First GPS Baseline Results from the North Andes

The CASA UNO GPS (Global Positioning System) experiment (January-February 1988) has provided the first epoch baseline measurements for the study of plate motions and crustal deformation in and around the North Andes. Two dimensional horizontal baseline repeatabilities are as good as 5 parts in 108 for short baselines (100-1000km), and better than3 parts in 108 for long baselines (\u3e1000km). Vertical repeatabilities are typically 4 -6 cm, with a weak dependence on baseline length. The expected rate of plate convergence across the Colombia Trench is 6-8 cm/yr, which should be detectable by the repeat experiment planned for 1991. Expected deformation rates within the North Andes are of the order of 1 cm/yr, which may be detectable with the 1991 experiment

Cytogenetic Prognostication Within Medulloblastoma Subgroups

PURPOSE: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. PATIENTS AND METHODS: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. RESULTS: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. CONCLUSION: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials

Budget scoring of alternative financing methods for defense requirements

MBA Professional ReportThis research investigates procurement scoring and the Department of Defense's (DoD) use of alternative financing methods, such as leases and public-private ventures. One of the major impediments to using alternative forms of procurement financing for acquiring defense capabilities is in the budgetary treatment, or "scoring," of these initiatives by the Congressional Budget Office (CBO), the Office of Management and Budget (OMB) and the congressional Budget Committees. The current scoring policy that has been applied to many initiatives essentially negates the financial advantage for using alternative forms of financing. Therefore, this research examines existing policies and their adherence to statutes and the role of the various government organizations and committees in actual recording of obligations and outlays related to financing alternatives used by federal agencies. Preliminary evidence suggests that this emerging area has major importance for future DoD acquisitions in a resource-constrained environment. Included are recommendations for changes in budgetary scoring that encompass the full scope of federal obligations and expenditures while promoting efficient, more rapid and fiscally responsible acquisitions.http://archive.org/details/budgetscoringofl1094510247Approved for public release; distribution is unlimited

The Budget Scoring Alternatives Financing Methods for Defense Requirements

4th Annual Acquisition Research Symposium of the Naval Postgraduate School: Acquisition Research: Creating Synergy for Informed ChangeThis research investigates procurement scoring and the Department of Defense’s (DoD) use of alternative financing methods, such as leases and public-private ventures. One of the major impediments to using alternative forms of procurement financing for acquiring defense capabilities is in the budgetary treatment, or “scoring,” of these initiatives by the Congressional Budget Office (CBO), the Office of Management and Budget (OMB) and the congressional Budget Committees. The current scoring policy that has been applied to many initiatives essentially negates the financial advantage for using alternative forms of financing. Therefore, this research examines existing policies and their adherence to statutes and the role of the various government organizations and committees in actual recording of obligations and outlays related to financing alternatives used by federal agencies. Preliminary evidence suggests that this emerging area has major importance for future DoD acquisitions in a resource-constrained environment. Included are recommendations for changes in budgetary scoring that encompass the full scope of federal obligations and expenditures while promoting efficient, more rapid and fiscally responsible acquisitions.Prepared for: Naval Postgraduate School, Monterey, California 93943Approved for public release; distribution is unlimited

First GPS Baseline Results from the North Andes

The CASA UNO GPS (Global Positioning System) experiment (January-February 1988) has provided the first epoch baseline measurements for the study of plate motions and crustal deformation in and around the North Andes. Two dimensional horizontal baseline repeatabilities are as good as 5 parts in 108 for short baselines (100–1000 km), and better than 3 parts in 108 for long baselines (\u3e1000 km). Vertical repeatabilities are typically 4–6 cm, with a weak dependence on baseline length. The expected rate of plate convergence across the Colombia Trench is 6–8 cm/yr, which should be detectable by the repeat experiment planned for 1991. Expected deformation rates within the North Andes are of the order of 1 cm/yr, which may be detectable with the 1991 experiment

Subgroup-specific structural variation across 1,000 medulloblastoma genomes.

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy