One of the most common disabilities in the US, hearing loss, is reported by The National Institutes of Health to affect approximately 36 million Americans. One of the major contributing factors to this loss in hearing is the loss of the sensory hair cells (HCs) within the cochlea. Also in the mammalian cochlea, six major groups of supporting cell (SC) subtypes reside in close proximity to HCs and may have the potential to regenerate HCs after damage. These subtypes include cells of the greater epithelial ridge, inner phalangeal/border cells, inner and outer pillar cells, Deiters’ cells, Hensen cells, and Claudius cells. During embryonic development, progenitor cells differentiate into HCs or one of the SC subtypes by Notch-mediated lateral inhibition. In the neonatal mouse cochlea, many studies have shown that inhibition of Notch signaling allows SCs to convert into HCs in both normal undamaged cochleae, as well as in drug-damaged cochlear explants. This mechanism is also implicated during spontaneous HC regeneration that occurs in non-mammalian vertebrates. We and others have recently observed that spontaneous HC regeneration can also occur in the neonatal mouse cochlea. However, little is known about the molecular mechanism or the SC subtypes which act as the source of regenerated HCs. In the neonatal mouse cochlea, HCs were killed in vivo at birth using a genetically-modified mouse model to express a toxin in HCs. Subsequently, SCs formed new HCs by either direct transdifferentiation, where no cell division occurred, or by mitotic regeneration. My dissertation investigated the role of Notch signaling in the ability of SC subtypes to regenerate HCs after damage. My central hypothesis is that after HC ablation is induced at birth, Notch signaling is partially eliminated and therefore lateral inhibition is lost in neonatal SCs in a subtype specific manner, which allows some SCs, but not others, to differentiate into and regenerate HCs. Aim 1 focused on changes in the Notch signaling pathway in response to HC damage during the window of spontaneous HC regeneration. Changes in the expression of genes in the Notch pathway were measured using real time qPCR, immunostaining, and in situ hybridization. The Notch effector HeyL was increased in the apical one-third of the cochlea while other Notch players are decreased. The most notable example is the Notch effector Hes5, which is directly responsible for inhibiting HC fate, and was reduced in outer pillar cells and Deiters’ cells, but not in other SC subtypes. From this we conclude that Notch signaling is reduced differentially among SC subtypes. In Aim 2 we investigated whether inhibition of Notch signaling is required for spontaneous HC regeneration to occur by maintaining active Notch signaling in all SCs in the context of HC damage. We hypothesized that maintaining active Notch signaling after HC damage will prevent SC-to-HC conversion thus preventing HC regeneration. We found significantly fewer regenerated HCs while maintaining Notch expression compared to controls with HC damage and no manipulation of Notch signaling. Therefore we conclude loss of Notch mediated lateral inhibition is required for the majority of spontaneous HC regeneration. In Aim 3 we investigated the ability of different SC subtypes to regenerate HCs by fate-mapping SC subtypes during the HC regeneration process. Since fate-mapping creates a permanent label in targeted cells, we can track their potential change in cell fate or reentry in the cell cycle after HC damage. We hypothesized that pillar cells and Deiters’ cells are the source for spontaneously regenerated HC within the neonatal mouse cochlea based on our results from Aim 1. We used three CreER mouse lines to fate-map distinct groups of SC subtypes during the HC damage and regeneration process. More pillar and Deiters’ cells regenerated HCs after damage than other SC populations. We found that outer pillar cells and Deiters’ cells are capable of downregulating the cell cycle inhibitor, p27Kip1, after HC damage. Therefore we investigated the ability of SC subtypes to mitotically regenerate HCs by including a mitotic tracer along with fate-mapping. A larger proportion of mitotically regenerated HCs came from pillar and Deiters’ cells. From these experiments, we conclude that outer pillar and Deiters’ cells are the source for the majority of spontaneously regenerated HCs in vivo. This knowledge will allow targeted investigation into outer pillar cells and Deiters’ cells that maintain regenerative plasticity at postnatal ages. Understanding how these cells change with age will inform efforts to induce HC regeneration in more mature cochleae. Additionally, understanding how Notch signaling regulates this regenerative plasticity will lead to the development of potential targets for the treatment of hearing loss.

