Capturing How Objects Flow At Runtime

Most of today's dynamic analysis approaches are based on method traces. However, in the case of object-orientation understanding program execution by analyzing method traces is complicated because the behavior of a program depends on the sharing and the transfer of object references (aliasing). We argue that trace-based dynamic analysis is at a too low level of abstraction for object-oriented systems. We propose a new approach that captures the life cycle of objects by explicitly taking into account object aliasing and how aliases propagate during the execution of the program. In this paper, we present in detail our new meta-model and discuss future tracks opened by it.

Analyzing, Capturing and Taming Software Change

Software systems need to continuously change to remain useful. Change appears in several forms and needs to be accommodated at different levels. We propose ChangeBoxes as a mechanism to encapsulate, manage, analyze and exploit changes to software systems. Our thesis is that only by making change explicit and manipulable can we enable the software developer to manage software change more effectively than is currently possible. Furthermore we argue that we need new insights into assessing the impact of changes and we need to provide new tools and techniques to manage them. We report on the results of some initial prototyping efforts, and we outline a series of research activities that we have started to explore the potential of ChangeBoxes.

Effectiveness, safety and cost-effectiveness of homeopathy in general practice - summarized health technology assessment

Introduction: The Health Technology Assessment report on effectiveness, cost-effectiveness and appropriateness of homeopathy was compiled on behalf of the Swiss Federal Office for Public Health (BAG) within the framework of the 'Program of Evaluation of Complementary Medicine (PEK)'. Materials and Methods: Databases accessible by Internet were systematically searched, complemented by manual search and contacts with experts, and evaluated according to internal and external validity criteria. Results: Many high-quality investigations of pre-clinical basic research proved homeopathic high-potencies inducing regulative and specific changes in cells or living organisms. 20 of 22 systematic reviews detected at least a trend in favor of homeopathy. In our estimation 5 studies yielded results indicating clear evidence for homeopathic therapy. The evaluation of 29 studies in the domain 'Upper Respiratory Tract Infections/Allergic Reactions' showed a positive overall result in favor of homeopathy. 6 out of 7 controlled studies were at least equivalent to conventional medical interventions. 8 out of 16 placebocontrolled studies were significant in favor of homeopathy. Swiss regulations grant a high degree of safety due to product and training requirements for homeopathic physicians. Applied properly, classical homeopathy has few side-effects and the use of high-potencies is free of toxic effects. A general health-economic statement about homeopathy cannot be made from the available data. Conclusion: Taking internal and external validity criteria into account, effectiveness of homeopathy can be supported by clinical evidence and professional and adequate application be regarded as safe. Reliable statements of cost-effectiveness are not available at the moment. External and model validity will have to be taken more strongly into consideration in future studies.

NONLINEAR TUBE-FITTING FOR THE ANALYSIS OF ANATOMICAL AND FUNCTIONAL STRUCTURES

We are concerned with the estimation of the exterior surface of tube-shaped anatomical structures. This interest is motivated by two distinct scientific goals, one dealing with the distribution of HIV microbicide in the colon and the other with measuring degradation in white-matter tracts in the brain. Our problem is posed as the estimation of the support of a distribution in three dimensions from a sample from that distribution, possibly measured with error. We propose a novel tube-fitting algorithm to construct such estimators. Further, we conduct a simulation study to aid in the choice of a key parameter of the algorithm, and we test our algorithm with validation study tailored to the motivating data sets. Finally, we apply the tube-fitting algorithm to a colon image produced by single photon emission computed tomography (SPECT)and to a white-matter tract image produced using diffusion tensor `imaging (DTI).

Control algorithms for large scale adaptive optics

In this dissertation, the problem of creating effective large scale Adaptive Optics (AO) systems control algorithms for the new generation of giant optical telescopes is addressed. The effectiveness of AO control algorithms is evaluated in several respects, such as computational complexity, compensation error rejection and robustness, i.e. reasonable insensitivity to the system imperfections. The results of this research are summarized as follows: 1. Robustness study of Sparse Minimum Variance Pseudo Open Loop Controller (POLC) for multi-conjugate adaptive optics (MCAO). The AO system model that accounts for various system errors has been developed and applied to check the stability and performance of the POLC algorithm, which is one of the most promising approaches for the future AO systems control. It has been shown through numerous simulations that, despite the initial assumption that the exact system knowledge is necessary for the POLC algorithm to work, it is highly robust against various system errors. 2. Predictive Kalman Filter (KF) and Minimum Variance (MV) control algorithms for MCAO. The limiting performance of the non-dynamic Minimum Variance and dynamic KF-based phase estimation algorithms for MCAO has been evaluated by doing Monte-Carlo simulations. The validity of simple near-Markov autoregressive phase dynamics model has been tested and its adequate ability to predict the turbulence phase has been demonstrated both for single- and multiconjugate AO. It has also been shown that there is no performance improvement gained from the use of the more complicated KF approach in comparison to the much simpler MV algorithm in the case of MCAO. 3. Sparse predictive Minimum Variance control algorithm for MCAO. The temporal prediction stage has been added to the non-dynamic MV control algorithm in such a way that no additional computational burden is introduced. It has been confirmed through simulations that the use of phase prediction makes it possible to significantly reduce the system sampling rate and thus overall computational complexity while both maintaining the system stable and effectively compensating for the measurement and control latencies.

