Prediction of osteoporotic hip fracture in postmenopausal women through patient-specific FE analyses and machine learning

[EN] A great challenge in osteoporosis clinical assessment is identifying patients at higher risk of hip fracture. Bone Mineral Density (BMD) measured by Dual-Energy X-Ray Absorptiometry (DXA) is the current gold-standard, but its classification accuracy is limited to 65%. DXA-based Finite Element (FE) models have been developed to predict the mechanical failure of the bone. Yet, their contribution has been modest. In this study, supervised machine learning (ML) is applied in conjunction with clinical and computationally driven mechanical attributes. Through this multi-technique approach, we aimed to obtain a predictive model that outperforms BMD and other clinical data alone, as well as to identify the best-learned ML classifier within a group of suitable algorithms. A total number of 137 postmenopausal women (81.4 +/- 6.95 years) were included in the study and separated into a fracture group (n = 89) and a control group (n = 48). A semi-automatic and patient-specific DXA-based FE model was used to generate mechanical attributes, describing the geometry, the impact force, bone structure and mechanical response of the bone after a sideways-fall. After preprocessing the whole dataset, 19 attributes were selected as predictors. Support Vector Machine (SVM) with radial basis function (RBF), Logistic Regression, Shallow Neural Networks and Random Forest were tested through a comprehensive validation procedure to compare their predictive performance. Clinical attributes were used alone in another experimental setup for the sake of comparison. SVM was confirmed to generate the best-learned algorithm for both experimental setups, including 19 attributes and only clinical attributes. The first, generated the best-learned model and outperformed BMD by 14pp. The results suggests that this approach could be easily integrated for effective prediction of hip fracture without interrupting the actual clinical workflow.This study was partially funded by two grants Catedra UPVFundacion Quaes, obtained by Eduardo Villamor Medina and Antonio Cutillas Pardines, and one FPI grant (FPI-SP20170111) from the Universitat Politecnica de Valencia obtained by Eduardo Villamor Medina.Villamor, E.; Monserrat Aranda, C.; Del Río, L.; Romero-Martín, J.; Rupérez Moreno, MJ. (2020). Prediction of osteoporotic hip fracture in postmenopausal women through patient-specific FE analyses and machine learning. Computer Methods and Programs in Biomedicine. 193:1-11. https://doi.org/10.1016/j.cmpb.2020.105484S111193Holt, G., Smith, R., Duncan, K., Hutchison, J. D., & Reid, D. (2009). Changes in population demographics and the future incidence of hip fracture. 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C., Schiffers, N., Pandorf, T., Radermacher, K., Weichert, D., & Forst, R. (2000). Critical evaluation of known bone material properties to realize anisotropic FE-simulation of the proximal femur. Journal of Biomechanics, 33(10), 1325-1330. doi:10.1016/s0021-9290(00)00069-5Eckstein, F., Wunderer, C., Boehm, H., Kuhn, V., Priemel, M., Link, T. M., & Lochmüller, E.-M. (2003). Reproducibility and Side Differences of Mechanical Tests for Determining the Structural Strength of the Proximal Femur. Journal of Bone and Mineral Research, 19(3), 379-385. doi:10.1359/jbmr.0301247Orwoll, E. S., Marshall, L. M., Nielson, C. M., Cummings, S. R., Lapidus, J., … Cauley, J. A. (2009). Finite Element Analysis of the Proximal Femur and Hip Fracture Risk in Older Men. Journal of Bone and Mineral Research, 24(3), 475-483. doi:10.1359/jbmr.081201Choi, W. J., Cripton, P. A., & Robinovitch, S. N. (2014). 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Osteoporosis International, 23(2), 513-520. doi:10.1007/s00198-011-1569-2Schileo, E., Taddei, F., Cristofolini, L., & Viceconti, M. (2008). Subject-specific finite element models implementing a maximum principal strain criterion are able to estimate failure risk and fracture location on human femurs tested in vitro. Journal of Biomechanics, 41(2), 356-367. doi:10.1016/j.jbiomech.2007.09.009Mautalen, C. A., Vega, E. M., & Einhorn, T. A. (1996). Are the etiologies of cervical and trochanteric hip fractures different? Bone, 18(3), S133-S137. doi:10.1016/8756-3282(95)00490-4Yang, S., Leslie, W. D., Luo, Y., Goertzen, A. L., Ahmed, S., Ward, L. M., … Lix, L. M. (2017). Automated DXA-based finite element analysis for hip fracture risk stratification: a cross-sectional study. Osteoporosis International, 29(1), 191-200. doi:10.1007/s00198-017-4232-8Testi, D., Viceconti, M., Cappello, A., & Gnudi, S. (2002). 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Orientational transitions in a nematic confined by competing surfaces

