Thesis(MPhil)--University of Stellenbosch, 2007. / ENGLISH ABSTRACT: The determination of what the concept ‘sustainable competitive advantage’ means within a service environment and the consequent establishment of key resources within Pam Golding Properties and the role that leadership and the creation of a learning organisation play, formed the core of this study. The case study was therefore undertaken to glean relevant information from reality in order to determine which resources that can be described as intangible assets and competences contribute in a sustainable manner to the organisation’s competitive advantage in a dynamic and changing business environment. Existing and historical resources including leadership and learning within the organisation were identified by means of semi-structured interviews with a range of company executives. These resources were then assessed by means of questionnaires that were distributed to a wide range of stakeholders within the organisation in terms of value for the client, sustainability and transferability. These outcomes, in turn, provided the basis for conclusions and recommendations for future utility in order to maintain competitive advantage that would ultimately lead to sustained superior performance on all fronts. The findings that were made, culminated in a visual representation of leadership and organisational learning that form the core of the organisation and simultaneously illustrating their interdependence with the other key resources, namely organisational culture, the Pam Golding Properties brand, reputation, teamwork, relationships, systems and procedures, managers and agents. These resources form the essence of the organisation. The organisational culture within Pam Golding Properties that is representative of the core values of integrity, honesty, sincerity and service delivery was found to be the overall resource that provides the organisation with sustainable competitive advantage. This was closely followed by the value of the brand and reputation, teamwork and inter-personal relationships, the utilisation of efficient systems and procedures and the recruitment and retention of competent managers and agents. Organisational leadership was found to instil confidence in the organisation. A common, shared vision that is understood and underwritten by all employees is however lacking and change needs to be managed in such a way that the organisation’s core ideology is not compromised, but an envisioned future should be communicated throughout. The brand carries out the promise of the culture and core values, but can be tarnished if the reputation for service excellence is not upheld and it can lose credibility if expectations are not met. The brand thus needs protection from within and this can only happen if the people in the organisation share in the process of and toward an envisioned future. It was established that meaningful change presupposes continual improvement in a dynamic, yet sustainable organisation. It was therefore also recommended that a concerted effort be made to actively promote and strive towards the company becoming a true learning organisation in order to sustain its culture, brand, reputation and other intangible assets and competences. In the event that these and other recommendations in terms of resources are seriously considered and strived for by company leaders, this organisation should be an example to the rest of the world regarding sustainable competitive advantage. / AFRIKAANSE OPSOMMING: Die bepaling van wat die konsep ‘volhoubare mededingende voordeel’ beteken binne ‘n diensomgewing en die daaropvolgende vasstelling van sleutelhulpbronne binne Pam Golding Eiendomme en die rol wat leierskap en die skep van ‘n leerorganisasie speel, het die kern van hierdie studie gevorm. Die gevallestudie is dus onderneem om toepaslike inligting vanuit realiteit te werf, om sodoende vas te stel watter hulpbronne wat as ontasbare bates en bevoegdhede beskryf kan word, op ‘n volhoubare wyse tot die organisasie se mededingende voordeel bydra in ‘n dinamiese en veranderende sake-omgewing. Bestaande en historiese hulpbronne insluitend leierskap en leer binne die organisasie is geïdentifiseer by wyse van semi-gestruktueerde onderhoude wat met ‘n aantal uitvoerende lede van die maatskappy gevoer is. Hierdie hulpbronne is daarna deur middel van vraelyste wat aan ‘n breë reeks insethouers binne die organisasie versprei is, geëvalueer in terme van waarde vir die kliënt, volhoubaarheid en oordraagbaarheid. Hierdie uitkomste het weer die basis verskaf vir afleidings en voorstelle wat gemaak is ten opsigte van toekomsbruikbaarheid om