Aspects of the impact of apartheid on commerce and industry in the Western Cape, 1960 to 1990

Includes abstract.Includes bibliographical references (leaves 147-155).The thesis considers the economic performance of South Africa, from the substantial and sustained growth from 1960 to 1974, followed by a period when the South African economy weakened. The Western Cape economy was not reliant on mining, but had a more stable economy relying on agriculture, property and financial services, and later in the period developed high-tech service industries. Business in South Africa suffered punitive rates of tax to pay for the country's apartheid policies. The establishment of the Bantustans as a homeland for the black ethnic groups was a cornerstone of the National Party policy and the cost burden was enormous with the provision of all the trappings of full nationhood. The job reservation policies, which reserved skilled occupations created a skill shortage in the country and towards the end of the period by necessity the policy 'frayed at the edges'. Western Cape business also suffered the impact of the coloured labour preference policy, which was designed to prevent the movement of blacks to the Western Cape

Business, state and society in the Western Cape from 1960 to 1990

This research examines the relationship between business, the state and society in South Africa -- particularly the Western Cape -- over the period from 1960 to 1990, viewed against the background of economic conditions in this region, South Africa and the world. Utilising a development history approach, it is based on an extensive study of primary and secondary documentation, supplemented by a panel of in-depth interviews and observation. This study finds that the relationship between business and apartheid incorporated both functional and dysfunctional elements, although over time the benefits diminished and the costs multiplied. The latter, Regulation Theory suggests, is true for any institutional order, but it could be argued that, under apartheid, the particularly fragile and contradictory nature of the institutional arrangement made inevitable crises more rapid and more pronounced. On the one hand, apartheid restricted the economic development of the country, as a result of a range of factors from skills shortages to the visible waste of resources on grand ideological projects and security; as suggested by Resource Curse Theory, minerals windfalls tend to encourage irresponsible behaviour by governments. On the other hand, certain businesses prospered, notably the Afrikaner business sector. All business benefited from the overall growth of the 1950s and 1960s, whilst niche players often did quite well even during the 1980s. Further, the South African businessmen, both English- and Afrikaans-speaking, were skilful in adapting to the difficult conditions brought about by apartheid, and in many cases they prospered. As highlighted by Business Systems Theory, embedded social ties and informal relations may help either support or compensate for formal regulatory pressures. Many of these general trends were particularly accentuated in the Western Cape. The fact that business protests against government policies were often more motivated by concerns as to future property rights and of social disorder, rather than human rights, does indeed raise serious moral issues. However, in helping encourage political reform, they may have made a positive contribution. This study is founded on three related strands of thinking within the political economy tradition, Resource Curse Theory, Regulation Theory and Business Systems Theory, with the emerging common ground between these three bodies of thought being highlighted. As suggested by Resource Curse Theory, non-mineral producing regions tend to be particularly adversely affected in mineral rich countries, and there is little doubt that the region bore all the costs of the collapse of the gold price in the 1980s, and lacked the deeper capital base of the now Gauteng region to cushion the shock. Whilst apartheid may, as we have seen, have served conservative sectors of agriculture and mining quite well for many years, it also involved large costs incurred through social engineering experiments and the increasing demands of the security establishment. Resource Curse Theory suggests that national economies become dangerously dependent on the vagaries of commodities markets, and that the process of institutional design and evolution is hampered by assumptions of easy money which may temporary resolve the negative consequences of any institutional shortcomings. The poor price of gold in much of the 1980s brought about a crisis in the system, and, there is little doubt that this contributed to the demise of the order. As suggested by Resource Curse Theory, the experience of the Western Cape, a region of the country poor in minerals, was often one of inefficient and wasteful state intervention, coupled with increasingly poor performance of non-mineral related industries. Indeed, the effects of the recession of the 1980s were most pronounced in non-mineral producing areas of the country, particularly in the Western Cape. Regulation Theory highlights that no set of institutions and practices is ever totally coherent and functional, but at specific times may work to promote both certain types of economic activity and overall growth. It is wrong to suggest that because an order only works for some players at specific times it is simply dysfunctional or does not work properly at all. However, over time, internal contradictions mount and the benefits diminish. A particular feature of the apartheid order was that some of its core benefits at its height were particularly concentrated on some players (segments of Afrikaner commerce and industry, mining and agriculture), whilst the costs were shared across a wider range of players, with a disproportionate burden being borne by the black majority. A further feature was that the costs were often indirect and spread over many years if the benefits were sometimes immediate: this would include the persistent dysfunctionality of much of the South African education system and the criminal ecosystem that was nurtured through sanctions busting. Internal contradictions and spreading dysfunctionality rarely leads to a conscious and coherent period of institutional redesign, but rather an incoherent, experimental and contested process, such as characterized late apartheid reforms, and, indeed, the post February-1990 negotiation process. Finally, again at a theoretical level, as Business Systems Theory highlights, it is important to take account of the formal and informal ties interlinking firms in different sectors in the region, and firms and government, and the extent to which regions within a particular country may follow very distinct developmental trajectories. The benefits and the costs of the system diffused unevenly in the region, giving many players both a stake in the existing order, and an interest in some or other type of reform

Process theory and research: Exploring the dialectic tension

We contest that although the notion of process is increasingly being applied to the study of organizations, these attempts are hampered by significant methodological shortcomings. We claim that the value of process theory is under-utilized because most attempts to apply process theory end up reverting to conventional non-process methods. We suggest that the cause of this reversion is primarily the challenge of making sense, of fixing the world, propelling us from process into the world of substance. To break free of these limitations we propose an approach that takes the researchers? audience alongside the subject processes rather than attempting to clinically intersect them. We illuminate this paper with our own story vignettes concerning the fortunes of an idea that passes by the name of value based management (VBM). 1 These vignettes are meant to both exemplify and disrupt the theoretical narrative

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels.

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

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31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS