A Case Study of Long QT Regulation: A Regulatory Tennis Game Across the Atlantic

This paper has been written in a context of vivid transatlantic discussions about regulation and precaution. The study is looking at a specific and topical issue of drug safety regulation, the so‐called QT interval. The QT interval is commonly described as a reflection of how long it takes to “recharge” heart cells after they have been stimulated to beat, and it has been argued that both natural and drug induced lengthening of this interval may lead to a increased risk of death. The paper is based on interviews with all the major regulatory bodies responsible for the regulation of QT prolongation. The research focused on a number of key questions, starting with the “story” behind present QT regulation. It describes the debates that emerged in the 1992s about the significance of QT variations, and the existing level of uncertainty, on whether long QT is something we should worry about or not. Looking at the QT regulation story, no doubt the regulator answered this question by “yes”. However, there are still some divergences about the magnitude of the risk between experts and non experts, between Europeans and Americans, between ‘insiders’ and ‘outsiders’, which the paper explores in its complexity. Finally, the paper is introducing a conceptual model to analyse these developments, the so‐called “regulatory tennis game” that shaped the present regulation. It is also stressing some of the intrinsic problems of the “expert driven bi‐partite model” for making evidence based decisions about risk.     

Short PR interval

A short PR interval may be associated with an otherwise normal electrocardiogram or a myriad of bizarre electrocardiographic abnormalities. Clinically, the individual may be asymptomatic or experience a variety of complex arrhythmias, which may be disabling and rarely cause sudden death. In life insurance applicants, it is important to recognize these abnormalities and to assess their risk appropriately.     

The association between the length of the QT interval and mortality in the Cardiovascular Health Study: a mortality analysis

Prolonged QT interval was found to be associated with increased cardiac and all-cause mortality in a subgroup of the Cardiovascular Health Study (CHS). A mortality analysis is presented of this study, underscoring the need to use the appropriate expected group.     

Tall R wave in lead V1

Tall R waves in lead V1 present the life insurance company medical director with a diagnostic dilemma. This ECG pattern may be present in applicants with right bundle branch block, right ventricular hypertrophy, Wolff-Parkinson-White syndrome, posterior myocardial infarction, hypertrophic cardiomyopathy, muscular dystrophy, dextrocardia, misplaced precordial leads, as well as in normal individuals. This ECG case study discusses the ECG features involved in the differential diagnosis.     

Early repolarization ECG pattern--still a benign finding?

A life insurance applicant with an early repolarization pattern on his electrocardiogram (ECG) previously assessed as a standard risk, wishes to increase the amount of his coverage. The risk assessment implications of recent studies of early repolarization ECG patterns are reviewed.     

Mechanisms for improving reliability and reducing risk by stochastic and deterministic separation

The paper provides for the first time a comprehensive introduction into the mechanisms through which the method of separation achieves risk reduction and into the ways it can be implemented in engineering designs. The concept stochastic separation of critical random events on a time interval, which consists of guaranteeing with a specified probability a specified degree of distancing between the random events, is introduced. Efficient methods for providing stochastic separation by reducing the duration times of overlapping critical random events on a time interval are presented. The paper shows that the probability of overlapping of critical events, randomly appearing on a time interval, is practically insensitive to the distribution of their duration times and to the variance of the duration times as long as the mean of the duration times remains the same. A rigorous proof is presented that this statement is valid even for two random events on a time interval. The paper also provides insight into various mechanisms through which deterministic separation improves reliability and reduces risk. It is demonstrated that the separation on properties is an efficient technique for compensating the drawbacks associated with homogeneous properties. It is demonstrated that improving reliability by including redundancy, improving reliability by segmentation and some of the deliberate weak link techniques and stress limiters techniques for reducing risk are effectively special cases of a deterministic separation. Finally, the paper demonstrates that in a number of cases, the way to extract benefit from the method of separation is to build and analyse a mathematical model based on the method of separation. A comprehensive classification of the discussed methods for stochastic and deterministic separation is also presented.     

Giant negative T waves

Marked T wave inversion in a life insurance applicant's ECG may suggest high risk. Careful analysis of the ECG, an informative attending physician statement, and judicious use of additional testing allows the medical director to put this striking ECG abnormality in its proper context.     

Poor R-wave progression

Poor R-wave progression is a common ECG pattern, which is often inconclusively interpreted by medical directors. Although this ECG pattern is commonly attributed to anterior myocardial infarction, it may also be caused by left bundle branch block, Wolff-Parkinson-White syndrome, right and left ventricular hypertrophy as well as by faulty ECG recording technique. Failure to make a definitive interpretation of this pattern may result in a delay or loss of business.     

The Brugada syndrome--an electrocardiogram with important mortality implications

The electrocardiogram (ECG) is a valuable screening tool for increased risk in underwriting life insurance applicants. This article discusses a recently described ECG pattern associated with a high risk of sudden unexpected death.     

Mortgage contract design and systemic risk immunization

This paper provides theoretical results for the design of contracts used in the market for residential household mortgages and mortgage securities. Critical elements in the problem of immunizing systemic risk through efficient contract design are identified. Using an extension of classical immunization theory, this paper demonstrates that systemic risk of long amortization mortgage contracts is reduced when term to maturity of the contract at origination is significantly less than the amortization period. In addition, incorporating prepayment and limited recourse default options into the mortgage contract increases systemic risk when compared with full recourse mortgage contracts having yield maintenance prepayment penalties. The theoretical results are used to evaluate the systemic risk management problems that have plagued the US mortgage funding system.     

A model for evaluating extreme risks with stochastic sustainability criteria: a case study of soil remediation on landfill sites

This article addresses the issue of risk management for extreme events. The term stochastic sustainability will be defined in relation to the risk management of extreme events. On the basis of stochastic sustainability, a risk evaluation function is defined as an efficient reserve to remedy contaminations just as a premium rating in insurance policy. A term of generalized safety loading is used as a key concept to evaluate the degree of extremeness of risk. A simple model of the environmental or infrastructure systems is used to illustrate the procedure of risk evaluation where stochastic sustainability is required in case of accidental

environmental contamination. A case study of soil contamination at landfill sites is presented as an example to test this risk evaluation function.     

Asymptomatic ST segment elevation

Asymptomatic ST segment elevation in a life insurance applicant's ECG raises several prognostically important possibilities such as myocardial infarction, pericarditis, Brugada syndrome and early repolarization. This ECG case study discusses the ECG features involved in the differential diagnosis.     

The limits of diversification when losses may be large

Recent results in value at risk analysis show that, for extremely heavy-tailed risks with unbounded distribution support, diversification may increase value at risk, and that generally it is difficult to construct an appropriate risk measure for such distributions. We further analyze the limitations of diversification for heavy-tailed risks. We provide additional insight in two ways. First, we show that similar non-diversification results are valid for a large class of risks with bounded support, as long as the risks are concentrated on a sufficiently large interval. The required length of the support depends on the number of risks available and on the degree of heavy-tailedness. Second, we relate the value at risk approach to more general risk frameworks. We argue that in markets for risky assets where the number of assets is limited compared with the (bounded) distribution support of the risks, unbounded heavy-tailed risks may provide a reasonable approximation. We suggest that this type of analysis may have a role in explaining various types of market failures in markets for assets with possibly large negative outcomes.     

Forecasting Intraday Volatility and Value-at-Risk with High-Frequency Data

In this paper, we develop modeling tools to forecast Value-at-Risk and volatility with investment horizons of less than one day. We quantify the market risk based on the study at a 30-min time horizon using modified GARCH models. The evaluation of intraday market risk can be useful to market participants (day traders and market makers) involved in frequent trading. As expected, the volatility features a significant intraday seasonality, which motivates us to include the intraday seasonal indexes in the GARCH models. We also incorporate realized variance (RV) and time-varying degrees of freedom in the GARCH models to capture more intraday information on the volatile market. The intrinsic tail risk index is introduced to assist with understanding the inherent risk level in each trading time interval. The proposed models are evaluated based on their forecasting performance of one-period-ahead volatility and Intraday Value-at-Risk (IVaR) with application to the 30 constituent stocks. We find that models with seasonal indexes generally outperform those without; RV can improve the out-of-sample forecasts of IVaR; student GARCH models with time-varying degrees of freedom perform best at 0.5 and 1 % IVaR, while normal GARCH models excel for 2.5 and 5 % IVaR. The results show that RV and seasonal indexes are useful to forecasting intraday volatility and Intraday VaR.     

区间数信息下的风险投资群决策评价研究

随着中国风险投资行业不断扩张,为了避免高风险,需要多位决策人员共同参与投资项目的评价。而决策人员面对复杂系统更适合以区间数给出评价。本文提出风险投资的3个评价指标,运用粒子群算法集结区间数信息,构建群决策全局最优偏好矩阵,采用可能度矩阵和排序向量法确定次序。最后的应用研究结果表明,该方法具有一定的可行性和科学性,有利于风险投资项目评价的发展。     

