Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 4 uppsatser. Även tryckt utgåva.

The objective of this study was to examine the link between radiographic measures of bone quality and total knee implant migration as measured by radiostereometric analysis (RSA). Two uncemented total knee arthroplasty studies (n=65) with RSA and bone mineral density (BMD) exams up to two years post surgery, and one study with cemented total knees with one year RSA data (n=18) were examined. Radiograph image texture analysis was used to characterize the bone microarchitecture, and a feasibility study was conducted to determine if a given x-ray machine could be used to obtain bone mineral density at the same time as the RSA exams. Random ForestTM ensemble classification tree statistical models classified patients into groups based on implant migration with a range of cut-points. Models based on bone texture parameters measured from the two year radiographs had a sensitivity of 87.5% and specificity of 80% when classifying patients who had more than 0.3mm maximum total point motion (MTPM) at two years using the one year exam as reference. Other cut-points were examined, with models generally having a lower specificity if the acceptable migration was smaller, and lower sensitivity if higher migrations were tolerable. In a predictive model, post-operative bone texture could be used to create a model with a sensitivity of 75% and a specificity of 80% when predicting those subjects with cemented implants who went on to more than 0.4mm total migration by one year. Bone mineral density of the proximal tibia, as determined by clinical scanners, was not found to increase the accuracy of implant migration group classification. An empirical fit to central regions of a purposed-built cross-wedge calibration phantom returned residuals of less than ±1.5% for the bone-equivalent thicknesses. The coefficient of variation of the region greyscale values in three images spread over three days is under 4%, showing the stability of the system to hold a calibration between phantom exams and patient scans. Scatter and dynamic range issues will need to be considered for an accurate calibration across the full range of areal bone mineral densities in the distal femur and proximal tibia.

AIM: Bone changes in size and density in response to different levels of stress. Alterations to bone mineral density (BMD) appear to occur in a site specific manner. Even though BMD has been examined in many populations there is a paucity of data looking at strength-power athletes, such as throwers. Therefore, the purpose of this study was to examine the BMD of a group of USA Division I collegiate throwers (e.g. shot put, discus, etc.). METHODS: Seven throwers (4 males; 3 females) who were 19.0 ± 0.9 years had their BMD compared to an age matched control group (n=14; 8 women and 6 men) and normative data. BMD was measured with dual X-ray absorptometry. Potential right/left side and sex difference in BMD were also examined. Maximal isometric strength was assessed using a mid-thigh pull while standing on a forceplate which generated force-time curves. Peak force (PF) and normalized peak force (PFa) were then correlated with BMDs. RESULTS: Generally, throwers had denser bones with male throwers tending to have a greater total BMD (P≤0.05). The dominant arm BMD was slightly greater when compared to non-dominant arm (P≤0.05). Furthermore, total body BMD was related to PF (r=0.68, r2 =0.46) and PFa (r=0.56, r2=0.31). CONCLUSIONS: Throwers have greater BMDs than non-athletes and most other athletes. However, throwers only showed a small indication of sidedness. It is likely that the BMDs observed in this study stem from the training intervention (e.g. whole body heavy lifting) undertaken by this population.

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International Telemetering Conference Proceedings / October 28-31, 1996 / Town and Country Hotel and Convention Center, San Diego, California / The Ballistic Missile Defense Organization (BMDO) is developing new Theater Missile Defense (TMD) and National Missile Defense (NMD) weapon systems to defend against the expanding ballistic missile threat. In the arms control arena, theater ballistic missile threats have been defined to include systems with reentry velocities up to five kilometers per second and strategic ballistic missile threats have reentry velocities that exceed five kilometers per second. The development and testing of TMD systems such as the Army Theater High Altitude Area Defense (THAAD) and the Navy Area Theater Ballistic Missile Defense (TBMD) Lower Tier, and NMD systems such as the Army Exoatmospheric Kill Vehicle and the Army Ground-Based Radar, pose exceptional challenges that stem from extreme acquisition range and high telemetry data transfer rates. Potential Central Pacific range locations include U.S. Army Kwajalien Atoll/Kwajalein Missile Range (USAKA/KMR) and the Pacific Missile Range Facility (PMRF) with target launches from Vandenberg Air Force Base, Wake Island, Aur Atoll, Johnston Island, and, possibly, an airborne platform. Safety considerations for remote target launches dictate utilization of high-data-rate, on-board instrumentation; technical performance measurement dictates transmission of focal plane array data; and operational requirements dictate intercepts at exoatmospheric altitudes and long slant ranges. The high gain, high data rate, telemetry acquisition requirements, coupled with loss of the upper S-band spectrum, may require innovative approaches to minimize electronic noise, maximize telemetry system gain, and fully utilize the limited S-band telemetry spectrum. The paper will address the emerging requirements and will explore the telemetry design trade space.

