Does introduction of thresholds in decision aids benefit the patient?: Comparison between findings-based and threshold-based diagnostic decision aids.

PURPOSE: To assess how different diagnostic decision aids perform in terms of sensitivity, specificity, and harm. METHODS: Four diagnostic decision aids were compared, as applied to a simulated patient population: a findings-based algorithm following a linear or branched pathway, a serial threshold-based strategy, and a parallel threshold-based strategy. Headache in immune-compromised HIV patients in a developing country was used as an example. Diagnoses included cryptococcal meningitis, cerebral toxoplasmosis, tuberculous meningitis, bacterial meningitis, and malaria. Data were derived from literature and expert opinion. Diagnostic strategies' validity was assessed in terms of sensitivity, specificity, and harm related to mortality and morbidity. Sensitivity analyses and Monte Carlo simulation were performed. RESULTS: The parallel threshold-based approach led to a sensitivity of 92% and a specificity of 65%. Sensitivities of the serial threshold-based approach and the branched and linear algorithms were 47%, 47%, and 74%, respectively, and the specificities were 85%, 95%, and 96%. The parallel threshold-based approach resulted in the least harm, with the serial threshold-based approach, the branched algorithm, and the linear algorithm being associated with 1.56-, 1.44-, and 1.17-times higher harm, respectively. Findings were corroborated by sensitivity and Monte Carlo analyses. CONCLUSION: A threshold-based diagnostic approach is designed to find the optimal trade-off that minimizes expected harm, enhancing sensitivity and lowering specificity when appropriate, as in the given example of a symptom pointing to several life-threatening diseases. Findings-based algorithms, in contrast, solely consider clinical observations. A parallel workup, as opposed to a serial workup, additionally allows for all potential diseases to be reviewed, further reducing false negatives. The parallel threshold-based approach might, however, not be as good in other disease settings.

Geometric morphometric analyses provide evidence for the adaptive character of the Tanganyikan cichlid fish radiations.

The cichlids of East Africa are renowned as one of the most spectacular examples of adaptive radiation. They provide a unique opportunity to investigate the relationships between ecology, morphological diversity, and phylogeny in producing such remarkable diversity. Nevertheless, the parameters of the adaptive radiations of these fish have not been satisfactorily quantified yet. Lake Tanganyika possesses all of the major lineages of East African cichlid fish, so by using geometric morphometrics and comparative analyses of ecology and morphology, in an explicitly phylogenetic context, we quantify the role of ecology in driving adaptive speciation. We used geometric morphometric methods to describe the body shape of over 1000 specimens of East African cichlid fish, with a focus on the Lake Tanganyika species assemblage, which is composed of more than 200 endemic species. The main differences in shape concern the length of the whole body and the relative sizes of the head and caudal peduncle. We investigated the influence of phylogeny on similarity of shape using both distance-based and variance partitioning methods, finding that phylogenetic inertia exerts little influence on overall body shape. Therefore, we quantified the relative effect of major ecological traits on shape using phylogenetic generalized least squares and disparity analyses. These analyses conclude that body shape is most strongly predicted by feeding preferences (i.e., trophic niches) and the water depths at which species occur. Furthermore, the morphological disparity within tribes indicates that even though the morphological diversification associated with explosive speciation has happened in only a few tribes of the Tanganyikan assemblage, the potential to evolve diverse morphologies exists in all tribes. Quantitative data support the existence of extensive parallelism in several independent adaptive radiations in Lake Tanganyika. Notably, Tanganyikan mouthbrooders belonging to the C-lineage and the substrate spawning Lamprologini have evolved a multitude of different shapes from elongated and Lamprologus-like hypothetical ancestors. Together, these data demonstrate strong support for the adaptive character of East African cichlid radiations.