mededingende voordeel te behou wat uiteindelik tot volhoubare superieure verrigting op alle fronte sal lei. Die bevindings wat gemaak is, het in ‘n visuele voorstelling van leierskap en organisasieleer gekulmineer, wat die kern van die organisasie uitmaak en tegelykertyd hul interafhanklikheid illustreer ten opsigte van die ander sleutelhulpbronne, naamlik organisasie-kultuur, die Pam Golding Eiendomme handelsnaam, reputasie, spanwerk, verhoudings, stelsels en prosedures, bestuurders an agente. Hierdie hulpbronne maak die essensie van die organisasie uit. Die organisasie-kultuur binne Pam Golding Eiendomme wat verteenwoordigend is van die kernwaardes van integriteit, eerlikheid, opregtheid en dienslewering het as die oorhoofse hulpbron uitgestaan wat die organisasie van volhoubare mededingende voordeel verseker. Dis gevolg deur die waarde van die handelsnaam en reputasie, spanwerk en inter-persoonlike verhoudings, die benutting van doeltreffende stelsels en prosedures en die werwing en retensie van bekwame bestuurders en agente. Daar is bevind dat organisasie-leierskap vertroue in die organisasie skep. ‘n Gemeenskaplike, gedeelde visie wat deur al die werknemers verstaan en onderskryf word, kom egter kort en verandering behoort op só ‘n wyse bestuur te word, dat die organisasie se kern-ideologie nie onder verdenking gebring word nie, maar ‘n gevisioneerde toekoms behoort deurgaans gekommunikeer te word. Die handelsnaam dra die belofte van die kultuur en kernwaardes uit, maar kan skade opdoen as die reputasie vir diensuitnemendheid nie onderhou word nie en dan kan geloofwaardigheid ingeboet word indien daar nie aan verwagtinge voldoen word nie. Die handelsnaam moet dus van binne uit beskerm word en dit kan slegs gebeur indien die mense in die organisasie aan die proses van ‘n gevisioneerde toekoms deelneem. Dit is bevind dat betekenisvolle verandering aaneenlopende verbetering in ‘n dinamiese, dog volhoubare organisasie veronderstel. Daar is dus ook voorgestel dat ‘n doelbewuste poging aangewend word dat die wording van ‘n ware leerorganisasie aktief gepromoveer en nagestreef behoort te word om sodoende die kultuur, handelsnaam, reputasie en ander ontasbare bates en bevoegdhede vol te kan hou. Indien hierdie en ander voorstelle ten opsigte van hulpbronne ernstig deur die maatskappy se leiers bedink en nagestreef word, behoort hierdie organisasie vir die res van die wêreld ‘n voorbeeld van volhoubare mededingende voordeel te wees.

Before market authorization of new medicines, their efficacy and safety are evaluated using randomized controlled trials. While there is no doubt about the scientific value of randomized trials, they are usually conducted in selected populations with questionable generalizability to routine care.  In the digital data revolution era, with healthcare data growing at an unprecedented rate, drug monitoring in routine care is still highly under-utilized. Although many countries have access to data on prescription drugs at the individual level in ambulatory care, such data are often missing for hospitals. This is a growing problem considering the clear trend towards more new and expensive drugs administered in the hospital setting. The aim of this thesis was therefore to develop methods for extracting data on drug use from a hospital-based electronic health record system and further to build and evaluate models for real-time monitoring of effectiveness and safety of new drugs in routine care using data from electronic health records and regional and national health care registers. Using the developed techniques, we were able to demonstrate drug use and health service utilization for inflammatory bowel disease and to evaluate the comparative effectiveness and safety of antiarrhythmic drugs. With a rapidly evolving drug development, it is important to optimize the evaluation of effectiveness, safety and health economic value of new medicines in routine care. We believe that the models described in this thesis could contribute to fulfil this need.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / In order to help individuals feel more engaged within work organizations and more satisfied with their jobs, employers have started to administer stay interviews within organizations, with the end goal being to retain organizational members. Stay interviews have become a proactive solution to the retention problem and have been seen as an alternative to the exit interview. This study proposes that through the use of stay interviews, organizational members will feel more engaged, satisfied, and committed to an organization, which will ultimately result in the retention of organizational members.

