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BLOOD SAMPLING: Blood samples are collected using two sampling methods at different time points (indicated on the timeline above); DBS sampling (max 39 samples/patient) and venous blood sampling (max 13 samples/patient). Venous blood sampling will be performed during a standard outpatient clinic in one of the participating centres, and forwarded to the Laboratory for Therapeutic and Diagnostic Antibodies in Leuven for further analyses. DBS samples will be send directly to the Laboratory for Therapeutic and Diagnostic Antibodies in Leuven through classical mailing. DBS sampling will be performed by the patient during the outpatient clinic (at same moment as venous punctures, max 13 samples/patient) and at home for the intermediate values (max 26 samples/patient). Patients will be taught how to perform a finger prick during the outpatient clinic. A conversion factor will be defined. Determination of concentration-time profile and exposure of golimumab in the individual patients will be performed by intensive sampling for 3 to 4.5 months. Time point of max concentration, intermediate concentration, and trough concentration will be determined in each patient. Note: A similar procedure will be adopted to measure free anti-golimumab antibody concentrations on the DBS using a drug sensitive assay. Free anti-golimumab antibody concentrations will be measured when the serum golimumab concentration is below limit of quantification. MEASUREMENT OF GOLIMUMAB AND ANTI-GOLIMUMAB ANTIBODY CONCENTRATIONS: Golimumab concentrations will be measured using a sandwich type ELISA, in which golimumab is captured between an immobilized monoclonal antibody towards golimumab (MA-GLM) 171D8 and an added horseradish peroxidase (HRP)-labeled MA-GLM159B8. The assay was developed and validated, analytically (external and internal) and clinically, as described by Detrez et al. Golimumab concentrations will be measured on every sample. Free anti-golimumab antibody concentrations will be measured using a drug sensitive assay. Total anti-golimumab antibody concentrations will be measured using a drug tolerant assay. Development and validation (analytical + clinical) of these assays is described by Detrez et al. Total anti-golimumab antibody concentrations will be measured on every venous sample. Free anti-golimumab antibody concentrations will be measured when the serum golimumab concentration is below limit of quantification on both venous sample and DBS sample (based on adalimumab serum concentrations measured in by our laboratory, we expect that 11% of samples measured within the first year of treatment have an undetectable golimumab concentration). BASELINE CHARACTERISTICS: - Baseline characteristics will include: sex, age at diagnosis, weight, body mass index, disease extent, smoking status (never, ex, active), primary sclerosing cholangitis, haemoglobin, serum albumin, and C-reactive protein - Previous medical characteristics will include previous use of mesalamine, steroids, immunosuppressive agents, ciclosporin, infliximab, adalimumab, vedolizumab, … - Current medical characteristics will include use of mesalamine, use of steroids (dosing, duration since initiation), use of immunosuppressive agents (dosing, duration since initiation), use of golimumab (dosing, duration since initiation, last dose), … QUESTIONNAIRE REGARDING PATIENT FRIENDLINESS: • At the end of the study the participants will be requested to fill out a questionnaire regarding the patient friendliness of the dried blood spot (DBS) methodology This retrospective multi-centric Belgian prospective trial will involve 10 patients initiating or under maintenance subcutaneous golimumab therapy for moderate-to-severe colitis at the University Hospitals Leuven (Leuven, Belgium) or AZ Groeninge (Kortrijk, Belgium) Patients will (have) receive(d) standard induction therapy with golimumab 200mg at week 0, and golimumab 100mg at week 2. Maintenance therapy will (have) start(ed) at week 6, with 50 or 100mg of golimumab every 4 weeks, depending on body weight (50mg every 4 weeks for patients with a body weight of less than 80kg, and 100mg for the others) Patients will come to the hospital for clinical evaluation, blood sampling and golimumab administration following daily clinical practice. The patients will be requested to perform several dry blood spot analyses at home.

A Validated questionnaire the Female Sexual Function Index (FSFI) and total vaginal lengths will be used to evaluate patients pre-operatively, at 4-6 weeks post-operatively, and 6 months post operatively. The FSFI will also be sent to the patient 12 months post operatively. These data will be used to assess sexual function and total vaginal length in patients undergoing minimally invasive hysterectomy. The study endpoint will occur after the 12 month follow-up questionnaire. Additionally, all complications following surgery will be tracked over the study period for comparison. The purpose of this study is to evaluate the possible impacts of two techniques of vaginal cuff closure during robotic hysterectomy. We aim to compare vertical vs horizontal vaginal cuff closure and the impact that these techniques have on vaginal length, sexual function, and overall complication rates.

Organ response to anti-plasma cell therapy in AL amyloidosis tends to lags behind hematologic response as chemotherapy may not clear pre-formed organ amyloid. Doxycycline has been shown to have inhibitory effects on amyloid fibril formation as well as de-fibrillogenic effects and shown to be beneficial in in vitro, murine models and other preclinical studies. The investigators will prospectively evaluate the safety and efficacy of doxycycline in AL amyloidosis patients when used in conjunction with anti-plasma cell chemotherapy. In this study the investigators want to find out more about the addition of the antibiotic, doxycycline, to standard anti-amyloid therapy in people with amyloidosis. The investigators want to find out whether doxycycline improves the response to standard anti-amyloid therapy and whether it causes any problems (side effects).

As part of the Prehospital Stroke Study at the Universitair ziekenhuis Brussel (PreSSUB) project, the investigators have developed and tested several prototypes for prehospital telemedicine. The current system consists of commercially available hardware and a Web-based telemedicine platform. The data are transmitted to a multimedia server unit over a mobile (ultra)broadband connection (3G or 4G). Data privacy is secured by password-protected logins, role-based access control, and hypertext transfer protocol secure encryption. The results of a feasibility study using the 4G network in healthy volunteers have been reported and feasibility data using the 3G network in healthy volunteers are available (unpublished data). The investigators recently evaluated the safety, technical feasibility and reliability of in-ambulance telemedicine in patients during emergency missions by a Paramedic Intervention Team of the Universitair Ziekenhuis Brussel (Feasibility study on AmbulanCe-based Telemedicine, FACT) and yielded satisfactory results (paper under review, trial registered at clinicaltrials.gov: NCT02119598). Telestroke consultations should include standardized evaluation of key stroke features, which can be obtained by application of validated clinical scales (e.g. Glasgow Coma Scale for evaluation of consciousness). Prehospital assessment of stroke severity remains challenging and inspired researchers to develop adapted scales, among which the Unassisted TeleStroke Scale (UTSS). The UTSS has shown to be a rapid, simple, quantitative measure for the evaluation of stroke severity through telemedicine, without need for assistance from a third party at the patient's bedside. Moreover, it has been shown that this scale can be used for ambulance-based telemedicine for emergent patient transportation. The PreSSUB trial I builds further on the reassuring data obtained in a general patient population during emergency missions in the FACT study and will focus on prehospital telemedicine for patients with suspicion of acute stroke only. The PreSSUB trial I will focus on prehospital telemedicine for patients with suspicion of acute stroke. The study is designed as a prospective monocentric observational trial on the safety, feasibility and reliability of in-ambulance telemedicine for patients with suspicion of acute stroke during transportation by the Paramedic Intervention Team of the Universitair Ziekenhuis Brussel.

There are limited data from Thailand on the aetiology of LRTI but no data on mortality of hospitalised children. Thai children < 1 year accounted for circa one third of LRTIs in children who were treated as out or inpatients in whom influenza was isolated in 6 (2.7%) of 271 children and RSV in 44 (20%). At the Queen Sirikit hospital, Bangkok, influenza A and B and RSV accounted for approximately 11% (9/80), 2.5% (2/80) and 6% (5/80) of children < 1 year, respectively. This study included children with underlying diseases like congenital heart disease and chronic lung disease. A small laboratory series of 110 children at Siriraj hospital with LRTIs infections (Pilaipan Puthavathana, personal communication) identified RSV A/B (17%), metapneumovirus (14%), parainfluenza 1 (12%) and adenovirus (12%), influenza B (6%), influenza A (4%), coronaviruses (3%), Parainfluenza 3 (2%) and 2 (0%). The number of drugs registered for treating influenza is limited to oral Oseltamivir, amantadine and rimantadine and inhaled zanamivir. As a result of the 2009 influenza A/H1N1, clinical guidelines have been updated to include children less than one years old . However, regulatory studies of oseltamivir excluded children under 1 year based on preclinical data in rats in which there were deaths in young rats (7 days old) but none in 14 days old rats given large doses of Oseltamivir. Higher concentrations of Oseltamivir were found in the brains of the younger rats which was thought to be due immaturity of the blood brain barrier. There is, however, some clinical experience with Oseltamivir in the under ones from Japan, Thailand, Germany , the USA , and additional experience with 2009 pH1N1 . The doses used were 2 mg/kg bid which is consistent with the dose recommended in the UK for children who weigh less than 15 kg (30 mg bid for 5 days). At the Queen Sirikit hospital, Oseltamivir has been given to a very small number of children < 1 year with severe influenza with good effect (T. Chotpitayasunondh, unpublished observations). This experience is similar to that of others i.e. good clinical outcomes and apparently good tolerability. An Oseltamivir pharmacokinetic study in children age 1-5 years showed that the dose of 2 mg/kg resulted in plasma-concentration time curves (AUC) similar to the AUC accepted in adult. However, the younger the child, the lower the AUC level; never the less, there are still insufficient pharmacokinetics data in children under