Tse Hok Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 68-69). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgement --- p.iii / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Background Study --- p.4 / Chapter 2.1 --- Channel Assignment in Multicarrier CDMA Systems --- p.4 / Chapter 2.1.1 --- Channel Throughput --- p.5 / Chapter 2.1.2 --- Greedy Approach to Channel Assignment --- p.6 / Chapter 2.2 --- Generalised Assignment Problem --- p.7 / Chapter 2.2.1 --- Branch and Bound Approach for GAP --- p.8 / Chapter 2.2.2 --- Genetic Algorithm for GAP --- p.10 / Chapter 2.3 --- Negative Cycle Detection --- p.11 / Chapter 2.3.1 --- Labeling Method --- p.11 / Chapter 2.3.2 --- Bellman-Ford-Moore algorithm --- p.13 / Chapter 2.3.3 --- Amortized Search --- p.14 / Chapter 3 --- Multi-objective Assignment Problem --- p.15 / Chapter 3.1 --- Multi-objective Assignment Problem --- p.16 / Chapter 3.2 --- NP-Hardness --- p.18 / Chapter 3.3 --- Transformation of the Multi-objective Assignment Problem --- p.19 / Chapter 3.4 --- Algorithm --- p.23 / Chapter 3.5 --- Example --- p.25 / Chapter 3.6 --- A Special Case - Linear Objective Function --- p.32 / Chapter 3.7 --- Performance on the assignment problem --- p.33 / Chapter 4 --- Goal Programming Model for Channel Assignment Problem --- p.35 / Chapter 4.1 --- Motivation --- p.35 / Chapter 4.2 --- System Model --- p.36 / Chapter 4.3 --- Goal Programming Model for Channel Assignment Problem --- p.38 / Chapter 4.4 --- Simulation --- p.39 / Chapter 4.4.1 --- Throughput Optimization --- p.40 / Chapter 4.4.2 --- Best-First-Assign Algorithm --- p.41 / Chapter 4.4.3 --- Channel Swapping Algorithm --- p.41 / Chapter 4.4.4 --- Lower Bound --- p.43 / Chapter 4.4.5 --- Result --- p.43 / Chapter 4.5 --- Future Works --- p.50 / Chapter 5 --- Extended Application on the General Problem --- p.51 / Chapter 5.1 --- Latency Minimization --- p.52 / Chapter 5.2 --- Generalised Assignment Problem --- p.53 / Chapter 5.3 --- Quadratic Assignment Problem --- p.60 / Chapter 6 --- Conclusion --- p.65 / Bibliography --- p.67

Cheung Ching Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 64-65). / Abstracts in English and Chinese. / Acknowledgement --- p.i / Abstract --- p.ii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Multiple Comparison Procedures --- p.1 / Chapter 1.2 --- Multiple Comparisons with a control --- p.2 / Chapter 1.3 --- Multiple Comparisons with a control in two-way designs --- p.5 / Chapter 1.4 --- Example --- p.12 / Chapter 1.5 --- Thesis Objectives --- p.13 / Chapter 2 --- Evaluation of Power (Homogeneous Variance) --- p.14 / Chapter 2.1 --- Definition and the use of power --- p.14 / Chapter 2.2 --- Setup and Notations --- p.15 / Chapter 2.3 --- Evaluation of power --- p.16 / Chapter 2.4 --- Computational Details --- p.19 / Chapter 2.4.1 --- Algorithm --- p.19 / Chapter 2.4.2 --- Results --- p.20 / Chapter 2.5 --- Numerical Example --- p.39 / Chapter 3 --- Evaluation of Power (Heterogeneous Variances) --- p.42 / Chapter 3.1 --- Setup and Notations --- p.42 / Chapter 3.2 --- Evaluation of power --- p.43 / Chapter 3.3 --- Results --- p.45 / Chapter 3.3.1 --- All-pairs Power --- p.46 / Chapter 3.3.2 --- Any-pair Power --- p.53 / Chapter 3.4 --- Numerical Example --- p.60 / Chapter 4 --- Conclusions --- p.63 / References --- p.64

