A pilot study on subject-based comprehensive steroid profiling: novel biomarkers to detect testosterone misuse in sports.

Context:  Until now, the testosterone/epitestosterone (T/E) ratio is the main marker for detection of testosterone (T) misuse in athletes. As this marker can be influenced by a number of confounding factors, additional steroid profile parameters indicating T misuse can provide substantiating evidence of doping with endogenous steroids. The evaluation of a steroid profile is currently based upon population statistics. Since large inter-individual variations exist, a paradigm shift towards subject-based references is ongoing in doping analysis. Objective:  Proposition of new biomarkers for the detection of testosterone in sports using extensive steroid profiling and an adaptive model based upon Bayesian inference. Subjects:  6 healthy male volunteers were administered with testosterone undecanoate. Population statistics were performed upon steroid profiles from 2014 male Caucasian athletes participating in official sport competition. Design:  An extended search for new biomarkers in a comprehensive steroid profile combined with Bayesian inference techniques as used in the Athlete Biological Passport resulted in a selection of additional biomarkers that may improve detection of testosterone misuse in sports. Results:  Apart from T/E, 4 other steroid ratios (6α-OH-androstenedione/16α-OH-dehydroepiandrostenedione, 4-OH-androstenedione/16α-OH-androstenedione, 7α-OH-testosterone/7β-OH-dehydroepiandrostenedione and dihydrotestosterone/5β-androstane-3α,17β-diol) were identified as sensitive urinary biomarkers for T misuse. These new biomarkers were rated according to relative response, parameter stability, detection time and discriminative power. Conclusion:  Newly selected biomarkers were found suitable for individual referencing within the concept of the Athlete's Biological Passport. The parameters showed improved detection time and discriminative power compared to the T/E ratio. Such biomarkers can support the evidence of doping with small oral doses of testosterone.

Evolutionary history of the greater white-toothed shrew (Crocidura russula) inferred from analysis of mtDNA, Y, and X chromosome markers.

We investigate the evolutionary history of the greater white-toothed shrew across its distribution in northern Africa and mainland Europe using sex-specific (mtDNA and Y chromosome) and biparental (X chromosome) markers. All three loci confirm a large divergence between eastern (Tunisia and Sardinia) and western (Morocco and mainland Europe) lineages, and application of a molecular clock to mtDNA divergence estimates indicates a more ancient separation (2.25 M yr ago) than described by some previous studies, supporting claims for taxonomic revision. Moroccan ancestry for the mainland European population is inconclusive from phylogenetic trees, but is supported by greater nucleotide diversity and a more ancient population expansion in Morocco than in Europe. Signatures of rapid population expansion in mtDNA, combined with low X and Y chromosome diversity, suggest a single colonization of mainland Europe by a small number of Moroccan shrews >38 K yr ago. This study illustrates that multilocus genetic analyses can facilitate the interpretation of species' evolutionary history but that phylogeographic inference using X and Y chromosomes is restricted by low levels of observed polymorphism.

Implementing statistical learning methods through Bayesian networks. Part 1: a guide to Bayesian parameter estimation using forensic science data

As a thorough aggregation of probability and graph theory, Bayesian networks currently enjoy widespread interest as a means for studying factors that affect the coherent evaluation of scientific evidence in forensic science. Paper I of this series of papers intends to contribute to the discussion of Bayesian networks as a framework that is helpful for both illustrating and implementing statistical procedures that are commonly employed for the study of uncertainties (e.g. the estimation of unknown quantities). While the respective statistical procedures are widely described in literature, the primary aim of this paper is to offer an essentially non-technical introduction on how interested readers may use these analytical approaches - with the help of Bayesian networks - for processing their own forensic science data. Attention is mainly drawn to the structure and underlying rationale of a series of basic and context-independent network fragments that users may incorporate as building blocs while constructing larger inference models. As an example of how this may be done, the proposed concepts will be used in a second paper (Part II) for specifying graphical probability networks whose purpose is to assist forensic scientists in the evaluation of scientific evidence encountered in the context of forensic document examination (i.e. results of the analysis of black toners present on printed or copied documents).

Uses of also in oral semi-informal German

In recent grammars and dictionaries also (`therefore, so, well¿) continues to be preferably presented as an adverb with a conclusive-consecutive connective function that essentially corresponds to its use in formal written German. Its function as a modal particle is documented, however, since the beginnings of what is known as Partikelforschung, though not all its uses have been systematically investigated contrasting oral and written German, either in mode or concept. In this article we analyse the uses of also in semi-informal oral interactions on the basis of empirical data (from a subsample of the VARCOM corpus). Specifically, we will analyse the presence and frequency of also at the beginning of a sentence or sequence, the functions it serves as a logical-semantic connector or discourse and interaction marker and the interrelations between these functions, in order to contrast these results with the description of also provided by current reference works.