Thesis advisor: Joseph O'Keefe / Effective instructional leadership is central to principal practice. Thus, the Massachusetts Model System for Educator Evaluation (MMSEE) mandates that all principals demonstrate proficiency in instructional leadership to be considered proficient overall. Given this mandate, it is imperative that central office administrators (COAs) support principals in this regard. Accordingly, this qualitative single case study examined how COAs in one Massachusetts district supported principals’ instructional leadership. Analyses of documents and semi-structured interview data found that COAs supported principals’ instructional leadership through professional development for supervising and evaluating teachers, preparation of school improvement plans, and increased staffing of assistant principals and academic coaches. However, principals reported interim feedback and summative evaluations as not supporting their growth as instructional leaders. To address this gap in support with instructional leadership, recommendations included assigning additional COAs to evaluate principals for consistent and targeted feedback, reviewing MMSEE performance expectations with principals, and including principal voice in the district decision-making process. / Thesis (EdD) — Boston College, 2016. / Submitted to: Boston College. Lynch School of Education. / Discipline: Educational Leadership and Higher Education.

I Sverige lever mellan 20- 40 procent av befolkningen med en psykisk ohälsa. Behandlingen av psykisk ohälsa, utifrån en humanistisk människosyn, inriktar sig på en hälsofrämjande process genom att stödja och stärka individen genom stödjande samtal. Syfte; Syftet med denna studie var att beskriva sjuksköterskors erfarenheter av stödjande samtal inom psykiatrisk öppenvård. Metod; En kvalitativ studie genomfördes där data samlades in med hjälp av semistrukturerade intervjuer av sjuksköterskor inom psykiatrisk öppenvård. Data analyserades med hjälp av en konventionell innehållsanalys. I studien inkluderades totalt 12 sjuksköterskor. Resultat; Stödjande samtal beskrevs av sjuksköterskorna som en viktig och bärande del i relationen mellan sjuksköterska och patient inom psykiatrisk vård. Arbetslivserfarenhet och tillgänglighet beskrevs som betydande faktorer för stödjande samtal. Konklusion; Det fanns en upplevd otydlighet av innehåll och mål med stödjande samtal hos sjuksköterskorna. Otydliga riktlinjer för stödjande samtal kan leda till att sjuksköterskorna blir stressade. Rutiner och struktur är viktiga faktorer och det kan medföra att sjuksköterskorna blir mer stresståliga och finner en ökad trygghet i att utföra stödjande samtal. / In Sweden, 20- 40 percent of people live with a mental illness. The treatment of mental illness is based on a humanistic approach, focusing on health promotion by supporting and strengthening the individual through supportive conversations. Purpose; The purpose of this study was to describe nurses' experiences of supportive conversations in their work with psychiatric outpatients. Method; A qualitative study was conducted, in which data were collected using semi-structured interviews with nurses in outpatient psychiatric care. Data were analyzed by conventional content analysis. The study included a total of 12 nurses. Results; Supporting conversations was described by nurses as an important and fundamental part of the relationship between nurse and patient in psychiatric outpatients. Experience and availability were described as significant factors for supporting conversations. Conclusion; Nurses experienced that content for supporting conversations and aims were indistinct. Indistinct guidelines for supportive conversations may lead to nurses becoming stressed. Routine and structure are important factors that may result in nurses working better under pressure and feeling more confident in supporting conversations.

Today's workforce demands the ability to multi-task. Enterprise Resource Planning (ERP) aids businesses by attempting to integrate all departments and functions across a company to create a single software program that runs off one database. An investigation of ERP and supporting technologies was conducted to determine if organizations utilized the full potential of the systems they installed. The researcher investigated companies that have installed ERP systems, and with the use of an online survey, determined the extent to which the companies utilized the full potential of the systems. The study was also conducted to learn the best practices that can be used in ERP system implementation, system maintenance, system expansion, and related activities to recommend to individuals and organizations that can benefit from the research. A link to an online questionnaire was sent to ERP end-users and implementers via email. This mode of distribution was the most efficient because survey participants were able to access the questionnaire in real time and the researcher was also able to retrieve the responses instantaneously. The responses were retrieved and recorded in an Excel database and pivot tables were used to analyze the data. The data collected from 18 different types of businesses revealed 8 major software packages, over 80% of the organizations sponsored end-user training, and the impetus for implementing ERP focused on three unanimous reasons: reduced cost, increased productivity, and increased efficiency. While the responses were fewer than anticipated, the results supported the researcher's hypothesis that ERP systems are typically not fully utilized to their full potential. The researcher noted that 60% to 70% of the ERP systems installed were underutilized. This was determined by calculating the percentage of ERP modules utilized in a single system versus the total available modules that can be fully utilized. Additionally, the research literature supported the hypothesis that the underutilization of an ERP system compromises its anticipated benefits and does not support the null hypothesis that there are no significant relationships among technologies (project management, business process re-engineering, and customer relationship management) used to develop and support the utilization of ERP systems.

