| 1. |
- Brugulat-Serrat, Anna, et al.
(författare)
-
APOE -ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals
- 2023
-
Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine whether the APOE-ε4 allele modulates the relationship between regional β-amyloid (Aβ) accumulation and cognitive change in middle-aged cognitively unimpaired (CU) participants. Methods: The 352 CU participants (mean aged 61.1 [4.7] years) included completed two cognitive assessments (average interval 3.34 years), underwent [18F]flutemetamol Aβ positron emission tomography (PET), T1w magnetic resonance imaging (MRI), as well as APOE genotyping. Global and regional Aβ PET positivity was assessed across five regions-of-interest by visual reading (VR) and regional Centiloids. Linear regression models were developed to examine the interaction between regional and global Aβ PET positivity and APOE-ε4 status on longitudinal cognitive change assessed with the Preclinical Alzheimer’s Cognitive Composite (PACC), episodic memory, and executive function, after controlling for age, sex, education, cognitive baseline scores, and hippocampal volume. Results: In total, 57 participants (16.2%) were VR+ of whom 41 (71.9%) were APOE-ε4 carriers. No significant APOE-ε4*global Aβ PET interactions were associated with cognitive change for any cognitive test. However, APOE-ε4 carriers who were VR+ in temporal areas (n = 19 [9.81%], p = 0.04) and in the striatum (n = 8 [4.14%], p = 0.01) exhibited a higher decline in the PACC. The temporal areas findings were replicated when regional PET positivity was determined with Centiloid values. Regionally, VR+ in the striatum was associated with higher memory decline. As for executive function, interactions between APOE-ε4 and regional VR+ were found in temporal and parietal regions, and in the striatum. Conclusion: CU APOE-ε4 carriers with a positive Aβ PET VR in regions known to accumulate amyloid at later stages of the Alzheimer’s disease (AD) continuum exhibited a steeper cognitive decline. This work supports the contention that regional VR of Aβ PET might convey prognostic information about future cognitive decline in individuals at higher risk of developing AD. ClinicalTrials.gov Identifier: NCT02485730. Registered 20 June 2015 https://clinicaltrials.gov/ct2/show/NCT02485730 and ClinicalTrials.gov Identifier:NCT02685969. Registered 19 February 2016 https://clinicaltrials.gov/ct2/show/NCT02685969.
|
|
| 2. |
- Carraminana, Albert, et al.
(författare)
-
Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV)
- 2019
-
Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
|
|
| 3. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 4. |
- Akinci, Muge, et al.
(författare)
-
Subjective cognitive decline and anxious/depressive symptoms during the COVID-19 pandemic : what is the role of stress perception, stress resilience, and β-amyloid?
- 2022
-
Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The COVID-19 pandemic may worsen the mental health of people reporting subjective cognitive decline (SCD) and therefore their clinical prognosis. We aimed to investigate the association between the intensity of SCD and anxious/depressive symptoms during confinement and the underlying mechanisms. Methods: Two hundred fifty cognitively unimpaired participants completed the Hospital Anxiety and Depression Scale (HADS) and SCD-Questionnaire (SCD-Q) and underwent amyloid-β positron emission tomography imaging with [18F] flutemetamol (N = 205) on average 2.4 (± 0.8) years before the COVID-19 confinement. During the confinement, participants completed the HADS, Perceived Stress Scale (PSS), Brief Resilience Scale (BRS), and an ad hoc questionnaire on worries (access to primary products, self-protection materials, economic situation) and lifestyle changes (sleep duration, sleep quality, eating habits). We investigated stress-related measurements, worries, and lifestyle changes in relation to SCD. We then conducted an analysis of covariance to investigate the association of SCD-Q with HADS scores during the confinement while controlling for pre-confinement anxiety/depression scores and demographics. Furthermore, we introduced amyloid-β positivity, PSS, and BRS in the models and performed mediation analyses to explore the mechanisms explaining the association between SCD and anxiety/depression. Results: In the whole sample, the average SCD-Q score was 4.1 (± 4.4); 70 (28%) participants were classified as SCD, and 26 (12.7%) were amyloid-β-positive. During the confinement, participants reporting SCD showed higher PSS (p = 0.035) but not BRS scores (p = 0.65) than those that did not report SCD. No differences in worries or lifestyle changes were observed. Higher SCD-Q scores showed an association with greater anxiety/depression scores irrespective of pre-confinement anxiety/depression levels (p = 0.002). This association was not significant after introducing amyloid-β positivity and stress-related variables in the model (p = 0.069). Amyloid-β positivity and PSS were associated with greater HADS irrespective of pre-confinement anxiety/depression scores (p = 0.023; p < 0.001). The association of SCD-Q with HADS was mediated by PSS (p = 0.01). Conclusions: Higher intensity of SCD, amyloid-β positivity, and stress perception showed independent associations with anxious/depressive symptoms during the COVID-19 confinement irrespective of pre-confinement anxiety/depression levels. The association of SCD intensity with anxiety/depression was mediated by stress perception, suggesting stress regulation as a potential intervention to reduce affective symptomatology in the SCD population in the face of stressors.
|
|
| 5. |
- Arnela, Marc, et al.
(författare)
-
A semi-polar grid strategy for the three-dimensional finite element simulation of vowel-vowel sequences
- 2017
-
Ingår i: Proceedings of the Annual Conference of the International Speech Communication Association, INTERSPEECH 2017. - : The International Speech Communication Association (ISCA). ; , s. 3477-3481
-
Konferensbidrag (refereegranskat)abstract
- Three-dimensional computational acoustic models need very detailed 3D vocal tract geometries to generate high quality sounds. Static geometries can be obtained from Magnetic Resonance Imaging (MRI), but it is not currently possible to capture dynamic MRI-based geometries with sufficient spatial and time resolution. One possible solution consists in interpolating between static geometries, but this is a complex task. We instead propose herein to use a semi-polar grid to extract 2D cross-sections from the static 3D geometries, and then interpolate them to obtain the vocal tract dynamics. Other approaches such as the adaptive grid have also been explored. In this method, cross-sections are defined perpendicular to the vocal tract midline, as typically done in 1D to obtain the vocal tract area functions. However, intersections between adjacent cross-sections may occur during the interpolation process, especially when the vocal tract midline quickly changes its orientation. In contrast, the semi-polar grid prevents these intersections because the plane orientations are fixed over time. Finite element simulations of static vowels are first conducted, showing that 3D acoustic wave propagation is not significantly altered when the semi-polar grid is used instead of the adaptive grid. The vowel-vowel sequence [ɑi] is finally simulated to demonstrate the method.
|
|
| 6. |
|
|
| 7. |
- Arnela, Marc, et al.
(författare)
-
Finite element generation of vowel sounds using dynamic complex three-dimensional vocal tracts
- 2016
-
Ingår i: Proceedings of the 23rd international congress on sound and vibration. - : INT INST ACOUSTICS & VIBRATION. - 9789609922623
-
Konferensbidrag (refereegranskat)abstract
- Three-dimensional (3D) numerical simulations of the vocal tract acoustics require very detailed vocal tract geometries in order to generate good quality vowel sounds. These geometries are typically obtained from Magnetic Resonance Imaging (MRI), from which a volumetric representation of the complex vocal tract shape is obtained. Static vowel sounds can then be generated using a finite element code, which simulates the propagation of acoustic waves through the vocal tract when a given train of glottal pulses is introduced at the glottal cross-section. A more challenging problem to solve is that of generating dynamic vowel sounds. On the one hand, the acoustic wave equation has to be solved in a computational domain with moving boundaries, which entails some numerical difficulties. On the other hand, the finite element meshes where acoustic wave propagation is computed have to move according to the dynamics of these very complex vocal tract shapes. In this work this problem is addressed. First, the acoustic wave equation in mixed form is expressed in an Arbitrary Lagrangian-Eulerian (ALE) framework to account for the vocal tract wall motion. This equation is numerically solved using a stabilized finite element approach. Second, the dynamic 3D vocal tract geometry is approximated by a finite set of cross-sections with complex shape. The time-evolution of these cross-sections is used to move the boundary nodes of the finite element meshes, while inner nodes are computed through diffusion. Some dynamic vowel sounds are presented as numerical examples.
|
|
| 8. |
- Arnela, Marc, et al.
(författare)
-
Influence of lips on the production of vowels based on finite element simulations and experiments
- 2016
-
Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; 139:5, s. 2852-2859
-
Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional (3-D) numerical approaches for voice production are currently being investigated and developed. Radiation losses produced when sound waves emanate from the mouth aperture are one of the key aspects to be modeled. When doing so, the lips are usually removed from the vocal tract geometry in order to impose a radiation impedance on a closed cross-section, which speeds up the numerical simulations compared to free-field radiation solutions. However, lips may play a significant role. In this work, the lips' effects on vowel sounds are investigated by using 3-D vocal tract geometries generated from magnetic resonance imaging. To this aim, two configurations for the vocal tract exit are considered: with lips and without lips. The acoustic behavior of each is analyzed and compared by means of time-domain finite element simulations that allow free-field wave propagation and experiments performed using 3-D-printed mechanical replicas. The results show that the lips should be included in order to correctly model vocal tract acoustics not only at high frequencies, as commonly accepted, but also in the low frequency range below 4 kHz, where plane wave propagation occurs.
|
|
| 9. |
- Arnela, Marc, et al.
(författare)
-
Influence of vocal tract geometry simplifications on the numerical simulation of vowel sounds
- 2016
-
Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; 140:3, s. 1707-1718
-
Tidskriftsartikel (refereegranskat)abstract
- For many years, the vocal tract shape has been approximated by one-dimensional (1D) area functions to study the production of voice. More recently, 3D approaches allow one to deal with the complex 3D vocal tract, although area-based 3D geometries of circular cross-section are still in use. However, little is known about the influence of performing such a simplification, and some alternatives may exist between these two extreme options. To this aim, several vocal tract geometry simplifications for vowels [ɑ], [i], and [u] are investigated in this work. Six cases are considered, consisting of realistic, elliptical, and circular cross-sections interpolated through a bent or straight midline. For frequencies below 4–5 kHz, the influence of bending and cross-sectional shape has been found weak, while above these values simplified bent vocal tracts with realistic cross-sections are necessary to correctly emulate higher-order mode propagation. To perform this study, the finite element method (FEM) has been used. FEM results have also been compared to a 3D multimodal method and to a classical 1D frequency domain model.
|
|
| 10. |
- Arnela, Marc, et al.
