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The work in this thesis is a study of excimer laser induced damage in optical materials. This includes characterization of the focused laser radiation, development of sensitive techniques for the early detection of laser damage and finally laser damage studies at 193 nm and 248 nm in crystalline materials, metal mirrors and dielectric coatings. Characterization of the focused laser radiation involved pulse energy, temporal pulse profile and spatial profile measurements. This was assisted by development of a laser attenuator using a variable length liquid cell with a dynamic range of 25 dB. Non-linear absorption phenomena were observed in liquids at high intensities. Beam profiling methods were used to show the intensity distribution in the focal region of a lens was reproducible and approximated to a 2-D Gaussian function [continued]…

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The purpose of this study was to determine if the Glasgow Coma Scale (GCS) provides a valid indication of severity after closed head injury. A second purpose was to determine the nature of the deficits seen with head injured persons shortly after injury.The subjects were 69 patients ages 13 through 26 selected from consecutive closed head injury admissions to a large acute care hospital. The subjects received comprehensive neuropsychological testing after having passed the Galveston Orientation and Amnesia Test.Two a priori hypotheses were specified for each of eight neuropsychological test groupings (i.e., motor, memory, visuographic, achievement, abstraction and concept formation, language, problem solving, and psychometric intelligence). For each of the eight test groupings two, one-way multivariate analyses of covariance (MANCOVA) were used to determine statistical significance. Premorbid IQ was used as a covariate in all of the analyses. Specifically, these a priori contrasts were GCS group (8 compared with GCS group 9-15 and GCS group 9-12 compared with GCS group 13-15. Each of the significant MANCOVA tests was followed with discriminant analysis.The results revealed that 15 out of the 16 null hypotheses were rejected (p<.05 or less) thus providing clear evidence for the usefulness of the GCS as an indicator of the severity of injury. Most notable of the results is that the GCS group comparison of 9-12 and 13-15 reached significance in seven of the eight comparisons. Given this finding, there seems justification for the GCS division of 9-12 denoting a moderately injured group and 13-15 denoting a mildly injured group as was proposed in previous research. Redundancy indexes of 6% to 25% were obtained which indicated small to relatively large effect sizes for the various criterion variates.With discriminant analysis it was determined that accurate classification into GCS groups could be achieved in 64% to 94% of the cases based upon a combination of premorbid IQ and the criterion variates. This represented an increase in classification accuracy of from 13% to 51%to be over what could be accomplished with knowledge of the premorbid IQ alone. The motor test composite, problem solving test composite and abstraction and concept formation composite revealed the highest rates of reclassification.

The subject matter of this work is a non-pecuniary damage which is a specific type of damage. The author scrutinises the features of the non-pecuniary damage, which also have impact on the peculiarities of the compensation for this type of damage. The specific nature of a non-pecuniary damage may also be revealed through the aims of this damage, which, in the author’s point of view, are compensation and prevention. The author both analyses the concept of non-pecuniary damage and fundamental principles and aspects of its compensation. The author doubts about the constitutional background of a so-called exclusive regulation of non-pecuniary damage’s compensation, and states that the compensatory amount of a non-pecuniary damage shall not be restricted by either minimum or maximum limits.

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The C-terminal region of breast cancer susceptibility gene 1 (BRCA1) contains a pair of tandem BRCT repeats that are critical for the tumour suppressor function of BRCA1. BRCT repeats are present in a large of number of proteins that are implicated in the cellular response to DNA damage. A subset of tandem BRCT domains, including those of BRCA1, functions as phosphorecognition modules. Aside from BRCA1, the precise molecular mechanisms of the BRCT repeats of other proteins remain largely unknown. We determined the crystal structure of the tandem BRCT domain of human mediator of DNA checkpoint 1 (MDC1) at 1.45 Å resolution. Our structural and biochemical studies suggest that the tandem BRCT domain of MDC1 functions as the predominant histone variant, γH2AX phosphorecognition module and that the interaction is critically dependent on the free carboxylate group of the γH2AX C-terminal tail. We also determined the crystal structure of the tandem BRCT domain of human BARD1, the in vivo binding partner of BRCA1. Our structure uncovers a degenerate phosphopeptide binding pocket that lacks the key arginine critical for phosphopeptide interactions in other BRCT proteins. Our biochemical studies reveal that a flexible tether links ankyrin and BRCT domains in BARD1. Furthermore, the linker is required for the interactions between the CstF-50 WD-40 domain and BARD1, allowing the BARD1 C-terminus to convey DNA damage signals directly to RNA polymerase. Finally, using protease-based and phosphopeptide pull-down assays, we directly assessed the structural and functional effects of 117 single amino acid substitutions in the BRCA1 BRCT domain derived from breast cancer screening programs. None of the variants showing enhanced sensitivity to proteolytic digestion were found to be active in peptide binding, indicating that these missense mutations contribute to BRCA1 loss of function through protein destabilizing effects. A subset of structurally stable variants was defective in peptide binding activity, suggesting that these variants may disrupt the phosphopeptide binding pocket. Taken together, the results reveal that 32% of the variants show structural stability and peptide binding activity that were indistinguishable from those of wild type.

