Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Background: Understanding the contribution of divergent individual response patterns remains a key objective in identifying mechanisms of inflammation and potential factors limiting the resolution of inflammation. The purpose of this research project was to investigate downstream effects of inflammation following exercise-induced muscle damage in human subjects. Methods: For three different studies, a total of 53 untrained healthy male participants were recruited and divided into a non-exercising control (n=13) and exercise-induced muscle damage groups (n=40). The study design for the three studies was the same (with few exceptions): Downhill running (DHR) (12 x 5min bouts, 10% decline, 15 km.h-1) with blood samples taken pre, post, after 2 and 4 hours post-exercise (2h, 4h) and on days 1, 2, 3, 4 and 7 (d1-d7). Serum was analysed for creatine kinase activity (CK), myoglobin (Mb), cortisol, cytokine (TNFα, IL-1ra, IL-1β, IL-4, IL-6, IL-8, IL-10, sIL-6R), chemokine (G-CSF, MIP-1β) and adhesion factor (sICAM-1, sP-selectin) concentrations. Tissue degradation was assessed by serum matrix metalloprotease (MMP-9) and myeloperoxidase (MPO) content. White blood cell differential count was determined and the surface expression of various cluster of differentiation factors (CD11b, CD163, CD68, CD88, CD34) as well as intracellular MPO were assessed in whole bood using flow cytometry. Nuclear localization of the inflammatory mediator NFĸB in isolated perhipheral blood mononuclear cells (PBMCs) was determined using immunofluorescence microscopy. Muscle biopsies (vastus lateralis) taken at baseline, 4h, d1 and d2 were analysed for fibre type, inflammatory and stress-induced pathways (STAT3, IĸBα, p38MAPK), myogenic factors (MyoD, myogenin), neutrophil activity (MPO) and satellite cell number (Pax7). Results: Participants in the DHR group were subdivided into those with a normal recovery (DHR1) and those who developed secondary damage (DHR2). CK peaked on d1 in both subgroups (DHR1: 1512 ± 413 u.L-1, DHR2: 1434 ± 202 u.L-1) and again on d4 only in the DHR2 group (1110 ± 184 u.L-1). A similar IL-6 and IL-10 response was evident immediately post DHR in all individuals. Additional IL-6 was released in the DHR2 subgroup peaking at 4h (10.3 ± 4.2 pg.mL-1) whereas IL-10 had returned to baseline. IL-1ra (23.6 ± 8.8 pg.mL-1), CD68+ (5%) and CD163+ (3%) monocytes were significantly higher in the DHR2 subgroup. Neutrophil count at 2h (DHR1: 8.6 ± 0.8 x109 cells.L-1, DHR2: 11.4 ± 1.8 x109 cells.L-1) was significantly (p<0.02) correlated to CK activity on d4. PBMC NFĸB p65 nuclear localization was slightly less at 2h in the DHR2 compared to the DHR1 and control groups. Intramuscular STAT3 signalling and MPO were significantly higher in the DHR2 compared to the DHR1 subgroup at 4h and d2 respectively. The progenitor cell response was similar for all DHR individuals with an increase in Pax7+ SC observed at 4h (0.06 ± 0.01 Pax+ SCs/fibre) and d1 (0.07 ± 0.02 Pax+ SCs/fibre). Conclusion: Healthy young men can be divided into those with a adequate and those with a less efficient capacity to control the post damage inflammatory response. The early cytokine response, especially IL-6, seems to be a key role player in the cascade of events leading to late secondary skeletal muscle damage. / AFRIKAANSE OPSOMMING: Agtergrond: Die begrip van uiteenlopende individuele reaksie patrone, is belangrik in die identifisering van faktore asook meganismes betrokke in die ontwikkeling en resolusie van inflammasie. Die doel van hierdie navorsingsprojek was om die gevolge van oefening-geïnduseerde spierskade en inflammasie te ondersoek in menslike proefpersone. Metodiek: ‘n Totaal van 53 gesonde mans is tydens drie verskillende studies, gegroepeer in ’n kontrole (geen oefening) (n=13) en oefening geinduseerde spier skade (DHR) groep (n=40). Die uitleg van de studies was eenders (met min uitsonderings): Afdraende hardloop (12 x 5min hardloop sessies, 10% afdraende, 15km.h-1) met bloed monsters geneem voor, na, 2 ure, 4 ure (pre, post, 2h, 4h) en op dag 1, 2, 3, 4 en 7 (d1-7). Serum is ontleed vir die volgende: kreatien kinase aktiwiteit (CK), kortisol, sitokiene (TNFα, IL-1ra, IL-1β, IL-4, IL-6, IL-8, IL-10, sIL-6R), chemokien (G-CSF, MIP-1β) en adhesie molekuul (sICAM-1, sP-selectin) konsentrasies. Weefsel degradasie is vasgestel deur die teenwoordigheid van matriks metalo-protease-9 (MMP-9) en miëloperoksidase (MPO) in serum te meet. Differensiële witbloed sel (WBC) telling asook die teenwoordigheid van sekere differensiasie faktore (CD11b, CD163, CD68, CD88, CD34) op die sel oppervlak asook intrasellulêre MPO vlakke is bepaal deur gebruik te maak van vloeisitometrie. Die lokalisering van NFĸB in die selkerne van geïsoleerde bloed mononukleêre selle (PBMC) is bepaal deur fluoriserende mikroskopie. Spierbiopsies (vastus lateralis) geneem tydens rus (basislyn), na 4h, en op d1 en d2 is ontleed vir veseltipe, inflammatoriese en stresverwante faktore (STAT3, IĸBα, p38 MAPK), miogeniese faktore (myoD, myogenin), neutrofiel aktiwiteit (MPO) en aantal satelliet selle (Pax7). Resultate: Deelnemers in die DHR-groep is onderverdeel in twee groepe. Persone wat normaalweg herstel het is saam gegroepeer (DHR1) en diegene wat sekondêre skade ontwikkel het is saam gegroepeer (DHR2). CK aktiwiteit in serum het hoogtepunte bereik op d1 in beide subgroepe (DHR1: 1512 ± 413 u.L-1, DHR2: 1434 ± 202 u.L-1) en weer op d4 in die DHR2 groep (1110 ± 184 u.L-1). 