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Point-of-Care Vertical Flow Assay Testing Using Saliva in Lupus Patients
No full textLupus Nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) characterized by kidney inflammation and damage. Early diagnosis is critical, as 30% of patients progress to end-stage renal disease. Current diagnostic methods are invasive and time-consuming, highlighting need for rapid, non-invasive point-of-care tool, especially in under-resourced settings. This study investigates a saliva-based Vertical Flow Assay (VFA) to detect LN-specific antibodies. The VFA utilizes a nitrocellulose membrane spotted with double-stranded DNA (dsDNA), HEp-2 cell lysate for antinuclear antibodies (ANA), biotinylated bovine serum albumin (bio-BSA) as a positive control, and assay diluent as a negative control. Samples were applied, followed by a biotinylated anti-IgG detection antibody and streptavidin-conjugated gold nanoparticles for signal enhancement. Results were processed using ImageJ software. Testing with standard serum samples showed a moderate correlation between signal intensity and antibody concentration for anti-dsDNA (R2=0.564) and ANA antibodies within a range of 0-20 IU, indicating reasonable linearity. The assay demonstrated higher sensitivity to dsDNA antibodies at elevated concentrations. Coefficient of variation values for anti-dsDNA and ANA were 25% and 24%, respectively, demonstrating consistent reproducibility across operators. Preliminary patient samples effectively distinguished between healthy individuals and those with LN based on visual signal intensity. An Observance Score system was implemented for eye assessment of VFA results. Future work will expand the study to a larger patient cohort to further validate the assay's sensitivity, specificity, and clinical utility, aiming to establish it as a reliable point-of-care diagnostic for lupus nephritis.Biomedical Engineering, Department ofHonors Colleg
Difficulty in Emotion Regulation and Self-Concealment as Mediators of the Link Between Psychological Distress and Disordered Eating Behavior in Emerging Adult Women
No full textObjective: Emerging adulthood often involves a greater degree of disordered eating behaviors, especially among women. In this psychosocial context, extant evidence suggests that psychological distress is a major contributing factor to disordered eating behaviors. The present cross-sectional study examined whether psychological distress was positively associated with disordered eating behavior in a sample of emerging adult women, and whether difficulty in emotion regulation, self-concealment, or both together, at least partially explained this association. Method: Participants were 723 emerging adult women aged 18 to 25 years old (Mage = 19.5, SDage = 1.6) who were recruited from a four-year public university in Hawaii, USA. Upon the completion of the informed consent procedure, they voluntarily completed an online survey package that included the self-report measures assessing disordered eating behavior, psychological distress, difficulties in emotion regulation, and self-concealment. Results: We found that psychological distress was positively associated with disordered eating behaviors. We also found that both difficulty in emotion regulation and self-concealment partially accounted for the positive association between psychological distress and disordered eating behavior. Discussion: Future research should examine the conceptual and applied implications of these findings further
Integrated Curriculum in Critical Care Clerkship for Medical Students: Impact on Professional Growth
No full textBackground: Traditional curricula for medical education provide a horizontal, chronological delivery of basic sciences followed by clinical exposure. This approach compromises cohesive organizational thinking on disease management due to a fragmentation in learning. Vertically integrated curricula present basic sciences embedded in a clinical context and reinforce basic science concepts during clinical rotation, thus providing contextualized learning and enhancing motivation for mastery. This approach promotes knowledge retention and acquisition of skills through the repetitive and progressive development of concepts. Purpose: An integrated critical care curriculum provides a strong foundation in the patient care areas of eliciting history, physical examination, clinical reasoning, and patient management. It also fosters practice-based learning (PBL). This educational model integrates evidence-based care with informed practice, commitment to reflective practice, and an emphasis on personal growth that establishes better learning and residency preparedness. Variances and effectiveness in curricular delivery can also impact students' career choices. This study hopes to understand students' perceptions of the integrated curricular approach, self-evaluation in patient care, medical knowledge, and PBL. Methods: This qualitative study used a phenomenological hermeneutic approach to explore student experiences in an integrated curricular training environment. Eight participants who have completed at least a one-week elective in critical care medicine were invited to participate. Field