American-style football participation is associated with high risks to a spectrum of sports-related brain injury involving acute reactions and chronic manifestations. Traditional methods of identifying injury have proven ineffective at protecting athletes and mitigating risk as they rely on the presence and recognition of inconsistent symptom expression. This is, in part, due to the lack of an objective measure of quantifying exposure. Brain trauma profiling was defined to capture a spectrum of exposure by incorporating the primary characteristics that associate with risk of neurological injury. This profile includes strain magnitude associated with impact, frequency at which impacts are experienced, time interval between impacts, over the duration of exposure. Trauma profiling methods differentiated player field position in professional American-style football where three unique trauma profiles were identified based on similarities among the characteristics of trauma. Regional strain from common head impacts showed that distribution was independent of field position regardless of variation in impact conditions. Rather, brain regions vulnerable to strains were dictated by the frequency and magnitude that govern the position profile. The extent of tissue volume involved in common head impacts was field position dependent. Skill positions tended to experience impacts involving greater tissue volumes reaching deeper white matter structures, but were infrequent. Impacts common to line positions typically involved less brain tissue of predominately superficial cortical gray matter, but were experienced at high frequency counts. The primary findings from this research show that brain trauma profiling may be used as an objective measurement tool to define exposure. The results indicate that exposure is not uniform and that brain trauma and injury risk can be described using unique combinations of these characteristics. Regional areas vulnerable to strain are dictated by the frequency and magnitude of impact and therefore in order to effectively protect against brain injury, both characteristics need to be managed. Lastly, this research demonstrates that either few impacts involving high brain volume or frequent impacts with little brain volume involvement may both result in brain dysfunction. Brain trauma profiling methods has broad application in future research. This measurement tool will be useful in identifying how injury occurs in various sports, military units, and particularly important for vulnerable populations and the developing brain. This knowledge is instrumental in establishing risk prevention strategies and public health policies for specific environments.

Although unintentional weight loss (UWL) and depressive symptoms are critical outcomes following diagnosis and treatment for head and neck cancer (HNC), there is a limited understanding of how they influence one another over time. As part of a large, prospective study on HNC outcomes, growth curve modeling was used to evaluate 564 patients’ trajectories of depressive symptoms and percentage UWL and analyze longitudinal associations between these variables across the first year following HNC diagnosis. The hypothesized temporal precedence model was not supported—pretreatment depressive symptoms predicted neither total percentage weight loss at 6 months (t(561) = -1.50, p = .13), nor rates of curvilinear change in percentage weight loss over time (t(561) = 1.38, p = .17). The opposite temporal precedence model also lacked support—early weight loss predicted neither level of depressive symptoms at 6 months (t (432) = 0.24, p = .81), nor rates of linear change in depressive symptoms over time (t (432) = 1.31, p = .19). Instead, a pattern of concurrent covariation emerged—changes in depressive symptoms over time were associated with concurrent changes in UWL (t (1148) = 2.05, p = .041) and changes in UWL over time were associated with concurrent changes in depressive symptoms (t (556) = 2.43, p = .015). That is, to the extent that depressive symptoms increased on a monthly basis, patients lost incrementally more weight than was lost due to the passage of time, and to the extent that weight loss increased on a monthly basis, depressive symptoms also increased. Together, these bidirectional results depicted an ongoing transactional interplay between depressive symptoms and UWL across time, such that changes in either variable resulted in deviations from the average trajectory of the other variable. Patient-reported pain and eating abilities emerged as potential mechanisms through which these variables influence one another. The results have important clinical implications, indicating that ongoing screening and treatment for depression and weight loss throughout the first year after HNC could benefit patients’ psychological and nutritional outcomes alike.

It is well known that sitting posture is associated with discomfort and a number of musculoskeletal disorders. Seat manufacturers have made great strides toward developing seats for equipment which helped in alleviating the vibration transferring to the lower area of the spine; however, increased neck and head motion resulting from these seat designs may have been overlooked. Many cervical spine studies have been developed to estimate the response of the head and neck; however, these current studies do not take head and neck posture into account. The objective of this work was to study and demonstrate the difference in human biomechanical response to WBV when they use different neck postures. Four head and neck postures: up, down, to the side, and normal (straight forward) were investigated. Ten male subjects with ages ranging from 19 to 28 years were used to test each of the four postures, using the discrete sinusoidal frequencies of 2, 3, 4, 5, 6, 7, and 8 Hz at constant amplitudes of 0.8 m/s^2 RMS and 1.15 m/s^2 RMS in the x-direction (fore-and-aft). Subjects were seated in a rigid seat rigidly mounted to a vibration platform and vibration was generated using a six-degree-of-freedom man-rated shaker table. Subjects were tightly coupled to the seat back, using a neoprene vest and 5 straps, in an effort to reduce any relative motion between the seat and the subject. Subjects reported their head and neck discomfort using the Borg CR-10 scale with each of the postures, and then gave a second discomfort rating for the normal posture for each combination. Motion capture and accelerometer data were used to acquire the motion of the seat, C7 vertebrae, and center-of-head motion. The 3D motion of selected points on the heads and necks of the subjects were acquired using a twelve-camera Vicon motion capture system. Accelerometer data at the head, C7, and seat was used to verify the motion capture data. For the head-down posture, the magnitude of the discomfort function was higher than the normal posture. The head-to-side and head-up postures have shown less discomfort have shown less discomfort in the critical resonance area; however, these postures show roughly the same discomfort as the normal posture in other frequency ranges. In these postures, the subjects are using major neck-back muscles which create a stiffer system and may explain why there is a shift in the second peak in the head-to-side and head-up postures. Interestingly, the head-to-side and head-up postures show a similar trend as the normal posture, however, the peak transmissibility is attenuated. In addition, the subject's average discomfort was lower in this range compared to the normal posture. The head-down posture had the highest transmissibility and discomfort overall and suggests that workers in vibration environments should reduce any head-down postures to avoid unwanted head accelerations and discomfort. This work has demonstrated the importance of considering the head-neck posture in future seat-design studies.

Cancer cells are believed to exist in a condition of metabolic oxidative stress compared to normal cells because of inherent mitochondrial dysfunction. Cancer cells up regulate antioxidant defense mechanisms to combat the toxic effect of reactive oxygen species (ROS). Many anticancer agents block ROS detoxification mechanisms and utilize oxidative stress to cause cytotoxicity to cancer cells. However, ROS also up-regulate many pro-survival signaling pathways that may mediate resistance to chemotherapy. I hypothesize that ROS induces both cytotoxicity and pro-survival mechanisms in cells treated with chemotherapeutic agents such as the EGFR inhibitor erlotinib. This thesis explores how oxidative stress may induce both pro-survival and pro-death mechanisms in HNSCC cells and how this can be exploited to increase the cytotoxicity of erlotinib. The combined use of buthionine-[S,R]-sulfoximine, an inhibitor of glutathione and auranofin, an inhibitor of thioredoxin metabolism enhanced human head and neck cancer cell killing by a mechanism involving oxidative stress both in vitro and in vivo and sensitized cells to erlotinib in vitro. However, in other studies erlotinib as a single agent induced oxidative stress and this was mediated by NADPH oxidase 4 (NOX4). NOX4 mediated oxidative stress activated a process called autophagy which protected cancer cells from cytotoxic effect of erlotinib and inhibition of autophagy sensitized cells to erlotinib in vitro. These studies show that oxidative stress may have a dual role in cancer chemotherapy. ROS generated from various drug treatments can cause oxidative damage of cells culminating in cell death. However, it may also activate autophagy protecting cells against the stress and leading to decreased efficacy of the treatment. Hence inhibiting autophagy and hydroperoxide metabolism can be effective treatment modalities to enhance the cytotoxicity of erlotinib and achieve maximum therapeutic efficacy.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22038号 / 医博第4523号 / 新制||医||1038(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 松村 由美, 教授 富樫 かおり / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