Osteoporosis is a significant public health problem in the U.S. It not only affects the physical well-being of the older women but also creates a substantial financial burden for the health care system. The mainstay of osteoporosis medications is bisphosphonate treatment of which alendronate and risedronate are the most commonly prescribed in clinical practice. However, there have been no head-to-head randomized controlled trials (RCTs) evaluating the effects of these two bisphosphonates on fracture outcomes. In the absence of RCTs, observational studies are necessary to provide alternative evidence on the comparative effectiveness between alendronate and risedronate on fracture outcomes. However, existing observational studies have provided inconclusive results partially due to residual confounding from unobserved variables such as patients’ health status or behavior. IV analysis may be one method to address unmeasured confounding bias in observational studies. While it has not been applied in bisphosphonate research, it has been used in research on a variety of other prescription medications. In this dissertation, we applied the IV approach with an IV, date of generic alendronate availability, to evaluate the comparative effectiveness between alendronate and risedronate using observational data. This dissertation improved current research in several ways. First, we extended the IV approach to research on bisphosphonates. Second, compared with the current observational studies on bisphosphonates, this dissertation may more accurately estimate the relative effects between alendronate and risedronate because IV analysis is not subject to unmeasured confounding bias. Third, the study results extended the current evidence of the comparative effectiveness between the two most commonly prescribed bisphosphonates. Finally, we proposed and provided empirical evidence of a new IV that might be used for future prescription drug research. The finding of this dissertation can be summarized from three aspects. First, we found that the evidence supported the validity of the date of generic availability as an IV in the study of bisphosphonates. Second, applying IV approach to study the comparative effectiveness of alendronate and risedronate, we found that alendronate and risedronate were comparable to reduce the risk of 12-month non-vertebral fractures in older women. Since generic alendronate is availability on the market while generic risedronate is not, promoting the use of alendronate may help reduce the healthcare cost and not sacrifice the clinical effectiveness. Finally, by comparing the proposed IV with a popular IV-physician preference, we found that both the calendar time IV based on the date of generic availability and the physician preference appeared to be valid. It might be practically easier to use the calendar time IV than the physician preference IV.

Indiana University-Purdue University Indianapolis (IUPUI) / Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors, and its activation is associated with high histological grade and advanced cancer stage. STAT3 has been shown to play important roles in multiple aspects of cancer aggressiveness including proliferation, survival, self-renewal, migration, invasion, angiogenesis and immune response by regulating the expression of diverse downstream target genes. Thus, inhibiting STAT3 promises to be an attractive strategy for treatment of advanced tumors with metastatic potential. We firstly identified a STAT3 inhibitor, inS3-54, by targeting the DNA-binding site of STAT3 using an in-silico screening approach; however, inS3-54 was finally found not to be appropriate for further studies because of low specificity on STAT3 and poor absorption in mice. To develop an effective and specific STAT3 inhibitor, we identified 89 analogues for the structure-activity relationship analysis. By using hematopoietic progenitor cells isolated from wild-type and STAT3 conditional knockout mice, further studies showed that three analogues (A18, A26 and A69) only inhibited STAT3-dependent colony formation of hematopoietic progenitor cells, indicating a higher selectivity for STAT3 than their parental compound, inS3-54. These compounds were found to (1) inhibit STAT3-specific DNA binding activity; (2) bind to STAT3 protein; (3) suppress proliferation of cancer cells harboring aberrant STAT3 signaling; (4) inhibit migration and invasion of cancer cells and (5) inhibit STAT3-dependent expression of downstream targets by blocking the binding of STAT3 to the promoter regions of responsive genes in cells. In addition, A18 can reduce tumor growth in a mouse xenograft model of lung cancer with little effect on body weight. Taken together, we conclude that it is feasible to inhibit STAT3 by targeting its DNA-binding domain for discovery of anticancer therapeutics.

Indiana University-Purdue University Indianapolis (IUPUI) / ALDH isoenzymes are known to impact the sensitivity of certain neoplastic cells toward cyclophosphamides and its analogs. Despite its bone marrow toxicity, cyclophos-phamide is still used to treat various recalcitrant forms of cancer. When activated, cyclo-phosphamide forms aldophosphamide that can spontaneously form the toxic phospho-ramide mustard, an alkylating agent unless detoxified by ALDH isozymes to the carbox-yphosphamide metabolite. Prior work has demonstrated that the ALDH1A1 and ALDH3A1 isoenzymes can convert aldophosphamide to carboxyphosphamide. This has also been verified by over expression and siRNA knockdown studies. Selective small molecule inhibitors for these ALDH isoenzymes are not currently available. We hypothe-sized that novel and selective small molecule inhibitors of ALDH3A1 would enhance cancer cells’ sensitivity toward cyclophosphamide. If successful, this approach can widen the therapeutic treatment window for cyclophosphamides; permitting lower effective dos-ing regimens with reduced toxicity. An esterase based absorbance assay was optimized in a high throughput setting and 101, 000 compounds were screened and two new selective inhibitors for ALDH3A1, which have IC50 values of 0.2 µM (CB7) and 16 µM (CB29) were discovered. These two compounds compete for aldehyde binding, which was vali-dated both by kinetic and crystallographic studies. Structure activity relationship dataset has helped us determine the basis of potency and selectivity of these compounds towards ALDH3A1 activity. Our data is further supported by mafosfamide (an analog of cyclo-phosphamide) chemosensitivity data, performed on lung adenocarcinoma (A549) and gli-oblastoma (SF767) cell lines. Overall, I have identified two compounds, which inhibit ALDH3A1’s dehydrogenase activity selectively and increases sensitization of ALDH3A1 positive cells to aldophosphamide and its analogs. This may have the potential in improving chemotherapeutic efficacy of cyclophosphamide as well as to help us understand better the role of ALDH3A1 in cells. Future work will focus on testing these compounds on other cancer cell lines that involve ALDH3A1 expression as a mode of chemoresistance.

