Genetic testing with primary prevention and moral hazard

We develop a model where a free genetic test reveals whether the individual tested has a low or high probability of developing a disease. A costly prevention effort allows high-risk agents to decrease the probability of developing the disease. Agents are not obliged to take the test, but must disclose its results to insurers. Insurers offer separating contracts which take into account the individual risk, so that taking the test is associated to a discrimination risk. We study the individual decisions to take the test and to undertake the prevention effort as a function of the effort cost and of its e¢ ciency. We obtain that, if effort is observable by insurers, agents undertake the test only if the effort cost is neither too large nor too low. If the effort cost is not observable by insurers, they face a moral hazard problem which induces them to under-provide insurance. We obtain the counterintuitive result that moral hazard increases the value of the test if the effort cost is low enough. Also, agents may perform the test for lower levels of prevention e¢ ciency when effort is not observable

Risk-assessment practices in the private rental sector : implications for low-income renters (Final Report)

This report focuses on risk-assessment practices in the private rental market, with particular consideration of their impact on low-income renters. It is based on the fieldwork undertaken in the second stage of the research process that followed completion of the Positioning Paper. The key research question this study addressed was: What are the various factors included in ‘risk-assessments’ by real estate agents in allocating ‘affordable’ tenancies? How are these risks quantified and managed? What are the key outcomes of their decision-making? The study builds on previous research demonstrating that a relatively large proportion of low-cost private rental accommodation is occupied by moderate- to high-income households (Wulff and Yates 2001; Seelig 2001; Yates et al. 2004). This is occurring in an environment where the private rental sector is now the de facto main provider of rental housing for lower-income households across Australia (Seelig et al. 2005) and where a number of factors are implicated in patterns of ‘income–rent mismatching’. These include ongoing shifts in public housing assistance; issues concerning eligibility for rent assistance; ‘supply’ factors, such as loss of low-cost rental stock through upgrading and/or transfer to owner-occupied housing; patterns of supply and demand driven largely by middle- to high-income owner-investors and renters; and patterns of housing need among low-income households for whom affordable housing is not appropriate. In formulating a way of approaching the analysis of ‘risk-assessment’ in rental housing management, this study has applied three sociological perspectives on risk: Beck’s (1992) formulation of risk society as entailing processes of ‘individualisation’; a socio-cultural perspective which emphasises the situated nature of perceptions of risk; and a perspective which has drawn attention to different modes of institutional governance of subjects, as ‘carriers of specific indicators of risk’. The private rental market was viewed as a social institution, and the research strategy was informed by ‘institutional ethnography’ as a method of enquiry. The study was based on interviews with property managers, real estate industry representatives, tenant advocates and community housing providers. The primary focus of inquiry was on ‘the moment of allocation’. Six local areas across metropolitan and regional Queensland, New South Wales, and South Australia were selected as case study localities. In terms of the main findings, it is evident that access to private rental housing is not just a matter of ‘supply and demand’. It is also about assessment of risk among applicants. Risk – perceived or actual – is thus a critical factor in deciding who gets housed, and how. Risk and its assessment matter in the context of housing provision and in the development of policy responses. The outcomes from this study also highlight a number of salient points: 1.There are two principal forms of risk associated with property management: financial risk and risk of litigation. 2. Certain tenant characteristics and/or circumstances – ability to pay and ability to care for the rented property – are the main factors focused on in assessing risk among applicants for rental housing. Signals of either ‘(in)ability to pay’ and/or ‘(in)ability to care for the property’ are almost always interpreted as markers of high levels of risk. 3. The processing of tenancy applications entails a complex and variable mix of formal and informal strategies of risk-assessment and allocation where sorting (out), ranking, discriminating and handing over characterise the process. 4. In the eyes of property managers, ‘suitable’ tenants can be conceptualised as those who are resourceful, reputable, competent, strategic and presentable. 5. Property managers clearly articulated concern about risks entailed in a number of characteristics or situations. Being on a low income was the principal and overarching factor which agents considered. Others included: - unemployment - ‘big’ families; sole parent families - domestic violence - marital breakdown - shift from home ownership to private rental - Aboriginality and specific ethnicities - physical incapacity - aspects of ‘presentation’. The financial vulnerability of applicants in these groups can be invoked, alongside expressed concerns about compromised capacities to manage income and/or ‘care for’ the property, as legitimate grounds for rejection or a lower ranking. 6. At the level of face-to-face interaction between the property manager and applicants, more intuitive assessments of risk based upon past experience or ‘gut feelings’ come into play. These judgements are interwoven with more systematic procedures of tenant selection. The findings suggest that considerable ‘risk’ is associated with low-income status, either directly or insofar as it is associated with other forms of perceived risk, and that such risks are likely to impede access to the professionally managed private rental market. Detailed analysis suggests that opportunities for access to housing by low-income householders also arise where, for example: - the ‘local experience’ of an agency and/or property manager works in favour of particular applicants - applicants can demonstrate available social support and financial guarantors - an applicant’s preference or need for longer-term rental is seen to provide a level of financial security for the landlord - applicants are prepared to agree to specific, more stringent conditions for inspection of properties and review of contracts - the particular circumstances and motivations of landlords lead them to consider a wider range of applicants - In particular circumstances, property managers are prepared to give special consideration to applicants who appear worthy, albeit ‘risky’. The strategic actions of demonstrating and documenting on the part of vulnerable (low-income) tenant applicants can improve their chances of being perceived as resourceful, capable and ‘savvy’. Such actions are significant because they help to persuade property managers not only that the applicant may have sufficient resources (personal and material) but that they accept that the onus is on themselves to show they are reputable, and that they have valued ‘competencies’ and understand ‘how the system works’. The parameters of the market do shape the processes of risk-assessment and, ultimately, the strategic relation of power between property manager and the tenant applicant. Low vacancy rates and limited supply of lower-cost rental stock, in all areas, mean that there are many more tenant applicants than available properties, creating a highly competitive environment for applicants. The fundamental problem of supply is an aspect of the market that severely limits the chances of access to appropriate and affordable housing for low-income rental housing applicants. There is recognition of the impact of this problem of supply. The study indicates three main directions for future focus in policy and program development: providing appropriate supports to tenants to access and sustain private rental housing, addressing issues of discrimination and privacy arising in the processes of selecting suitable tenants, and addressing problems of supply.

Female greater wax moths reduce sexual display behavior in relation to the potential risk of predation by echolocating bats

Female greater wax moths Galleria mellonella display by wing fanning in response to bursts of ultrasonic calls produced by males. The temporal and spectral characteristics of these calls show some similarities with the echolocation calls of bats that emit frequency-modulated (FM) signals. Female G. mellonella therefore need to distinguish between the attractive signals of male conspecifics, which may lead to mating opportunities, and similar sounds made by predatory bats. We therefore predicted that (1) females would display in response to playbacks of male calls; (2) females would not display in response to playbacks of the calls of echolocating bats (we used the calls of Daubenton's bat Myotis daubentonii as representative of a typical FM echolocating bat); and (3) when presented with male calls and bat calls during the same time block, females would display more when perceived predation risk was lower. We manipulated predation risk in two ways. First, we varied the intensity of bat calls to represent a nearby (high risk) or distant (low risk) bat. Second, we played back calls of bats searching for prey (low risk) and attacking prey (high risk). All predictions were supported, suggesting that female G. mellonella are able to distinguish conspecific male mating calls from bat calls, and that they modify display rate in relation to predation risk. The mechanism (s) by which the moths separate the calls of bat and moth must involve temporal cues. Bat and moth signals differ considerably in duration, and differences in duration could be encoded by the moth's nervous system and used in discrimination.

Using upper bounds on attainable discrimination to select discrete valued features

Selection of features that will permit accurate pattern classification is a difficult task. However, if a particular data set is represented by discrete valued features, it becomes possible to determine empirically the contribution that each feature makes to the discrimination between classes. This paper extends the discrimination bound method so that both the maximum and average discrimination expected on unseen test data can be estimated. These estimation techniques are the basis of a backwards elimination algorithm that can be use to rank features in order of their discriminative power. Two problems are used to demonstrate this feature selection process: classification of the Mushroom Database, and a real-world, pregnancy related medical risk prediction task - assessment of risk of perinatal death.

