Dynamic Nanoindentation and Short-Range Order in Equiatomic NiCoCr Medium-Entropy Alloy Lead to Novel Density Wave Ordering.

Chemical short-range order is believed to be a key contributor to the exceptional properties of multicomponent alloys. However, its direct validation and confirmation has been highly elusive in most compounds. Recent studies for equiatomic NiCoCr alloys have shown that thermal treatments (i.e., annealing and aging) may facilitate and manipulate such ordering. In this work, by using molecular simulations, we show that nanomechanical probes, such as nanoindentation, may be utilized toward further manipulation of chemical short-range order, providing explicit validation pathways. By using well established interatomic potentials, we perform hybrid molecular-dynamics-Monte Carlo at room temperature to demonstrate that particular dwell nanoindentation protocols can lead, through thermal Monte Carlo equilibration, to local reorganization under the indenter tip, toward a density-wave stripe pattern. We characterize the novel density-wave structures, which are highly anisotropic and dependent on local, nanoindentation-induced stress concentrations, and we show how they deeply originate from intrinsic features of interelemental interactions. Furthermore, we show that these novel patterns consistently scale with the incipient plastic zone, under the indenter tip, justifying their observation at experimentally feasible nanoindentation depths.

Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España / Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study

Introducción: Las ataxias (AT) y paraparesias espásticas hereditarias (PEH) son síndromes neu-rodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH en Espa˜na en2019.Pacientes y métodos: Estudio transversal, multicéntrico, descriptivo y retrospectivo de lospacientes con AT y PEH, desde marzo de 2018 a diciembre de 2019 en toda Espa˜na.Resultados: Se obtuvo información de 1933 pacientes procedentes de 11 Comunidades Autóno-mas, de 47 neurólogos o genetistas. Edad media: 53,64 a˜nos ± 20,51 desviación estándar (DE);938 varones (48,5%), 995 mujeres (51,5%). En 920 pacientes (47,6%) no se conoce el defectogenético. Por patologías, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados dePEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24casos/100.000 habitantes. La AT dominante más frecuente es la SCA3. La AT recesiva más fre-cuente es la ataxia de Friedreich (FRDA). La PEH dominante más frecuente es la SPG4, y la PEHrecesiva más frecuente es la SPG7.Conclusiones: La prevalencia estimada de AT y PEH en nuestra serie es de 7,73 casos/100.000habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se haconseguido un diagnóstico genético. A pesar de las limitaciones, este estudio puede contribuira estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones más frecuentespara hacer los screenings por comunidades, y favorecer los ensayos clínicos.(AU)

Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes.We aimed to determine the prevalence of these disorders in Spain in 2019.Patients and methods: We conducted a cross-sectional, multicentre, retrospective, descrip-tive study of patients with ataxia and hereditary spastic paraplegia in Spain between March2018 and December 2019. Results: We gathered data from a total of 1933 patients from 11 autonomous communities,provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51)years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect wasunidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%)had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegiawere estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequenttype of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia wasFriedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in oursample was SPG4, and the most frequent recessive type was SPG7.Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic para-plegia was 7.73 cases per 100 000 population. This rate is similar to those reported for othercountries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, ourstudy provides useful data for estimating the necessary healthcare resources for these patients,raising awareness of these diseases, determining the most frequent causal mutations for localscreening programmes, and promoting the development of clinical trials.(AU)

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Understanding Severe Asthma Through Small and Big Data in Spanish Hospitals: The PAGE Study.

BACKGROUND: Data on the prevalence of severe asthma (SA) are limited. Electronic health records (EHRs) offer a unique research opportunity to test machine learning (ML) tools in epidemiological studies. Our aim was to estimate the prevalence of SA among asthma patients seen in hospital asthma units, using both ML-based and traditional research methodologies. Our secondary objective was to describe patients with nonsevere asthma (NSA) and SA over a follow-up of 12 months. METHODS: PAGE is a multicenter, controlled, observational study conducted in 36 Spanish hospitals and split into 2 phases: a cross-sectional phase for estimation of the prevalence of SA and a prospective phase (3 visits in 12 months) for the follow-up and characterization of SA and NSA patients. A substudy with ML was performed in 6 hospitals. Our ML tool uses EHRead technology, which extracts clinical concepts from EHRs and standardizes them to SNOMED CT. RESULTS: The prevalence of SA among asthma patients in Spanish hospitals was 20.1%, compared with 9.7% using the ML tool. The proportion of SA phenotypes and the features of patients followed up were consistent with previous studies. The clinical predictions of patients' clinical course were unreliable, and ML found only 2 predictive models with discriminatory power to predict outcomes. CONCLUSION: This study is the first to estimate the prevalence of SA in hospitalized asthma patients and to predict patient outcomes using both standard and ML-based research techniques. Our findings offer relevant insights for further epidemiological and clinical research in SA.

Understanding Severe Asthma Through Small and Big Data in Spanish Hospitals: The PAGE Study

Background: Data on the prevalence of severe asthma (SA) are limited. Electronic health records (EHRs) offer a unique research opportunity to test machine learning (ML) tools in epidemiological studies. Our aim was to estimate the prevalence of SA among asthma patients seen in hospital asthma units, using both ML-based and traditional research methodologies. Our secondary objective was to describe patients with nonsevere asthma (NSA) and SA over a follow-up of 12 months. Methods: PAGE is a multicenter, controlled, observational study conducted in 36 Spanish hospitals and split into 2 phases: a cross-sectional phase for estimation of the prevalence of SA and a prospective phase (3 visits in 12 months) for the follow-up and characterization of SA and NSA patients. A substudy with ML was performed in 6 hospitals. Our ML tool uses EHRead technology, which extracts clinical concepts from EHRs and standardizes them to SNOMED CT. Results: The prevalence of SA among asthma patients in Spanish hospitals was 20.1%, compared with 9.7% using the ML tool. The proportion of SA phenotypes and the features of patients followed up were consistent with previous studies. The clinical predictions of patients’ clinical course were unreliable, and ML found only 2 predictive models with discriminatory power to predict outcomes. Conclusion: This study is the first to estimate the prevalence of SA in hospitalized asthma patients and to predict patient outcomes using both standard and ML-based research techniques. Our findings offer relevant insights for further epidemiological and clinical research in SA (AU)

Antecedentes: Los datos sobre la prevalencia del asma grave (SA) son limitados. La implantación de las historias clínicas electrónicas (EHR) ofrece una oportunidad única de investigación con tecnologías de aprendizaje máquina (ML) en los estudios epidemiológicos. El objetivo fue estimar la prevalencia del SA entre los pacientes atendidos en las unidades de asma hospitalarias, utilizando el ML como la metodología de investigación tradicional. Los objetivos secundarios fueron describir los pacientes con asma no grave (NSA) y con SA durante un período de seguimiento de 12 meses. Métodos: El estudio PAGE es un estudio multicéntrico, controlado y observacional realizado en 36 hospitales españoles y dividido en dos fases: una primera fase transversal para la estimación de la prevalencia de AS, y una segunda fase prospectiva (3 visitas en 12 meses) para el seguimiento y caracterización de los pacientes con SA y NSA. Se incluyó un subestudio con ML en 6 hospitales. Resultados: Se obtuvo una prevalencia de SA del 20,1% entre los pacientes asmáticos, frente al 9,7% de la herramienta ML. La proporción de fenotipos de SA y las características de los pacientes en seguimiento fueron consistentes con estudios anteriores. Las predicciones clínicas de la evolución de los pacientes fueron poco fiables, mientras que el ML sólo encontró dos modelos predictivos con potencial discriminatorio para predecir resultados. Conclusión: Este estudio es el primero en estimar la prevalencia del SA, en una población hospitalaria de pacientes con asma, y en predecir los resultados de los pacientes utilizando técnicas estándar y de ML (AU)

Practical recommendations for the clinical evaluation of patients with hereditary ataxia and hereditary spastic paraplegia.

Hereditary ataxia (HA) and hereditary spastic paraplegia (HSP) are rare diseases; as such, they are rarely managed in general neurology consultations. We present a set of brief, practical recommendations for the diagnosis and management of these patients, as well as a standardised procedure for comprehensive evaluation of disability. We provide definitions for HA and "HA plus," and "pure" and "complicated" HSP; describe the clinical assessment of these patients, indicating the main complementary tests and clinical scales for physical and psychological assessment of the patients; and summarise the available treatments. These recommendations are intended to facilitate daily neurological practice and to unify clinical criteria and disability assessment protocols for patients with HA and HSP.

Analysis of response of severe eosinophilic asthmatic patients to benralizumab

Introduction Clinical trials and real-life studies have been published showing effectiveness of benralizumab in severe eosinophilic asthmatic patients. The aim of the present study is to describe super-responders to benralizumab in a series of 79 patients who completed at least 1 year of treatment, and to compare super-responders with non super-responders. Methods This is a multicenter study of the Register of Severe Asthma of the Region of Murcia (RE-ASGRAMUR) Group performed in eight hospitals under the conditions of routine clinical practice. Patients with zero exacerbations and no oral corticosteroid therapy for asthma were considered super-responders. We analyzed clinical, functional, and inflammatory parameters of selected patients. Results In all, 50 of the 79 patients (63%) met the super-responder criteria. In addition, 36% of the patients (26/71) were considered as complete responders to treatment (super--responder + Asthma Control Test [ACT] ≥ 20 + forced expiratory volume in 1 s [FEV1] ≥ 80%). The super--responders were significantly older in age (P = 0.0029), had higher eosinophils count (P = 0.0423), higher proportion of nasal polyps (P = 0.036), and they had less severe disease at baseline. After 1 year of treatment, the super-responders had higher levels of ACT questionnaire (23 vs 19, P = 0.0007) and better percentage of FEV1 (83 vs 75, P = 0.0359). Conclusion Almost two of the three patients treated with benralizumab were super--responders after 1 year of treatment and 36% had a complete response. Super-responders were associated with older age, higher eosinophils count, had nasal polyposis as comorbidity, and had less severe disease at baseline. This data illustrated the good real-life response of patients with severe eosinophilic asthma to the treatment with benralizumab (AU)

Estudio comparativo de efectividad entre la Hipnosis y la intervención Cognitivo-Conductual para la Deshabituación Tabáquica / Comparative study of effectiveness between Hypnosis and Cognitive-Behavioral intervention for Smoking Cessation

Introducción: El consumo de tabaco es la primera causa de muerte evitable. A muchos fumadores les gustaría dejar el hábito. Aun así, a pesar de la eficacia demostrada de las intervenciones, muchos no están dispuestos a realizar un intento debido a las altas tasas de recaída y al miedo a los efectos secundarios de los tratamientos empleados, inclinándose a probar métodos alternativos.Objetivo: Conocer si la intervención avanzada individual (multicomponente cognitiva-conductual) es más efectiva que la intervención con hipnoterapia en pacientes fumadores, como tratamiento para dejar de fumar.Metodología: Estudio cuasiexperimental. Se incluyeron pacientes fumadores con antecedentes de patología respiratoria. Fueron asignados, según su preferencia, a un grupo de intervención avanzada individual en tabaquismo (grupo A) - al que se realizó una terapia multicomponente para dejar de fumar- o a un grupo de hipnoterapia (grupo B) en el que se realizó hipnosis para dejar de fumar.Todos los pacientes recibieron el tratamiento farmacológico y las pautas de actuación habituales que se utilizan en las consultas externas para tratar la enfermedad.Resultados: Se encontraron diferencias significativas en la cesación del consumo de tabaco a los 6 meses, encontrándose valores inferiores tanto en el abandono como en la disminución del consumo en los pacientes a los que se les realizó hipnoterapia versus terapia multicomponente (p 0,023 y p 0,031 respectivamente). Conclusiones: La intervención para el abandono del tabaco que incorpora la hipnosis no ha demostrado ser tan eficaz como la terapia multicomponente en la población estudiada. (AU)

Introduction: Tobacco use is the number one preventable cause of death. Many smokers would like to kick the habit. Still, despite the proven efficacy of the interventions, many are reluctant to try due to high relapse rates and fear of side effects of the treatments used, and are inclined to try alternative approaches.Objetive: To know if the individual advanced intervention (cognitive-behavioural multicomponent) is more effective than the intervention with hypnotherapy in smokers, as a treatment to quit smoking.Methodology: Quasi-experimental study. Smokers with a history of respiratory pathology were included. They were assigned, according to their preference, to an advanced individual smoking cessation intervention group (group A) - which underwent multicomponent therapy to quit smoking - or to a hypnotherapy group (group B) in which hypnosis was performed to quit smoking. of smoking.All patients received the pharmacological treatment and the usual action guidelines that are used in outpatient clinics to treat the disease.Results: Significant differences were found in the cessation of tobacco consumption at 6 months, with lower values both in quitting and in the reduction of consumption in patients who underwent hypnotherapy versus multicomponent therapy (p 0.023 and p 0.031, respectively).Conclusions: Smoking cessation intervention incorporating hypnosis has not been shown to be as effective as multicomponent therapy in the population studied. (AU)

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

PAGE Study: Summary of a Study Protocol to Estimate the Prevalence of Severe Asthma in Spain Using Big Data Methods.

BACKGROUND AND OBJECTIVES: Background: The proposal and the initiative for the Prevalence of Severe Asthma in Hospital Units in Spain (PAGE) study came about because of the widespread implementation of electronic medical records and the limited data available on the prevalence of severe asthma in hospitals in our setting. Objectives: The primary objective was to determine the prevalence of severe asthma in the outpatient clinics of allergy and pulmonology departments in Spain. The secondary objectives were to describe the most prevalent characteristics and phenotypes of severe asthma, to evaluate the selection criteria for receiving approved biological treatments for this disease, and to estimate consumption of resources. Furthermore, digital technology and new data collection sources made it possible to reuse information stored in electronic medical records (Big Data). The study was performed using one such tool, Savana. METHODS: The PAGE study was a multicenter, nonexperimental, observational, cross-sectional study in the first phase and a prospective study in the second phase. The study was controlled and population-based, with 2-stage selection of patients by random sampling. The research was carried out in 40 hospitals selected using convenience sampling in order to ensure geographical representativeness in Spain. RESULTS: This manuscript describes the study design and protocol. CONCLUSIONS: Our study design was sufficiently robust to avoid bias and to establish the prevalence of patients with severe asthma in Spanish hospitals. It was also the first to incorporate new tools that can help in routine clinical practice and research, such as big data analysis software, and to evaluate the reliability and efficiency of these tools.

PAGE Study: Summary of a Study Protocol to Estimate the Prevalence of Severe Asthma in Spain Using Big Data Methods

Background: The proposal and the initiative for the Prevalence of Severe Asthma in Hospital Units in Spain (PAGE) study came about because of the widespread implementation of electronic medical records and the limited data available on the prevalence of severe asthma in hospitals in our setting. Objectives: The primary objective was to determine the prevalence of severe asthma in the outpatient clinics of allergy and pulmonology departments in Spain. The secondary objectives were to describe the most prevalent characteristics and phenotypes of severe asthma, to evaluate the selection criteria for receiving approved biological treatments for this disease, and to estimate consumption of resources. Furthermore, digital technology and new data collection sources made it possible to reuse information stored in electronic medical records (Big Data). The study was performed using one such tool, Savana. Methods: The PAGE study was a multicenter, nonexperimental, observational, cross-sectional study in the first phase and a prospective study in the second phase. The study was controlled and population-based, with 2-stage selection of patients by random sampling. The research was carried out in 40 hospitals selected using convenience sampling in order to ensure geographical representativeness in Spain. Results: This manuscript describes the study design and protocol. Conclusions: Our study design was sufficiently robust to avoid bias and to establish the prevalence of patients with severe asthma in Spanish hospitals. It was also the first to incorporate new tools that can help in routine clinical practice and research, such as big data analysis software, and to evaluate the reliability and efficiency of these tools (AU)

[The management of asthma as a chronic inflammatory disease and global health problem: A position paper from the scientific societies]. / El manejo del asma como enfermedad inflamatoria crónica y problema sanitario global: documento de posicionamiento de las sociedades científicas.

Asthma is the most prevalent respiratory disease worldwide and it can affect people of all ages and is potentially fatal. Today, maintenance treatments are available that are effective in most patients, yet a significant proportion have poorly controlled disease, despite the resources on offer. This document, endorsed by members of the Spanish medical societies involved in the treatment of asthma, is intended to draw the attention of society and professionals to this problem in Spain. It focuses on the clinical, diagnostic and therapeutic aspects of asthma, and proposes some actions for improvement as regards patients and healthcare professionals which, in view of the current results arising from inadequate asthma control, might be beneficial to improve outcomes for both patients and public health.