Osteogenesis imperfecta (OI) is a heterogeneous disease of connective tissue, the cardinal symptom being fractures and severity ranging from mild to lethal. Dominant mutations in collagen I, encoded by COL1A1 and COL1A2, cause >90% of cases. To delineate genotype-phenotype correlations and pharmaco-genetic response, collagen I was sequenced in 150 unrelated Swedish families and clinical data were collected in Paper I. Mutation type, gene affected, and N- to C-terminal location correlated with phenotype and severity. Bisphosphonate response assessed by calculated yearly change in lumbar spine bone mineral density (BMD) was inversely related to age and BMD at treatment initiation. Mutations associated with a more severe phenotype exhibited an increased response after 2 years; however, all types of OI responded well. To investigate the effect of naturally occurring variations in collagen I, the only common coding single nucleotide polymorphism (rs42524 in COL1A2) was genotyped in 2004 healthy men in Paper II. Heterozygous genotype was associated with decreased BMD and an increased risk of stroke. An adolescent with repeated fractures despite a markedly high BMD harbored a unique C-terminal procollagen cleavage-site mutation in COL1A1, which motivated extensive investigations in concert with a similar COL1A2 case in Paper III. The probands were found to have impaired procollagen processing, incorporation of collagen with retained C-propeptide in matrix and increased mineral to matrix ratio, which demonstrates that C-propeptide cleavage is crucial to normal bone mineralization and structure. Bisphosphonate therapy has insufficient effect in OI, and as classical OI is a dominant disorder severe cases would benefit from silencing of the mutated allele. In Paper IV and V small interfering RNAs (siRNAs) were used to allele-specifically target primary human bone cells heterozygous for I) a coding polymorphism in COL1A2 and II) insertion/deletions in the 3’UTR of COL1A1 and COL1A2. Results were promising with altered allele ratios and decreased mRNA levels in the predicted fashion. To summarize, this thesis found that collagen I is crucial to bone and connective tissue and that collagen I mutations create markedly diverse phenotypes. Age, BMD and pharmaco-genetic effects influence the response to bisphosphonate therapy in individuals with OI; however, novel approaches are needed. Utilizing allele-specific siRNAs may be a way forward in the treatment of severe OI.

