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Transfer by Design: Learning in the Flow of Work During Complex and Changing Times
No full textRapid technological advancements and global disruptions, as witnessed in the COVID-19 pandemic, are driving an increasingly volatile, uncertain, complex, and ambiguous world of work. In-demand jobs change rapidly, as do the tasks within occupations and the tools, mediums, and environments in which work takes place. While these shifts present significant challenges, they also offer immense opportunities, necessitating that both new and existing workers develop adaptability and resilience. However, many traditional approaches to workforce learning require substantial time and resources, often emphasizing narrow, role-specific skills. These approaches vary widely in quality and can lead to unintended consequences, highlighting the need for more nuanced learning strategies.
This dissertation comprises four independent yet interrelated studies conducted within two multinational consulting firms. Drawing on semi-structured interviews, Studies One and Two examine how individuals navigate modern apprenticeship programs. Study One identifies key pedagogical features of these programs in hybrid contexts, emphasizing learning through developmental relationships. Study Two highlights the networked nature of learning within modern apprenticeships and demonstrates that proximity to experienced mentors enhances apprenticeship experiences. Both studies underscore the importance of strong developmental relationships characterized by frequent communication, worked examples, and shared thinking.
Studies Three and Four explore the experiences of mid-career consultants who frequently undergo rapid role transitions. Study Three, based on extensive interviews across two consulting firms, reveals that learning transfer, the ability to apply learning in one context to a novel one, is not an isolated process but a dynamic one embedded within interpersonal relationships, developmental contexts, and complex cultural environments. Study Four employs design-based research methods to identify features and behaviors that enable workers to transfer their existing knowledge, skills, and abilities to new
contexts. It finds that the presence of pro-transfer features and behaviors in relationships with experienced mentors is associated with improved performance on transfer tasks and greater confidence in one’s ability to transfer learning.
Together, these studies suggest that fostering adaptability and resilience in the workforce requires the intentional design, enactment, and sustainment of positive developmental relationships with experienced mentors in the workplace.Educatio
Analysis of Carbon Reduction Potential in China’s Civil Aviation Industry (2027-2060)
No full textChina has committed to peak carbon emissions by 2030 and achieve carbon neutrality by 2060, placing considerable pressure on high-emission sectors to decarbonize. Yet the aviation sector currently lacks a national-level reduction target or roadmap. In contrast, the European Union and the United States have already set clear aviation decarbonization strategies, increasing pressure on China to respond.
This research evaluated future emission trends under a Business-as-Usual (BaU) model and assessed the effectiveness of key policy measures, particularly Sustainable Aviation Fuels (SAF) and structural changes in transportation such as High-Speed Rail (HSR) reforms. It aimed to answer three questions: (1) How will China’s air travel demand change under the BaU model? (2) What is the potential of structural adjustments, especially HSR substitution, to reduce emissions? (3) To what extent could policy incentives drive further reductions?
Under the BaU model, I estimated China’s future air travel demand using authoritative projections of economic growth and population structure. With 2019 as the baseline, demand was projected to reach 1.15 times the 2019 level by 2035 and more than double by 2060, underscoring the need for additional measures to achieve net-zero.
Building on this baseline, the analysis examined HSR’s substitution effect by evaluating China’s major 2019 civil aviation routes and calculating replacement potential based on travel times between origin–destination pairs. Future scenarios considered possible HSR speed increases: by 2035, no infrastructure upgrades but operational adjustments such as timetable changes; and by 2060, infrastructure improvements. Results projected that, with 2019 as the baseline year, approximately 23.1% of air travel would shift to HSR by 2035, increasing to 37.6% by 2060.
When GDP growth, demographic change, and HSR substitution were jointly considered—while excluding aircraft efficiency improvements—aviation kerosene demand was estimated at 31.17Mt by 2035 and 44.88 million tonnes by 2060. Rising fuel demand highlighted the urgent need to curb aircraft carbon emissions while accommodating mobility growth.