'n Soortgelyke IL-6 en IL-10 reaksie is onmiddellik na oefening (in al die proefpersone) waargeneem. Addisionele IL-6 is vrygestel in die DHR2 subgroep en het ’n hoogtepunt bereik na 4h (10.3 ± 4.2 pg.mL-1), terwyl IL-10 reeds teruggekeer het na rustende waardes. IL-1ra (23.6 ± 8.8 pg.mL-1), CD68+ (5%) en CD163+ (3%) monosiete was aansienlik hoër in die DHR2 subgroep. Neutrofieltelling na 2h (DHR1: 8.6 ± 0.8 x109cells.L-1, DHR2: 11.4 ± 1.8 x109cells.L-1) het verband (p <0,02) gehou met CK-aktiwiteit op d4. In vergelyking met die DHR1 en kontrole groep was die lokalisering van NFĸB p65 in PBMC selkerne na 2h effens minder in die DHR2 subgroep. STAT3- en MPO-vlakke in die spiere was aansienlik hoër in die DHR2 subgroep as in die DHR1 subgroep na 4h en op d2 onderskeidelik. Die spierherstel proses was eenders vir alle individue wat aan die oefening deelgeneem het; 'n toename in Pax7+ Satelietselle (SC) is waargeneem na 4h (0.06 ± 0.01 Pax+ SC/spiervesel) en op d1 (0.07 ± 0.02 Pax+ SC/spiervesel). Gevolgtrekking: Gesonde jong mans kan verdeel word in diegene met 'n bevoegde en diegene met 'n minder doeltreffende vermoë om oefenings-geïnduseerde spierskade en die inflammatoriese reaksie te beheer. Die sitokien-reaksie, veral IL-6, blyk om 'n belangrike rolspeler in die ontwikkeling van sekondêre skeletspierskade te wees.

Thesis (MPhil (Philosophy))--University of Stellenbosch, 2008. / The merger of organisations has been extensively utilised in many industries. This has occurred globally and locally. Some mergers have become successful while others have failed to achieve their goals. The failure of mergers could be attributed to insufficient attention to certain organisational elements. When institutions merged, they become vulnerable to diversity and conflict. They also experience human variability. Organisational mergers present challenges that could be associated with humanity. This could be precipitated by various beliefs, values and norms. Conflict and diversity could be reduced by implementing certain organisational elements. This study is based on the developments of structure and culture as remedial organisational elements to reduce instability in merged institutions. These elements serve as mechanisms in dealing with the repercussions of the merger. The special focus of this study is higher education mergers. The primary objective is to gain an insight into the ramification and the impact of the merger. This includes the effectiveness of the newly designed internal processes. In accomplishing this, the study has applied a cultural and structural model to merged institutions. It has also examined various types of culture and structural literature theory extensively. From this it has discovered that these elements play a crucial role in reducing organisational conflict in mergers. It has also been found that merger consequences are less severe in organisations with similar backgrounds.

Today's challenge for workforce management lies in providing a healthy, safe and productive working culture where people are valued, empowered and respected. Workforce diversity is becoming an essential aspect of the global workforce, and ageing is the most prominent and significant factor in this regard. Diversity brings many opportunities and challenges, as workers with different backgrounds, cultures, working attitudes, behaviours and age work together, and in future, the key to organizational effectiveness and sustainability will heavily depend on developing and sustaining inclusive work environments where people with their differences can co-exist safely and productively. Manufacturing organizations expect the highest levels of productivity and quality, but unfortunately the manufacturing system design process does not take into account human variability issues caused by age, skill, experience, attitude towards work etc. This thesis focuses on proposing an inclusive design methodology to address the design needs of a broader range of the population. However, the promotion and implementation of an inclusive design method is challenging due to the lack of relevant data and lack of relevant tools and methods to help designers. This research aims to support the inclusive design process by providing relevant data and developing new design methodologies. The inclusive design methodology suggested in this thesis is a three step approach for achieving a safe and sustainable work environment for workers, with special concern for older workers. The methodology is based on the provision of relevant human capabilities data, the capture and analysis of difference in human behaviour and the use of this knowledge in a digital human modelling tool. The research is focused on manual assembly through a case study in the furniture manufacturing industry and joint mobility data from a wide-ranging population has been analysed and the task performing strategies and behaviours of workers with different levels of skills have been recorded and analysed. It has been shown that joint mobility significantly decreases with age and disability and that skilful workers are likely to adopt safer and more productive working strategies. A digital human modelling based inclusive design strategy was found to be useful in addressing the design needs of older workers performing manufacturing assembly activities. This strategy validates the concept of using human capabilities data for assessing the level of acceptability of any adopted strategy for older workers, and suggests that the strategies adopted by skilful workers are more likely to be equally acceptable for older and younger workers keeping in view differences in their joint mobility. The overall purpose of this thesis is to present a road map towards the promotion and implementation of the inclusive design method for addressing workforce challenges and in future the same strategies might be implemented within a variety of other industrial applications. The proposed three step inclusive design methodology and getting a reasonable understanding of human variability issues along with the use of human capabilities data (joint mobility in this case) in a human modelling system for design assessment at a pre-design stage can be considered as the major contributions of this research.