Bakgrund: Telefonsjuksköterskors arbetsuppgifter är att råda, stötta och göra bedömningar i en komplex situation. Studier har gjorts på telefonsjuksköterskors erfarenhet i telefonrådgivning men få har inkluderat observation. Syfte: Denna studie syftar till att beskriva hur telefonsjuksköterskor använder webbaserat beslutsstöd i telefonrådgivning på vårdcentral och deras erfarenheter av detta. Metod: Studien är kvalitativ med beskrivande design. Observationer och halvstrukturerade intervjuer utfördes på vårdcentral. Sex distriktssköterskor som hade arbetat minst ett år i telefonrådgivning deltog. Analys: Data från observationerna och intervjuerna bearbetades med kvalitativ innehållsanalys. Resultat: Telefonsjuksköterskorna använde dataprogrammet Rådgivningsstödet Webb (RGS Webb) som en stödjande funktion vilket skapade trygghet. För stora textmassor med långa sökvägar försvårade arbetet. Faktorer som organisatorisk tidspress, avsaknad av hjälpmedel för kommunikation med patienter som talar annat språk och lång erfarenhet minskade användandet av RGS Webb.  Diskussion: Telefonsjuksköterskorna upplevde stöd i att RGS Webb gav mycket och korrekt information som kunde ges till vårdtagare. Detta ledde till säkrare bedömningar som ökade patientsäkerheten. RGS Webb upplevdes svårarbetat med mycket textmassor. Utbildning behövs inom informationsteknik eftersom sjuksköterskorna idag förväntas vara stora användare av IT. Slutsats: RGS Webb stödjer, påminner, skapar trygghet och ger ny kunskap. Svårigheter som fanns utgjorde hinder i användandet och RGS Webb användes i mindre utsträckning eller inte alls. / Background: The telephone nurse's duties are to advise, support and make assessments in a complex situation. Studies have been conducted on the telephone nurse's experience in telephone counseling, but few have included observation. Aim: This study aims at describing how telephone nurses use computer decision support system in telephone counseling at the health center and their experiences with this. Method: The study is qualitative with descriptive design. Observations and semi-structured interviews were conducted at the health center. Six district nurses who had worked for at least one year in telephone consulting participated. Analysis: The data from the observations and interviews were processed using qualitative content analysis. Result: The telephone nurse used the computer decision support system (RGS Webb) as a supportive feature, which created security. Too large text pads with long paths made work difficult. Factors such as organizational time pressure, lack of tools for communication with patients who speak other languages and long experience reduced the use of RGS Webb. Discussion: The telephone nurse found support in the fact that RGS Webb provided very accurate information that could be given to caregivers. This leads to safer assessments that increase patient safety. RGS Webb was experienced hard-working with a lot of text masses. Education is needed in information technology because nurses today are expected to be major users of IT. Conclusion: RGS Webb supports, reminds, creates security and provides new knowledge. Difficulties that existed were barriers to use and RGS Webb was used to a lesser extent or not at all.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Regulator of G-protein Signaling (RGS) proteins temporally regulate the G protein signaling cascades initiated by GPCR activation. Reports have established dysregulation of RGS expression in a variety of disease states including several cancers. Additionally, use of genetic ablation techniques has implicated RGS proteins in a variety of other disease states through the native action of the RGS i.e. not a consequence of dysregulation of RGS expression. Therefore identification and optimization of small molecule lead compounds that alter RGS protein function has emerged as a promising therapeutic strategy. In this thesis, we use high throughput screening to interrogate small molecule libraries targeting two RGS proteins, RGS6 and RGS17. RGS6 has been reported as an essential mediator of doxorubicin induced cardiotoxicity, alcohol induced cardio and hepatotoxicity, anxiety, depression, and alcohol dependence. RGS17 has largely been implicated in a variety of cancer pathogenesis, with reported over expression in prostate, lung, breast, and hepatocellular carcinomas. Chapter 2 of this work focuses on the screening efforts targeting RGS6. Three separate screening campaigns interrogating over 20K compounds led to the identification of 3 small molecules that inhibit the RGS6: Gαo protein protein interaction with appreciable selectivity over control assays. The development of a cell based protein interaction assay is discussed, and the compounds were investigated using this system. All compounds tested did not appreciably alter signal over control, meaning that the cellular activity of these compounds remains ambiguous. Chapter 3 details the screening and follow up efforts targeting RGS17. The primary screening and/or follow up of four separate screening campaigns interrogating over 110K compounds is discussed. In total, 10 identified leads and a panel of analogs were subjected to significant follow up evaluation. All compounds were found to be cysteine dependent. The second generation RGS17 inhibitors (UI series) were determined to be both cytostatic and cytotoxic against lung and prostate cancer cell lines in culture, although whether this is due to RGS17 dependent mechanisms or due to general promiscuity of the compounds remains to be determined. Lead compounds from a library provided by the NCI were found to have cellular activity and were subjected to an investigation of structure