Characterization of lecticans in normal brain and glioma: A complex tale of post-translational modification and processing

Matthews, Russell Thomas Yale University 2001 해외박사(DDOD)

The development of virtually all cells in an organism depends upon interactions with the molecules in their environment. The extracellular matrix (ECM) organizes the extracellular space and plays a critical role in directing these interactions. The central nervous system (CNS) is the most complex tissue in the body, containing a vast variety of cell types, organized in an inordinately specific manner with exquisitely precise connectivity between cells. The assembly of this complex organization requires a heterogeneous and dynamic ECM. Understanding the composition and regulation of the ECM is critical for understanding the development and function of the CNS. Lecticans, a group of glycoproteins comprised of aggrecan, versican, neurocan, and BEHAB/brevican, are the major hyaluronan-binding chondroitin sulfate proteoglycans (CSPGs) in the ECM of the CNS. Lecticans, through their interactions with HA and a variety of other molecules within the extracellular space, are uniquely positioned to organize the ECM of the CNS. Here we have investigated the role lecticans and post-translational processing of lecticans play in creating the extraordinary diversity of the ECM of the CNS. Previous work with the monoclonal antibodies Cat-301, Cat-315, and Cat-316 showed that these antibodies recognize a remarkably diverse family of HA-binding CSPGs in the ECM of the adult CNS. We show here that all three of these antibodies recognize aggrecan, but differentially glycosylated isoforms of aggrecan. These findings have broad implications for the role that diversity of glycosylation plays in creating unique ECM microenvironments in the CNS. In addition, we examined post-translational modification of another lectican, BEHAB/brevican, in the progression of primary glial tumors in the CNS. While previous work showed that expression of BEHAB/brevican is upregulated in glioma, we show here that it is not just increased expression, but cleavage of the full-length protein that mediates it function in these tumors. Finally, we identified the protease responsible for BEHAB/brevican cleavage as ADAMTS-4. Together these observations indicate that post-translational modifications of lecticans are critical to the function of these molecules and the organization of the ECM of the CNS.

Cross Border Health Collaborative Leadership

Matthews, Charles E., III ProQuest Dissertations & Theses University of Cali 2017 해외박사(DDOD)

Background: There are many health and economic disparities present in bor-der regions of countries. Addressing those disparities in a collaborative manner in the border region is paramount. Leading such border collaborative organizations successfully requires a certain leadership approach. Objective: This research sought to explore what cross border health collabo-rative leadership approaches were deemed important by current cross border lead-ers and actors performing cross border work in the US-Mexico and Ireland-North-ern Ireland border regions. Methods: A forty statement (8 categories), Likert type quantitative survey was developed with the goal of exploring the importance of leadership themes and or actions in developing and coordinating cross border health collaboratives. The cross border setting (n=159) included the border regions of the Republic of Ireland (IRE), Northern Ireland (NIRE), Mexico (MX) and the United States (U.S.). An exploratory factor analysis was utilized in this endeavor. Results: Upon completion of the exploratory factor analysis the survey instru-ment was reduced to five categories and 20 statements. The five leadership themes/categories (with Cronbach Alpha measure) that were identified were Communicate to Engage the Collaborative (.77), Steer the Collaborative (.74), Understand the Members of the Collaborative (.69), Manage the Collaborative (.71) and Strategic Relationship Building for the Collaborative .59). The respondents from both border regions agreed on important leadership approaches needed to lead and develop a border health collaborative. Conclusions: An initial/preliminary 20 statement survey instrument was de-veloped with adequate construct validity as well as internal reliability to assist in the exploration of what leadership approaches are important in developing cross border health collaboratives. The findings from this study align with recently pub-lished cross-border toolkits from Europe and the US-Mexico border region that de-scribe the manner in which cross-border leaders and actors should proceed in de-veloping and coordinating projects and cross-border collaboratives.

The Reliability and Validity of a Simulated Airway Model that Quantifies Physical Forces Exerted During Endotracheal Intubation in a Clinically Demanding Scenario

Matthews, Robert W Virginia Commonwealth University 2011 해외박사(DDOD)

The main purpose of this research was the development of an experimental model that allows for the assessment of pressure and thereby, the forces associated with interventions related to airway management. The foundation of this research was to develop, and assess the validity and reliability, of a method of quantifying the force experienced by a patient during airway management. Following IRB approval and the development of a unique simulation model that employs transducers situated in key anatomical locations to determine forces, a multivariate profile analysis with covariate of experience using a MANCOVA approach was conducted. The statistical design consisted of 102 subjects testing the dependent measure of pressure for the following techniques: Fiberoptic intubation, the Fastrach(TM) LMA, the # 3 C-Mac video laryngoscope, and the TrachlightRTM. Independent variables analyzed were practitioner types: emergency medicine physicians, certified registered nurse anesthetists, and anesthesiologists, all tested over five locations: Chicago, Las Vegas, Atlanta, Seattle, and Boston, with a co-variable of experience. Analysis demonstrated no difference in force attributed to the location, the airway provider or their interactions. This was contrasted by the finding that 81% of the variance in pressure scores was due to differences in airway techniques. The mannequin was also able to discern a subpopulation within techniques which lends to its validity. The mannequin preformed consistently regarding reproducible findings following the setup and dismantling over time and locations. This would seem to begin to form the bases of a valid and reliable tool for this and future research.

