Healthcare professionals such as speech and language therapists are expected to change their practice throughout their career. However, from a practice perspective, there is a lack of knowledge around what practice change is, what it really takes, and why there are different trajectories. Consequently, therapists, managers and commissioners lack empirical evidence on which to base decisions about enabling practice change. In addition, intervention researchers lack basic sociological research around implementation that could inform their research designs, reporting and impact. This case-based sociological inquiry, underpinned by critical realist assumptions, was designed to address this knowledge gap. It includes a two-stage qualitative synthesis of 53 (then 16) studies where speech and language therapists explained the work of their practice in depth, and a primary qualitative study focused on one professional jurisdiction, children with speech sound difficulties (SSD). Forty two speech and language therapists from three NHS areas and independent practice in Scotland participated in individual interviews or self-organised pairs or focus groups to discuss in depth how and why they had changed their practice with these children. A variety of comparative methods were used to detail, understand and explain this particular aspect of the social world. The resulting theory of SSD practice change comprises six configured cases of practice change (Transforming; Redistributing; Venturing; Personalising; Delegating; Refining) emerging from an evolving and modifiable practice context. The work that had happened across four key aspects of this context (Intervention; Candidacy; Caseload; Service) explained what made each case possible, and how practice had come to be one way rather than another. Among its practical applications, the theory could help services plan more realistic practice change. In addition, the inductively developed layered model of SSD intervention change has the potential to contribute to speech and language therapy education as well as methodological discussions around complex interventions.

Indiana University-Purdue University Indianapolis (IUPUI) / Neurofibromatosis Type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 tumor suppressor gene. Neurofibromin is the protein product of NF1 and functions as a negative regulator of Ras activity in both hematopoietic and vascular wall cells, which are critical for maintaining blood vessel homeostasis. NF1 patients are predisposed to chronic inflammation and premature cardiovascular disease, including development of large arterial aneurysms, which may result in sudden death secondary to their rupture. However, the molecular pathogenesis of NF1 aneurysm formation is completely unknown. Utilizing a novel model of Nf1 murine aneurysm formation, we demonstrate that heterozygous inactivation of Nf1 (Nf1+/-) results in enhanced aneurysm formation with myeloid cell infiltration and increased reactive oxygen species in the vessel wall. Using cell lineage-restricted transgenic mice, we show that loss of a single Nf1 allele in myeloid cells is sufficient to recapitulate the Nf1+/- aneurysm phenotype in vivo. Additionally, oral administration of simvastatin, a statin with antioxidant and anti-inflammatory effects, significantly reduced aneurysm formation in Nf1+/- mice. Finally, the antioxidant apocynin was administered orally and also resulted in a significant reduction of Nf1+/- aneurysms. These data provide genetic and pharmacologic evidence that neurofibromin-deficient myeloid cells are the central cellular triggers for aneurysm formation in a novel model of NF1 vascular disease, implicated oxidative stress as the key biochemical mechanisms of NF1 aneurysm formation and provide a potential therapeutic target for NF1 vasculopathy.

Afrikaans text / Besorgdheid het in die gemeenskap bestaan oar die toenemende getalle kinders wat binne die stedelike konteks van Pretoria op straat leef en werk. Hierdie navorsing is onderneem om die behoeftes van die kinders aan te spreek en om alternatiewe wyses te vind om met hulle te werk. 'n Konteks is geskep sodat na hulle stemme geluister kon word. nag 'n alternatief tot "tradisionele" vorme van gesinsterapie bruikbaar is, op sekere voorwaardes, soos aangedui in hoofstuk vier. Sleutelwoorde: reflekterende span; "straatkinders"; ekosistemiese benadering; ekologie; epistemologie; konstruktivisme; objektivisme; kubernetika; sisteemteorie; mikro-, meso- en makrosisteme; sirkulere en liniere punktuasie Ekosistemiese beginsels is aanvanklik benut, maar was nie vir die span wat saamgewerk het, betekenisvol nie. 'n Gevallestudie-ontwerp was nuttig om die ontwikkeling en "opleiding" van die span wat sou saamwerk, te beskryf, asook die benutting van ekosistemiese beginsels tydens dienste aan die "straatkinders" en hulle gesinne by ltumeleng. Die navorsing het aangedui dat 'n ekosistemiese benadering tot gesinsterapie as / The community showed concern about the increasing number of children living and working on the streets within the urban context of Pretoria. This researchwas undertaken to address the needs of these children and to find alternative ways of working with them. A context was created so that their voices could be heard. Ecosystemic principles were initially used, but were not meaningful to the team who worked together. A case study design proved useful in developing and "training" of the team who would be working together, as well as applying ecosystemic principles while making services available to the "street children" and their families in ltumeleng. The research indicated that an ecosystemic approach to family therapy could be used as an alternative to "traditional" forms of family therapy, subject to certain conditions, as stipulated in Chapter Four. / Social Work / M.A. (Sosiale Wetenskappe (Geestesgesondheid))

Afrikaans text / Besorgdheid het in die gemeenskap bestaan oar die toenemende getalle kinders wat binne die stedelike konteks van Pretoria op straat leef en werk. Hierdie navorsing is onderneem om die behoeftes van die kinders aan te spreek en om alternatiewe wyses te vind om met hulle te werk. 'n Konteks is geskep sodat na hulle stemme geluister kon word. nag 'n alternatief tot "tradisionele" vorme van gesinsterapie bruikbaar is, op sekere voorwaardes, soos aangedui in hoofstuk vier. Sleutelwoorde: reflekterende span; "straatkinders"; ekosistemiese benadering; ekologie; epistemologie; konstruktivisme; objektivisme; kubernetika; sisteemteorie; mikro-, meso- en makrosisteme; sirkulere en liniere punktuasie Ekosistemiese beginsels is aanvanklik benut, maar was nie vir die span wat saamgewerk het, betekenisvol nie. 'n Gevallestudie-ontwerp was nuttig om die ontwikkeling en "opleiding" van die span wat sou saamwerk, te beskryf, asook die benutting van ekosistemiese beginsels tydens dienste aan die "straatkinders" en hulle gesinne by ltumeleng. Die navorsing het aangedui dat 'n ekosistemiese benadering tot gesinsterapie as / The community showed concern about the increasing number of children living and working on the streets within the urban context of Pretoria. This researchwas undertaken to address the needs of these children and to find alternative ways of working with them. A context was created so that their voices could be heard. Ecosystemic principles were initially used, but were not meaningful to the team who worked together. A case study design proved useful in developing and "training" of the team who would be working together, as well as applying ecosystemic principles while making services available to the "street children" and their families in ltumeleng. The research indicated that an ecosystemic approach to family therapy could be used as an alternative to "traditional" forms of family therapy, subject to certain conditions, as stipulated in Chapter Four. / Social Work / M.A. (Sosiale Wetenskappe (Geestesgesondheid))