notes, interview transcripts, and artifacts such as student notes or concept maps were used. A structured data analysis using Moustakas' approach was performed by horizontalization and coding to identify common themes and patterns. Interpretations were derived from emerging themes and subthemes, understanding the interplay of the curricular strategy's structural description, the medical students' imaginative variation, and the researcher's observation lens. Results: Eight medical students in their fourth year of training who had completed at least 4 weeks of ICU clerkship were enrolled and interviewed. Based on their clinical experience, they were able to discuss their perceptions of integrated critical care training. The emerging themes of their perceived curricular delivery were categorized based on faculty engagement, student expectation, review of integrated knowledge, variability in curricular delivery and educational tools used, opportunities for transdisciplinary learning, and high-impact curricular components. The critical care curriculum achieved a significant level of trainee perception on integrated, transdisciplinary, and multi-system knowledge essential for complex patient management. Conclusion: The results provided an understanding of students' perceptions of an integrated curriculum and its effect on patient care, medical knowledge, and PBL
Multiobjective RF Communication Networks: Theory and Hardware Implementation
No full textCommunication networks play a central role in many fields of modern technology, from industry to agriculture, to defense, to development of urban or rural areas. Regardless of the medium this dissertation is found on, either paper or a digital copy, it was brought to your hands thanks to an exchange of information between my computer and some server closer to your location. Even more with the evolution of cell phones and the advent of the Internet of Things (IoT), reliable, resilient and high speed networks are the backbone of modern society. By virtue of the pivotal role of networks, great focus is placed on the optimization of their cost. The cost of a network can be expressed in terms of several different factors: the cost of adding a node, the cost of transmitting a signal from a node to the other, the cost of reorganizing the network if a node fails, to name a few. If nodes have to perform additional tasks, possibly unrelated to communication, additional costs may need to be considered, and the resources of the underlying system may need to be shared between conflicting activities. Conflict, in this case, is defined as the tendency of two or more cost functions to have the same trend (decreasing or increasing) when the same system resource is consumed. Optimization of multiple concurrent costs, also known as Multi-objective optimization, is a branch of mathematics that generalizes single cost optimization, and to do so it introduces specific definitions and tools. This manuscript contributes to research on optimization of communication networks in two ways: on one side, by focusing on general algorithms that provide a quantitative guidance for network designers, to build a network that simultaneously optimizes some selected concurrent costs. On the other side, by developing a hardware solution that realizes a very specific transmission scheme for an individual network node: beamforming. Instead of a single antenna broadcasting information in the spatial directions dictated by its design, beamforming entails a system of antennas that collectively enhance broadcasting only in selected directions, exploiting constructive and destructive interference of the electromagnetic field. Beamforming has the advantage of focusing transmission power, limiting both energy waste and eavesdropping of information. Beamforming is widely used in radars and satellites, and in smaller scale, also in cellphones
Enhancing Hex-dominant Meshes: Generation, Evaluation, and Simplification
No full textHex-dominant mesh generation has recently received increasing attention from researchers and the simulation community due to its robustness compared to pure hex-mesh generation techniques. However, simulation algorithms require a limited number of cell types and mesh elements of desired quality to perform physics-based simulations over complex geometries. Unfortunately, in practice, most automatic hex-dominant generation algorithms for various geometries may contain unpredictable mesh elements, low-quality components, and undesired configurations. Furthermore, the hex-dominant meshing community lacks effective strategies for evaluating mesh structures or performing post-processing operations on these meshes. To address these challenges, this dissertation analyzed the demands aligned with the key stages in the meshing pipeline and contributed to the following areas: First, I designed a new hex-dominant mesh generation pipeline with an effective mesh extraction strategy. The generation pipeline links field information for feature alignment and utilizes a Voronoi diagram for geometry representation, which enables the pipeline to excel in both global and local controllability. The extraction strategy significantly improves generation performance. Second, I introduced