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Directed self-assembly (DSA) of block copolymers is an emergent technique for nano-lithography, but is limited in the range of structures possible in a single fabrication step. Here we expand on traditional DSA chemical patterning. A blend of lamellar- and cylinder-forming block copolymers assembles on specially designed surface chemical line gratings, leading to the simultaneous formation of coexisting ordered morphologies in separate areas of the substrate. The competing energetics of polymer chain distortions and chemical mismatch with the substrate grating bias the system towards either line/space or dot array patterns, depending on the pitch and linewidth of the prepattern. This is in contrast to the typical DSA, wherein assembly of a single-component block copolymer on chemical templates generates patterns of either lines/spaces (lamellar) or hexagonal dot arrays (cylinders). In our approach, the chemical template encodes desired local spatial arrangements of coexisting design motifs, self-assembled from a single, sophisticated resist.

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This is the era of image-guided surgery and molecular neurosurgery for brain tumors; it is a time that promises to do for cerebral cortical tumors what microsurgery did for skull base tumors in the last generation. It should carry the precision and effectiveness of surgery far beyond anything dreamed of by Cushing and the early pioneers.

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Self-assembled devices composed of periodic arrays of 10-nanometer-diameter cobalt nanocrystals display spin-dependent electron transport. Current-voltage characteristics are well described by single-electron tunneling in a uniform array. At temperatures below 20 kelvin, device magnetoresistance ratios are on the order of 10%, approaching the maximum predicted for ensembles of cobalt islands with randomly oriented preferred magnetic axes. Low-energy spin-flip scattering suppresses magnetoresistance with increasing temperature and bias-voltage.

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We show a simple, robust, chemical route to the fabrication of ultrahigh-density arrays of nanopores with high aspect ratios using the equilibrium self-assembled morphology of asymmetric diblock copolymers. The dimensions and lateral density of the array are determined by segmental interactions and the copolymer molecular weight. Through direct current electrodeposition, we fabricated vertical arrays of nanowires with densities in excess of 1.9 x 10(11) wires per square centimeter. We found markedly enhanced coercivities with ferromagnetic cobalt nanowires that point toward a route to ultrahigh-density storage media. The copolymer approach described is practical, parallel, compatible with current lithographic processes, and amenable to multilayered device fabrication.

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BACKGROUND: Children with high-risk neuroblastoma have a poor outcome. In this study, we assessed whether myeloablative therapy in conjunction with transplantation of autologous bone marrow improved event-free survival as compared with chemotherapy alone, and whether subsequent treatment with 13-cis-retinoic acid (isotretinoin) further improves event-free survival. METHODS: All patients were treated with the same initial regimen of chemotherapy, and those without disease progression were then randomly assigned to receive continued treatment with myeloablative chemotherapy, total-body irradiation, and transplantation of autologous bone marrow purged of neuroblastoma cells or to receive three cycles of intensive chemotherapy alone. All patients who completed cytotoxic therapy without disease progression were then randomly assigned to receive no further therapy or treatment with 13-cis-retinoic acid for six months. RESULTS: The mean (+/-SE) event-free survival rate three years after the first randomization was significantly better among the 189 patients who were assigned to undergo transplantation than among the 190 patients assigned to receive continuation chemotherapy (34+/-4 percent vs. 22+/-4 percent, P=0.034). The event-free survival rate three years after the second randomization was significantly better among the 130 patients who were assigned to receive 13-cis-retinoic acid than among the 128 patients assigned to receive no further therapy (46+/-6 percent vs. 29+/-5 percent, P=0.027). CONCLUSIONS: Treatment with myeloablative therapy and autologous bone marrow transplantation improved event-free survival among children with high-risk neuroblastoma. In addition, treatment with 13-cis-retinoic acid was beneficial for patients without progressive disease when it was administered after chemotherapy or transplantation.

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PURPOSE: The goal of this study was to determine the incidence of metastatic sites in neuroblastoma and the extent to which metastatic sites correlate with age, tumor biology, and survival. PATIENTS AND METHODS: All 648 patients with stage IV and IVS neuroblastoma registered on Children's Cancer Group protocols 3881 and 3891 were analyzed. Metastatic site data were provided by treating institutions and reviewed in patients with central nervous system (CNS), intracranial, lung, or "other" metastases. RESULTS: The incidence of metastatic sites at diagnosis was 70.5% in bone marrow, 55.7% in bone, 30.9% in lymph nodes, 29.6% in liver, 18.2% in intracranial and orbital sites, 3.3% in lung, and 0.6% in CNS. Event-free survival (EFS) was decreased in patients with bone, bone marrow, CNS, intracranial/ orbital, lung, and pleural metastases, and improved in those with liver and skin metastases. In infants, MYCN amplification and unfavorable Shimada histopathology correlated with increased frequencies of bone and intracranial or orbital metastases. In older patients, MYCN amplification correlated with increased frequencies of intracranial or orbital, liver, and lung metastases. Multivariate analysis revealed that metastatic site is not an independent prognostic factor. CONCLUSIONS: Metastatic pattern in neuroblastoma differs with age and correlates with tumor biological features and EFS. These correlations could reflect changes in host or tumor biological features with age resulting in differences in metastatic capacity or tumor affinity for specific sites.