Feature selection using expected attainable discrimination

We propose expected attainable discrimination (EAD) as a measure to select discrete valued features for reliable discrimination between two classes of data. EAD is an average of the area under the ROC curves obtained when a simple histogram probability density model is trained and tested on many random partitions of a data set. EAD can be incorporated into various stepwise search methods to determine promising subsets of features, particularly when misclassification costs are difficult or impossible to specify. Experimental application to the problem of risk prediction in pregnancy is described.

HIV/AIDS-related institutional mistrust among multiethnic men who have sex with men: effects on HIV testing and risk behaviors.

OBJECTIVE: To investigate relationships between institutional mistrust (systematic discrimination, organizational suspicion, and conspiracy beliefs), HIV risk behaviors, and HIV testing in a multiethnic sample of men who have sex with men (MSM), and to test whether perceived susceptibility to HIV mediates these relationships for White and ethnic minority MSM. METHOD: Participants were 394 MSM residing in Central Arizona (M age = 37 years). Three dimensions of mistrust were examined, including organizational suspicion, conspiracy beliefs, and systematic discrimination. Assessments of sexual risk behavior, HIV testing, and perceived susceptibility to HIV were made at study entry (T1) and again 6 months later (T2). RESULTS: There were no main effects of institutional mistrust dimensions or ethnic minority status on T2 risk behavior, but the interaction of systematic discrimination and conspiracy beliefs with minority status was significant such that higher levels of systematic discrimination and more conspiracy beliefs were associated with increased risk only among ethnic minority MSM. Higher levels of systematic discrimination were significantly related to lower likelihood for HIV testing, and the interaction of organizational suspicion with minority status was significant such that greater levels of organizational suspicion were related to less likelihood of having been tested for HIV among ethnic minority MSM. Perceived susceptibility did not mediate these relationships. CONCLUSION: Findings suggest that it is important to look further into the differential effects of institutional mistrust across marginalized groups, including sexual and ethnic minorities. Aspects of mistrust should be addressed in HIV prevention and counseling efforts.

Importance of prostate volume in the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators: results from the prostate biopsy collaborative group.

OBJECTIVES: To compare the predictive performance and potential clinical usefulness of risk calculators of the European Randomized Study of Screening for Prostate Cancer (ERSPC RC) with and without information on prostate volume. METHODS: We studied 6 cohorts (5 European and 1 US) with a total of 15,300 men, all biopsied and with pre-biopsy TRUS measurements of prostate volume. Volume was categorized into 3 categories (25, 40, and 60 cc), to reflect use of digital rectal examination (DRE) for volume assessment. Risks of prostate cancer were calculated according to a ERSPC DRE-based RC (including PSA, DRE, prior biopsy, and prostate volume) and a PSA + DRE model (including PSA, DRE, and prior biopsy). Missing data on prostate volume were completed by single imputation. Risk predictions were evaluated with respect to calibration (graphically), discrimination (AUC curve), and clinical usefulness (net benefit, graphically assessed in decision curves). RESULTS: The AUCs of the ERSPC DRE-based RC ranged from 0.61 to 0.77 and were substantially larger than the AUCs of a model based on only PSA + DRE (ranging from 0.56 to 0.72) in each of the 6 cohorts. The ERSPC DRE-based RC provided net benefit over performing a prostate biopsy on the basis of PSA and DRE outcome in five of the six cohorts. CONCLUSIONS: Identifying men at increased risk for having a biopsy detectable prostate cancer should consider multiple factors, including an estimate of prostate volume.

