From a different angle: A novel approach to health valuation

The value of a health state is typically described relative to the value of an optimal state, specifically as a ratio ranging from unity (equal to optimal health) to negative infinity. Incorporating potentially infinite values is a challenging issue in the econometrics of health valuation. In this paper, we apply a directional statistics approach based on the assumption of wavering preference. Unlike ratio statistics, directional statistics are based on polar coordinates (angle, radius). The range of angles is bounded between 45 degrees (unity) and negative 90 degrees (i.e., negative infinity); therefore, mean angles are well behaved and negate the impetus behind arbitrary data manipulations. Using time trade-off (TTO) responses from the seminal Measurement and Valuation of Health study, we estimate 243 EQ-5D health state values by minimizing circular variance with and without radial weights. For states with published values greater than zero (i.e., better-than-death), the radially weighted estimates are nearly identical to the published values (Mean Absolute Difference 0.07; Lin’s rho 0.94). For worse-than-death states, the estimates are substantially lower than the published values (Mean Absolute Difference 0.186; Lin’s rho 0.576). For the worst EQ-5D state (33333), the published value is -0.59 and the directional estimate is -1.11. By taking a directional statistics approach, we circumvent problems inherent to ratio statistics and the systematic bias introduced by arbitrary data manipulations. The predictions suggest that published estimates overvalue severe states. This paper examines TTO responses; however, it may be extended to all forms of health valuation

Keep it simple: ranking health states yields values similar to cardinal measurement approaches

Abstract OBJECTIVES: To examine the relationship between ordinal and cardinal valuation of health states. STUDY DESIGN AND SETTING: We analyzed rank, visual analog scale (VAS), and time trade-off (TTO) responses for 52 health states defined using the EQ-5D classification system developed by the EuroQol Group. We analyzed 179,431 responses from 11,483 subjects in eight countries: Slovenia, Argentina, Denmark, Japan, Netherlands, Spain, United Kingdom, and United States. We first compared responses across methods by frequency of ties and values below dead. Ordinal associations between methods were evaluated using Spearman's correlation and Kendall's tau. Next, we estimated numerical values from rank responses using country-specific conditional logit models. After anchoring predicted values on a common scale, we further investigated the cardinal relationships between rank, VAS, and TTO-based values using Pearson's rho and quadratic regression. RESULTS: For each country, rank responses are less likely than TTO responses to be tied and to indicate that states are worse than dead. In all countries, rank responses show a strong linear correlation with both TTO (Pearson's rho=0.88-0.99) and VAS (rho=0.91-0.98) responses. However, rank-ba

Level-Spacing Distributions and the Bessel Kernel

The level spacing distributions which arise when one rescales the Laguerre or Jacobi ensembles of hermitian matrices is studied. These distributions are expressible in terms of a Fredholm determinant of an integral operator whose kernel is expressible in terms of Bessel functions of order $\alpha$. We derive a system of partial differential equations associated with the logarithmic derivative of this Fredholm determinant when the underlying domain is a union of intervals. In the case of a single interval this Fredholm determinant is a Painleve tau function.Comment: 18 pages, resubmitted to make postscript compatible, no changes to manuscript conten

Fredholm Determinants, Differential Equations and Matrix Models

Orthogonal polynomial random matrix models of NxN hermitian matrices lead to Fredholm determinants of integral operators with kernel of the form (phi(x) psi(y) - psi(x) phi(y))/x-y. This paper is concerned with the Fredholm determinants of integral operators having kernel of this form and where the underlying set is a union of open intervals. The emphasis is on the determinants thought of as functions of the end-points of these intervals. We show that these Fredholm determinants with kernels of the general form described above are expressible in terms of solutions of systems of PDE's as long as phi and psi satisfy a certain type of differentiation formula. There is also an exponential variant of this analysis which includes the circular ensembles of NxN unitary matrices.Comment: 34 pages, LaTeX using RevTeX 3.0 macros; last version changes only the abstract and decreases length of typeset versio

Lacustrine stromatolites: Useful structures for environmental interpretation – an example from the Miocene Ebro Basin

The significance of stromatolites as depositional environmental indicators and the underlying causes of lamination in the lacustrine realm are poorly understood. Stromatolites in a ca 600 m thick Miocene succession in the Ebro Basin are good candidates to shed light on these issues because they are intimately related to other lacustrine carbonate and sulphate facies, grew under variable environmental conditions and show distinct lamination patterns. These stromatolites are associated with wave-related, clastic-carbonate laminated limestones. Both facies consist of calcite and variable amounts of dolomite. Thin planar stromatolites (up to 10 cm thick and less than 6 m long) occurred in very shallow water. These stromatolites represented first biological colonization after: (i) subaerial exposure in the palustrine environment (i.e. at the beginning of deepening cycles); or (ii) erosion due to surge action, then coating very irregular surfaces on laminated limestones (i.e. through shallowing or deepening cycles). Sometimes they are associated with evaporative pumping. Stratiform stromatolites (10 to 30 cm high and tens of metres long) and domed stromatolites (10 to 30 cm high and long) developed in deeper settings, between the surge periods that produced hummocky cross-stratification and horizontal lamination offshore. Changes in stromatolite lamina shape, and thus in the growth forms through time, can be attributed to changes in water depth, whereas variations in lamina continuity are linked to water energy and sediment supply. Growth of the stromatolites resulted from in situ calcite precipitation and capture of minor amounts of fine-grained carbonate particles. Based on texture, four types of simple laminae are distinguished. The simple micrite and microsparite laminae can be grouped into light and dark composite laminae, which represent, respectively, high and low Precipitation/Evaporation ratio periods. Different lamination patterns provide new ideas for the interpretation of microbial laminations as a function of variations in climate-dependent parameters (primarily the Precipitation/Evaporation ratio) over variable timescales

High-density single cell mRNA sequencing to characterize circulating tumor cells in hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) release tumor cells to the bloodstream, which can be detected using cell surface markers. Despite numerous reports suggest a direct correlation between the number of circulating tumor cells (CTCs) and poor clinical outcomes, few studies have provided a thorough molecular characterization of CTCs. Due to the limited access to tissue samples in patients at advanced stages of HCC, it is crucial to develop new technologies to identify HCC cancer drivers in routine clinical conditions. Here, we describe a method that sequentially combines image flow cytometry and high density single-cell mRNA sequencing to identify CTCs in HCC patients. Genome wide expression profiling of CTCs using this approach demonstrates CTC heterogeneity and helps detect known oncogenic drivers in HCC such as IGF2. This integrated approach provides a novel tool for biomarker development in HCC using liquid biopsy

Stop looking angry and smile, please: start and stop of the very same facial expression differentially activate threat- and reward-related brain networks

Static pictures of emotional facial expressions have been found to activate brain structures involved in the processing of emotional stimuli. However, in everyday live, emotional expressions are changing rapidly, and the processing of the onset vs the offset of the very same emotional expression might rely on different brain networks, presumably leading to different behavioral and physiological reactions (e.g. approach or avoidance). Using functional magnetic resonance imaging, this was examined by presenting video clips depicting onsets and offsets of happy and angry facial expressions. Subjective valence and threat ratings clearly depended on the direction of change. Blood oxygen level dependent responses indicate both reward- and threat-related activations for the offset of angry expressions. Comparing onsets and offsets, angry offsets were associated with stronger ventral striatum activation than angry onsets. Additionally, the offset of happy and the onset of angry expressions showed strong common activity in the lateral orbitofrontal cortex bilaterally, the left amygdala and the left insula, whereas the onset of happy and the offset of angry expressions induced significant activation in the left dorsal striatum. In sum, the results confirm different activity in motivation-related brain areas in response to the onset and offset of the same emotional expression and highlight the importance of temporal characteristics of facial expressions for social communication

Analytical Results for Individual and Group Selection of Any Intensity

The idea of evolutionary game theory is to relate the payoff of a game to reproductive success (= fitness). An underlying assumption in most models is that fitness is a linear function of the payoff. For stochastic evolutionary dynamics in finite populations, this leads to analytical results in the limit of weak selection, where the game has a small effect on overall fitness. But this linear function makes the analysis of strong selection difficult. Here, we show that analytical results can be obtained for any intensity of selection, if fitness is defined as an exponential function of payoff. This approach also works for group selection (= multi-level selection). We discuss the difference between our approach and that of inclusive fitness theory