4,807 Works

The Impact of Full Nurse Practitioner Scope of Practice Policy on Access to Care in the Privately Insured

ABSTRACT Esita Patel: The Impact of Full Nurse Practitioner Scope of Practice Policy on Access to Care in the Privately Insured (Under the direction of Dr. Barbara Mark) A greater understanding of how state-level nurse practitioner (NP) scope of practice (SOP) policies shape access to care is needed in the context of today’s rapidly expanding NP workforce. Prior work suggests a positive association between NP SOP and access to preventive services, however most studies fail...

Extensions of Methods for Clinical Trials: (1) Randomization-based ANCOVA for Longitudinal Clinical Trials with Missing Data, Particularly the Sequential Parallel Comparison Design, and (2) Methods for Clarifying Criteria for Study Continuation at Interim Analysis

Randomization-based analysis of covariance (ANCOVA) is a useful analysis for randomized clinical trials when covariate-adjusted estimates of treatment effects are needed, but statistical assumptions for parametric methods cannot be verified. Li (2017) and Wiener et al. (2019) present methods to apply randomization-based ANCOVA to studies with the sequential parallel comparison design (SPCD) in settings where hypothesis testing or confidence interval estimation is needed. SPCD is a two-period crossover design, typically adopted by trials with high...

Spatial and Temporal Variability of Exchange Between Stream Waters and the Hyporheic Zone Using Laboratory Flume Experiments, Field Tracers, and Transient Storage Modeling

Groundwater-surface water interactions play a major role in regulating global water quality because they integrate diverse fluxes of water and its constituents within and beyond drainage basin boundaries. The hyporheic zone is the top portion of the unconfined, near-stream aquifer beneath and adjacent to streambed environments and facilitates riverine groundwater-surface water interactions. This continual transfer of water, dissolved constituents, particulate matter, and energy throughout the streambed is termed hyporheic exchange. As such, hyporheic exchange has...

B7-H3-directed chimeric antigen receptor T cells for the treatment of glioblastoma multiforme

Glioblastoma multiforme (GBM) has continued to pose an immense clinical challenge that, despite decades of research elucidating its complex tumor biology and development of various therapeutic modalities, still holds a grim survival to all patients. The molecular heterogeneity of GBM within and across tumors, as well as its immunosuppressive environments have been the most challenging obstacles to overcome in this disease, and so far they remain insurmountable. In this dissertation, I lay out advances this...

Examining Undergraduate Public Health Education as a Pipeline to the Public Health Workforce

Undergraduate public health (UGPH) education in the U.S. has grown rapidly since the start of the 20th century and has been identified as potential strategy for strengthening the public health workforce. The objective of this research was to examine UGPH education as a pipeline to public health careers and identify the knowledge and skills graduates need to be well-prepared to enter the public health workforce. First, we characterized the postbaccalaureate education and employment of public...

Neural dynamic adaptation of extended amygdala to stress and anxiety

Anxiety disorders constitute changes across behavioral, physiological, and psychological dimensions that are driven by expanse neural circuits. However, the bed nucleus of the stria terminalis (BNST), a component of the extended amygdala, plays a crucial role in regulating many aspects of these changes. For instance, activation of specific cells within BNST can drive freezing behavior and while others control physiological arousal. Still, many studies using rodent models have focused on only a handful of behavioral...

PIER PAOLO PASOLINI AND THE SPACE OF THE “RIVOLUZIONE ANTROPOLOGICA”

I propose in my dissertation a broadened reading of Pasolini’s idea of an anthropological revolution taking place in Italy during the 1970s, assuming spatial studies as the privileged perspective for my analysis. The expression “rivoluzione antropologica” occurs only in Pasolini’s production of the last years, and it refers to a sudden transformation of human nature that Pasolini recognizes as being particularly effective in the lower strata of society. I argue that most of Pasolini’s production,...

