The repair of DNA damage is vital to the health and survival of organisms and their cells. In humans, there exist several disorders that involve the inefficient processing or repair of DNA damage. Cellular sensitivity to DNA-damaging agents is a hallmark of repair-deficient syndromes which are often associated with an increased risk of cancer. In this work, I have investigated the repair of cisplatin-damaged DNA by utilizing host cell reactivation and cellular capacity assays that assess DNA repair using adenovirus (Ad) as a probe. Cisplatin is a widely used chemotherapeutic drug that induces both intrastrand and interstrand crosslinks in DNA. The host cell reactivation (HCR) assay examines the ability) of host cells to repair and hence, replicate cisplatin-damaged Ad DNA. This assay is believed to primarily be a measure of bulk nucleotide excision DNA repair. The cellular capacity assay examines the ability of cisplatin-damaged cells to support the replication of undamaged Ad DNA, and is thought to reflect the repair of the active cellular genes necessary for Ad replication. The repair of cisplatin-damaged DNA was studied in three human genetic syndromes -Roberts syndrome (RS), xeroderma pigmentosum (XP) and Li-Fraumeni syndrome (LFS). Fanconi's anemia (FA) cells were also used as a contml strain. RS is characterized by growth retardation, limb reductions and craniofacial abnormalities. Cell; from a subset of RS patients, termed RS+, are hypersensitive to several DNA-damaging agents, and it has been suggested that this hypersensitivity may result from a deficiency in the DNA repair capacity of these cells. (XP patients are sensitive to ultra violet light and are prone to the development of skin cancers. Cells from these patients are deficient in the nucleotide excision repair (NER) pathway responsible for repair of UV -induced lesions.) Patients with FA have a variety of congenital abnormalities, including a high susceptibility to leukemia. FA cells are sensitive to DNAcrosslinking agents such as mitomycin C (MMC) and cisplatin. Using the HCR and cellular capacity assays, deficiencies in DNA repair were detected in the XP and FA fibroblasts but not in the RS+ fibroblasts when compared to normal strains. The NERdeficient XP cells showed a significant reduction in both HCR of cisplatin-damaged Ad and in their capacity to support Ad replication following cellular cisplatin damage suggesting that cisplatin damage is repaired at least in part by the NER pathway. The normal HCR and capacity response of the RS+ cells compared to the XP cells suggests that the hypersensitivity of RS+ cells to DNA damage is not due to a deficiency in NER. The FA cells had normal HCR of cisplatin-damaged Ad but were significantly reduced in their capacity to support Ad replication following cisplatin treatment which was attributed to a defici,~ncy in the repair of DNA interstrand crosslinks. RS+ cells were not reduced in their capc.city to support Ad DNA replication, suggesting that the RS+ cellular hypersensitivity doe; not result from a deficiency in interstrand crosslink repair as seen with FA cells. LFS is a cancer prone syndrome that involves mutations in the p53 tumour suppressor gene. It was found that HCR of cisplatin-damaged Ad was normal in both p53-heterozygous and -hemizygous LFS cells, whereas the NER-deficient XP cells had significantly reduced HCR. The capacity of cisplatin-damaged, p53-heterozygous LFS fibroblasts was significantly reduced compared to normal cells. This suggests that although the LFS fibroblasts appear to have normal bulk NER, as shown by HCR, they appear to be deficier in the repair of the actively transcribed cellular genes necessary for viral replication. These results suggest a role for p53 in the repair of cisplatin damage of active genes. / Thesis / Master of Science (MS)