by Ying-wang Wong. / Year shown on spine: 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 41-44). / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- Multiple Comparison Procedures --- p.1 / Chapter 1.2 --- Familywise Error Rate --- p.3 / Chapter 1.3 --- One-step Procedures Versus Stepwise Procedures --- p.4 / Chapter 1.4 --- Pairwise Multiple Comparisons --- p.5 / Chapter 1.5 --- Pairwise Multiple Comparisons in Two-Way Designs --- p.6 / Chapter 1.6 --- Objectives --- p.8 / Chapter 2. --- Pairwise Multiple Comparisons in One-Way Designs with Covariates --- p.9 / Chapter 2.1 --- The General ANCOVA Model --- p.9 / Chapter 2.2 --- Pairwise Comparisons --- p.12 / Chapter 3. --- Pairwise Comparisons in Two-Way Layout with Covariates --- p.15 / Chapter 3.1 --- The Model --- p.15 / Chapter 3.2 --- The Test Statistics --- p.16 / Chapter 3.3 --- Computation of Upper Percentage Points --- p.17 / Chapter 3.4 --- Approximation Procedure --- p.21 / Chapter 3.5 --- Two-Way Layout with One Covariate --- p.21 / Chapter 4. --- Numerical Examples --- p.23 / Appendix A - An Algorithm in Solving Equation (3.2.4) for the value of ta --- p.35 / Appendix B - Evaluation of Multivariate Normal Probabilities --- p.38 / References --- p.41

Lau, Sin Yi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 64-66). / Abstracts in English and Chinese. / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Multiple Comparison Procedures --- p.1 / Chapter 1.2 --- Multiple Comparisons with a control --- p.2 / Chapter 1.3 --- Multiple Comparisons with a control in directional- mixed families --- p.5 / Chapter 1.4 --- Examples --- p.8 / Chapter 1.5 --- Thesis Objectives --- p.10 / Chapter 2 --- Evaluation of Power --- p.12 / Chapter 2.1 --- Definition and the Use of Power --- p.12 / Chapter 2.2 --- Computational Details --- p.13 / Chapter 2.3 --- All-pairs Power --- p.13 / Chapter 2.4 --- Any-pair Power --- p.15 / Chapter 2.5 --- Average Power --- p.16 / Chapter 2.6 --- Algorithm --- p.16 / Chapter 2.7 --- Results --- p.19 / Chapter 2.7.1 --- All-pairs Power --- p.20 / Chapter 2.7.2 --- Any-pair Power --- p.23 / Chapter 2.7.3 --- Average Power --- p.26 / Chapter 3 --- Sample Size Determination --- p.29 / Chapter 3.1 --- The required sample size for a pre-assigned all-pairs power --- p.31 / Chapter 3.2 --- The required sample size for a pre-assigned any-pair power --- p.41 / Chapter 3.3 --- The required sample size for a pre-assigned average power --- p.51 / Chapter 4 --- An Illustrative Example --- p.61 / Chapter 5 --- Conclusions --- p.63 / References --- p.64

Die schubförmige Multiple Sklerose (MS) ist eine chronisch-entzündliche, demyelinisierende, multifokale Erkrankung des Zentralnervensystems (ZNS). Autoreaktive immunologische Prozesse, insbesondere der T-Zell vermittelten Immunität, leisten einen entscheidenden Beitrag zur Pathogenese der schubförmigen MS. Ein wesentlicher Schritt in immunpathogenetischen Modellen ist die transendotheliale Migration von Immunzellen über die Blut-Hirn-Schranke. Die Interaktion des very late antigen 4 (VLA-4) mit dem vascular cell adhesion molecule 1 (VCAM-1) und mit Fibronectin leistet einen wesentlichen Beitrag zur Extravasation von T Zellen in das ZNS. Auf dieser Schlüsselfunktion des VLA-4 gründet die Therapie mit Natalizumab, einem monoklonalen Antikörper gegen die α4 Integrinkette. Ziel der vorliegenden Studie war es, die Auswirkungen der Therapie der schubförmigen MS mit Natalizumab auf die transendotheliale Migration von CD4+CD25+FOXP3+ und CD4+HLA-G+ regulatorischen T Zellen (Treg) und auf die antiproliferative Funktion