Stress-strain response and microstructural evolution of a FeMnCAl TWIP steel during tension-compression tests

© 2016. The stress-strain response of a Fe-17.5Mn-0.7C-2Al TWIP steel during cyclic loading has been investigated by means of tension-compression tests within the strain limits of ±2%, ±5% and ±10%. In addition, the microstructural evolution during the ±5% cyclic test has also been studied. The difference between the forward and reverse stress for each pre-strain has been analyzed at 0.2% offset strain and at the strains in which forward and reverse curves were parallel in order to study the Bauschinger effect (BE) and permanent softening, respectively. The evolution of the BE with pre-strain for this steel is similar to other FeMnC TWIP steels, that is, increasing values of BE are obtained as the pre-strain increases. However, its absolute values are half those reported in the literature on other FeMnC steels. This diminution of the BE is related to the lower activity of mechanical twinning in FeMnCAl TWIP steels at the pre-strains herein investigated, which promotes less polarized stresses in the matrix due to the lower dislocation storage capacity.Regarding permanent softening, the evolution is similar to that of the BE and the same analysis can be applied. During reverse compression, a slight increase of twin thickness and twin spacing with respect to the first tensile stage took place. This fact might be linked to the lower flow stress observed in the permanent softening period during reverse straining.Peer ReviewedPostprint (author's final draft

Acute non compressive myelopathies

[eng] BACKGROUND: Acute transverse myelitis (ATM) may be the prelude of a wide range of diseases such as Multiple Sclerosis (MS), autoimmune, infectious, post-vacunal, post-radiotherapy and tumor related disorders. Nonetheless, the underlying etiology remains elusive in up to 16% of ATM patients. In 2002, the Transverse Myelitis Consortium Working Group (TMCWG) proposed some criteria in order to unify the concept of idiopathic ATM (IATM). ATM may present as a longitudinal extensive transverse myelitis (LETM) on the spinal Magnetic Resonance Imaging. LETM is a cardinal symptom of Neuromyelitis optica (NMO), an autoimmune chronic disease characterized by recurrent optic neuritis (ON) or LETM. In 2004, a pathogenic antibody, known as aquaporin-4 antibody (AQP4–ab) was directly related to NMO or limited forms of the disease such as LETM. Nonetheless, up to 50% of LETM patients are AQP4-ab seronegative. Recently, antibodies against the myelin- oligodendrocyte glycoprotein (MOG-ab) have been described in AQP4-ab seronegative NMO patients or limited forms of the disease. AIMS: The current work is divided in three studies. In the first study, we aimed to describe the MS conversion ratio and to identify baseline factors related to MS conversion, as well as to analyze baseline prognostic factors of disability in IATM patients fulfilling the 2002 TMCWG. In the second study, we sought to describe the etiological LETM spectrum and to analyze baseline prognostic factors related to outcome in this subgroup of patients. Finally, in the third study, we set out to describe the frequency of MOG-ab in AQP4-ab seronegative LETM and searched for differences between MOG-ab positive and negative AQP4-ab seronegative LETM patients. METHODOLOGY: The first and second studies were performed in a single center and we reviewed the epidemiological, clinical, laboratory and radiological data of 85 IATM patients fulfilling the TMCWG and 72 LETM patients. The third study is a multicenter European study with data collected in a prospective manner. AQP4-ab or MOG- ab were detected by immunohistochemistry in the two first studies and by cell based assays in the third study. All data were retrospectively analyzed. RESULTS: At the end of the first study, 13% of IATM converted to MS and an early onset of symptoms was related to MS conversion. However, laboratory findings such a negative result in the combination of oligoclonal bands (OCB) and IgG index in the cerebrospinal fluid (CSF) ruled out MS conversion. We observed that LETM and urinary sphincter dysfunction were independent baseline prognostic factors related to disability and that up to 37% of IATM patients had a final modified Rankin Score more (mRS) ≥ 2. In LETM patients, the idiopathic group and MS were the most frequent disorders involved (30.5% and 25%, respectively). NMO or limited forms were observed in less than 5%. The mRS was ≥2 at the end of follow-up in 72.2%. The presence of higher disability at onset of symptoms and elderly were independent baseline prognostic factors of disability. Up to 23% of patients presenting with AQP4-ab seronegative LETM tested positive for MOG-ab in serum. MOG-ab positive patients were younger, had CSF pleocytosis more frequently and had better outcome. Moreover, MOG-ab positive patients also showed an increase risk of ON relapse and NMO conversion. CONCLUSIONS: We identified that a subgroup of IATM patients may convert to MS, even when fulfilling the 2002 TMCWG criteria. Functional recovery in IATM is poorer in patients with urinary sphincter dysfunction at admission or LETM on MRI. We established the LETM etiological spectrum. In this subgroup of patients, while idiopathic and MS group were the most frequently involved, others such as NMO were marginally observed. Older age and clinically severe disease at onset were independent prognostic factors of poorer functional recovery in LETM patients. Finally we found that MOG-ab are present in a proportion of AQP4-ab seronegative LETM patients defining a subgroup of patients with clinical distinctive features, higher risk of ON relapses, and better outcome.[spa] Las mielitis transversas agudas (MTA) pueden ser el comienzo de una amplia diversidad de enfermedades, siendo la más frecuente la Esclerosis Múltiple (EM). Hasta en el 16% de los pacientes que presentan una MTA, la etiología será desconocida. Un consorcio internacional (TMCWG) propuso en el año 2002 unos criterios con el fin de unificar el concepto de MTA idiopática (MTAI). Las MTA pueden presentarse como una afectación extensa de la médula espinal (LETM), siendo ésta una característica de la Neuromielitis óptica (NMO). Los anticuerpos aquaporina 4 (AQP4-ac) se objetivan en la mayoría de estos pacientes y formas limitadas de esta enfermedad, como la LETM. Sin embargo, una proporción de estos pacientes no presentan AQP4-ac y otros anticuerpos como los anticuerpos contra myelin oligodendrocyte glycoprotein (MOG-ac) han sido recientemente asociados. El presente trabajo se divide en tres estudios (dos unicéntricos y un tercero multicéntrico europeo) que tienen como objetivo describir las características de los pacientes con una MTAI, pacientes con LETM así como identificar las características de aquellos pacientes con una LETM que presenten MOG-ac. Se identificó un subgrupo no despreciable de pacientes que convertirán a EM aunque cumplan los criterios de la TMCGW para MTAI. Además se objetivó que el pronóstico es peor en pacientes con una MTAI que presentan disfunción urinaria y LETM al comienzo de los síntomas. Por otra parte, describimos el espectro etiológico de pacientes con LETM, objetivando que en la mayor parte de ellos, la causa es idiopática. Los pacientes con una LETM tendrán peor pronóstico a más edad y a mayor discapacidad al inicio de los síntomas. Finalmente, encontramos que hasta un 23% de los pacientes que presentan LETM y son seronegativos para AQP4-ac, tienen MOG-ac en el suero. Estos pacientes presentan características clínicas distintivas, mayor riesgo de neuritis óptica, de recidivas y mejor pronóstico que los pacientes sin el anticuerpo