one year . The clinical significance of reduced in vitro sensitivity is unclear owing to the paucity of human data but these mutations are likely to result in reduced antiviral efficacy of Oseltamivir and the adamantanes against H1N1. Furthermore, amantadine treatment of influenza frequently results in the rapid development of amantadine resistance in both H1N1 and H2N3 viruses, resulting in continued virus replication, thus, making this drug less than ideal for treating influenza. Currently, there is limited adamantane resistant H1N1 but widespread adamantane resistant in H3N2. H3N2 and influenza B remain sensitive to Oseltamivir. The adamantanes have no activity against influenza B. The emergence of resistance poses difficulties for the treatment of influenza in children less than one but oseltamivir represents at present the optimal choice for treating such children. Therefore, this protocol will assess the effect of oral Oseltamivir at doses recommended by the WHO to see if they are applicable to Thai children. Currently, there is no treatment for children less than one year of age with influenza related lower respiratory tract infection that is either considered standard or registered in any country. This dismal scenario exists even though influenza related LRTI is a significant illness causing morbidity and mortality, especially in children less than 6 months of age. Avian influenza has been reported rarely in children less than one. There are no data in Vietnam and very few data in Thailand on the burden of influenza in children less than one. This young age group suffers high mortality. Oseltamivir may be beneficial in such children. This is basis of this trial.

Design: multidisciplinary and multicentre randomized controlled trial Study population/inclusion criteria : all women, not previously operated for stress incontinence, seeking help for urinary stress incontinence where conservative therapy in particular physiotherapy has failed and are opting and candidates for surgical therapy will be asked to participate in our study. Incontinence must have been demonstrated on physical examination and/or micturition diary. Patients can be included by gynaecologists or urologists who are cooperating in the study. Intervention: consists of the non performance of urodynamics in the studygroup. The control group will undergo urodynamics as is at present the norm. In all patients the next items will be recorded at inclusion: 1. History and clinical examination 2. 48h-Bladder(voiding and incontinence) diary, 3. 48h-Pad test 4. Validated Quality of Life questionnaires (SF 36, Euroqol 5D, UDI, IIQ) 5. Urinalysis for the detection of urinary tract infection. 6. Residual urine measured by ultrasound. At this point an interim decision will be made for surgery. At that moment patients are informed about the study. After obtaining informed consent the patients are randomly assigned to undergo urodynamic testing or not. In the study group the decision for intervention will be based on the history and clinical examination only and will be the same as the interim decision which is surgery. In the control group this decision will be based on history and clinical examination IN COMBINATION with the result of the urodynamic testing. It can be a decision to proceed with surgery (estimated at 2/3rd of the women) or conservative usually medication. The T0(moment of intervention) is defined as the moment of the first intervention which is by definition surgery in the study group and either surgery or conservative in the control group. After the intervention additional therapy is possible in both arms. The follow-up period will be 24 months after T0 , in which the same parameters as pre-operative will be assessed. These items will be assessed at: 6 weeks post intervention (PI) 3 months PI 6 months PI 12 months PI 24 months PI Urodynamics, in the control group, will be performed according to ICS standards and consist of free flow, fillingscystometry, pressure flow study and a urethral pressure profilometry in rest and during stress. The outcomes will be matched to urodynamic findings to indicate the possible useful parts of the urodynamic findings. Post operative urodynamics is NOT part of the study. The primary outcome of this study is the improvement of Urogenital Distress Inventory (UDI) at 24 months after baseline and the power calculation is performed using the non-inferiority assumption. The mean improvement in UDI in both groups is expected to be 35 with standard deviation 10.(22) A difference in mean improvement of 8 or less is considered non-inferior. As this condition is allowed for one third of the total group (those women in the non-UDI group, who would not have been operatively treated), this results in a difference in mean improvement of 2.7 or less between the UDI and non-UDI group. Then effectively 130 women in each group are needed to reach a power of 70% using one-sided testing at 0.05. Considering an expected percentage lost to follow up of ca. 10%, in total 290 women (145 in each group) will be included in this study. Multivariate analysis of covariance with group, centre and the baseline covariate as independent variables will be used to estimate differences in improvement of the UDI after 24 months between the groups with 95% confidence intervals. As the UDI is skewed, data will be logtransformed prior to analysis. Other variables (ie Incontinence Impact Questionnaire) will be analysed similar. Economic evaluation: For each patient, utilisation of health care services will be recorded prospectively, using Case Record Forms, including urodynamic testing, surgery for SUI, re-operations, medical treatment for detrusor instability, care for urinary incontinence, and care for