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Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD). Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts. Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157). Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (−1.8 [95% CI −2.3, −1.3] vs. −1.9 [95% CI −2.6, −1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]). Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.

Historical centers of Europe and Croatia are often formed by unreinforced masonry building aggregates that developed as the layout of the city or village was densified. In these aggregates, adjacent buildings can share structural walls with an older and a newer unit connected either by interlocking or just by a layer of mortar. Observations after for example the recent Central Italy and Croatia earthquakes showed that joints between the buildings were often damaged. This indicated a possible out-of-phase behaviour of units which can lead to the interaction which is demanding to capture with numerical models. The analysis of such building aggregates is difficult due to the lack of guidelines, as the advances were impeded by the scarce experimental data. The SERA project AIMS (Seismic Testing of Adjacent Interacting Masonry Structures) comprised a shake-table test of an aggregate of two buildings under two horizontal components of dynamic excitation, accompanied by the blind prediction competition. Each group was provided with a complete set of construction drawings, material properties, testing sequence and the list of measurements to be reported. After the results were reported, participants were able to compare the results, apply actual accelerations, and update their models within the postdiction phase. The prediction and postdiction of EPFL model were based on an equivalent frame model with a newly developed macroelement able to simulate both the in-plane and out-of-plane behaviour of unreinforced masonry piers, and a newly developed 3D material model allowing to simulate the interaction between the units. This paper deals with the prediction submitted by the EPFL team and discusses the results and possible pitfalls in modelling assumptions leading to unsatisfying prediction. Lessons learned are applied by updating the model for the postdiction analyses and discussing the updated results with the goal to improve the way we model unreinforced masonry aggregates using the equivalent frame approach.

Fibre-reinforced polymers (FRP) strengthening can be applied to decrease the seismic vulnerability of existing masonry buildings, both with regard to in-plane and out-of-plane failure mechanisms. Experimentally, the impact of strengthening solutions has been thoroughly studied. There are, however, few efficient and reliable numerical modeling approaches that can accurately capture the effect of such strengthening on the seismic response of the masonry building. Therefore, we herein develop and validate a modeling approach to capture the effect of FRP strengthening on the behaviour of masonry walls. To model this effect, we use a recently developed macro-element, which can capture both in-plane and out-of-plane failure modes. In the macro-element, the intervention is modelled by adding fibres representing the longitudinal FRP strips to the section model. These fibres were modelled as linear elastic in tension up to the failure with a zero compressive strength. Transversal FRP strips effect the shear strength, and in the macro-element, this is accounted for by increasing the cohesion in the equation for the shear strength. To validate the model, we also compare the numerical simulations with existing experimental results obtained from the literature. Overall, the proposed modeling approach accurately predicts the in-plane and out-of-plane response, implying that equivalent frame models can predict the response of masonry buildings with FRP-strengthened walls. To conclude, the models described in this paper can be used for a time-efficient assessment. Moreover, it can help in selecting the optimal strengthening approach for future retrofitting. This aspect is especially important for the cultural heritage structures, where excessive retrofitting should be avoided.

Introduction In 2009, we described a possible founder effect of autosomal dominant Segawa disease in Cordoba (Spain) due to mutation c.265C>T (p. Q89*) in the GCH1 gene. We present a retrospective multicentre study aimed at improving our knowledge of Segawa disease in Spain and providing a detailed phenotypic-genotypic description of patients. Methods Clinical-genetic information were obtained from standardized questionnaires that were completed by the neurologists attending children and/or adults from 16 Spanish hospitals. Results Eighty subjects belonging to 24 pedigrees had heterozygous mutations in GCH1. Seven genetic variants have been described only in our cohort of patients, 5 of which are novel mutations. Five families not previously described with p. Q89* were detected in Andalusia due to a possible founder effect. The median latency to diagnosis was 5 years (IQR 0–16). The most frequent signs and/or symptoms were lower limb dystonia (38/56, 67.8%, p = 0.008) and diurnal fluctuations (38/56, 67.8%, p = 0.008). Diurnal fluctuations were not present in the phenotypes other than dystonia. Fifty-three of 56 symptomatic patients were treated with a levodopa/decarboxylase inhibitor for (mean ± SD) 12.4 ± 8.12 years, with 81% at doses lower than 350 mg/day (≤5 mg/kg/d in children). Eleven of 53 (20%) patients had non-responsive symptoms that affected daily life activities. Dyskinesias (4 subjects) were the most prominent adverse effects. Conclusion This study identifies 5 novel mutations and supports the hypothesis of a founder effect of p. Q89* in Andalusia. New insights are provided for the phenotypes and long-term treatment responses, which may improve early recognition and therapeutic management.