(författare)
-
MRI-based vocal tract representations for the three-dimensional finite element synthesis of diphthongs
- 2019
-
Ingår i: IEEE Transactions on Audio, Speech, and Language Processing. - : IEEE Press. - 1558-7916 .- 1558-7924. ; 27:12, s. 2173-2182
-
Tidskriftsartikel (refereegranskat)abstract
- The synthesis of diphthongs in three-dimensions (3D) involves the simulation of acoustic waves propagating through a complex 3D vocal tract geometry that deforms over time. Accurate 3D vocal tract geometries can be extracted from Magnetic Resonance Imaging (MRI), but due to long acquisition times, only static sounds can be currently studied with an adequate spatial resolution. In this work, 3D dynamic vocal tract representations are built to generate diphthongs, based on a set of cross-sections extracted from MRI-based vocal tract geometries of static vowel sounds. A diphthong can then be easily generated by interpolating the location, orientation and shape of these cross-sections, thus avoiding the interpolation of full 3D geometries. Two options are explored to extract the cross-sections. The first one is based on an adaptive grid (AG), which extracts the cross-sections perpendicular to the vocal tract midline, whereas the second one resorts to a semi-polar grid (SPG) strategy, which fixes the cross-section orientations. The finite element method (FEM) has been used to solve the mixed wave equation and synthesize diphthongs [${\alpha i}$] and [${\alpha u}$] in the dynamic 3D vocal tracts. The outputs from a 1D acoustic model based on the Transfer Matrix Method have also been included for comparison. The results show that the SPG and AG provide very close solutions in 3D, whereas significant differences are observed when using them in 1D. The SPG dynamic vocal tract representation is recommended for 3D simulations because it helps to prevent the collision of adjacent cross-sections.
|
|
| 11. |
- Brugulat-Serrat, Anna, et al.
(författare)
-
Enhancing the Sensitivity of Memory Tests: Reference Data for the Free and Cued Selective Reminding Test and the Logical Memory Task from Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels.
- 2021
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 84:1, s. 119-128
-
Tidskriftsartikel (refereegranskat)abstract
- Cognitive performance of a given individual should be interpreted in the context of reference standards obtained in cognitively healthy populations. Recent evidence has shown that removing asymptomatic individuals with biomarker evidence of Alzheimer's disease pathology from normative samples increases the sensitivity of norms to detect memory impairments. These kind of norms may be useful for defining subtle cognitive decline, the transitional cognitive decline between normal cognition and mild cognitive impairment.The present study aims to provide norms for the Free and Cued Selective Reminding Test (FCSRT) and the Logical Memory subtest of the Wechsler Memory Scale-IV in a sample of individuals aged 50-70 years with normal levels of amyloid-β and tau cerebrospinal fluid (CSF) biomarkers.The sample was composed of 248 individuals from the ALFA+ study with negative amyloid-β and tau CSF biomarker levels. Regression-based norms were developed, including adjustments for age, education, and sex when applicable.We found that education was associated with the performance in all the variables of both tests while age had a marginal effect only in the delayed free recall of the FCSRT. Sex was also related to the performance in the FCSRT, with women outperforming men. Equations to calculate z-scores and normative percentile tables were created. As compared with previously published norms the reference data presented were more sensitive but less specific, as expected.The use of the norms provided in this work, in combination with the already published conventional norms, may contribute to detecting subtle memory impairment.
|
|
| 12. |
- Dabbaghchian, Saeed, et al.
(författare)
-
Reconstruction of vocal tract geometries from biomechanical simulations
- 2018
-
Ingår i: International Journal for Numerical Methods in Biomedical Engineering. - : John Wiley & Sons. - 2040-7939 .- 2040-7947.
-
Tidskriftsartikel (refereegranskat)abstract
- Medical imaging techniques are usually utilized to acquire the vocal tract geometry in 3D, which may then be used, eg, for acoustic/fluid simulation. As an alternative, such a geometry may also be acquired from a biomechanical simulation, which allows to alter the anatomy and/or articulation to study a variety of configurations. In a biomechanical model, each physical structure is described by its geometry and its properties (such as mass, stiffness, and muscles). In such a model, the vocal tract itself does not have an explicit representation, since it is a cavity rather than a physical structure. Instead, its geometry is defined implicitly by all the structures surrounding the cavity, and such an implicit representation may not be suitable for visualization or for acoustic/fluid simulation. In this work, we propose a method to reconstruct the vocal tract geometry at each time step during the biomechanical simulation. Complexity of the problem, which arises from model alignment artifacts, is addressed by the proposed method. In addition to the main cavity, other small cavities, including the piriform fossa, the sublingual cavity, and the interdental space, can be reconstructed. These cavities may appear or disappear by the position of the larynx, the mandible, and the tongue. To illustrate our method, various static and temporal geometries of the vocal tract are reconstructed and visualized. As a proof of concept, the reconstructed geometries of three cardinal vowels are further used in an acoustic simulation, and the corresponding transfer functions are derived.
|
|
| 13. |
- Dabbaghchian, Saeed, et al.
(författare)
-
Simulation of vowel-vowel utterances using a 3D biomechanical-acoustic model
- 2021
-
Ingår i: International Journal for Numerical Methods in Biomedical Engineering. - Wiley : Wiley-Blackwell. - 2040-7939 .- 2040-7947. ; 37:1
-
Tidskriftsartikel (refereegranskat)abstract
- A link is established between biomechanical and acoustic 3D models for the numerical simulation of vowel-vowel utterances. The former rely on the activation and contraction of relevant muscles for voice production, which displace and distort speech organs. However, biomechanical models do not provide a closed computational domain of the 3D vocal tract airway where to simulate sound wave propagation. An algorithm is thus proposed to extract the vocal tract boundary from the surrounding anatomical structures at each time step of the transition between vowels. The resulting 3D geometries are fed into a 3D finite element acoustic model that solves the mixed wave equation for the acoustic pressure and particle velocity. An arbitrary Lagrangian-Eulerian framework is considered to account for the evolving vocal tract. Examples include six static vowels and three dynamic vowel-vowel utterances. Plausible muscle activation patterns are first determined for the static vowel sounds following an inverse method. Dynamic utterances are then generated by linearly interpolating the muscle activation of the static vowels. Results exhibit nonlinear trajectory of the vocal tract geometry, similar to that observed in electromagnetic midsagittal articulography. Clear differences are appreciated when comparing the generated sound with that obtained from direct linear interpolation of the vocal tract geometry. That is, interpolation between the starting and ending vocal tract geometries of an utterance, without resorting to any biomechanical model.
|
|
| 14. |
- Dabbaghchian, Saeed, et al.
