Methods to Facilitate the Capture, Use, and Reuse of Structured and Unstructured Clinical Data.

Electronic health records (EHRs) have great potential to improve quality of care and to support clinical and translational research. While EHRs are being increasingly implemented in U.S. hospitals and clinics, their anticipated benefits have been largely unachieved or underachieved. Among many factors, tedious documentation requirements and the lack of effective information retrieval tools to access and reuse data are two key reasons accounting for this deficiency. In this dissertation, I describe my research on developing novel methods to facilitate the capture, use, and reuse of both structured and unstructured clinical data. Specifically, I develop a framework to investigate potential issues in this research topic, with a focus on three significant challenges. The first challenge is structured data entry (SDE), which can be facilitated by four effective strategies based on my systematic review. I further propose a multi-strategy model to guide the development of future SDE applications. In the follow-up study, I focus on workflow integration and evaluate the feasibility of using EHR audit trail logs for clinical workflow analysis. The second challenge is the use of clinical narratives, which can be supported by my innovative information retrieval (IR) technique called “semantically-based query recommendation (SBQR)”. My user experiment shows that SBQR can help improve the perceived performance of a medical IR system, and may work better on search tasks with average difficulty. The third challenge involves reusing EHR data as a reference standard to benchmark the quality of other health-related information. My study assesses the readability of trial descriptions on ClinicalTrials.gov and found that trial descriptions are very hard to read, even harder than clinical notes. My dissertation has several contributions. First, it conducts pioneer studies with innovative methods to improve the capture, use, and reuse of clinical data. Second, my dissertation provides successful examples for investigators who would like to conduct interdisciplinary research in the field of health informatics. Third, the framework of my research can be a great tool to generate future research agenda in clinical documentation and EHRs. I will continue exploring innovative and effective methods to maximize the value of EHRs.PHDInformationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135845/1/tzuyu_1.pd

Sistema de miografia óptica para reconhecimento de gestos e posturas de mão

Orientador: Éric FujiwaraDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia MecânicaResumo: Nesse projeto, demonstrou-se um sistema de miografia óptica como uma alternativa promissora para monitorar as posturas da mão e os gestos do usuário. Essa técnica se fundamenta em acompanhar as atividades musculares responsáveis pelos movimentos da mão com uma câmera externa, relacionando a distorção visual verificada no antebraço com a contração e o relaxamento necessários para dada postura. Três configurações de sensores foram propostas, estudadas e avaliadas. A primeira propôs monitorar a atividade muscular analisando a variação da frequência espacial de uma textura de listras uniformes impressa sobre a pele, enquanto que a segunda se caracteriza pela contagem de pixels de pele visível dentro da região de interesse. Ambas as configurações se mostraram inviáveis pela baixa robustez e alta demanda por condições experimentais controladas. Por fim, a terceira recupera o estado da mão acompanhando o deslocamento de uma série de marcadores coloridos distribuídos ao longo do antebraço. Com um webcam de 24 fps e 640 × 480 pixels, essa última configuração foi validada para oito posturas distintas, explorando principalmente a flexão e extensão dos dedos e do polegar, além da adução e abdução do último. Os dados experimentais, adquiridos off-line, são submetidos a uma rotina de processamento de imagens para extrair a informação espacial e de cor dos marcadores em cada quadro, dados esses utilizados para rastrear os mesmos marcadores ao longo de todos os quadros. Para reduzir a influência das vibrações naturais e inerentes ao corpo humano, um sistema de referencial local é ainda adotado dentro da própria região de interesse. Finalmente, os dados quadro a quadro com o ground truth são alimentados a uma rede neural artificial sequencial, responsável pela calibração supervisionada do sensor e posterior classificação das posturas. O desempenho do sistema para a classificação das oito posturas foi avaliado com base na validação cruzada com 10-folds, com a câmera monitorando o antebraço pela superfície interna ou externa. O sensor apresentou uma precisão de ?92.4% e exatidão de ?97.9% para o primeiro caso, e uma precisão de ?75.1% e exatidão de ?92.5% para o segundo, sendo comparável a outras técnicas de miografia, demonstrando a viabilidade do projeto e abrindo perspectivas para aplicações em interfaces humano-robôAbstract: In this work, an optical myography system is demonstrated as a promising alternative to monitor hand posture and gestures of the user. This technique is based on accompanying muscular activities responsible for hand motion with an external camera, and relating the visual deformation observed on the forearm to the muscular contractions/relaxations for a given posture. Three sensor designs were proposed, studied and evaluated. The first one intended to monitor muscular activity by analyzing the spatial frequency variation of a uniformly distributed stripe pattern stamped on the skin, whereas the second one is characterized by reckoning visible skin pixels inside the region of interest. Both designs are impracticable due to their low robustness and high demand for controlled experimental conditions. At last, the third design retrieves hand configuration by tracking visually the displacements of a series of color markers distributed over the forearm. With a webcam of 24 fps and 640 × 480 pixels, this design was validated for eight different postures, exploring fingers and thumb flexion/extension, plus thumb adduction/abduction. The experimental data are acquired offline and, then, submitted to an image processing routine to extract color and spatial information of the markers in each frame; the extracted data is subsequently used to track the same markers along all frames. To reduce the influence of human body natural and inherent vibrations, a local reference frame is yet adopted in the region of interest. Finally, the frame by frame data, along with the ground truth posture, are fed into a sequential artificial neural network, responsible for sensor supervised calibration and subsequent posture classification. The system performance was evaluated in terms of eight postures classification via 10-fold cross-validation, with the camera monitoring either the underside or the back of the forearm. The sensor presented a ?92.4% precision and ?97.9% accuracy for the former, and a ?75.1% precision and ?92.5% accuracy for the latter, being thus comparable to other myographic techniques; it also demonstrated that the project is feasible and offers prospects for human-robot interaction applicationsMestradoEngenharia MecanicaMestre em Engenharia Mecânica33003017CAPE