Accurate and efficient simulation of multiphase flow in a heterogeneous reservoir by using error estimate and control in the multiscale finite-volume framework

The multiscale finite-volume (MSFV) method is designed to reduce the computational cost of elliptic and parabolic problems with highly heterogeneous anisotropic coefficients. The reduction is achieved by splitting the original global problem into a set of local problems (with approximate local boundary conditions) coupled by a coarse global problem. It has been shown recently that the numerical errors in MSFV results can be reduced systematically with an iterative procedure that provides a conservative velocity field after any iteration step. The iterative MSFV (i-MSFV) method can be obtained with an improved (smoothed) multiscale solution to enhance the localization conditions, with a Krylov subspace method [e.g., the generalized-minimal-residual (GMRES) algorithm] preconditioned by the MSFV system, or with a combination of both. In a multiphase-flow system, a balance between accuracy and computational efficiency should be achieved by finding a minimum number of i-MSFV iterations (on pressure), which is necessary to achieve the desired accuracy in the saturation solution. In this work, we extend the i-MSFV method to sequential implicit simulation of time-dependent problems. To control the error of the coupled saturation/pressure system, we analyze the transport error caused by an approximate velocity field. We then propose an error-control strategy on the basis of the residual of the pressure equation. At the beginning of simulation, the pressure solution is iterated until a specified accuracy is achieved. To minimize the number of iterations in a multiphase-flow problem, the solution at the previous timestep is used to improve the localization assumption at the current timestep. Additional iterations are used only when the residual becomes larger than a specified threshold value. Numerical results show that only a few iterations on average are necessary to improve the MSFV results significantly, even for very challenging problems. Therefore, the proposed adaptive strategy yields efficient and accurate simulation of multiphase flow in heterogeneous porous media.

Adaptive tracking of EEG oscillations.

Neuronal oscillations are an important aspect of EEG recordings. These oscillations are supposed to be involved in several cognitive mechanisms. For instance, oscillatory activity is considered a key component for the top-down control of perception. However, measuring this activity and its influence requires precise extraction of frequency components. This processing is not straightforward. Particularly, difficulties with extracting oscillations arise due to their time-varying characteristics. Moreover, when phase information is needed, it is of the utmost importance to extract narrow-band signals. This paper presents a novel method using adaptive filters for tracking and extracting these time-varying oscillations. This scheme is designed to maximize the oscillatory behavior at the output of the adaptive filter. It is then capable of tracking an oscillation and describing its temporal evolution even during low amplitude time segments. Moreover, this method can be extended in order to track several oscillations simultaneously and to use multiple signals. These two extensions are particularly relevant in the framework of EEG data processing, where oscillations are active at the same time in different frequency bands and signals are recorded with multiple sensors. The presented tracking scheme is first tested with synthetic signals in order to highlight its capabilities. Then it is applied to data recorded during a visual shape discrimination experiment for assessing its usefulness during EEG processing and in detecting functionally relevant changes. This method is an interesting additional processing step for providing alternative information compared to classical time-frequency analyses and for improving the detection and analysis of cross-frequency couplings.

Absence of epidemic threshold in scale free networks with degree correlations

Random scale-free networks have the peculiar property of being prone to the spreading of infections. Here we provide for the susceptible-infected-susceptible model an exact result showing that a scale-free degree distribution with diverging second moment is a sufficient condition to have null epidemic threshold in unstructured networks with either assortative or disassortative mixing. Degree correlations result therefore irrelevant for the epidemic spreading picture in these scale-free networks. The present result is related to the divergence of the average nearest neighbors degree, enforced by the degree detailed balance condition.

Adaptive diversity in heterogeneous environments for populations regulated by a mixture of soft and hard selection

The stable co-existence of two haploid genotypes or two species is studied in a spatially heterogeneous environment submitted to a mixture of soft selection (within-patch regulation) and hard selection (outside-patch regulation) and where two kinds of resource are available. This is analysed both at an ecological time-scale (short term) and at an evolutionary time-scale (long term). At an ecological scale, we show that co-existence is very unlikely if the two competitors are symmetrical specialists exploiting different resources. In this case, the most favourable conditions are met when the two resources are equally available, a situation that should favour generalists at an evolutionary scale. Alternatively, low within-patch density dependence (soft selection) enhances the co-existence between two slightly different specialists of the most available resource. This results from the opposing forces that are acting in hard and soft regulation modes. In the case of unbalanced accessibility to the two resources, hard selection favours the most specialized genotype, whereas soft selection strongly favours the less specialized one. Our results suggest that competition for different resources may be difficult to demonstrate in the wild even when it is a key factor in the maintenance of adaptive diversity. At an evolutionary scale, a monomorphic invasive evolutionarily stable strategy (ESS) always exists. When a linear trade-off exists between survival in one habitat versus that in another, this ESS lies between an absolute adjustment of survival to niche size (for mainly soft-regulated populations) and absolute survival (specialization) in a single niche (for mainly hard-regulated populations). This suggests that environments in agreement with the assumptions of such models should lead to an absence of adaptive variation in the long term.

