Swain: Stata module to correct the SEM chi-square overidentification test in small sample sizes or complex models. Statistical Software Components S457617, Boston College Department of Economics.

Swain corrects the chi-square overidentification test (i.e., likelihood ratio test of fit) for structural equation models whethr with or without latent variables. The chi-square statistic is asymptotically correct; however, it does not behave as expected in small samples and/or when the model is complex (cf. Herzog, Boomsma, & Reinecke, 2007). Thus, particularly in situations where the ratio of sample size (n) to the number of parameters estimated (p) is relatively small (i.e., the p to n ratio is large), the chi-square test will tend to overreject correctly specified models. To obtain a closer approximation to the distribution of the chi-square statistic, Swain (1975) developed a correction; this scaling factor, which converges to 1 asymptotically, is multiplied with the chi-square statistic. The correction better approximates the chi-square distribution resulting in more appropriate Type 1 reject error rates (see Herzog & Boomsma, 2009; Herzog, et al., 2007).

Improved statistical analysis of low abundance phenomena in bimodal bacterial populations.

Accurate detection of subpopulation size determinations in bimodal populations remains problematic yet it represents a powerful way by which cellular heterogeneity under different environmental conditions can be compared. So far, most studies have relied on qualitative descriptions of population distribution patterns, on population-independent descriptors, or on arbitrary placement of thresholds distinguishing biological ON from OFF states. We found that all these methods fall short of accurately describing small population sizes in bimodal populations. Here we propose a simple, statistics-based method for the analysis of small subpopulation sizes for use in the free software environment R and test this method on real as well as simulated data. Four so-called population splitting methods were designed with different algorithms that can estimate subpopulation sizes from bimodal populations. All four methods proved more precise than previously used methods when analyzing subpopulation sizes of transfer competent cells arising in populations of the bacterium Pseudomonas knackmussii B13. The methods' resolving powers were further explored by bootstrapping and simulations. Two of the methods were not severely limited by the proportions of subpopulations they could estimate correctly, but the two others only allowed accurate subpopulation quantification when this amounted to less than 25% of the total population. In contrast, only one method was still sufficiently accurate with subpopulations smaller than 1% of the total population. This study proposes a number of rational approximations to quantifying small subpopulations and offers an easy-to-use protocol for their implementation in the open source statistical software environment R.

The pattern of health care use of older prisoners in Switzerland.

Introduction: Population ageing is a worldwide phenomenon that forces us to make radical changes on multiple levels of society. So far, studies have concluded that the health, both physical and mental, of prisoners in general and older prisoners in particular is worse than that of the general population. Prisoners are reported to age faster as compared to adults in the community. However, to date, very little is known about the actual healthcare conditions of older prisoners and almost no substantial knowledge is available concerning their patterns of healthcare use. Method: A quantitative study was conducted in four prisons for male prisoners in Switzerland, including two open and two closed prisons situated in different cantons. In this study, medical records of older prisoners (50+) were obtained from the respective authority upon consent and total anonymity was ensured. Data gathered from all available medical records included basic demographic information, education and prison sentencing. Healthcare data obtained were extensive in nature encompassing data related to illness types, number of visits to different health care providers and hospitals. The corresponding reasons for visits and outcomes of these visits were extracted. All data are analysed using statistical software SPSS 20.0. Results: Data were extracted for a total of 50 older prisoners living in Switzerland. The chosen prisons are located in German-speaking cantons. Preliminary results show that the age average was 56 years. For more than half, this was their first imprisonment. Nevertheless, a third of them were sentenced to measures (Art. 64 Swiss Criminal Code) which means that the length of the detention is indefinite and while release is possible it is in most cases not very likely. This entails that these prisoners will grow old in prison and some will even spend their remaining years there. Concerning their health, a third of the sample reported respiratory and cardiovascular illnesses and half reported suffering from some form of musculoskeletal related pain. Older prisoners were prescribed on average only 3.5 medications, which is significantly fewer than the number of medication prescribed to younger prisoners, whose data were also sampled. Conclusion: Access to healthcare is a right given to all prisoners through the principle of equivalence which is generally exercised in Switzerland. Prisoners growing old in prison will represent a challenge for prison health care services.

HIERFSTAT, a package for R to compute and test hierarchical F-statistics

The package HIERFSTAT for the statistical software R, created by the R Development Core Team, allows the estimate of hierarchical F-statistics from a hierarchy with any numbers of levels. In addition, it allows testing the statistical significance of population differentiation for these different levels, using a generalized likelihood-ratio test. The package HIERFSTAT is available at http://www.unil.ch/popgen/softwares/hierfstat.htm.