Currently, SAF is internationally recognized as the primary technological pathway for aviation decarbonization, with hydroprocessed esters and fatty acids (HEFA) as the only commercially viable route. As used cooking oil (UCO) remains the primary SAF feedstock but is in limited supply, even efficient nationwide collection would not provide sufficient capacity to achieve a 20% reduction in aviation emissions from 2019 levels by 2035. Therefore, China must accelerate commercialization of alternative SAF pathways through R&D support, while also adopting policies such as mandatory blending targets and carbon credit schemes to stimulate emissions reduction in the aviation sector.Extension Studie
Infinite root systems in algebra and geometry
No full textGiven a root system, we study sets of roots, called biclosed sets, introduced by Matthew Dyer to generalize the Kazhdan-Lusztig conjecture. Biclosed sets generalize the notion of a set of positive roots.
Most of their properties are standard for finite root systems and completely conjectural for infinite root systems. We prove several conjectures of Dyer about biclosed sets for affine root systems. In particular, we show that they form a lattice under containment order and coincide with the initial sections of reflection orders. Using those results, we apply biclosed sets to the study of torsion classes in Calabi-Yau categories. In particular, we show that biclosed sets give rise to generalized stability conditions on the representation category of an affine preprojective algebra and coincide with the restriction of torsion classes to the subcategory of spherical objects. In the case of type , biclosed sets case admit an explicit combinatorial model which can be interpreted (conjecturally) in terms of homological mirror symmetry; we use this model to parametrize the spherical objects of the representation category. We further use these result to give the first construction of Cambrian lattices for affine-type cluster algebras, giving a Coxeter-theoretic description of the exchange graph of the cluster algebra.
We then turn to applications of biclosed sets in the Bruhat order on a Coxeter group, giving the first proof of EL-shellability not influenced by Hecke algebras, a generalization of the Gelfand-Serganova theorem on Coxeter matroids to infinite Coxeter groups, and a description of the faces of Bruhat interval polytopes. We also prove the broadest known case of the combinatorial invariance conjecture for Kazhdan--Lusztig -polynomials in the symmetric group, and prove a related conjecture of Google DeepMind and Geordie Williamson in the case of lower intervals in the symmetric group.Mathematic
Geometry and Design in Palladio's Architecture
No full textAndrea Palladio (1508-80) is among the most loved and influential of the architects of the Italian Renaissance, famous for his elegantly proportioned buildings and for his treatise on architecture, the Quattro Libri dell’Architettura, first published in Venice in 1570. However, in terms of our understanding of exactly how Palladio achieved his‘elegantly proportioned’results, surprisingly little is known. Palladio does say that good proportions are very important, but he never explains his own methods, nor any more general theory of design. What Palladio does instead is to present us with a set of examples. The Quattro Libri as it stands is a collection of these examples, ancient and modern, some built and some not. Many attempts have been made to decode Palladio’s system, the most influential of which remains Wittkower’s treatment in his book Architectural Principles in the Age of Humanism (1949). Wittkower’s harmonic proportions hypothesis has fallen out of favour, but the more fundamental questions Wittkower poses have not gone away. Whether Palladio used a particular geometric or proportional system within his design process, and if so, what precisely that process or system was, remains a subject of intense interest and research.
This dissertation aims to significantly advance our understanding of the process that Palladio used to design his buildings. It does this by identifying the geometric basis of his design method. First it shows that the equilateral triangle, and its related forms, was integral to his design process, indeed it was ubiquitous. Recognising this allows us to move past the limitations of previous analyses which have viewed his designs using the framework of a two-dimensional Cartesian grid. Relationships which were previously overlooked become obvious, such as those based on the ratio of an equilateral triangle’s base to its height: 1: √3/2. Secondly, this dissertation demonstrates that an understanding of Palladio’s use of these specific proportions, and the numerical ratios used to approximate them, makes interpreting his designs straightforward. Once we are familiar with Palladio’s number systems, we can explain his marked dimensions and his unmarked dimensions. The methods shown allow us to decode Palladio’s designs in plan and in elevation, as a whole and in detail, with orders and without orders, as well as Palladio’s own designs for the five orders, results that were previously out of reach. This dissertation concludes that this method of working was not unique to Palladio. Rather the use of geometric templates, with forms based on the equilateral triangle, was common practice among pre-modern architects. Palladio appears to have developed his own geometric methods based on methods still in use that had survived within the craft techniques of medieval masonry, and which can be traced back, and which Palladio reconnected, to ancient Roman practice.
For purposes of comparison, this study also analyses several ancient Roman and medieval designs using these same methods. The examples and methods demonstrated will also be of interest to historians of these periods, to historians of science, and to those interested in the history of knowledge, in particular the craft, metrology, and mathematics used by ancient, medieval, and Renaissance master masons and carpenters. The methods and principles demonstrated may also be of interest to practicing architects, to professors of architectural practice and architectural theory, as well as to those more generally interested in design, and in the history of design. In addition to Palladio, references are made to the methods of Vitruvius, Villard de Honnecourt, Cesare Cesariano, Falconetto, Sebastiano Serlio, Antonio da Sangallo the Younger, Vignola, Vincenzo Scamozzi, and Ottavio Bertotti Scamozzi.
The dissertation is divided into two parts. The first half is centred on a geometry primer, followed by selected examples of how Palladio applied his geometry to architecture. The second half provides a comprehensive set of case studies. The primer is designed to introduce the reader, step-by-step, to the fundamental geometric concepts, number systems, and methods used by Palladio. So equipped, the reader will be able to understand, weigh, and evaluate the arguments, evidence, and examples which follow. The reader will also be equipped to examine additional buildings, from any pre-modern period, with respect to the possible presence and usage of such geometries and methods.
Chapter 1 introduces Palladio’s use of geometry and considers Palladio’s ancient, medieval, and contemporary sources for such methods. Chapter 2 contains the geometry primer. The primer introduces a look-up table (Appendix 3) to help the reader become familiar with the number systems which Palladio uses hand-in-hand with his geometry. Chapter 3 considers Palladio’s application of his geometric methods to architecture, including his use of short-cuts, and types (typologies), and his approach to design in elevation, in plan, and in three dimensions. Chapter 3 includes an explanation of Palladio’s method of budgeting for wall thicknesses, and the role of the orders within his geometric design system. Chapters 4 to 7 contain case studies. The case study chapters examine and explain Palladio’s use of these methods across four general classes of design problem. These are: (1) Palladio’s designs for the five orders, as published in his own Quattro Libri, (2) Palladio’s designs for Vitruvian ideal temple types, as designed by Palladio for the Barbaro Vitruvius, (3) Palladio’s designs for his own buildings, and (4) Palladio’s reconstructions of ancient Roman buildings.History of Art and Architectur
Geomechanical modeling of ground surface deformation related to thrust and reverse fault earthquakes
No full textThrust and reverse fault earthquakes show complex patterns of surface fault rupture that pose substantial hazards to critical infrastructure, including buildings, energy production and transmission facilities, telecommunication systems, and other facilities. These scarps are often highly variable along-strike, with a range of geomorphic expressions from smooth monoclinal profiles to pop-up structures and even highly localized direct fault displacements. To properly design and protect our critical infrastructure, we need the ability to forecast specific ground deformation characteristics, which has proven a challenge given the wide range of possible fault scarp morphologies. There is a paucity of historical earthquakes with surface rupture measurements, limiting our ability to make accurate forecasts based simply on empirical approaches. Thus, this dissertation develops a physics-based approach to model this phenomenon that evaluates a range of geological site conditions – including fault and sediment properties – using numerical modeling techniques to develop a statistical suite of potential ground surface deformation characteristics associated with thrust and reverse fault earthquakes.
