MULTIPLE DISEASES IN CARRIER PROBABILITY ESTIMATION: ACCOUNTING FOR SURVIVING ALL CANCERS OTHER THAN BREAST AND OVARY IN BRCAPRO

Mendelian models can predict who carries an inherited deleterious mutation of known disease genes based on family history. For example, the BRCAPRO model is commonly used to identify families who carry mutations of BRCA1 and BRCA2, based on familial breast and ovarian cancers. These models incorporate the age of diagnosis of diseases in relatives and current age or age of death. We develop a rigorous foundation for handling multiple diseases with censoring. We prove that any disease unrelated to mutations can be excluded from the model, unless it is sufficiently common and dependent on a mutation-related disease time. Furthermore, if a family member has a disease with higher probability density among mutation carriers, but the model does not account for it, then the carrier probability is deflated. However, even if a family only has diseases the model accounts for, if the model excludes a mutation-related disease, then the carrier probability will be inflated. In light of these results, we extend BRCAPRO to account for surviving all non-breast/ovary cancers as a single outcome. The extension also enables BRCAPRO to extract more useful information from male relatives. Using 1500 familes from the Cancer Genetics Network, accounting for surviving other cancers improves BRCAPRO’s concordance index from 0.758 to 0.762 (p = 0.046), improves its positive predictive value from 35% to 39% (p < 10−6) without impacting its negative predictive value, and improves its overall calibration, although calibration slightly worsens for those with carrier probability < 10%. Copyright c 2000 John Wiley & Sons, Ltd.

Accounting for warping and differential drying shrinkage mechanisms in the design of jointed plain concrete payments

When a concrete slab experiences differential volume change due to temperature, moisture, and shrinkage gradients, it deforms. The stresses induced by these differential volume changes can reduce the pavement’s fatigue life. Differential volume change is quantified by the equivalent temperature difference required to deform a comparable flat slab to the same shape as the actual slab. This thesis presents models to predict the equivalent temperature difference due to moisture warping and differential drying shrinkage. Moisture warping occurs because a portion of drying shrinkage is reversible, while differential drying shrinkage is due to the irreversible portion of drying shrinkage. The amount of reversible shrinkage was investigated for concretes made with different types of aggregate, including lightweight and recycled. Another source of differential volume change is built-in curl, which is caused by temperature gradients at the time of paving. This thesis also presents a comparison of methods used to quantify built-in curl.

Analysts' Forecast Accuracy in Germany: The Effect of Different Accounting Principles and Changes of Accounting Principles

This paper assesses the influence of an adoption of IAS/IFRS or US GAAP on the financial analysts’ forecast accuracy in a homogenous institutional framework. Our findings suggest that the forecast accuracy is higher for estimates based on IFRS or US GAAP data than for forecasts based on German GAAP data.Moreover, in the year of switching from German GAAP to US GAAP the forecast accuracy is lower than in other years. The paper contributes to prior research by providing evidence about the usefulness of international accounting data and about the adoption effects of a change to such accounting principles.

A Simple Accounting-based Valuation Model for the Debt Tax Shield

This paper describes a simple way to integrate the debt tax shield into an accounting-based valuation model. The market value of equity is determined by forecasting residual operating income, which is calculated by charging operating income for the operating assets at a required return that accounts for the tax benefit that comes from borrowing to raise cash for the operations. The model assumes that the firm maintains a deterministic financial leverage ratio, which tends to converge quickly to typical steady-state levels over time. From a practical point of view, this characteristic is of particular help, because it allows a continuing value calculation at the end of a short forecast period.

Decision-usefulness of ideal cost- and ideal value accounting for valuation and stewardship

This paper contrasts the decision-usefulness of prototype accounting regimes based on perfect accounting for value, i.e. ideal value accounting (IVA), and perfect matching of cost, i.e. ideal cost accounting (ICA). The regimes are analyzed in the context of a firm with overlapping capacity investments where projects earn excess returns and residual income is utilized as performance indicator. Provided that IVA and ICA systematically differ based on the criterion of unconditional conservatism, we assess their respective decision-usefulness for different valuation- and stewardship-scenarios. Assuming that addressees solely observe current accounting data of the firm, ICA provides information which is useful for valuation and stewardship without reservation whereas IVA entails problems under specific assumptions.

Accounting for baseline differences and measurement error in the analysis of change over time

If change over time is compared in several groups, it is important to take into account baseline values so that the comparison is carried out under the same preconditions. As the observed baseline measurements are distorted by measurement error, it may not be sufficient to include them as covariate. By fitting a longitudinal mixed-effects model to all data including the baseline observations and subsequently calculating the expected change conditional on the underlying baseline value, a solution to this problem has been provided recently so that groups with the same baseline characteristics can be compared. In this article, we present an extended approach where a broader set of models can be used. Specifically, it is possible to include any desired set of interactions between the time variable and the other covariates, and also, time-dependent covariates can be included. Additionally, we extend the method to adjust for baseline measurement error of other time-varying covariates. We apply the methodology to data from the Swiss HIV Cohort Study to address the question if a joint infection with HIV-1 and hepatitis C virus leads to a slower increase of CD4 lymphocyte counts over time after the start of antiretroviral therapy.

Estimating Diagnostic Test Accuracies for Brachyspira hyodysenteriae Accounting for the Complexities of Population Structure in Food Animals

For swine dysentery, which is caused by Brachyspira hyodysenteriae infection and is an economically important disease in intensive pig production systems worldwide, a perfect or error-free diagnostic test ("gold standard") is not available. In the absence of a gold standard, Bayesian latent class modelling is a well-established methodology for robust diagnostic test evaluation. In contrast to risk factor studies in food animals, where adjustment for within group correlations is both usual and required for good statistical practice, diagnostic test evaluation studies rarely take such clustering aspects into account, which can result in misleading results. The aim of the present study was to estimate test accuracies of a PCR originally designed for use as a confirmatory test, displaying a high diagnostic specificity, and cultural examination for B. hyodysenteriae. This estimation was conducted based on results of 239 samples from 103 herds originating from routine diagnostic sampling. Using Bayesian latent class modelling comprising of a hierarchical beta-binomial approach (which allowed prevalence across individual herds to vary as herd level random effect), robust estimates for the sensitivities of PCR and culture, as well as for the specificity of PCR, were obtained. The estimated diagnostic sensitivity of PCR (95% CI) and culture were 73.2% (62.3; 82.9) and 88.6% (74.9; 99.3), respectively. The estimated specificity of the PCR was 96.2% (90.9; 99.8). For test evaluation studies, a Bayesian latent class approach is well suited for addressing the considerable complexities of population structure in food animals.

On the right path? Land concessions in Laos

Land investment is booming in Laos, driven especially by demand for resources among its rapidly developing neighbours. Still, Laos remains one of the poorest countries in Southeast Asia. The government hopes that projects linked to land investments will improve local productivity, infrastructure, and poverty rates. But there are many risks to local livelihoods and the environment. Ensuring that land investment truly benefits the broader population demands effective regulation and strong political will. This policy brief provides key insights and recommendations drawn from the national inventory of land concessions and leases, the most comprehensive accounting of such land deals to date for a single country.