Thesis advisor: Martin Scanlan / District improvement research highlights the importance of central office leaders and building principals in reform efforts. A growing body of literature emphasizes the importance of the relationship between central office leaders and principals in the context of turnaround school reform. Drawing on research from Honig (2012), the assistance relationship consistently surfaced as a key element of success when selecting and implementing learning time as a turnaround measure. This study aims to explore the assistance relationship between central office leaders and principals in the selection and implementation of learning time. This qualitative study draws upon observations and document review to answer the research questions, and is one strand of a larger research project studying how central office leaders support principals through an assistance relationship in a district in receivership. This individual strand concludes that the selection and implementation of learning time opportunities, without consideration to the principals and without the assistance of central office leaders, can’t happen. This strand advances our understanding of how an effective assistance relationship can work in a district in receivership. I concluded that central office leaders and principals interviewed selected and implemented like learning time opportunities. Future researchers may continue to enrich this growing body of literature by examining these findings and testing all or some of the five key practices in a like district. The results, implications for districts in receivership, and future research are discussed. This strand’s findings can serve as a companion for central office leaders who are working with principals to select and implement learning time opportunities in order to improving achievement levels in underperforming schools and districts across our country. / Thesis (EdD) — Boston College, 2018. / Submitted to: Boston College. Lynch School of Education. / Discipline: Educational Leadership and Higher Education.

Background: Breast cancer is a complex disease, both phenotypically and etiologically. Accordingly, the responses to various treatments in the adjuvant setting among individuals vary considerably. There is a demand for tools that can distinguish patients who may benefit or may suffer from particular systemic treatments. We hypothesized that combination of data on genetic biomarkers with data from traditional clinical and pathophysiological (clinicopathologic) factors using traditional Cox model or Support Vector Machine (SVM) method, a new machine learning method, may provide a better tool for prediction of benefits to chemotherapy for the treatment of early breast cancer than using either biomarker or clinicopathologic data alone. Methods: This project included 531 patients from NCIC-CTG MA.5 trial who had data on both clinicopathologic factors, such as age, tumor size, ER status, type of surgery, tumor grade and lymph node involvement, and biomarkers assayed on tissue microarrays (TMAs), including HER2, p53, CA9, MEP21, clusterin, pAKT, COX2 and TOP2A. The Cox model and SVM methods were used to develop prognostic indices for relapse-free or overall survival with either data from TMAs and clinicopathologic assessments alone or their combination. The prognostic indices developed were then examined for their value as predictive classifiers for benefits from CEF treatment. The power of the predictive classifiers derived was evaluated and compared using the bootstrap approach. Results: None of the prognostic indices developed were found to have significant predictive value, although the prognostic index developed using SVM method based on only biomarkers yielded a marginal significant p-value (p=0.0527) for the interaction between classifier and treatment. In accordance with results published previously, the interaction between the classifier developed based on HER2 or TOP2A and treatment was significant (p=0.02 and 0.04 respectively). Comparisons based on the bootstrap approach indicate classifiers developed based on SVM performed better than those based on the Cox model method. Conclusions: Combination of data using biomarkers and clinical-pathological factors, and using either the traditional COX model method or the new machine learning method was not shown to perform better than two single previously known biomarkers in prediction of response to CEF treatment for early breast cancer. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2010-04-27 10:16:11.811

The use of Information and Communication Technology (ICT) has an immense potential to improve the support needs of learners with visual impairments as well as their self-sufficiency and self-reliance. In the last nine years, the South African government introduced inclusive education, through White Paper 6 that requires that Learning, Teaching and Support Material, including ICTs be provided to learners with visual impairments. The provision of Assistive Technology devices (ATs) is essential to learners with visual impairments full involvement in learning through the use of ICTs. Furthermore, literature indicates that many studies were done in the use of ICTs in teaching and learning, specifically for learners with diverse visual impairments. Recommendations were also supplied by these studies on how and when to use ICTs in the teaching and learning of visually impaired learners. The empirical research of this study revealed that ICTs are essential tools for visually impaired learners to enhance their learning. It also drew attention to the fact that despite the commitments of White Paper 6 schools for the visually impaired are not yet supplied with appropriate ICTs and educators are not adequately trained to apply ICTs in teaching and learning. / Thesis (M.Ed.)--North-West University, Vaal Triangle Campus, 2011

