BIASES IN USEFULNESS ASSESSMENT: THE REALIZED VALUE OF GENERATIVE SUPPORT SYSTEMS

Research on information systems (IS) adoption and acceptance has frequently relied upon self-reported measures of system usefulness. In this study, we compare self-reported with computer-monitored measures of usefulness. In a series of group experiments, participants were asked to assess the usefulness of three applications—two Generativity Support applications and one Baseline application that served as a benchmark. With no exceptions, self-reported usefulness was consistently lower than computer-monitored usefulness. Although the two Generativity Support applications provided a significant added value to enhancing group performance—as demonstrated by computer-monitored measures of usefulness—groups rated these applications as less useful than the Baseline application. We explain this paradox using the Technological Frames theory to argue that the Baseline application was rated as more useful because it fitted better with the users’ existing technological frames. The Generativity Support applications, however, violated users’ existing technological frames and therefore were rated as less useful, despite their positive effect on group performance. These results demonstrate how anchoring can lead to misperception of usefulness that in turn may hinder the diffusion of innovation in spite of its technological advantage. Furthermore, our findings suggest that research on IS acceptance should adopt multiple measures of usefulness simultaneously and use self-reported measures with caution, in particular when evaluating new, unfamiliar systems

Heating of Nanoshells by Near-infrared Radiation: A Rapid and Minimally-invasive method for destroying tumors

The purpose of this project is to model a novel and promising cancer treatment that involves the destruction of tumor cells by the direct injection of biocompatible nanoparticles (gold-silicon nanoshells) and their subsequent heating with near-infrared radiation. The use of near infra-red radiation gives this procedure an advantage over other thermal ablation treatments for cancer since light at this range (700-900 nm) is not significantly absorbed by chromopores in human tissue and can therefore penetrate more deeply (Hirsch et al., 2003). The method is also quick and minimally invasive. Using the simulation software FIDAP, we analyzed the diffusion of the nanoshells into a spherical tumor after being injected into its center. The change in temperature of the tumor due to the exposure of the nanoshells to near-infrared light was also studied. We found out that when 50 microliters of nanoshell solution (concentration of 1.5 e10 nanoshells/ml) is introduced to a 1-cm diameter tumor, it takes 29 hours for the nanoshells to fill up the tumor. At this point, exposure of the tumor with a laser (800 nm, power = 5.6 W/m2) for 10 min raised the temperature of the entire tumor to at least 45?C, effectively destroying it. Further analysis on the effect of nanoshell distribution on the temperatures obtained showed that it has negligible effect. All distributions tested (0%, 25%, 50%, 75% and 100%) resulted in the entire tumor being heated above 45?C. The laser can therefore be immediately applied to the tumor right after injection. Nanoshell concentration vs. time and temperature vs. time profiles for the tumor for various treatment conditions were also obtained. The results of the mathematical modeling will help further studies of this treatment. Although the method still needs to be refined, it should provide an effective new treatment for the destruction of breast carcinomas and other localized tumors

Robust adaptive immune response against Babesia microti infection marked by low parasitemia in a murine model of sickle cell disease.

The intraerythrocytic parasite Babesia microti is the number 1 cause of transfusion-transmitted infection and can induce serious, often life-threatening complications in immunocompromised individuals including transfusion-dependent patients with sickle cell disease (SCD). Despite the existence of strong long-lasting immunological protection against a second infection in mouse models, little is known about the cell types or the kinetics of protective adaptive immunity mounted following Babesia infection, especially in infection-prone SCD that are thought to have an impaired immune system. Here, we show, using a mouse B microti infection model, that infected wild-type (WT) mice mount a very strong adaptive immune response, characterized by (1) coordinated induction of a robust germinal center (GC) reaction; (2) development of follicular helper T (TFH) cells that comprise ∼30% of splenic CD4+ T cells at peak expansion by 10 days postinfection; and (3) high levels of effector T-cell cytokines, including interleukin 21 and interferon γ, with an increase in the secretion of antigen (Ag)-specific antibodies (Abs). Strikingly, the Townes SCD mouse model had significantly lower levels of parasitemia. Despite a highly disorganized splenic architecture before infection, these mice elicited a surprisingly robust adaptive immune response (including comparable levels of GC B cells, TFH cells, and effector cytokines as control and sickle trait mice), but higher immunoglobulin G responses against 2 Babesia-specific proteins, which may contain potential immunogenic epitopes. Together, these studies establish the robust emergence of adaptive immunity to Babesia even in immunologically compromised SCD mice. Identification of potentially immunogenic epitopes has implications to identify long-term carriers, and aid Ag-specific vaccine development. © 2018 by The American Society of Hematology

Chondrogenesis of Stem/Progenitor Cells by Chemotaxis Using Novel Cell Homing Systems