We use spherical cap harmonic (SCH) basis functions to analyse and reconstruct the morphology of scanned genus-0 rough surface patches with open edges. We first develop a novel one-to-one conformal mapping algorithm with minimal area distortion for parameterising a surface onto a polar spherical cap with a prescribed half angle. We then show that as a generalisation of the hemispherical harmonic analysis, the SCH analysis provides the most added value for small half angles, i.e., for nominally flat surfaces where the distortion introduced by the parameterisation algorithm is smaller when the surface is projected onto a spherical cap with a small half angle than onto a hemisphere. From the power spectral analysis of the expanded SCH coefficients, we estimate a direction-independent Hurst exponent. We also estimate the wavelengths associated with the orders of the SCH basis functions from the dimensions of the first degree ellipsoidal cap. By windowing the spectral domain, we limit the bandwidth of wavelengths included in a reconstructed surface geometry. This bandlimiting can be used for modifying surfaces, such as for generating finite or discrete element meshes for contact problems. The codes and data developed in this paper are made available under the GNU LGPLv2.1 license., Comment: Preprint accepted for publication in Powder Technology

This paper presents a benchmark exercise for the seismic assessment of unreinforced masonry (URM) buildings as a follow-up of a blind prediction test organized in the context of the European Conference of Earthquake Engineering Series. The blind prediction exercise was aimed at better defining the open issues in current procedures for modeling and performing seismic analysis of URM buildings, by highlighting the uncertainty that can influence the results. This work presents an overview of the approaches used by different research teams and the scope of predictions. The benchmark structure was a three-story building with traditional European architecture from which two Cases were considered: A) stone masonry walls and flexible horizontal diaphragms and B) brick masonry walls and rigid horizontal diaphragms. A wide range of approaches was used by the participating teams concerning modeling strategies, methods of analysis and criteria for the attainment of limit states, which are here addressed as potential sources for the dispersion of predictions. The results were compared in terms of capacity curves, predicted failure mechanisms compatible with the fulfillment of limit states of near collapse and damage limitation, and related minimum values of peak ground acceleration (PGA). The results show an overall good agreement for damage patterns and collapse mechanisms in both benchmark structures, presenting some differences in the type of failure mode and its extent. However, the scatter of predicted capacity curves and critical PGAs is very high, especially for the Case with brick masonry and rigid diaphragms, indicating that clearer procedures in the building codes are required for professionals., This work was partly financed by FCT/MCTES through national funds (PIDDAC) under the R&D Unit Institute for Sustainability and Innovation in Structural Engineering (ISISE), under reference UIDB/04029/2020.

