A Theoretical Model of the Psychological Processes of Surrogate Decision-Making at Adult End-of-Life in the Intensive Care Unit: A Case Study Design Using Cognitive Task Analysis

Thesis advisor: Pamela J. GraceSignificance/Background: Surrogate decision-makers (SDMs) take part in 1.5 million end-of-life (EOL) decisions per year. Most find the role burdensome, often do not make decisions concordant with patients' wishes, and many suffer negative psychological aftereffects. Specific Aims: 1) Identify and describe the psychological processes of recent SDMs for adults at EOL in the intensive care unit (ICU) and 2) develop a theoretical model of SDMs' psychological processes. Methods/Analysis: Descriptive, multiple case study research design using a cognitive task analysis (CTA) interviewing approach. Participants completed an in-depth semi-structured CTA interview and a demographic form. Verbatim transcribed interviews were encoded and analyzed until theoretical saturation was met. Results: Nineteen SDMs (female=11) with a mean age of 59 years (± 11) who made decisions for patients (mean age, 67±13 years) who died in the ICU completed interviews. Data analysis yielded 27 psychological processes representing the hypothesized theoretical links amongst 20 individual psychological concepts. The PREDICAMENTS model (Psychology, Reasoning, and Ethics Demonstrated In Choices about the Acceptability of Medical Treatments and Patient Conditions Encountered in Life Threatening Situations) of surrogate decision-making was assembled from these psychological processes and concepts. The model depicts a complex web of psychological processes wherein SDMs ultimately express acceptance or rejection of medical treatments and/or the patient's physical condition based on their perception of the acceptability (or lack thereof) of medical treatments and/or the patient's physical condition. Conclusions: The PREDICAMENTS model offers an initial picture of the underlying psychological processes operating in SDMs decision-making. Implications for Practice and Research: The PREDICAMENTS model can be used to assess and understand SDMs' thought processes, emotions, and ethical concerns. Further research is needed to test and corroborate constructs and linkages in this model with the aim of developing decision support interventions. Ethicists need to discuss the implications of this descriptive theoretical model for the normative ethical standards expected of SDMs.Thesis (PhD) — Boston College, 2013.Submitted to: Boston College. Connell School of Nursing.Discipline: Nursing

Study of Stable Cathodes and Electrolytes for High Specific Density Lithium-Air Battery

Future NASA missions require high specific energy battery technologies, greater than 400 Wh/kg. Current NASA missions are using "state-of-the-art" (SOA) Li-ion batteries (LIB), which consist of a metal oxide cathode, a graphite anode and an organic electrolyte. NASA Glenn Research Center is currently studying the physical and electrochemical properties of the anode-electrolyte interface for ionic liquid based Li-air batteries. The voltage-time profiles for Pyr13FSI and Pyr14TFSI ionic liquids electrolytes studies on symmetric cells show low over-potentials and no dendritic lithium morphology. Cyclic voltammetry measurements indicate that these ionic liquids have a wide electrochemical window. As a continuation of this work, sp2 carbon cathode and these low flammability electrolytes were paired and the physical and electrochemical properties were studied in a Li-air battery system under an oxygen environment

Pulmonary artery interventions after Norwood procedure: Does type or position of shunt predict need for intervention?

ObjectivesPulmonary artery stenosis is a potential complication after Norwood palliation for hypoplastic left heart syndrome. It is unclear whether the shunt type or position in the Norwood procedure is associated with the risk of the development of pulmonary artery stenosis. We examined the risk of pulmonary artery stenosis and the need for pulmonary artery intervention in children undergoing the Norwood procedure with either the right ventricle to pulmonary artery conduit or modified Blalock-Taussig shunt.MethodsA retrospective review was performed of all patients who underwent the Norwood procedure from January 1, 2003, to September 1, 2011. The data from 100 patients were reviewed, including catheterization and echocardiographic data, right ventricle to pulmonary artery conduit (n = 67, right shunt position in 17 and left in 50), and right ventricle to pulmonary artery (n = 33). The primary outcome measure was the need for operative or catheter-based pulmonary artery intervention.ResultsNo patients in the right ventricle to pulmonary artery group required catheterization-based pulmonary artery interventions. Surgical pulmonary arterioplasty was performed frequently and equally in both the right ventricle to pulmonary artery and right ventricle to pulmonary artery groups at the bidirectional Glenn procedure. Catheter-based pulmonary arterioplasty was performed more frequently in the right ventricle to pulmonary artery conduit group, especially when the conduit was positioned to the right side of the neoaorta. These patients had a 12.73 increased odds of a pulmonary artery intervention compared with the left to right ventricle to pulmonary artery conduit (P = .04).ConclusionsConsistent with a previous multicenter randomized trial, patients who received a right ventricle to pulmonary artery conduit versus a right ventricle to pulmonary artery have a greater risk of requiring pulmonary artery interventions. Patients with right ventricle to pulmonary artery conduit placement to the right underwent a greater number of pulmonary artery interventions but demonstrated overall improved growth of the branch pulmonary arteries compared with the patients receiving a left-sided right ventricle to pulmonary artery conduit

Investigation of Structure and Transport in Li-Doped Ionic Liquid Electrolytes: [pyr14][TFSI], [pyr13][FSI], [EMIM][BF4]

