Quantitative stereophotogrammetric & MRI evaluation of ankle articular cartilage and ankle joint contact characteristics

Osteoarthritis and degenerative cartilage diseases affect millions of people. Therefore, there is huge interest in developing new therapies to repair, replace and/or regenerate cartilage. This necessitates advances in techniques which make earlier non-invasive diagnosis and objective quantitative evaluations of new therapies possible. Most previous research has focused on the knee and neglected the ankle joint. Hence, the aims of this thesis are to describe and quantify the geometric properties of ankle cartilage, to evaluate joint contact characteristics and develop techniques which allow quantitative measurements to be made in vivo. Chapters 3 and 6 describe the application of a high resolution stereophotography system for making highly accurate 3-D geometric models from which quantitative measurements of cartilage parameters and joint area contact can be made. Chapters 4 and 5 report the testing of image analysis algorithms designed to segment cartilage sensitive MR images. Work focused on initially on a semi-automated 2-D segmentation approach and subsequently on a pilot study of 3-D automated segmentation algorithm. The stereophotographic studies were highly accurately and demonstrated that ankle cartilage thickness is greater than previously reported with the thickest cartilage occurring where cartilage injuries are most commonly seen. Furthermore, joint contact area is larger than previously believed and corresponds to the regions of the thickest cartilage over the talar shoulders. The image analysis studies show that it is possible to accurately and reproducibly segment the thin cartilage layers of the ankle joint using a semi-automated approach. The feasibility of a fully automated 3D method for future clinical use is also shown. In conclusion this thesis presents novel methods for examining ankle articular cartilage in vitro and in vivo, showing that the thickest cartilage occurs in highly curved regions over the shoulders of the talus which correspond to regions of greatest contact. Importantly, the image analysis techniques may be used for future clinical monitoring of patients sustaining cartilage injuries or undergoing cartilage repair therapies

Quantitative stereophotogrammetric & MRI evaluation of ankle articular cartilage and ankle joint contact characteristics

Osteoarthritis and degenerative cartilage diseases affect millions of people. Therefore, there is huge interest in developing new therapies to repair, replace and/or regenerate cartilage. This necessitates advances in techniques which make earlier non-invasive diagnosis and objective quantitative evaluations of new therapies possible. Most previous research has focused on the knee and neglected the ankle joint. Hence, the aims of this thesis are to describe and quantify the geometric properties of ankle cartilage, to evaluate joint contact characteristics and develop techniques which allow quantitative measurements to be made in vivo. Chapters 3 and 6 describe the application of a high resolution stereophotography system for making highly accurate 3-D geometric models from which quantitative measurements of cartilage parameters and joint area contact can be made. Chapters 4 and 5 report the testing of image analysis algorithms designed to segment cartilage sensitive MR images. Work focused on initially on a semi-automated 2-D segmentation approach and subsequently on a pilot study of 3-D automated segmentation algorithm. The stereophotographic studies were highly accurately and demonstrated that ankle cartilage thickness is greater than previously reported with the thickest cartilage occurring where cartilage injuries are most commonly seen. Furthermore, joint contact area is larger than previously believed and corresponds to the regions of the thickest cartilage over the talar shoulders. The image analysis studies show that it is possible to accurately and reproducibly segment the thin cartilage layers of the ankle joint using a semi-automated approach. The feasibility of a fully automated 3D method for future clinical use is also shown. In conclusion this thesis presents novel methods for examining ankle articular cartilage in vitro and in vivo, showing that the thickest cartilage occurs in highly curved regions over the shoulders of the talus which correspond to regions of greatest contact. Importantly, the image analysis techniques may be used for future clinical monitoring of patients sustaining cartilage injuries or undergoing cartilage repair therapies

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies.publishedVersio

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies

Persistent urban impacts on surface waterPersistent urban impacts on surface water quality via impacted groundwater in Red Butte Creek