Thin reinforced concrete walls may fail due to out-of-plane instability when subjected to seismic loading. While previous numerical studies on wall instability have focused on the behaviour of members with two layers of vertical reinforcement, this work addresses the response of walls with a single layer of rebars. Such walls are particular prone to out-of-plane failure when subjected to cyclic in-plane loading. The numerical investigations herein performed simulate the aforementioned local behaviour and validate it against experimental measurements. A parametric study on the effect of boundary conditions shows that imposing an out-of-plane displacement or a rotation at the storey height increases the vulnerability to instability. It is also seen that the storey height itself is an influencing variable. The second part of this study proposes an improved equivalent boundary element model for the assessment of wall instability. Existing mechanical models, based on pinned-pinned boundary conditions, represent the boundary element over the height of the plastic hinge. This work shows that such models often underestimate the critical tensile strain triggering out-of-plane failure. A new equivalent boundary element model is proposed where a bilinear axial displacement profile defined a priori is applied. The latter is shown to satisfactorily approximate the vertical strain profile in wall boundary elements and to lead to better estimates of the critical strain triggering out-of-plane failure.

After an earthquake, the residual stiffness and strength of structural elements are typically estimated based on a qualitative visual inspection of cracks that is prone to error. In this paper a ne...

This paper presents the results of a series of shake-table tests on a half-scale, four-storey building with reinforced concrete and unreinforced masonry walls. Due to the lack of reference tests, the seismic behaviour of such mixed structures is poorly understood. The test unit was subjected to several runs of increasing intensity yielding performance states between minor damage and near collapse. Before the test, the expected peak table accelerations leading to different limit states were estimated using the capacity spectrum method, and the predicted values corresponded rather well to actual sustained accelerations. Next to these analyses, the paper describes the test unit, instrumentation and input motion, and comments on the response of the mixed structure in terms of damage evolution and global response quantities, such as force–displacement response and drift and acceleration profiles. The raw and post-processed data sets are made publically available, and all relevant information with regard to data organisation and post-processing procedure is described in an appendix to this paper. The test serves therefore as a benchmark for the validation of numerical models of such mixed structures. The project aims at providing a foundation for the development of seismic design and assessment methods of mixed structures, which are currently not covered by structural codes, including Eurocode 8.

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer’s disease (AD), and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD.

Purpose of the review The study of platelets in the context of neurodegenerative diseases is intensifying, and increasing evidence suggests that platelets may play an important role in the pathogenesis of neurodegenerative disorders. Therefore, we aim to provide a comprehensive overview of the role of platelets and their diverse activation pathways in the development of these diseases. Recent findings Platelets participate in synaptic plasticity, learning, memory, and platelets activated by exercise promote neuronal differentiation in several brain regions. Platelets also contribute to the immune response by modulating their surface protein profile and releasing pro- and anti-inflammatory mediators. In Alzheimer's disease, increased levels of platelet amyloid precursor protein raise the production of amyloid-beta peptides promoting platelet activation, triggering at the same time amyloid-beta fibrillation. In Parkinson's disease, increased platelet α-synuclein is associated with elevated ROS production and mitochondrial dysfunction. Summary In this review, we revise different platelet activation pathways, those classically involved in hemostasis and wound healing, and alternative activation pathways recently described in the context of neurodegenerative diseases, especially in Alzheimer's disease.

TThe supports of out-of-plane loaded unreinforced masonry walls in buildings are subjected to a motion that is filtered and amplified by the building structure and, in some cases, can be significantly different from the ground motion. Moreover, because these walls span one or several storeys, their top and bottom supports are subjected to motions that differ in phase and amplitude. In state-of-the-art assessment procedures for the out-of-plane stability of masonry walls any effect of a relative support motion is neglected. The objective of this paper is to study the effect of the relative support motion on the response of out-of-plane loaded vertically-spanning unreinforced masonry walls. The acceleration capacity of the walls is investigated by means of a discrete element model representative of different wall configurations. A set of ground motions covering a wide range of peak ground acceleration and peak ground displacement is used as input to the simulations. The relative motion between the wall supports is included in the model in a systematic way: firstly, through a motion that is non-synchronous but of equal amplitude; secondly, through a motion that is synchronous but of different amplitude. The effect of the relative support motion is studied on different wall configurations where the elastic modulus of masonry, the wall height-to-thickness ratio, the wall effective thickness and the overburden at the top wall are varied. The study shows that, because of the relative support motion, the acceleration capacity of the walls can drop by 20% and, in the cases where the overburden is high, by more than 50%.