The characteristics of carbon fiber composites have enabled these materials to be accepted as replacements for metal parts in industry. However, due to their unsymmetrical material properties, carbon fiber composites are susceptible to damage, such as a delamination, which can cause premature failure in the structure. This has resulted in the need for nondestructive testing methods that can provide quick, reliable results so that these parts can be tested while in service. In this study, an approach was examined that involved a pencil lead break to excite multiple wave modes in a composite plate in an effort to identify key characteristics based on the wavespeed and frequency. These characteristics were then compared to models based on boundary conditions to generate dispersion curves using the transfer matrix method for whole composite plates that were either undamaged or damaged. To first test this approach, experiments were performed on multilayer isotropic plates and then on a composite plate. The results for all cases showed that modes could be excited by the pencil lead break in the undamaged region of the plates that were not theoretical possible in a delaminated region. Also modes that were specific to the delaminated region were excited and this allowed for a clear comparison between the two regions. This approach could be placed into practice to provide routine testing to detect delamination for in-service, carbon fiber composite parts. / Master of Science / The physical properties of high strength and low weight and the economic benefits of carbon fiber composites has resulted in these materials replacing metals in several industries. It is important, however, to be aware that the change in materials used impacts the different types of damage composites experience compared to conventional metals. One type of damage that could cause a composite part to fail is a delamination or a separation of layers. In order to identify if this damage has occurred, it is beneficial to have an inspection technique that will not damage the part. In this study, a technique was tested that involved breaking a piece of pencil lead on a plate in order to generate multiple wave modes that would propagate in the plate. Based on boundary conditions caused by the damage in the plate, the speed of the wave and frequency content could be compared to an undamaged plate to identify a delamination. A model was created to compare experimental results and demonstrated that using wavespeed and frequency could identify a delamination. The experimental results compared well with the model dispersion curves for a plate with and without a delamination suggesting this approach could be placed into practice to provide routine testing to detect delamination for in-service, carbon fiber composite parts.

To improve the recoverability and survivability of aircraft after damage, a better understanding of the flight dynamics and the structural loads is needed. However, damage can introduce asymmetries that complicate the modeling. An extended vortex lattice code is used to model the quasi-steady aerodynamic forces. The vortex lattice method provides the force distribution which is not available elsewhere. Snapshots from the vortex lattice model are used to generate a reduced order model (ROM). This ROM contains non-linear terms to account for non-linearities that the damage can introduce. The ROM is coupled with equations of motion which are able to account for instantaneous shifts in the center of gravity caused by the damage. This methodology is applied to the generic transport model (GTM) with the loss of a portion of the port wing tip. This model is used to examine the effects of the damage on the aircraft's trim and the stability of that trim. This model is also used to calculate the aerodynamic, inertial, and propulsive loads on the wing as the aircraft is maneuvering. / Master of Science

This study surveyed school-based speech language pathologists regarding their expectations for children returning to school after suffering a traumatic brain injury. Limited literature exists discussing the coordination procedures that should occur between hospital and school personnel. The survey was developed based on the existing literature and was sent to school-based speech language pathologists in the state of Indiana. A total of 38% of the surveys were completed and returned. Results of the surveys found that many of the coordination procedures in the literature were not consistently being followed. Participants who reported having experience with this population in the schools seemed more aware of the procedures that should be followed, based on their answers to the survey questions. It can be concluded, based on the results of the surveys, that increased knowledge and experience of school personnel about the effects, implications, and needs of students with traumatic brain injury would benefit children returning to the school environment after sustaining this type of injury. / Department of Speech Pathology & Audiology