INTRODUCTION: Sensory systems within the head provide us with rich perceptual information and may require complex control of the head during locomotion when changing direction. Head position in space is maintained by head on trunk motion as well as lower extremity kinematic modifications, such as increased knee flexion and increased stance time in order to facilitate shock attenuation and reduce vertical CoM displacement. It has been established that the body organizes its degrees of freedom of the trunk, pelvis and lower extremities differently during anticipated and unanticipated sidestepping, which raises the question of how these modifications affect head control during change of direction tasks. METHODS: Fourteen collegiate soccer players performed 7 anticipated and 7 unanticipated sidestepping tasks. Kinematic data were recorded using an 11-camera motion capture system (Qualysis, Inc., Gothenburg, Sweden) sampling at 240 Hz. Head and trunk orientation was quantified at penultimate toe off. A modified vector coding analysis was used to quantify the coordination and coordination variability between the head and trunk during the anticipated and unanticipated side-stepping trials. Differences in head-trunk orientation and coordination pattern frequencies were assessed with a paired t-test with an . One-dimensional statistical parametric mapping (SPM1D) was used to compare coordination variability waveforms. RESULTS: The head (p < 0.01, ES = 0.82) and trunk (p < 0.05, ES = 0.59) were significantly more oriented toward the new travel direction during anticipated compared to unanticipated sidestepping. No significant differences in transverse or sagittal plane coordination were observed throughout the change of direction stride. However, during unanticipated sidestepping we observed significantly reduced in-phase head-trunk coordination during the preparatory phase in the sagittal (p = 0.04, ES = 0.63) and transverse (p = 0.02, ES = 0.73) planes but did not find differences in the stance or post-transition phases. Coordination variability did not differ between anticipated and unanticipated conditions. Irrespective of planning time, greater transverse plane coordination variability was observed during the flight phases compared to the stance phase (p < 0.01) of the change of direction stride. Sagittal plane coordination variability was significantly greater during the preparatory phase than the stance phase (p < 0.01), and stance phase coordination variability was significantly greater than post-transition phase variability (p < 0.01). SIGNIFICANCE: Our results suggest differences in coordination between the head and trunk between anticipated and unanticipated sidestepping emerge during the preparatory phase of the change of direction stride, from penultimate step toe off to transition step heel strike. Anticipated and unanticipated sidestepping are different tasks, but individuals are consistent in the way the head-trunk coupling is controlled. Relating variability to task goals may allow for a better understanding of the beneficial aspects of variability observed at the head.

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This diploma thesis deals with the design of a robot head, which is intended for transfering plastic buckets from the belt conveyor to the pallet. The document comprises of the analysis of various solutions, the part with calculations of selected components, the pneumatic circuit design and the proposal for a periodic service system. The complete drawing documentation can be found in the appendixes.

In the introductory part of the thesis, there is a description of machining technologies used in the production of body. This is followed by a detailed analyse of the current technology of production of this component with an emphasis on finding its problematic parts, including a proposal of the options of the rationalization. After the methods of rationalization assesment, a new technological process was developed and the alternative tools were proposed. Considerable time and money savings were achieved by this rationalization. In the discussion section, there were designed some options of solving problems arising during the installation of this rationalization into working.

The thesis deals the preliminary draft of the small two-seat helicopter with a piston engine. The aim of the thesis is not to propose a helicopter across the extent of the problems. Therefore we have chosen only selected issues which can be managed in the range of work. The introduction is focused on defining the general requirements imposed on proposed helicopter, formulating the basic conceptual and structural design according to the building regulation the relevant category. These ranges create a based assumption for right evaluation of the statistical analysis of the helicopters of the same or very near parameters category. Subsequently, there were defined the basic parameters of the proposed helicopter which make possible to solve the performance characteristics in the vertical and backward flight. The work is also focused on design of the rotor head of main rotor for the proposed helicopter, the definition of load acting on the rotor head, waving analysis and calculation of centrifugal forces acting on the main rotor blades. The design of the rotor head and also the helicopter as a whole will be graphically processed in the program Dassault Systemes Catia.