Triggering of volcanic activity by large earthquakes

Statistical analyses of temporal relationships between large earthquakes and volcanic eruptions suggest seismic waves may trigger eruptions even over great (>1000 km) distances, although the causative mechanism is not well constrained. In this study the relationship between large earthquakes and subtle changes in volcanic activity was investigated in order to gain greater insight into the relationship between dynamic stresses propagated by surface waves and volcanic response. Daily measurements from the Ozone Monitoring Instrument (OMI), onboard the Aura satellite, provide constraints on volcanic sulfur-dioxide (SO2) emission rates as a measure of subtle changes in activity. Time series of SO2 emission rates were produced from OMI data for thirteen persistently active volcanoes from 1 October 2004 to 30 September 2010. In order to quantify the affect of earthquakes at teleseismic distances, we modeled surface-wave amplitudes from the source mechanisms of moment magnitude (Mw) ≥7 earthquakes, and calculated the Peak Dynamic Stress (PDS). We assessed the influence of earthquakes on volcanic activity in two ways: 1) by identifying increases in the SO2 time series data and looking for causative earthquakes and 2) by examining the average emission rate before and after each earthquake. In the first, the SO2 time series for each volcano was used to calculate a baseline threshold for comparison with post-earthquake emission. Next, we generated a catalog of responses based on sustained SO2 emission increases above this baseline. Delay times between each SO2 response and each prior earthquake were analyzed using both the actual earthquake catalog, and a randomly generated catalog of earthquakes. This process was repeated for each volcano. Despite varying multiple parameters, this analysis did not demonstrate a clear relationship between earthquake-generated PDS and SO2 emission. However, the second analysis, which was based on the occurrence of large earthquakes indicated a response at most volcanoes. Using the PDS calculations as a filtering criterion for the earthquake catalog, the SO2 mass for each volcano was analyzed in 28-day windows centered on the earthquake origin time. If the average SO2 mass after the earthquake was greater than an arbitrary percentage of pre-earthquake mass, we identified the volcano as having a response to the event. This window analysis provided insight on what type of volcanic activity is more susceptible to triggering by dynamic stress. The volcanoes with very open systems included in this study, Ambrym, Gaua, Villarrica, Erta Ale and, Turrialba, showed a clear response to dynamic stress while the volcanoes with more closed systems, Merapi, Semeru, Fuego, Pacaya, and Bagana, showed no response.

Multi-parametric classification of Alzheimer's disease and mild cognitive impairment: the impact of quantitative magnetization transfer MR imaging

Multi-parametric and quantitative magnetic resonance imaging (MRI) techniques have come into the focus of interest, both as a research and diagnostic modality for the evaluation of patients suffering from mild cognitive decline and overt dementia. In this study we address the question, if disease related quantitative magnetization transfer effects (qMT) within the intra- and extracellular matrices of the hippocampus may aid in the differentiation between clinically diagnosed patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI) and healthy controls. We evaluated 22 patients with AD (n=12) and MCI (n=10) and 22 healthy elderly (n=12) and younger (n=10) controls with multi-parametric MRI. Neuropsychological testing was performed in patients and elderly controls (n=34). In order to quantify the qMT effects, the absorption spectrum was sampled at relevant off-resonance frequencies. The qMT-parameters were calculated according to a two-pool spin-bath model including the T1- and T2 relaxation parameters of the free pool, determined in separate experiments. Histograms (fixed bin-size) of the normalized qMT-parameter values (z-scores) within the anterior and posterior hippocampus (hippocampal head and body) were subjected to a fuzzy-c-means classification algorithm with downstreamed PCA projection. The within-cluster sums of point-to-centroid distances were used to examine the effects of qMT- and diffusion anisotropy parameters on the discrimination of healthy volunteers, patients with Alzheimer and MCIs. The qMT-parameters T2(r) (T2 of the restricted pool) and F (fractional pool size) differentiated between the three groups (control, MCI and AD) in the anterior hippocampus. In our cohort, the MT ratio, as proposed in previous reports, did not differentiate between MCI and AD or healthy controls and MCI, but between healthy controls and AD.