Constraining ACT-R models of decision strategies: An experimental paradigm

It has been repeatedly debated which strategies people rely on in inference. These debates have been difficult to resolve, partially because hypotheses about the decision processes assumed by these strategies have typically been formulated qualitatively, making it hard to test precise quantitative predictions about response times and other behavioral data. One way to increase the precision of strategies is to implement them in cognitive architectures such as ACT-R. Often, however, a given strategy can be implemented in several ways, with each implementation yielding different behavioral predictions. We present and report a study with an experimental paradigm that can help to identify the correct implementations of classic compensatory and non-compensatory strategies such as the take-the-best and tallying heuristics, and the weighted-linear model.

Factors affecting visual analysis in single-case designs

Visual inspection remains the most frequently applied method for detecting treatment effects in single-case designs. The advantages and limitations of visual inference are here discussed in relation to other procedures for assessing intervention effectiveness. The first part of the paper reviews previous research on visual analysis, paying special attention to the validation of visual analysts" decisions, inter-judge agreement, and false alarm and omission rates. The most relevant factors affecting visual inspection (i.e., effect size, autocorrelation, data variability, and analysts" expertise) are highlighted and incorporated into an empirical simulation study with the aim of providing further evidence about the reliability of visual analysis. Our results concur with previous studies that have reported the relationship between serial dependence and increased Type I rates. Participants with greater experience appeared to be more conservative and used more consistent criteria when assessing graphed data. Nonetheless, the decisions made by both professionals and students did not match sufficiently the simulated data features, and we also found low intra-judge agreement, thus suggesting that visual inspection should be complemented by other methods when assessing treatment effectiveness.

Genetical and environmental analyses of yield in six biparental soybean crosses

The yearly genetic progress obtained by breeding for increased soybean yield has been considered acceptable worldwide. It is common sense, however, that this progress can be improved further if refined breeding techniques, developed from the knowledge of the genetic mechanisms controlling soybean yield, are used. In this paper, data from four cultivars and/or lines and their derived sets of F2, F3, F7, F8, F9 and F10 generations assayed in 17 environments were analyzed to allow an insight of the genetic control of soybean yield under different environmental conditions. The general picture was of a complex polygene system controlling yield in soybeans. Additive genetic effects predominated although dominance was often found to be significant. Complications such as epistasis, linkage and macro and micro genotype x environment (G x E) interactions were also commonly detected. The overall heritability was 0.29. The relative magnitude of the additive effects and the complicating factors allowed the inference that the latter are not a serious problem to the breeder. The low heritability values and the considerable magnitude of G x E interactions for yield, however, indicated that careful evaluation through experiments designed to allow for the presence of these effects is necessary for successful selection.

ABCtoolbox: a versatile toolkit for approximate Bayesian computations.

BACKGROUND: The estimation of demographic parameters from genetic data often requires the computation of likelihoods. However, the likelihood function is computationally intractable for many realistic evolutionary models, and the use of Bayesian inference has therefore been limited to very simple models. The situation changed recently with the advent of Approximate Bayesian Computation (ABC) algorithms allowing one to obtain parameter posterior distributions based on simulations not requiring likelihood computations. RESULTS: Here we present ABCtoolbox, a series of open source programs to perform Approximate Bayesian Computations (ABC). It implements various ABC algorithms including rejection sampling, MCMC without likelihood, a Particle-based sampler and ABC-GLM. ABCtoolbox is bundled with, but not limited to, a program that allows parameter inference in a population genetics context and the simultaneous use of different types of markers with different ploidy levels. In addition, ABCtoolbox can also interact with most simulation and summary statistics computation programs. The usability of the ABCtoolbox is demonstrated by inferring the evolutionary history of two evolutionary lineages of Microtus arvalis. Using nuclear microsatellites and mitochondrial sequence data in the same estimation procedure enabled us to infer sex-specific population sizes and migration rates and to find that males show smaller population sizes but much higher levels of migration than females. CONCLUSION: ABCtoolbox allows a user to perform all the necessary steps of a full ABC analysis, from parameter sampling from prior distributions, data simulations, computation of summary statistics, estimation of posterior distributions, model choice, validation of the estimation procedure, and visualization of the results.