von FOXP3+ Treg zu untersuchen. Zentrale Hypothese war, dass Natalizumab über eine universelle Blockade der Immunzellinvasion in das ZNS hinaus immunmodulatorisch wirkt. Unter Verwendung eines prospektiven, longitudinalen Studiendesigns wurden die T Zellen von RR-MS Patienten unter Therapie mit Natalizumab (n=31) sowie von stabilen RR-MS Patienten ohne Therapie und gesunden Spendern in jeweils zwei in vitro Modellen der Blut-Hirn-Schranke sowie Treg vermittelter Immuntoleranz untersucht. FOXP3+ regulatorische T-Zellen banden weniger Natalizumab und exprimierten weniger VLA-4 als nicht-regulatorische T Helferzellen, bewahrten unter Therapie jedoch einen höheren Anteil ihrer ursprünglichen VLA-4 Expression. FOXP3+ Treg gesunder Spender wiesen in vitro höhere Migrationsraten über mikrovaskuläre humane Hirnendothelzellen als nicht-regulatorische T Helferzellen auf und akkumulierten innerhalb der T-Zell Population nach Migration. Dagegen reicherten sich FOXP3+ Treg von MS Patienten in Folge der Migration nur nach Vorbehandlung des Endothel mit inflammatorischen Zytokinen an, nicht jedoch ohne diese Vorbehandlung. Natalizumab beeinträchtigte die transendotheliale Migration von FOXP3+ Treg und nicht-regulatorischen T Helferzellen von MS Patienten in vergleichbaren Ausmaßen. HLA-G+ Treg zeigten in den Migrationsanalysen ein den FOXP3+ Treg entgegengesetztes Muster und wiesen ausschließlich in der MS, nicht jedoch im Gesunden, eine höhere Migrationsrate auf als HLA-G- T Helferzellen. Diese Akkumulation von HLA-G+ Treg in der migrierten Zellfraktion ließ sich nach Therapiebeginn nicht mehr nachweisen. Eine ergänzende Einzelfallstudie zu Auswirkungen des LFA-1 Antagonisten Efalizumab auf Treg ergab Hinweise auf eine Schlüsselfunktion dieses Integrins für die Migration von FOXP3+ Treg. Die Analyse der FOXP3+ Treg Suppressorfunktion zeigte eine schrittweise Zunahme des suppressiven Einflusses von FOXP3+ Treg auf die Reifung dendritischer Zellen unter Natalizumabtherapie. Zeitlich parallel kam es zu einem Ungleichgewicht in der Expression von LFA-1 auf der Oberfläche von FOXP3+ Treg und nicht-regulatorischen T Helferzellen. Zusammenfassend stützt die Studie die Hypothese immunmodulatorischer Effekte von Natalizumab in der schubförmigen Multiplen Sklerose, insbesondere auf den Antagonismus von regulatorischen und Effektor-T Zellen. Die Arbeit belegt, dass Natalizumab in vivo über die Blockade von VLA-4 hinaus modulatorisch in das Netzwerk von Adhäsionsmolekülen auf T Zellen eingreift. Die Studienergebnisse ergeben ein Überwiegen regulatorischer Einflüsse auf die Reifung dendritischer Zellen unter Therapie. Berichte zum Beitrag von LFA-1 zur Suppressorfunktion von FOXP3+ Treg werden durch Daten der vorliegenden Studie unterstützt und um Hinweise auf eine zusätzliche, spezifische Bedeutung des Integrins zur präferentiellen Diapedese dieser Treg über die Blut-Hirn-Schranke im Gesunden erweitert. Zudem liefert die Arbeit erstmals Hinweise auf einen Defekt der transendothelialen Migration von FOXP3+ Treg über die Blut-Hirn-Schranke in der schubförmigen Multiplen Sklerose, der zur Entstehung neuer Läsionen beitragen könnte. / Relapsing-remitting multiple sclerosis (MS) is a multifocal, chronic, inflammatory, demyelinating disease of the central nervous system (CNS). Autoreactive processes, in particular T-cell mediated immunity, are essential to the pathogenesis of MS. A pivotal step in immunopathogenetic models is the diapedesis of