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BACKGROUND: Endoscopic retrograde cholangiography is the most commonly utilized tool for the identification of common bile duct stones (CBDS) before laparoscopic cholecystectomy, whereas the role of magnetic resonance cholangiography (MRC) for patient evaluation before laparoscopic cholecystectomy is currently undefined. METHODS: We prospectively evaluated the efficacy of MRC for the identification of CBDS among patients with high risk for choledocholithiasis. Patient selection was based on clinical, sonographic, and laboratory criteria. Standard cholangiograms were obtained when possible for verification of MRC results. RESULTS: Ninety-nine patients underwent evaluation with preoperative MRC. CBDS was visualized in 30% of patients. MRC sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 85%, 90%, 77%, 94%, and 89%, respectively. CONCLUSIONS: MRC is useful for the evaluation of patients with suspected choledocholithiasis. Advantages of MRC include its noninvasive nature, ease of application, and accuracy in identifying and estimating the size of CBDS. Application of MRC in this setting reduces the need for diagnostic endoscopic retrograde cholangiography. Future investigations should be directed at the development of cost-effective utilization strategies for MRC application.

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BACKGROUND/PURPOSE: Pediatric truncal vascular injuries are rare, but the reported mortality rate is high (35% to 55%), and similar to that in adults (50% to 65%). This report examines the demographics, mechanisms of injury, associated trauma, and results of treatment of pediatric patients with noniatrogenic truncal vascular injuries. METHODS: A retrospective review (1986 to 1996) of a pediatric (< or = 17 years old) trauma registry database was undertaken. Truncal vascular injuries included thoracic, abdominal, and neck wounds. RESULTS: Fifty-four truncal vascular injuries (28 abdominal, 15 thoracic, and 11 neck injuries) occurred in 37 patients (mean age, 14+/-3 years; range, 5 to 17 years); injury mechanism was penetrating in 65%. Concomitant injuries occurred with 100% of abdominal vascular injuries and multiple vascular injuries occurred in 47%. Except for aortic and one SMA injury requiring interposition grafts, these wounds were repaired primarily or by lateral venorrhaphy. Nonvascular complications occurred more frequently in patients with abdominal injuries who were hemodynamically unstable (systolic blood pressure [BPS] <90) on presentation (19 major complications in 11 patients versus one major complication in five patients). Thoracic injuries were primarily blunt rupture or penetrating injury to the thoracic aorta (nine patients). Thoracic aortic injuries were treated without bypass, using interposition grafts. In patients with thoracic aortic injuries, there were no instances of paraplegia related to spinal ischemia (clamp times, 24+/-4 min); paraplegia occurred in two patients with direct cord and aortic injuries. Concomitant injuries occurred with 83% of thoracic injuries and multiple vascular injuries occurred in 25%. All patients with thoracic vascular injuries presenting with BPS of less than 90 died (four patients), and all with BPS 90 or over survived (eight patients). There were 11 neck wounds in 9 patients requiring intervention, and 8 were penetrating. Overall survival was 81%; survival from abdominal vascular injuries was 94%, thoracic injuries 66%, and neck injuries 78%. CONCLUSIONS: Survival and subsequent complications are related primarily to hemodynamic status at the time of presentation, and not to body cavity or vessel injured. Primary anastomosis or repair is applicable to most nonaortic wounds. The mortality rate in pediatric abdominal vascular injuries may be lower than previously reported.