Satellite discrimination of Karenia mikimotoi and Phaeocystis harmful algal blooms in European coastal waters: Merged classification of ocean colour data

The detection of dense harmful algal blooms (HABs) by satellite remote sensing is usually based on analysis of chlorophyll-a as a proxy. However, this approach does not provide information about the potential harm of bloom, nor can it identify the dominant species. The developed HAB risk classification method employs a fully automatic data-driven approach to identify key characteristics of water leaving radiances and derived quantities, and to classify pixels into “harmful”, “non-harmful” and “no bloom” categories using Linear Discriminant Analysis (LDA). Discrimination accuracy is increased through the use of spectral ratios of water leaving radiances, absorption and backscattering. To reduce the false alarm rate the data that cannot be reliably classified are automatically labelled as “unknown”. This method can be trained on different HAB species or extended to new sensors and then applied to generate independent HAB risk maps; these can be fused with other sensors to fill gaps or improve spatial or temporal resolution. The HAB discrimination technique has obtained accurate results on MODIS and MERIS data, correctly identifying 89% of Phaeocystis globosa HABs in the southern North Sea and 88% of Karenia mikimotoi blooms in the Western English Channel. A linear transformation of the ocean colour discriminants is used to estimate harmful cell counts, demonstrating greater accuracy than if based on chlorophyll-a; this will facilitate its integration into a HAB early warning system operating in the southern North Sea.

No association between hOGG1, XRCC1, and XPD polymorphisms and risk of reflux esophagitis, Barrett's Esophagus, or esophageal adenocarcinoma: Results from the factors influencing the Barrett's adenocarcinoma relationship case-control study

Reflux of gastric contents can lead to development of reflux esophagitis and Barrett's esophagus. Barrett's esophagus is a risk factor for esophageal adenocarcinoma. Damage to DNA may lead to carcinogenesis but is repaired through activation of pathways involving polymorphic enzymes, including human 8-oxoguanine glycosylase 1 (hOGG1), X-ray repair cross-complementing 1 (XRCC1), and xeroderma pigmentosum group D (XPD). Of the single nucleotide polymorphisms identified in these genes, hOGG1 Ser 326Cys, XRCC1 Arg 399Gln, and XPD Lys 751Gln are particularly common in Caucasians and have been associated with lower DNA repair capacity. Small studies have reported associations with XPD Lys 751Gln and esophageal adenocarcinoma. XRCC1 Arg 399Gln has been linked to Barrett's esophagus and reflux esophagitis. In a population-based case-control study, we examined associations of the hOGG1 Ser 326Cys, XRCC1 Arg 399Gln, and XPD Lys 751Gln polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Genomic DNA was extracted from blood samples collected from cases of esophageal adenocarcinoma (n = 210), Barrett's esophagus (n = 212), reflux esophagitis (n = 230), and normal population controls frequency matched for age and sex (n = 248). Polymorphisms were genotyped using Taq-Man allelic discrimination assays. Odds ratios and 95% confidence intervals were obtained from logistic regression models adjusted for potential confounding factors. There were no statistically significant associations between these polymorphisms and risk of esophageal adenocarcinoma, Barrett's esophagus, or reflux esophagitis.

Cyclooxygenase-2 and inducible nitric oxide synthase gene polymorphisms and risk of reflux esophagitis, Barrett's Esophagus, and esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma has increased in recent years, and Barrett's esophagus is a recognized risk factor. Gastroesophageal reflux of acid and/or bile is linked to these conditions and to reflux esophagitis. Inflammatory disorders can lead to carcinogenesis through activation of "prosurvival genes," including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Increased expression of these enzymes has been found in esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Polymorphic variants in COX-2 and iNOS genes may be modifiers of risk of these conditions. In a population-based case-control study, we examined associations of the COX-2 8473 T>C and iNOS Ser 608 Leu (C>T) polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Genomic DNA was extracted from blood samples collected from cases of esophageal adenocarcinoma (n = 210), Barrett's esophagus (n = 212), and reflux esophagitis (n = 230) and normal population controls frequency matched for age and sex (n = 248). Polymorphisms were genotyped using TaqMan allelic discrimination assays. Odds ratios and 95% confidence intervals were obtained from logistic regression models adjusted for potential confounding factors. The presence of at least one COX-2 8473 C allele was associated with a significantly increased risk of esophageal adenocarcinoma (adjusted odds ratio, 1.58; 95% confidence interval, 1.04-2.40). There was no significant association between this polymorphism and risk of Barrett's esophagus or reflux esophagitis or between the iNOS Ser 608 Leu polymorphism and risk of these esophageal conditions. Our study suggests that the COX-2 8473 C allele is a potential genetic marker for susceptibility to esophageal adenocarcinoma.

