Smitten Hips: costs, complexities and consequences of hip fracture for 2552 Australian patients hospitalised in 2008–09. Analyses of linked Department of Veterans’ Affairs databases

This work describes hospital management and its aftermaths for a sample of 2552 elderly Australians with hip fracture. Administrative databases for hospital, residential aged care and community services were obtained from the Department of Veterans’ Affairs (DVA). Patient-level linkages within and between databases were enabled using unique code numbers assigned by DVA. An historical and epidemiological overview of Australian and international reports, with particular reference to declining age-related incidence includes a caseload projection for Australia to 2051 using national data in the public domain. Five specific research studies describe the total hospital stay for initial management, hospital-related cost (in 2009), the proportions of hospital stay due to acute care, rehabilitation and other reasons, and factors associated with greater use of resources. Mortality for this elderly population is shown at final hospital discharge, and at follow-up to 4 years, with determinant factors for these outcomes. The six Australian states used widely different hospital resources initial management but achieved very similar 12-month outcomes. Patients referred to rehabilitation incurred much higher total hospital costs, but likelihood of subsequent independent living was not improved. The Thesis demonstrates the necessity of data linkage for adequate analysis of services and outcomes for patients with complex condition

Smitten Hips: costs, complexities and consequences of hip fracture for 2552 Australian patients hospitalised in 2008–09. Analyses of linked Department of Veterans’ Affairs databases

This work describes hospital management and its aftermaths for a sample of 2552 elderly Australians with hip fracture. Administrative databases for hospital, residential aged care and community services were obtained from the Department of Veterans’ Affairs (DVA). Patient-level linkages within and between databases were enabled using unique code numbers assigned by DVA. An historical and epidemiological overview of Australian and international reports, with particular reference to declining age-related incidence includes a caseload projection for Australia to 2051 using national data in the public domain. Five specific research studies describe the total hospital stay for initial management, hospital-related cost (in 2009), the proportions of hospital stay due to acute care, rehabilitation and other reasons, and factors associated with greater use of resources. Mortality for this elderly population is shown at final hospital discharge, and at follow-up to 4 years, with determinant factors for these outcomes. The six Australian states used widely different hospital resources initial management but achieved very similar 12-month outcomes. Patients referred to rehabilitation incurred much higher total hospital costs, but likelihood of subsequent independent living was not improved. The Thesis demonstrates the necessity of data linkage for adequate analysis of services and outcomes for patients with complex condition

Selection of an alternative production part approval process to improve weapon systems production readiness

This thesis conducted an examination related to the Department of Defense (DOD) weapons systems production approval practices. Current practices result in poor weapons system production outcomes that reduce fleet readiness in DOD weapons systems acquisition. The Government Accountability Office (GAO) has reported concerns related to a lack of manufacturing knowledge at production start as causal to poor production outcomes. A comparison of DOD practices against non-DOD industrial production approval processes addressing causality and improvement opportunity provided new insight not found in acquisition research. An analysis of alternatives identified best practices to improve production capability and readiness. Key findings revealed that the automotive production approval process followed industry best practices that fully addressed problems identified by the GAO. Non-DOD industries used a more prescriptive Quality Management System (QMS) that enabled a more disciplined manufacturing development and demonstration of production capability prior to production commitment. Commercial surveys in the literature confirmed the benefits of the automotive prescriptive QMS. The more successful QMS approach can be applied to DOD acquisition practices reducing costs and improving fleet readiness.http://archive.org/details/selectionofnlter1094556139Civilian, Department of the NavyApproved for public release; distribution is unlimited

Tissue Inhibitor of Metalloproteinase–3 (TIMP-3) induces FAS dependent apoptosis in human vascular smooth muscle cells

Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD). TIMP-3 induced apoptosis did not cause mitochondrial depolarisation, increase activation of caspase-9 and was not inhibited by over-expression of B-cell Lymphoma 2 (Bcl2), indicating a mitochondrial independent/type-I death receptor pathway. TIMP-3 increased levels of the First Apoptosis Signal receptor (FAS) and depletion of FAS with shRNA showed TIMP-3-induced apoptosis was FAS dependent. TIMP-3 induced formation of the Death-Inducing Signalling Complex (DISC), as detected by immunoprecipitation and by immunofluorescence. Cellular-FADD-like IL-1 converting enzyme-Like Inhibitory Protein (c-FLIP) localised with FAS at the cell periphery in the absence of TIMP-3 and this localisation was lost on TIMP-3 expression with c-FLIP adopting a perinuclear localisation. Although TIMP-3 inhibited FAS shedding, this did not increase total surface levels of FAS but instead increased FAS levels within localised regions at the cell surface. A Disintegrin And Metalloproteinase 17 (ADAM17) is inhibited by TIMP-3 and depletion of ADAM17 with shRNA significantly decreased FAS shedding. However ADAM17 depletion did not induce apoptosis or replicate the effects of TIMP-3 by increasing localised clustering of cell surface FAS. ADAM17-depleted cells could activate caspase-3 when expressing levels of TIMP-3 that were otherwise sub-apoptotic, suggesting a partial role for ADAM17 mediated ectodomain shedding in TIMP-3 mediated apoptosis. We conclude that TIMP-3 induced apoptosis in VSMCs is highly dependent on FAS and is associated with changes in FAS and c-FLIP localisation, but is not solely dependent on shedding of the FAS ectodomain