Lesbians who engage in public bondage, discipline, dominance, submission and sadomasochism (BDSM)

Matthews, Marcia A Widener University 2005 해외박사(DDOD)

This phenomenological study looked at the previous research and therapy on bondage, discipline, dominance, submission and sadomasochistic (BDSM) sex play from psychodynamic, behavioral and sociological perspectives. This collective body of research generally focused on gay and straight men and lacked an investigation of BDSM from the individuals' subjective experiences. More specifically, research was lacking on lesbians who engage in public BDSM sex play. Thus, the purpose of this study was to examine the subjective experiences of lesbians who engage in public BDSM in order to advance current knowledge of the lesbian BDSM scene. Using a phenomenological approach, six face-to-face in-depth interviews were conducted. In these interviews, the participants were asked to describe: how they had gotten into public BDSM sex play, what the experience was like for them, and what effects participanting in the scene had on their lives. The data were analyzed using the process recommended by Moustakas (1994). All of the women expressed having some interest in exploring BDSM, some since childhood or for many years before actually getting involved in the scene. Some of them had initial misgivings about their interest in BDSM, but when the opportunity presented itself, they took it. As "newbies", the women were socialized into the scene. All of the women experienced feelings of nervousness or anticipation prior to scene play and most of the women engaged in negotiation. During scene play, tops reported being hyperaware of everything going on, getting into performing and being exhibitionists. Bottoms reported feeling "in the zone" in which they were allowed to selfishly concentrate on the sensations of their bodies while being "safe" and cared for. Both tops and bottoms experienced an exchange of energy/power. After scene play and during aftercare, participants reported catharsis and healing, feeling cherished, protected and sexually satisfied. The major theme that pervaded throughout the stages of scene play was one of connection with one's partner and the overall community. A sense of fun and sexual satisfaction was also pervasive. Three major themes emerged from the effects that BDSM sex play has on the women's overall lives. The women gained a sense of empowerment and skills that improved their overall relationships. While these themes were overwhelmingly positive, a minor concern about others' misunderstanding of BDSM also emerged.

Socialization influences on sexual health behaviors among African American men: Utilizing an inter-group and intra-group approach to health disparities

Matthews, Derrick Deshun The University of North Carolina at Chapel Hill 2013 해외박사(DDOD)

The large and persistent racial disparity in HIV and STD infection among men has prompted researchers to identify determinants driving differences in sexual health behaviors. However, the process which men develop sexual health behavior early in life remains an understudied factor in the production of sexual health disparities. Additionally, the study of African American men's health behaviors is frequently limited by only comparing their experiences to men of other racial groups. This dissertation explores sources of variation in the relationship between health socialization and sexual health behaviors both across and within race. Manuscript 1 examined racial differences in the effects that peers and fathers have on the age of first sex and condom use during adolescence and young adulthood. Using data from the National Longitudinal Study of Adolescent Health, analyses revealed that peers and fathers influenced the age of first sex. These effects did not differ by race, though African American men became sexually active more quickly than White men. There was no racial difference in rates of condom use, nor did any socialization effects from adolescence carry over to young adulthood. Manuscript 2 explored variability in condom use among African American men using data from the African American Men's Health and Social Life Study. A latent class approach was employed to explore the joint effects of racial and masculine identity on condom use. Analysis yielded four distinct classes of racial and masculine identity, though these profiles did not explain variability in condom use. However, early life paternal sexual health socialization was positively associated with condom behavior. These findings suggest that those agents who shape the development of sexual health behavior, particularly fathers, play an important role in delaying sexual initiation and possibly condom use. Based on results, interventions should work with fathers to leverage their existing influence, and foster additional opportunities for father-son communication about sexual health. The large racial difference in the timing of sexual initiation, coupled with the lack of racial difference in condom use, suggests that additional research is needed into structural factors driving the racial disparity in HIV and STD infection among men.

Investigations and modeling of efferent inhibition in chicken short hair cells

Matthews, Tonya M The Johns Hopkins University 2006 해외박사(DDOD)

