Statins and the vasculopathy of systemic sclerosis: potential therapeutic agents?

It has been postulated that endothelial cell injury is the initiating event in the pathogenesis of systemic sclerosis, causing attraction, attachment, migration and infiltration of activated T-cells and subsequent production of cytokines and growth factors. As a result of the action of these cytokines and growth factors, chemoattraction of fibroblasts into the vessel wall and transdifferentiation of resident fibroblasts and smooth muscle cells into myofibroblasts occur leading to fibrosis and exaggerated collagen deposition in the vessel wall. To date, the therapeutic options for the vasculopathy of systemic sclerosis have been limited to drugs that cause vasodilation and inhibit platelet aggregation and only a few agents have shown vascular remodeling effects. Therapeutic agents that could potentially modify the course of this vasculopathy may have a disease-modifying effect, particularly, if instituted in the early stages of the disease. Extensive recent studies have shown that statins display numerous effects independent of their well-established lipid-lowering effect that may be of potential benefit in preventing vascular injury and ischemic vascular events. Here, we review the current literature, which suggests that statins may have a modifying effect on the vasculopathy of systemic sclerosis

Systemic sclerosis: current views of its pathogenesis.

Systemic sclerosis (SSc) is an autoimmune disorder of unknown etiology characterized by severe and often progressive cutaneous and visceral fibrosis, pronounced alterations in the microvasculature, and numerous cellular and humoral immune abnormalities. Clinically, SSc is very heterogeneous, encompassing a spectrum ranging from mild limited forms of skin sclerosis with minimal internal organ involvement to severe skin and multiple internal organ fibrosis. Mortality and morbidity in SSc are very high and are directly related to the extent of the fibrotic and microvascular alterations. A better understanding of the pathogenesis of this incurable disorder will help to better target and design effective therapy in the future

Fine-tuning a context-aware system application by using user-centred design methods

Context-Aware Systems in the home environment can provide an effective solution for supporting wellbeing and autonomy for the elderly. The definition and implementation of the system architecture for a particular assisted living healthcare application entail both technological and usability challenges. If issues regarding users’ concerns and desires are taken into account in the early stages of the system development users can benefit substantially more from this technology. In this paper, we describe our initial experiences with different user-centred design methods, as they are applied in the process of fine-tuning a context-aware system architecture to improve quality of life for elderly THR patients (Total Hip Replacement). The insights resulting from this approach result in a clearer functional specification towards a better fit with the user needs regarding information need of the patient as well as the physiotherapist. Important system requirements as timing and content of the feedback are much more fruitful in an earlier phase of the development process. User-centred design methods help to better understand the needed functional features of a context-aware system, thereby saving time and helping developers to improve adoption of the system by the users

What Happened to Risk Management During the 2008-09 Financial Crisis?

When dealing with market risk under the Basel II Accord, variation pays in the form of lower capital requirements and higher profits. Typically, GARCH type models are chosen to forecast Value-at-Risk (VaR) using a single risk model. In this paper we illustrate two useful variations to the standard mechanism for choosing forecasts, namely: (i) combining different forecast models for each period, such as a daily model that forecasts the supremum or infinum value for the VaR; (ii) alternatively, select a single model to forecast VaR, and then modify the daily forecast, depending on the recent history of violations under the Basel II Accord. We illustrate these points using the Standard and Poor’s 500 Composite Index. In many cases we find significant decreases in the capital requirements, while incurring a number of violations that stays within the Basel II Accord limits.risk management;violations;conservative risk strategy;aggressive risk strategy;value-at-risk forecast

GFC-Robust Risk Management Strategies under the Basel Accord

A risk management strategy is proposed as being robust to the Global Financial Crisis (GFC) by selecting a Value-at-Risk (VaR) forecast that combines the forecasts of different VaR models. The robust forecast is based on the median of the point VaR forecasts of a set of conditional volatility models. This risk management strategy is GFC-robust in the sense that maintaining the same risk management strategies before, during and after a financial crisis would lead to comparatively low daily capital charges and violation penalties. The new method is illustrated by using the S&P500 index before, during and after the 2008-09 global financial crisis. We investigate the performance of a variety of single and combined VaR forecasts in terms of daily capital requirements and violation penalties under the Basel II Accord, as well as other criteria. The median VaR risk management strategy is GFC-robust as it provides stable results across different periods relative to other VaR forecasting models. The new strategy based on combined forecasts of single models is straightforward to incorporate into existing computer software packages that are used by banks and other financial institutions.Value-at-Risk (VaR);daily capital charges;optimizing strategy;robust forecasts;violation penalties;global financial crisis;Basel II Accord;aggressive risk management strategy;conservative risk management strategy

A decision rule to minimize daily capital charges in forecasting value-at-risk

Under the Basel II Accord, banks and other Authorized Deposit-taking Institutions (ADIs) have to communicate their daily risk estimates to the monetary authorities at the beginning of the trading day, using a variety of Value-at-Risk (VaR) models to measure risk. Sometimes the risk estimates communicated using these models are too high, thereby leading to large capital requirements and high capital costs. At other times, the risk estimates are too low, leading to excessive violations, so that realised losses are above the estimated risk. In this paper we propose a learning strategy that complements existing methods for calculating VaR and lowers daily capital requirements, while restricting the number of endogenous violations within the Basel II Accord penalty limits. We suggest a decision rule that responds to violations in a discrete and instantaneous manner, while adapting more slowly in periods of no violations. We apply the proposed strategy to Standard & Poor’s 500 Index and show there can be substantial savings in daily capital charges, while restricting the number of violations to within the Basel II penalty limits.value-at-risk;daily capital charges;optimizing strategy;risk forecasts;endogenous violations;frequency of violations