Digital Commons Network^™

Information-Theoretic Path Planning For Safe And Adaptive Nanobot Drug Delivery, Nagesh Bheesetty, John H. Park, Sujatha Alla, Winifred M. Lo, Aditya Nimmagadda, Mohamadmahdi Samandari, Jae H. Lee

Engineering Management & Systems Engineering Faculty Publications

We present a safe and efficient path planning framework for nanobot navigation in complex vascular networks, enabling precise drug delivery to hard-to-reach tumor regions such as those found in the lungs. The proposed method introduces a safe and efficient path planning strategy that integrates a utility-based function to balance two key goals: exploring uncertain areas to gather valuable information and avoiding hazardous regions to ensure safe and reliable delivery. We evaluate a simplified swarm-based nanobot navigation scenario using synthetic vascular maps that mimic the structural complexity of lung tumor blood vessels. Environmental uncertainty is modeled from vessel topology, blockage density, …

Can You Hear Me Now?, Daniel Gonzalez, Amanda Moore

Faculty Publications

No abstract provided.

The Relationship Between Enablement Sentiment And Kpi Achievement, Stefanie Boyer, David E. Fleming, Michael Rodriguez, Tom Tonkin

Marketing Department Faculty Journal Articles

Sales enablement (defined as the "activities, systems, processes and information that support and promote knowledge-based sales interactions with client and prospects” (Gartner, n.d.)) has evolved from a tactical resource to a strategic organizational function, crucial for aligning sales and marketing. Despite its importance, there is a lack of research on how 'sentiment' (perceptions toward enablement) influnces key performance indicators (KPI). This exploratory survey of sales and enablement professionals investigates sentiment across individual, team, and company levels, and its relationship with KPI achievement. Results reveal positive relationships between sentiment and performance outcomes at all levels with organizational sentiment being the strongest …

Putting The L In Elsi: Legal Methods For Bioethics Research, Anya E R Prince, Benjamin Berkman, Donald Ford, Dov Fox, Christi Guerrini, Amy Koopmann, Natalie Ram, Jessica L Roberts, Kayte Spector-Bagdady, Sonia Suter

Center for Medical Ethics and Health Policy Staff Publications

Lawyers and law professors are increasingly involved in interdisciplinary scientific teams and grant research to answer ethical, legal and policy questions related to biomedical topics. Yet, the methods that lawyers use to conduct legal research and analysis are not always familiar to scientists and social scientists conducting peer review of a proposed project with legal aims or a publication reporting a legal study. To better facilitate interdisciplinary ethical, legal, and social implications collaboration, there is a need to better explain how legal research methodologies can provide robust tools to address a range of nuanced biomedical questions. This paper explores …

Can I Get A Witness? The Ethical Dimensions Of Family Presence In Patient Suffering, Jennifer Blumenthal-Barby, Trevor M Bibler, Holland Kaplan, Adam Omelianchuk, Joanna Smolenski

Center for Medical Ethics and Health Policy Staff Publications

For patients who are suffering, the bedside presence of a family member can provide comfort, and many people hold that there is moral value in being present with a conscious, suffering patient. Yet what is the moral significance of the absence of family members when a patient is minimally conscious or unconscious and not aware of their absence? Clinicians are often troubled when family members and surrogate decision-makers who are able to spend a significant amount of time at an unconscious, seriously ill patient's bedside do not do so. Clinicians feel frustrated that they must bear the burden of witnessing …

Clinicians’ Views On A Patient Decision Aid For Deep Brain Stimulation In Parkinson’S Disease, Hillary S King, Jennifer Blumenthal-Barby, Benjamin H Levi, Sol De Jesus, Harini Sarva, Laura Y Cabrera

Center for Medical Ethics and Health Policy Staff Publications

Introduction: For people with Parkinson's disease (PD), deciding whether to pursue deep brain stimulation (DBS) has become increasingly complex. Evidence suggests current approaches to collaborative decision-making may fall short of accepted standards. Thus, a decision support intervention, such as a patient decision aid (PtDA) may be warranted. PtDAs have been shown to improve patients' knowledge, expectations, and participation in decision-making for other, similar healthcare decisions. We therefore sought to assess neurologists' awareness of, and experience using, PtDAs, and to solicit their opinions on the ideal features of a PtDA for PD patients considering DBS.