a new 3D hexahedral mesh visual analysis system that highlights poor-quality areas with an aggregated glyph, emphasizes overlapping elements, and offers multi-level analysis through multiple views to effectively evaluate various mesh models and compare the performance of mesh generation and optimization algorithms for hex meshes. Third, I developed the first framework for analyzing hex-dominant meshes. It extends the base complex of pure hex-meshes by including non-hex elements. I also introduced a strategy to extract a cleaned (optimized) valence-based singularity graph wireframe to study the structure of both meshes and sheets. Fourth, I presented a first structure-informed simplification framework aimed at reducing the number of non-hex cells in hex-dominant meshes. My framework eliminates non-hex cells by using a novel relation graph that captures the connections involving edges and extracted sub-structures. I conducted comprehensive evaluations for each contribution, which demonstrated the advantages of my methods and their potential impact on related communities
Leveraging Gaussian Process Sampling for Sensitivity Analysis and Optimization in Engineering Design
No full textHigh-fidelity simulations and physical experiments are fundamental in engineering analysis and design. However, their high computational cost often prohibits their application in global sensitivity analysis (GSA), optimization, and automated structural health monitoring (SHM). Gaussian processes (GPs) are proposed as a promising solution to this challenge. GPs inherently facilitate efficient sampling strategies, enabling informed decision-making under uncertainty by extracting information from a subset of potential functions for the model of interest. Despite their widespread use in machine learning and scientific computing, and the potential they hold for realizing intelligent infrastructural systems via Digital Twin, GP sampling strategies have received little attention in engineering applications. This thesis thus presents the mathematical foundations of GPs and provides a detailed implementation of two sampling methods—Fourier decomposition-based and pathwise conditioning—for generating approximate stochastic functions from GPs. It then discusses the application of these sampled stochastic functions in engineering tasks such as GSA, single-objective optimization, and multi-objective optimization. Towards realizing intelligent engineering systems, this thesis finally proposes a DT framework that leverages GP for efficient model updating and optimal decision-making
A Bilevel Optimization Framework for Adversarial Control of Gas Pipeline Operations
No full textCyberattacks on pipeline operational technology systems pose growing risks to energy infrastructure. This study develops a physics-informed simulation and optimization framework for analyzing cyber–physical threats in petroleum pipeline networks. The model integrates networked hydraulic dynamics, SCADA-based state estimation, model predictive control (MPC), and a bilevel formulation for stealthy false-data injection (FDI) attacks. Pipeline flow and pressure dynamics are modeled on a directed graph using nodal pressure evolution and edge-based Weymouth-type relations, including control-aware equipment such as valves and compressors. An extended Kalman filter estimates the full network state from partial SCADA telemetry. The controller computes pressure-safe control inputs via MPC under actuator constraints and forecasted demands. Adversarial manipulation is formalized as a bilevel optimization problem where an attacker perturbs sensor data to degrade throughput while remaining undetected by bad-data detectors. This attack–control interaction is solved via Karush–Kuhn–Tucker (KKT) reformulation, which results in a tractable mixed-integer quadratic program. Test gas pipeline case studies demonstrate the covert reduction in service delivery under attack. Results show that undetectable attacks can cause sustained throughput loss with minimal instantaneous deviation. This reveals the need for integrated detection and control strategies in cyber–physical infrastructure
Development of a Microfluidic Platform for Safe and Efficient Leukapheresis in Pediatric Patients
No full textLeukapheresis is a medical procedure in which a patient’s blood is passed through an apheresis machine to separate white blood cells (WBC) from red blood cells (RBC) and platelets (PLT), which are then returned to the patient. It is a life-saving therapy for patients with symptomatic hyperleukocytosis (a common condition in acute leukemias) and is also used to collect cells for treatments such as CAR-T cell therapy. Although well-tolerated by adults, leukapheresis involves significant risks for small pediatric patients, primarily because the extracorporeal volume (ECV) of a typical centrifugation-based leukapheresis machine represents a particularly large fraction of the pediatric patient’s total blood volume. To address these concerns, this dissertation explores microfluidic cell separation as a safe alternative technology due to its dramatically low void volumes. We first review recently developed passive microfluidic technologies to evaluate their potential for leukapheresis