Community environment, cognitive impairment and dementia in later life: results from the Cognitive Function and Ageing Study

Background: Few studies have investigated the impact of the community environment, as distinct from area deprivation, on cognition in later life. This study explores cross-sectional associations between cognitive impairment and dementia and environmental features at the community level in older people. Method: The postcodes of the 2424 participants in the year-10 interview of the Cognitive Function and Ageing Study in England were mapped into small area level geographical units (Lower-layer Super Output Areas) and linked to environmental data in government statistics. Multilevel logistic regression was conducted to investigate associations between cognitive impairment (defined as MMSE3 in GMS-AGECAT) and community level measurements including area deprivation, natural environment, land use mix and crime. Sensitivity analyses tested the impact of people moving residence within the last two years. Results: Higher levels of area deprivation and crime were not significantly associated with cognitive impairment and dementia after accounting for individual level factors. Living in areas with high land use mix was significantly associated with a nearly 60% reduced odds of dementia (OR: 0.4; 95% CI: 0.2, 0.8) after adjusting for individual level factors and area deprivation, but there was no linear trend for cognitive impairment. Increased odds of dementia (OR: 2.2, 95% CI: 1.2, 4.2) and cognitive impairment (OR: 1.4, 95% CI: 1.0, 2.0) were found in the highest quartile of natural environment availability. Findings were robust to exclusion of the recently relocated. Conclusion: Features of land use have complex associations with cognitive impairment and dementia. Further investigations should focus on environmental influences on cognition to inform health and social policies

The association between community environment and cognitive function: a systematic review.

PURPOSES: The aim of this study is to review the published evidence on the association between community environment and cognitive function in older people, focusing on the findings and a critique of the existing studies. METHODS: A literature search was conducted to identify studies linking the community environment and cognitive function in older people. The results and methodological factors, including the definition of community, individual level characteristics and the measurements of cognitive function and community environment were extracted from each study. The measurements of community environment were mainly categorized into two types: compositional, generated by aggregating individual and household data (community-level socioeconomic status, deprivation index) and contextual, targeting at the features of built or social environment in local areas (green space, street conditions, crime rate). RESULTS: Fourteen of the fifteen studies used compositional measurements such as community-level socioeconomic status and deprivation index and significant associations were found in eleven studies. Some individual level factors (ethnicity, genotype and socioeconomic status) were found to modify the association between community environment and cognitive function. Few contextual measurements were included in the existing studies. A conceptual framework for the pathway from community environment to cognitive function of older people is provided in this review. CONCLUSIONS: To disentangle the additional effect of place from individual risk factors and investigate the casual direction of community environment and cognition in later life, longitudinal studies with measurements targeting built and social environments of community and change of cognitive functions over time need to be included in future studies.Yu-Tzu Wu received a PhD scholarship from the Cambridge Trust, University of Cambridge. A. Matthew Prina is supported by the Medical Research Council [Grant number K021907/1].This is the final published manuscript. It is published by Springer here: http://dx.doi.org/10.1007/s00127-014-0945-

Prevalence of dementia in East Asia: a synthetic review of time trends.

OBJECTIVE: This study aims to synthesise evidence on time trends of dementia prevalence in East Asian countries including Japan, China, South Korea and Taiwan and assess the impact of the societal changes on future prevalence. METHOD: Relevant reviews and recent nationwide studies in East Asia were identified to investigate changes in prevalence of dementia over time taking into account the potential impact of methodological factors and study designs. RESULTS: The robust evidence that has been interpreted to suggest a substantial increasing trend over time is less compelling once fundamental differences in study methods and populations across individual surveys are considered. In Japan, longitudinal studies in small areas suggest the potential increase of prevalence after 2000. Increasing trends in China, South Korea and Taiwan over the last 20-30 years are based on the literature review without adjustment for methodological differences. Economic development and huge societal changes alongside the rise of non-communicable disease in East Asia could lead to increasing prevalence of dementia in the future once those cohorts with high risk of dementia reached their older age. CONCLUSION: Current evidence is not sufficient to suggest increasing trends of dementia prevalence in East Asia. Longitudinal studies with representative samples and stable methodology are needed to provide fundamental information of the epidemiology of dementia and identify important risk factors in East Asian societies.There is no specific funding contributing to this study. Yu-Tzu Wu received a PhD scholarship from the Cambridge Trust, University of Cambridge. Fiona E. Matthews was supported by the Medical Research Council [grant number U105292687].This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/gps.4297/abstract

Dementia: time trends and policy responses.

