Indiana University-Purdue University Indianapolis (IUPUI) / ALDH isoenzymes are known to impact the sensitivity of certain neoplastic cells toward cyclophosphamides and its analogs. Despite its bone marrow toxicity, cyclophos-phamide is still used to treat various recalcitrant forms of cancer. When activated, cyclo-phosphamide forms aldophosphamide that can spontaneously form the toxic phospho-ramide mustard, an alkylating agent unless detoxified by ALDH isozymes to the carbox-yphosphamide metabolite. Prior work has demonstrated that the ALDH1A1 and ALDH3A1 isoenzymes can convert aldophosphamide to carboxyphosphamide. This has also been verified by over expression and siRNA knockdown studies. Selective small molecule inhibitors for these ALDH isoenzymes are not currently available. We hypothe-sized that novel and selective small molecule inhibitors of ALDH3A1 would enhance cancer cells’ sensitivity toward cyclophosphamide. If successful, this approach can widen the therapeutic treatment window for cyclophosphamides; permitting lower effective dos-ing regimens with reduced toxicity. An esterase based absorbance assay was optimized in a high throughput setting and 101, 000 compounds were screened and two new selective inhibitors for ALDH3A1, which have IC50 values of 0.2 µM (CB7) and 16 µM (CB29) were discovered. These two compounds compete for aldehyde binding, which was vali-dated both by kinetic and crystallographic studies. Structure activity relationship dataset has helped us determine the basis of potency and selectivity of these compounds towards ALDH3A1 activity. Our data is further supported by mafosfamide (an analog of cyclo-phosphamide) chemosensitivity data, performed on lung adenocarcinoma (A549) and gli-oblastoma (SF767) cell lines. Overall, I have identified two compounds, which inhibit ALDH3A1’s dehydrogenase activity selectively and increases sensitization of ALDH3A1 positive cells to aldophosphamide and its analogs. This may have the potential in improving chemotherapeutic efficacy of cyclophosphamide as well as to help us understand better the role of ALDH3A1 in cells. Future work will focus on testing these compounds on other cancer cell lines that involve ALDH3A1 expression as a mode of chemoresistance.

Indiana University-Purdue University Indianapolis (IUPUI) / The passive properties of the venous wall are important in the development of venous pathology. Increase in venous pressure due to retrograde flow (reflux) and obstruction of venous flow by intrinsic and extrinsic means are the two possible mechanisms for venous hypertension. Reflux is the prevailing theory in the etiology of venous insufficiency. The objective of this thesis is to quantify the passive biomechanical response and structural remodeling of veins subjected to chronic venous reflux and hypertension. To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured chronically in canines by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound (IVUS) was utilized to investigate the passive biomechanical response of both control common iliac veins (from 9 dogs) and common iliac veins subjected to chronic venous reflux and hypertension (from 9 dogs). The change in thickness and constituent composition as a result of chronic venous reflux and hypertension was quantified using multiphoton microscopy (MPM) and histological evaluation. Biomechanical results indicate that the veins stiffened and became less compliant when exposed to eight weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be a result of a significant increase in wall thickness (p < 0.05) and a significant increase in the collagen to elastin ratio (p < 0.05). After eight weeks of chronic reflux, the circumferential Cauchy stress significantly reduced (p < 0.05) due to wall thickening, but was not restored to control levels. This provided a useful model for development and further analysis of chronic venous insufficiency and assessment of possible intervention strategies.

Indiana University-Purdue University Indianapolis (IUPUI) / Ignition of a combustible mixture by a transient jet of hot reactive gas is important for safety of mines, pre-chamber ignition in IC engines, detonation initiation, and in novel constant-volume combustors. The present work is a numerical study of the hot-jet ignition process in a long constant-volume combustor (CVC) that represents a wave-rotor channel. The mixing of hot jet with cold mixture in the main chamber is first studied using non-reacting simulations. The stationary and traversing hot jets of combustion products from a pre-chamber is injected through a converging nozzle into the main CVC chamber containing a premixed fuel-air mixture. Combustion in a two-dimensional analogue of the CVC chamber is modeled using global reaction mechanisms, skeletal mechanisms, and detailed reaction mechanisms for four hydrocarbon fuels: methane, propane, ethylene, and hydrogen. The jet and ignition behavior are compared with high-speed video images from a prior experiment. Hybrid turbulent-kinetic schemes using some skeletal reaction mechanisms and detailed mechanisms are good predictors of the experimental data. Shock-flame interaction is seen to significantly increase the overall reaction rate due to baroclinic vorticity generation, flame area increase, stirring of non-uniform density regions, the resulting mixing, and shock compression. The less easily ignitable methane mixture is found to show higher ignition delay time compared to slower initial reaction and greater dependence on shock interaction than propane and ethylene. The confined jet is observed to behave initially as a wall jet and later as a wall-impinging jet. The jet evolution, vortex structure and mixing behavior are significantly different for traversing jets, stationary centered jets, and near-wall jets. Production of unstable intermediate species like C2H4 and CH3 appears to depend significantly on the initial jet location while relatively stable species like OH are less sensitive. Inclusion of minor radical species in the hot-jet is observed to reduce the ignition delay by 0.2 ms for methane mixture in the main chamber. Reaction pathways analysis shows that ignition delay and combustion progress process are entirely different for hybrid turbulent-kinetic scheme and kinetics-only scheme.

Indiana University-Purdue University Indianapolis (IUPUI) / This qualitative study was successful in utilization of grounded theory methodology to ascertain nurses’ decision-making processes following their awareness of having made a medical error, as well as how and/or if they corrected and reported the error. Significant literature documents the existence of medical errors; however, this unique study interviewed thirty nurses from adult intensive care units seeking to discover through a detailed interview process their individual stories and experiences, which were then analyzed for common themes. Common themes led to the development of a theoretical model of thought processes regarding error reporting when nurses made an error. Within this theoretical model are multiple processes that outline a shared, time-orientated sequence of events nurses encounter before, during, and after an error. One common theme was the error occurred during a busy day when they had been doing something unfamiliar. Each nurse expressed personal anguish at the realization she had made an error, she sought to understand why the error happened and what corrective action was needed. Whether the error was reported on or told about depended on each unit’s expectation and what needed to be done to protect the patient. If there was no perceived patient harm, errors were not reported. Even for reported errors, no one followed-up with the nurses in this study. Nurses were left on their own to reflect on what had happened and to consider what could be done to prevent error recurrence. The overall impact of the process of and the recovery from the error led to learning from the error that persisted throughout her nursing career. Findings from this study illuminate the unique viewpoint of licensed nurses’ experiences with errors and have the potential to influence how the prevention of, notification about and resolution of errors are dealt with in the clinical setting. Further research is needed to answer multiple questions that will contribute to nursing knowledge about error reporting activities and the means to continue to improve error-reporting rates

Indiana University-Purdue University Indianapolis (IUPUI) / Steven Millhauser has been recognized for his abilities as both a novelist and a writer of short fiction. Yet, he has evaded definitive categorization because his fiction does not fit into any one category. Millhauser’s fiction has defied clean categorization specifically because of his regular oscillation between the modes of realism and fantasy. Much of Millhauser’s short fiction contains images of labyrinths: wandering narratives that appear to split off or come to a dead end, massive structures of branching, winding paths and complex mysteries that are as deep and impenetrable as the labyrinth itself. This project aims to specifically explore the presence of labyrinthine elements throughout Steven Millhauser’s short fiction. Millhauser’s labyrinths are either described spatially and/or suggested in his narrative form; they are, in other words, spatial and/or discursive. Millhauser’s spatial labyrinths (which I refer to as ‘architecture’ stories) involve the lengthy description of some immense or underground structure. The structures are fantastic in their size and often seem infinite in scale. These labyrinths are quite literal. Millhauser’s discursive labyrinths demonstrate the labyrinthine primarily through a forking, branching and repetitive narrative form. Millhauser’s use of the labyrinth is at once the same and different than preceding generations of short fiction. Postmodern short fiction in the 1960’s and 70’s used labyrinthine elements to draw the reader’s attention to the story’s textuality. Millhauser, too, writes in the experimental/fantastic mode, but to different ends. The devices of metafiction and realism are employed in his short fiction as agents of investigating and expressing two competing visions of reality. Using the ‘tricks’ and techniques of postmodern metafiction in tandem with realistic detail, Steven Millhauser’s labyrinthine fiction adjusts and reapplies the experimental short story to new ends: real-world applications and thematic expression.