The purpose of this research was to investigate the efficacy of a 12 week isokinetic conditioning progam for the lower limbs in 12 young adults with acquired brain injury. There is strong evidence that young adults following ABI (Acquired Brain Injury) have on-going issues with physical impairments and functional limitations many years after their brain injury, and that these limitations are substantial and restrictive. As most therapy resources are available for early rehabilitation only, and these resources are mainly located in large cities, there are many people who are not receiving rehabilitation to support their on-going progress. / There is a paucity of studies investigating conditioning programs in young adults with ABI, and the effect of focusing treatment on the negative rather than the positive features of the Upper Neurone Syndrome (UMNS). The dose prescription for strengthening programs is uncertain, the effect of resistive exercise on tone is controversial and the changes following exercise on muscle strength, muscle power, functional abilities, and quality of life are largely unknown. / The research was in the form of a series of single case studies, with an A-B-A design. For each subject, a series of isokinetic (strength, power, tone) and mobility (gait speed and time to rise from a chair) baseline assessments and 6 subsequent assessments at 2-weekly intervals were performed. The last assessment was performed 4 weeks after cessation of the program to determine any carryover effect. The Short Form-36 questionnaire (SF-36) and semi-structured interviews were administered pre- and post- exercise to reflect the life satisfaction of subjects, and their perspective of any changes in response to the conditioning program. / The multiple isokinetic and mobility measures provided data for analysis of individual cases which were managed statistically, and for clinically significant change. Data was also analysed for the group. Group isokinetic and mobility measures were compared at pre-exercise, post-exercise and 4 weeks following cessation of the conditioning program using repeated measures analysis of variance. / The isokinetic exercise program, on a Kin Com dynamometer, consisted of nine sets of maximal contractions at velocities of 60 and 90 deg/s for unilateral knee flexors and extensors, and ankle plantarflexors and dorsiflexors. These sets were divided into three cycles of six reciprocal contractions. Subjects attended twice weekly for 12 weeks. / The conditioning program resulted in significant improvements in peak torque and power of ankle plantarflexors and peak torque of knee extensors for the group. In addition, functional improvements resulted, in particular fast walking activity, repeated chair rises and participation in activities the subjects valued. There was a carryover effect after the program ceased for some measures. There was no deleterious effect on tone in response to the exercise program. Quality of life of all subjects assessed by using the SF36 questionnaire improved in the area of physical functioning. Occupational status, vitality, self-esteem and optimism were further common themes of improvement obtained from interview data at the completion of the exercise program. / This study demonstrated that a 12 week intensive, resistive, conditioning program produced significant improvement in muscle performance in ankle plantarflexors, knee extensors, function, and participation in valued activities, as well as in feelings of well-being, in a group of ABI subjects. There were no adverse symptoms in response to the high intensity, high repetition exercise protocol at the ankle, indicating that the exercise protocol is suitable for strengthening ankle muscles in individuals following ABI who have a broad range of abilities. / Three subjects experienced knee pain and stiffness in response to the exercise program. These three TBI subjects, who had the highest functional mobility of the group, were able to develop higher torques when exercising, and, the twice weekly, maximal, isokinetic conditioning program might have been excessive for these subjects. The other nine subjects with moderate to severe muscle weakness of knee muscles did not suffer any adverse knee symptoms in response to the conditioning program, and demonstrated improvements in muscle performance of knee muscles. Therefore, when exercising knee muscles, a similar intensive protocol should only be utilized when the individuals have marked or moderate weakness of knee muscles. / These results indicate that a change in therapeutic approach is needed and that the focus for treatment should shift from the positive to the negative features of the UMNS. Rehabilitation of individuals following ABI should incorporate muscle conditioning programs for the lower limbs. Also, many individuals who are currently not receiving therapy may benefit from muscle strengthening exercises. It is important that further research is conducted to establish the most useful conditioning protocol for individuals following ABI. / Thesis (PhDPhysiotherapy)--University of South Australia, 2005.