Thesis (M.S.)--University of Delaware, 2006. / Principal faculty advisor: James G. Richards, College of Health Sciences. Includes bibliographical references.

BACKGROUND: Differences in disease-modifying therapy (DMT) prescribing patterns between different groups of neurologists have not been explored. HYPOTHESIS: MS-specialist neurologists use a broader range of DMTs in contrast to generalist neurologists who preferentially prescribe Avonex. METHODS: Ontario neurologist demographic and geographical characteristics were linked to 2009 DMT prescription data. Lorenz curves and Gini coefficients were constructed to examine prescribing patterns; separating neurologist characteristics dichotomously and separating Avonex from the other DMTs. Gini Coefficients were compared using jack-knife statistical techniques to derive 95% confidence intervals. RESULTS: Prescriptions are highly concentrated with 12% of Ontario neurologists prescribing 80% of DMTs. High-volume prescribers show a broader range of DMT use while low-volume prescribers tend to use a particular DMT. CONCLUSIONS: The majority of DMTs are prescribed by a small subset of neurologists. High-volume prescribers show more variability in DMT use while low-volume prescribers tend to individually focus on a narrower range of DMTs.

BACKGROUND: Differences in disease-modifying therapy (DMT) prescribing patterns between different groups of neurologists have not been explored. HYPOTHESIS: MS-specialist neurologists use a broader range of DMTs in contrast to generalist neurologists who preferentially prescribe Avonex. METHODS: Ontario neurologist demographic and geographical characteristics were linked to 2009 DMT prescription data. Lorenz curves and Gini coefficients were constructed to examine prescribing patterns; separating neurologist characteristics dichotomously and separating Avonex from the other DMTs. Gini Coefficients were compared using jack-knife statistical techniques to derive 95% confidence intervals. RESULTS: Prescriptions are highly concentrated with 12% of Ontario neurologists prescribing 80% of DMTs. High-volume prescribers show a broader range of DMT use while low-volume prescribers tend to use a particular DMT. CONCLUSIONS: The majority of DMTs are prescribed by a small subset of neurologists. High-volume prescribers show more variability in DMT use while low-volume prescribers tend to individually focus on a narrower range of DMTs.

With extremely wide bandwidth and good channel properties, optical fibers have brought fast and reliable data transmission to todays data communications. However, to handle heavy traffic flowing through optical physical links, much faster processing speed is required or else congestion can take place at network nodes. Also, to provide people with voice, data and all categories of multimedia services, distinguishing between different data flows is a requirement. To address these router performance, Quality of Service /Class of Service and traffic engineering issues, Multi-Protocol Label Switching (MPLS) was proposed for IP-based Internetworks. In addition, routers flexible in hardware architecture in order to support ever-evolving protocols and services without causing big infrastructure modification or replacement are also desirable. Therefore, reconfigurable hardware implementation of MPLS was proposed in this project to obtain the overall fast processing speed at network nodes. The long-term goal of this project is to develop a reconfigurable MPLS router, which uniquely integrates the best features of operations being conducted in software and in run-time-reconfigurable hardware. The scope of this thesis includes system architecture and service algorithm considerations, Verilog coding and testing for an actual device. The hardware and software co-design technique was used to partition and schedule the protocol code for execution on both a general-purpose processor and stream-based hardware. A novel RPS scheme that is practically easy to build and can realize pipelined packet-by-packet data transfer at each output was proposed to take the place of the traditional crossbar switching. In RPS, packets with variable lengths can be switched intelligently without performing packet segmentation and reassembly. Primary theoretical analysis of queuing issues was discussed and an improved multiple queue service scheduling policy UD-WRR was proposed, which can reduce packet-waiting time without sacrificing the performance. In order to have the tests carried out appropriately, dedicated circuitry for the MPLS functional block to interface a specific MAC chip was implemented as well. The hardware designs for all functions were realized with a single Field Programmable Gate Array (FPGA) device in this project. The main result presented in this thesis was the MPLS function implementation realizing a major part of layer three routing at the reconfigurable hardware level, which advanced a great step towards the goal of building a router that is both fast and flexible.

With extremely wide bandwidth and good channel properties, optical fibers have brought fast and reliable data transmission to todays data communications. However, to handle heavy traffic flowing through optical physical links, much faster processing speed is required or else congestion can take place at network nodes. Also, to provide people with voice, data and all categories of multimedia services, distinguishing between different data flows is a requirement. To address these router performance, Quality of Service /Class of Service and traffic engineering issues, Multi-Protocol Label Switching (MPLS) was proposed for IP-based Internetworks. In addition, routers flexible in hardware architecture in order to support ever-evolving protocols and services without causing big infrastructure modification or replacement are also desirable. Therefore, reconfigurable hardware implementation of MPLS was proposed in this project to obtain the overall fast processing speed at network nodes. The long-term goal of this project is to develop a reconfigurable MPLS router, which uniquely integrates the best features of operations being conducted in software and in run-time-reconfigurable hardware. The scope of this thesis includes system architecture and service algorithm considerations, Verilog coding and testing for an actual device. The hardware and software co-design technique was used to partition and schedule the protocol code for execution on both a general-purpose processor and stream-based hardware. A novel RPS scheme that is practically easy to build and can realize pipelined packet-by-packet data transfer at each output was proposed to take the place of the traditional crossbar switching. In RPS, packets with variable lengths can be switched intelligently without performing packet segmentation and reassembly. Primary theoretical analysis of queuing issues was discussed and an improved multiple queue service scheduling policy UD-WRR was proposed, which can reduce packet-waiting time without sacrificing the performance. In order to have the tests carried out appropriately, dedicated circuitry for the MPLS functional block to interface a specific MAC chip was implemented as well. The hardware designs for all functions were realized with a single Field Programmable Gate Array (FPGA) device in this project. The main result presented in this thesis was the MPLS function implementation realizing a major part of layer three routing at the reconfigurable hardware level, which advanced a great step towards the goal of building a router that is both fast and flexible.