The research study investigated management strategies through which school effectiveness could be enhanced in primary schools situated in Gauteng Province. The enhancement of school effectiveness necessitated the discussion on school improvement to find ways to turn around the situation in dysfunctional schools in the province. The province is characterised by urban and suburban areas, townships, and informal settlements. Teachers in schools in these areas are well qualified. However, different challenges in these areas impact upon the enhancement of school effectiveness. A literature review was conducted to provide a conceptual framework and explain concepts such as effective management, administration, leadership, principal effectiveness, and teacher effectiveness. The literature review also investigated the factors that impact upon school effectiveness and school improvement and explored the historical development of School Effectiveness Research (SER) in the United States of America, Europe, Australia, and Africa to expound the problem investigated. An empirical investigation using a qualitative approach was conducted. Six primary schools were selected using purposive sampling to ensure that different demographic areas were covered in the research. Purposive sampling allowed the researcher to target schools from high and low socio-economic areas because they often experience different challenges concerning to school effectiveness. Data were collected through individual interviews with principals and officials from the Gauteng Department of Education (GDE) at the district and teachers in focus groups. Key findings were identified. Participants from the three categories respectively identified several characteristics of effective schools which concurred with the literature on school effectiveness. They also identified two features of effective schools which were unique to the study: in effective schools, there is little or no learner and teacher absenteeism; and school values which shape the behaviour of learners are clearly articulated. School values include trustworthiness, respectfulness, honesty, responsibility, striving for excellence and good leadership. School effectiveness is hindered by the current process of appointing principals which does not always succeed in selecting principals with the required leadership qualities and management skills. Further, the incorrect implementation of the Integrated Quality Management System (IQMS) in schools hinders teacher development and leads to poor teacher performance. / Die navorsingstudie ondersoek bestuurstrategieë waardeur die effektiwiteit van primêre skole, geleë in die Provinisie van Gauteng verhoog kan word. Die verhoging van effektiwiteit in skole het die bespreking oor skoolverbetering genoodsaak om maniere te vind om die situasie in disfunksionele skole in die provinisie om te draai. Die provinsie word gekenmerk deur landelike en stedelike gebiede, lokasies, en informele nedersetttings. Onderwysers van skole in hierdie gebiede is goed gekwalifiseerd. Verskeie uitdagings in hierdie gebiede het egter n uitwerking op die verhoging van effektiwiteit in skole. ʼn Literêre oorsig is uitgevoer om n konseptuele raamwerk te voorsien en om konsepte soos effektiewe bestuur, administrasie, leierskap, effektiwiteit van die skoolhoof, en onderwysers te verduidelik. ʼn Kwalitatiewe benadering is gebruik om die empiriese ondersoek uit te voer. Ses primêre skole is gekies en doelgerigte steekproefneming is gebruik om te verseker dat verskillende demografiese gebiede deel was van die navorsing. Doelgerigte steekproefneming het die navorser toegelaat om skole van hoë en lae sosio-ekonomiese gebiede te