Debate: The potential role of estrogen in the prevention of heart disease in women after menopause

The observational studies of hormone users are compromised by systematic biases that lead to an overestimation of benefit and an underestimation of risk. Studies of mechanism could support either benefit or harm. The results of clinical trials of oral hormone therapy in women with existing coronary heart disease (CHD) have been uniformly disappointing. The largest trial found an early increased risk for CHD and for venous thromboembolism. Postmenopausal hormone therapy should not be considered for CHD prevention until methods for excluding high-risk women have been established, and until the results of the long-term trials have shown benefit. There is a need for clinical trials of nonoral estrogens

Cardiothoracic surgery training in South Africa: Where to from here?

Standing in the operating theatre and seeing a heart’s function improve after replacing a stenotic aortic valve, or repairing an incompentent mitral valve or revascularising obstructed coronary arteries is an amazing experience. Very few people have the oppurtunity to see a heart come to life when we removethe aortic cross clamp after cardiac surgery. Blood fl ushes the cardioplegia out of the coronaries, the myocardial cells fuel its sodium, potassium and calcium pumps from the life giving blood, and the heart starts beating: a miracle we get to witness every day

Modelling and evaluation of adaptive control techniques in satellite orientation during large actuator gain changes

Thesis (MScEng)--University of Stellenbosch, 2004.ENGLISH ABSTRACT: Improvements in the area of satellite orientation control in the presence of large actuator gain changes are investigated. Gain changes primarily originate from actuator failures, but may also result from intermittent sensor availability and geomagnetic field effects. The stability and performance of a classic LQR control solution under these conditions is analyzed through simulation, and two adaptive schemes are developed to improve the response. The adaptive schemes mix elements from bang-bang control to increase performance, and banded control to increase robustness. These control schemes are thoroughly tested through simulation and the results are compared with those obtained for the classic solution. Extensive modelling of the system in the MATLAB™ environment is done to support the analysis of the controllers, and hardware sensors are built to provide realistic orientation measurements to the controllers.AFRIKAANSE OPSOMMING: Verbeterings in die veld van satelliet oriëntasie beheer in die gevalle waar die aktueerders groot veranderinge in aanwins toon, word ondersoek. Aanwins veranderinge word primêr veroorsaak deur aktueerder falings, maar kan ook deur diskontinue sensor metings en magneetveld effekte van die aarde veroorsaak word. Die stabiliteit en gehalte van 'n klassieke LQR beheer strategie onder hierdie omstandighede word ondersoek deur simulasie, en twee aanpasbare beheer strategieë word ontwikkelom die oordrag te verbeter. Die aanpasbare beheer strategieë meng elemente van "bang-bang" beheer om die gehalte te verbeter, en gebande beheer tegnieke om die robuustheid van die stelsel te verbeter. Hierdie beheer strategieë is deeglik in simulasies getoets en die resultate is vergelyk met dié van die klassieke beheerder. Ekstensiewe modelleering van die stelsel is in die MATLAB™ omgewing gedoen om die beheerders te analiseer, en hardeware sensore is gebou om realistiese orientasie metings aan die beheerders te verskaf

Effective communication planning for high-performance civil engineering project teams

In the area of project management, it is well understood that effective communication processes impact positively on project performance. Despite this, project teams still struggle to develop effective communication plans that address their project communication needs. The evidence of this is that many project problems are attributed to poor communication. The literature addresses the needs and shortcomings of group communication and communication planning in general; but there is however, a scarcity of literature describing how to plan for the internal communication needs of high-performance civil engineering teams. With the limited literature available on the topic, this study seeks to validate how effective the current communication planning methods are at Aurecon in meeting the communication needs of its project teams. This qualitative research project is a case study of communication planning within the project teams at Aurecon in Port Elizabeth. A semi-structured interview process was followed, addressing specific questions, without limiting the direction of the interviews. Project team members, working on high performance projects, were asked for their thoughts, feelings and suggestions about existing communication practices and project communication planning. Overall, it was found that the existing communication-planning practices at Aurecon did not have any beneficial effect on how team members communicate. It was concluded that project teams would benefit from improved communication-planning processes that are more inclusive of their specific communication needs. Organisations working on high-performance projects will benefit directly from the research, which challenges these organisations to think more broadly about how they plan for communication at a project level. The research provides practical suggestions for improving the way that teams plan their communication processes; and it does so by focusing on the communication needs of the team members. Recommendations are made to professional bodies, tertiary institutions, project organisations – and most importantly – to project team members themselves. The recommendations to project team members include taking ownership of communication practices, asserting their views, as well as making their needs known