(författare)
-
Synthesis of vowels and vowel-vowel utterancesusing a 3D biomechanical-acoustic model
- 2018
-
Ingår i: IEEE/ACM Transactions on Audio, Speech, and Language Processing. - 2329-9290.
-
Tidskriftsartikel (refereegranskat)abstract
- A link is established between a 3D biomechanicaland acoustic model allowing for the umerical synthesis of vowelsounds by contraction of the relevant muscles. That is, thecontraction of muscles in the biomechanical model displacesand deforms the articulators, which in turn deform the vocaltract shape. The mixed wave equation for the acoustic pressureand particle velocity is formulated in an arbitrary Lagrangian-Eulerian framework to account for moving boundaries. Theequations are solved numerically using the finite element method.Since the activation of muscles are not fully known for a givenvowel sound, an inverse method is employed to calculate aplausible activation pattern. For vowel-vowel utterances, two different approaches are utilized: linear interpolation in eithermuscle activation or geometrical space. Although the former isthe natural choice for biomechanical modeling, the latter is usedto investigate the contribution of biomechanical modeling onspeech acoustics. Six vowels [ɑ, ə, ɛ, e, i, ɯ] and three vowel-vowelutterances [ɑi, ɑɯ, ɯi] are synthesized using the 3D model. Results,including articulation, formants, and spectrogram of vowelvowelsounds, are in agreement with previous studies.Comparingthe spectrogram of interpolation in muscle and geometrical spacereveals differences in all frequencies, with the most extendeddifference in the second formant transition.
|
|
| 15. |
- Dabbaghchian, Saeed, et al.
(författare)
-
Synthesis of VV utterances from muscle activation to sound with a 3d model
- 2017
-
Ingår i: Proceedings of the Annual Conference of the International Speech Communication Association, INTERSPEECH 2017. - : The International Speech Communication Association (ISCA). ; , s. 3497-3501
-
Konferensbidrag (refereegranskat)abstract
- We propose a method to automatically generate deformable 3D vocal tract geometries from the surrounding structures in a biomechanical model. This allows us to couple 3D biomechanics and acoustics simulations. The basis of the simulations is muscle activation trajectories in the biomechanical model, which move the articulators to the desired articulatory positions. The muscle activation trajectories for a vowel-vowel utterance are here defined through interpolation between the determined activations of the start and end vowel. The resulting articulatory trajectories of flesh points on the tongue surface and jaw are similar to corresponding trajectories measured using Electromagnetic Articulography, hence corroborating the validity of interpolating muscle activation. At each time step in the articulatory transition, a 3D vocal tract tube is created through a cavity extraction method based on first slicing the geometry of the articulators with a semi-polar grid to extract the vocal tract contour in each plane and then reconstructing the vocal tract through a smoothed 3D mesh-generation using the extracted contours. A finite element method applied to these changing 3D geometries simulates the acoustic wave propagation. We present the resulting acoustic pressure changes on the vocal tract boundary and the formant transitions for the utterance [Ai].
|
|
| 16. |
- Dabbaghchian, Saeed, et al.
(författare)
-
Using a Biomechanical Model and Articulatory Data for the Numerical Production of Vowels
- 2016
-
Ingår i: Interspeech 2016. ; , s. 3569-3573
-
Konferensbidrag (refereegranskat)abstract
- We introduce a framework to study speech production using a biomechanical model of the human vocal tract, ArtiSynth. Electromagnetic articulography data was used as input to an inverse tracking simulation that estimates muscle activations to generate 3D jaw and tongue postures corresponding to the target articulator positions. For acoustic simulations, the vocal tract geometry is needed, but since the vocal tract is a cavity rather than a physical object, its geometry does not explicitly exist in a biomechanical model. A fully-automatic method to extract the 3D geometry (surface mesh) of the vocal tract by blending geometries of the relevant articulators has therefore been developed. This automatic extraction procedure is essential, since a method with manual intervention is not feasible for large numbers of simulations or for generation of dynamic sounds, such as diphthongs. We then simulated the vocal tract acoustics by using the Finite Element Method (FEM). This requires a high quality vocal tract mesh without irregular geometry or self-intersections. We demonstrate that the framework is applicable to acoustic FEM simulations of a wide range of vocal tract deformations. In particular we present results for cardinal vowel production, with muscle activations, vocal tract geometry, and acoustic simulations.
|
|
| 17. |
- Degirmenci, Niyazi Cem, et al.
(författare)
-
A Unified Numerical Simulation of Vowel Production That Comprises Phonation and the Emitted Sound
- 2017
-
Ingår i: Proceedings of the Annual Conference of the International Speech Communication Association, INTERSPEECH 2017. - : The International Speech Communication Association (ISCA). ; , s. 3492-3496
-
Konferensbidrag (refereegranskat)abstract
- A unified approach for the numerical simulation of vowels is presented, which accounts for the self-oscillations of the vocal folds including contact, the generation of acoustic waves and their propagation through the vocal tract, and the sound emission outwards the mouth. A monolithic incompressible fluid-structure interaction model is used to simulate the interaction between the glottal jet and the vocal folds, whereas the contact model is addressed by means of a level set application of the Eikonal equation. The coupling with acoustics is done through an acoustic analogy stemming from a simplification of the acoustic perturbation equations. This coupling is one-way in the sense that there is no feedback from the acoustics to the flow and mechanical fields. All the involved equations are solved together at each time step and in a single computational run, using the finite element method (FEM). As an application, the production of vowel [i] has been addressed. Despite the complexity of all physical phenomena to be simulated simultaneously, which requires resorting to massively parallel computing, the formant locations of vowel [i] have been well recovered.
|
|
| 18. |
- Delaby, Constance, et al.