GENOME-SCALE APPROACHES TO IDENTIFYING NOVEL REGULATORS OF FIBROLAMELLAR CARCINOMA

Fibrolamellar carcinoma (FLC) is a rare liver cancer that primarily affects adolescents and young adults without any prior history of liver disease. First-line treatment of FLC is surgical resection, however many patients already have metastatic disease at the time of their diagnosis. Additionally, FLC tumors are often resistant to chemotherapy, greatly demonstrating the need for the development of novel therapeutics for this cancer. Unfortunately, little is known about the underlying biology of this disease and...

Part 4: Pediatric basic and advanced life support 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care

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More than 20 000 infants and children have a cardiac arrest per year in the United States. In 2015, emergency medical service–documented out-of-hospital cardiac arrest (OHCA) occurred in more than 7000 infants and children.

Social decline in the psychosis prodrome: Predictor potential and heterogeneity of outcome

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Background: While an established clinical outcome of high importance, social functioning has been emerging as possibly having a broader significance to the evolution of psychosis and long term disability. In the current study we explored the association between social decline, conversion to psychosis, and functional outcome in individuals at clinical high risk (CHR) for psychosis. Methods: 585 subjects collected in the North American Prodrome Longitudinal Study (NAPLS2) were divided into 236 Healthy Controls (HCs), and...

Persistent negative symptoms in youth at clinical high risk for psychosis: A longitudinal study

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Background: Severity of negative symptoms has been associated with poor functioning, cognitive deficits, and defeatist beliefs in schizophrenia patients. However, one area that remains understudied is persistent negative symptoms (PNS). Negative symptoms, including PNS, have been observed in those at clinical high-risk (CHR) for psychosis. The aim of this study was to determine if PNS were associated with functioning, neurocognition, and defeatist beliefs in a CHR sample. Method: CHR participants (n = 764) were recruited...

The association between migrant status and transition in an ultra-high risk for psychosis population

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Purpose: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. Methods: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance...

Viral vector-based gene therapies in the clinic

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Gene therapies are currently one of the most investigated therapeutic modalities in both the preclinical and clinical settings and have shown promise in treating a diverse spectrum of diseases. Gene therapies aim at introducing a gene material in target cells and represent a promising approach to cure diseases that were thought to be incurable by conventional modalities. In many cases, a gene therapy requires a vector to deliver gene therapeutics into target cells; viral vectors...

Surface Modifications for Improved Delivery and Function of Therapeutic Bacteria

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Live therapeutic bacteria (LTBs) hold promise to treat microbiome-related diseases. However, few approaches to improve the colonization of LTBs in the gastrointestinal tract exist, despite colonization being a prerequisite for efficacy of many LTBs. Here, a modular platform to rapidly modify the surface of LTBs to enable receptor-specific interactions with target surfaces is reported. Inspired by bacterial adhesins that facilitate colonization, synthetic adhesins (SAs) are developed for LTBs in the form of antibodies conjugated to...

Non-invasive delivery strategies for biologics

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Biologics now constitute a significant element of available medical treatments. Owing to their clinical and commercial success, biologics are a rapidly growing class and have become a dominant therapeutic modality. Although most of the successful biologics to date are drugs that bear a peptidic backbone, ranging from small peptides to monoclonal antibodies (~500 residues; 150 kDa), new biologic modalities, such as nucleotide-based therapeutics and viral gene therapies, are rapidly maturing towards widespread clinical use. Given...

Fabrication of fillable microparticles and other complex 3D microstructures

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Three-dimensional (3D) microstructures created by microfabrication and additive manufacturing have demonstrated value across a number of fields, ranging from biomedicine to microelectronics. However, the techniques used to create these devices each have their own characteristic set of advantages and limitations with regards to resolution, material compatibility, and geometrical constraints that determine the types of microstructures that can be formed. We describe a microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), and create injectable pulsatile...

Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes

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Intravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust pulmonary intravascular macrophage clearance of nanoparticles in mediating adverse cardiopulmonary distress in pigs irrespective of complement activation. Specifically, we show that delaying particle recognition by...

