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Theory and Methods for Spatiotemporal Point Processes
No full textIn this dissertation we study several related problems under the general umbrella of spatiotemporal counting/point processes. We study counting processes in two distinct contexts.
First, we study a clinical problem of assessing medical response or non-response to a treatment on the basis of known biomarker values. This problem commonly occurs in oncology,
where measures of objective response are critical to drug approval, but may require long
periods of total follow-up with limited cohorts. In this context it is critical for researchers
to be able to efficiently estimate biomarker cutoff values as soon as possible. However, as
trials take long periods of time there will generally be substantial incomplete data at interim
analysis. We find that conventional estimators for handling missing data may reduce bias
relative to conventional estimators in realistic scenarios. We provide recommendations that
applied researchers use a variety of estimators and use careful sensitivity analyses to guide
conclusions drawn from them.
Second, we study point processes in a spatial context, where we develop new methods for
utilizing point process valued data as covariates in spatial regression. We illustrate the new
method through several simulation scenarios and an analysis of the impact of contributory
sources of air pollution in western Pennsylvania.
Finally, we study a problem of causal inference with a point process valued outcome:
severe asthma exacerbation events in western Pennsylvania. We develop causal estimands
and associated estimators to study the relationship between unconventional natural gas
production and severe asthma in western Pennsylvania. As part of this work we develop a
formal theory for incorporation of mechanistic considerations in causal inference.
Contribution to Public Health:
This dissertation contributes to public health in multiple ways. In the clinical trials portion we assess the potential of common statistical methods for bias reduction in clinical trials
at interim analysis, an important objective for drug development. The spatial epidemiology
work contributes to a growing literature assessing the impact of industrial activity and air
pollution on human health. The theoretical work contributes to public health by providing foundations for causal interpretation of observational studies and enabling new research
designs
Investigating Relationships Between Healthcare Worker Hand Hygiene and Healthcare-Associated Infections in Pediatric Populations: An Interventional Study
No full textHealthcare-associated infections (HAIs) are a public health burden that contribute to significant morbidity, mortality, hospital stays, and healthcare costs. HAIs disproportionately affect certain groups who often require special infection prevention and control (IPC) considerations, such as immunocompromised, neonatal, and pediatric populations. Hand hygiene (HH) is the most effective strategy to reduce HAIs. Yet HH compliance among healthcare workers (HCWs) often does not meet recommended guidelines, necessitating education and interventions to increase adherence. This study assessed the impact of an HH campaign on HCW HH compliance and examined subsequent HAI incidence at a mid-size pediatric acute care hospital in the United States. The campaign used staff education, increased administrative oversight, and real-time HH compliance monitoring from overt and covert hand hygiene observers to determine HH adherence. To address HAI trends, patient data from electronic health records were compiled, analyzed, and used in HAI calculations.
Pre-intervention baseline data was collected over a 3-month period and analyzed in comparison to 3-months of intervention and 2-months of post-intervention data. Upon completion of the post-intervention period, changes in HH compliance were compared to the shifts in incidence of HAIs. The results showed a significant whole-house increase in HH compliance, rising from a 79.8% pre-intervention compliance to a 93.7% compliance at the end of the post-intervention period. Highly trafficked and high-risk areas like the Emergency Department, the Rehabilitation Unit, and the Pediatric Intensive Care Unit increased in HH compliance. Subsequently, there was a decrease in whole-house HAIs, with a pre-intervention average rate of 4.45 and a post-intervention average rate of 3.18. Three out of eight examined HAI subtypes examined had average post-intervention period rates that were less than their pre-intervention rate.
Findings from this HH campaign and HAI data analysis highlight the importance of targeted IPC interventions. The success of the intervention underscores the value of prioritizing HH and HH initiatives for healthcare workers and their patients’ health and safety. Outside of just reducing HAIs, HH provides a cost-effective measure that can reduce the strain on healthcare systems. This intervention reinforces the necessity of HH and IPC measurements to maintain and improve public health
Clarifying roles of Borrelia burgdorferi outer surface proteins during disease dissemination and pathogenesis to aid in prediction of optimal immunogenic targets for point of care testing alternatives
No full textThe testing paradigm for Lyme disease diagnosis has remained largely unchallenged and unchanged for nearly 30 years. Many of the challenges associated with new diagnostic developments are attributed towards Borrelia’s quick hematogenous dissemination into body tissues and challenges associated with characterization of the bacteria’s many proteins that can be utilized for identification. For these presented challenges, identification of Borrelia burgdorferi via its proteins is often quickly dismissed and considered unfeasible. However, continued efforts to identify Borrelia’s proteins and their functions, as well as advancements in diagnostic assays, may suggest a second, more in-depth evaluation using circulating antigens of Borrelia burgdorferi for plausible diagnostic alternatives. The goals of this review were to gain a better understanding of the outer surface protein profile of Borrelia burgdorferi B31, specifically their functions as they correlate to pathogenesis and dissemination. Understanding when and where certain proteins are expressed may aid in narrowing down potential candidates for further evaluation as immunotargets for point-of-care antigen-based assays. In summation, additional research is critically needed to further define the characteristics and protein profile of Borrelia burgdorferi. While this review highlights many possible targets available for further study, 11 proteins in total are recommended for further analysis. Highlighting the knowledge gaps on Borrelia proteins is of public health importance for identifying immunotargets to improve diagnostic success and serve as possible vaccine targets to reduce the overwhelming burden of disease as the most common vector borne disease in the U.S
Automated and Manual Assembly of Computational Models for Biological Systems: Applications to Macrophage Activation and CAR-T cells
No full textDevelopment and updating of computational models representing complex biological systems and processes is extremely challenging. Researchers today have access to vast sets of information about molecular entities and interactions, through querying public databases, examining published models, and extracting content from literature using machine reading engines. It is the sheer vastness of this available data that has inspired systems and computational biologists to endeavor to automate the process of model creation and extension. In this work, we quantify the complexity and combinatoric-nature of true automated model assembly. We discuss how current modelers make assumptions and simplifications that change an impossible, intractable problem into one that modern computers can begin to solve. From fully automated assembly, we transition to semi-automated model assembly and extension, in which we discuss how the combinatoric nature of graph problems becomes more difficult when simulating a dynamic system and how rudimentary error functions are more likely to find local minima than global solution. Finally, two human-curated models are presented: one of macrophage priming, activation, and communication; and another of T cell-antibody-tumor cell ternary body formation. Taken together, this dissertation presents a holistic perspective on the current challenges and advances in the field of automated, semi-automated, and human-curated model assembly with applications in biological systems
Balance and the Brain: Accelerometry Signal Features and Associations with Neuroimaging
No full textOne third of people aged 65 and older fall every year, accounting for the majority of injury-related hospitalizations and deaths in older adults. With age, balance becomes a less automatic process and requires more attention. As a result, performing concurrent attention tasks can interfere with a person’s balance increasing risk for falls. It is important to understand how and the extent to which cognitive tasks may affect postural control, especially in older adults who are at higher risk for falls. However, the relationship between dual-task cognition and postural control is not well established. In this dissertation, we explore this relationship from three points of view: the output, the modulator, and the foundation. The output is balance performance which was monitored and quantified using accelerometers: a widely accessible, affordable, and portable sensor that can be used in clinical and community settings. Using accelerometry signal features from postural control assessment, we examine how balance automaticity is affected after performing 1) short cognitive tasks and 2) an exercise intervention. To further probe the importance of concurrent cognitive tasks on balance performance, we shift our focus to the modulator: attention. Attention was represented by neural activity levels in the prefrontal cortex (PFC) as measured by functional near-infrared spectroscopy. We examine whether PFC activity relates to postural control performance 1) during dual-task experiments and 2) due to an intervention. Lastly, we investigate the foundation of this relationship by going deeper into the brain to further elucidate the role of cortical control in balance. We evaluate the functional connectivity between cortical and subcortical brain regions that are highly involved in balance control. Associations between postural control performance and brain characteristics could lead to balance accelerometry metrics being used as biomarkers for underlying neurobiology. Advancing our knowledge of postural control will yield insight in how to improve balance assessments and interventions, ultimately leading to more effective reductions in fall risk
Data Set for Manuscript: The need for better metrics for floor-tile topography: Conventional metrics correlate only modestly with shoe-floor friction
No full textRoughness and waviness metrics collected with stylus profilometry are commonly used in the characterization of flooring topography due to previously reported correlations between these metrics and friction performance. Yet, their predictive ability across heterogeneous flooring products has yet to be characterized. In this data set, we report four topography parameters and the oily coefficient of friction across four shoe products for 23 floors
Undergraduate Writing Pedagogy in an Era of Digital Ubiquity
No full textIn academia, there remains a broad cultural divide between STEM and the humanities that was identified over half a century ago by C.P. Snow. However, the nature of this divide has changed in recent years as a scientific tool, the digital computer, has become ubiquitous in daily life. The humanities must now contend with how to account for this specialized-yet-ubiquitous technology within its various disciplines, and it is in this contention that I believe composition pedagogy is well-situated to support undergraduate education and bridge the cultural divide. The use of digital technology can be taught via concepts from composition pedagogy to undergraduates at sufficient levels of generality to support their use of the technology in their home disciplines and post-college work.
This approach is an extension of how composition studies has dealt with the incorporation of writing technology into the classroom. In doing so, it attempts to account for perspectives from both STEM and humanities cultures, considering not only what composition pedagogy and humanities perspectives might bring to the teaching of computing, but also how to effectively engage students in technical learning as they familiarize themselves with how to make use of a specialist technology in their lives and work
Iron-Catalyzed C–H Functionalization of Alkenes for Addition to Conjugated Electrophiles
No full textAllylic C(sp3)–H functionalization of simple alkenes, and subsequent coupling with Michael acceptors in a base metal catalyzed process offers a practical and modular approach to a variety of scaffolds. In this dissertation, the redox-neutral deprotonative generation of catalytic allyliron intermediates using a pentamethylcyclopentadienyliron(II) dicarbonyl catalyst provides an allyl anion equivalent for addition into α,β-unsaturated carbonyl derivatives. A wide range of alkene substrates serve as allyl pronucleophiles and undergo 1,4-conjugate addition to chalcone type electrophiles and other enones. Furthermore, Michael addition of alkenes to a collection of cyclic and acyclic nitrogen-containing compounds featuring C–C unsaturation, such as maleimides and enaminones, is also described. For some sterically hindered electrophiles, an alternative linear regioselectivity was observed. A preliminary investigation into the formation of these unexpected products is discussed
The Relationship between UES Distension and Laryngeal Shortening
No full textAims: We sought to determine whether correlations exist between UES distension (UESD) and laryngeal shortening (LS) in a patient group and healthy population, and whether there were clinically and statistically significant differences in LS and UESD between these groups.
Methods: Forty-seven inpatients referred for videofluoroscopic (VFSS) assessment due to clinical evidence or suspicion of dysphagia, and 47 healthy age-matched controls underwent standard VFSS examination. The maximal distention of the UES and the displacement of the laryngeal framework toward the hyoid, called laryngeal shortening (LS), were measured on each frame of each swallow event.
Results: There were no significant correlations between LS and UESD in either patients (p = 0.58) or healthy participants (p = .94). UESD was statistically and clinically greater (p<0.0001; d= -1.0, large effect) in patients than healthy participants. Conversely, patients exhibited statistically and clinically less LS than healthy participants (p=0.001; d=0.67 moderate effect).
Conclusion: UESD and LS were not correlated as hypothesized, however, the clinically significant differences between LS and UESD in patients and healthy participants suggest that LS may be affecting other aspects of the swallow. Limitations include a small sample size and a limited number of swallows per participant. Clinical implications of the results will be discussed
Design of High-Capacitance Polymers: Side Chain Length and Polarity Effects on Permittivity
No full textDielectric polymers (DPs) are attracting attention for applications in energy storage devices and potential as greener materials. This work serves to expand and explore a variation of side chain (SC) DPs, which addresses one major challenge, inherently low permittivity. This design of SCDPs combines a long aliphatic backbone, having low permittivity and loss, with conjugated SCs, having high permittivity and loss, and is expected to demonstrate these characteristics. Cast films, subjected to a dipole-aligning external field, achieved high permittivities. Effective dipole orientation, facilitated by backbone flexibility and SC conjugation for electron mobility, increased the induced dipole.
A series of polymers with an alkyl backbone and variable length phenylene ethynylene (PhE) SCs were prepared. Diolefin macromonomers, containing a halogenated phenyl, were polymerized via ADMET. Sonogashira coupling of PhE units gave SCs that were 1, 2, and 3 units long, and post-polymerization coupling gave polymers termed: poly-dimer, with two phenyls; poly-trimer, with three phenyls; poly-tetramer, with four phenyls. PhE units were of 2 types: a 2,5-alkoxy functionalized phenyl, for improved solubility, and a 4-nitrile functionalized phenyl, to enhance polarity.
The effects of conjugation length, polarity, and poling the polymers’ permittivities were studied. Sample films, prepared by solution deposition between brass electrodes, were characterized by broadband dielectric spectroscopy at 20 °C and 1 kHz. The type of solvent used showed little effect, whereas the amount of solvent present changed the materials’ response significantly. All unpoled polymers exhibited high permittivities: backbone and poly-tetramer ~4.3; poly-dimer ~4.6; poly-trimer ~4.9. Poling at a 15-volt potential increased their permittivities: backbone ~4.9; poly-dimer ~12.4; poly-trimer ~7.1; poly-tetramer ~5.9. This increase over the unpoled samples demonstrated their potential as high-performance DPs. After poling, the backbone’s small increase, Δε'=0.6, was expected. Surprisingly, as the SC length increased, the Δε' decreased, showing a maximum of: poly-dimer Δε'=7.8; poly-trimer Δε'=2.2; poly-tetramer Δε'=1.6. Alignment of increasingly longer SCs was expected to yield incrementally higher permittivities. One explanation, since permittivities were highly dependent on mobility, longer SCs may remain partially hindered to rotation, despite plasticization. The correlation between SC length and poled permittivity indicates hinderance may increase with SC length and prevent maximum alignment