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Summary: We have calculated the biological variation (BV) of different bone metabolism biomarkers on a large, well-described cohort of subjects. BV is important to calculate reference change value (or least significant change) which allows evaluating if the difference observed between two consecutive measurements in a patient is biologically significant or not. Introduction: Within-subject (CVI) and between-subject (CVG) biological variation (BV) estimates are essential in determining both analytical performance specifications (APS) and reference change values (RCV). Previously published estimates of BV for bone metabolism biomarkers are generally not compliant with the most up-to-date quality criteria for BV studies. We calculated the BV and RCV for different bone metabolism markers, namely β-isomerized C-terminal telopeptide of type I collagen (β-CTX), N-terminal propeptide of type I collagen (PINP), osteocalcin (OC), intact fibroblast growth factor 23 (iFGF-23), and uncarboxylated-unphosphorylated Matrix-Gla Protein (uCuP-MGP) using samples from the European Biological Variation Study (EuBIVAS). Methods: In the EuBIVAS, 91 subjects were recruited from six European laboratories. Fasting blood samples were obtained weekly for ten consecutive weeks. The samples were run in duplicate on IDS iSYS or DiaSorin Liaison instruments. The results were subjected to outlier and variance homogeneity analysis before CV-ANOVA was used to obtain the BV estimates. Results: We found no effect of gender upon the CVI estimates. The following CVI estimates with 95% confidence intervals (95% CI) were obtained: β-CTX 15.1% (14.4–16.0%), PINP 8.8% (8.4–9.3%), OC 8.9% (8.5–9.4%), iFGF23 13.9% (13.2–14.7%), and uCuP-MGP 6.9% (6.1–7.3%). Conclusions: The EuBIVAS has provided updated BV estimates for bone markers, including iFGF23, which have not been previously published, facilitating the improved follow-up of patients being treated for metabolic bone disease. [ABSTRACT FROM AUTHOR]

Abstract Background Objective interpretation of laboratory test results used to diagnose and monitor diabetes mellitus in part requires the application of biological variation data (BVD). The quality of published BVD has been questioned. The aim of this study was to quality assess publications reporting BVD for diabetes-related analytes using the Biological Variation Data Critical Appraisal Checklist (BIVAC); to assess whether published BVD are fit for purpose and whether the study design and population attributes influence BVD estimates and to undertake a meta-analysis of the BVD from BIVAC-assessed publications. Methods Publications reporting data for glucose, HbA 1c , adiponectin, C-peptide, fructosamine, insulin like growth factor 1 (IGF-1), insulin like growth factor binding protein 3 (IGFBP-3), insulin, lactate and pyruvate were identified using a systematic literature search. These publications were assessed using the BIVAC, receiving grades A, B, C or D, where A is of highest quality. A meta-analysis of the BVD from the assessed studies utilised weightings based upon BIVAC grades and the width of the data confidence intervals to generate global BVD estimates. Results BIVAC assessment of 47 publications delivered 1 A, 3 B, 39C and 4 D gradings. Publications relating to adiponectin, C-peptide, IGF-1, IGFBP-3, lactate and pyruvate were all assessed as grade C. Meta-analysis enabled global BV estimates for all analytes except pyruvate, lactate and fructosamine. Conclusions This study delivers updated and evidence-based BV estimates for diabetes-related analytes. There remains a need for delivery of new high-quality BV studies for several clinically important analytes. Highlights • Reliable Biological Variation estimates are necessary for optimal diagnosis and monitoring of DM. • This study provides updated and evidence-based estimates of CV I and CV G values for DM. • This systematic review and quality assessment of published data will deliver BVD sets to be made available on the EFLM BV website. [ABSTRACT FROM AUTHOR]