The less amorous Gammarus: predation risk affects mating decisions in Gammarus duebeni (Amphipoda)

We examined the trade-off between the behaviours associated with predator avoidance and mate acquisition in the mate-guarding amphipod crustacean Gammarus duebeni. We used laboratory experiments to investigate the impact of olfactory predator cues on activity, mate choice and mate-guarding behaviour of males and females. Pair formation declined under perceived risk of predation, reflecting reduced activity of both males and females and hence a reduced likelihood of encountering a mate. We also observed a reduction in the choosiness of both males and females. Under increased perceived predation risk, assessment of the female by the male was more likely to be followed by pair formation, and males showed a nonsignificant trend towards reduced discrimination in favour of large females and were less tenacious in their pair bond when they paired during exposure to predator cues. Females also showed less resistance behaviour, suggesting that both males and females trade off the costs of maximizing current reproductive success against the benefits of predator avoidance for survival and reproduction in the future. We discuss the implications of such context-dependent mating behaviours for ecological interactions between species and suggest that predators, via the effects of perceived predation risk on mate choice and mate guarding in the prey species, induce trait-mediated indirect effects with the potential to influence population dynamics and community structure. (C) 2008 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Contribution of 30 Biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: The MONICA, risk, genetics, archiving and monograph (MORGAM) biomarker project

Background— Cardiovascular risk estimation by novel biomarkers needs assessment in disease-free population cohorts, followed up for incident cardiovascular events, assaying the serum and plasma archived at baseline. We report results from 2 cohorts in such a continuing study.
Methods and Results— Thirty novel biomarkers from different pathophysiological pathways were evaluated in 7915 men and women of the FINRISK97 population cohort with 538 incident cardiovascular events at 10 years (fatal or nonfatal coronary or stroke events), from which a biomarker score was developed and then validated in the 2551 men of the Belfast Prospective Epidemiological Study of Myocardial Infarction (PRIME) cohort (260 events). No single biomarker consistently improved risk estimation in FINRISK97 men and FINRISK97 women and the Belfast PRIME Men cohort after allowing for confounding factors; however, the strongest associations (with hazard ratio per SD in FINRISK97 men) were found for N-terminal pro-brain natriuretic peptide (1.23), C-reactive protein (1.23), B-type natriuretic peptide (1.19), and sensitive troponin I (1.18). A biomarker score was developed from the FINRISK97 cohort with the use of regression coefficients and lasso methods, with selection of troponin I, C-reactive protein, and N-terminal pro-brain natriuretic peptide. Adding this score to a conventional risk factor model in the Belfast PRIME Men cohort validated it by improved c-statistics (P=0.004) and integrated discrimination (P<0.0001) and led to significant reclassification of individuals into risk categories (P=0.0008).
Conclusions— The addition of a biomarker score including N-terminal pro-brain natriuretic peptide, C-reactive protein, and sensitive troponin I to a conventional risk model improved 10-year risk estimation for cardiovascular events in 2 middle-aged European populations. Further validation is needed in other populations and age groups.

Genetic Markers Enhance Coronary Risk Prediction in Men: The MORGAM Prospective Cohorts

Background: More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design.

Methods: Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived.

Results: Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events.

Conclusions: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.

Risk, Recovery and Capacity: Competing or Complementary Approaches to Mental Health Social Work

Mental health social workers have a central role in providing support to people with mental health problems and in the use of coercion aimed at dealing with risk. Mental health services have traditionally focused on monitoring symptoms and ascertaining the risks people may present to themselves and/or others. This well-intentioned but negative focus on deficits has contributed to stigma, discrimination and exclusion experienced by service users. Emerging understandings of risk also suggest that our inability to accurately predict the future makes risk a problematic foundation for compulsory intervention. It is therefore argued that alternative approaches are needed to make issues of power and inequality transparent. This article focuses on two areas of practice: the use of recovery based approaches, which promote supported decision making and inclusion; and the assessment of a person’s ability to make decisions, their mental capacity, as a less discriminatory gateway criterion than risk for compulsory intervention.

Prediction of breast cancer risk based on profiling with common genetic variants

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.