Influència de l'educació sanitària en l'adaptació dels pacients ostomitzats a la nova situació produïda per l'ostomia digestiva

Introducció: Les persones ostomitzades presenten una sèrie de canvis de tipus fisiològic, psicològic i social, els quals els obliga a adaptar-se a la seva vida diària. Per adaptar-se a aquesta nova situació utilitzen una sèrie d'estratègies d'afrontament, sent l'acceptació el producte final. Per a que les estratègies adoptades siguin les més efectives, han de rebre una educació sanitària adequada.Contràriament, l'escassetat d'educació sanitària o l'educació sanitària inadequada que reben aquests pacients és un problema real que ens trobem en l'actualitat.Objectiu: Conèixer si l'educació sanitària rebuda pels pacients ostomitzats, té influencia en la seva adaptació a la nova situació produïda per l'ostomia digestiva.Metodologia: Estudi qualitatiu fenomenològic, on les dades es recolliran a través d'entrevistessemiestructurades a pacients amb ostomia digestiva, els quals van rebre l'alta hospitalària fa almenys 2 mesos. Les entrevistes seran gravades, transcrites i analitzades, utilitzant en aquest últim pas la triangulació d'investigadors. La mostra serà de tipus intencional, la seleccionaré a l'Hospital Universitàri de Bellvitge entre els pacients que acudeixen a la consulta de la infermera estomaterapeuta, i el seu tamany estarà definit per la saturació teòrica. L'estudi estarà reglat en tot moment pel dret a la intimitat, incloent en aquest l'anonimat i la confidencialitat, i el dret a la lliure decisió.Consideracions finals: Inclou una explicació argumentada sobre els meus punts febles i forts del treball, una reflexió sobre la satisfacció amb les competències que he adquirit i finalment una autoavaluació dels resultats del meu aprenentatge.

Entrenament d'un ciclista esprinter mitjançant la força explosiva: avaluació dels efectes d'un entrenament específic

La principal fita dels ciclistes ha estat sempre l’entrenament per millorar les seves condicions i prestacions fisiològiques. Al llarg dels anys, el ciclisme com pràcticament tot l’esport s’ha anat modernitzant, no només tecnològicament. Això ha provocat l’aparició d’especialistes, corredors destinats a destacar, només en unes determinades condicions, per sobre els demés. Una d’aquestes condicions més restringides son les arribades massives, terreny dels anomenats esprinters, els quals brillen per sobre els demés degut a la seva potència, velocitat punta i arrancada. L’entrenament d’aquesta tipologia d’especialitat ha deixat entreveure varies ambigüitats i algunes problemàtiques de fonament teòric. L’esprint en el ciclisme es dona després d’un gran desgast de les reserves energètiques i de fatiga muscular. Per tant, entrenar-lo amb blocs de velocitat no té lògica. Tampoc es una opció viable el recurs que molts equips utilitzen: agafar corredors joves de la pista, i que la seva genètica (fibres ràpides) i les seves característiques de pistard1 facin la resta, perquè al pas dels anys perden aquesta exclusivitat. Aquest estudi es proposa buscar una manera de treballar i potenciar l’esprint del ciclista a partir de la força explosiva, garantint preservar les condicions aeròbiques per tal de que no perjudiqui per altra banda la seva resistència. Per tal d’aconseguir-ho, s’efectuaran uns tests. Un focalitzat en mesurar les prestacions en un esprint dels subjectes. L’altra es basarà en avaluar la força explosiva d’aquets, a partir de salts verticals. Un cop obtinguts els resultats de la primera tanda, els subjectes seran sotmesos a un entrenament combinat de sobrecàrrega, per tal de observar, en la segona tanda, si els resultats son significatius. Com a conclusió, es podria destacar el fet de millora en la majoria d’aspectes en tots els tests per part de tots els subjectes, i que probablement, hi ha una correlació significativa entre la força explosiva i la capacitat per esprintar, tot i que s’haurien de corroborar els resultats amb una mostra més gran.

Gene Ontology Function prediction in Mollicutes using Protein-Protein Association Networks

Abstract Background: Many complex systems can be represented and analysed as networks. The recent availability of large-scale datasets, has made it possible to elucidate some of the organisational principles and rules that govern their function, robustness and evolution. However, one of the main limitations in using protein-protein interactions for function prediction is the availability of interaction data, especially for Mollicutes. If we could harness predicted interactions, such as those from a Protein-Protein Association Networks (PPAN), combining several protein-protein network function-inference methods with semantic similarity calculations, the use of protein-protein interactions for functional inference in this species would become more potentially useful. Results: In this work we show that using PPAN data combined with other approximations, such as functional module detection, orthology exploitation methods and Gene Ontology (GO)-based information measures helps to predict protein function in Mycoplasma genitalium. Conclusions: To our knowledge, the proposed method is the first that combines functional module detection among species, exploiting an orthology procedure and using information theory-based GO semantic similarity in PPAN of the Mycoplasma species. The results of an evaluation show a higher recall than previously reported methods that focused on only one organism network.