Ionic liquid electrolytes have been proposed as a means of improving the safety and cycling behavior of advanced lithium batteries; however, the properties of these electrolytes under high lithium doping are poorly understood. Here, we employ both polarizable molecular dynamics simulation and experiment to investigate the structure, thermodynamics and transport of three potential electrolytes, N-methyl-N-butylpyrrolidinium bis(trifluoromethylsufonyl)imide ([pyr14][TFSI]), N- methyl-N-propylpyrrolidinium bis(fluorosufonyl)imide ([pyr13][FSI]), and 1-ethyl-3-- methylimidazolium boron tetrafluoride ([EMIM][BF4]), as a function of Li (-) salt concentration and temperature. Structurally, Li(+) is shown to be solvated by three anion neighbors in [pyr14][TFSI] and four anion neighbors in both [pyr13][FSI] and [EMIM][BF4], and at all levels of xLi we find the presence of lithium aggregates. Furthermore, the computed density, diffusion, viscosity, and ionic conductivity show excellent agreement with experimental data. While the diffusion and viscosity exhibit a systematic decrease and increase, respectively, with increasing xLi, the contribution of Li(+) to ionic conductivity increases until reaching a saturation doping level of xLi 0.10. Comparatively, the Li(+) conductivity of [pyr14][TFSI] is an order of magnitude lower than that of the other liquids, which range between 0.1-0.3 mScm. The differences in Li(+) transport are reflected in the residence times of Li(+) with the anions, which are revealed to be much larger for [pyr14][TFSI] (up to 100 ns at the highest doping levels) than in either [EMIM][BF4] or [pyr13][FSI]. Finally, we comment on the relative kinetics of Li(+) transport in each liquid and we present strong evidence for transport through anion exchange (hopping) as opposed to the net motion of Li(+) with its solvation shell (vehicular)

Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy and is characterized by insulin resistance and decreased circulating glucagon-like peptide-1 (GLP-1). GDM resolves rapidly after delivery implicating the placenta in the disease. This study examines the biological functions that cause this pathology. The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EVs) into the maternal circulation, which is enhanced in GDM. Dipeptidyl peptidase IV (DPPIV) is known to play a role in type 2 diabetes by breaking down GLP-1, which in turn regulates glucose-dependent insulin secretion. STB-EVs from control and GDM women were analysed. We show that normal human placenta releases DPPIV-positive STB-EVs and that they are higher in uterine than paired peripheral blood, confirming placental origin. DPPIV-bound STB-EVs from normal perfused placentae are dose dependently inhibited with vildagliptin. DPPIV-bound STB-EVs from perfused placentae are able to breakdown GLP-1 . STB-EVs from GDM perfused placentae show greater DPPIV activity. Importantly, DPPIV-bound STB-EVs increase eightfold in the circulation of women with GDM. This is the first report of STB-EVs carrying a biologically active molecule that has the potential to regulate maternal insulin secretion

Lack of a functioning P2X7 receptor leads to increased susceptibility to toxoplasmic ileitis

Background: Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis. Principal Findings: Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This suscep-tibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen interme-diates and altered regulation of elements of NFκB activation in P2X7R-deficient mice. Conclusions: Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation

Agency and Amplification: A Comparison of Manual and Computational Thematic Analyses by Public Health Researchers

© Gauthier, Pelletier, Carrier, Dionne, Dube, Meyer, Wallace | ACM, 2023. This is the author's version of the work. It is posted here for your personal use. Not for redistribution. The definitive Version of Record was published in Proceedings of the ACM on Human-Computer Interaction, https://doi.org/10.1145/3567552.Computational techniques offer a means to overcome the amplified complexity and resource-intensity of qualitative research on online communities. However, we lack an understanding of how these techniques are integrated by researchers in practice, and how to address concerns about researcher agency in the qualitative research process. To explore this gap, we deployed the Computational Thematic Analysis Toolkit to a team of public health researchers, and compared their analysis to a team working with traditional tools and methods. Each team independently conducted a thematic analysis of a corpus of comments from Canadian news sites to understand discourses around vaccine hesitancy. We then compared the analyses to investigate how computational techniques may have influenced their research process and outcomes. We found that the toolkit provided access to advanced computational techniques for researchers without programming expertise, facilitated their interaction and interpretation of the data, but also found that it influenced how they approached their thematic analysis.NSERC, Discovery Grant 2015-06585 || Canadian Immunization Research Network, Grant FRN\#15194

Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation

As researchers begin probing deep coverage sequencing data for increasingly rare mutations and subclonal events, the fidelity of next generation sequencing (NGS) laboratory methods will become increasingly critical. Although error rates for sequencing and polymerase chain reaction (PCR) are well documented, the effects that DNA extraction and other library preparation steps could have on downstream sequence integrity have not been thoroughly evaluated. Here, we describe the discovery of novel C > A/G > T transversion artifacts found at low allelic fractions in targeted capture data. Characteristics such as sequencer read orientation and presence in both tumor and normal samples strongly indicated a non-biological mechanism. We identified the source as oxidation of DNA during acoustic shearing in samples containing reactive contaminants from the extraction process. We show generation of 8-oxoguanine (8-oxoG) lesions during DNA shearing, present analysis tools to detect oxidation in sequencing data and suggest methods to reduce DNA oxidation through the introduction of antioxidants. Further, informatics methods are presented to confidently filter these artifacts from sequencing data sets. Though only seen in a low percentage of reads in affected samples, such artifacts could have profoundly deleterious effects on the ability to confidently call rare mutations, and eliminating other possible sources of artifacts should become a priority for the research community.National Human Genome Research Institute (U.S.) (HG03067-05