immune cells across the blood-brain barrier. Transendothalial migration of encephalitogenic T cells across the blood-brain barrier depends critically on the interaction between very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) as well as fibronectin. The therapeutic rationale for natalizumab, a monoclonal antibody against the α4 chain of VLA-4, is based on this pivotal role of VLA-4 for T-cell diapedesis. This study aimed to examine transendothelial migration of CD4+CD25+FOXP3+ and CD4+HLA-G+ regulatory T cells (Treg) as well as the suppressive capacity of FOXP3+ Treg in relapsing-remitting multiple sclerosis under natalizumab therapy. The study tested the hypothesis that natalizumab exerts immunmodulatory effects beyond a universal blockade of immune cell invasion into the CNS. T cells from MS patients under natalizumab therapy (n=31) were compared to T cells from stable MS patients without treatment and from healthy controls according to a prospective, longitudinal study design. Two in vitro models of the blood-brain barrier and two models of Treg-mediated tolerance were employed. FOXP3+ regulatory T cells exhibited reduced natalizumab binding and VLA-4 expression when compared to non-regulatory T helper cells but preserved a greater proportion of their initial VLA-4 expression under natalizumab therapy. FOXP3+ Treg from healthy controls showed enhanced migration across human brain microvascular endothelial cells when compared to non-regulatory T cells in vitro and accumulated within the T-cell population after migration. FOXP3+ Treg from MS patients, in contrast, accumulated only after pre-treatment of the endothelium with inflammatory cytokines. Natalizumab inhibited transendothelial migration of FOXP3+ Treg and non-regulatory T cells to a similar extent. HLA-G+ Treg showed a reverse pattern in these migration assays: HLA-G+ Treg from MS patients, but not from healthy controls, exhibited enhanced migratory rates when compared to non-regulatory, HLA-G- TH cells. This accumulation of HLA-G+ Treg within the fraction of migrated cells could no longer be detected any more after initiation of natalizumab therapy. The results of a supplementary single case study on the effects of the LFA-1 antagonist efalizumab on Treg pointed towards a pivotal role of this integrin for the preferential migration of FOXP3+ Treg. Suppression of the maturation of dendritic cells by FOXP3+ Treg gradually increased under natalizumab therapy. A growing imbalance in the surface distribution of LFA-1 among FOXP3+ Treg and non-regulatory TH cells parallelled this recovery of MS Treg suppression. In summary, this study supports the hypothesis of immunomodulatory effects of natalizumab in relapsing-remitting multiple sclerosis, particularly on the antagonism between regulatory and effector T cells. The study documents interference of natalizumab with the network of adhesion molecules on T cells in vivo that extends beyond its blockade of VLA-4. Furthermore, it demonstrates a dominance of Treg-mediated suppression on the maturation of dendritic cells under therapy. It supports recent reports on a pivotal role of LFA-1 for suppressive mechanisms of FOXP3+ Treg and points towards a similar relevance for preferential Treg migration across the blood-brain barrier. Lastly, the study provides the first evidence for deficient transendothelial migration of FOXP3+ Treg in multiple sclerosis, which could contribute to early lesion formation.