activity relationships via commercially available compounds. The active form of three of these compounds was found to be a degradation product, which is likely due to decomposition of furan or methyl furan moieties that these compounds shared. One compound demonstrated robust SAR which allowed for the generation of schemes detailing putative inhibitory mechanisms. Finally, the role of RGS17 in the transition from epithelial to mesenchymal phenotypes is investigated. RGS17 was found to cause a sub population of PC3 cells to shift to mesenchymal phenotype, indicating that RGS17 may indeed play a role in this transition. Chapter 4 focuses on efforts to investigate variable potencies of published RGS4 inhibitors against a panel of RGS proteins, with the goal of gleaning insight in to structural characteristics that influence the inhibitability of RGS proteins. Most compounds tested were found to be more potent inhibitors of RGS14 rather than RGS4 in biochemical assays. We developed the NanoBit protein complementation assay to assess the interaction of RGS proteins with either Gαi1 or Gαq in a cellular context, and used this system to investigate compound selectivity in a cellular context. The compounds tested showed selectivity for RGS2, RGS4, and RGS14 over the other RGS proteins tested. The structural differences between the RGS proteins is discussed. Chapter 5 focuses on the future directions the lab may take with respect to the projects outlined in the previous chapters. This includes the screening of more targeted libraries or even virtual screening for RGS6, the development of in vivo assessment tools for RGS17, and an expanded structural examination of RGS proteins including NMR and crystal structure analysis. Additionally, the development of the NanoBit system to interrogate RGS protein interactions that are not RGS: Gα interactions is discussed.

Dissertation (Ph.D.)--University of South Florida, 2006. / Includes vita. Includes bibliographical references (leaves 110-125). Also available online via the World Wide Web.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder producing a clinical syndrome of bradykinesia, rigidity and resting tremor. These motor symptoms appear due to the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and loss of dopamine in the striatum, which subsequently leads to an imbalance of the basal ganglia motor circuit. The most effective pharmacological treatment for PD is L-3,4-dihydroxyphenylalanine (L-DOPA), the immediate metabolic precursor of dopamine, which effectively restores motor function. L-DOPA is catabolised into dopamine and replaces neurotransmitter loss in PD. However, long-term L-DOPA treatment leads to abnormal involuntary movements (AIMs), such as L-DOPA-induced dyskinesia (LID), which reduces the quality of life in PD patients. Currently, there are no reliable pharmacological treatments for these motor complications. Clinical and preclinical studies have shown that development and expression of LID is linked to unregulated dopamine release and plasticity-induced changes of striatal dopaminergic and non-dopaminergic signalling pathways. The activities of these pathways can be modulated by neurotransmitter receptors of a specific classification, the G-protein-coupled receptor (GPCR) family. In turn, GPCRs are regulated by certain endogenous proteins, the regulators of G-protein signalling (RGS) proteins. Numerous RGS protein subtypes are expressed in the striatum but their roles in PD and LID remain poorly understood. Given the modulatory function of RGS proteins in the striatum, these endogenous factors may have pathophysiological roles in the expression of motor symptoms in PD and LID. The studies presented in this thesis investigated the roles of RGS proteins in the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD and LID. Rats received unilateral 6-OHDA lesions of the right medial forebrain bundle to induce severe dopamine denervation. L-DOPA/benserazide (6/15 mg/kg) was then administered once daily for at least 21 days to induce stable abnormal involuntary movements (AIMs). In Chapter 2 of this thesis, increased levels of RGS2 and RGS4 mRNA were found in the rostral striatum of the unilateral 6-OHDA-lesioned rat model of LID. Moreover, elevated levels of RGS4 mRNA were specific to sensorimotor regions and positively correlated with AIMs severity. These molecular and behavioural data suggest that RGS4 proteins are involved in the expression of LID. In Chapters 3 and 4, behavioural studies conducted in the unilateral 6-OHDA-lesioned rat model of LID showed that acute inhibition of striatal RGS4 proteins reduced the expression of AIMs and improved overall motor function. Moreover, repeated de novo treatment with RGS4 protein inhibitors, in combination with L-DOPA, attenuated the development of AIMs and reduced the overexpression of preproenkephalin-B, a molecular marker of LID. These behavioural and molecular data suggest that blockade of RGS4 proteins can reduce the induction of LID. In Chapter 5, in vivo microdialysis conducted in the unilateral 6-OHDA-lesioned rat model of LID showed that systemic administration of RGS4 protein inhibitors, in combination with L-DOPA, attenuated unregulated striatal dopamine efflux. These data suggest that RGS4 proteins may regulate specific G-protein coupled receptors, such as 5-HT1A receptors, that modulate striatal dopamine release. In conclusion, the work presented in this thesis shows that RGS4 proteins play a pathophysiological role in the expression and development of LID. These proteins could mediate regulation of key neurotransmitter receptors involved in LID, making them a potential therapeutic target for the development of future treatments.

Thesis advisor: Larry H. Ludlow / In the field of teacher education, it is well documented that the most influential part is the clinical component, often referred to as student teaching or the practicum experience (Cochran-Smith, 1991; Darling-Hammond, 2014; Evertson, 1990). During the practicum, there exists a triad of three individuals: a university supervisor, a K-12 classroom teacher (often referred to as the cooperating teacher), and the teacher candidate. While much research has been conducted on teacher candidates and the cooperating teacher role, there has been a lack of research on the role of the university supervisor. The lack of measurement instruments to assess the quality of the university supervisor puts teacher education programs at a disadvantage, both from a programmatic improvement standpoint, as well as meeting accreditation requirements. This dissertation provides an answer to this issue, creating a new instrument that assesses the quality of the university supervisor, from the perspective of teacher candidates. This instrument is constructed under the Rasch-Guttman Scenario (RGS) framework, as most clearly defined by Ludlow, Baez-Cruz, et al. (2020). The RGS framework derives its influence from the works of George Rasch (1960/80) as well as Louis Guttman’s facet theory (Guttman 1954; Guttman 1957). The result is a new scale, entitled the University Supervisor Quality (USQ) scale, consisting of nine scenario items. All nine items include four facets that comprise the construct of university supervisor quality: resourcefulness, constructive feedback, mentorship, and collaboration. The results of this dissertation suggest that the utilization of the RGS framework is successful for developing a scale about university supervisor quality. In addition, the use of cognitive interviews provide valuable insight into the development of scales using the RGS framework. This scale has the potential for use in teacher education programs for evaluating the quality of their supervisors, and to utilize as evidence for accreditation purposes. / Thesis (PhD) — Boston College, 2022. / Submitted to: Boston College. Lynch School of Education. / Discipline: Educational Research, Measurement and Evaluation.

Thesis advisor: Larry H. Ludlow / In 2019, as in previous years, White students outperformed African American, Hispanic, and American Indian/Alaska Natives in a variety of K-12 outcomes (Darling-Hammond, 2007; de Brey et al., 2019; Jacob & Ludwig, 2008; National Education Association, 2015). The urgency of the opportunity/achievement gap is clear, as the current cohort of students under 5 years of age marks a turning point in student population demographics as the first in which 50 percent are part of a minority race or ethnic group (U.S. Census Bureau, 2015). Sociocultural integration (SCI) is included in the frameworks of successful bilingual programs (Howard et al., 2007; Scanlan & López, 2014). SCI considers the dynamics of relationships with oneself and others as being built in the context of one’s racial/ethnic, cultural, and linguistic background (Brisk, 2006; Feinauer & Howard, 2014). Acceptance and appreciation of cultural difference is critical for teachers (Bennett, 2003) and a number of pedagogical frameworks center teachers’ role of cultural brokerage as a pathway to fostering positive student outcomes (Grant & Sleeter, 2006; Suárez-Orozco & Suárez-Orozco, 2001; Villegas & Lucas, 2002). In this dissertation, I defined sociocultural integration in a teacher-centered way, and explicitly incorporate teachers’ racial/ethnic identity development in the evolution of their actions to support SCI. Second, I operationalized this definition and built a scale for measuring SCI using innovative “lived experiences” scenario items according to the Rasch/Guttman Scenario scale development methodology (Ludlow et al., 2020). The SCI Scale for Teachers showed desirable psychometric properties and is well suited to increase use due to ease of interpretability. / Thesis (PhD) — Boston College, 2021. / Submitted to: Boston College. Lynch School of Education. / Discipline: Educational Research, Measurement and Evaluation.