Análisis y diagnóstico de las obras huérfanas: una perspectiva internacional

Se presenta un estado de la cuestión e iniciativas relacionadas con la temática obras huérfanas y búsqueda diligente en los siguientes países seleccionados como referentes internacionales: Australia, Canadá, Estados Unidos y el conjunto de los 28 estados miembros de la Unión Europea. El estudio se basa en un análisis de contenido de las fuentes de información citadas en el epígrafe de fuentes y bibliografía de cada uno de los estudios de caso analizados. El informe es el resultado de la investigación realizada por los firmantes del mismo en relación con la orientación del “Observatorio de Obras Huérfanas y Búsqueda Diligente” constituido con la misión de proporcionar directrices y pautas a aquellas instituciones documentales españolas que se propongan iniciar y desarrollar procesos de búsqueda diligente para la declaración de obras huérfanas

Is There a Solution to the Orphan Works Problem? Exploring the International Models

Aspects related to copyright and orphan works become a real obstacle for cultural institutions wishing to undertake major projects for the digitisation and on-line availability of their collections. Although some countries have already established models to try to solve the problem of orphan works, others are still discussing possible options. The paper explores the current situation of the schemes in place internationally to deal with the problems associated with orphan works and how these are being applied by cultural institutions regarding the digital dissemination of their collections. The methodology consisted in a systematic review of the research results as an exploratory analytical technique for the collection of relevant information. Results highlighted that global situation is uncertain and none of the formulas studied enables full and effective digitisation and digital dissemination of the world’s cultural heritage. Further advances are necessary for the creation of diligent search procedures

Retinal Optical Coherence Tomography in Neuromyelitis Optica

Retina; Pérdida visualRetina; Visual lossRetina; Pèrdua visualBackground and Objectives To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts. Methods The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG–seropositive patients with NMOSD and 72 healthy controls (HCs). Participants underwent OCT with central reading including quality control and intraretinal segmentation. The primary outcome was thickness of combined ganglion cell and inner plexiform (GCIP) layer; secondary outcomes were thickness of peripapillary retinal nerve fiber layer (pRNFL) and visual acuity (VA). Results Eyes with ON (NMOSD-ON, N = 260) or without ON (NMOSD-NON, N = 241) were assessed compared with HCs (N = 136). In NMOSD-ON, GCIP layer (57.4 ± 12.2 μm) was reduced compared with HC (GCIP layer: 81.4 ± 5.7 μm, p < 0.001). GCIP layer loss (−22.7 μm) after the first ON was higher than after the next (−3.5 μm) and subsequent episodes. pRNFL observations were similar. NMOSD-NON exhibited reduced GCIP layer but not pRNFL compared with HC. VA was greatly reduced in NMOSD-ON compared with HC eyes, but did not differ between NMOSD-NON and HC. Discussion Our results emphasize that attack prevention is key to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies ameliorating attack-related damage, especially during a first attack, are an unmet clinical need. Mild signs of neuroaxonal changes without apparent vision loss in ON-unaffected eyes might be solely due to contralateral ON attacks and do not suggest clinically relevant progression but need further investigation.Guthy-Jackson Charitable Foundation (GJCF) and German Research Foundation (DFG)