The relationship between lesion volume in children with traumatic brain injury (TBI) and IQ scores was investigated in this study. Participants included eight children between the ages of 8-12 years with primarily right hemisphere TBIs and 16 normals who were matched based on age and gender. Archival data employing the Wechsler Intelligence Scale for Children - III (WISC-III) scores was the source of Verbal IQ (VIQ), Performance IQ (PIQ), and Full Scale IQ (FSIQ) scores. Severity of injury was determined using the Glasgow Coma Scale (GCS) which was contained in the same archival database. Lesion volume was determined utilizing National Institute of Health (NIH) Image (Version 1.76) and magnetic resonance imaging scans of the injured children. The area of the lesion was outlined, using the freehand line tool, on successive slices, summed, and multiplied by the corresponding acquisition slice gap to obtain a measure of total volume. Results indicated that lesion volume does not explain a significant portion of the variance associated with TBI. Severely injured children had lower IQs than children with mild or no injury. Additionally, children with right hemisphere injuries had significantly lower VIQ, PIQ, and FSIQ scores than normals. Qualitative analyses revealed that lesion volume appears to be related to the change in IQ scores during recovery. Typically, children with larger lesions (e.g., more severe injury) had greater functional losses and had greater gains to make; therefore, they demonstrated greater changes in IQ score as compared to less severely injured children. Predicting the area of deficit based upon lesion location yielded results congruent with chance. Results appear to reinforce the complexity of TBI; no single piece of data explains a significant portion of the variance associated with this phenomenon. Future research should strive toExamine and control for the numerous factors associated with TBI (e.g., age, lesion location, lesion volume, premorbid abilities, parental education, GCS score, gender, use of standard test battery, and many others) within a single study. Efforts to provide optimal treatment and recovery of TBI patients could be informed by such research. / Department of Counseling Psychology and Guidance Services

Récemment, notre laboratoire a démontré pour la première fois, que la protéine Damaged DNA Binding 2 (DDB2) possédait une activité régulatrice négative de l’expression basale de la superoxyde dismutase mitochondriale (SOD Mn) en se fixant sur un élément de réponse dans la région promotrice de son gène. Cette protéine était connue jusque là pour sa participation dans le système de réparation de l’ADN par excision de nucléotides. L’objectif de ce travail a été de définir précisément l’implication de ces deux protéines dans la croissance des cellules d’adénocarcinome mammaire, en développant des modèles cellulaires dont l’expression de la SOD Mn ou de la DDB2 est modulée expérimentalement. Nos résultats montrent pour la 1ère fois, que la SOD Mn est surexprimée dans les cellules tumorales mammaires insensibles aux oestrogènes (ER-) et ayant un pouvoir métastatique, et non dans les cellules épithéliales mammaires normales et les cellules ER+. L’inhibition de l’expression de la SOD Mn entraîne une stimulation de la croissance et une diminution de l’invasivité cellulaires, associées à une activité réduite de la métalloprotéinase 9. L’addition d’antioxydants, éliminant spécifiquement l’H2O2 issu de l’activité élevée de la SOD Mn, entraîne à la fois une inhibition de la croissance et du pouvoir invasif des cellules ER-. Ces résultats révèlent que la SOD Mn participe aux capacités invasives des cellules ER- via la production d’H2O2. Nous avons également montré pour la 1ère fois, que la DDB2 présente une activité oncogénique dans les cellules tumorales mammaires sensibles aux oestrogènes (ER+), non seulement parce que son gène est surexprimé, mais également parce qu’elle active leur prolifération en agissant sur la phase de transition G1/S et sur la progression dans la phase S du cycle cellulaire. Contrairement à la SOD Mn, l’expression de la DDB2 n’est pas observée dans les cellules tumorales mammaires ER-. De même à partir de biopsies provenant de patientes atteintes d’un cancer du sein, nous avons montré que la DDB2 est significativement plus exprimée dans les tumeurs les moins agressives et exprimant le récepteur aux oestrogènes. En montrant l’importance de la SOD Mn et la DDB2 dans la croissance et l’invasion des cellules tumorales mammaires, l’ensemble de ce travail révèle ainsi ces deux protéines comme des marqueurs prédictifs potentiels de la progression tumorale, et ouvre de nombreuses perspectives en cancérologie mammaire. / Recently, our laboratory demonstrated for the first time, that Damaged DNA Binding 2 (DDB2) played a role as a negative transcriptional regulator on the mitochondrial superoxide dismutase (MnSOD) expression through its binding to a specific DNA sequence located into the promoter of MnSOD gene. DDB2 was known as a protein which participates in the nucleotide excision repair of DNA. The goal of this study was to define precisely the involvement of the both proteins in the growth of mammary adenocarcinoma cells, using experimental procedures to modulate their expression in the breast cancer cell lines. Our results show for the first time that MnSOD is overexpressed in the estrogen receptor (ER) negative and metastatic breast tumor cells, but not in normal epithelial mammary cells and ER-positive tumor cells. Inhibition of MnSOD expression stimulates proliferation but decreases the invasive ability and the metalloproteinase 9 activity of tumor cells. Elimination of H2O2 from the elevated MnSOD activity by addition of specific antioxidants decreases proliferation as well as invasive ability of tumor cells, suggesting that the role of MnSOD in the invasive ability of tumor cells is mediated by H2O2. We have shown too for the first time that DDB2 has an oncogenic activity in the ER-positive breast tumor cells, because its gene is overexpressed and stimulates the proliferation by activating the entry of cells in the G1/S transition phase and the S phase progression. In contrast to MnSOD, DDB2 expression is not observed in ER-negative breast tumor cells, but is higher in ER-positive than in ER-negative tumor samples from patients with breast carcinoma. Taken together, our findings demonstrate that both MnSOD and DDB2 play a role in the growth and invasiveness of tumor cells and may become a promising candidate as a predictive markers in breast cancer. More studies will be need to define molecular mechanism controlling this activity of these both proteins.