Learning about Bayesian networks for forensic interpretation : An example based on the "the problem of multiple propositions"

Both, Bayesian networks and probabilistic evaluation are gaining more and more widespread use within many professional branches, including forensic science. Notwithstanding, they constitute subtle topics with definitional details that require careful study. While many sophisticated developments of probabilistic approaches to evaluation of forensic findings may readily be found in published literature, there remains a gap with respect to writings that focus on foundational aspects and on how these may be acquired by interested scientists new to these topics. This paper takes this as a starting point to report on the learning about Bayesian networks for likelihood ratio based, probabilistic inference procedures in a class of master students in forensic science. The presentation uses an example that relies on a casework scenario drawn from published literature, involving a questioned signature. A complicating aspect of that case study - proposed to students in a teaching scenario - is due to the need of considering multiple competing propositions, which is an outset that may not readily be approached within a likelihood ratio based framework without drawing attention to some additional technical details. Using generic Bayesian networks fragments from existing literature on the topic, course participants were able to track the probabilistic underpinnings of the proposed scenario correctly both in terms of likelihood ratios and of posterior probabilities. In addition, further study of the example by students allowed them to derive an alternative Bayesian network structure with a computational output that is equivalent to existing probabilistic solutions. This practical experience underlines the potential of Bayesian networks to support and clarify foundational principles of probabilistic procedures for forensic evaluation.

[(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma.

BACKGROUND: To compare morphological gross tumor volumes (GTVs), defined as pre- and postoperative gadolinium enhancement on T1-weighted magnetic resonance imaging to biological tumor volumes (BTVs), defined by the uptake of (18)F fluoroethyltyrosine (FET) for the radiotherapy planning of high-grade glioma, using a dedicated positron emission tomography (PET)-CT scanner equipped with three triangulation lasers for patient positioning. METHODS: Nineteen patients with malignant glioma were included into a prospective protocol using FET PET-CT for radiotherapy planning. To be eligible, patients had to present with residual disease after surgery. Planning was performed using the clinical target volume (CTV = GTV union or logical sum BTV) and planning target volume (PTV = CTV + 20 mm). First, the interrater reliability for BTV delineation was assessed among three observers. Second, the BTV and GTV were quantified and compared. Finally, the geometrical relationships between GTV and BTV were assessed. RESULTS: Interrater agreement for BTV delineation was excellent (intraclass correlation coefficient 0.9). Although, BTVs and GTVs were not significantly different (p = 0.9), CTVs (mean 57.8 +/- 30.4 cm(3)) were significantly larger than BTVs (mean 42.1 +/- 24.4 cm(3); p < 0.01) or GTVs (mean 38.7 +/- 25.7 cm(3); p < 0.01). In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended >or= 10 and 20 mm from the margin of the gadolinium enhancement. CONCLUSION: Using FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients.

Missouri River Studies: Alluvial Morphology and Engineering Soil Classification, HR-1, Progress Report, 1960

The primary purposes of this investigation are: 1) To delineate flood plain deposits with different geologic and engineering properties. 2) To provide basic data necessary for any attempt at stabilizing flood plain deposits. The alluvial valley of the Missouri River adjacent to Iowa was chosen as the logical place to begin this study. The river forms the western boundary of the state for an airline distance of approximately 139 miles; and the flood plain varies from a maximum width of approximately 18 miles (Plates 2 and 3, Sheets 75 and 75L) to approximately 4 miles near Crescent, Iowa (Plate 8, Sheet 66). The area studied includes parts of Woodbury, Monona, Harrison, Pottawattamie, Mills, and Fremont counties in Iowa and parts of Dakota, Thurston, Burt, Washington, Douglas, Sarpy, Cass and Otoe counties in Nebraska. Plate l is an index map of the area under consideration.

Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports.

Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5β-androstane-3α,17β-diol and 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol as best biomarkers for DHT administration and DHEA/E, 16α-hydroxydehydroepiandrosterone/E, 7β-hydroxydehydroepiandrosterone/E and 5β-androstane-3α,17β-diol/5α-androstane-3α,17β-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained.The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids. Copyright © 2010 John Wiley & Sons, Ltd.