We use the distinct element method (DEM) to model the near-surface coseismic deformation observed in thrust and reverse fault earthquakes. DEM is a deterministic modeling approach that is highly effective at reproducing the behavior of fault systems and the granular mechanics of soils and sediments in the shallow subsurface, making it especially well-suited for simulating geologic processes associated with ground surface rupture during large earthquakes. DEM treats aggregate materials as collections of circular disks (in 2D) or spheres (in 3D) that can move independently, with mechanical interactions governed by elastic and frictional contact laws that allow for complex elastic or pseudoplastic behavior. The particles can be bonded together using various contact bond models (we use the parallel-bond contact model) to impart cohesion, tensile strength, and other mechanical micro-properties which approximate natural soil and sediment mechanics. The models deform based on the displacement of boundary conditions at a prescribed velocity and timestep. This approach enables DEM to capture the emergence and evolution of structures like fractures, secondary faults, flexural slip surfaces, folds, and to realistically model sediment deposition, compaction, dilation, and deformation. By varying input parameters such as particle packing density and strength, DEM simulations can evaluate a wide range of natural geologic and soil properties, providing valuable insight into both faulting processes and granular mechanics in sediments and soils.
Chapter 1 explores an initial suite of 2D DEM experiment across a select group of fault dips and sediment strengths to evaluate a range of surface deformation characteristics observed in thrust and reverse fault earthquakes. We calibrated the 2D DEM models to analog sandbox fault models in Cole & Lade (1984) as well as the 3D DEM models from Garcia & Bray (2018a,b). We performed 45 total models which explore shallow (20º), moderate (40º), and steep (60º) fault dips in weak, moderate, and strong sediment that is 5 m deep above bedrock. The key findings of this initial suite of 2D DEM models reveal that numerical models can replicate the natural, geomorphic characteristics of fault scarps. Additionally, we propose a classification of fault scarp morphologies for the 3 main geometries observed in the models: 1, monoclinal scarps; 2, pressure ridge scarps; and 3, simple scarps. Monoclinal scarps form a single, inclined dip panel at the surface. Pressure ridge scarps form backthrusts that contribute to additional uplift above the flat surface of the hanging wall block in a “pop-up” structure. Simple scarps represent a direct fault displacement that is indicative of the fault dip at depth, generating a scarp overhang. Each of these scarp morphologies were represented by unique geomorphic characteristics that could be subsequently modified via hanging wall collapse. Collapse modified features include tensile fracturing at the crest of the scarp that forms blocks of colluvium that gravitationally collapse down the scarp face. The surface deformation characteristics of the scarp height, deformation zone width, and scarp dip were measured every 0.5 m of slip up to 5.0 m of total displacement in the models. This dataset revealed that each of the scarp classes have quantifiable geomorphic characteristics that could improve seismic hazard assessments based on geological site conditions.
Chapter 2 explores the same initial suite of 45 2D DEM models to train a machine learning script that measures the model results with higher accuracy and resolution than the previous 0.5 m of slip. This machine learning script was based on computer vision (CV) script packages and used object detection to identify the key geomorphic characteristics of fault scarps and automatically differentiate between scarp classes. From this classification system, measurements of the surface deformation characteristics (SDC) such as the scarp height (Us), uplift above the flat surface of the hanging wall (Us – Ud), deformation zone width (DZW), and scarp dip were obtained every 0.05 m of slip. We applied this machine learning script to significantly increase the number of SDC measurements by an order of magnitude, yielding 100 measurements per DEM model.
Chapter 3 expands the initial suite of 2D DEM models to examine the influence of additional model parameters and support statistical analyses of ground surface deformation characteristics and geomorphic expressions of fault scarps in thrust and reverse fault earthquakes based on local geological site information. Specifically, we tested 2,459 experiments of homogeneous sediment strengths and 975 experiments of heterogeneous sediment strengths in dense, medium-dense, and loose sediment for depths of 3, 5, and 10 m above a planar fault that dips between 20º and 70º. The hanging wall of the fault in these models displaces up to 5.0 m at a continuous rate of 0.3 m/s. For homogeneous sediment strengths, we evaluated a range from weak to strong sediment in 5 increments that vary the cohesive and tensile strengths of the contact bonds. We also varied the cohesion and tensile strength relative to one another for a total of 13 options. For the heterogeneous sediment strengths, we assessed vertical strength gradients where the base is stronger than the uppermost layers in uniform increments, vertically randomized sediment strengths, and a cohesive top unit above moderate strength sediment. This resulted in a total of 3,434 2D DEM experiments and 346,834 SDC measurements taken every 0.05 m of slip using the same machine learning model as described in Chapter 2. We performed a statistical analysis of ground surface deformation patterns in conjunction with model input parameters to correlate geological site conditions with resultant fault scarp morphologies. We found that the most influential parameters on the patterns of ground surface deformation are the accumulation of slip on a fault, fault dip, sediment depth, and sediment strength. We directly compare these measurements of SDC to historic earthquake ruptures from established fault rupture databases – such as the Fault Displacement Hazards Initiative (FDHI) – as well as the 1952 M7.8 Kern County, California earthquake (Buwalda & St. Amand, 1955). The DEM results effectively describe the range of historic surface rupture observations in these datasets, with improved fits obtained by incorporating additional information about the earthquake size (slip), fault geometry, and surface deformation style. Based on these results, we propose that this dataset can supplement the surface rupture measurements in FDHI and help forecast potential patterns of future surface rupture hazards given specific site characteristics.
Chapter 4 extends the modeling to three-dimensions and examines along-strike variability of fault scarps in thrust and reverse fault earthquakes. Thrust and reverse fault earthquakes are inherently complex and often show significant along-strike variability in the geomorphic expression of the fault scarp, although the geological conditions that yield this variability are largely unknown. Thus, we developed 18 3D DEM models to investigate the influence of fault dip and sediment strength on the along-strike variability of fault scarps. We tested fault dips of 20º, 40º, and 60º for weak and strong sediment and a case where the fault dip varied along-strike from 20º to 70º in 1º increments. Additionally, we performed a case study of randomized sediment strength heterogeneities. These 3D models successfully reproduce main fault scarp types – monoclinal, pressure ridge, and simple – aligning with surface rupture characteristics previously identified in 2D modeling. Our key results showed that the fault dip primarily determined the scarp class whereas variations in the sediment strength, specifically the randomized heterogeneities, influenced the geomorphic characteristics of scarps within that scarp class. Overall, the 3D models support the relationships of ground surface deformation characteristics (scarp class, width, height) established in previous 2D DEM results and replicate measurements of historical earthquake scarps from the Fault Displacement Hazards Initiative (FDHI) and SUrface Ruptures due to Earthquakes (SURE) datasets. These 3D DEM models provide insights into how fault dip and sediment strength govern along-strike transitions in fault scarp morphology. We propose that the combination of 2D and 3D DEM model results can aid Fault Displacement Hazard Assessments (FDHA) and infer patterns of surface ruptures based on local geological site conditions.
Chapter 5 extends the initial suite of 3D DEM models to evaluate the influence of faulting and sediment parameters on the along-strike geomorphic variability of fault scarps observed during thrust and reverse fault earthquakes. We performed 81 3D DEM experiments which explored 4 main model cases: 1, a planar, cylindrical dipping fault at depth; 2, variable fault dip along-strike from 20º to 70º; 3, variable fault seed length along-strike of a planar, dipping fault; and 4, rotating the fault relative to the slip orientation to induce slip obliquity by 30º, 45º, and 60º. We evaluated both homogenous and heterogeneous sediment strengths in a dense sediment assemblage that is 3 m deep. The homogeneous sediment strengths considered weak, moderate, and strong sediment while the heterogeneous sediment assemblages tested randomized heterogeneities and a cohesive top unit. These experiments revealed that uniform, planar faults in homogeneous sediment produce cylindrical (or symmetrical) fault scarp morphologies with little to no variability along-strike. In contrast, variability in the fault dip yielded significant changes in the scarp class along-strike from pressure ridges to monoclinal scarps and simple scarps. This reinforces the conclusion that fault dip plays a primary role in determining scarp class, while the sediment strength influences the style of geomorphic characteristics within the given scarp class. The increasing slip obliquity models converge on the geomorphic expressions of strike slip style faults with increasingly smaller deformation zone widths. We compared the SDC measurements from the 2D and 3D DEM models to measurements of natural surface ruptures in historical earthquakes in the FDHI and SURE datasets. We find that the DEM models effectively capture the range of observed scarp heights and deformation zone widths from historical ruptures and fill the gaps in our understanding from limited historical earthquake events. Furthermore, the geomorphic features of distributed fracturing, splays, backthrusts, and blocks of colluvium that vary along-strike in natural surface ruptures (such as the 1999 Chi-Chi, Taiwan, 2008 Wenchuan, China, and 2013 Bohol, Philippines earthquakes) are replicated in these 3D DEM models such that individual geological site conditions can effectively be modeled in the DEM space. Therefore, we can forecast the potential patterns of future ground surface deformation using local geological site conditions.
Ultimately, we propose that these 2D and 3D DEM models can supplement current FDHA datasets to better inform forecasts of anticipated ground surface deformation for given geological site and faulting conditions using both deterministic and probabilistic approaches. This capacity to forecast future surface rupture characteristics significantly improves available seismic hazard assessments and aid efforts to mitigate the loss of critical resources and sensitive infrastructure systems.Earth and Planetary Science
Activation-dependent lentiviruses promote selective expansion and transduction of antigen-specific T cells
No full textTumor-infiltrating lymphocyte (TIL) therapy has shown recent promise in the treatment of advanced melanoma. However, current manufacturing pipelines make use of bulk-expanded TILs, without the ability to select for bona fide tumor-reactive clonotypes. Thus, new methodologies are required to enhance the selectivity and potency of autologous TILs, while leaving bystander T cells untouched. Here, we demonstrate an approach to target recently-activated T cells via display of agonistic ligands that bind to a marker of early T cell activation (4-1BB, CD137) on the surface of a lentiviral (LV) particle. These pseudotyped LV vectors specifically recognize human 4-1BB in cell lines and primary T cells, promoting the selective activation and expansion of antigen-specific T cells from rare starting populations after antigen stimulation. Moreover, anti-4-1BB LVs specifically transduce antigen-specific T cells with user-defined genetic cargoes that can be used to both track individual clonotypes via single-cell sequencing and enhance their cytotoxic function to extend survival in a xenograft model of human melanoma. We also demonstrate that anti-4-1BB LVs can be directly added to tumor-associated lymphocytes and TIL-containing tumor fragments, promoting the transduction of patient-specific T cells ex vivo. Overall, this platform offers the ability to target antigen-specific T cells (CD4+, CD8+) in an antigen-agnostic, MHC-independent manner with potential applications in adoptive cell therapy manufacturing pipelines and TCR identification efforts.Immunolog
Precision Medicine: Biomarkers of Genome Integrity in Guiding Better Lung Cancer Outcomes
No full textLung cancer remains the leading cause of cancer mortality, and standard treatments such as radiotherapy (RT) and chemotherapy act through DNA damage. Yet patients show substantial variability in both treatment response and side effects. Because DNA repair is central to maintaining genome integrity and differs across individuals and life stages, assessing genome integrity could help identify which patients will benefit most from therapy while minimizing harmful outcomes. My dissertation focuses on developing and applying genome-integrity biomarkers to better understand treatment response and prognosis in lung cancer. I focused on three complementary domains: functional DNA repair capacity measured by fluorescence multiplex host cell reactivation (FM-HCR), telomere length dynamics during and after RT, and germline genetic variation. Across this work, I established strategies to adapt functional DNA repair assays for population studies, demonstrating that they capture meaningful inter-individual differences. I showed that changes in telomere length over the course of treatment provide stronger signals for predicting side effects than single, static measurements. And by integrating genetic data with functional measures, I found that certain genetic variants influence repair capacity and contribute to differences in treatment toxicity and prognosis. Together, these studies highlight the value of linking functional and genomic measures of genome integrity. By bringing these approaches together, my work provides a framework for using genome-integrity biomarkers to guide more personalized RT decisions and improve long-term outcomes in lung cancer patients.Population Health Science
Attenuation of the Post-Movement Beta Rebound in Patients with Epilepsy
No full textEpilepsy is a condition defined by persistent risk of seizures: episodes of aberrant electrical activity that disrupt normal brain function and place individuals at higher risk of psychiatric disorders, cognitive impairment, and death. Clinicians today do not have high performing, highly accessible measures for diagnosing epilepsy. The current mainstay of data gathering in epilepsy is electroencephalography (EEG) of spontaneous brain activity interpreted by human experts. EEG often does not yield abnormal electrical signatures of epilepsy, but these known signatures have high sensitivity and specificity for epilepsy. Because long-term neural changes in response to seizures can make future seizures more likely, a good prognosis in epilepsy requires early diagnosis and treatment. Because antiseizure medications (ASMs) can have serious adverse cognitive and behavioral effects, avoiding harm also requires accurate diagnosis. Improving the performance and accessibility of epilepsy diagnostic tools is therefore crucial for improving patient outcomes.