Metaphyseal bony outgrowths are a well-recognized feature of fibrodysplasia ossificans progressiva (FOP) phenotype, but its genuine frequency, topographic distribution, morphological aspect, and potential implications are not fully established. To better ascertain the frequency and characteristics of osteocartilaginous exostoses in FOP disease, we conducted a cross-sectional radiological study based on all the traceable cases identified in a previous comprehensive national research. Metaphyseal exostoses were present in all the 17 cases of FOP studied. Although most often arising from the distal femoral (where metaphyseal exostoses adopt a peculiar not yet reported appearance) and proximal tibial bones, we have found that they are not restricted to these areas, but rather can be seen scattered at a variety of other skeletal sites. Using nuclear magnetic resonance imaging, we show that these exophytic outgrowths are true osteochondromas. As a whole, these results are in agreement with data coming from the literature review. Our study confirms the presence of metaphyseal osteochondromas as a very frequent trait of FOP phenotype and an outstanding feature of its anomalous skeletal developmental component. In line with recent evidences, this might imply that dysregulation of BMP signaling, in addition to promoting exuberant heterotopic ossification, could induce aberrant chondrogenesis and osteochondroma formation. Unveiling the molecular links between these physiopathological pathways could help to illuminate the mechanisms that govern bone morphogenesis. [ABSTRACT FROM AUTHOR]

We present results on the K*(892)+ production in proton-proton collisions at a beam energy of E = 3.5 GeV, which is hitherto the lowest energy at which this mesonic resonance has been observed in nucleon-nucleon reactions. The data are interpreted within a two-channel model that includes the 3-body production of K*(892)+ associated with the Lambda- or Sigma-hyperon. The relative contributions of both channels are estimated. Besides the total cross section sigma(p+p→K*(892)++X) = 9.5 +- 0.9 +1.1-0.9±0.7 μub, that adds a new data point to the excitation function of the K*(892)+ production in the region of low excess energy, transverse momenta and angular spectra are extracted and compared with the predictions of the two-channel model. The spin characteristics of K*(892)+ are discussed as well in terms of the spin-alignment. [ABSTRACT FROM AUTHOR]

An exclusive analysis of the four-body final states +p+p++Ko and So+p+p++Ko measured with HADES for p+p collisions at a beam kinetic energy of 3.5 GeV is presented. The analysis uses various phase space variables, such as missing mass and invariant mass distributions, in the four-particle event selection (p,p+,p+,p-) to find cross sections of the different production channels, contributions of the intermediate resonances ++ and S(1385)+, and corresponding angular distributions. A dominant resonant production is seen, where the reaction ++++K0 has a cross section about ten times higher (29.45±0.08+1.67-1.46±2.06µb) than the analogous nonresonant reaction (2.57±0.02+0.21-1.98±0.18µb). A similar result is obtained in the corresponding S0 channels with 9.26±0.05+1.41-0.31±0.65µb in the resonant and 1.35±0.02+0.10-1.35±0.09µb in the nonresonant reactions [ABSTRACT FROM AUTHOR]

A high-statistic data sample of Ar(1.76 AGeV)+KCl events recorded with HADES is used to search for a hypertriton signal. An upper production limit per centrality-triggered event of $ 1.04\times 10^{-3}$ on the 3 $ \sigma$ level is derived. Comparing this value with the number of successfully reconstructed $ \Lambda$ hyperons allows to determine an upper limit on the ratio $ N_{_{\Lambda}^{3}H}/N_{\Lambda}$ , which is confronted with statistical and coalescence-type model calculations. [ABSTRACT FROM AUTHOR]

A real-time wavelet-matched optical correlator is implemented by using four-wave mixing via reflection gratings. Photorefractive crystals BSO with different thickness are used in the experimental set-up. The square modulus of the Fourier transform of the Mexican-hat wavelet has been utilized to implement the wavelet filtering. The edge enhancement property of the wavelet transform is experimentally demonstrated in this scheme. Several non-binary filters with different dilation factors have been considered for different crystal thicknesses. When proper dilation factors are used, a higher robustness to the noise introduced by the finite crystal depth is obtained. The convenience to use a non-binary filter is experimentally demonstrated. [Copyright &y& Elsevier]

Flow coefficients v_{n} of the orders n=1-6 are measured with the High-Acceptance DiElectron Spectrometer (HADES) at GSI for protons, deuterons, and tritons as a function of centrality, transverse momentum, and rapidity in Au+Au collisions at sqrt[s_{NN}]=2.4  GeV. Combining the information from the flow coefficients of all orders allows us to construct for the first time, at collision energies of a few GeV, a multidifferential picture of the angular emission pattern of these particles. It reflects the complicated interplay between the effect of the central fireball pressure on the emission of particles and their subsequent interaction with spectator matter. The high precision information on higher order flow coefficients is a major step forward in constraining the equation of state of dense baryonic matter.