Growing population centers along mountain watersheds put added stress on sensitive hydrologic systems and create water quality impacts downstream. We examined the mountain-to-urban transition in watersheds on Utah’s Wasatch Front to identify mechanisms by which urbanization impacts water resources. Rivers in the Wasatch flow from the mountains directly into an urban landscape, where they are subject to channelization, stormwater runoff systems, and urban inputs to water quality from sources such as road salt and fertilizer. As part of an interdisciplinary effort within the iUTAH project, multiple synoptic surveys were performed and a variety of measurements were made, including basic water chemistry along with discharge, water isotopes, and nutrients. Red Butte Creek, a stream in Salt Lake City, does not show significant urban impact to water quality until several kilometers after it enters the city where concentrations of solutes such as chloride and nitrate more than triple in a gaining reach. Groundwater springs discharging to this gaining section demonstrate urban-impacted water chemistry, suggesting that during baseflow a contaminated alluvial aquifer significantly controls stream chemistry. By combining hydrometric and hydrochemical observations we were able to estimate that these groundwater springs were 17-20% urban runoff. We were then able to predict the chemistry of urban runoff that feeds into the alluvial aquifer. Samples collected from storm culverts, roofs, and asphalt during storms had chemistry values within the range of those predicted by the mixing model. This evidence that urbanization affects the water quality of baseflow through impacted groundwater suggests that stormwater mitigation may not be sufficient for protecting urban watersheds, and quantifying these persistent groundwater mediated impacts is necessary to evaluate the success of restoration efforts. Further work involves using fluorescence analysis of dissolved organic matter chemistry and microbial genomics to identify “fingerprints” of urban impacts to water quality

Abatacept limits breach of self-tolerance in a Murine model of arthritis via effects on the generation of T follicular helper cells

Abatacept modulates CD28-mediated T cell costimulation and is efficacious in the treatment of rheumatoid arthritis (RA). Its mechanism of action has not been fully elucidated but will likely reveal critical pathologic pathways in RA. We show that abatacept substantially modulated Ag-specific T and B cell responses in vivo. Ag-specific T cell proliferation was reduced, and the acquisition of an activated phenotype, characterized by upregulation of CD69, OX40, ICOS, and programmed death-1 and downregulation of CD62L, was suppressed. Furthermore, abatacept suppressed the production of inflammatory cytokines, such as IFN-{gamma} and IL-17. These effects were associated with a failure of Ag-specific T cells to acquire the CXCR5+ICOS+ T follicular helper cell phenotype. This, in turn, led to a failure of these cells to enter B cell follicles, resulting in reduced specific Ab responses, despite normal B cell clonal expansion. To test the pathologic significance of this, we used a novel model of RA associated with breach of self-tolerance to self-Ag and demonstrated that abatacept prevented the emergence of self-reactivity. Thus, CD28-dependent signaling is required for optimal T follicular helper cell maturation and expansion, and its inhibition prevents loss of self-tolerance in a model of articular pathology. Thus, we provide a novel mode of action for abatacept with profound implications for its potential usefulness in early inflammatory arthropathies associated with autoantibody expression

Persistent Urban Influence on Surface Water Quality via Impacted Groundwater

Growing urban environments stress hydrologic systems and impact downstream water quality. We examined a third-order catchment that transitions from an undisturbed mountain environment into urban Salt Lake City, Utah. We performed synoptic surveys during a range of seasonal baseflow conditions and utilized multiple lines of evidence to identify mechanisms by which urbanization impacts water quality. Surface water chemistry did not change appreciably until several kilometers into the urban environment, where concentrations of solutes such as chloride and nitrate increase quickly in a gaining reach. Groundwater springs discharging in this gaining system demonstrate the role of contaminated baseflow from an aquifer in driving stream chemistry. Hydrometric and hydrochemical observations were used to estimate that the aquifer contains approximately 18% water sourced from the urban area. The carbon and nitrogen dynamics indicated the urban aquifer also serves as a biogeochemical reactor. The evidence of surface water–groundwater exchange on a spatial scale of kilometers and time scale of months to years suggests a need to evolve the hydrologic model of anthropogenic impacts to urban water quality to include exchange with the subsurface. This has implications on the space and time scales of water quality mitigation efforts