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Debanding in Frequency-Modulated bSSFP MRI: High-Resolution Neuroimaging
Get PDFBalanced Steady-state Free Precession (bSSFP) is an MR pulse sequence used widely in neuroimaging due to high signal- and contrast-to-noise ratios, especially with respect to fluids and fat, suitable for applications such as visualization of proximal cranial nerves and the inner ear. However, off-resonance artifacts appear as “dark bands” of severe signal loss. These artifacts appear in areas that deviate from the center resonance frequency at multiples of the repetition frequency (1/repetition time [TR]) and are prevalent in regions with strong magnetic tissue susceptibility variations. Furthermore, the “dark bands” become spatially concentrated as TR lengthens with increases in imaging resolution, limiting achievable spatial resolution.
Several methods exist to mitigate or eliminate the presence of these “dark bands” in areas of magnetic field inhomogeneity at the expense of SNR, imaging speed, contrast, and/or sharpness. Here, we propose the use of frequency modulated bSSFP to develop a method which focuses on maintaining or improving upon traditional on-resonance bSSFP contrast even when acquiring high spatial resolution.
The approach includes the use of repeated frequency modulations during 3D bSSFP to continually cycle dark bank locations, a ky-kz undersampling pattern designed to maximize accuracy, and image reconstruction based on the combination of low- order fitting of the frequency response and image patch-based sparsity.
The method was validated in calibrated gel phantoms with known relaxation times and applied to cadaver imaging subjects.
The proposed approach demonstrates high-resolution acquisitions with isotropic 0.4 mm voxels and preserved image sharpness, without extension of scan time.
Furthermore, the proposed approach yields quantitative pixel-wise information allowing for the future development of techniques including dictionary-based tissue relaxation parameter mapping and automatic segmentation
Time-dependent cox model for long asymptomatic malaria infections within a longitudinal cohort in a high transmission area
No full textMalaria transmission is highly heterogeneous, with a small subset of infected individuals disproportionately contributing to its transmission. This critical subgroup, termed the infectious reservoir, is defined by persistent asymptomatic malaria infections lasting three or more consecutive months. However, the factors associated with prolonged asymptomatic parasitemia remain poorly understood.
This study investigates whether time-varying exposures influence the risk of developing prolonged asymptomatic infection. Using longitudinal data from a high transmission setting, we apply a three-stage analytical approach. First, we estimate survival probabilities using Kaplan-Meier curves and compare survival between subgroups defined by baseline age, gender, village, mosquito counts, and bet net exposure. Second, we fit Cox proportional hazards models, testing model performance, and the proportional hazards assumption. Third, we incorporate time-dependent covariates, specifically mosquito exposure and bed net use, into extended Cox models to assess their dynamic effects.
In the simple Cox model, increased mosquito exposure (HR = 1.66, p = 0.0029) and reduced bed net use (HR = 0.94, p = 0.0136) are significantly associated with higher hazard of entering the infectious reservoir. In contrast, time-dependent Cox analysis yields more precise and statistically robust associations through narrower confidence intervals and reduced p values. Notably, the effect estimate for bed net use remains relatively consistent but becomes more significant (HR = 0.91, p = 0.0005), while the estimate for mosquito exposure is substantially attenuated (HR = 1.05, p = 0.0054), suggesting a more modest yet still significant effect. These findings highlight the value of incorporating time-varying covariates when modeling infectious diseases, as it better captures the dynamic nature of exposure, potentially informing more effective and targeted intervention strategies
EFFECTS OF PHARMACOLOGIC CELLULAR STRESSORS ON THE PRESENTATION OF A NON-CLASSICAL PEPTIDE-MHC COMPLEX