Over the course of several decades, the foster youth population continues to grow due to various forms of abuse that have occurred in the biological home. Many foster children experience multiple placements which ultimately cause a significant amount of trauma due to placement instability. The study examined trauma of instability among foster youth and discussed interventions that could be implemented when working with resource families and foster youth within the field of social work. A post-positivism paradigm was used to focus on understanding the trauma of placement instability. A total of six face-to-face interviews of master’s level social workers were conducted to obtain qualitative data. The interviews consisted of a variety of both descriptive, structural, and contrast questions to explore trauma and common behaviors of foster youth who experienced instability. All data obtained from the interviews were recorded, transcribed, and analyzed through open coding, axial coding, and selective coding by traditional means. Content analysis was used to identify four themes: Impact of Multiple Placements, Useful Interventions, Benefits of Stability, and Family Characteristics. The following research study contributes to social work practice by providing useful interventions such as: teaching, modeling, self-regulation and self-awareness techniques for youth and foster families to address instability. This also includes training families to be trauma-informed caretakers and pre-screening foster families to identify the best match for children to reduce instability.

Multiple sclerosis (MS) is the most prevalent neurological disease of the central nervous system (CNS) in young adults and is characterized by inflammation, demyelination and axonal pathology that result in multiple neurological and cognitive deficits. The focus of MS research remains on modulating the immune response, but common therapeutic strategies are only effective in slowing down disease progression and attenuating the symptoms; they cannot cure the disease. Developing an option to prevent neurodegeneration early on would be a valuable addition to the current standard of care for MS. Based on our results we suggest that application of nimodipine could be an effective way to target both neuroinflammation and neurodegeneration. We performed detailed analyses of neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and in in vitro experiments regarding the effect of the clinically well-established L-type calcium channel antagonist nimodipine. Nimodipine treatment attenuated the course of EAE and spinal cord histopathology. Furthermore, it promoted remyelination. The latter could be due to the protective effect on oligodendrocytes and oligodendrocyte precursor cells (OPCs) we observed in response to nimodipine treatment. To our surprise, we detected calcium channel-independent effects on microglia, resulting in apoptosis. These effects were cell type-specific and independent of microglia polarization. Apoptosis was accompanied by decreased levels of nitric oxide (NO) and inducible NO synthase (iNOS) in cell culture as well as decreased iNOS expression and reactive oxygen species (ROS) activity in EAE. Overall, application of nimodipine seems to generate a favorable environment for regenerative processes and could therefore be a novel treatment option for MS, combining immunomodulatory effects while promoting neuroregeneration. / Multiple Sklerose (MS) ist die häufigste neurologische Erkrankung des zentralen Nervensystems (ZNS) von jungen Erwachsenen und charakterisiert durch Inflammation, Demyelinisierung und axonale Pathologie. Diese Prozesse bewirken zahlreiche neurologische und kognitive Defizite. Der Schwerpunkt in der MS-Forschung besteht derzeit vor allem in der Modulation der Immunantwort, jedoch sind herkömmliche Therapiestrategien bislang nur in der Lage die Progression der Erkrankung zu verlangsamen und die Symptome zu lindern, die Krankheit kann jedoch immer noch nicht geheilt werden. Die Möglichkeit, den Prozess der Neurodegeneration früh aufzuhalten, würde eine wertvolle Ergänzung zu herkömmlichen Therapien darstellen. Basierend auf den Ergebnissen dieser Studie schlagen wir vor, dass die Applikation von Nimodipin eine elegante Möglichkeit wäre, um sowohl die Neuroinflammation als auch die -degeneration zu bekämpfen. Um den Effekt des klinisch gut etablierten Calciumkanal-Antagonisten Nimodipin zu untersuchen, haben wir detaillierte Analysen der Degeneration in der experimentellen autoimmunen Enzephalomyelitis (EAE), einem Tiermodell der MS, und in in vitro Untersuchungen durchgeführt. Applikation von Nimodipin verringerte das klinische Erscheinungsbild der EAE sowie die Histopathologie des Rückenmarkes. Außerdem förderte es die Regeneration. Die Ursache für letzteres liegt vermutlich am protektiven Effekt der Behandlung mit Nimodipin auf die Oligodendrozyten und deren Vorläuferzellen. Überraschenderweise, konnten wir Calciumkanal-unspezifische Effekte auf Mikroglia feststellen, die in Apoptose resultierten und sowohl Zelltyp-spezifisch als auch unabhängig von der Polarisierung der Mikrogliazellen waren. Apoptose wurde begleitet von reduzierten Spiegeln an Stickstoffmonoxid (NO) und der induzierbaren NO Synthase (iNOS) in Zellkultur, sowie einer reduzierten Expression von iNOS und dem geringeren Vorkommen von reaktiven oxygenen Spezies (ROS) in der EAE. Zusammenfassend gehen wir davon aus, dass die Applikation von Nimodipin eine günstige Umgebung für regenerative Prozesse schafft. Daher stellt die Applikation dieser Substanz eine neue Behandlungsmöglichkeit für die MS dar, insbesondere da sie Möglichkeiten der Immunmodulation mit der Förderung von Neuroregeneration verbindet.

Doctor of Philosophy / Multiple sclerosis (MS) is the most common neurological disease affecting young adults. MS affects approximately 1 in 1000 people and, like other autoimmune diseases, women are more likely to be affected than men. The illness typically onsets between the ages of 20 and 40, and hence usually affects women of child-bearing age. The course of the MS is often unclear for years after diagnosis and since most women are diagnosed in their child-bearing years, they often have to make reproductive choices before their prognosis is clear and while the future remains uncertain. For women with MS, starting a family is an individual choice that needs to balance the importance of motherhood for the woman and her partner against the risks that she will be unable to care for the infant or child as a result of increasing disability. In other areas of medicine where finely balanced decisions are required, there has been a recent proliferation of decision aids that aim to inform people of the benefits and risks of opposing courses of action. In addition, decision aids help patients to weigh their values against the risks and benefits to make an informed decision. Despite the existence of over 200 decision aids to help patients consider decisions related to their medical conditions, not one exists that deals with the decision of whether or not to have a family for women with a chronic disability, such as MS. This thesis developed and evaluated a decision aid for women with MS to help them decide whether to start, forego or enlarge their families. The study utilised the criteria set out for the development of decision aids, according to the Cochrane Systematic Review of Patient Decision Aids (O'Connor et al., 2003). The first aim was to determine the proportion of women who are undecided about the motherhood choice and for whom a decision aid may be relevant. Results found that the motherhood choice was relevant to 46% of the women who responded to an initial mail-out. The second study aimed to establish women’s current concerns and thoughts regarding pregnancy and motherhood, and their response to the pilot decision aid. Twenty women participated in qualitative interviews and results supported previous findings that the mother’s health concerns, coping with parenting and societal attitudes are significant concerns when considering this decision. This study further identified concerns from different groups that had a direct impact on the decision to have children, including the experience of parenting, the child’s well-being and the timing and pressure of the decision. The main study was a randomised controlled trial of the decision aid aiming to determine whether the decision aid facilitated decision-making in women with MS. The study confirmed that the decision aid presented a balanced view to women, increased knowledge, reduced decisional conflict, increased decisional self-efficacy and certainty of the decision, and was free from adverse effects on psychopathology. The final component of the study was a 12 month follow-up which aimed to explore the long-term effectiveness of the decision aid and what aspects were valued by the women who received it. It was found that over time, women in the intervention group did maintain their certainty, but women in the control group also became more certain of their choice. At follow-up, the difference in certainty was no longer significant between the two groups. However, women did report that the intervention was useful in (a) providing access to information previously unavailable or difficult to obtain, (b) facilitating communication between women, their partners and health care professionals, (c) aiding them in considering and utilising their networks of support, and (d) preparing them for potential difficulties. In summary, this thesis developed and evaluated a decision aid for women with MS who are considering motherhood. The results showed that many women were undecided and, in the absence of good information on the topic, many women had concerns about pregnancy and parenthood. The decision aid was shown to be effective across a range of measures and free from adverse psychological effects. Hence, this is evidence-based resource can now be recommended for those women with MS who are currently contemplating motherhood.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Thesis (Ph.D.)--University of Delaware, 2007. / Principal faculty advisor: Todd D. Royer, Dept. of Health, Nutrition, and Exercise Sciences. Includes bibliographical references.