Methods: Sixteen United States-based neurology clinicians …

Toward Ethical Provenance Tracking: The Ga4gh Model Data Access Agreement (Daa), Alexander Bernier, Bartha Maria Knoppers, Jonathan Lawson, Robyn Mcdougall, Maili Raven-Adams, Vasiliki Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Standardizing contractual clauses that govern data access enables research institutions to responsibly steward genomic and related health data while enabling its efficient downstream reuse.

Methods: We describe a document analysis study using both qualitative and comparative law analytical approaches to identify the most common categories of clauses from 29 different data access agreements used by human biomedical research consortia globally. We furthermore characterized the legal positions and standard practices for each common element of the agreement and synthesized across them to develop model clauses. A total of 3 discussion sessions were organized virtually to refine the clauses among members …

Nanoparticle Albumin-Bound Paclitaxel And Nivolumab For Pd-1 Inhibitor-Refractory Recurrent Or Metastatic Head And Neck Squamous-Cell Carcinoma, Douglas Adkins, Jessica C Ley, Christine Auberle, Brendan Knapp, Jesse Zaretsky, Jingxia Liu, Peter Oppelt

2020-Current year OA Pubs

INTRODUCTION: Standard therapy for PD-1 inhibitor-refractory recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC) has limited activity. Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, a process driven by constitutively hyper-activated EGFR/RAS/PIK3CA signaling, which is common in HNSCC. Nanoparticle albumin-bound (nab)-paclitaxel is active in PD-1 inhibitor-naïve RM-HNSCC and alters immune cells to potentially prime tumor response and reverse resistance to PD-1 inhibitors.

METHODS: In a single-arm phase 2 trial, patients with PD-1 inhibitor-refractory RM-HNSCC received nab-paclitaxel and nivolumab given in 28-day cycles. The primary endpoint was objective response rate (ORR), using RECIST1.1. Key secondary endpoints were …

Application Of Machine Learning To Blood-Based Biomarkers Of Alzheimer's Disease In Down Syndrome, Patrick H Luckett, Melissa Petersen, Sid O'Bryant, Mark Mapstone, Brad T Christian, Benjamin Handen, Elizabeth Head, Beau M Ances, Alzheimer's Biomarker Consortium‐Down Syndrome

2020-Current year OA Pubs

INTRODUCTION: Blood-based biomarkers can improve Alzheimer's disease (AD) characterization in Down syndrome (DS). This study applied hierarchical clustering and machine learning-based feature selection to identify biomarkers associated with disease progression.

METHODS: Cross-sectional blood-based biomarkers were analyzed from 211 DS participants (

RESULTS: The strongest predictors overall were neurofilament light chain (NfL), tau/amyloid beta (Aβ)40, Aβ42/Aβ40, alpha-2-macroglobulin (A2M), and interleukin (IL)-10. Within the CS group, NfL, tau/Aβ40, A2M, and IL-10 were strong predictors. In MCI, Aβ42/Aβ40, NfL, A2M, and IL-10 were strong predictors. In DS-AD, Aβ42/Aβ40, NfL, and tau/Aβ40 were the top predictors. Cluster membership varied based on disease stage.

DISCUSSION: …

A Neurophenomenological Perspective On The Self And Spirituality: The Role Of The Affective Core Self, Michael J. Winkelman, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

The self is central to spirituality because the self is necessary for consciousness, and spiritual relations are fundamentally about the self. Diverse research illustrates the role of the downregulation of the right parietal lobe (rPL) in the spontaneous manifestation of spiritual experiences and during meditative practices. The functions of the rPL are central to the self, especially the embodied self. Disturbances of the rPL and embodied self-functions are associated with spiritual experience, exemplified in their association with “selflessness.” Many forms of self appear incompatible with spiritual and mystical experiences. An exception is the affective core self, the most ancient form …

Perception Of Dementia Risk Among Black Adults: An Ecological Analysis Of Causal Loop Diagrams With A Structural And Social Determinant Of Health Composite Index, Jean-Francois Trani, Ramkrishna K Singh, Alexis Ib Walker, Semere Bekena, Yiqi Zhu, Ganesh M Babulal, Robbie Hart

2020-Current year OA Pubs

INTRODUCTION: To investigate drivers of dementia risk disparities among older Black Americans using a community-based system dynamics (CBSD) approach.

METHODS: Over 18 months, 234 participants created 36 causal loop diagrams (CLDs) on dementia risk. An ecological analysis compared structural differences across groups based on scores on a structural and social determinants of health composite index (S/SDOH-CI).

RESULTS: Groups in the highest SDOH-CI quantile were more likely to identify key protective pathways linking mental health, substance use, exercise, medication, and community support to reduce dementia risk. In contrast, fewer than 25% of low-SDOH-CI groups identified these connections, and under 15% recognized …

Development Of Colonic Polyposis In A Woman With Chronic Myeloid Leukemia Treated With Dasatinib, Guido Pelaez, Behram Suha Yildiz, Mert Candan, Mohammad Ismail, Francesca Vacca, Marianna B Ruzinova, Samuel Ballentine, Kathleen Byrnes, Armin Ghobadi

2020-Current year OA Pubs

INTRODUCTION: Chronic myeloid leukemia (CML) is a hematopoietic malignancy driven by constitutive tyrosine kinase activity. Dasatinib, a second-generation (2G) tyrosine kinase inhibitor (TKI), is a preferred treatment due to its superior, durable, and rapid response rates. While dasatinib has known gastrointestinal (GI) side effects, colonic polyposis is a rare complication, not well described in the literature.

CASE PRESENTATION: Upon routine colonoscopy, a 66-year-old woman with chronic-phase CML was incidentally discovered to have asymptomatic colonic polyposis after 11 months of dasatinib therapy. Histopathology revealed reactive inflammatory changes without evidence of dysplasia or neoplasia. The polyposis resolved completely after cessation of dasatinib. …

Treating Alzheimer's Disease In A Person Living With Hiv, David B Clifford, Tammie L S Benzinger, Jee-Young Han, Savannah Powles, Madeline Paczynski, Beau M Ances, J William Campbell

2020-Current year OA Pubs

INTRODUCTION: Human immunodeficiency virus (HIV) therapies now support survival into advanced ages by suppressing HIV replication and preserving immune function. Alzheimer's disease (AD), the most common neurologic degenerative condition, may now be treated with anti-amyloid therapies (AAT). HIV was an exclusionary criterion in clinical trials for AAT, leaving the safety and efficacy of these medications unknown in this setting.

METHODS: We report the development of AD supported by careful evaluations and biomarkers over a 10-year period in a person living with well-controlled HIV infection.

RESULTS: AD was diagnosed with consistent clinical and biomarker evidence. AAT was successfully administered without complications. …

Biological Aging Acceleration In Major Depressive Disorder: A Multi-Omics Analysis, Breno Satler Diniz, Shangshu Zhao, Gabin Drouard, Eero Vuoksimaa, Miina Ollikainen, Eric J Lenze, Ming Xu, Richard H Fortinsky, George A Kuchel, Jaakko Kaprio, Chia-Ling Kuo

2020-Current year OA Pubs

Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ-specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ-specific levels-including the brain-in both cohorts, with stronger associations than those observed with systemic epigenetic aging. Systemic and brain-specific proteomic aging acceleration were linked to higher risks of incident MDD and a greater risk of Alzheimer's disease, …

Excellent Survival Following Low-Intensity Approaches Prior To Allo-Hsct In Ph+ All: A Comprehensive Meta-Analysis, Lacey S. Williams, Wenners Ballard Iii, Deniz Ozisik, Charles Scott Dorris, Kepher Makambi, Scott Rowley, Kieron Dunleavy, John Dipersio, Alaa Ali

2020-Current year OA Pubs

No abstract provided.

Novel Insights Into Early Alzheimer's Disease: Quantitative Gradient Recalled Echo Mri Reveals Preatrophic Neuronal And Myelin Injury Concurrent With Emerging Amyloid Pathology, Satya V V N Kothapalli, Tammie L S Benzinger, Randall J Bateman, Melody Li, Cihat Eldeniz, John C Morris, Dmitriy A Yablonskiy

2020-Current year OA Pubs

BACKGROUND: Brain amyloid accumulation is considered an early sign of Alzheimer's disease (AD) pathology, appearing decades before manifestation of clinical symptoms. However, very little is known about neurodegeneration during this early AD stage. Herein we use quantitative gradient recalled echo (qGRE) magnetic resonance imaging (MRI) to reveal preatrophic microstructural neuronal and myelin damage concurrent with amyloid pathology.

METHODS: qGRE MRI and positron emission tomography (PET) amyloid [

RESULTS: qGRE detected significantly lower gray matter neuronal density and white matter myelination in the group of participants with amyloid level below the conventional amyloid-positive threshold (mean cortical standardized uptake value ratio of …

Comparison Of Positive Dysphotopsia Rates Between Au00t0, Mx60e, Pcb00/Zcb00, And Sn60wf Intraocular Lenses, Jonathan L. Tong, Maggie J. Xing, Arsham Sheybani

2020-Current year OA Pubs

No abstract provided.

The Association Between Major Depressive Disorder, Plasma Biomarkers Of Alzheimer's Disease, And Mild Behavioral Impairment Among Older Adults, Yiqi Zhu, Jean-Francois Trani, Ramkrishna K Singh, Semere Bekena, Jonathan Williams, Eric J Lenze, Ganesh M Babulal

2020-Current year OA Pubs

INTRODUCTION: Plasma biomarkers and mild behavioral impairment (MBI) are associated with dementia risk, but their relationships with major depressive disorder (MDD) are understudied. This study aimed to examine associations between plasma biomarkers of Alzheimer's disease (AD) and MBI among older adults with and without MDD.

METHODS: Older adults aged ≥65 were recruited from longitudinal studies of depression and AD (

RESULTS: Older adults with MDD were more likely to endorse MBI. After adjustment, Aβ42/Aβ40 and p-tau217/np-tau217 positivity were associated with MBI among those with MDD but not among those without.

DISCUSSION: Neuropsychatric symptoms (NPS) and biomarkers are AD risk factors. …

Reliability Of Remote Self-Administered Web-Based Digital Cognitive Measures And Comparison To In-Person Neuropsychological Tests: Stricker Learning Span, Symbols Test, And The Mayo Test Drive Screening Battery Composite, Morgan A Hughes, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

INTRODUCTION: We describe the reliability of remote self-administered digital cognitive measures completed via the Mayo Test Drive (MTD) web-based platform.

METHODS: A total of 1846 participants (mean age = 70, SD = 12, range 31-101; 48% male; 96% White; 99% non-Hispanic; 97% cognitively unimpaired) with two to four complete MTD sessions at ∼7.5-month intervals were included. Test-retest reliability was assessed using single-rating, absolute-agreement, and two-way mixed intraclass correlation coefficients (ICCs) with 95% confidence intervals. ICCs for in-person-administered traditional neuropsychological measures were compared to MTD for a subset of 244 participants. Analyses also compared reliability across demographic, residential, and session context …

The Impact Of Congenital Heart Disease On The Timing Of Alzheimer's Disease In Down Syndrome, Julianne G Clina, Beau Ances, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS.

METHODS: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (

RESULTS: People with CHD scored lower for visuospatial ability (

DISCUSSION: Presence of CHD may influence AD progression in DS.

HIGHLIGHTS: In adults with Down syndrome (DS), those with congenital heart disease (CHD) had higher amyloid beta and reached the …

Antihypertensive Medications And Risk Of Alzheimer's Disease: Evidence For Specific Medication Use, Osvaldo J. Laurido-Soto, Alejandra Camacho-Soto, Irene M. Faust, Kassu M. Beyene, Aaron Katz, Jordan A. Killion, Brad A. Racette

2020-Current year OA Pubs

No abstract provided.

Criterion And Convergent Validity Of Plasma Biomarkers In Early-Onset Alzheimer's Disease: Initial Findings From Leads, Dustin B Hammers, Kyle Womack, Erik Musiek, Et Al.

2020-Current year OA Pubs

No abstract provided.

Alzheimer's Disease Stage 1 And 2: Biology, Diagnostics, And Treatment, Suzanne E. Schindler, Sarah M. Hartz, Et Al.

2020-Current year OA Pubs

No abstract provided.

Plasma P-Tau217 And Apoe Genotype: Prodromal Alzheimer's Disease Staging, Ann M Stowe, Ellen Binder, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Plasma phosphorylated tau (p-tau)217 levels and apolipoprotein E (

METHODS: We measured

RESULTS: Plasma p-tau217 was 57% higher in subjects with at least one

DISCUSSION: Plasma p-tau217 demonstrated elevation in the

Establishing Demographic-Based Normative Values For Neurofilament Light Chain And Glial Fibrillary Acidic Protein In Serum And Plasma Samples, Tyler L Borko, Salim Chahin, Et Al.

2020-Current year OA Pubs

BACKGROUND: Interpretation of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels in blood requires reference ranges from healthy cohorts, accounting for demographic features.

OBJECTIVE: To compare serum and plasma NfL and GFAP in healthy individuals, accounting for age, sex, and body mass index (BMI).

METHODS: Adolescents through older adults were recruited at Colorado community events and a senior clinic. A neurologist reviewed self-reported medical histories. Paired serum and EDTA plasma samples were assayed using the Quanterix SR-X Simoa Neuro 4-Plex. Log-linear models estimated percent change per year of age, per BMI unit, and sex ratios. GFAP used …

Effect Of A Pregnancy Lifestyle Intervention Embedded Into A Home Visiting Program On Child Neurodevelopment, Sarah S Farabi, Rosemary Bass, Amit Mathur, Cindy Schwarz, Candice Woolfolk, Richard Stein, Samuel Klein, Debra Haire-Joshu, Alison G Cahill

2020-Current year OA Pubs

Maternal obesity is associated with a higher risk of abnormal child neurodevelopment. The aim of this study was to determine the effect of a lifestyle intervention embedded into a home visiting program, Parents as Teachers (PAT), on 18-month neurodevelopment in the offspring. Pregnant women (9-15 weeks) of African American Race, 18-45 years old, first-trimester BMI 25.0-45.0 kg/m

The Role Of Home Visiting In Addressing Postpartum Care Gaps: Evidence From A Large Community Sample, Aishwarya Vijay, Allison Kemner, Karen Hoerchler, Abigail Edwards, Jeannie C Kelly, Rachel G Tabak, Mark D Huffman, Zainab Mahmoud

2020-Current year OA Pubs

BackgroundMaternal mortality in the United States has doubled over the last two decades, primarily due to cardiovascular disease, with more than half of deaths occurring postpartum. Despite national calls to action, attendance at postpartum clinic visits remains low. The role of alternative care delivery strategies, such as home visiting, remains insufficiently studied.ObjectiveTo describe postpartum clinic visit attendance among participants in a large national home visiting program, identify sociodemographic and clinical factors associated with attendance, and examine how timing and duration of enrollment relate to postpartum follow-up.DesignWe conducted a retrospective cohort study of pregnancy episodes among mothers enrolled in the Parents …

Strategies To Optimize Skill Acquisition And Prevent Skill Decay For The Air Transport Clinician, Mckayley Green, Aaron J Lacy, James L Li, John E Schneider

2020-Current year OA Pubs

No abstract provided.

Participatory Systems Modeling In Implementation Research: Exploring Benefits, Facilitators, And Future Needs, Natalie Riva Smith, Jennifer L Cruz, Jessica Gannon, Stephanie Mazzucca-Ragan

2020-Current year OA Pubs

BACKGROUND: Implementation science increasingly uses participatory systems modeling (PSM) approaches to handle the complexity inherent to implementation science issues. To support the process of integrating PSM with implementation science, we aimed to understand and explicate the benefits, facilitators, and future needs of applying PSM to implementation research.

METHODS: We conducted semi-structured qualitative interviews with 23 researchers (n = 18) and practitioners (n = 5). We purposively sampled participants and identified additional participants through recommendations. Interviews were inductively analyzed. Key concepts were identified via iterative description, comparison, and conceptualization.

RESULTS: Engagement with people in the system was typically focused in earlier …

Immortalization And Characterization Of Schwann Cell Lines Derived From Nf1-Associated Cutaneous Neurofibromas, Hua Li, Angela Hirbe, Et Al.

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition in which patients are heterozygous for a disruptive pathogenic variant in the NF1 gene. The most characteristic feature of the condition NF1 is the neurofibroma, a benign, multi-cellular tumor which initiates when a cell of the Schwann cell lineage gains a somatic pathogenic variant of the other NF1 allele. Neurofibromas developing at nerve termini in the skin are termed "cutaneous" neurofibromas (cNFs), while those developing within larger nerves are termed "plexiform." Most patients develop cNFs beginning in late childhood or early adulthood, continuing throughout life at variable rates. Some patients may …