This paper describes quasi-static cyclic shear-compression tests on six plastered single-leaf stone masonry walls. Of the six walls, four are tested under different axial load ratios, performing a cyclic load history with two cycles per increasing drift demand. Three are tested under the same axial load ratio but are subjected to different load histories, namely, one monotonic loading, one cyclic loading with two cycles per drift level and one cyclic loading with one hundred cycles per drift level. Stiffness, force capacity and drift measures corresponding to six different limit states of the walls are extracted from each test and the effect of the axial load ratio and of the load history on these parameters is investigated. Changing the axial load ratio on the tested walls confirms findings from previous studies, according to which, with increasing axial load the wall stiffness and the force capacity increase while the ultimate drift decreases. Varying the number of cycles in the applied load history brings new findings, showing that all the drift measures of the walls, especially those corresponding to limit states attained in the post-peak regime, are very sensitive to the number of cycles applied while the stiffness and the force capacity are not. These trends are shown in the paper and compared against code and literature provisions for in-plane loaded walls. One face of each wall is plastered and the damage of the plaster is compared to the damage of the stone and mortar. This information is required when assessing the non-structural damage of the walls.

The force-displacement behavior of masonry elements depends on the properties of their constituents, mortar and unit, as well as on their typology, i.e., the shape and size of the units and the patterns they generate. Up until now, only few numerical studies investigated the influence of the masonry typology on the mechanical properties of the masonry. The lack of research is caused by both the difficulty of generating specific stone masonry typologies, which vary depending on geographical regions, construction periods, and building technology, and the difficulty of conducting detailed micro-modeling analyses. Building on our recent developments of a typology generator and a detailed micro-modeling method based on cohesive elements, we investigate the relation between masonry typology and maximum shear resistance. After calibration of the model for shear-compression tests, the study examines the validity of Mann and Muller’s theory at the nonlinear stage, clarifies the role of the line of minimum trace in characterizing effective interlocking, and investigates the correlation of maximum shear resistance with various indexes. We show that the effect of the interlocking between units on the shear strength is overestimated by the Mann-Muller model. This study provides a fundamental contribution to our understanding of the influence of masonry typology on the masonry shear strength.

A unidirectional shake-table test was performed on the half-scale prototype of a natural stone masonry building aggregate, to investigate the seismic performance of this type of historical construction and to assess the effectiveness of two retrofit solutions. The specimen represented a building aggregate with two adjacent three-storey units, connected along one side as if they were built at different times. Double-leaf stone masonry with undressed blocks and river pebbles was used for the walls. Timber floors constituted flexible diaphragms in their planes. Roofs with different timber truss configurations and heights covered the two units. Improved wall-to-diaphragm connections and tie rods were pre-installed, although initially not fastened, on the prototype. Both retrofit systems were activated after significant damage was reached testing the unstrengthened specimen. This paper describes the seismic behaviour of the prototype, focusing on the effects of the retrofit interventions on damage mechanism evolution, lateral displacement demand, hysteretic response, and dynamic properties degradation.

This data paper presents the quasi-static uniaxial cyclic tests of 24 reinforced concrete members, of which 22 feature lap splices and 2 are reference units with continuous reinforcement. The objective of the experimental program is to investigate the influence of lap splice length ( ls), confining reinforcement, and loading history on the behavior of lap splices. Particular attention is placed on the measurement of local deformation quantities, such as lap splice strains and rebar-concrete slip. Details of the geometry and reinforcement layout of the specimens as well as the employed test setup, instrumentation, and loading protocols are provided. The global behavior of the test units, including the observed crack pattern and failure modes, are discussed. The organization of the experimental data, which are made available for public use under DOI: 10.5281/zenodo.1205887, is outlined in detail.