The predominant approach for cartilage tissue engineering involves cell transplantation with or without cytokine delivery, biomaterial scaffolds, bioreactors, applied mechanical stimulation and altered oxygen tension. Despite its scientific merit, cell delivery faces drawbacks including scarce cell availability, donor site trauma, possible immune rejection and potential tumorigenesis. Tissue regeneration by cell homing is a novel concept and may offer the advantage of accelerated clinical translation. Promising results have been shown using a cell homing approach to engineer a number of tissue types including dental pulp, vascular tissue and bone. Various stem/progenitor cell populations are present in tissues adjacent to an articular cartilage defect including subsets of cells that have the ability to differentiate into cartilage-like tissue. Furthermore, several factors have been elucidated that stimulate stem/progenitor cell homing and selected cytokines have been discovered to be potent at inducing chondrogenic differentiation of stem/progenitor cells. Cell homing is an exciting area of regenerative medicine but many critical questions remain such as cell origin, homing distance, and effective chemotactic cues. In addition to currently studied cell homing cues, other cytokines present during inflammation that are not typically known for their homing abilities might be helpful in recruiting additional cells to the scaffold and improving the quality of cartilage tissue formation. The effect of concurrently exposing a cell population to multiple cytokine signals, similar to conditions that cells experience in vivo, has not been fully investigated. Determining which cytokine or groups of cytokines that induce high levels of chemotaxis would be critical for designing effective bioactive scaffolds for cell recruitment and chondrogenesis. This thesis develops novel systems to characterize stem/progenitor cell migration and uses the knowledge gained from these systems to develop new methods for inducing chondrogenesis by cytotactic homing. First, the concept of stem/progenitor cell homing for cartilage tissue regeneration is reviewed (Chapter 1). Next, a system was developed for the in vitro recruitment and chondrogenesis of Adipose Stem Cells (ASCs), Mesenchymal Stem Cells (MSCs) and Synovium Stem Cells (SSCs), all of which are natively located adjacent to a full-thickness articular cartilage defect (Chapter 2). Using microfluidic principles, novel assay systems were designed and built to characterize the process of stem cell migration in the presence of single and competing cytokine signals (Chapter 3). An in-depth study was conducted investigating the process of stem/progenitor cell migration in the presence of competing cytokine signals (Chapter 4). Lastly, the knowledge gained through extensive chemokine testing using these novel assay systems was used to develop a bioactive scaffold to induce cell homing and chondrogenesis for rhinoplasty augmentation in a rat model (Chapter 5). The novel migration devices developed herein offer a rare opportunity for screening of cell homing efficacy, potentially applicable to any stem cell population including embryonic, iPS, skeletal, muscular, neural, cardiac and adipose. A number of basic biological concepts have been examined by studies using these devices such as cell motility behavior and optimal migratory distances. The competitive cytotactic assay system provided new insight into stem cell behavior in response to gradients of multiple cytotactic cues, thus mimicking native in vivo conditions. By determining combinations of cytokines effective at maximizing cell homing, novel approaches for cartilage tissue engineering without the need for cell delivery, were developed for rhinoplasty augmentation. These systems for inducing chondrogenesis by chemotactic homing were shown to be an effective alternative to cell transplantation for cartilage tissue regeneration therapies

Identification of the optimal biologic to enhance endogenous stem cell recruitment

The goal of this project is to identify the optimal biologic to recruit mesenchymal stem cells (MSCs) to the site of an injury. A direct comparison between different biologics with putative chemoattractant properties will provide a quantification of the number of cells and the distance that they migrate towards each biologic. Biologics that are commonly used to enhance musculoskeletal regeneration such as leukocyte-poor platelet rich plasma (PRP), leukocyte-rich PRP, interleukin-1 receptor antagonist protein (IRAP), bone marrow aspirate, and bone marrow aspirate concentrate (BMAC) will be used in a microfluidics device designed to measure cell migration. BMAC commonly recruited the greatest number of cells; however, these results were not uniformly replicable. A new approach utilizing a U-slide chemotaxis device is now being used to obtain more consistent results. Identification of the biologic product that recruits stem cells best can lead to direct clinic application of said biologic for immediate use in lesions to recruitment endogenous stem cells for increased healing

Biases in usefulness assessment: the realized value of generative support systems

Research on information systems (IS) adoption and acceptance has frequently relied upon self-reported measures of system usefulness. In this study, we compare self-reported with computer-monitored measures of usefulness. In a series of group experiments, participants were asked to assess the usefulness of three applications—two Generativity Support applications and one Baseline application that served as a benchmark. With no exceptions, self-reported usefulness was consistently lower than computer-monitored usefulness. Although the two Generativity Support applications provided a significant added value to enhancing group performance—as demonstrated by computer-monitored measures of usefulness—groups rated these applications as less useful than the Baseline application. We explain this paradox using the Technological Frames theory to argue that the Baseline application was rated as more useful because it fitted better with the users’ existing technological frames. The Generativity Support applications, however, violated users’ existing technological frames and therefore were rated as less useful, despite their positive effect on group performance. These results demonstrate how anchoring can lead to misperception of usefulness that in turn may hinder the diffusion of innovation in spite of its technological advantage. Furthermore, our findings suggest that research on IS acceptance should adopt multiple measures of usefulness simultaneously and use self-reported measures with caution, in particular when evaluating new, unfamiliar systems