We present the first observation of K^{-} and ϕ absorption within nuclear matter by means of π^{-}-induced reactions on C and W targets at an incident beam momentum of 1.7  GeV/c studied with HADES at SIS18/GSI. The double ratio (K^{-}/K^{+})_{W}/(K^{-}/K^{+})_{C} is found to be 0.319±0.009(stat)_{-0.012}^{+0.014}(syst) indicating a larger absorption of K^{-} in heavier targets as compared to lighter ones. The measured ϕ/K^{-} ratios in π^{-}+C and π^{-}+W reactions within the HADES acceptance are found to be equal to 0.55±0.04(stat)_{-0.07}^{+0.06}(syst) and to 0.63±0.06(stat)_{-0.11}^{+0.11}(syst), respectively. The similar ratios measured in the two different reactions demonstrate for the first time experimentally that the dynamics of the ϕ meson in nuclear medium is strongly coupled to the K^{-} dynamics. The large difference in the ϕ production off C and W nuclei is discussed in terms of a strong ϕN in-medium coupling. These results are relevant for the description of heavy-ion collisions and the structure of neutron stars.

Results on the production of the double strange cascade hyperon Ξ^{-} are reported for collisions of p(3.5  GeV)+Nb, studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18 at GSI Helmholtzzentrum for Heavy-Ion Research, Darmstadt. For the first time, subthreshold Ξ^{-} production is observed in proton-nucleus interactions. Assuming a Ξ^{-} phase-space distribution similar to that of Λ hyperons, the production probability amounts to P_{Ξ^{-}}=[2.0±0.4(stat)±0.3(norm)±0.6(syst)]×10^{-4} resulting in a Ξ^{-}/(Λ+Σ^{0}) ratio of P_{Ξ^{-}}/P_{Λ+Σ^{0}}=[1.2±0.3(stat)±0.4(syst)]×10^{-2}. Available model predictions are significantly lower than the measured Ξ^{-} yield.

Predicting the localization of a protein has become a useful practice for inferring its function. Most of the reported methods to predict subcellular localizations in Gram-negative bacterial proteins make use of standard protein representations that generally do not take into account the distribution of the amino acids and the structural information of the proteins. Here, we propose a protein representation based on the structural information contained in the pairwise statistical contact potentials. The wavelet transform decodes the information contained in the primary structure of the proteins, allowing the identification of patterns along the proteins, which are used to characterize the subcellular localizations. Then, a support vector machine classifier is trained to categorize them. Cellular compartments like periplasm and extracellular medium are difficult to predict, having a high false negative rate. The wavelet-based method achieves an overall high performance while maintaining a low false negative rate, particularly, on "periplasm" and "extracellular medium". Our results suggest the proposed protein characterization is a useful alternative to representing and predicting protein sequences over the classical and cutting edge protein depictions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Nowadays, the use of Wearable User Interfaces has been extensively growing in medical monitoring applications. However, production and manufacture of prototypes without automation tools may lead to non viable results since it is often common to find an optimization problem where several variables are in conflict with each other. Thus, it is necessary to design a strategy for balancing the variables and constraints, systematizing the design in order to reduce the risks that are present when it is exclusively guided by the intuition of the developer. This paper proposes a framework for designing wearable ECG monitoring systems using multi-objective optimization. The main contributions of this work are the model to automate the design process, including a mathematical expression relating the principal variables that make up the criteria of functionality and wearability. We also introduce a novel yardstick for deciding the location of electrodes, based on reducing interference from ECG by maximizing the electrode-skin contact.

A comparative analysis of four multi-label classification methods is performed in order to determine the best topology for the problem of protein function prediction, using support vector machines as base classifiers. Comparisons are done in terms of performance and computational cost of parallelized versions of the algorithms, for determining its applicability in high-throughput scenarios. Results show that the performance of the binary relevance strategy, together with a technique of class balance, remains above several recently proposed techniques for the problem at hand, while employing the smallest computational cost when parallelized. However, stacked classfiers and chain classifications can be conveniently used in pipelines, due to the low number of false positives reported.