A CT-based study investigating the relationship between pedicle screw placement and stimulation threshold of compound muscle action potentials measured by intraoperative neurophysiological monitoring.

PURPOSE: Neurophysiological monitoring aims to improve the safety of pedicle screw placement, but few quantitative studies assess specificity and sensitivity. In this study, screw placement within the pedicle is measured (post-op CT scan, horizontal and vertical distance from the screw edge to the surface of the pedicle) and correlated with intraoperative neurophysiological stimulation thresholds. METHODS: A single surgeon placed 68 thoracic and 136 lumbar screws in 30 consecutive patients during instrumented fusion under EMG control. The female to male ratio was 1.6 and the average age was 61.3 years (SD 17.7). Radiological measurements, blinded to stimulation threshold, were done on reformatted CT reconstructions using OsiriX software. A standard deviation of the screw position of 2.8 mm was determined from pilot measurements, and a 1 mm of screw-pedicle edge distance was considered as a difference of interest (standardised difference of 0.35) leading to a power of the study of 75 % (significance level 0.05). RESULTS: Correct placement and stimulation thresholds above 10 mA were found in 71 % of screws. Twenty-two percent of screws caused cortical breach, 80 % of these had stimulation thresholds above 10 mA (sensitivity 20 %, specificity 90 %). True prediction of correct position of the screw was more frequent for lumbar than for thoracic screws. CONCLUSION: A screw stimulation threshold of >10 mA does not indicate correct pedicle screw placement. A hypothesised gradual decrease of screw stimulation thresholds was not observed as screw placement approaches the nerve root. Aside from a robust threshold of 2 mA indicating direct contact with nervous tissue, a secondary threshold appears to depend on patients' pathology and surgical conditions.

Adaptive colour polymorphism of Acrida ungarica H. (Orthoptera: Acrididae) in a spatially heterogeneous environment

Intra-specific colour polymorphism provides a cryptic camouflage from predators in heterogeneous habitats. The orthoptera species, Acrida ungarica (Herbst, 1786) possess two well-distinguished colour morphs: brown and green and displays several disruptive colouration patterns within each morph to improve the crypsis. This study focused on how the features of the background environment relate to the proportion of the two morphs and to the intensity of disruptive colouration patterns in A. ungarica. As the two sexes are very distinct with respect to mass and length, we also distinctively tested the relationship for each sex. In accordance with the background matching hypothesis, we found that, for both sexes, the brown morph was in higher proportion at sites with a brown-dominant environment, and green morphs were in higher proportion in green-dominant environments. Globally, individuals in drier sites and in the drier year also had more intense disruptive colouration patterns, and brown morphs and females were also more striped. Colour patterns differed largely between populations and were significantly correlated with relevant environmental features. Even if A. ungarica is a polymorphic specialist, disruptive colouration still appears to provide strong benefits, particularly in some habitats. Moreover, because females are larger, they are less able to flee, which might explain the difference between sexes

An adaptive multiscale method for density-driven instabilities

Accurate modeling of flow instabilities requires computational tools able to deal with several interacting scales, from the scale at which fingers are triggered up to the scale at which their effects need to be described. The Multiscale Finite Volume (MsFV) method offers a framework to couple fine-and coarse-scale features by solving a set of localized problems which are used both to define a coarse-scale problem and to reconstruct the fine-scale details of the flow. The MsFV method can be seen as an upscaling-downscaling technique, which is computationally more efficient than standard discretization schemes and more accurate than traditional upscaling techniques. We show that, although the method has proven accurate in modeling density-driven flow under stable conditions, the accuracy of the MsFV method deteriorates in case of unstable flow and an iterative scheme is required to control the localization error. To avoid large computational overhead due to the iterative scheme, we suggest several adaptive strategies both for flow and transport. In particular, the concentration gradient is used to identify a front region where instabilities are triggered and an accurate (iteratively improved) solution is required. Outside the front region the problem is upscaled and both flow and transport are solved only at the coarse scale. This adaptive strategy leads to very accurate solutions at roughly the same computational cost as the non-iterative MsFV method. In many circumstances, however, an accurate description of flow instabilities requires a refinement of the computational grid rather than a coarsening. For these problems, we propose a modified iterative MsFV, which can be used as downscaling method (DMsFV). Compared to other grid refinement techniques the DMsFV clearly separates the computational domain into refined and non-refined regions, which can be treated separately and matched later. This gives great flexibility to employ different physical descriptions in different regions, where different equations could be solved, offering an excellent framework to construct hybrid methods.