(författare)
-
Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.
- 2022
-
Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 18:10, s. 1868-1879
-
Tidskriftsartikel (refereegranskat)abstract
- The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests.We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients.The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis.This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.
|
|
| 19. |
- Ferrando, Carlos, et al.
(författare)
-
Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV) : a multicentre, randomised, controlled clinical trial
- 2024
-
Ingår i: The Lancet Respiratory Medicine. - : Elsevier. - 2213-2600 .- 2213-2619. ; 12:3, s. 195-206
-
Tidskriftsartikel (refereegranskat)abstract
- Background It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. Methods This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age >= 18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lungprotective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. Findings Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0 center dot 39 [95% CI 0 center dot 28 to 0 center dot 56]), with an absolute risk difference of -9 center dot 23 (95% CI -12 center dot 55 to -5 center dot 92). Recruitment manoeuvre-related adverse events were reported in five patients. Interpretation Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. Funding Instituto de Salud Carlos III and the European Regional Development Funds. Copyright (c) 2023 Elsevier Ltd. All rights reserved.
|
|
| 20. |
- Flume, Mathias, et al.
(författare)
-
Approaches to manage affordability of high budget impact medicines in key EU countries
- 2018
-
Ingår i: Journal of market access and health policy. - : Taylor & Francis. - 2001-6689. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The launch of hepatitis C (HCV) drugs such as sofosbuvir or ledipasvir has fostered the question of affordability of novel high budget impact therapies even in countries with high domestic product. European countries have developed a variety of mechanisms to improve affordability of such therapies, including affordability thresholds, price volume agreements or caps on individual product sales, and special budgets for innovative drugs. While some of these mechanisms may help limit budget impact, there are still significant progresses to be made in the definition and implementation of approaches to ensure affordability, especially in health systems where the growth potential in drug spending and/or in the patient contribution to health insurance are limited. Objectives: In this article, we will review how seven countries in western Europe are approaching the question of affordability of novel therapies and are developing approaches to continue to reward new sciences while limiting budget impact. We will also discuss the question of affordability of cost-effective but hugely expensive therapies and the implications for payers and for the pharmaceutical industry. Results: There is clearly not one solution that is used consistently across countries but rather a number of tools that are combined differently in each country. This illustrates the difficulty of managing affordability within different legal frameworks and within different health care system architectures.
|
|
| 21. |
- Franch, Xavier, et al.
(författare)
-
How do Practitioners Perceive the Relevance of Requirements Engineering Research?
- 2022
-
Ingår i: IEEE Transactions on Software Engineering. - : Institute of Electrical and Electronics Engineers Inc.. - 0098-5589 .- 1939-3520. ; 48:6, s. 1947-1964
-
Tidskriftsartikel (refereegranskat)abstract
- Context: The relevance of Requirements Engineering (RE) research to practitioners is vital for a long-term dissemination of research results to everyday practice. Some authors have speculated about a mismatch between research and practice in the RE discipline. However, there is not much evidence to support or refute this perception. Objective: This paper presents the results of a study aimed at gathering evidence from practitioners about their perception of the relevance of RE research and at understanding the factors that influence that perception. Method: We conducted a questionnaire-based survey of industry practitioners with expertise in RE. The participants rated the perceived relevance of 435 scientific papers presented at five top RE-related conferences. Results: The 153 participants provided a total of 2,164 ratings. The practitioners rated RE research as essential or worthwhile in a majority of cases. However, the percentage of non-positive ratings is still higher than we would like. Among the factors that affect the perception of relevance are the paper?s links to industry, the research method used, and respondents? roles. The reasons for positive perceptions were primarily related to the relevance of the problem and the soundness of the solution, while the causes for negative perceptions were more varied. The respondents also provided suggestions for future research, including topics researchers have studied for decades, like elicitation or requirement quality criteria. Conclusions: The study is valuable for both researchers and practitioners. Researchers can use the reasons respondents gave for positive and negative perceptions and the suggested research topics to help make their research more appealing to practitioners and thus more prone to industry adoption. Practitioners can benefit from the overall view of contemporary RE research by learning about research topics that they may not be familiar with, and compare their perception with those of their colleagues to self-assess their positioning towards more academic research. IEEE
|
|
| 22. |
- Franch, Xavier, et al.
(författare)
-
How do Practitioners Perceive the Relevance of Requirements Engineering Research? An Ongoing Study
- 2017
-
Ingår i: 2017 IEEE 25TH INTERNATIONAL REQUIREMENTS ENGINEERING CONFERENCE (RE). - : IEEE. - 2332-6441. - 9781538631911 ; , s. 382-387
-
Konferensbidrag (refereegranskat)abstract
- The relevance of Requirements Engineering (RE) research to practitioners is a prerequisite for problem-driven research in the area and key for a long-term dissemination of research results to everyday practice. To understand better how industry practitioners perceive the practical relevance of RE research, we have initiated the RE-Pract project, an international collaboration conducting an empirical study. This project opts for a replication of previous work done in two different domains and relies on survey research. To this end, we have designed a survey to be sent to several hundred industry practitioners at various companies around the world and ask them to rate their perceived practical relevance of the research described in a sample of 418 RE papers published between 2010 and 2015 at the RE, ICSE, FSE, ESEC/FSE, ESEM and REFSQ conferences. In this paper, we summarize our research protocol and present the current status of our study and the planned future steps.
|
|
| 23. |
- Harrison, Sam, et al.