No full textThe adaptive immune response relies on precise antigen processing and presentation to CD8+ cytotoxic T cells and NK cells through major histocompatibility complex class I (MHC-I) molecules. At the heart of the antigen processing pathway are the human endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2. These enzymes are classically known for their crucial role in trimming peptides to optimal lengths for peptide:MHC-I (pMHC-I) complex presentation. Recently, ERAP1 and ERAP2 have been associated with broader physiological processes, including the unfolded protein response (UPR) and autophagy, alluding to a potential connection between cellular stress responses and immunosurveillance. With this study, we sought to determine if there were connections between ER stress and autophagy and Qa-1b restricted FL9 (QFL) epitope presentation, a murine non-classical pMHC-I complex known to be presented on the surface of antigen presenting cells (APCs) deficient in murine aminopeptidase ERAAP function. Using pharmacological modulators of autophagy and ER stress—bafilomycin A1, KU-0063794, thapsigargin, and tunicamycin—we evaluated their effects on QFL presentation, autophagic flux, and ER stress signaling markers in murine APC lines. Our results revealed bafilomycin A1 treatment reliably increased autophagy marker LC3-II expression, indicative of decreased autophagic flux, other pharmacological reagents did not significantly alter autophagy markers due to potential antibody affinity limitations. Thapsigargin treatment induced robust T cell hybridoma complicating interpretations of antigen-dependent immune responses. Fluorescence microscopy suggested differing ER morphology corresponding with specific pharmacological treatment, with KU-0063794 notably inducing ER puncta formation, suggesting an altered autophagic state. Significant technical limitations constrained overarching conclusions with respect to pharmacological ER stress-induced QFL presentation. Despite this, the findings of our study emphasize the complexity of interplay between ER aminopeptidases, ER stress, autophagy, and antigen presentation. Future studies employing more sensitive QFL detection, enhanced co-localization imaging techniques, and additional cellular models are vital to conclusively define these interactions
The role of NMyc downregulated gene 1 in testosterone paradox
No full textAndrogen deprivation therapy (ADT) has been the mainstay of treatment for metastatic prostate
cancer since the recognition by Dr. Charles Huggins in 1941 of its remarkable palliative benefits. In
lesser-known work, Huggins proposed that therapeutic response in hormonally-responsive cancers
could also be achieved through treatment with high doses of hormones, a strategy he called
“hormonal interference.” This paradoxical growth inhibition by supraphysiological testosterone (Supra
T), has been demonstrated in vitro and in vivo preclinical studies. Based on these preclinical
observations, a clinical trial was initiated at Hopkins that entailed administration of high dose of
testosterone termed “bipolar androgen therapy” (BAT). BAT is effective in 30% of prostate cancer.
Understanding molecular features that constitutes a high responder will help delineate pathways that
can be modulated to synergize with BAT, and lead to developing of biomarkers that would predict
response to BAT. Towards this goal, we explored the role of myc and its downstream regulated gene
NDRG1 in response to SupraT. Our data suggests that while c-myc and N-myc do not influence the
effect of SupraT on growth of prostate cancer they can affect the immune response triggered by
SupraT. This effect is acute in cells that lack the NDRG1. NDRG1 is able to influence SupraT immune
response by affecting both the canonical and non-canonical NFKB signaling. This is clinically relevant
as overexpression of c-myc or N-myc or downregulation of NDRG1 may serve as markers of BAT
resistance
Indigenous Joy: Activating Protective Health Outcomes via Ojibwe Cultural Immersion
Get PDFBackground: Cultural revitalization initiatives that reclaim and celebrate traditional life ways assert Indigenous self-determination and activate cultural protective health factors. Although joy has been found to offer benefits to emotional, psychological and social aspects of wellbeing, relatively little is known about what constitutes an Indigenous conceptualization of joy. This dissertation takes on a strengths-based approach to research in deep collaboration with the Indigenous community partner; Elders, teachers, youth, and their families from an Ojibwe cultural immersion program in Minnesota, US. Objective: The major objective of this research is to promote cultural revitalization as a viable pathway for health promotion among Indigenous populations. This work reorientates traditional Western public health to consider Indigenous perspectives of health as a holistic interconnected relationship between an individual’s social, environmental and spiritual world, rather than narrowly perseverating on a specific component of physical or mental health. This research extends previous evidence that demonstrates the value of cultural measurement among Indigenous populations, by focusing on joy as a protective health outcome activated by engagement in an Ojibwe cultural immersion camp. Methods: The specific study aims sought to 1. identify foundational health promotion values in the immersion program model through in-depth interviews, 2. describe Indigenous conceptions of joy via participatory cultural activities and listening sessions, and 3. determine the main factors that facilitate Indigenous experiences of joy with group model building creative participatory activities. Results: Aim 1 presents a thick description of the immersion program model, highlighting the importance of Indigenous leadership and pedagogy. Aim 2 offers six conceptualizations of joy (emotional dimensions, creative expression, flow, spending time outdoors, social dimensions, and healing) and five conceptualizations of Indigenous joy (solid experiences, food sovereignty, humor, community, upholding traditions). Aim 3 results culminate into a system model that depicts Indigenous joy experiences. Conclusions: This research underscores the need for culturally grounded public health initiatives that recognize the important complexity of Indigenous cultural revitalization, and prioritize joy as a necessary conduit to thriving wellbeing
The Case for Subsidizing GLP-1s in the United States as a Harm Reduction Strategy to Reduce Cardiometabolic Disease from Multiple Interlocking Forms of Food-Related Disadvantage
Get PDFThis paper examines the current therapeutic use of glucagon-like peptide 1 (GLP-1) receptor agonists primarily to treat Type II Diabetes and advocates for expanding the use of GLP-1s to combat other cardiometabolic conditions, like obesity. Expanding the on-label use of GLP-1s could help to ameliorate negative health outcomes associated with overweight and obesity and offer a preventative measure against the onset of Type II Diabetes. Drawing on empirical evidence, the paper then illustrates that the burden of cardiometabolic conditions like obesity and Type II Diabetes, disproportionately impacts populations that experience multiple interlocking forms of food-related disadvantage (i.e., food insecurity, lack of access to healthy food, etc.) Recent studies have demonstrated increased efficacy of GLP-1s’ ability to modulate dietary habits, which could offer a direct intervention to reduce the harms associated with experiencing food-related disadvantage. As such, there is a critical argument for increasing access to GLP-1s in communities that face food-related disadvantage as a harm reduction strategy that could subsequently reduce the burden of cardiometabolic disease. Given the exorbitant price of GLP-1s and the current landscape of health insurance across the United States, the paper concludes by explicating the need for GLP-1 subsidies to improve access to the medication for low-income populations that experience food-related disadvantage. Such subsidies can uphold distributive justice by reducing socioeconomic health disparities and mitigating the modifiable harms associated with multiple interlocking forms of food-related disadvantage
Deep Autofocus for Motion Compensation in Cone-Beam Computed Tomography
Get PDFCone-beam computed tomography (CBCT) is increasingly used in interventional radiology, providing 3D imaging for procedure planning, guidance, and outcome assessment. In neuroradiology, CBCT is a critical tool for various applications, including brain perfusion, radiotherapy, and stroke diagnosis. For interventional procedures in the abdomen, CBCT enables visualization of the three-dimensional vascular configuration, a crucial aspect of selective treatment, such as super-selective transarterial chemoembolization. However, a key limitation of CBCT is its moderately long acquisition time, which makes images susceptible to artifacts caused by patient motion, degrading image quality despite common motion control protocols such as patient immobilization and breath-holding.
Autofocus algorithms for motion compensation in CBCT can mitigate motion artifacts in existing data by incorporating estimated patient motion during reconstruction, thereby improving image quality and reducing the need for repeated scans. However, conventional autofocus methods often struggle with robust motion estimation and accurate representation of complex motion in clinical data. Leveraging recent advancements in machine learning, this thesis aims to develop deep autofocus algorithms that address the limitations of conventional autofocus methods to achieve reliable motion compensation. Learning-based metrics, based on deep convolutional neural networks (CNNs), are developed as cost functions for motion compensation algorithms, promoting anatomical realism and reducing motion-related artifacts in reconstructed images. An efficient autofocus framework is developed for fast and reliable convergence, including differentiable reconstruction, gradient-based optimization, and adaptive sampling strategies. Advanced encoding of spatiotemporal information using implicit neural models is also explored for capturing complex multi-organ motion and the dynamics of X-ray contrast agents, crucial for visualizing blood flow in angiography tasks.
Deep autofocus motion compensation was validated through simulation studies, phantom scans using clinical CBCT systems, cadaver experiments, and real clinical data. The results demonstrated that the proposed algorithms effectively mitigate motion artifacts in interventional CBCT images, recovering detailed structures across various degrees of motion degradation. This thesis demonstrates that incorporating deep learning into autofocus algorithms is an effective strategy to improve the reliability and usability of CBCT in interventional radiology
AI-Assisted Tools for Research Development: An Assessment of Current Policies, Best Practices, and Potential Use Cases
Get PDFThe general release of Chat GPT-4 in November 2022 sent shockwaves of excitement, fear, and anticipation throughout the world. The new natural-language capabilities of Chat GPT-4 promised to revolutionize the workplace with computers carrying out knowledge-work that was previously the purview of the educated professional class. On one hand, management imagined a powerful new cost- and labor-saving tool capable of accelerating or replacing laborious workplace tasks. White collar workers, on the other hand, feared a world where they could be replaced entirely. Three years later, how do we separate hype or fear mongering from the actual, practical applications? What kind of competitive advantage does AI offer to management
and workers that make an investment in AI resources and training? Does AI provide enough return to make a positive case for this investment? As universities look to build or grow their research portfolio, how could current AI tools be leveraged to support the efforts of research development in higher education? Can research institutions afford to ignore these potentially powerful tools? While initial results are promising, current technology has its limitations, and is far from the all-encompassing, revolutionary technology that it has been made out to be. With experience and understanding of these tools, there is some value to be gleaned from pursuing AI in the research development workplace. However, these tools are best conceptualized as worker assistants, streamlining repetitive and time-consuming tasks, but with the need of experienced direction to be worthwhile. AI can capably support current expertise and duties but requires too much experienced management and verification to dramatically upend current practices. Offices in need
of additional support may consider AI as an option to speed or support existing activities, but it is unlikely to provide a decisive, competitive advantage
Penalized for Precarious Support: A Luck Egalitarian Critique of the Social Support Criterion Used in Determining Organ Transplant Eligibility
Get PDFThe social support criterion is a significant factor used by U.S. transplant centers to
determine whether someone is eligible to be placed on the transplant list. Although intended to
fairly allocate scarce donor organs, it exacerbates inequities to transplant accessibility, unfairly
excluding nearly one-fifth of individuals seeking transplant listing. Ethical concerns regarding
this criterion have already been widely discussed, particularly due to bias in assessing the
adequacy of support and inconclusive evidence that a strong social network improves transplant
outcomes. However, luck egalitarianism— the view that individuals should not be penalized for
circumstances beyond their control—has largely been overlooked in this context. Inadequate
social support is a circumstance largely shaped by mental health conditions, complicated familial
dynamics, geographic isolation, and socioeconomic status. Excluding candidates on this basis
reinforces structural inequities.
This paper begins by demonstrating how luck egalitarianism is already implicitly
operating in the transplant system, particularly in the case of Alcohol-Related End Stage Liver
Disease, and should be extended to evaluate the social support criterion. After establishing its
relevance, the concept of luck egalitarianism is then applied to critique the use of the social
support criterion, drawing on official OPTN guidelines and ethical principles. Finally, this paper
addresses the objection that removing this criterion would necessitate the elimination of all other
non-voluntary criteria, such as poor medical status and financial instability. Ultimately, the social
support criterion is unjust as it penalizes individuals for circumstances outside of their control
without sufficient utilitarian justification for doing so. Transplant centers should instead expand
social support programs to help candidates meet necessary standards for listing
The Animals of Empire: Human-Animal Relationships at Iron Age Sam'al (Zincirli Höyük, Türkiye)
No full textThis dissertation investigates the dynamic relationships between humans and animals at Iron Age Zincirli Höyük (ancient Sam’al), focusing on how the Neo-Assyrian Empire negotiated, reshaped, and integrated multispecies communities as it extended its control over the region. Drawing on zooarchaeological data, historical sources, and the field of human-animal studies, this study examines the economic, social, and political roles of domestic livestock—caprines, cattle, and pigs—and wild taxa within the sociopolitical and economic structures of Sam’al from its Syro-Hittite origins through its transformation into an Assyrian provincial capital (ca. 9th–7th centuries BCE).
The analysis highlights how the Neo-Assyrian Empire had to contend with and adapt pre-existing human-animal relationships while imposing systems of taxation, redistribution, and labor that aligned with its imperial agenda. Caprines, long associated with mobility, ambiguous capital, and local identity, transitioned from semi-autonomous pastoral herding to a more centralized resource managed in Sam’al’s hinterland. Cattle, valued for their meat and labor, became symbols of Assyrian agricultural productivity and were closely tied to imperial ideals of control and economic integration. Pigs, initially central to household autonomy and localized subsistence, were increasingly marginalized and integrated into broader systems of urban meat distribution, reflecting shifts in domestic labor and market specialization. The Neo-Assyrian Empire’s interventions were not merely top-down impositions but involved ongoing negotiations with Sam’al’s human and animal communities. The study of urban meat distribution reveals differentiated access to animal resources across neighborhoods and social strata, underscoring the role of animals in reinforcing social hierarchies, provisioning strategies, and community interdependence. Wild taxa and ritual spaces further illuminate how animals mediated civic identity and religious practices, providing continuity with local traditions even amid imperial transformations.
By positioning animals as active participants in Sam’al’s political economy and social fabric, this dissertation argues that the Neo-Assyrian Empire’s expansion relied on its ability to reconfigure human-animal relationships. The findings illuminate the enduring influence of multispecies interactions in shaping ancient imperialism, offering broader insights into the role of animals in human history