Maintenance of polymorphism : a theoretical approach using multilocus systems

Résumé La thématique de cette thèse peut être résumée par le célèbre paradoxe de biologie évolutive sur le maintien du polymorphisme face à la sélection et par l'équation du changement de fréquence gamétique au cours du temps dû, à la sélection. La fréquence d'un gamète xi à la génération (t + 1) est: !!!Equation tronquée!!! Cette équation est utilisée pour générer des données utlisée tout au long de ce travail pour 2, 3 et 4 locus dialléliques. Le potentiel de l'avantage de l'hétérozygote pour le maintien du polymorphisme est le sujet de la première partie. La définition commune de l'avantage de l'hétérozygote n'etant applicable qu'a un locus ayant 2 allèles, cet avantage est redéfini pour un système multilocus sur les bases de précédentes études. En utilisant 5 définitions différentes de l'avantage de l'hétérozygote, je montre que cet avantage ne peut être un mécanisme général dans le maintien du polymorphisme sous sélection. L'étude de l'influence de locus non-détectés sur les processus évolutifs, seconde partie de cette thèse, est motivée par les travaux moléculaires ayant pour but de découvrir le nombre de locus codant pour un trait. La plupart de ces études sous-estiment le nombre de locus. Je montre que des locus non-détectés augmentent la probabilité d'observer du polymorphisme sous sélection. De plus, les conclusions sur les facteurs de maintien du polymorphisme peuvent être trompeuses si tous les locus ne sont pas détectés. Dans la troisième partie, je m'intéresse à la valeur attendue de variance additive après un goulot d'étranglement pour des traits sélectionés. Une études précédente montre que le niveau de variance additive après goulot d'étranglement augmente avec le nombre de loci. Je montre que le niveau de variance additive après un goulot d'étranglement augmente (comparé à des traits neutres), mais indépendamment du nombre de loci. Par contre, le taux de recombinaison a une forte influence, entre autre en regénérant les gamètes disparus suite au goulot d'étranglement. La dernière partie de ce travail de thèse décrit un programme pour le logiciel de statistique R. Ce programme permet d'itérer l'équation ci-dessus en variant les paramètres de sélection, recombinaison et de taille de populations pour 2, 3 et 4 locus dialléliques. Cette thèse montre qu'utiliser un système multilocus permet d'obtenir des résultats non-conformes à ceux issus de systèmes rnonolocus (la référence en génétique des populations). Ce programme ouvre donc d'intéressantes perspectives en génétique des populations. Abstract The subject of this PhD thesis can be summarized by one famous paradox of evolu-tionary biology: the maintenance of polymorphism in the face of selection, and one classical equation of theoretical population genetics: the changes in gametic frequencies due to selection and recombination. The frequency of gamete xi at generation (t + 1) is given by: !!! Truncated equation!!! This equation is used to generate data on selection at two, three, and four diallelic loci for the different parts of this work. The first part focuses on the potential of heterozygote advantage to maintain genetic polymorphism. Results of previous studies are used to (re)define heterozygote advantage for multilocus systems, since the classical definition is for one diallelic locus. I use 5 different definitions of heterozygote advantage. And for these five definitions, I show that heterozygote advantage is not a general mechanism for the maintenance of polymorphism. The study of the influence of undetected loci on evolutionary processes (second part of this work) is motivated by molecular works which aim at discovering the loci coding for a trait. For most of these works, some coding loci remains undetected. I show that undetected loci increases the probability of maintaining polymorphism under selection. In addition, conclusions about the factor that maintain polymorphism can be misleading if not all loci are considered. This is, therefore, only when all loci are detected that exact conclusions on the level of maintained polymorphism or on the factor(s) that maintain(s) polymorphism could be drawn. In the third part, the focus is on the expected release of additive genetic variance after bottleneck for selected traits. A previous study shows that the expected release of additive variance increases with an increase in the number of loci. I show that the expected release of additive variance after bottleneck increases for selected traits (compared with neutral), but this increase is not a function of the number of loci, but function of the recombination rate. Finally, the last part of this PhD thesis is a description of a package for the statistical software R that implements the Equation given above. It allows to generate data for different scenario regarding selection, recombination, and population size. This package opens perspectives for the theoretical population genetics that mainly focuses on one locus, while this work shows that increasing the number of loci leads not necessarily to straightforward results.