The effect of confinement on the orientational structure of a nematic liquid crystal model has been investigated by using a version of density-functional theory (DFT). We have focused on the case of a nematic confined by opposing flat surfaces, in slab geometry (slit pore), which favor planar molecular alignment (parallel to the surface) and homeotropic alignment (perpendicular to the surface), respectively. The spatial dependence of the tilt angle of the director with respect to the surface normal has been studied, as well as the tensorial order parameter describing the molecular order around the director. For a pore of given width, we find that, for weak surface fields, the alignment of the nematic director is perpendicular to the surface in a region next to the surface favoring homeotropic alignment, and parallel along the rest of the pore, with a interface separating these regions (S phase). For strong surface fields, the director is distorted uniformly, the tilt angle exhibiting a linear dependence with the distance normal to the surface (L phase). Our calculations reveal the existence of a first-order transition between the two director configurations, which is driven by changes in the surface field strength, and also by changes in the pore width. In the latter case the transition occurs, for a given surface field, between the S phase for narrow pores and the L phase for wider pores. A link between the L-S transition and the anchoring transition observed for the semi-infinite case is proposed. We also provide calculations with a phenomenological approach that yields the same main result that DFT in the scale length where this is valid.Comment: submitted to PR

Cenozoic deformation of Iberia: a model for intraplate mountain building and basin development based on analogue modelling

Inferences from analogue models support lithospheric folding as the primary response to large-scale shortening manifested in the present day topography of Iberia. This process was active from the late Oligocene-early Miocene during the Alpine orogeny and was probably enhanced by reactivation of inherited Variscan faults. The modeling results confirm the dependence of fold wavelength on convergence rate and hence the strength of the layers of the lithosphere such that fold wavelength is longest for fast convergence rates favoring whole lithosphere folding. Folding is associated with the formation of dominantly pop-up type mountain ranges in the brittle crust and thickening of the ductile layers in the synforms of the buckle folds by flow. The mountain ranges are represented by upper crustal pop-ups forming the main topographic relief. The wavelengths of the topographic uplifts, both, in model and nature suggest mechanical decoupling between crust and mantle. Moreover, our modeling results suggest that buckling in Iberia took place under rheological conditions where the lithospheric mantle is stronger than the lower crust. The presence of an indenter, inducing oblique shortening in response to the opening of the King's Trough in the north western corner of the Atlantic Iberian margin controls the spacing and obliquity of structures. This leads to the transfer of the deformation from the moving walls towards the inner part of the model, creating oblique structures in both brittle and ductile layers. The effect of the indenter, together with an increase on the convergence rate produced more complex brittle structures. These results show close similarities to observations on the general shape and distribution of mountain ranges and basins in Iberia, including the Spanish Central System and Toledo Mountains.Peer reviewe

BiFiSo-CSIC: balance de una lucha multidisciplinar contra la pandemia

En marzo de 2020 se declaró el estado de emergencia en España a raíz de una pandemia causada por el virus llamado SARS-CoV-2. La enfermedad, denominada COVID-19, produce una gran letalidad en personas de edad avanzada. Estas excepcionales circunstancias dictaron medidas inéditas en nuestro país: confinamiento domiciliario, cierre de colegios y comercios no esenciales. El Consejo Superior de Investigaciones Científicas (CSIC) reaccionó de inmediato: recién iniciado el confinamiento todos los investigadores de esta institución fueron convocados para dedicar parte de su tiempo a investigar sobre la pandemia. La respuesta fue instantánea y personas de todas las áreas de investigación se brindaron a contribuir con su granito de arena. Lo que al principio iba a suponer una media del 20% del tiempo de cada investigador pasó a ocupar toda la jornada: y así hasta hoy. En este contexto surge el proyecto BiFiSo, en el cual desde la biología, la filosofía o la antropología hemos estudiado y explicado la pandemia, complementando mutuamente la visión de nuestras respectivas especialidades.Consejo Superior de Investigaciones Científicas aporta financiación como institución fundacional de The Conversation ES. Universidad de Málaga aporta financiación como institución colaboradora de The Conversation ES.Peer reviewe

Hidratos de gas marinos: ¿un recurso futuro de gas natural para Europa? M.