teiken omdat hulle dikwels verskillende uitdagings aangaande die effektiwiteit van skole ervaar. Data is versamel deur indivduele onderhoude met skoolhoofde en amptenare van Gauteng Onderwys Departement (GDE) by die distrik en deur fokusgroep onderhoude met onderwysers. Sleutelbevindinge was soos volg. Deelnemers uit die drie kategoriëë het onderskeidelik geidentifiseer met verskeie eienskappe van effektiewe skole wat ooreenstem met die literatuur op effektiwiteit in skole. Hulle het ook twee kenmerke van effektiewe skole wat uniek was tot die studie geïdentifiseer: in effektiewe skole is daar min of geen afwesigheid van leerders en onderwysers; en skoolwaardes wat die gedrag van leerders vorm word duidelik verwoord. Skoolwaardes sluit betroubaarheid, respek, eerlikheid, verantwoordelikheid, strewe na uitenmendheid en goeie leierskap in. Effektiwiteit in skole word verhinder deur die huidge proses van aanstelling van skoolhoofde wat nie altyd daarin slaag om skoolhoofde te kies wat die nodige leierskap en bestuurseienskappe het nie. Verder, die verkeerde implementering van die Geïntegreerde Bestuurstelsel (IQMS) in skole belemmer die ontwikkeling en lei tot swak prestasie van onderwysers. / Dinyakisiso tse tsa go ithuta di be di tsomana le mekgwanakgwana ya bolaodi bja thuto go tiisetsa gore dikolo tsa motheo Profentsheng ya Gauteng di soma mesomo yeo e nepagetsego. Tiisetso ya go soma mesomonepagetsego ya sekolo e dirile gore go ahlaahliwe hlabollo ya dikolo go humana ditselana tseo ka tsona re ka hlabolang dikolo tseo di sa someng botse mo profentsheng. Profentshe ya Gauteng e na le dikolo tsa motsesetoropong le tsa mo go bego go dula batho basweu fela. Barutisi mo mafelong a ba na le di thuto tse maleba. Fela, dihlotlo tseo dileng gona mo mafelong a di huetsa tiistso ya go soma mesomonepagatso sekolong. Go dirilwe tekololeswa ya dingwalwa go hlalosa dikgopolo tse bjalo ka taolonepagatso, boetapele, mesomonepagatso ya hlogo ya sekolo le mesomonepagatso ya morutisi. Tekololeswa ya dingwalwa e nyakisisitse dintlha tseo di huetsang mesomonepagetso sekolong le hlabollo ya sekolo go lebeletswe tswetsopele ya dinyakisiso tsamesomonepagatso ya dikiolo dinageng tsa United States of America, Europa, Australia le Afrika go hlalosa bothata bjo bo nyakisiswago. Go dirilwe dinyakisiso ka poledisano go somiswa mokgwa wa kwalitetifi. Go kgethilwe dikolo tse tshela tsa fase ka go somisa kgetho ka maikemisetso go direla gore go akaretswe dikolo go tswa mafelong a go fapana. Kgetho ka maikemisetso e dumelela monyakisisi go tswa mafelong a batho ba go ba le sa bona le mafelong a batho ba go hloka sa bona ka ge ba itemogela dihlotlo tse fapaneng mesomonepagatso. Tshedimoso ye e kgobokeditswe ka dipoledisano le dihlogo tsa dikolo motho a le nosi le bahlankedi bammuso wa Kgoro ya Thuto ya Kgauteng motho a le nosi le dipoledisano ka sehlopha. Dintlha tsa dipoelo di be di le mo go latelago: Batseakarolo go tswa mafapeng a go fapana ba hlaotse diponagalo tsa dikolo tseo disomago ka nepagalo tseo di dumelelanago le tekololeswa ya dingwalwa. Gape ba hlaotse dipanagalo tse dingwe tsa moswana nosi: Dikolo tsa go soma ka nepagalo ga di na barutwana goba barutisi ba go se tle sekolong. Meano ya sekolo e akaretsa botshephegi, tlhompho, boikarabelo le go somela bobotse ka go fetisa le boetapele bjo bo botse. Mosomonepagatso ya sekolo e sitiswa ke tshepediso ya go thwala dihlogo tsa dikolo yeo ka nako tse dinwe e sitago ke go hlaola hlogo ya sekolo yeo e nago le boetapele le bolaodi bjo bo botse. Gape, go tsentshatirisong wo o fasagetseng wa tshepetso ya bolaodi bja hlabollo ya barutisi go sitisa tswelopele. / Educational Management and Leadership / Ph. D. (Education Management)