(författare)
-
Review of multiport power converters for distribution network applications
- 2024
-
Ingår i: Renewable and Sustainable Energy Reviews. - 1879-0690 .- 1364-0321. ; 203
-
Forskningsöversikt (refereegranskat)abstract
- Multiport power converters integrate three or more energy devices into a single (potentially highly controllable and efficient) hub. These characteristics suggest that multiport power converters may be valuable for the decarbonisation of distribution networks, where the increase of converter-interfaced devices has degraded system reliability and efficiency. This review analyses the suitability of a wide range of multiport power converter solutions for four example distribution network applications (where previous studies have focussed on a limited range of topologies or applications) and the research areas that can progress their maturity. A review of grid codes and standards overviews the base capability that multiport power converters are likely to require, some of which are carried forward as requirements for a novel comparison tool. The comparison tool is developed to qualify and score reviewed topologies in terms of a range of features that are weighted for the applications. Isolated and partially-isolated topologies perform well due to their flexibility to be configured for the specifications and their operational capabilities (including modularity and voltage decoupling). Further research should focus on the complex control interactions between ports and scaling of these topologies for medium voltages. In contrast, many direct current non-isolated topologies do not qualify due to their low flexibility to be configured for the applications. This suggests that future research could focus on the development of a more flexible non-isolated multiport power converter configuration to take advantage of the high efficiency and low footprint that these topologies might otherwise offer for low voltage applications.
|
|
| 24. |
- López-Martos, David, et al.
(författare)
-
Awareness of episodic memory and meta-cognitive profiles: associations with cerebrospinal fluid biomarkers at the preclinical stage of the Alzheimer’s continuum
- 2024
-
Ingår i: Frontiers in Aging Neuroscience. - 1663-4365. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The lack of cognitive awareness, anosognosia, is a clinical deficit in Alzheimer’s disease (AD) dementia. However, an increased awareness of cognitive function, hypernosognosia, may serve as a marker in the preclinical stage. Subjective cognitive decline (SCD) might correspond to the initial symptom in the dynamic trajectory of awareness, but SCD might be absent along with low awareness of actual cognitive performance in the preclinical stage. We hypothesized that distinct meta-cognitive profiles, both hypernosognosia and anosognosia, might be identified in preclinical-AD. This research evaluated the association between cerebrospinal fluid (CSF) AD biomarkers and the awareness of episodic memory, further exploring dyadic (participant-partner) SCD reports, in the preclinical Alzheimer’s continuum. Methods: We analyzed 314 cognitively unimpaired (CU) middle-aged individuals (mean age: 60, SD: 4) from the ALFA+ cohort study. Episodic memory was evaluated with the delayed recall from the Memory Binding Test (MBT). Awareness of episodic memory, meta-memory, was defined as the normalized discrepancy between objective and subjective performance. SCD was defined using self-report, and dyadic SCD profiles incorporated the study partner’s report using parallel SCD-Questionnaires. The relationship between CSF Aβ42/40 and CSF p-tau181 with meta-memory was evaluated with multivariable regression models. The role of SCD and the dyadic contingency was explored with the corresponding stratified analysis. Results: CSF Aβ42/40 was non-linearly associated with meta-memory, showing an increased awareness up to Aβ-positivity and a decreased awareness beyond this threshold. In the non-SCD subset, the non-linear association between CSF Aβ42/40 and meta-memory persisted. In the SCD subset, higher Aβ-pathology was linearly associated with increased awareness. Individuals presenting only study partner’s SCD, defined as unaware decliners, exhibited higher levels of CSF p-tau181 correlated with lower meta-memory performance. Discussion: These results suggested that distinct meta-cognitive profiles can be identified in preclinical-AD. While most individuals might experience an increased awareness associated with the entrance in the AD continuum, hypernosognosia, some might be already losing insight and stepping into the anosognosic trajectory. This research reinforced that an early anosognosic profile, although at increased risk of AD-related decline, might be currently overlooked considering actual diagnostic criteria, and therefore its medical attention delayed.
|
|
| 25. |
- López-Martos, David, et al.
(författare)
-
Reference Data for Attentional, Executive, Linguistic, and Visual Processing Tests Obtained from Cognitively Healthy Individuals with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels.
- 2023
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 95:1, s. 237-249
-
Tidskriftsartikel (refereegranskat)abstract
- Conventional neuropsychological norms likely include cognitively unimpaired (CU) individuals with preclinical Alzheimer's disease (AD) pathology (amyloid-β, tau, and neurodegeneration) since they are based on cohorts without AD biomarkers data. Due to this limitation, population-based norms would lack sensitivity for detecting subtle cognitive decline due to AD, the transitional stage between healthy cognition and mild cognitive impairment. We have recently published norms for memory tests in individuals with normal cerebrospinal fluid (CSF) AD biomarker levels.The aim of the present study was to provide further AD biomarker-based cognitive references covering attentional, executive function, linguistic, and visual processing tests.We analyzed 248 CU individuals aged between 50-70 years old with normal CSF Aβ, p-tau, and neurodegeneration (t-tau) biomarker levels. The tests included were the Trail Making Test (TMT), Semantic Fluency Test, Digit and Symbol Span, Coding, Matrix Reasoning, Judgement of Line Orientation and Visual Puzzles. Normative data were developed based on regression models adjusted for age, education, and sex when needed. We present equations to calculate z-scores, the corresponding normative percentile tables, and online calculators.Age, education, and sex were associated with performance in all tests, except education for the TMT-A, and sex for the TMT-B, Coding, and Semantic Fluency. Cut-offs derived from the current biomarker-based reference data were higher and more sensitive than standard norms.We developed reference data obtained from individuals with evidence of non-pathologic AD biomarker levels that may improve the objective characterization of subtle cognitive decline in preclinical AD.
|
|
| 26. |
- Milà-Alomà, Marta, et al.