JULIDE: a software tool for 3D reconstruction and statistical analysis of autoradiographic mouse brain sections.

In this article we introduce JULIDE, a software toolkit developed to perform the 3D reconstruction, intensity normalization, volume standardization by 3D image registration and voxel-wise statistical analysis of autoradiographs of mouse brain sections. This software tool has been developed in the open-source ITK software framework and is freely available under a GPL license. The article presents the complete image processing chain from raw data acquisition to 3D statistical group analysis. Results of the group comparison in the context of a study on spatial learning are shown as an illustration of the data that can be obtained with this tool.

Implementing statistical learning methods through Bayesian networks (Part 2): bayesian evaluations for results of black toner analyses in forensic document examination

This paper presents and discusses the use of Bayesian procedures - introduced through the use of Bayesian networks in Part I of this series of papers - for 'learning' probabilities from data. The discussion will relate to a set of real data on characteristics of black toners commonly used in printing and copying devices. Particular attention is drawn to the incorporation of the proposed procedures as an integral part in probabilistic inference schemes (notably in the form of Bayesian networks) that are intended to address uncertainties related to particular propositions of interest (e.g., whether or not a sample originates from a particular source). The conceptual tenets of the proposed methodologies are presented along with aspects of their practical implementation using currently available Bayesian network software.

A statistical shape model of the human second cervical vertebra.

PURPOSE: Statistical shape and appearance models play an important role in reducing the segmentation processing time of a vertebra and in improving results for 3D model development. Here, we describe the different steps in generating a statistical shape model (SSM) of the second cervical vertebra (C2) and provide the shape model for general use by the scientific community. The main difficulties in its construction are the morphological complexity of the C2 and its variability in the population. METHODS: The input dataset is composed of manually segmented anonymized patient computerized tomography (CT) scans. The alignment of the different datasets is done with the procrustes alignment on surface models, and then, the registration is cast as a model-fitting problem using a Gaussian process. A principal component analysis (PCA)-based model is generated which includes the variability of the C2. RESULTS: The SSM was generated using 92 CT scans. The resulting SSM was evaluated for specificity, compactness and generalization ability. The SSM of the C2 is freely available to the scientific community in Slicer (an open source software for image analysis and scientific visualization) with a module created to visualize the SSM using Statismo, a framework for statistical shape modeling. CONCLUSION: The SSM of the vertebra allows the shape variability of the C2 to be represented. Moreover, the SSM will enable semi-automatic segmentation and 3D model generation of the vertebra, which would greatly benefit surgery planning.

Benchmarking therapeutic drug monitoring software: A review of available computer tools

Therapeutic drug monitoring (TDM) aims to optimize treatments by individualizing dosage regimens based on the measurement of blood concentrations. Dosage individualization to maintain concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculations currently represent the gold standard TDM approach but require computation assistance. In recent decades computer programs have been developed to assist clinicians in this assignment. The aim of this survey was to assess and compare computer tools designed to support TDM clinical activities. The literature and the Internet were searched to identify software. All programs were tested on personal computers. Each program was scored against a standardized grid covering pharmacokinetic relevance, user friendliness, computing aspects, interfacing and storage. A weighting factor was applied to each criterion of the grid to account for its relative importance. To assess the robustness of the software, six representative clinical vignettes were processed through each of them. Altogether, 12 software tools were identified, tested and ranked, representing a comprehensive review of the available software. Numbers of drugs handled by the software vary widely (from two to 180), and eight programs offer users the possibility of adding new drug models based on population pharmacokinetic analyses. Bayesian computation to predict dosage adaptation from blood concentration (a posteriori adjustment) is performed by ten tools, while nine are also able to propose a priori dosage regimens, based only on individual patient covariates such as age, sex and bodyweight. Among those applying Bayesian calculation, MM-USC*PACK© uses the non-parametric approach. The top two programs emerging from this benchmark were MwPharm© and TCIWorks. Most other programs evaluated had good potential while being less sophisticated or less user friendly. Programs vary in complexity and might not fit all healthcare settings. Each software tool must therefore be regarded with respect to the individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Computer-assisted TDM is gaining growing interest and should further improve, especially in terms of information system interfacing, user friendliness, data storage capability and report generation.

Mfge8 Expression In Conjunctival Melanocytic Proliferations

Purpose: Milk fat globule epidermal growth factor-8 (MFGE8) is a secreted phosphatidylserine-binding protein that has been involved in phagocytosis, as well as in VEGF dependent neovascularization. In a study evaluating protein expression in membrane rafts of cutaneous melanoma at different stages of progression, MFGE8 expression was only identified in membrane rafts of metastatic cutaneous melanoma cell lines. Furthermore, MFGE8, identified at higher level in the vertical growth phase of cutaneous melanoma, promoted tumor growth in vivo, enhanced invasion in vitro and metastatic spread in a mouse model. The purpose of this study was to assess the expression of MFGE8 in conjunctival melanocytic proliferations.Methods: MFGE8 expression was assessed by immunohistochemistry in 66 melanocytic conjunctival proliferations including 21 conjunctival naevi, 20 Primary Acquired Melanosis (PAM) including (4 PAM without atypia and 16 PAM with atypia) and 25 conjunctival melanomas. Expression was independently assessed by 2 pathologists. Relevant clinico-pathological data were retrieved. Statistical anaylis was performed using JUMP 8 software.Results: The concordance between the 2 pathologists had an 87,5% agreement on the first independent assessment of MFGE8 expression. Complete agreement was further reached after joint revision of discordant cases. In the naevi, MFGE8 expression was found in only 4 cases (3 subepithelial cases and 1 composed combined naevus). In the PAM group, MFGE8 was identified in 1 PAM without atypia and 10 PAM with atypia. In the melanoma group, MFGE8 expression was observed in 68% of cases. The expression of MFGE8 in the conjunctival melanocytic proliferation was significantly higher in the melanoma (p=0,0009) and in the PAM (p=0,0169) than in naevi. Within the PAM subgroup, we found no significant correlation between MFGE8 expression and the presence of atypia in the respective specimen examined so far.Conclusions: We demonstrate a significant higher expression of MFGE8 in conjunctival melanoma compared to benign melanocytic lesions, suggesting that this protein may play a role in tumor progression of conjunctival melanocytic proliferations. Further experimental studies should be performed to better characterize MFGE8 involvement in conjunctival melanoma tumorigenesis.

MSight: an image analysis software for liquid chromatography-mass spectrometry.

Images obtained from high-throughput mass spectrometry (MS) contain information that remains hidden when looking at a single spectrum at a time. Image processing of liquid chromatography-MS datasets can be extremely useful for quality control, experimental monitoring and knowledge extraction. The importance of imaging in differential analysis of proteomic experiments has already been established through two-dimensional gels and can now be foreseen with MS images. We present MSight, a new software designed to construct and manipulate MS images, as well as to facilitate their analysis and comparison.

Chemical profiling of different hashish seizures by gas chromatography-mass spectrometry and statistical methodology: a case report

Limited information is available regarding the methodology required to characterize hashish seizures for assessing the presence or the absence of a chemical link between two seizures. This casework report presents the methodology applied for assessing that two different police seizures were coming from the same block before this latter one was split. The chemical signature was extracted using GC-MS analysis and the implemented methodology consists in a study of intra- and inter-variability distributions based on the measurement of the chemical profiles similarity using a number of hashish seizures and the calculation of the Pearson correlation coefficient. Different statistical scenarios (i.e., a combination of data pretreatment techniques and selection of target compounds) were tested to find the most discriminating one. Seven compounds showing high discrimination capabilities were selected on which a specific statistical data pretreatment was applied. Based on the results, the statistical model built for comparing the hashish seizures leads to low error rates. Therefore, the implemented methodology is suitable for the chemical profiling of hashish seizures.

3D visualization software to analyze topological outcomes of topoisomerase reactions.

The action of various DNA topoisomerases frequently results in characteristic changes in DNA topology. Important information for understanding mechanistic details of action of these topoisomerases can be provided by investigating the knot types resulting from topoisomerase action on circular DNA forming a particular knot type. Depending on the topological bias of a given topoisomerase reaction, one observes different subsets of knotted products. To establish the character of topological bias, one needs to be aware of all possible topological outcomes of intersegmental passages occurring within a given knot type. However, it is not trivial to systematically enumerate topological outcomes of strand passage from a given knot type. We present here a 3D visualization software (TopoICE-X in KnotPlot) that incorporates topological analysis methods in order to visualize, for example, knots that can be obtained from a given knot by one intersegmental passage. The software has several other options for the topological analysis of mechanisms of action of various topoisomerases.