Proteomic risk markers for coronary heart disease and stroke: validation and mediation of randomized trial hormone therapy effects on these diseases

Background: We previously reported mass spectrometry-based proteomic discovery research to identify novel plasma proteins related to the risk of coronary heart disease (CHD) and stroke, and to identify proteins with concentrations affected by the use of postmenopausal hormone therapy. Here we report CHD and stroke risk validation studies for highly ranked proteins, and consider the extent to which protein concentration changes relate to disease risk or provide an explanation for hormone therapy effects on these outcomes. Methods: Five proteins potentially associated with CHD (beta-2 microglobulin (B2M), alpha-1-acid glycoprotein 1 (ORM1), thrombospondin-1(THBS1), complement factor D pre-protein (CFD), and insulin-like growth factor binding protein 1 (IGFBP1)) and five potentially associated with stroke (B2M, IGFBP2, IGFBP4, IGFBP6, and hemopexin (HPX)) had high discovery phase significance level ranking and an available ELISA assay, and were included in case-control validation studies within the Women’s Health Initiative (WHI) hormone therapy trials. Protein concentrations, at baseline and 1 year following randomization, were assessed for 358 CHD cases and 362 stroke cases, along with corresponding disease-free controls. Disease association, and mediation of estrogen-alone and estrogen plus progestin effects on CHD and stroke risk, were assessed using logistic regression. Results: B2M, THBS1, and CFD were confirmed (P <0.05) as novel CHD risk markers, and B2M, IGFBP2, and IGFBP4 were confirmed as novel stroke disease risk markers, while the assay for HPX proved to be unreliable. The change from baseline to 1 year in B2M was associated (P <0.05) with subsequent stroke risk, and trended similarly with subsequent CHD risk. Change from baseline to 1 year in IGFBP1 was also associated with CHD risk, and this change provided evidence of hormone therapy effect mediation. Conclusions: Plasma B2M is confirmed to be an informative risk marker for both CHD and stroke. The B2M increase experienced by women during the first year of hormone therapy trial participation conveys cardiovascular disease risk. The increase in IGFBP1 similarly conveys CHD risk, and the magnitude of the IGFBP1 increase following hormone therapy may be a mediator of hormone therapy effects. Plasma THBS1 and CFD are confirmed as CHD risk markers, and plasma IGFBP4 and IGFBP2 are confirmed as stroke risk markers. Clinical trials registration ClinicalTrials.gov identifier: NCT0000061

Genetic variants in the MRPS30 region and postmenopausal breast cancer risk

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Sex hormone associations with breast cancer risk and the mediation of randomized trial postmenopausal hormone therapy effects

Introduction: Paradoxically, a breast cancer risk reduction with conjugated equine estrogens (CEE) and a risk elevation with CEE plus medroxyprogesterone acetate (CEE + MPA) were observed in the Women’s Health Initiative (WHI) randomized controlled trials. The effects of hormone therapy on serum sex hormone levels, and on the association between baseline sex hormones and disease risk, may help explain these divergent breast cancer findings. Methods: Serum sex hormone concentrations were measured for 348 breast cancer cases in the CEE + MPA trial and for 235 cases in the CEE trial along with corresponding pair-matched controls, nested within the WHI trials of healthy postmenopausal women. Association and mediation analyses, to examine the extent to which sex hormone levels and changes can explain the breast cancer findings, were conducted using logistic regression. Results: Following CEE treatment, breast cancer risk was associated with higher concentrations of baseline serum estrogens, and with lower concentrations of sex hormone binding globulin. However, following CEE + MPA, there was no association of breast cancer risk with baseline sex hormone levels. The sex hormone changes from baseline to year 1 provided an explanation for much of the reduced breast cancer risk with CEE. Specifically, the treatment odds ratio (95% confidence interval) increased from 0.71 (0.43, 1.15) to 0.92 (0.41, 2.09) when the year 1 measures were included in the logistic regression analysis. In comparison, the CEE + MPA odds ratio was essentially unchanged when these year 1 measures were included. Conclusions: Breast cancer risk remains low following CEE use among women having favorable baseline sex hormone profiles, but CEE + MPA evidently produces a breast cancer risk for all women similar to that for women having an unfavorable baseline sex hormone profile. These patterns could reflect breast ductal epithelial cell stimulation by CEE + MPA that is substantially avoided with CEE, in conjunction with relatively more favorable effects of either regimen following a sustained period of estrogen deprivation. These findings may have implications for other hormone therapy formulations and routes of delivery. Trial registration clinicaltrials.gov identifier: NCT00000611

Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events.

Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women\u27s Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratioor =2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL rati