Genetic Testing for Breast and Ovarian Cancer: Implications for Life Insurance

As the science of genetic testing progresses, the debate surrounding the uses of genetic information intensifies. In February, President Clinton signed an executive order prohibiting federal agencies from using such information to make hiring, promotion, or placement decisions. Concerns about privacy and discrimination have led many states to propose or enact statutes that prohibit health insurers from using genetic test results in their underwriting decisions. However, few statutes address access to these results by the life insurance industry. This Issue Brief summarizes the current debate on whether life insurers should have access to genetic testing information for breast and ovarian cancer, and provides actuarial insight into the potential effect of such testing on the voluntary term insurance market

Price Elasticity of Demand for Term Life Insurance and Adverse Selection

This paper provides an empirical estimate of price' and risk' elasticities of demand for term life insurance for those who purchase some insurance. It finds that the elasticity with respect to changes in premiums is generally higher than the elasticity with respect to changes in risk. It also finds that the elasticity, in the range of -0.3 to -0.5, is sufficiently low that adverse selection in term life insurance is unlikely to lead to a death spiral and may not even lead to measured effects of adverse selection on total purchases.

Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals.

Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

An economic analysis of demutualization in the insurance industry

The insurance industry is currently experiencing a wave of organizational structure changes as many property-liability and life-health mutual companies are converting to stock charter, a process known as demutualization. Given the long-lived coexistence of mutuals and stocks, these conversions are receiving attention from regulators, investors and consumers. This dissertation focuses on the demutualization process and investigates why certain mutuals undergo this change. The primary motivation for conversion is access to capital. By statute, mutual firms are limited in their capital-raising activities while stock firms can attract funds through a variety of stock and debt offerings. The creation of a tradable currency allows the financial market to reward efficient behavior and enhances the effectiveness of management incentive compensation plans. Demutualization may also be motivated by the potential for efficiency gains. Improvements in efficiency can be realized with a reallocation of resources, which may not be possible under the mutual organizational form. Mutual managers may recognize the potential for efficiency gains, but not expend the effort since they would not receive the commensurate compensation. Demutualization creates the proper incentives. By examining the financial characteristics of firms that demutualize, changes in business practices in the years surrounding conversion can be observed. To facilitate the appropriate comparisons, control samples of mutual insurers and stock insurers are identified. Data are obtained from annual financial statements; variables measuring performance and business focus are constructed. Determinants of the conversion decision are explored through logistic regression. Using Data Envelopment Analysis, efficiency levels are estimated. In the years before demutualization, converting property-liability mutuals have significantly lower surplus-to-asset ratios; this capital constraint eases after conversion. No other performance changes are observed. These firms experience little efficiency gain in the year after demutualization, possibly since they require time to adjust to the stock organizational form. Converting life-health mutuals hold a significantly lower proportion of liquid assets; in addition, they have a higher proportion of separate accounts under management. This liquidity constraint and increased focus on a higher managerial discretion activity drive the demutualization decision. For both property-liability and life-health converting mutuals, support for the access to capital hypothesis is found