A low cost scheme for high precision dual-wavelength laser metrology

A novel method capable of delivering relative optical path length metrology with nanometer precision is demonstrated. Unlike conventional dual-wavelength metrology which employs heterodyne detection, the method developed in this work utilizes direct detection of interference fringes of two He-Ne lasers as well as a less precise stepper motor open-loop position control system to perform its measurement. Although the method may be applicable to a variety of circumstances, the specific application where this metrology is essential is in an astrometric optical long baseline stellar interferometer dedicated to precise measurement of stellar positions. In our example application of this metrology to a narrow-angle astrometric interferometer, measurement of nanometer precision could be achieved without frequency-stabilized lasers although the use of such lasers would extend the range of optical path length the metrology can accurately measure. Implementation of the method requires very little additional optics or electronics, thus minimizing cost and effort of implementation. Furthermore, the optical path traversed by the metrology lasers is identical with that of the starlight or science beams, even down to using the same photodetectors, thereby minimizing the non-common-path between metrology and science channels.Comment: 17 pages, 4 figures, accepted for publication in Applied Optic

Dissecting flux balances to measure energetic costs in cell biology: techniques and challenges

Life is a nonequilibrium phenomenon: metabolism provides a continuous supply of energy that drives nearly all cellular processes. However, very little is known about how much energy different cellular processes use, i.e. their energetic costs. The most direct experimental measurements of these costs involve modulating the activity of cellular processes and determining the resulting changes in energetic fluxes. In this review, we present a flux balance framework to aid in the design and interpretation of such experiments, and discuss the challenges associated with measuring the relevant metabolic fluxes. We then describe selected techniques that enable measurement of these fluxes. Finally, we review prior experimental and theoretical work that has employed techniques from biochemistry and nonequilibrium physics to determine the energetic costs of cellular processes.Comment: 27 pages, 3 figure

A Quantitative and High-Throughput Approach to Gene Regulation in Escherichia coli

Measurements in biology have reached a level of precision that demands quantitative modeling. This is particularly true in the field of gene regulation, where concepts from physics such as thermodynamics have allowed for accurate models to be made. Many issues remain. DNA sequencing is routine enough to sequence new genomes in days and cheap enough to use deep sequencing to perform precision measurements, but our ability to interpret the wealth of genomic data is lagging behind, especially in the realm of gene regulation. The primary reason is that we lack any information what so ever as to the basic regulatory details of approximately 65 percent of operons even in E. coli, the best understood organism in biology. As a result we cannot use our hard won modeling efforts to understand any of these operons. This work takes steps to address these issues. First we use 30 LacI mutants as a test case to prove that we can make quantitatively accurate models of gene expression and sequence-dependent binding energies of transcription factors and RNA polymerase. Next we note that much of the quantitative insight available on transcriptional regulation relies on work on only a few model regulatory systems such as LacI as was considered above. We develop an approach, through a combination of massively parallel reporter assays, mass spectrometry, and information-theoretic modeling that can be used to dissect bacterial promoters in a systematic and scalable way. We demonstrate that we can uncover a qualitative list of transcription factor binding sites as well as their associated quantitative details from both well-studied and previously uncharacterized promoters in E. coli. Finally we extend the above method to over 100 E. coli promoters using over 12 growth conditions. We show the method recapitulates known regulatory information. Then, we examine regulatory architectures for more than 80 promoters which previously had no known regulation. In many cases, we identify which transcription factors mediate their regulation. The method introduced clears a path for fully characterizing the regulatory genome of E. coli and advances towards the goal of using this method on a wide variety of other organisms including other prokaryotes and eukaryotes such as Drosophila melanogaster.</p

AUTOMOTIVE DESIGN-TO LIFE-CYCLE CRITERIA FOR LOWERING WARRANTY COSTS AND IMPROVING OWNERSHIP EXPERIENCE THROUGH THE USE OF A NEW "BINARY DECISION MODEL" AND APPLICATION OF A "WARRANTY INDEX"

Financial challenges facing the automotive sector require identification of new opportunities for quality improvement. A new Design-To Life-Cycle-Cost strategy is introduced that applies a unique "Binary Decision Logic Model" that classifies corrective action opportunity into Life-Cycle categories. The intended result is to lower a manufacture's warranty costs and improve ownership experience. This is done by setting Design-To goals in a Life-Cycle way for Reliability and Serviceability. The sample space for data to drive this change of process is found in an existing warranty system with data elements consisting of failure occurrence, failure symptom, mileage, part cost, and labor cost. One can investigate new factors, such as the "Warranty Index," that parses the corrective action in favor of lowering part costs or labor costs found in a typical service event. The data considers opportunities over mileage and time domains to improve vehicle quality over the Life-Cycle

MPAthic: Quantitative Modeling of Sequence-Function Relationships for massively parallel assays

Massively parallel assays (MPAs) are being rapidly adopted for studying a wide range of DNA, RNA, and protein sequence-function relationships. However, the software available for quantitatively modeling these relationships is severely limited. Here we describe MPAthic, a software package that enables the rapid inference of such models from a variety of MPA datasets. Using both simulated and previously published data, we show that the modeling capabilities of MPAthic greatly improve on those of existing software. In particular, only MPAthic can accurately quantify the strength of epistatic interactions. These capabilities address a major need in the analysis of MPA data