urinary retention. By multiplying these volumes of care with unit cost prices, direct medical costs incurred by SUI during the follow up period will be calculated for each patient. For unit cost prices, national guidelines will be used (CVZ, 2004). For costs of care for urinary incontinence and urinary retention, data from the literature will be used, converted to 2006 prices. We incorporated the health related quality of life questionnaire euroqol 5D in our study to be able to calculate QALYs (quality-adjusted life-years), which is a measure of health outcomes. A QALY is the change in quality of life induced by the treatment multiplied by the duration of the treatment effect and it provides the number of QALYs gained. QALYs can then be related to medical costs to arrive at a final common denominator of cost/QALY. This parameter can be used to compare the cost-effectiveness of the treatment. To test the value of preoperatively performed urodynamics with regard to outcome of surgery for stress urinary incontinence (SUI) and to examine whether not performing urodynamics preoperatively is more cost effective than performing urodynamics preoperatively using the non-inferiority assumption.

All consecutive patients who had their first-ever ischemic stroke symptoms within the previous month will be asked to enroll in the study. Baseline measurements will be assessed in all patients. Patients without language problems or life-threatening conditions will be asked to answer the structured lifestyle questionnaire. Age- and sex-matched controls without a stroke history will be recruited among patients' friends, relatives and the care-givers of other patients, and will be requested to complete the same questionnaire. People who visit hospital for health check-ups may also be included as controls. After the first assessment, all patients will be followed every 3 months during visits to the outpatient department or by telephone. Participants will be asked about recurrence of stroke, occurrence of post-stroke epilepsy, and functional outcomes on the modified Rankin Scale. In the case of patients who have died, information will be obtained from their last practitioner or care-giver. Sample size and power calculation. The sample sizes were calculated based on the frequency of psychological distress, which is the most interesting potential risk factor for ischemic stroke in the young. According to a previous report comparing psychological distress in ischemic stroke patients and healthy controls,8 the frequency of stress was 50.3% in the ischemic stroke patients and 38.6% in the healthy controls; a difference of 11.7%. To detect such a difference with a power of 90% and alpha of 0.05 with a drop-out rate of 20%, a sample size of at least 470 patients and 470 controls will be needed (PASS 13). Clinical information. Demographic and clinical information will be collected on admission.The data include age, gender, traditional risk factors for stroke (hypertension, diabetes, hyperlipidemia, smoking and coronary heart disease), medication history (anti-hypertensives, anti-diabetics, anti-platelets and statins) and other comorbidities. Hypertension is defined as previous use of antihypertensive medication, systolic blood pressure ≥140 mmHg or diastolic BP ≥90 mmHg at discharge, diabetes as previous use of antidiabetic medication or fasting blood glucose ≥126 mg/dL, and hyperlipidemia as previous use of lipid-lowering agents, fasting serum total cholesterol ≥240 mg/dL or low-density lipoprotein ≥160 mg/dL. With regard to cigarette smoking, subjects will be classified as current, former, or non-smokers. Number of pack-years will be noted for former and current smokers. History of coronary heart disease is defined as previous angina pectoris, myocardial infarction, or coronary artery bypass grafting. Patients will also be asked about any other comorbid diseases. Stroke characteristics and laboratory investigations. Data on stroke characteristics will be collected at admission, including symptoms at time of onset and pre-hospital delay. Severity of stroke will be measured on the National Institutes of Health Stroke Scale (NIHSS) by physicians certified by the Clinical Research Center for Stroke in Korea. The course of the disease during admission will be established, including treatments and complications. On discharge, each case of ischemic stroke will be classified according to the TOAST classification. Modified Rankin Scale (mRS) and Barthel index scores will also be obtained at discharge. Laboratory investigations including complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, urinalysis, urine pregnancy test, serum electrolytes, liver function test, renal function tests, chest X-ray and electrocardiogram will be checked in the emergency department. Other specific laboratory investigations such as fasting blood glucose, hemoglobin A1C, lipid panel test, thyroid function test, rheumatologic panel tests, hypercoagulable panel tests, heavy metal tests, homocysteine and α-galactosidase will be checked on the day after admission, following overnight fasting. For the genetic test for CADASIL, investigators will ask for a further informed consent. All patients will undergo cardiac evaluation during the admission period, including 24-hour Holter monitoring, transthoracic echocardiography and transesophageal echocardiography. Neuroimaging. Brain imaging studies will be interpreted by more than one neuro-radiologist at each center without any knowledge of the clinical information. Standardized magnetic resonance image (MRI) sequences will be recommended to all participating centers. The minimal requirements for brain imaging studies are diffusion-weighted images, FLAIR images, T2-weighted images, and gradient echo images. All participants will undergo additional vascular imaging studies such as CT angiography, MR angiography or digital subtraction angiography. Based on the neuroimaging, ischemic stroke location, size and vascular territories will be noted. The diagnosis and treatment of stroke will follow the standard guidelines of each coordinating center. Life style questionnaires. After making the baseline measurements, a standardized life style questionnaire will be provided to all patients who do not have a language problem. Age- and sex-matched healthy controls will be asked the same questions. The standardized questionnaire again requests demographic data such as age, gender, height, weight, abdominal circumference, traditional risk factors, medication history and other comorbidities. Newly-added demographic data include family history of risk factors, ABO type, marital status, living status, economic status, educational status and presence of pain and headache. Marital status is classified as married, single, divorced or widowed. Living status is classified as alone, with spouse, with family, or with non-family member. Economic status is classified into five categories (500 USD/month, 500~1500 USD/month, 1500~3000 USD/month, 3000~5000 USD/month and >5000 USD/month) and educational status is classified into six categories (none, 12 years). Questions about headaches are mainly focused on migraine: headache character, location, frequency, duration, aura, aggravating factors, medication history and family history. Only women will answer questions about obstetric history in terms of age at menarche and menopause (if participants have experienced them), use of oral contraceptives, history of hormone replacement therapy, and history of hysterectomy or oophorectomy. Women who have experienced pregnancy are asked about gravidity, number of children, years of births, mode of delivery, duration of maternal lactation, and number of miscarriages or abortions. Lifestyle factors such as alcohol consumption, dietary habits, exercise and sleep patterns are included in the questions. Alcohol consumption is defined as type of alcoholic drink, amount per day and date when consumption began. Dietary habits include meal frequency and consumption of salts, meats, vegetables and 7 types of beverages (coffee, black tea, oolong tea, green tea, ginseng tea, fruit juice and carbonated beverage) during the past year. Exercise will be calculated according to the International Physical Activity Questionnaire (IPAQ), which is a standardized instrument for measuring the amount of exercise.9 Duration of sleep, sleep latency, frequency of waking-up after sleep onset (WASO), snoring severity, duration of naps, history of using sleeping pills and length of time in bed without sleeping will be reported to evaluate sleep patterns. Investigators will also add the validated Korean version of the Epworth Sleepiness Scale for measuring daytime sleepiness,10 and questions about restless leg syndrome. Psychological distress will be analyzed by a composite measure of occupational distress, perceived stress, and depression. For occupational distress, both occupational status and job strain will be analyzed. Not only occupation type but also period of service in the current and previous occupation will be noted to evaluate occupational status. Average daily working hours, commuting method (car, bus, subway, walk or other) and commuting time (less than 30 minutes, 30 minutes to 1 hour, 1 hour to 2 hours or more than 2 hours) will also be recorded. Job strain will be investigated by means of a job content questionnaire (JCQ) validated in the Korean language. Perceived stress and depression will be answered on the basis of premorbid status. The Perceived Stress Scale (PSS) and Center of Epidemiologic Studies Depression scale (CES-D) Korean version, which have been validated in the relevant fields, will be used to measure the subjective status of patients and controls. Statistical analysis. The study will comprise 470 case-control pairs. Means with standard deviations will be calculated for continuous variables, and numbers with percentages will be obtained for discrete variables. To assess the relationship between characteristics and ischemic stroke in young adults, investigators will use paired t-tests for continuous variables and chi-square tests for proportions. For nonparametric variables, the Mann-Whitney U test will be used. Conditional logistic regression analysis will be employed to assess differences between cases and matched controls by estimating odds ratios (ORs) and 95% confidence intervals (CIs). Adjusted ORs for risk factors will be derived from multivariable logistic regression models. These will include all collected variables with possible significance. Kaplan-Meier survival analysis will be used to estimate cumulative risk of mortality, recurrent vascular events and post-stroke seizure. Hazard ratios for the previously-mentioned secondary objectives will be calculated by Cox regression analysis, and assumptions of proportionality will be confirmed by time-dependent covariate analysis. All the statistical analyses will be two-sided and will use IBM SPSS 21. The main objective of this study is to determine the risk factors and etiologies of ischemic stroke in Korean young adults. Both well-documented risk factors and little known life-style related risk factors such as life-style habits, psychological distress including occupational distress, perceived stress and depression will be evaluated by comparison with healthy controls using a structured questionnaire. Secondary objectives are to determine stroke outcomes such as mortality, recurrent vascular events and post-stroke epilepsy in these patients.

At the time of the inception of this study, there were no published randomized controlled trial on the efficacy of the Biopatch in reducing bloodstream infections. Preliminary data has shown that the Biopatch decreases colonization of the catheter exit site and thereby decrease bloodstream infections but this was at that time only theoretical. We proposed to perform a prospective randomized controlled trial to study the effect of the use of a commercially-available chlorhexidine-impregnated sponge (Biopatch) as part of central venous catheter care on catheter-related bloodstream infections among patients in two Barnes-Jewish Hospital ICUs.

PRIMARY OBJECTIVES: l. To compare the overall survival of patients receiving bevacizumab plus everolimus and everolimus alone among patients with advanced renal cell carcinoma progressing after first line vascular epidermal growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) treatment. SECONDARY OBJECTIVES: I. To compare the progression-free survival and proportion who experience an objective response (defined as complete clinical response [cCR] + partial response [PR]) in patients with advanced renal cell carcinoma receiving bevacizumab plus everolimus and everolimus alone. II. To compare grade 3 or higher toxicity in patients receiving each treatment regimen. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive everolimus orally (PO) once daily (QD) on days 1-28. ARM II: Patients receive everolimus PO QD on days 1-28 and bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 8 weeks until disease progression and then every 6 months for up to 5.5 years. This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.

PRIMARY OBJECTIVES: I. To determine whether carboplatin radiosensitization increases long term event-free survival for high risk medulloblastoma/primitive neuroectodermal tumor (PNET) patients. II. To determine whether isotretinoin increases long term event-free survival for high risk medulloblastoma/PNET patients. SECONDARY OBJECTIVES: I. To compare residual disease response to radiation alone versus radiation plus carboplatin. II. To identify molecular prognostic indicators suitable for patient stratification in future trials. III. To evaluate the health-related quality of life (HRQOL) during phases of active treatment specific to treatment modalities. IV. To describe the neuropsychological functioning of the study population and to evaluate the relationship between neuropsychological status and health related quality of life. OUTLINE: Patients are randomized to 1 of 4 treatment arms. ARM I (standard chemoradiotherapy and standard maintenance therapy): CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD) five days a week for 6 weeks. Patients also receive vincristine sulfate intravenously (IV) over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim subcutaneously (SC) or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. ARM II (standard chemoradiotherapy plus carboplatin and standard maintenance therapy): CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm I. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm I. ARM III (standard chemoradiotherapy, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin): CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm I. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin orally (PO) twice daily (BID) on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm I maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. ARM IV (standard chemoradiotherapy plus carboplatin, standard maintenance therapy plus isotretinoin, and continuation therapy with isotretinoin): CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm II. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm III. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm III. After completion of study treatment, patients are followed up periodically for up to 10 years. This randomized phase III trial studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cisplatin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Isotretinoin may help chemotherapy work better by making tumor cells more sensitive to the drugs. Radiation therapy uses high-energy x-rays to kill tumor cells. Carboplatin may make tumor cells more sensitive to radiation therapy. It is not yet known which chemotherapy and radiation therapy regimen is more effective in treating brain tumors.