Indiana University-Purdue University Indianapolis (IUPUI) / While the majority of chronic pain patients report receiving inadequate care, there is evidence that female and Black patients receive less analgesic medications and treatment for their chronic pain compared to male and White patients, respectively. While treatment disparities have been evidenced in the literature, there is little understanding of provider-factors, such as their decision-making awareness and attitudes, which may contribute to the differences in treatment. This investigation employed quantitative and qualitative procedures to examine the relationship between patient demographics and chronic pain treatment variability, providers’ awareness of these non-medical influences on their decisions, and the extent to which providers’ gender and racial attitudes associate with their treatment decisions. Twenty healthcare trainees made pain treatment decisions (opioid, antidepressant, physical therapy, pain specialty referral) for 16 computer-simulated patients presenting with chronic low back pain; patient sex and race were manipulated across vignettes. Participants then selected among 9 factors, including patient demographics, to indicate which factors influenced their treatment decisions for the simulated patients and completed gender and racial attitude measures. After online study completion, follow-up semi-structured interviews were conducted to discuss the medical/non-medical factors that influence trainees’ clinical treatment decisions. Quantitative analysis indicated that 5%-25% of trainees were actually influenced (p<0.10) by patient sex and race in their treatments, and on the whole, trainees gave higher antidepressant ratings to White than Black patients (p<.05). Fifty-five percent demonstrated concordance, or awareness, between their actual and reported use of patient demographics. Follow-up McNemar’s test indicated trainees were generally aware of the influence of demographics on their decisions. Overall, gender and racial attitudes did not associate with trainees’ treatment decisions, except trainees’ complementary stereotypes about Black individuals were positively associated with their opioid decisions for White patients. During qualitative interviews, aware and unaware trainees discussed similar themes related to sex and racial/ethnic differences in pain presentation and tailoring treatments. We found that (1) a subset of trainees were influenced by patient sex and race when making chronic pain treatment decisions, (2) trainees were generally aware of the influence of patient demographics, and (3) trainees discussed differences in pain presentation based on patients’ sex and ethnic origin. These findings suggest trainees’ are influenced by patient demographics and hold stereotypes about patient populations, which may play a role in their decision-making.

The advance of digitization influences medical sciences in various areas, increasingly including medical education. Therefore the Teaching Department of the Medical Faculty of the University of Leipzig constantly considers new technical developments and their possibilities for use in medical teaching. The focus is on the fact that teaching should be supplemented and explicitly not replaced by digital media. Virtual reality (hereinafter referred to as 'VR') represents a technology that can be expected to offer promising potential. In order to determine to what extent VR represents an added value for the study of human medicine and which hardware and software is suitable, the project VRmed – Virtual Reality in Medical Teaching was initiated in the Media section of the Teaching Department of the MF. This was funded as part of the Digital Fellowship Program by the University Didactic Center Saxony and the Working Group E-Learning of the LRK Saxony. The present report represents the final report of the project, which was created on its own initiative. In order to investigate the question of implementation possibilities for medical studies, four VR glasses (three different models) and four VR applications were purchased. Two simulation applications and two anatomy applications were selected as applications. The former are i:medtasim and StepVR applications. In addition, the anatomy applications 3D Organon VR Anatomy and Medicalholodeck were purchased. The initially extensive multi-stage evaluation with lecturers and students could not be implemented in 2020/2021 due to the pandemic-related restrictions and was therefore only applied in limited extent. Thus, hardware and software were evaluated qualitatively and in depth in the context of three presentation events by lecturers and media didactics. In particular, the simulation