In recent years, dementia has been considered a public health priority and become a topic of major political interest. Recent reviews and studies have reported with varying degrees of alarm an impending and existing "dementia epidemic" with increasing predicted trends in prevalence and enormous numbers of people with dementia particularly in low- and middle-income countries (LMICs). However, robust evidence from dementia research in high-income countries suggests stable or decreased prevalence over the last decades. Current evidence is not sufficient to suggest increasing trends of prevalence in LMICs once variation in methodological factors and study populations are taken into account. Changes in diagnostic methods over the last decades substantially influence the identification of dementia cases with systematic difference between the resulting individual prevalence studies. Potential geographical variations at the country level might indicate potential risk factors at population levels or systematic difference in clinical application of dementia diagnosis. Although it is important and necessary to use information from dementia research for evidence-based policymaking, over-interpretation of results without carefully considering underlying factors could exaggerate the findings and influence policy planning in ways which do not serve current and future population best. Planning of dementia policy needs to take full cognisance of the provenance of the data being used and be integrated with policies which optimise health across the lifecourse.Yu-Tzu Wu received a PhD scholarship from the Cambridge Trust, University of Cambridge. Fiona E. Matthews was supported by the Medical Research Council [grant number U105292687].This is the accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.maturitas.2014.06.02

Community environment, cognitive impairment and dementia in later life: results from the Cognitive Function and Ageing Study

Background: Few studies have investigated the impact of the community environment, as distinct from area deprivation, on cognition in later life. This study explores cross-sectional associations between cognitive impairment and dementia and environmental features at the community level in older people. Method: The postcodes of the 2424 participants in the year-10 interview of the Cognitive Function and Ageing Study in England were mapped into small area level geographical units (Lower-layer Super Output Areas) and linked to environmental data in government statistics. Multilevel logistic regression was conducted to investigate associations between cognitive impairment (defined as MMSE3 in GMS-AGECAT) and community level measurements including area deprivation, natural environment, land use mix and crime. Sensitivity analyses tested the impact of people moving residence within the last two years. Results: Higher levels of area deprivation and crime were not significantly associated with cognitive impairment and dementia after accounting for individual level factors. Living in areas with high land use mix was significantly associated with a nearly 60% reduced odds of dementia (OR: 0.4; 95% CI: 0.2, 0.8) after adjusting for individual level factors and area deprivation, but there was no linear trend for cognitive impairment. Increased odds of dementia (OR: 2.2, 95% CI: 1.2, 4.2) and cognitive impairment (OR: 1.4, 95% CI: 1.0, 2.0) were found in the highest quartile of natural environment availability. Findings were robust to exclusion of the recently relocated. Conclusion: Features of land use have complex associations with cognitive impairment and dementia. Further investigations should focus on environmental influences on cognition to inform health and social policies

GPER-induced signaling is essential for the survival of breast cancer stem cells.

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER- /PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs

Ischemic conditioning by short periods of reperfusion attenuates renal ischemia/reperfusion induced apoptosis and autophagy in the rat

Prolonged ischemia amplified iscehemia/reperfusion (IR) induced renal apoptosis and autophagy. We hypothesize that ischemic conditioning (IC) by a briefly intermittent reperfusion during a prolonged ischemic phase may ameliorate IR induced renal dysfunction. We evaluated the antioxidant/oxidant mechanism, autophagy and apoptosis in the uninephrectomized Wistar rats subjected to sham control, 4 stages of 15-min IC (I15 × 4), 2 stages of 30-min IC (I30 × 2), and total 60-min ischema (I60) in the kidney followed by 4 or 24 hours of reperfusion. By use of ATP assay, monitoring O2-. amounts, autophagy and apoptosis analysis of rat kidneys, I60 followed by 4 hours of reperfusion decreased renal ATP and enhanced reactive oxygen species (ROS) level and proapoptotic and autophagic mechanisms, including enhanced Bax/Bcl-2 ratio, cytochrome C release, active caspase 3, poly-(ADP-ribose)-polymerase (PARP) degradation fragments, microtubule-associated protein light chain 3 (LC3) and Beclin-1 expression and subsequently tubular apoptosis and autophagy associated with elevated blood urea nitrogen and creatinine level. I30 × 2, not I15 × 4 decreased ROS production and cytochrome C release, increased Manganese superoxide dismutase (MnSOD), Copper-Zn superoxide dismutase (CuZnSOD) and catalase expression and provided a more efficient protection than I60 against IR induced tubular apoptosis and autophagy and blood urea nitrogen and creatinine level. We conclude that 60-min renal ischemia enhanced renal tubular oxidative stress, proapoptosis and autophagy in the rat kidneys. Two stages of 30-min ischemia with 3-min reperfusion significantly preserved renal ATP content, increased antioxidant defense mechanisms and decreased ischemia/reperfusion enhanced renal tubular oxidative stress, cytosolic cytochrome C release, proapoptosis and autophagy in rat kidneys