Los hidratos de gas son compuestos cristalinos donde una molécula de gas, principalmente metano, queda atrapada en una red de moléculas de agua en forma de hielo. La importancia de los hidratos de gas en la naturaleza es muy alta ya que constituye una fuente alternativa de energía y a su vez juegan un papel importante en el delicado equilibrio del clima a nivel global y en los riesgos geológicos en el ámbito marino. La acción COST MIGRATE está diseñada con el fin de integrar la experiencia de un gran número de grupos de investigación europeos y agentes del sector para promover el desarrollo de conocimientos multidisciplinarios sobre el potencial de los hidratos de gas como fuente de energía en Europa. Dos de los objetivos de esta acción son realizar un inventario europeo de hidratos de gas explotables y evaluar los riesgos ambientales. En este trabajo se muestran los principales indicios de hidratos de gas en los márgenes europeos incluida la Península Ibérica, con una primera aproximación sobre el espesor y situación de la zona de estabilidad de hidratos de gas en el margen Ibérico.Gas hydrates are crystalline compounds where a molecule of gas, mainly methane, is trapped in a cage of icewater molecules. The importance of gas hydrates in nature is very high because it is an alternative source of energy and play a major role in the delicate balance of the global climate and in the marine geological risks. MIGRATE COST action is designed to integrate the experience of a large number of European research groups and industrial players to promote the development of multidisciplinary knowledge on the potential of gas hydrates as energy resource in Europe. Two of the objectives of the action aim to estimate the European inventory of exploitable gas hydrates and to assess environmental risks. In this work we show the occurrences of gas hydrates described in European margins including the Iberian Peninsula, with a first approximation on the thickness and location of the area of stability of gas hydrates in the Iberian margin.COST Action ES1405 (MIGRATE)Versión del edito

Guía de práctica clínica SENPE/SEGHNP/SEFH sobre nutrición parenteral pediátrica

Introduction: Parenteral nutrition (PN) in childhood is a treatment whose characteristics are highly variable depending on the age and pathology of the patient. Material and methods: The Standardization and Protocols Group of the Spanish Society for Parenteral and Enteral Nutrition (SENPE) is an interdisciplinary group formed by members of the SENPE, the Spanish Society of Gastroenterology, Hepatology and Pediatric Nutrition (SEGHNP) and the Spanish Society of Hospital Pharmacy (SEFH) that intends to update this issue. For this, a detailed review of the literature has been carried out, looking for the evidences that allow us to elaborate a Clinical Practice Guide following the criteria of the Oxford Center for Evidence-Based Medicine. Results: This manuscript summarizes the recommendations regarding indications, access routes, requirements, modifications in special situations, components of the mixtures, prescription and standardization, preparation, administration, monitoring, complications and home NP. The complete document is published as a monographic number. Conclusions: This guide is intended to support the prescription of pediatric PN. It provides the basis for rational decisions in the context of the existing evidence. No guidelines can take into account all of the often compelling individual clinical circumstances.Introducción: la nutrición parenteral (NP) en la infancia es un tratamiento cuyas características son muy variables en función de la edad y la patología que presente el paciente. Material y métodos: el grupo de Estandarización y Protocolos de la Sociedad Española de Nutrición Parenteral y Enteral (SENPE) es un grupo interdisciplinar formado por miembros de la SENPE, Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP) y Sociedad Española de Farmacia Hospitalaria (SEFH) que pretende poner al día este tema. Para ello, se ha realizado una revisión pormenorizada de la literatura buscando las evidencias que nos permiten elaborar una Guía de Práctica Clínica siguiendo los criterios del Oxford Centre for Evidence-Based Medicine. Resultados: este manuscrito expone de forma resumida las recomendaciones en cuanto a indicaciones, vías de acceso, requerimientos, modificaciones en situaciones especiales, componentes de las mezclas, prescripción y estandarización, preparación, administración, monitorización, complicaciones y NP domiciliaria. El documento completo se publica como número monográfico. Conclusiones: esta guía pretende servir de apoyo para la prescripción de la NP pediátrica. Constituye la base para tomar decisiones en el contexto de la evidencia existente. Ninguna guía puede tener en cuenta todas las circunstancias clínicas individuale

Transcriptomics of Haemophilus (Glässerella) parasuis serovar 5 subjected to culture conditions partially mimetic to natural infection for the search of new vaccine antigens