(författare)
-
CSF Synaptic Biomarkers in the Preclinical Stage of Alzheimer Disease and Their Association With MRI and PET: A Cross-sectional Study.
- 2021
-
Ingår i: Neurology. - 1526-632X. ; 97:21
-
Tidskriftsartikel (refereegranskat)abstract
- To determine whether CSF synaptic biomarkers are altered in the early preclinical stage of the Alzheimer continuum and associated with Alzheimer disease (AD) risk factors, primary pathology, and neurodegeneration markers.This cross-sectional study was performed in the Alzheimer's and Families (ALFA+) cohort, comprising middle-aged cognitively unimpaired participants. CSF neurogranin and growth-associated protein-43 (GAP-43) were measured with immunoassays, and synaptosomal-associated protein-25 (SNAP-25) and synaptotagmin-1 were measured with immunoprecipitation mass spectrometry. AD CSF biomarkers β-amyloid (Aβ)42/40, phosphorylated tau (p-tau), and total tau and the neurodegeneration biomarker neurofilament light chain (NfL) were also measured. Participants underwent structural MRI and fluorodeoxyglucose and Aβ PET imaging. General linear modeling was used to test the associations between CSF synaptic biomarkers and risk factors, Aβ pathology, tau pathology, and neurodegeneration markers.All CSF synaptic biomarkers increased with age. CSF neurogranin was higher in females, while CSF SNAP-25 was higher in APOE ε4 carriers. All CSF synaptic biomarkers increased with higher Aβ load (as measured by CSF Aβ42/40 and Aβ PET Centiloid values), and it is important to note that the synaptic biomarkers were increased even in individuals in the earliest stages of Aβ deposition. Higher CSF synaptic biomarkers were also associated with higher CSF p-tau and NfL. Higher CSF neurogranin and GAP-43 were significantly associated with higher brain metabolism but lower cortical thickness in AD-related brain regions.CSF synaptic biomarkers increase in the early preclinical stages of the Alzheimer continuum even when a low burden of Aβ pathology is present, and they differ in their association with age, sex, APOE ε4, and markers of neurodegeneration.ClinicalTrials.gov Identifier NCT02485730.
|
|
| 27. |
- Palpatzis, Eleni, et al.
(författare)
-
Lifetime Stressful Events Associated with Alzheimer's Pathologies, Neuroinflammation and Brain Structure in a Risk Enriched Cohort
- 2024
-
Ingår i: ANNALS OF NEUROLOGY. - 0364-5134 .- 1531-8249.
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD.MethodsThis cross-sectional cohort study included 1,290 CU participants (aged 48-77) from the ALFA cohort with SLE, lumbar puncture (n = 393), and/or structural magnetic resonance imaging (n = 1,234) assessments. Using multiple regression analyses, we examined the associations of total SLEs with cerebrospinal fluid (1) phosphorylated (p)-tau181 and A beta 1-42/1-40 ratio, (2) interleukin 6 (IL-6), and (3) GM volumes voxel-wise. Further, we performed stratified and interaction analyses with sex, history of psychiatric disease, and evaluated SLEs during specific life periods.ResultsWithin the whole sample, only childhood and midlife SLEs, but not total SLEs, were associated with AD pathophysiology and neuroinflammation. Among those with a history of psychiatric disease SLEs were associated with higher p-tau181 and IL-6. Participants with history of psychiatric disease and men, showed lower A beta 1-42/1-40 with higher SLEs. Participants with history of psychiatric disease and women showed reduced GM volumes in somatic regions and prefrontal and limbic regions, respectively.InterpretationWe did not find evidence supporting the association of total SLEs with AD, neuroinflammation, and atrophy pathways. Instead, the associations appear to be contingent on events occurring during early and midlife, sex and history of psychiatric disease. ANN NEUROL 2024
|
|
| 28. |
- Pelkmans, Wiesje, et al.
(författare)
-
Astrocyte biomarkers GFAP and YKL-40 mediate early Alzheimer's disease progression.
- 2023
-
Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279. ; 20:1, s. 483-93
-
Tidskriftsartikel (refereegranskat)abstract
- We studied how biomarkers of reactive astrogliosis mediate the pathogenic cascade in the earliest Alzheimer's disease (AD) stages.We performed path analysis on data from 384 cognitively unimpaired individuals from the ALzheimer and FAmilies (ALFA)+ study using structural equation modeling to quantify the relationships between biomarkers of reactive astrogliosis and the AD pathological cascade.Cerebrospinal fluid (CSF) amyloid beta (Aβ)42/40 was associated with Aβ aggregation on positron emission tomography (PET) and with CSF p-tau181 , which was in turn directly associated with CSF neurofilament light (NfL). Plasma glial fibrillary acidic protein (GFAP) mediated the relationship between CSF Aβ42/40 and Aβ-PET, and CSF YKL-40 partly explained the association between Aβ-PET, p-tau181 , and NfL.Our results suggest that reactive astrogliosis, as indicated by different fluid biomarkers, influences the pathogenic cascade during the preclinical stage of AD. While plasma GFAP mediates the early association between soluble and insoluble Aβ, CSF YKL-40 mediates the latter association between Aβ and downstream Aβ-induced tau pathology and tau-induced neuronal injury.Lower CSF Aβ42/40 was directly linked to higher plasma GFAP concentrations. Plasma GFAP partially explained the relationship between soluble Aβ and insoluble Aβ. CSF YKL-40 mediated Aβ-induced tau phosphorylation and tau-induced neuronal injury.
|
|
| 29. |
- Ryghaug, Marianne, et al.