The use of Information and Communication Technology (ICT) has an immense potential to improve the support needs of learners with visual impairments as well as their self-sufficiency and self-reliance. In the last nine years, the South African government introduced inclusive education, through White Paper 6 that requires that Learning, Teaching and Support Material, including ICTs be provided to learners with visual impairments. The provision of Assistive Technology devices (ATs) is essential to learners with visual impairments full involvement in learning through the use of ICTs. Furthermore, literature indicates that many studies were done in the use of ICTs in teaching and learning, specifically for learners with diverse visual impairments. Recommendations were also supplied by these studies on how and when to use ICTs in the teaching and learning of visually impaired learners. The empirical research of this study revealed that ICTs are essential tools for visually impaired learners to enhance their learning. It also drew attention to the fact that despite the commitments of White Paper 6 schools for the visually impaired are not yet supplied with appropriate ICTs and educators are not adequately trained to apply ICTs in teaching and learning. / Thesis (M.Ed.)--North-West University, Vaal Triangle Campus, 2011

Background: Concerns have been well documented about women either dying or developing severe morbidities from prolonged and obstructed labour. These concerns have noted that maternity care during labour has not been of a sufficient standard to improve the outcome for women giving birth in Malawi. This ‘failure to save’ women remains, despite assertions that obstructed and prolonged labour can be prevented through appropriate decision making during the progress and management of labour. Midwives in Malawi form the majority of maternity healthcare workers and an important aspect of their decision-making role is to assess the progress of labour when caring for women in labour. To date, there has been limited exploration of either midwifery decision making during labour or the contextual factors that influence midwives’ decision making. The aim of this study was to explore how Malawian midwives make decisions during the first stage of labour in a hospital setting and to identify the contextual factors that influence their decision making. Design and Method: Using a qualitative ethnographic research approach, 27 participant observations, 26 follow-up interviews and document reviews comprised the data collection. Nine Malawian nurse-midwives who worked at a tertiary (n=5) and a secondary referral hospital (n=4), with a mixture of qualifications and experiences, participated. Each nurse midwife was observed three times with subsequent follow-up interviews. Interviews were conducted in a vernacular language, audio-taped, transcribed, translated into English and back translated into vernacular language. Qualitative data analysis software, NVivo 10, was used to assist with data management for the analysis. All data was analysed using the principle of theme and category formation. Findings: Three major themes were identified - contextual factors influencing midwifery decision making - the role of cue acquisition - the role of the partograph during care of women in the first stage of labour. Integration of the themes has led to the development of a proposed conceptual model of ‘supporting normality’ during the first stage of labour, which suggests that the midwives strived to make decisions during the care of women in labour with the aim of supporting the normal physiological processes of labour. The first theme illustrates that for Malawian midwives, decision making is a complex and contextually dependent undertaking. In everyday practice, decision making was influenced by multiple and competing factors but the midwives developed strategies to manage and control the context of their practice and facilitate decision making. The role of cue acquisition comprised a six-stage subprocess illustrating the ways in which midwives utilise assessment data to reason and make decisions during the care of women in labour. These processes involved the midwives building a case for each woman’s labour progression by piecing together segments of information they obtained. This process was striking when there was uncertainty in a woman’s progress of labour as they used deductive thinking by cross-checking data obtained across the labour progression span. There was a constant forward and backward moving of thought processes supported by actions that uncovered real case-building evidence for informing decisions about whether to intervene or not. The model further indicates the role of the partograph, which alerted midwives to the presence of progress or non-progress of labour. Although the partograph acted as an adjunct to the midwives’ decision making that could indicate opportunities for early intervention in labour if labour appeared not to be progressing, the midwives were sometimes cautious about its interpretation. This thesis has expanded on current theoretical knowledge of decision making by elaborating on the processes midwives employ to make decisions as they care for women in labour. It also illuminates the impact of contextual factors on decision making, and elucidates various strategies midwives use to advance their professional role. The emerging conceptual model provides implications for future midwifery practice, education and policy both in Malawi and worldwide.

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