflammation in acute stage of KD. Hsieh et al. reported that KD without high dose aspirin had the same treatment response after IVIG. Therefore it is still unclear about the necessarily of high dose aspirin in acute stage of KD.~This study was conduct to investigate the role of high dose aspirin in acute stage of KD via a multi-center randomized control trail, and we plan to achieve the followings till year 2017:~Enroll 300 KD patients from multiple medical centers . Randomize group patients as group 1: with high dose aspirin (more than 30/mg/kd/day) until fever subsided and shift to low dose aspirin (3-5mg/kg/day, N=150); and group 2: without high dose aspirin during acute febrile stage, only use low dose aspirin (N=150).~Compare data including fever days, admission duration, laboratory data (CBC/DC, GOT/GPT, BUN/Cr, Alb, ESR, CRP, 2D echo), IVIG treatment response and CAL formation rate (followed at least 1 year).
Inclusion criteria: inclusion criteria: (both 1 and 2)

 1. All subjects are children who fulfilled the criteria for Kawasaki Disease (American Heart Association criteria).

 Fever > 5 days, and 4 of the 5 following symptoms

 Diffuse mucosal inflammation (strawberry tongue, dry and fissured lips)

 Bilateral non-purulent conjunctivitis,

 Dysmorphous skin rashes,

 Indurative angioedema over the hands and feet

 Cervical lymphadenopathy. (One or more nodule at lease 1.5 cm in diameter) 2. KD patients are treated with IVIG at each hospital after informed contents are obtained.

Exclusion criteria: :

 Patients whose symptoms did not full fit the Kawasaki Disease criteria.

 Had an acute fever for < 5 days and >10 days

 Incomplete collection of each followed-up data (CBC/DC, GOT/GPT, BUN/Cr, Albumin, ESR, C-Reactive Protein, 2D echocardiography)

 IVIG treatment at other hospital before refers to study centers.

 Treatment with corticosteroids, other than inhaled forms, in the previous 2 weeks before enrollment;

 The presence of a disease known to mimic Kawasaki disease.

 Previous diagnosis of Kawasaki disease

 Inability to take aspirin


Modalities of Renal Replacement Therapy in Pediatric Acute Kidney Injury

Summary: Limited prospective data is available to compare morbidity and mortality between renal replacement modalities in pediatric acute renal failure.~In the absence of clear standard of care, the choice of the extra renal replacement therapy modality is subject to clinical judgement, practical aspects, and costs.~This study will supply important data about usual modalities of pediatric acute extra renal replacement therapy and their impact on patient outcome and renal recovery. An obvious next step will be to conduct a randomized controlled trial comparing the different strategies.
Inclusion criteria: inclusion criteria:

 Age < 18 years, including the newborn ;

 Acute kidney injury as defined by pRIFLE classification requiring extra renal replacement therapy, whatever is the method.

Exclusion criteria: :

 Treatment by extra renal replacement therapy for terminal renal failure;

 History of renal transplantation;

 Extra renal replacement therapy for an inborn errors of metabolism without acute renal failure;

 Extra renal replacement therapy in the context of a drug intoxication without acute renal failure;

 Treatment by technique in MARS (Molecular Adsorbent Recirculating System);

 Modified ultrafiltration during surgery.

['acute extra renal replacement therapy']


Re-directed T Cells for the Treatment (FAP)-Positive Malignant Pleural Mesothelioma

Summary: MPM patients are not eligible for surgical procedures like decortication or pleuro-pneumectomy and have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x10e6 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor (CAR) recognizing FAP which serves as target structure in MPM.~Trial with immunomodulatory product / biological
Inclusion criteria: inclusion criteria:

 Histologically or cytologically confirmed and documented malignant pleural mesothelioma with pleural effusion,

 Signed Informed Consent after being informed,

 Patients medically and/or functionally at screening not accessible for surgical treatment

 Bone marrow function: hemoglobin >/= 100 g/L; white blood cell count (WBC) >/= 1.0 x 109/L; absolute neutrophile count (ANC) >/= 0.5 x 109/L; platelet count >/= 100 x 109/L,

 Hepatic: aspartate transaminase (AST) and alanine transaminase (ALT) </= 2.5 times upper limit of normal (ULN)); bilirubin </= 1.5 x ULN,

 Renal: creatinine = 176 umol/l and creatinine clearance = 45 mL/min,

 No concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents,

 The patient has received no major organ allograft,

 HIV-negative,

 HBV and HCV negative,

 No uncontrolled bleeding disorder,

 Patients of child-producing potential must agree to use contraception while enrolled in the study and for 24 months after the adoptive transfer.