Efferent inhibition of chicken short hair cells occurs when stimulator release acetylcholine onto the hair cells opening acetylcholine receptor channels, which allow calcium to flow into the cell (Art, JJ et al. 1982; Housley, GD and Ashmore, JF 1991; Fuchs, PA and Murrow, BW 1992). This calcium influx activates calcium-sensitive potassium channels whose large outward currents hyperpolarize the hair cell (Fuchs, PA and Murrow, BW 1992; Yuhas, WA and Fuchs, PA 1999). The acetylcholine receptor involved in this process is comprised of nicotinic subunits alpha9 and alpha10 and has a unique combined muscarinic-nicotinic pharmacological profile (Fuchs, PA and Murrow, BW 1992; Elgoyhen, AB et al. 1994; Blanchet, C et al. 1996; Hiel, H et al. 2000; Elgoyhen, AB et al. 2001; Lustig, LR et al. 2001). In part one of investigations presented in this thesis, alpha9 and alpha10 receptor subunits were localized to human lymphocytes. However, lymphocytes did not respond to acetylcholine in a manner useful to further study of efferent inhibition of hair cells. In the second part of the investigations presented here, the potassium channel of efferent inhibition of short hair cells was investigated. The chicken small-conductance calcium-sensitive potassium channel type 2 (gSK2) was localized to chicken short hair cells. Detailed electrophysiological analysis of cloned gSK2 channels showed that its properties were consistent with the properties of the potassium channel of short hair cell inhibition. Finally, in the third part of investigations presented here, the question of the ability SK2 channels and AChR channels to sustain short hair cell inhibition without additional calcium sources was explored using a computation model of the base of a short hair cell. While studies have shown that acetylcholine can induce hyperpolarizing currents in hair cells without triggering large increases in intracellular calcium (Evans, MG et al. 2000), it has also been shown that calcium-induced calcium release (CICR) can modulate the efferent response of hair cells (Sridhar, TS et al. 1995; Evans, MG et al. 2000; Lioudyno, M et al. 2004). The computational model presented here was designed with only SK2 channels and AChR channels (along with appropriate buffering and calcium extrusion mechanisms). With these components, the model showed that without CICR many properties of hair cell inhibition could be simulated. However, the model could not simulate the characteristic bell-shaped current-voltage relationship of hair cells without unacceptable consequences to response duration. In summary, these investigations present a three-pronged consideration of efferent inhibition of chicken short hair cells further elucidating the uniqueness of its acetylcholine receptor; identifying the potassium channel involved; and lending support to the hypothesis that SK2 channels and AChR channels alone are not sufficient for the process of inhibition.

Industrial organization and regional productivity growth in American manufacturing sectors

Matthews, Richard Allen Arizona State University 1995 해외박사

Customer/producer interaction in industrial product development : an interorganizational exchange perspective

Matthews, John Michael Harvard University 1995 해외박사

Addressing Social Needs and Creating Community Linkage Pathways for Vulnerable Populations in Primary Care Practice Settings

Matthews, Mindy M Yale University ProQuest Dissertations & Theses 2023 해외박사(DDOD)

Social risk factors, the social determinants of health associated with negative health outcomes, drive patient-level social needs that contribute to health inequalities, high medical cost, overutilization of services, and have a greater impact on morbidity, mortality, and quality of life than chronic diseases (Krist et al., 2020). While there seems to be a consensus on the importance of addressing social factors, most health systems lack the infrastructure to develop the screening and referral protocols required to address social needs (Alley et al., 2020). Primary care has been identified as a key setting to introduce strategies around identifying at-risk patients with social needs and linking them to community resources as they are typically the first point of health care access for most people (Valaitis et al., 2020). The goal of this project was to develop screening processes and workflows in primary care settings to connect patients to community resources using care navigational resources. A 10-week pilot was conducted at two practices. The implementation of screening tools, workflows, and referrals pathways were evaluated to understand the model's impact on care delivery and to make recommendations for scaling the processes to other practice sites. A total of 150 patients were screened, and 71 patients reported to having at least one social need. The importance of addressing social needs within insured populations was highlighted with nearly half of the patients screening positive. Providers were surveyed post-implementation using a five-point Likert scale questionnaire. They expressed positive overall feelings about the process. The project supports that integrating social factors into the provision of care moves practices towards the realization of whole-person care for the promotion of health and wellbeing.

Investigating the literature-based mock trial as a dramatic experience in the secondary English language arts classroom

Matthews-McGovern, Diane New York University 2007 해외박사(DDOD)

The purpose of this study was to examine the perceptions of participants from an English Language Arts classroom who became involved in a literature-based mock trial. A mock trial based on literature asks students to assume character or litigation roles in order to engage in a dramatized legal process that investigates both the characters and the literature itself. In looking at the mock trial, it is essential to see it as a structured activity that involves creative progression. The mock trial demands implicit agreement among students that generates productive work, which warrants close attention and informed observation. The research reveals the mock trial as a teaching tool, performance mode, and an innovative approach to reader-response theory. The mock trial draws upon the work David Booth has done in the area of story drama, which asks students to create their own stories bases on shared experiences and investigation of a text. Discovering how teachers and students feel about utilizing mock trial drama to enrich the classroom experience is significant to the ongoing promotion of integrating drama into the curriculum. Case study methodology was used because it is capable of examining in an open and flexible manner the social action of drama in its negotiated and framed setting. This dissertation examined from a teacher as researcher perspective how a language arts classroom experienced the various phases of a mock trial from pre-text to performance and how the subjects responded to it. "Professionals need to develop the ability to identify and understand problems of practice as well as to develop the ability to hypothesize alternatives, place new actions into practice, and evaluate the results of their teaching action" (Flood 445-6). To sum up, this research study observed participants and their interactions in a dramatic activity and studied the mock trial as a process that encourages role-play and negotiation among student-created characters based on the literature. It should be used to inform and add to the related research that asks what kind of inter-play exists among the characters that are created through drama, and how this exchange becomes part of a learning experience.