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PURPOSE: To identify a biologically favorable and unfavorable subset of patients with Evans stage III neuroblastoma and to determine whether treatment stratification would improve the event-free survival (EFS) for high-risk patients and maintain excellent EFS for the lower-risk patients. PATIENTS AND METHODS: Risk stratification was performed by age, MYCN gene copy number, Shimada histopathologic classification, and serum ferritin level. Lower-risk patients were treated on the less intensive Children's Cancer Group (CCG)-3881, whereas high-risk patients were treated on CCG-3891, which included more intensive multimodality therapy and, in some cases, autologous bone marrow transplantation (ABMT). RESULTS: Of 228 Evans stage III patients entered onto the study, 92% also met the definition of International Neuroblastoma Staging System (INSS) stage 3. One hundred forty-three patients met the lower-risk criteria, which included 89 patients less than 1 year of age and 54 patients 1 year of age or greater, and favorable biology, whereas 85 patients were 1 year of age or greater and biologically unfavorable. Biologically unfavorable patients 1 year of age or greater who underwent gross surgical resection had improved survival, whereas the outcome of infants or biologically favorable older patients did not change according to resection. The EFS rate at 4 years was 100% for the patients with favorable biology of any age, 90% for those less than 1 year of age but with at least one unfavorable characteristic, and 54% for Evans stage III patients 1 year of age or greater with unfavorable biology. Age, ferritin level, MYCN copy number, Shimada histopathology, primary site, and intraspinal extension were significant univariate prognostic factors for all patients, but only MYCN copy number and age were independent factors in multivariate analyses. CONCLUSION: The excellent survival of the biologically favorable group and the historically improved EFS of the biologically unfavorable group suggest that biologic staging should be used to define the prognosis and treatment of stage III neuroblastoma.

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Currently, approximately 67% of children diagnosed with cancer can be expected to survive more than 5 years. Among the most significant late effects of cancer therapy is the development of second malignant neoplasm (SMN). This study was performed to identify the factors associated with the development of second malignant neoplasms after treatment for soft tissue sarcomas in childhood. Retrospectively the charts of 20 children who developed second malignant neoplasms after treatment for primary childhood soft tissue sarcoma were reviewed. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment, family histories (when available), and outcome were recorded. The mean age of the patients (10 boys, 10 girls) was 8.5 years of age (range, 1 to 20 years). Most primary tumors were rhabdomyosarcoma (14/20) and occurred in an extremity (10/20). Ninety percent of the patients (18/20) had a complete response to treatment of the primary cancer. Eleven out of 20 received combined chemotherapy and radiation therapy. The most common secondary malignancy was a bone sarcoma (6/20), followed by brain tumors (n = 3), leukemia (n = 2), and other sarcomas (n = 2). Four of the bone sarcomas developed in the field of radiation treatment. Median follow-up was 16 years (range, 1 to 26 years). The median time to development of a SMN was 11.4 years (range, 1.5 to 21 years). Survival after a second malignancy was only 30%. Two patients developed a third malignant neoplasm. The occurrence of a secondary malignancy represents a serious complication of childhood cancer. Certain tumors are related directly to treatment such as osteosarcoma within irradiated fields and secondary leukemias or lymphomas after certain chemotherapy regimens. Combined radiotherapy and chemotherapy may play an additive role in the development of second malignant neoplasms. Genetic factors may predispose affected patients to the development of both primary and secondary malignancies. Close surveillance of children previously treated for childhood cancers is warranted.

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BACKGROUND: As more children survive childhood cancers, the population at risk for second malignant tumors increases. The development of melanoma as a second malignant tumor is not well described. METHODS: The M.D. Anderson Cancer Center's 50-year experience with patients who developed melanoma after treatment of a childhood cancer was retrospectively reviewed. RESULTS: One hundred seventy-two patients with a second malignancy were identified; 11 patients had melanoma as a second malignancy. The most common first malignancies were Hodgkin's disease, brain tumors, and retinoblastomas. Melanoma developed in an irradiated field in 4 patients. Six patients had lymphatic or distant metastasis at diagnosis. Five of 11 patients died of melanoma. CONCLUSIONS: Factors contributing to melanoma as a second malignancy may include genetic factors and the effects of chemotherapy and radiation. Survivors of childhood malignancy should be considered at risk for developing melanoma, and suspicious pigmented lesions should be carefully evaluated.

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A case of Meckel's diverticulum causing intussusception in an 8-year-old boy is presented. The Meckel's diverticulum was detected by using a Tc-99m-labeled antigranulocyte monoclonal antibody MN3 (Leukoscan; Immunomedics, Morris Plains, NJ), which is under clinical evaluation for the detection of atypical appendicitis at the authors' institution. Pathologic evaluation confirmed Meckel's diverticulitis with ileal-ileal intussusception.