Combined alpha-methylacyl coenzyme A racemase/p53 analysis to identify dysplasia in inflammatory bowel disease

Identification of dysplasia in inflammatory bowel disease represents a major challenge for both clinicians and pathologists. Clear diagnosis of dysplasia in inflammatory bowel disease is sometimes not possible with biopsies remaining "indefinite for dysplasia." Recent studies have identified molecular alterations in colitis-associated cancers, including increased protein levels of alpha-methylacyl coenzyme A racemase, p53, p16 and bcl-2. In order to analyze the potential diagnostic use of these parameters in biopsies from inflammatory bowel disease, a tissue microarray was manufactured from colons of 54 patients with inflammatory bowel disease composed of 622 samples with normal mucosa, 78 samples with inflammatory activity, 6 samples with low-grade dysplasia, 12 samples with high-grade dysplasia, and 66 samples with carcinoma. In addition, 69 colonoscopic biopsies from 36 patients with inflammatory bowel disease (28 low-grade dysplasia, 8 high-grade dysplasia, and 33 indefinite for dysplasia) were included in this study. Immunohistochemistry for alpha-methylacyl coenzyme A racemase, p53, p16 and bcl-2 was performed on both tissue microarray and biopsies. p53 and alpha-methylacyl coenzyme A racemase showed the most discriminating results, being positive in most cancers (77.3% and 80.3%) and dysplasias (94.4% and 94.4%) but only rarely in nonneoplastic epithelium (1.6% and 9.4%; P < .001). Through combining the best discriminators, p53 and alpha-methylacyl coenzyme A racemase, a stronger distinction between neoplastic tissues was possible. Of all neoplastic lesions, 75.8% showed a coexpression of alpha-methylacyl coenzyme A racemase and p53, whereas this was found in only 4 of 700 nonneoplastic samples (0.6%). alpha-methylacyl coenzyme A racemase/p53 coexpression was also found in 10 of 33 indefinite for dysplasia biopsies (30.3 %), suggesting a possible neoplastic transformation in these cases. Progression to dysplasia or carcinoma was observed in 3 of 10 p53/alpha-methylacyl coenzyme A racemase-positive, indefinite-for-dysplasia cases, including 1 of 7 cases without and 2 of 3 cases with p53 mutation. It is concluded that combined alpha-methylacyl coenzyme A racemase/p53 analysis may represent a helpful tool to confirm dysplasia in inflammatory bowel disease.

Algorithms For Automatic And Robust Registration Of 3D Head Scans

wo methods for registering laser-scans of human heads and transforming them to a new semantically consistent topology defined by a user-provided template mesh are described. Both algorithms are stated within the Iterative Closest Point framework. The first method is based on finding landmark correspondences by iteratively registering the vicinity of a landmark with a re-weighted error function. Thin-plate spline interpolation is then used to deform the template mesh and finally the scan is resampled in the topology of the deformed template. The second algorithm employs a morphable shape model, which can be computed from a database of laser-scans using the first algorithm. It directly optimizes pose and shape of the morphable model. The use of the algorithm with PCA mixture models, where the shape is split up into regions each described by an individual subspace, is addressed. Mixture models require either blending or regularization strategies, both of which are described in detail. For both algorithms, strategies for filling in missing geometry for incomplete laser-scans are described. While an interpolation-based approach can be used to fill in small or smooth regions, the model-driven algorithm is capable of fitting a plausible complete head mesh to arbitrarily small geometry, which is known as "shape completion". The importance of regularization in the case of extreme shape completion is shown.

Clinical outcome of single porcelain-fused-to-zirconium dioxide crowns: a systematic review

STATEMENT OF PROBLEM The increasing demand by patients for esthetic and metal-free restorations has driven the development of ceramic restorations with good esthetic and mechanical stability. Recent clinical studies have investigated the use of zirconium dioxide as a core material for complete crowns and computer-aided-design/computer-aided-manufacturing fabricated restorations. PURPOSE The aim of this systematic review was to evaluate the clinical survival rates of porcelain-fused-to-zirconia (PFZ) single crowns on anterior and posterior teeth and to compare them with metal ceramic (MC) crowns. MATERIAL AND METHODS A systematic search was conducted with PubMed and manual research to identify literature written in English that refers to in vivo studies published from January 1, 1950 through July 1, 2011. Clinical trials that evaluated PFZ and MC single crowns on natural teeth were selected for further analysis. Titles and/or abstracts of articles identified through the electronic searches were reviewed and evaluated for appropriateness. In addition, a hand search of relevant dental journals was peformed, and reference lists of culled articles were screened to identify publications. RESULTS The search resulted in a total of 488 initial matches. Nineteen studies with a total of 3621 crowns met the inclusion criteria. The survival rates of PFZ crowns (total 300) ranged from 92.7% to 100% for a follow-up time of 24 to 39 months, whereas those of MC crowns (total 3321) ranged from 70% to 100% for a follow-up time of 12 to 298 months. Studies that reported long-term results were found only for the MC crown group. CONCLUSIONS The scientific clinical data available to compare PFZ and MC crowns are limited. The survival rates may well be influenced by the selection and appropriate use of the veneering ceramic, and, therefore, additional prospective long-term clinical trials are necessary to draw reliable conclusions.