Use of location data for the surveillance, analysis, and optimization of clinical processes

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2006.Includes bibliographical references (leaves 33-35).Location tracking systems in healthcare produce a wealth of data applicable across many aspects of care and management. However, since dedicated location tracking systems, such as the oft mentioned RFID tracking system, are still sparsely deployed, a number of other data sources may be utilized to serve as a proxy for physical location, such as barcodes and manual timestamp entry, and may be better suited to indicate progress through clinical workflows. INCOMING!, a web-based platform that monitors and tracks patient progress from the operating room to the post-anesthesia care unit (PACU), is one such system that utilizes manual timestamps routinely entered as standard process of care in the operating room in order to track a patient's progress through the post-operative period. This integrated real time system facilitates patient flow between the PACU and the surgical ward and eases PACU workload by reducing the effort of discharging patients.(cont.) We have also developed a larger-scale integrated system for perioperative processes that integrates perioperative data from anesthesia and surgical devices and operating room (OR) / hospital information systems, and projects the real-time integrated data as a single, unified, easy to visualize display. The need to optimize perioperative throughput creates a demand for integration of the datastreams and for timely data presentation. The system provides improved context-sensitive information display, improved real-time monitoring of physiological data, real-time access to readiness information, and improved workflow management. These systems provide improved data access and utilization, providing context-aware applications in healthcare that are aware of a user's location, environment, needs, and goals.by Mark A. Meyer.S.M

Ordinal Probit Functional Regression Models with Application to Computer-Use Behavior in Rhesus Monkeys

Research in functional regression has made great strides in expanding to non-Gaussian functional outcomes, however the exploration of ordinal functional outcomes remains limited. Motivated by a study of computer-use behavior in rhesus macaques (\emph{Macaca mulatta}), we introduce the Ordinal Probit Functional Regression Model or OPFRM to perform ordinal function-on-scalar regression. The OPFRM is flexibly formulated to allow for the choice of different basis functions including penalized B-splines, wavelets, and O'Sullivan splines. We demonstrate the operating characteristics of the model in simulation using a variety of underlying covariance patterns showing the model performs reasonably well in estimation under multiple basis functions. We also present and compare two approaches for conducting posterior inference showing that joint credible intervals tend to out perform point-wise credible. Finally, in application, we determine demographic factors associated with the monkeys' computer use over the course of a year and provide a brief analysis of the findings

Robust anti-oxidant defences in the rice blast fungus Magnaporthe oryzae confer tolerance to the host oxidative burst

•Plants respond to pathogen attack via a rapid burst of reactive oxygen species (ROS). However, ROS are also produced by fungal metabolism and are required for the development of infection structures in Magnaporthe oryzae. •To obtain a better understanding of redox regulation in M. oryzae, we measured the amount and redox potential of glutathione (EGSH), as the major cytoplasmic anti-oxidant, the rates of ROS production, and mitochondrial activity using multi-channel four-dimensional (x,y,z,t) confocal imaging of Grx1-roGFP2 and fluorescent reporters during spore germination, appressorium formation and infection. •High levels of mitochondrial activity and ROS were localized to the growing germ tube and appressorium, but EGSH was highly reduced and tightly regulated during development. Furthermore, germlings were extremely resistant to external H2O2 exposure ex planta. EGSH remained highly reduced during successful infection of the susceptible rice cultivar CO39. By contrast, there was a dramatic reduction in the infection of resistant (IR68) rice, but the sparse hyphae that did form also maintained a similar reduced EGSH. •We conclude that M. oryzae has a robust anti-oxidant defence system and maintains tight control of EGSH despite substantial oxidative challenge. Furthermore, the magnitude of the host oxidative burst alone does not stress the pathogen sufficiently to prevent infection in this pathosystem.BBSR

Gut microbiota and brain function: an evolving field in neuroscience

There is a growing appreciation of the importance of gut microbiota to health and disease. This has been driven by advances in sequencing technology and recent findings demonstrating the important role of microbiota in common health disorders such as obesity. Moreover, the potential role of gut microbiota in influencing brain function, behavior, and mental health has attracted the attention of neuroscientists and psychiatrists. At the 29th International College of Neuropsychopharmacology (CINP) World Congress held in Vancouver, Canada, in June 2014, a group of experts presented the symposium, “Gut microbiota and brain function: Relevance to psychiatric disorders” to review the latest findings in how gut microbiota may play a role in brain function, behavior, and disease. The symposium covered a broad range of topics, including gut microbiota and neuroendocrine function, the influence of gut microbiota on behavior, probiotics as regulators of brain and behavior, and imaging the gut-brain axis in humans. This report provides an overview of these presentations

Heads or tails: L1 insertion-associated 5' homopolymeric sequences

<p>Abstract</p> <p>Background</p> <p>L1s are one of the most successful autonomous mobile elements in primate genomes. These elements comprise as much as 17% of primate genomes with the majority of insertions occurring via target primed reverse transcription (TPRT). Twin priming, a variant of TPRT, can result in unusual DNA sequence architecture. These insertions appear to be inverted, truncated L1s flanked by target site duplications.</p> <p>Results</p> <p>We report on loci with sequence architecture consistent with variants of the twin priming mechanism and introduce dual priming, a mechanism that could generate similar sequence characteristics. These insertions take the form of truncated L1s with hallmarks of classical TPRT insertions but having a poly(T) simple repeat at the 5' end of the insertion. We identified loci using computational analyses of the human, chimpanzee, orangutan, rhesus macaque and marmoset genomes. Insertion site characteristics for all putative loci were experimentally verified.</p> <p>Conclusions</p> <p>The 39 loci that passed our computational and experimental screens probably represent inversion-deletion events which resulted in a 5' inverted poly(A) tail. Based on our observations of these loci and their local sequence properties, we conclude that they most probably represent twin priming events with unusually short non-inverted portions. We postulate that dual priming could, theoretically, produce the same patterns. The resulting homopolymeric stretches associated with these insertion events may promote genomic instability and create potential target sites for future retrotransposition events.</p

Stability transitions for axisymmetric relative equilibria of Euclidean symmetric Hamiltonian systems

In the presence of noncompact symmetry, the stability of relative equilibria under momentum-preserving perturbations does not generally imply robust stability under momentum-changing perturbations. For axisymmetric relative equilibria of Hamiltonian systems with Euclidean symmetry, we investigate different mechanisms of stability: stability by energy-momentum confinement, KAM, and Nekhoroshev stability, and we explain the transitions between these. We apply our results to the Kirchhoff model for the motion of an axisymmetric underwater vehicle, and we numerically study dissipation induced instability of KAM stable relative equilibria for this system.Comment: Minor revisions. Typographical errors correcte

Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-derived Mesenchymal Stem Cells

Terminal differentiation of multipotent stem cells is achieved through a coordinated cascade of activated transcription factors and epigenetic modifications that drive gene transcription responsible for unique cell fate. Within the mesenchymal lineage, factors such as RUNX2 and PPARγ are indispensable for osteogenesis and adipogenesis, respectively. We therefore investigated genomic binding of transcription factors and accompanying epigenetic modifications that occur during osteogenic and adipogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (MSCs). As assessed by ChIP-sequencing and RNA-sequencing analyses, we found that genes vital for osteogenic identity were linked to RUNX2, C/EBPβ, retinoid X receptor, and vitamin D receptor binding sites, whereas adipocyte differentiation favored PPARγ, retinoid X receptor, C/EBPα, and C/EBPβ binding sites. Epigenetic marks were clear predictors of active differentiation loci as well as enhancer activities and selective gene expression. These marrow-derived MSCs displayed an epigenetic pattern that suggested a default preference for the osteogenic pathway; however, these patterns were rapidly altered near the Adipoq, Cidec, Fabp4, Lipe, Plin1, Pparg, and Cebpa genes during adipogenic differentiation. Surprisingly, we found that these cells also exhibited an epigenetic plasticity that enabled them to trans-differentiate from adipocytes to osteoblasts (and vice versa) after commitment, as assessed by staining, gene expression, and ChIP-quantitative PCR analysis. The osteogenic default pathway may be subverted during pathological conditions, leading to skeletal fragility and increased marrow adiposity during aging, estrogen deficiency, and skeletal unloading. Taken together, our data provide an increased mechanistic understanding of the epigenetic programs necessary for multipotent differentiation of MSCs that may prove beneficial in the development of therapeutic strategies

Bayesian Function-on-Function Regression for Multilevel Functional Data

Medical and public health research increasingly involves the collection of complex and high dimensional data. In particular, functional data—where the unit of observation is a curve or set of curves that are finely sampled over a grid—is frequently obtained. Moreover, researchers often sample multiple curves per person resulting in repeated functional measures. A common question is how to analyze the relationship between two functional variables. We propose a general function-on-function regression model for repeatedly sampled functional data on a fine grid, presenting a simple model as well as a more extensive mixed model framework, and introducing various functional Bayesian inferential procedures that account for multiple testing. We examine these models via simulation and a data analysis with data from a study that used event-related potentials to examine how the brain processes various types of images