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Because malignant fibrous histiocytoma (MFH) rarely occurs in children, the natural history of this tumor and prognostic factors predictive of outcome have not been well described. The charts of all pediatric patients with MFH seen at M.D. Anderson Cancer Center were reviewed with respect presentation, treatment, and outcome, in an attempt to determine prognostic factors that are predictive of survival. Forty-four pediatric patients were identified. Extremities were the most common tumor site (31 of 44 patients). Five patients presented with angiomatoid histology subtype; all subsequently survived. The estimated 5-year survival rate was 85% for clinical group I patients, 87% for clinical group II, 53% for clinical group III, and 0% for clinical group IV. The estimated 5-year survival rate was 95% for patients with tumors of less than 5 cm in diameter and 45% for those with larger tumors. Overall, the estimated 5-year survival rate was 71%. Significant prognostic factors found to affect survival (by univariate analysis) were clinical group, tumor size, and recurrence. Gender and race were not significant predictors. The use of chemotherapy and radiation was not found to improve the chance of survival, but this most likely reflected the more frequent use of adjuvant therapy in patients with unresectable or high-grade tumors. Although adequate surgical resection continues to be the most effective treatment, investigation of adjuvant chemotherapy and radiation therapy on protocol is warranted.

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A case of traumatic rupture of a wandering spleen in a 5-year-old girl is presented. To our knowledge, this is the first reported case of such injury in a child. The splenic injury was managed nonoperatively. The etiology and management of wandering spleen is discussed.

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OBJECTIVES: Laparoscopic examination of the contralateral inguinal ring has recently been advocated to exclude contralateral hernia in young children. We report a modification using nondisposable cystoscopic equipment, which is quick and reliable. METHODS: Either an 8 or 10 F soft straight catheter or a cystoscope sheath is passed through the open hernia sac. Air is insufflated into the abdomen with a syringe. Once the pneumoperitoneum is completed, a 4-mm cystoscope lens (110 degrees) is used to inspect the contralateral ring. RESULTS: Twenty-four children between the ages of 6 weeks and 4 years (median, 6 months) underwent exploration for presumed unilateral inguinal hernia and laparoscopic examination of the contralateral inguinal ring. Thirteen patients (54%) had an open processus vaginalis and underwent contralateral inguinal herniorrhaphy. No false-positive or false-negative results were found, and there were no complications associated with the procedure. CONCLUSIONS: This method of laparoscopic examination of the contralateral inguinal ring using nondisposable cystoscopic equipment is rapid, safe, reliable, and cost effective in evaluating a contralateral patent processus vaginalis. Laparoscopic examination spares the need for formal surgical exploration in patients with a closed processus vaginalis.

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PURPOSE: To investigate the frequency, presentation, clinical management, and prognosis of appendiceal carcinoid tumors in children. METHOD: A review of our institution's experience over 50 years. RESULTS: Twenty-two patients below the age of 20 presented with appendiceal carcinoid tumor. The mean age at presentation was 14.6 years. Twelve patients presented with symptoms of appendicitis. No tumor was > 2.0 cm in size. Only 2 patients underwent resection beyond appendectomy. No patient had recurrent or metastatic carcinoid tumor, and all but 1 patient (who died of ovarian choriocarcinoma) are alive without evidence of carcinoid tumors 1.5 to 30 years after diagnosis. CONCLUSIONS: Appendiceal carcinoid tumors in children are rarely life-threatening and the incidence of large tumors (> 2.0 cm) is very low. The role of right hemicolectomy in large (> 2.0 cm) tumors is questionable in this age group.

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To evaluate the outcome of neonatal malignant solid tumors, we reviewed the records of 222 infants under the age of 1 year with malignant disease who were treated at the University of Texas M.D. Anderson Cancer Center over a 40-year period. Forty-five cases of neonatal (< 30 days old at the time of presentation) malignancies were found. Thirty-two infants had solid tumors and form the basis of this report. Diagnoses included soft tissue sarcoma (13), brain tumor (5), neuroblastoma (6), retinoblastoma (3), malignant melanoma (2), hemangiopericytoma (2), and nephroblastoma (1). The mean age at which initial signs and symptoms were noted was 9 days of life. Fifty-nine percent (19) presented within the first week of life, and 47% (15) presented at birth. The mean age at histological diagnosis was 54 days. The head and neck region was the most common site (18), followed by trunk (9), and extremities (5). Thirty-one patients underwent surgical resection of the primary tumor. Thirteen of those neonates received no additional chemotherapy and/or radiation therapy, whereas 18 received some combination of surgery plus perioperative chemotherapy and/or radiation therapy. Overall survival was 78% (25 of 32) with an average follow-up of 8 years (range, 2 months to 29 years). There were no survivors among those patients with distant metastatic disease at the time of diagnosis. Despite delays, prognosis is excellent in the absence of distant metastatic disease, particularly for extracranial tumors.

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