Cell-mediated delivery of nanoparticles: Taking advantage of circulatory cells to target nanoparticles

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Cellular hitchhiking leverages the use of circulatory cells to enhance the biological outcome of nanoparticle drug delivery systems, which often suffer from poor circulation time and limited targeting. Cellular hitchhiking utilizes the natural abilities of circulatory cells to: (i) navigate the vasculature while avoiding immune system clearance, (ii) remain relatively inert until needed and (iii) perform specific functions, including nutrient delivery to tissues, clearance of pathogens, and immune system surveillance. A variety of synthetic nanoparticles...

Management of patients with non-Hodgkin’s lymphoma: Focus on adoptive T-cell therapy

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Non-Hodgkin’s lymphoma (NHL) represents a heterogeneous group of malignancies with high diversity in terms of biology, clinical responses, and prognosis. Standard therapy regimens produce a 5-year relative survival rate of only 69%, with the critical need to increase the treatment-success rate of this patient population presenting at diagnosis with a median age of 66 years and many comorbidities. The evidence that an impaired immune system favors the development of NHL has opened the stage for...

Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment

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Background aims: Advantages associated with the use of cord blood (CB) transplantation include the availability of cryopreserved units, ethnic diversity and lower incidence of graft-versus-host disease compared with bone marrow or mobilized peripheral blood. However, poor engraftment remains a major obstacle. We and others have found that ex vivo fucosylation can enhance engraftment in murine models, and now ex vivo treatment of CB with fucosyltransferase (FT) VI before transplantation is under clinical evaluation (NCT01471067). However,...

Evaluation of cell-based and surrogate SARS-CoV-2 neutralization assays

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Determinants of protective immunity against SARS-CoV-2 infection require the development of well-standardized, reproducible antibody assays. This need has led to the emergence of a variety of neutralization assays. Head-to-head evaluation of different SARS-CoV-2 neutralization platforms could facilitate comparisons across studies and laboratories. Five neutralization assays were compared using forty plasma samples from convalescent individuals with mild-to-moderate COVID-19: four cell-based systems using either live recombinant SARS-CoV-2 or pseudotyped viral particles created with lentivirus (LV) or vesicular...

Generation of multi-leukemia antigen-specific T cells to enhance the graft-versus-leukemia effect after allogeneic stem cell transplant

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Adoptive immunotherapy with ex vivo expanded T cells is a promising approach to prevent or treat leukemia. Myeloid leukemias express tumor-associated antigens (TAA) that induce antigen-specific cytotoxic T lymphocyte (CTL) responses in healthy individuals. We explored the feasibility of generating TAA-specific CTLs from stem cell donors of patients with myeloid leukemia to enhance the graft-versus-leukemia effect after stem cell transplantation. CTL lines were manufactured from peripheral blood of 10 healthy donors by stimulation with 15mer...

The effects of education and family planning programs on fertility in Indonesia

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Numerous studies indicate that female education is a major determinant of fertility and that the estimated effects are large relative to other variables, including family planning program variables. There are, however, two serious deficiencies in the research relating educational attainment to fertility that could give rise to invalid inferences. First, many public programs, including health and family planning programs, may influence a woman’s decisions about education, and these indirect programmatic effects might be large. Second,...

Availability of health facilities and untilization of maternal and newborn postnatal care in rural Malawi

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Background: This study explored the role of health facility availability as it relates to maternal and newborn PNC use in rural Malawi. Methods: Malawi Demographic and Health Survey (MDHS) 2015–16 data, MDHS 2015–16 household cluster GPS data, Malawi Service Provision Assessment (MSPA) 2013–14 data and MSPA 2013–14 facility GPS data were used. Household clusters were spatially linked with facilities using buffers. Descriptive analyses were performed and generalized estimating equations (GEE) were used to determine the...

Cash Transfers, Early Marriage, and Fertility in Malawi and Zambia

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There is increasing interest in the ability of cash transfers to facilitate safe transitions to adulthood in low-income settings; however, evidence from scaled-up government programming demonstrating this potential is scarce. Using two experimental evaluations of unconditional cash transfers targeted to ultra-poor and labor-constrained households over approximately three years in Malawi and Zambia, we examine whether cash transfers delayed early marriage and pregnancy among youth aged 14 to 21 years at baseline. Although we find strong...

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