Seizures occur in the brain when the level of aberrant, synchronous excitatory activity in a focal epileptogenic circuit or generalized epileptogenic network exceeds the brain’s “seizure threshold” and involves wider areas of the brain. The seizure threshold depends on a balance of excitatory and inhibitory activity. A measure of cortical inhibitory tone could therefore inform epilepsy diagnosis, yet no clinical tool currently reports this property of the brain. Post-movement beta rebound (PMBR) is a response that occurs after movement detectable on quantitative EEG (qEEG) and is a putative marker of cortical inhibition. This dissertation introduces a method for quantifying the PMBR in human patients and tests the hypothesis that the PMBR is reduced in participants with epilepsy, congruent with the reduced seizure threshold in epilepsy, to evaluate whether the PMBR might be used to identify individuals with epilepsy.
This dissertation advances a method of systematic data processing for artifact rejection from EEG recordings as well as a method of PMBR quantification. Both methods are based on principled searches for parameters in a pilot dataset composed of EEG from 14 adults without epilepsy who completed a cue-response task. These protocols were then applied to a second dataset of 28 children and adults without epilepsy and 53 children and adults with epilepsy. These 81 participants completed an auditory discrimination go/no-go task during recording, which enabled assessment of behavioral performance and the analysis of trials containing stereotypical movements performed in a controlled context. A permutation testing protocol was devised to create an individualized measure of PMBR and enable evaluation of the test characteristics of the PMBR.
Participants without epilepsy displayed a positive correlation between age and PMBR power (r2 = 0.23, p = 1.2*10-2). PMBR power sharply increased shortly before adulthood (age 17.6 years). Participants with epilepsy did not have an association between age and PMBR power, and mature (> 17.6 years) participants without epilepsy had significantly greater PMBR power than participants with epilepsy (t-test p = 4.6*10-3). Participants without epilepsy still had significantly greater PMBR power than participants with epilepsy when participants with epilepsy were restricted to 1) patients without gross structural anomalies, 2) patients without moderate to severe cognitive disorders, 3) patients with focal epilepsy, 4) patients with generalized epilepsy, 5) patients with only absence seizures, 6) patients with drug resistant epilepsy, 7) patients without psychiatric disorders, 8) patients without any GABAergic ASMs, and 9) patients for whom recordings were captured at both their full dose of ASMs and when having withheld all ASMs. Permutation testing confirmed that more participants without epilepsy had greater PMBR power than participants with epilepsy (Z-test p = 1.2*10-4). Classification of epilepsy or not based on PMBR permutation testing had an ROC AUC of 0.92-0.95, with 67% specificity at 100% sensitivity and 69% sensitivity at 100% specificity, and high intra-individual reliability (r = 0.631).