Exclusion criteria: :

 Contra-indications to the class of TpP, e.g. known hypersensitivity or allergy to the investigational product,

 Contra-indications on ethical grounds,

 Women who are pregnant or breast feeding,

 Intention to become pregnant during the course of the study,

 Lack of safe contraception: Safe contraception is defined as follows:Female and male subjects of childbearing potential, using and willing to continue using a medically reliable method of double barrier contraception for the entire study duration and the next 2 years, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices in combination with preservatives. Or subjects who are using any other method considered sufficiently reliable by the investigator in individual cases.Subjects who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years are not considered as being of child bearing potential.

 Known or suspected non-compliance, drug or alcohol abuse

 Pericardial effusion of more than 100 ml. Pericardial involvement assessed by CT scan

 Patients with medical history of coronary heart disease (CHD), stroke or peripheral vascular disease (PVD),

 Patients with medical history of autoimmune disease such as multiple sclerosis, lupus, rheumatoid arthritis, inflammatory bowel disease or small vessel vasculitis,

 Regular intake of immune-modulating drugs,

 Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia or confusional state of the subject,

 Participation in another study with investigational drug within the 30 days preceding and during the present study,

 Previous enrolment into the current study,

 Enrolment of the investigator, his/her family members, employees and other dependent persons.

['Adoptive Transfer of re-directed T cells']


The D-KAF (Dalteparin in Knee-to-Ankle Fracture) Trial

Summary: It is known that patients who fracture their legs sometimes develop blood clots (known as deep vein thrombosis) in their legs. These clots may cause pain and swelling in the leg or they may detach and travel to the lungs producing shortness of breath, chest pain, and sometimes death. Unfortunately, it is not known how frequently these complications occur after leg fractures, or if the use of a blood thinner medication can effectively and safely prevent these clots. Doctors at hospitals across Canada are conducting a study in which patients who have surgery for leg fractures receive either a once-daily injection of a blood thinner, known as low molecular weight heparin, or a placebo injection for up to 14 days after their fractures. Neither the patients nor the doctors know which patient is on the medication and which patient is on placebo. All patients receive an ultrasound examination of their legs at 2 weeks after surgery to monitor for deep vein thrombosis. In addition, all patients are checked for symptoms of leg or lung clots and any side effects of the medication for 3 months. If the blood thinner is shown to be effective at reducing this complication and documented to be safe and cost-effective in this setting it will be recommended for use in such patients. If, on the other hand, the frequency of deep vein thrombosis is too low to justify the cost or inconvenience of taking this medication, this will also be an important finding.
Inclusion criteria: inclusion criteria:

 Age > 16 years

 Unilateral or bilateral, closed or open, fractures of the lower extremity distal to the knee including:

 Isolated fractures of the tibia including tibial plateau, shaft and plafond and medial malleolus

 Isolated fractures of the fibula including fibular head, fibular diaphysis,distal fibula and lateral malleolus

 Combined fractures of the tibia and fibula

 Tibia and/or fibula fractures may be accompanied by fractures of the patella and/or foot as well as ligamentous injuries as long as either the tibia or the fibula is involved

 Patients must be scheduled to undergo surgery (internal or external fixation) for repair of their fracture during the current admission

Exclusion criteria: :

 Patients presenting greater than 72 hours after injury

 Major injury involving other site(s)

 Lower extremity vascular injury requiring surgical repair

 Known systemic bleeding disorder or INR > 1.5, aPTT > 40 sec, or platelets < 50 x 109/L at baseline

 Active, uncontrolled bleeding (as determined by the attending surgeon or delegate)