Optimal commodity asset allocation with a coherent market risk modeling

This paper fills a fundamental gap in commodity price risk management and optimal portfolio selection literatures by contributing a thorough reflection on trading risk modeling with a dynamic asset allocation process and under the supposition of illiquid and adverse market settings. This paper analyzes, from a portfolio managers' perspective, the performance of liquidity adjusted risk modeling in obtaining efficient and coherent investable commodity portfolios under normal and adverse market conditions. As such, the author argues that liquidity risk associated with the uncertainty of liquidating multiple commodity assets over given holding periods is a key factor in formalizing and measuring overall trading risk and is thus an important component to model, particularly in the wake of the repercussions of the recent 2008 financial crisis. To this end, this article proposes a practical technique for the quantification of liquidity trading risk for large portfolios that consist of multiple commodity assets and whereby the holding periods are adjusted according to the specific needs of each trading portfolio. Specifically, the paper proposes a robust technique to commodity optimal portfolio selection, in a liquidity-adjusted value-at-risk (L-VaR) framework, and particularly from the perspective of large portfolios that have both long and short positions or portfolios that consist of merely pure long trading positions. Moreover, in this paper, the author develops a portfolio selection model and an optimization-algorithm which allocates commodity assets by minimizing the L-VaR subject to applying credible operational and financial constraints based on fundamental asset management considerations. The empirical optimization results indicate that this alternate L-VaR technique can be regarded as a robust portfolio management tool and can have many uses and applications in real-world asset management practices and predominantly for fund managers with large commodity portfolios.     

EBCT measured coronary artery calcium scores in asymptomatic life insurance applicants

EBCT measured coronary calcium is fast becoming a standard screening tool in asymptomatic patients with and without risk factors who apply for life insurance. Since atherosclerotic plaques become calcified as part of their natural history, the calcium score is an excellent measure of total atherosclerotic burden. Over the past 5 years, various clinical studies have confirmed the predictive value of the coronary calcium score for both soft (revascularization, MI) and hard (MI and sudden cardiac death) events incrementally and independently of traditional coronary risk factors identified by the Framingham Heart Study. Accurate assessment of cardiac mortality risk in asymptomatic applicants for life insurance should include both traditional risk factor assessments in combination with age and gender specific percentiles for coronary calcium. New data from both new and ongoing clinical trials will seek to further support the predictive value of coronary calcium scores as an independent and incremental predictor of hard cardiac events.     

Myocardial infarction or technical artifact?

Misplacement of recording electrodes can generate misleading patterns on the standard 12-lead electrocardiogram (ECG). Some lead placement errors are easily recognizable, others are more difficult to detect and can be quite important in risk selection because the resulting changes in ECG morphology can mimic other conditions such as myocardial infarction. Therefore, identification of incorrectly performed ECGs is an important task for the medical director.     

The role of negative associations and trust in risk perception of new hydrogen systems

In this study the moderating role of trust and negative affective associations on the inverse relationship between risk and benefit judgements is investigated. A survey (N = 406) was held in the Netherlands on the public perception of new hydrogen systems, during the time that a demonstration project with hydrogen buses was being undertaken. The data of the survey show that for the group of respondents with a negative evaluation of trust in actors involved, an inverse relationship between risk and benefit judgements can be observed. Furthermore, for the group of respondents that had elicited negative affective spontaneous associations with hydrogen in general, the inverse relationship was also found. The inverse relationship between risk and benefit judgements was not observed in the group not making these spontaneous associations. The strongest negative correlation between risk and benefit judgements was found for those who had a negative evaluation of trust and had elicited negative affective spontaneous associations. In all cases the general affective evaluation of hydrogen systems was the mediating factor in this inverse relationship between risk and benefit judgements. These findings provide evidence for the moderating role of trust and negative affective associations on the observed inverse relationship between perceived benefit and perceived risk.     

The Theory and Practice of Corporate Risk Management*

The financial crisis of 2008 and the resulting recession caught many companies unprepared and, in so doing, provided a stark reminder of the importance of effective risk management. While academic theory has long touted the benefits of risk management, companies have varied greatly in the ways and extent to which they put theory into practice. Drawing on a global survey of over 300 CFOs of non‐financial companies, the authors report that while most CFOs felt that their risk management programs have significant benefits, the risk management function in general needs more attention. A large percentage of the finance executives surveyed acknowledged that the most important corporate risks extend far beyond the CFO's direct reports, and that risk‐based thinking is not incorporated into everyday business activities or corporate strategies. A large majority of executives also said they were seeking a more widespread understanding of risk throughout their organizations—and many confessed their firms' inability, or lack of interest, in evaluating their own risk management functions. At the same time, the efforts of most companies to develop enterprise‐wide risk management (ERM) programs were said to fall well short of the comprehensive and highly coordinated programs envisioned by the proponents of such programs. Three areas of opportunity were clearly identified as having potential to improve corporate risk management in ways that increase firm value over an entire business cycle:

• ? Incorporate risk management thinking into the strategic planning process. Line executives, and not just technicians, need to be sensitive to risks, thereby building flexibility into the firm's business plan and its execution.
• ? Clearly define the objectives of the risk management function, in part by developing appropriate benchmarks. The risk management process should be subject to the same rigorous evaluation process that is used when measuring risks throughout the business.
• ? Instill a risk management culture throughout the organization. While an effective risk management function is necessary, only when employees at all levels of the company embrace risk management as part of their daily operations will the firm get maximum value from risk management.