11 p.Haemophilus (Glässerella) parasuis is the etiological agent of Glässer’s disease in pigs. Control of this disorder has been traditionally based on bacterins. The search for alternative vaccines has focused mainly on the study of outer membrane proteins. This study investigates the transcriptome of H. (G.) parasuis serovar 5 subjected to in vitro conditions mimicking to those existing during an infection (high temperature and iron-restriction), with the aim of detecting the overexpression of genes coding proteins exposed on bacterial surface, which could represent good targets as vaccine candidates. The transcriptomic approach identified 13 upregulated genes coding surface proteins: TbpA, TbpB, HxuA, HxuB, HxuC, FhuA, FimD, TolC, an autotransporter, a protein with immunoglobulin folding domains, another large protein with a tetratricopeptide repeat and two small proteins that did not contain any known domains. Of these, the first six genes coded proteins being related to iron extraction. Six of the proteins have already been tested as vaccine antigens in murine and/or porcine infection models and showed protection against H. (G.) parasuis. However, the remaining seven have not yet been tested and, consequently, they could become useful as putative antigens in the prevention of Glässer’s disease. Anyway, the expression of this seven novel vaccine candidates should be shown in other serovars different from serovar 5.S

Zipf's Law in Short-Time Timbral Codings of Speech, Music, and Environmental Sound Signals

Timbre is a key perceptual feature that allows discrimination between different sounds. Timbral sensations are highly dependent on the temporal evolution of the power spectrum of an audio signal. In order to quantitatively characterize such sensations, the shape of the power spectrum has to be encoded in a way that preserves certain physical and perceptual properties. Therefore, it is common practice to encode short-time power spectra using psychoacoustical frequency scales. In this paper, we study and characterize the statistical properties of such encodings, here called timbral code-words. In particular, we report on rank-frequency distributions of timbral code-words extracted from 740 hours of audio coming from disparate sources such as speech, music, and environmental sounds. Analogously to text corpora, we find a heavy-tailed Zipfian distribution with exponent close to one. Importantly, this distribution is found independently of different encoding decisions and regardless of the audio source. Further analysis on the intrinsic characteristics of most and least frequent code-words reveals that the most frequent code-words tend to have a more homogeneous structure. We also find that speech and music databases have specific, distinctive code-words while, in the case of the environmental sounds, this database-specific code-words are not present. Finally, we find that a Yule-Simon process with memory provides a reasonable quantitative approximation for our data, suggesting the existence of a common simple generative mechanism for all considered sound sources

Guía Mexicana de Práctica Clínica de Inmunoterapia 2011

Existen varias guías internacionales para la práctica clínica de in- munoterapia, que aplican solo parcialmente en México. La primera guía mexicana de inmunoterapia data de 1998

External validation of multidimensional prognostic indices (ADO, BODEx and DOSE) in a primary care international cohort (PROEPOC/COPD cohort)

Background: Due to the heterogeneous and systemic nature of the chronic obstructive pulmonary disease (COPD), the new guidelines are oriented toward individualized attention. Multidimensional scales could facilitate its proper clinical and prognostic assessment, but not all of them were validated in an international primary care cohort, different from the original ones used for model development. Therefore, our main aim is to assess the prognostic capacity of the ADO, BODEx and DOSE indices in primary care for predicting mortality in COPD patients and to validate the models obtained in subgroups of patients, classified by revised Global Initiative for Chronic Obstructive Lung Disease (2011) and updated Spanish Guideline (2014). Besides, we want to confirm that the prognostic capacity of all indices increases if the number of exacerbations is substituted by the interval between them and to assess the impact on health of the patient''s lifestyle, social network and adherence to treatment. Methods: Design: External validation of scales, open and prospective cohort study in primary care. Setting: 36 health centres in 6 European high, medium and low income countries. Subjects: 477 patients diagnosed with COPD, captured in clinical visit by their General Practitioner/Nurse. Predictors: Detailed patient history, exacerbations, lung function test and questionnaires at baseline. Outcomes: Exacerbations, all-cause mortality and specific mortality, within 5 years of recruitment. Analysis: Multivariate logistic regression and Cox regression will be used. Possible non-linear effect of the indices will be studied by using Structured Additive Regression models with penalised splines. Subsequently, we will assess different aspects of the regression models: discrimination, calibration and diagnostic precision. Clinical variables modulated in primary care and the interval between exacerbations will be considered and incorporated into the analysis. Discussion: The Research Agenda for General Practice/Family Medicine highlights that the evidence on predictive values of prognostic indices in primary care is scarce. A prospective cohort like that of PROEPOC/COPD provides good opportunities for research into COPD and make communication easier between family practitioners, nursing staff, pneumologists and other professionals, supporting a multi-disciplinary approach to the treatment of these patients. Trial registration:ISRCTN52402811. Date: 15/01/2015. Prospectively registered