An economic analysis of demutualization in the insurance industry

The insurance industry is currently experiencing a wave of organizational structure changes as many property-liability and life-health mutual companies are converting to stock charter, a process known as demutualization. Given the long-lived coexistence of mutuals and stocks, these conversions are receiving attention from regulators, investors and consumers. This dissertation focuses on the demutualization process and investigates why certain mutuals undergo this change. The primary motivation for conversion is access to capital. By statute, mutual firms are limited in their capital-raising activities while stock firms can attract funds through a variety of stock and debt offerings. The creation of a tradable currency allows the financial market to reward efficient behavior and enhances the effectiveness of management incentive compensation plans. Demutualization may also be motivated by the potential for efficiency gains. Improvements in efficiency can be realized with a reallocation of resources, which may not be possible under the mutual organizational form. Mutual managers may recognize the potential for efficiency gains, but not expend the effort since they would not receive the commensurate compensation. Demutualization creates the proper incentives. By examining the financial characteristics of firms that demutualize, changes in business practices in the years surrounding conversion can be observed. To facilitate the appropriate comparisons, control samples of mutual insurers and stock insurers are identified. Data are obtained from annual financial statements; variables measuring performance and business focus are constructed. Determinants of the conversion decision are explored through logistic regression. Using Data Envelopment Analysis, efficiency levels are estimated. In the years before demutualization, converting property-liability mutuals have significantly lower surplus-to-asset ratios; this capital constraint eases after conversion. No other performance changes are observed. These firms experience little efficiency gain in the year after demutualization, possibly since they require time to adjust to the stock organizational form. Converting life-health mutuals hold a significantly lower proportion of liquid assets; in addition, they have a higher proportion of separate accounts under management. This liquidity constraint and increased focus on a higher managerial discretion activity drive the demutualization decision. For both property-liability and life-health converting mutuals, support for the access to capital hypothesis is found

An economic analysis of demutualization in the insurance industry

The insurance industry is currently experiencing a wave of organizational structure changes as many property-liability and life-health mutual companies are converting to stock charter, a process known as demutualization. Given the long-lived coexistence of mutuals and stocks, these conversions are receiving attention from regulators, investors and consumers. This dissertation focuses on the demutualization process and investigates why certain mutuals undergo this change. The primary motivation for conversion is access to capital. By statute, mutual firms are limited in their capital-raising activities while stock firms can attract funds through a variety of stock and debt offerings. The creation of a tradable currency allows the financial market to reward efficient behavior and enhances the effectiveness of management incentive compensation plans. Demutualization may also be motivated by the potential for efficiency gains. Improvements in efficiency can be realized with a reallocation of resources, which may not be possible under the mutual organizational form. Mutual managers may recognize the potential for efficiency gains, but not expend the effort since they would not receive the commensurate compensation. Demutualization creates the proper incentives. By examining the financial characteristics of firms that demutualize, changes in business practices in the years surrounding conversion can be observed. To facilitate the appropriate comparisons, control samples of mutual insurers and stock insurers are identified. Data are obtained from annual financial statements; variables measuring performance and business focus are constructed. Determinants of the conversion decision are explored through logistic regression. Using Data Envelopment Analysis, efficiency levels are estimated. In the years before demutualization, converting property-liability mutuals have significantly lower surplus-to-asset ratios; this capital constraint eases after conversion. No other performance changes are observed. These firms experience little efficiency gain in the year after demutualization, possibly since they require time to adjust to the stock organizational form. Converting life-health mutuals hold a significantly lower proportion of liquid assets; in addition, they have a higher proportion of separate accounts under management. This liquidity constraint and increased focus on a higher managerial discretion activity drive the demutualization decision. For both property-liability and life-health converting mutuals, support for the access to capital hypothesis is found

Estimating adverse selection costs from genetic testing for breast and ovarian cancer: The case of life insurance

Genetic testing is a concern for insurers if they cannot use test results in underwriting. We model adverse selection in an insurance market with genetic testing for breast and ovarian cancer. Increased forces of mortality resulting from a family history of cancer or a positive test for a BRCA mutation are calculated. Using a Markov model, we estimate costs of adverse selection, assuming various testing and insurance purchase behaviors. Adverse selection should be controllable if companies apply strict underwriting rules, requesting cancer history and onset age for all first-degree relatives. If insurers fail to correctly identify the family history of the application and use it in pricing, adverse selection costs could become unbearable. GENETIC TESTING AND THE FEAR OF ADVERSE SELECTION Adverse selection can be defined as the process by which prospective policyholders may gain financial advantage through insurance purchase decisions based on risk characteristics known to them, but unknown and not revealed to the insurer. It is a source of concern for insurance companies because it could result in underpricing. Recent developments in the Human Genome Project, while offering medical prom

Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals.

Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells