Projection to latent spaces disentangles pathological effects on brain morphology in the asymptomatic phase of Alzheimer's disease

Alzheimer's disease (AD) continuum is defined as a cascade of several neuropathological processes that can be measured using biomarkers, such as cerebrospinal fluid (CSF) levels of Aß, p-tau, and t-tau. In parallel, brain anatomy can be characterized through imaging techniques, such as magnetic resonance imaging (MRI). In this work we relate both sets of measurements and seek associations between biomarkers and the brain structure that can be indicative of AD progression. The goal is to uncover underlying multivariate effects of AD pathology on regional brain morphological information. For this purpose, we used the projection to latent structures (PLS) method. Using PLS, we found a low dimensional latent space that best describes the covariance between both sets of measurements on the same subjects. Possible confounder effects (age and sex) on brain morphology are included in the model and regressed out using an orthogonal PLS model. We looked for statistically significant correlations between brain morphology and CSF biomarkers that explain part of the volumetric variance at each region-of-interest (ROI). Furthermore, we used a clustering technique to discover a small set of CSF-related patterns describing the AD continuum. We applied this technique to the study of subjects in the whole AD continuum, from the pre-clinical asymptomatic stages all the way through to the symptomatic groups. Subsequent analyses involved splitting the course of the disease into diagnostic categories: cognitively unimpaired subjects (CU), mild cognitively impaired subjects (MCI), and subjects with dementia (AD-dementia), where all symptoms were due to AD.This work has been partially supported by the project MALEGRA TEC2016-75976-R financed by the Spanish Ministerio de Economía y Competitividad and the European Regional Development Fund (ERDF). AC was supported by the Spanish Ministerio de Educación, Cultura y Deporte FPU Research Fellowship. JG holds a Ramón y Cajal fellowship (RYC-2013-13054).Peer ReviewedPostprint (published version

Projection to latent spaces disentangles specific cerebral morphometric patterns associated to aging and preclinical AD”,

Peer ReviewedPostprint (published version

Estudio del nivel sonoro de las armas de avancarga utilizadas en fiestas populares y recreación histórica

Introduction and Objectives: The popular manifestations associated with the festive use of ancient weapons or muzzleloader replicas have numerous and ancient references throughout our geography, but there was a lack of studies of the novel sounds derived from their use. A work was designed that would allow the analysis of the noise levels generated, in order to guide protection measures to its users. Material and method: Data from 24 weapons of 22 different types were collected, determining different measurement points, and the sonometric results were analyzed according to the types of weapon, distance to the shooter and frequency range. Results: The data obtained demonstrate higher sound levels for the bass tones, with averages of 102 to 117dB measured one meter from the shooter, with little attenuation at distances at 5 and 10 meters and without clinically relevant differences derived from the type of weapon. distance or powder charge. Conclusions: The sound levels generated by muzzleloaders advise recommending the appropriate protection measures, not finding clinically relevant differences for the different types of weapons used.Introducción y Objetivos: Las manifestaciones populares asociadas al uso festivo de armas antiguas o réplicas de avancarga tienen numerosas y antiguas referencias a lo largo de nuestra geografía, pero se carecía de estudios de los noveles sonoros derivados de su uso. Se diseño un trabajo que permitiera analizar los niveles de ruido generados, para poder orientar medidas de protección a sus usuarios. Material y método: Se recogieron datos de 24 armas de 22 tipos distintos, determinando distintos puntos de medición, y se analizaron los resultados sonométricos en función de los tipos de arma, distancia al tirador y rango de frecuencias. Resultados: Los datos obtenidos demuestran unos mayores niveles de sonido para los tonos graves, con medias de 102 a 117dB medidas a un metro del tirador, con poca atenuación en distancias a 5 y 10 metros y sin diferencias clínicamente relevantes derivadas del tipo de arma, distancia o carga de pólvora. Conclusiones: Los niveles de sonido generado por las armas de avancarga aconsejan recomendar las medidas adecuadas de protección, no hallándose diferencias clínicamente relevantes para los distintos tipos de armas utilizadas

Characteristic brain volumetric changes in the AD preclinical signature

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Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

Shared latent structures between imaging features and biomarkers in early stages of Alzheimer's disease

In this work, we identify meaningful latent patterns in MR images for patients across the Alzheimer’s disease (AD) continuum. For this purpose, we apply Projection to Latent Structures (PLS) method using cerebrospinal fluid (CSF) biomarkers (t-tau, p-tau, amyloid-beta) and age as response variables and imaging features as explanatory variables. Freesurfer pipeline is used to compute MRI surface and volumetric features resulting in 68 cortical ROIs and 84 cortical and subcortical ROIs, respectively. The main assumption of this work is that there are two main underlying processes governing brain morphology along the AD continuum: brain aging and dementia. We use two different and orthogonal PLS models to describe each process: PLS-aging and PLS-dementia. To define PLS-aging model we use normal aging subjects and age as predictor and response variables, respectively, while for PLS-dementia we only use demented subjects and biomarkers as response variables.Peer ReviewedPostprint (published version

Accuracy of a dynamic surgical guidance probe for screw insertion in the cervical spine: a cadaveric study

© 2016, Springer-Verlag Berlin Heidelberg. Study design: A fresh frozen cadaver study was conducted. Objective: To report the cortical breach rate using the dynamic surgical guidance (DSG) probe versus traditional freehand technique for cervical lateral mass, cervical pedicle and cervical laminar screws. Methods: Nine male fresh frozen cadaveric torsos were utilized for this study. Each investigator was assigned three specimens that were randomized by fixation point, side and order of technique for establishing a screw pilot hole. The technique for screw hole preparation utilized was either a DSG probe in the “on” mode or in the “off” mode using a freehand technique popularized by Lenke et al. Levels instrumented included C1 lateral mass, C2 pedicle screws and lamina screws, and C6–T1 pedicle screws. Fluoroscopy and other navigational assistance were not used for screw hole preparation or screw insertion. All specimens were CT imaged following insertion of all screws. A senior radiolo

Shared latent structures between imaging features and biomarkers in early stages of Alzheimer's disease

In this work, we identify meaningful latent patterns in MR images for patients across the Alzheimer’s disease (AD) continuum. For this purpose, we apply Projection to Latent Structures (PLS) method using cerebrospinal fluid (CSF) biomarkers (t-tau, p-tau, amyloid-beta) and age as response variables and imaging features as explanatory variables. Freesurfer pipeline is used to compute MRI surface and volumetric features resulting in 68 cortical ROIs and 84 cortical and subcortical ROIs, respectively. The main assumption of this work is that there are two main underlying processes governing brain morphology along the AD continuum: brain aging and dementia. We use two different and orthogonal PLS models to describe each process: PLS-aging and PLS-dementia. To define PLS-aging model we use normal aging subjects and age as predictor and response variables, respectively, while for PLS-dementia we only use demented subjects and biomarkers as response variables.Peer Reviewe

Magnetic resonance imaging and machine learning make a valuable combined tool for the screening of preclinical AD

Peer Reviewe

Projection to latent spaces disentangles specific cerebral morphometric patterns associated to aging and preclinical AD”,

Peer Reviewe