applications are considered to be helpful and useful extensions for teaching. The anatomy application 3D Organon VR Anatomy could also be used profitably in medical studies, especially in the early semesters. With regard to i:medtasim, there are initial considerations to include this in the curriculum as part of a medical elective. Another perspective is the establishment of a VR lab in which students and lecturers can freely use the technology. It should also be noted that VR is associated with many technical challenges and both the setup and the first use require expertise. In addition, the purchase is cost-intensive and hardware and software develop very quickly. Nevertheless, the potentials and the added value predominate. VR can be used to meet a wide range of learning types, practice scenarios bridge the gap between theory and practice, and students and lecturers can connect to technical developments.:1. Einleitung 2. Theoretische Hinführung 3. VR an Medizinischen Fakultäten und Universitäten außerhalb des Standorts Leipzig 4. Projektbeschreibung VRmed – Virtual Reality in der medizinischen Lehre Leipzig 5. VR Hardware und Software für den medizinischen Einsatz 6. Evaluation 7. Fazit und Ausblick 8. Literaturverzeichnis 9. Online-Quellen Anhang A) Projektstrukturplan B) Zeitplan C) Poster D) Evaluationsprotokolle / Das Voranschreiten der Digitalisierung beeinflusst die Medizin in verschiedenen Bereichen, weshalb deren Relevanz auch im Medizinstudium zunimmt. Daher werden im Referat Lehre der Medizinischen Fakultät der Universität Leipzig stetig neue technische Entwicklungen und deren Möglichkeiten für den Einsatz in der medizinischen Lehre betrachtet. Im Fokus steht, dass die Lehre ergänzt und explizit nicht durch digitale Medien ersetzt werden soll. Virtual Reality (im Folgenden „VR“) stellt dabei eine Technologie dar, die in der ersten Auseinandersetzung vielversprechende Potentiale erwarten lässt. Um festzustellen, inwiefern VR einen Mehrwert für das Humanmedizinstudium darstellt und welche Hard- und Software dabei in Frage kommt, wurde im Bereich Medien des Referats Lehre der MF das Projekt VRmed – Virtual Reality in der medizinischen Lehre initiiert. Dies wurde im Rahmen des Digital Fellowship-Programms vom Hochschuldidaktischen Zentrum Sachsen und dem Arbeitskreis E-Learning der LRK Sachsen gefördert. Der hier vorliegende Bericht stellt den Abschlussbericht des Projektes dar, welcher aus Eigenantrieb erstellt wurde. Um der Frage nach Implementierungsmöglichkeiten für das Medizinstudium nachzugehen, wurden vier VR-Brillen (drei verschiedene Modelle) und vier VR-Anwendungen angeschafft. Als Anwendungen wurden zwei Simulationsanwendungen und zwei Anatomieanwendungen ausgewählt. Bei ersterem handelt es sich um die Anwendungen i:medtasim und StepVR. Zudem wurden die Anatomieanwendungen 3D Organon VR Anatomy und Medicalholodeck eingekauft. Die zunächst umfangreich angelegte mehrstufige Evaluation mit Dozierenden und Studierenden konnte aufgrund der pandemiebedingten Einschränkungen in den Jahren 2020/2021 nicht umgesetzt werden und wurde eingegrenzt. Somit wurde Hard- und Software im Rahmen von drei Präsentationsveranstaltungen von Dozierenden und Mediendidaktiker:innen qualitativ und tiefgehend evaluiert. Insbesondere die Simulationsanwendungen werden als hilfreiche und sinnvolle Erweiterungen für die Lehre eingeschätzt. Auch die Anatomieanwendung 3D Organon VR Anatomy könnte im Medizinstudium, insbesondere in die frühen Semester, gewinnbringend eingesetzt werden. Bezüglich i:medtasim existieren erste Überlegungen, dies im Rahmen eines humanmedizinischen Wahlfachs in das Curriculum einzubinden. Eine weitere Perspektive ist die Etablierung eines VR-Labs, in dem Studierende und Dozierende die Technik frei nutzen können. Es bleibt auch festzuhalten, dass VR mit vielen technischen Herausforderungen verbunden ist und sowohl das Einrichten als auch die erste Nutzung Expertise bedürfen. Zudem ist die Anschaffung kostenintensiv und Hard- und Software entwickeln sich sehr schnell. Dennoch überwiegen die Potentiale und der Mehrwert. Durch VR kann vielfältigen Lerntypen begegnet werden, durch Übungsszenarien wird eine Brücke zwischen Theorie und Praxis geschlagen und Studierende wie auch Dozierende können an technische Entwicklungen anschließen.:1. Einleitung 2. Theoretische Hinführung 3. VR an Medizinischen Fakultäten und Universitäten außerhalb des Standorts Leipzig 4. Projektbeschreibung VRmed – Virtual Reality in der medizinischen Lehre Leipzig 5. VR Hardware und Software für den medizinischen Einsatz 6. Evaluation 7. Fazit und Ausblick 8. Literaturverzeichnis 9. Online-Quellen Anhang A) Projektstrukturplan B) Zeitplan C) Poster D) Evaluationsprotokolle