 Intracranial or other major bleed in the previous 4 weeks

 Ongoing need for anticoagulation for other reasons

 Previous DVT or PE (objectively proven or treated with anticoagulants)

 Known molecular hypercoagulable state

 Active cancer

 Inability to receive contrast dye because of pregnancy, contrast allergy, or renal failure (serum creatinine > 300 mmol/L)

 Hypersensitivity to heparin or LMWH (including history of HIT)

 Inability to arrange out-of-hospital study medication administration

 Anticipated inability to undergo endpoint duplex ultrasound or follow-up (day 14 ± 2, 6 weeks, 3 months)

 Inability or refusal to provide informed consent· Previous participation in this study

 Estimated weight less than 40 kg

['Low Molecular Weight Heparin (dalteparin)']

['Deep Vein Thrombosis', 'Pulmonary Embolism']


Physical Activity for Advanced Stage Cancer Patients

Summary: The purpose of this study is to understand if a home-based physical activity program can improve symptoms and physical function among patients with advanced stage cancer.
Inclusion criteria: inclusion criteria:

 have stage III or IV cancer diagnosis

 able to understand English

 have a Karnofsky Performance Status (KPS) score of 60% (able to care for most of the personal needs)

 have fatigue and/or two other target symptoms

 have been cleared by their provider to engage low to moderate intensity physical activities

Exclusion criteria: :

 are hospitalized

 have lesion or metastasis of bone

 have a cardiac pacemaker

 have a history of seizure or loss of consciousness

 have been using a Wii Fit

 diagnosed cognitive impairment

['Six Week Physical Activity Intervention', 'Progress Reporting']

Six Week Physical Activity Intervention
Progress Reporting


Biological Factors in Predicting Response to Treatment in Patients With Esophageal Cancer or Rectal Cancer

Summary: RATIONALE: Studying samples of tumor tissue and blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment.~PURPOSE: This clinical trial is studying how well biological factors work in predicting response to treatment in patients with esophageal cancer or rectal cancer.
Inclusion criteria: DISEASE CHARACTERISTICS:

 Histologically confirmed adenocarcinoma or squamous cell carcinoma of the esophagus or rectum

 Planning to receive neoadjuvant treatment, including radiotherapy or chemoradiotherapy

 PATIENT CHARACTERISTICS:

 Not pregnant or nursing

 No blood disorder

 Not deprived of freedom or protected by law

 PRIOR CONCURRENT THERAPY:

 See Disease Characteristics
Exclusion criteria:

['gene expression analysis', 'mutation analysis', 'polymorphism analysis', 'laboratory biomarker analysis', 'biopsy', 'endoscopic biopsy']

gene expression analysis
mutation analysis
polymorphism analysis
laboratory biomarker analysis
biopsy
endoscopic biopsy

['Colorectal Cancer', 'Esophageal Cancer']


Aprepitant Versus Ondansetron in Preoperative Triple-therapy Treatment of Nausea and Vomiting

Summary: This study is being done to determine the efficacies of two preventative drug combinations for postoperative nausea and vomiting in patients undergoing neurosurgery. The aim of this study is to compare the efficacy of using aprepitant instead of ondansetron in combination with dexamethasone and promethazine for post-operative nausea and vomiting prophylaxis. By completing this comparison study investigators will determine the most efficacious drug combination which will allow us to enhance the overall comfort and satisfaction of neurosurgical patients in the immediate postoperative period.
Inclusion criteria: inclusion criteria:

 Adult patients

 18 to 85 years of age

 Scheduled for neurosurgery requiring opening of the cranium and dura at Ohio State University Medical Center and who consent in writing to participate in this study are eligible.

Exclusion criteria: :

 Patients will be excluded from this study if they are

 prisoners

 pregnant women

 mentally ill

 under the age of 18 or over the age of 85

 American Society of Anesthesiologist (ASA) classification V

 alcohol or drug abusers

 have a cerebral perfusion pressure (CPP) greater than 150 mmHg or less than 50 mmHg.

['Aprepitant', 'Ondansetron', 'Promethazine', 'Dexamethasone']

Aprepitant Ondansetron Promethazine Dexamethasone

['Postoperative Nausea and Vomiting (PONV)', 'Nausea']