This thesis is based on studies of the ten-year community-based intervention programme entitled, the Vadstena Osteoporosis Prevention Project (VOPP). The specific aims of the research were to describe the effects of physical activity and training programmes on bone mass and balance performance in adults, to determine whether a fall risk prevention programme could motivate personal actions among the elderly, to ascertain whether the intervention programme could reduce the incidence of forearm and hip fractures. Two studies addressed training programmes for middle-aged and old people. First, VOPP participants who were aged 40–70 years and had low forearm bone mineral density (BMD) values were invited to take part in a one-year weight-bearing training study. Thirty of those individuals were included in the investigation. Additional bone mass measurements were performed at the hip and the lumbar spine, and balance and aerobic capacity were also tested. The training programme was performed twice a week (I). In the second study, healthy persons aged 70–75 years were invited to participate in a balance-training study. Fifteen persons joined an exercise group, and another fifteen were controls. The training programme comprised specific balance exercises and was carried out twice a week for nine weeks (II). The association between forearm BMD values and several lifestyle factors was explored in random samples of the population aged 20–72 years (n=880) in a cross-sectional study (III). Another study explored the association between calcaneal stiffness, forearm BMD, and lifestyle factors amongst participants aged 20–79 years (n=956) at the final registration of the VOPP (V). Effects of the VOPP interventions directed at environmental risk factors for falls and the promotion of physical activity were examined in people aged ≥ 65 years (IV). The incidence of forearm and hip fractures was studied amongst middle-aged and elderly individuals in the intervention and the control communities during the study period 1987–2001 (VI). The exercise group (n=15) in the weight-bearing training study showed increases in BMD at the greater trochanter (p<0.01), one-leg stance balance with the eyes closed and coordination tests (p<0.05), and aerobic capacity (p<0.05). No significant difference was found when the groups were compared concerning changes in the different tests during the intervention period (I). In the balance-training study, the exercise group showed post-training improvement in the following tests: standing on the right leg with eyes closed (p<0.01), standing on the right leg (p<0.01) and on the left leg (p<0.05) while turning the head, and walking 30 metres (p<0.01). There were significant differences between the groups in these tests when changes were compared at the post-intervention test (II). Age (p<0.0001) and body mass index (p≤.0001) were associated with forearm BMD in both sexes. Reported moderate physical activity levels in men were positively associated with forearm BMD (p<0.05) (III). In both sexes, reported moderate (p<0.05) and high (women p<0.05 and men p<0.001) physical activity levels were positively associated with calcaneal stiffness. The correlation coefficient between forearm BMD and calcaneal stiffness was 0.58 in women and 0.34 in men (V). Persons aged ≥ 65 years at the follow-up in 1994 reported more use of shoe/cane spikes and moderate physical activity levels compared to controls (IV). There was no change in the general incidence of forearm and hip fractures between the communities for the study period. However, there was a tendency towards decreasing incidence of forearm and trochanteric hip fracture in both sexes during the late intervention period in the intervention community (VI). A community-based intervention programme aimed at reducing the incidence of osteoporotic fractures must be regarded as a long-term project and should preferably be monitored over an extended post-intervention period. / On the day of the public defence the statuses of articles IV and V were Submitted and VI was Manuscript

Includes supplemental material. / Based on public law and Presidential mandate, ballistic missile defense development is a front-burner issue for homeland defense and the defense of U.S. and coalition forces abroad. Spearheaded by the Missile Defense Agency, an integrated ballistic missile defense system was initiated to create a layered defense composed of land-, air-, sea-, and space-based assets. The Ship Anti-Ballistic Response (SABR) Project is a systems engineering approach that suggests a conceptualized system solution to meet the needs of the sea portion of ballistic missile defense in the 2025-2030 timeframe. The system is a unique solution to the sea-based ballistic missile defense issue, combining the use of a railgun interceptor and a conformable aperture skin-of-the-ship radar system.

Seconde espèce de mollusque bivalve la plus exploitée au monde, la palourde japonaise Venerupis philippinarum représente un intérêt économique majeur. A l'échelle du bassin d'Arcachon, la maladie du muscle marron ou BMD (pour Brown Muscle Disease), pathologie émergente découverte en 2005 inquiète tout particulièrement le secteur de la pêche. Cette pathologie affecte le muscle adducteur postérieur de la palourde et perturbe l'ouverture-fermeture des valves. Cette perturbation entraine la remontée des individus à la surface du sédiment et la mort.Ces travaux de thèse ont porté d'une part sur l'épizootiologie de la maladie et son impact sur l'hôte et d'autre part sur l'identification de l'agent responsable de la maladie.Une étude sur la distribution des palourdes dans le bassin d'Arcachon (littoral Atlantique français) montre que la prévalence de la BMD a diminué entre 2010 et 2012. Toutefois cette baisse ne concerne pas les individus ayant atteint la taille légale de pêche (> 35mm). De plus, la maladie semble apparaitre chez des individus de plus en plus petit et risque donc d'accroitre la mortalité aux plus jeunes stades. L'analyse des facteurs environnementaux impliqués dans la distribution de la maladie souligne la corrélation entre la prévalence de la BMD et un hydrodynamisme relativement " calme ".La BMD affecte tout particulièrement le métabolisme énergétique de l'hôte, les mécanismes de réponse au stress oxydant et également le système immunitaire. De nombreuses fonctions sont surexprimées chez les hôtes malades mais d'autres voies comme celle de l'apoptose sont régulées négativement par l'agent infectieux.Si l'origine virale est maintenant une hypothèse solide (microscopie électronique, transcriptomique), la nature exacte de l'agent étiologique (famille virale) ne peut à ce jour être déterminée avec certitude. Des particules virales ont bien été observées dans les tissus malades mais pas dans les tissus sains, et ont pu être purifiées sur gradient de sucrose. Toutefois, les essais pour provoquer la maladie chez des individus sains ont échoué.