Overall, this dissertation characterizes the maturational trajectory of the PMBR as detected on EEG, finds that the PMBR is attenuated in epilepsy, develops an individualized PMBR test, and assesses the PMBR test’s characteristics as a potential diagnostic biomarker for epilepsy. The findings of this work demonstrate the promise of the PMBR as an exemplar of a qEEG biomarker that could improve epilepsy diagnosis, care, and outcomes.Neuroscienc
The ‘Sprawling-to-Parasagittal’ Transition: Evolution, Function, and Development of the Mammalian Hip Joint
No full textMammals are an ecologically diverse group of animals, yet nearly every extant species has limbs adducted underneath their body in a ‘parasagittal’ posture. In contrast, mammals evolved from ‘sprawling’ synapsid ancestors with limbs splayed out to the side. Despite more than a century’s worth of research, the precise timing and acquisition of mammalian posture along the ‘sprawling-to-parasagittal’ transition remains elusive. Modern technological advancements provide paleobiologists with a new toolkit for revisiting old questions, but the hindlimb has not yet been comprehensively investigated. In this dissertation, I use a multi-disciplinary approach to examine the evolution, function, and development of mammalian parasagittal posture, focusing on the hip joint and associated bones (i.e., pelvis and femur).
In Chapter 1, I focus on direct evidence from the extensive synapsid fossil record by investigating macroevolutionary patterns of pelvis and femur morphology. The evolution of synapsid pelvis and femur morphology included multiple, semi-independent adaptive optima with the largest-in-magnitude change for both bones occurring within prozostrodontian cynodonts and a final pulse of morphological change for the femur among stem therians – the latter of which aligns with evidence from musculoskeletal modeling of the forelimb and hindlimb in a limited number of taxa. The cranially-extended and elongate ilium, reduced pubo-ischiadic plate, and medially offset femoral head show the strongest patterns of change across synapsid evolution – all features associated with a more adducted limb. In Chapter 2, I explore how rarely-fossilized soft tissues (e.g., integument, muscles) constrain hip joint mobility in the extant sprawling tegu and the extant parasagittal Virginia opossum. I found that the integument keeps the distal femur elevated in tegu, preventing more adducted poses, while extrinsic musculature in the opossum prevents the femur from retracting and depressing beyond the extent of poses used in vivo during the stance phase of walking. While ‘deep thigh’ musculature is ancestral for synapsids, mammalian integument evolved at least by Mammaliaformes, if not earlier, and may have permitted more adducted limb poses. In Chapter 3, I explore the evolution of morphogenetic development for the pelvis and femur in the parasagittal mouse compared to the sprawling brown anole and axolotl, and I also compare it to macroevolutionary patterns of morphological evolution in synapsids. Broadly, I found that mouse pelvis and femur morphology is already distinct from anole and axolotl at the earliest cartilaginous stage of development (E13.5) and continues to proceed along a unique morphogenetic trajectory. Further, early stage mouse pelves and femora, potentially as a result of heterotopic change to cranially direct the ilium and medially offset the femoral head, are most similar in shape to eucynodonts and mammaliaforms, respectively, among synapsid subclades.Biology, Organismic and Evolutionar
Debugging and Help-seeking with Chatbots in CS1
No full textFor many beginner programmers, encountering errors in code can be frustrating and disheartening—leading some to questions their belonging in computer science (CS). In these moments, timely debugging help is essential to sustain motivation and foster learning. While students have traditionally turned to peers or teaching assistants for guidance, many now seek debugging support from conversational Large Language Models (LLMs). These chatbots offer promise in providing immediate help, but their ability to generate full-code solutions raises concerns about learning and over-reliance. As these tools become more prevalent, it is important to understand how they can be used to support student's in their debugging and how students seek-help with chatbots.
This dissertation explores how students interact with chatbots in introductory computer science courses (CS1) and opportunities to support debugging. The research is presented in a three-paper format. The first paper examines past debugging interventions before the rise of LLMs, identifying gaps that these tools could potentially address. The second paper presents findings from student interviews about their experiences using a course-integrated chatbot, highlighting how they engage with the debugging assistance throughout the semester and their evolving beliefs about appropriate chatbot use. The third study analyzes naturalistic chat data and survey responses in another CS1 course to investigate how students' goal-orientation and beliefs associate with their help-seeking behaviors. The findings from this dissertation offer insights into designing course chatbots and instructional framing around chatbot use to support students' debugging and learning.Educatio