This thesis deals with the criminal aspects of the patient's status as an injured party in the provision of health care. Author especially characterizes the criminal relationships between patients and health care facilities, their contents and background. In the first part of the thesis the author provides a legal framework for the health law, especially in the area of national and international law. It deals with crucial laws directly governing the healthcare law, and laws that are related to health law and greatly affect it. In the field of international law, the author deals mainly with the European Convention on Human Rights and the Convention on Biomedicine. At the level of the national rights of the author touches the area of constitutional order, in particular the Charter of Fundamental Rights and Freedoms as well as the partition law, which describes the particular treatment of health law, criminal law and civil law. In the second part of the thesis the author first defines the basic concepts and fundamental institutes occurring in health care. Eventually, the author of the second part focuses on the actual relationship between the patient and the medical facility where the first for the understanding of the issues dealing with the historical evolution of this relationship and later...

Thesis (M.A. (Pastoral))--North-West University, Potchefstroom Campus, 2008.

Thesis (Ph. D.)--York University, 2000. Graduate Programme in Psychology. / Typescript. Includes bibliographical references (leaves 64-76). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pNQ56232.

This study utilized a mail questionnaire to survey the views of parents residing in Texas regarding the educational needs of their adolescent (ages 14-18) with traumatic brain injury (TBI). Of the 233 parents of adolescents who were reported by hospitals as recently acquitting a TBI (in 1997, 1998, or 1999) of any level severity, 79 (34%) parents responded from across the state. Surprisingly, over half (N=41) of the parents responded by indicating that their adolescent did not have a TBI. This would suggest that the attending medical professionals might not have informed the parents of the long-term effects of a mild TBI. Twenty-five parents responded to the survey and rated psychology-related and transition-related services as the most needed special education and related services for their adolescent. Services were received by 40% of the adolescents, many under categories other than TBI, and the services most frequently received as a result of the TBI were: individualized academic instruction, homebound educational services, and occupational therapy. Of the parents whose adolescent did not receive services, and occupational therapy. OF the parents whose adolescent did not receive services, 44% felt their adolescent had unmet educational needs. Parents rated the following factors as the most critical to their adolescents’ educational needs being met: level of communication between the parent and the school, the school’s flexibility with the adolescent’s rapidly changing abilities and educational needs, the sensitivity of the educator to changes int eh adolescent and family’s daily lives stemming from the TBI, the educator taking an active role in helping the child socially re-adjust, and level of communication among the educators. The findings of this study illuminate the parents’ view of special education and related service needs for adolescents with TBI. In 1990, TBI became recognized as a category under which students may be eligible to receive special education and related services as stated in the individuals with Disabilities Act (IDEA). However, this study’s findings reflect that, at least in the parents’ perspective, many adolescents still have unmet educational needs and the needed services are lacking. / text