Low vitamin D status has been consistently associated with an increased risk of multiple sclerosis (MS). Further, preclinical and in vitro data demonstrate immune regulatory properties of 1,25-dihydroxyvitamin D that may be beneficial for patients with MS. To date evidence of beneficial in vivo immunomodulation by supplementation with vitamin D3 in humans is lacking. In a one-year, open-label, phase I/II dose-escalation study of vitamin D3 (average ~14,000 IU/d over one year) with calcium (1,200mg/d) in patients with MS, we compared the effects of treatment on safety outcomes, clinical outcomes and selected biomarkers of immune system activity, relative to matched MS patients [age, sex, disease duration, disease modifying therapy, and expanded disability status scale (EDSS)] randomized to receive no supplementation. Mean serum 25(OH)D concentrations were 78.1±27.0 nmol/L at baseline and at one-year were 82.7±34.8 and 179.1±76.1 nmol/L in control and treated groups, respectively. Serum and urinary calcium and all other safety outcomes were unchanged throughout the trial. Compared to controls, treated patients tended to have fewer relapses (McNemar, p=0.09) and a greater proportion had a stable or improved EDSS at study end (p=0.018). We observed significantly reduced lymphocyte proliferative responses to antigenic challenge in the treatment group at one year, compared to baseline and control group responses. High serum 25(OH)D concentrations were not associated with short-term adverse effects in patients with MS, but with evidence of clinical improvement and beneficial immunomodulation.

Low vitamin D status has been consistently associated with an increased risk of multiple sclerosis (MS). Further, preclinical and in vitro data demonstrate immune regulatory properties of 1,25-dihydroxyvitamin D that may be beneficial for patients with MS. To date evidence of beneficial in vivo immunomodulation by supplementation with vitamin D3 in humans is lacking. In a one-year, open-label, phase I/II dose-escalation study of vitamin D3 (average ~14,000 IU/d over one year) with calcium (1,200mg/d) in patients with MS, we compared the effects of treatment on safety outcomes, clinical outcomes and selected biomarkers of immune system activity, relative to matched MS patients [age, sex, disease duration, disease modifying therapy, and expanded disability status scale (EDSS)] randomized to receive no supplementation. Mean serum 25(OH)D concentrations were 78.1±27.0 nmol/L at baseline and at one-year were 82.7±34.8 and 179.1±76.1 nmol/L in control and treated groups, respectively. Serum and urinary calcium and all other safety outcomes were unchanged throughout the trial. Compared to controls, treated patients tended to have fewer relapses (McNemar, p=0.09) and a greater proportion had a stable or improved EDSS at study end (p=0.018). We observed significantly reduced lymphocyte proliferative responses to antigenic challenge in the treatment group at one year, compared to baseline and control group responses. High serum 25(OH)D concentrations were not associated with short-term adverse effects in patients with MS, but with evidence of clinical improvement and beneficial immunomodulation.

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Ce mémoire est centré sur l'étude des coefficients de corrélation partiels en régression linéaire multiple, à travers les tests de permutation. Ces tests sont nécessaires lorsque les suppositions du modèle linéaire ne sont pas verifiées, et l'application des tests classiques est erronnée. On présente les bases théoriques de trois méthodes de la littérature, Manly (1991), Freedman et Lane (1983) et Kennedy (1995), et on fait une étude de simulation afin de les comparer. On ajoute aux comparaisons le test paramétrique, ainsi qu'une méthode qu'on propose. On regarde l'erreur de type I et la puissance de ces tests. Un dernier volet du mémoire est la présentation des tests de Mantel (1967) et Smoose et al. (1986) qui sont des généralisations de ces méthodes de permutation pour la régression multiple à des matrices de distances. A titre d'exemple, ces différentes techniques de permutation sont appliquées sur des matrices de distances génétiques en relation avec des distances environnementales et des distances géographiques. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Échangeabilité, Test de permutation, Test de Mantel, Test de Mantel partiel, Régression multiple, Corrélation partielle, Résidus.

In the process of continuous scaling improvement under a single system-on-chip which contains millions of logic gates, testability of the design becomes more and more important and thus multiple scan tree test architecture can effectively reduce test time and test data simultaneously. In the current two-dimensional structure of the system-level chip, the interconnect has become one of the main factors in delay and power consumption, and thus optimizing interconnect becomes a very important topic. Especially, three-dimensional ICs, stacked multiple chips vertically by through-silicon-via technique, can be effective in reducing the length of the interconnects, power consumption and offering features of heterogeneous IC integration. In this research study, we consider three-dimensional chips in both respects of wire length and the scan output limits, and propose the test synthesis algorithm of multiple scan trees to reduce test cost for three dimensional integrated circuits.