and identify challenges that need addressing. Building on this analysis, we develop a high-throughput microfluidic platform to alleviate the limitations of conventional leukapheresis. In vitro, our microfluidic devices remove large WBC and leukemic blasts from undiluted human whole blood with high efficiency, while minimizing RBC and PLT loss. Highly-parallelized devices allow faster, clinically relevant flow rates with no drop in leukocyte collection efficiency. When attached to Sprague-Dawley rats, the devices reduce leukocyte counts by nearly half after a 3-hour procedure, with insignificant PLT loss and low ECV. Evaluation of plasma biomarkers and cytokines reveals no adverse effects compared to the surgical control, demonstrating the safety of this approach. Furthermore, feasibility studies in piglets demonstrate that our devices have a strong translational potential in a pediatric setting, while promising preliminary results for specific WBC subtype enrichment pave the way for this technology to be used for cellular collection procedures. Based on these results, this dissertation proposes that microfluidic leukapheresis is safe and effective at selectively removing leukocytes from circulation. These findings not only have the potential to make a life-saving therapy accessible to pediatric patients but can also improve other diagnostics and therapies such as circulating tumor cell detection, CAR-T cell therapy, and extracorporeal photopheresis
Immune Biomarkers and Detection Systems
No full textImmune biomarkers are crucial indicators of disease activity and immune response in various conditions. This study focuses on identifying immune biomarkers in lupus nephritis (LN) and Alzheimer’s disease (AD), and on developing a high-throughput detection system to measure multiple autoantibodies using a 96-well array format. LN, a kidney inflammation caused by systemic lupus erythematosus (SLE), was studied using Serological Proteome Analysis (SERPA), which identified 678 potential autoantibody targets. Fourteen of these were selected for further validation. To validate these targets, we developed a novel microwell autoantibody array system (MAAS) capable of analyzing up to 72 targets in a single well. Compared to traditional ELISAs, MAAS uses smaller sample volumes and fewer reagents, while offering greater automation and six times higher throughput than glass slide-based arrays. Using MAAS, we validated five autoantibodies: anti-HPGD, anti-S100A2, anti-ACLY, anti-PDIA3, and anti-HYOU1, as significantly elevated in LN patients. These markers also correlated with clinical indicators such as SLEDAI scores, proteinuria, and kidney inflammation. Additionally, the serum concentration of the antigen targets of these autoantibodies were evaluated via ELISA and we identified HYOU1 as highly predictive of LN disease activity. We also explored the potential of immune biomarkers in AD, in which the dysregulation of the immune system is a key player in disease progression. Interestingly, we identified V-set and immunoglobulin domain containing 4 (VSIG4), a receptor for complement C3b, as a novel potential serum biomarker. VSIG4 was elevated in AD patients and correlated with complement C3, with markers of inflammation, altered lipid metabolism and neuronal damage, and with cognitive performance. A longitudinal study showed that serum VSIG4 concentration consistently increased with age in AD patients and could be linked to AD risk factors, such as obesity. We were able to build a predictive model relating cognitive impairment to VSIG4 concentration. These findings highlight the potential of immune biomarkers in both LN and AD and demonstrate the effectiveness of the MAAS platform for multiplex detection
Inducing Interconnected Fractures in Granite via Pulsed Power Plasma Using Nanoparticles: A Waterless Stimulation Approach for Enhanced Geothermal Systems
No full textThis study introduces nanoparticle-enhanced pulsed power plasma stimulation (NP-3PS) as a waterless fracturing technology for enhanced geothermal systems (EGS), employing ultrafast high-pressure plasma discharges from a 20 kJ capacitor charged to 40 kV to initiate and propagate complex fractures in 8-inch (20.32 cm) granite cubes via single pulses of 10, 12, and 16 kJ and a staged 4 + 6 kJ sequence. A 2-inch (5.03 cm) borehole was filled with nanofluid containing 0.3 wt % aluminum NP (60–80 nm) suspended in 7 wt % potassium chloride (KCl) + 0.18 wt % guar gum to sustain thermite reactions and multi-cycle shockwaves, generating peak pressures exceeding 100,000 psi (690 MPa) within microseconds. Post-stimulation diagnostics using 13 µm micro-CT, thin-section microscopy, and acoustic velocity analysis revealed dense branched fractures, porosity increase from 1.3% to 4.6% (~250%), and thermal conductivity reduction of 9–16%, indicating enhanced permeability and convective heat-transfer potential. The NP-driven multi-pulse mechanism reactivated existing fractures at lower energy without wire replacement, establishing a quantitative framework linking plasma dynamics, rock damage evolution, and thermal response, thus confirming NP-3PS as a scalable and sustainable alternative to hydraulic fracturing for geothermal reservoir stimulation