Ambulanssjukvården ger patienterna adekvat vård i ett tidigare skede än tidigare. Patienternas vårdbehov bedöms prehospitalt och styrs till rätt vårdnivå. Ambulanssjuksköters-kan upplever att bedömning och hänvisning av patienter till annan vårdnivå än akutmottagningen (AKM) som utmanande. Det är särskilt svårt att bedöma patienter med ett primärvårdsbehov relaterat till att de ofta har ospecifika symptom. Till hjälp för ett systematiskt omhändertagande finns beslutsstöd, vilka kan vara riktlinjer, behandlingsanvisningar eller rådgivningsstöd. Bedömningarna ska ske på ett säkert sätt. Syftet med föreliggande uppsats var att explorativt undersöka hur ambulanssjuksköterskan arbetar med beslutsstödet RGS webb vid hänvisning av patienter till alternativ vårdnivå i Region Halland. Detta gjordes genom en retrospektiv journalgranskning av 1663 journaler med en kvantitativ ansats kring hur hänvisningen gått till. Mer än en femtedel av journalerna fick exkluderas pga. felkodning. Resultatet visade att i mer än hälften av fallen blev patienterna hänvisade att själva söka vårdcentral och ta sig dit självständigt. Majoriteten av de hänvisade patienterna var kvinnor. De äldsta patienterna hänvisades till hemsjukvården och de yngsta till att självständigt söka vård på vårdcentralen. En femtedel av de hänvisade patienterna sökte AKM inom 72 h. Fördelningen av antalet hänvisningar var jämn mellan stationerna. Genomsnittstiden för ett uppdrag med hänvisning till alternativ vårdnivå var ˜ 36 minuter. Slutsatsen är att en stor andel journaler var felkodade vilket kan relateras till en för kort implementeringsperiod. Ett förbättrat och utökat samarbete mellan hemsjukvård och ambulanssjukvården erfordras.

Chemokines are important chemical signals that guide lymphocyte movement within the immune system and promote the organization and functions of germinal centers (GCs) in the secondary lymphoid tissues. Previous studies have shown that GC T cells exhibit high expression of chemokine receptor 4, CXCR4, but that these cells are unable to migrate to the ligand for this receptor, the chemokine CXCL12. This “migratory paralysis” to CXCL12 was found to be correlated with the expression of two Regulators of G-protein Signaling, RGS13 and RGS16 in the GC T cells. The objective of my research was to determine whether RGS13 and RGS16 expression were associated with CXCL12-mediated CD4+ T cell migration. Because human GC T cells are rare and vary from one individual to another, I utilized two human neoplastic CD4+ T cell lines (i.e. Hut78 and SupT1) to facilitate and standardize my research. I also confirmed my observations using primary CD4+ T cells. Hut78 cells behaved similarly to GC T cells interms of CXCL12-mediated migration and RGS13 and RGS16 expression, while SupT1 cells appeared similar to CD4+ T cells that resided outside of GCs. The effect of RGS13 and RGS16 expression in the various CD4+ T cells was examined by altering the natural levels of these genes using RNA-mediated silencing and/or gene overexpression analysis after which, I examined the ability of the cells to migrate to CXCL12. RNA-mediated silencing of RGS16-, but not RGS13-, expression in Hut78 T cells resulted in a doubling of the migration rate in response to CXCL12. Over-expression of RGS13 or RGS16 in SupT1 and primary CD4+ T cells resulted in migration that was decreased by fifty percent. Because GC T cells demonstrated decreased migration to CXCL12 signals that may help them leave the GC, I reasoned that these cells may have an increased opportunity over other CD4+ T cells to become infected by the Human Immunodeficiency Virus (HIV) trapped on Follicular Dendritic Cells in the GCs of infected subjects. Examination of GC T cells obtained from HIV-infected subjects indicated that these cells were more frequently infected by HIV than other CD4+ T cells thereby confirming my postulate. My research indicated that RGS13 and RGS16 were associated with CXCL12-mediated CD4+ T cell migration and suggests that these molecules may play an important role in HIV pathogenesis within the GC.

No description available.