Predicting the localization of a protein has become a useful practice for inferring its function. Most of the reported methods to predict subcellular localizations in Gram-negative bacterial proteins have shown a low false positive rate. However, some subcellular compartmens like "periplasm" and "extracellular medium" are difficult to predict and remain high false negative rates. In this paper, a method based on representation from statistical contact potentials and wavelet transform is presented. The wavelet-based method achieves an overall high performance holding low false and negative rates particularly on periplasm and extracellular medium. Results suggest the contact potentials as an useful alternative to characterize protein sequences.

Predicting the sub-cellular localization of a protein can provide useful information to uncover its molecular functions. In this sense, numerous prediction techniques have been developed, which usually have been focused on global information of the protein or sequence alignments. However, several studies have shown that the functional nature of proteins is ruled by conserved sub-sequence patterns known as domains. In this paper, an alternative methodology (PfamFeat) for gram-positive bacterial sub-cellular localization was developed. PfamFeat is based on information provided by Pfam database, which stores a series of HMM-profiles describing common protein domains. The likelihood of a sequence, to be generated by a given HMM-profile, can be used to characterize sequences in order to use pattern recognition techniques. Success rates obtained with a simple one-nearest neighbor classifier demonstrate that this method is competitive with popular sub-cellular prediction algorithms and it constitutes a promising research trend.

Predict the function of unknown proteins is one of the principal goals in computational biology. The subcellular localization of a protein allows further understanding its structure and molecular function. Numerous prediction techniques have been developed, usually focusing on global information of the protein. But, predictions can be done through the identification of functional sub-sequence patterns known as motifs. For motifs discovery problem, many methods requires a predefined fixed window size in advance and aligned sequences. To confront these problems we proposed a method based on variable length motifs characterization and detection using the continuous wavelet transform (CWT) and a dissimilarity space representation. For analyzing the motifs results generated by our approach, we divide the entire dataset into training (60%) and validation (40%). A Support Vector Machine (SVM) classifier is used as predictor for validation set. The highest Sn = 82.58% and Sp = 92.86%, across 10-fold cross validation, is obtained for endosome proteins. Average results Sn = 74% and Sp = 75.58% are comparable to current state of the art. For data sets whose identity is low (< 40%), the motifs characterization and localization based on CWT shows a good performance and the interpretability of the subsequences in each subcellular localization.

We report first results on a deep subthreshold production of the doubly strange hyperon Xi;{-} in a heavy-ion reaction. At a beam energy of 1.76A GeV the reaction Ar + KCl was studied with the High Acceptance Di-Electron Spectrometer at SIS18/GSI. A high-statistics and high-purity Lambda sample was collected, allowing for the investigation of the decay channel Xi;{-} --> Lambdapi;{-}. The deduced Xi;{-}/(Lambda + Sigma;{0}) production ratio of (5.6 +/- 1.2&#95;{-1.7};{+1.8}) x 10;{-3} is significantly larger than available model predictions.

The invariant-mass spectrum of e+e- pairs produced in 12C+12C collisions at an incident energy of 2 GeV per nucleon has been measured for the first time. The measured pair production probabilities span over 5 orders of magnitude from the pi(0)-Dalitz to the rho/omega invariant-mass region. Dalitz decays of pi(0) and eta account for all the yield up to 0.15 GeV/c(2), but for only about 50% above this mass. A comparison with model calculations shows that the excess pair yield is likely due to baryon-resonance and vector-meson decays. Transport calculations based on vacuum spectral functions fail, however, to describe the entire mass region.

Reporting a nervous tumor diagnosed as Neurofibroma, which owing to its localisation, on the lower lip, and its possible origin, from a salivary gland, should be considered an extraordinary rarity. The AA, make a bibliographic review of the commonest sites of the growth, the histological description and consider some possible differential diagnosis with special emphasis to the schwannoma and the Recklinghausen's disease.