(författare)
-
A Social Sciences and Humanities research agenda for transport and mobility in Europe : key themes and 100 research questions
- 2023
-
Ingår i: Transport Reviews. - : Informa UK Limited. - 0144-1647 .- 1464-5327. ; 43:4, s. 755-779
-
Tidskriftsartikel (refereegranskat)abstract
- Transport and mobility systems need to be transformed to meet climate change goals and reduce negative environmental and social effects. Despite EU policies having targeted such problems for more than three decades, transitions have been slow and geographically uneven. For effective change to happen, transport and mobility research needs fresh perspectives and better integration of knowledge from the Social Sciences and Humanities. Based on a Horizon Scanning approach, which allowed for a great deal of openness and variety in scholarly viewpoints, this paper presents a novel research agenda consisting of 8 themes and 100 research questions that may contribute to achieving environmentally sustainable mobility transitions within Europe. This research agenda highlights the need to not only support technological solutions for low-carbon mobility, but the importance of transformative policies that include new processes of knowledge production, civic participation and epistemic justice. We contend that the agenda points to the need for further research on the dynamics of science-society interactions.
|
|
| 30. |
- Sánchez-Benavides, Gonzalo, et al.
(författare)
-
Amyloid-β positive individuals with subjective cognitive decline present increased CSF neurofilament light levels that relate to lower hippocampal volume.
- 2021
-
Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 104, s. 24-31
-
Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light chain (NfL) is an axonal protein that when measured in cerebrospinal fluid (CSF) serves as a biomarker of neurodegeneration. We aimed at investigating the association among CSF NfL, presence of Subjective Cognitive Decline (SCD) and hippocampal volume, and how CSF amyloid-β (Aβ) modifies these associations. We included 278 cognitively unimpaired participants from the Alfa+ cohort (78 SCD and 200 Controls). Linear models accounting for covariates (age, gender, and mood) were used to test the association between CSF NfL and SCD status, and between CSF NfL and bilateral hippocampal volumes. Interactions with Aβ were also explored. Individuals with SCD had higher CSF NfL and lower CSF Aβ42/40 than Controls. There was a significant interaction between SCD and CSF-Aβ42/40 levels. Stratified analyses showed a significant association between SCD and NfL only in Aβ+ individuals. Higher CSF NfL was significantly associated with lower hippocampal volume specifically in Aβ+ individuals with SCD. The presence of SCD in Aβ+ individuals may represent an early symptom in the Alzheimer's continuum related to incipient neurodegeneration.
|
|
| 31. |
- Seyff, Norbert, et al.
(författare)
-
End-user driven feedback prioritization
- 2017
-
Ingår i: CEUR Workshop Proceedings. - : CEUR-WS.
-
Konferensbidrag (refereegranskat)abstract
- End-user feedback is becoming more important for the evolution of software systems. There exist various communication channels for end-users (app stores, social networks) which allow them to express their experiences and requirements regarding a software application. End-users communicate a large amount of feedback via these channels which leads to open issues regarding the use of end-user feedback for software development, maintenance and evolution. This includes investigating how to identify relevant feedback scattered across different feedback channels and how to determine the priority of the feedback issues communicated. In this research preview paper, we discuss ideas for enduser driven feedback prioritization. © Copyright 2017 for this paper by its authors.
|
|
| 32. |
- Stade, Melanie, et al.
(författare)
-
Providing a user forum is not enough : First experiences of a software company with CrowdRE
- 2017
-
Ingår i: Proceedings - 2017 IEEE 25th International Requirements Engineering Conference Workshops, REW 2017. - : Institute of Electrical and Electronics Engineers Inc.. - 9781538634882 ; , s. 164-169
-
Konferensbidrag (refereegranskat)abstract
- Crowd-based requirements engineering (CrowdRE) is promising to derive requirements by gathering and analyzing information from the crowd. Setting up CrowdRE in practice seems challenging, although first solutions to support CrowdRE exist. In this paper, we report on a German software company's experience on crowd involvement by using feedback communication channels and a monitoring solution for user-event data. In our case study, we identified several problem areas that a software company is confronted with to setup an environment for gathering requirements from the crowd. We conclude that a CrowdRE process cannot be implemented ad-hoc and that future work is needed to create and analyze a continuous feedback and monitoring data stream. © 2017 IEEE.
|
|
| 33. |
- Suárez-Calvet, Marc, et al.
(författare)
-
Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer's continuum when only subtle changes in Aβ pathology are detected.
- 2020
-
Ingår i: EMBO molecular medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 12:12
-
Tidskriftsartikel (refereegranskat)abstract
- In Alzheimer's disease (AD), tau phosphorylation in the brain and its subsequent release into cerebrospinal fluid (CSF) and blood is a dynamic process that changes during disease evolution. The main aim of our study was to characterize the pattern of changes in phosphorylated tau (p-tau) in the preclinical stage of the Alzheimer's continuum. We measured three novel CSF p-tau biomarkers, phosphorylated at threonine-181 and threonine-217 with an N-terminal partner antibody and at threonine-231 with a mid-region partner antibody. These were compared with an automated mid-region p-tau181 assay (Elecsys) as the gold standard p-tau measure. We demonstrate that these novel p-tau biomarkers increase more prominently in preclinical Alzheimer, when only subtle changes of amyloid-β (Aβ) pathology are detected, and can accurately differentiate Aβ-positive from Aβ-negative cognitively unimpaired individuals. Moreover, we show that the novel plasma N-terminal p-tau181 biomarker is mildly but significantly increased in the preclinical stage. Our results support the idea that early changes in neuronal tau metabolism in preclinical Alzheimer, likely in response to Aβ exposure, can be detected with these novel p-tau assays.
|
|
| 34. |
|
|