The Effect of a threshold proportional reinsurance strategy on ruin probabilities

[spa] En un modelo de Poisson compuesto, definimos una estrategia de reaseguro proporcional de umbral : se aplica un nivel de retención k1 siempre que las reservas sean inferiores a un determinado umbral b, y un nivel de retención k2 en caso contrario. Obtenemos la ecuación íntegro-diferencial para la función Gerber-Shiu, definida en Gerber-Shiu -1998- en este modelo, que nos permite obtener las expresiones de la probabilidad de ruina y de la transformada de Laplace del momento de ruina para distintas distribuciones de la cuantía individual de los siniestros. Finalmente presentamos algunos resultados numéricos.

The expansion of amino-acid repeats is not associated to adaptive evolution in mammalian genes.

BACKGROUND: The expansion of amino acid repeats is determined by a high mutation rate and can be increased or limited by selection. It has been suggested that recent expansions could be associated with the potential of adaptation to new environments. In this work, we quantify the strength of this association, as well as the contribution of potential confounding factors. RESULTS: Mammalian positively selected genes have accumulated more recent amino acid repeats than other mammalian genes. However, we found little support for an accelerated evolutionary rate as the main driver for the expansion of amino acid repeats. The most significant predictors of amino acid repeats are gene function and GC content. There is no correlation with expression level. CONCLUSIONS: Our analyses show that amino acid repeat expansions are causally independent from protein adaptive evolution in mammalian genomes. Relaxed purifying selection or positive selection do not associate with more or more recent amino acid repeats. Their occurrence is slightly favoured by the sequence context but mainly determined by the molecular function of the gene.

MDCT arthrography of the hip: value of the adaptive statistical iterative reconstruction technique and potential for radiation dose reduction.

OBJECTIVE: The purpose of this article is to assess the effect of the adaptive statistical iterative reconstruction (ASIR) technique on image quality in hip MDCT arthrography and to evaluate its potential for reducing radiation dose. SUBJECTS AND METHODS: Thirty-seven patients examined with hip MDCT arthrography were prospectively randomized into three different protocols: one with a regular dose (volume CT dose index [CTDIvol], 38.4 mGy) and two with a reduced dose (CTDIvol, 24.6 or 15.4 mGy). Images were reconstructed using filtered back projection (FBP) and four increasing percentages of ASIR (30%, 50%, 70%, and 90%). Image noise and contrast-to-noise ratio (CNR) were measured. Two musculoskeletal radiologists independently evaluated several anatomic structures and image quality parameters using a 4-point scale. They also jointly assessed acetabular labrum tears and articular cartilage lesions. RESULTS: With decreasing radiation dose level, image noise statistically significantly increased (p=0.0009) and CNR statistically significantly decreased (p=0.001). We also found a statistically significant reduction in noise (p=0.0001) and increase in CNR (p≤0.003) with increasing percentage of ASIR; in addition, we noted statistically significant increases in image quality scores for the labrum and cartilage, subchondral bone, overall diagnostic quality (up to 50% ASIR), and subjective noise (p≤0.04), and statistically significant reductions for the trabecular bone and muscles (p≤0.03). Regardless of the radiation dose level, there were no statistically significant differences in the detection and characterization of labral tears (n=24; p=1) and cartilage lesions (n=40; p≥0.89) depending on the ASIR percentage. CONCLUSION: The use of up to 50% ASIR in hip MDCT arthrography helps to reduce radiation dose by approximately 35-60%, while maintaining diagnostic image quality comparable to that of a regular-dose protocol using FBP.