Idiopathic acute transverse myelitis: outcome and conversion to multiple sclerosis in a large series

Background: in 2002, the Transverse Myelitis Consortium Working Group (TMCWG) proposed the diagnostic criteria for idiopathic acute transverse myelitis (IATM) to delimit and unify this group of patients. This study aimed to describe the conversion rate to multiple sclerosis (MS) and variables associated with conversion, and to analyze functional outcome and prognostic factors associated with functional recovery in patients who fulfilled the current TMCWG criteria for definite and possible IATM. Methods: eighty-seven patients diagnosed with IATM between 1989 and 2011 were retrospectively reviewed. Two patients with positive neuromyelitis optica IgG serum antibodies were excluded. Epidemiological, clinical, laboratory, magnetic resonance imaging (MRI) data and outcome of 85 patients were analyzed. Results: eleven (13%) patients converted to MS after a median follow-up of 2.9 years (interquartile range 1.0-4.8). Early-age onset of symptoms was related to conversion to MS. Only 9.4% of patients with IATM were unable to walk unassisted at the end of follow-up. Urinary sphincter dysfunction (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.04-10.92) and longitudinally extensive transverse myelitis (LETM) on MRI (OR 12.34, 95% CI 3.38-45.00) were associated with a poorer outcome (Rankin ≥ 2). Conclusions: at least 13% of patients who fulfill the TMCWG criteria for definite and possible IATM will convert to MS. Functional recovery in IATM is poorer in patients with urinary sphincter dysfunction at admission or LETM on MRI

Baseline MxA mRNA expression predicts interferon beta response in multiple sclerosis patients

Background Myxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection, mostly used to evaluate its bioactivity. There is little available data on clinical utility of baseline MxA mRNA status. The objective of the study is to investigate whether baseline MxA mRNA expression can predict relapse and disease progression in multiple sclerosis patients treated with interferon-beta. Methods Baseline blood samples were obtained before the first interferon-beta dose was administered to evaluate MxA mRNA expression using real-time polymerase chain reaction (PCR). Demographic and clinical variables were prospectively recorded to define treatment responder and non responder groups. Results 104 patients were included in the study. Baseline MxA mRNA expression was significantly lower in the group of patients who met the definition of responders (1.07 vs 1.95, Student t test, p<0.0001). A threshold of 1.096 was established using Receiver Operating Characteristic analysis to differentiate between responders and non-responders (sensitivity 73.9%, specificity 69.0%). Survival analysis using this threshold showed that time to next relapse (p<0.0001) and to EDSS progression (p = 0.01) were significantly higher in patients with lower MxA titers. Conclusion The results suggest that baseline MxA mRNA levels may be useful for predicting whether multiple sclerosis patients will respond or not to interferon-beta treatment

Automatic classification of Candida species using Raman spectroscopy and machine learning

One of the problems that most affect hospitals is infections by pathogenic microorganisms. Rapid identification and adequate, timely treatment can avoid fatal consequences and the development of antibiotic resistance, so it is crucial to use fast, reliable, and not too laborious techniques to obtain quick results. Raman spectroscopy has proven to be a powerful tool for molecular analysis, meeting these requirements better than traditional techniques. In this work, we have used Raman spectroscopy combined with machine learning algorithms to explore the automatic identification of eleven species of the genus Candida, the most common cause of fungal infections worldwide. The Raman spectra were obtained from more than 220 different measurements of dried drops from pure cultures of each Candida species using a Raman Confocal Microscope with a 532 nm laser excitation source. After developing a spectral preprocessing methodology, a study of the quality and variability of the measured spectra at the isolate and species level, and the spectral features contributing to inter-class variations, showed the potential to discriminate between those pathogenic yeasts. Several machine learning and deep learning algorithms were trained using hyperparameter optimization techniques to find the best possible classifier for this spectral data, in terms of accuracy and lowest possible overfitting. We found that a one-dimensional Convolutional Neural Network (1-D CNN) could achieve above 80 % overall accuracy for the eleven classes spectral dataset, with good generalization capabilities.This work was supported by the R + D projects INNVAL19/17 (funded by Instituto de Investigación Valdecilla-IDIVAL), PID2019-107270RB-C21 (funded by MCIN/ AEI /10.13039/501100011033) and by Plan Nacional de I + D + and Instituto de Salud Carlos III (ISCIII), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0007), CIBERINFEC (CB21/13/00068), CIBER-BBN (BBNGC1601), cofinanced by European Development Regional Fund “A way to achieve Europe”. A. A. O.-S was financially supported by the Miguel Servet II program (ISCIII-CPII17-00011)