Under seismic actions, stone masonry buildings are prone to damage. To assess the severity of damaged masonry buildings and their failure modes, engineers connect these problems to surface crack features, such as the crack width and the extent of cracking. We aim to further these assessments in this study, wherein we propose using simple machine learning models to predict: 1) three ratios encoding the degradation of stiffness, strength, and displacement capacity of damaged rubble stone masonry piers as a function of the observed crack features and the applied axial load and shear span ratio; and 2) the pre-peak vs. post-peak regime, based on the crack features. When predicting the stiffness, force, and drift ratios, the prediction error is significantly reduced when the axial load and shear span ratio are included in the feature vector. Furthermore, when predicting the pre-peak vs. post-peak regime, simple machine learning models such as the k-nearest neighbor and the logistic regression result in remarkable accuracy. The obtained results have significant implications on the automated post-earthquake assessment of masonry buildings using image data. It is shown based on documented laboratory test data, that, by selecting proper crack features and incorporating information about the kinematic and static boundary conditions, even simple machine learning models can predict accurately the damage level caused to a rubble masonry pier. The three crack features used in this study are the maximum crack width, length density, and complexity dimension. The pipeline developed in this paper is general enough and is applicable to other masonry typologies and elements upon new evaluation of crack features and image data., Automation in Construction, 140, ISSN:0926-5805

Though flexible diaphragms play a role in the seismic behaviour of unreinforced masonry buildings, the effect of the connections between floors and walls is rarely discussed or explicitly modelled when simulating the response of such buildings. These flexible diaphragms are most commonly timber floors made of planks and beams, which are supported on recesses in the masonry walls and can slide when the friction resistance is reached. Using equivalent frame models, we capture the effects of both the diaphragm stiffness and the finite strength of wall-to-diaphragm connections on the seismic behaviour of unreinforced masonry buildings. To do this, we use a newly developed macro-element able to simulate both in-plane and out-of-plane behaviour of the masonry walls and non-linear springs to simulate wall-to-wall and wall-to-diaphragm connections. As an unretrofitted case study, we model a building on a shake table, which developed large in-plane and out-of-plane displacements. We then simulate three retrofit interventions: Retrofitted diaphragms, connections, and diaphragms and connections. We show that strengthening the diaphragm alone is ineffective when the friction capacity of the wall-to-diaphragm connection is exceeded. This also means that modelling an unstrengthened wall-to-diaphragm connection as having infinite stiffness and strength leads to unrealistic box-type behaviour. This is particularly important if the equivalent frame model should capture both global in-plane and local out-of-plane failure modes.

In this paper, we propose a simple global optimisation algorithm inspired by Pareto’s principle. This algorithm samples most of its solutions within prominent search domains and is equipped with a self-adaptive mechanism to control the dynamic tightening of the prominent domains while the greediness of the algorithm increases over time (iterations). Unlike traditional metaheuristics, the proposed method has no direct mutation- or crossover-like operations. It depends solely on the sequential random sampling that can be used in diversification and intensification processes while keeping the information-flow between generations and the structural bias at a minimum. By using a simple topology, the algorithm avoids premature convergence by sampling new solutions every generation. A simple theoretical derivation revealed that the exploration of this approach is unbiased and the rate of the diversification is constant during the runtime. The trade-off balance between the diversification and the intensification is explained theoretically and experimentally. This proposed approach has been benchmarked against standard optimisation problems as well as a selected set of simple and complex engineering applications. We used 26 standard benchmarks with different properties that cover most of the optimisation problems’ nature, three traditional engineering problems, and one real complex engineering problem from the state-of-the-art literature. The algorithm performs well in finding global minima for nonconvex and multimodal functions, especially with high dimensional problems and it was found very competitive in comparison with the recent algorithmic proposals. Moreover, the algorithm outperforms and scales better than recent algorithms when it is benchmarked under a limited number of iterations for the composite CEC2017 problems. The design of this algorithm is kept simple so it can be easily coupled or hybridised with other search paradigms. The code of the algorithm is provided in C++14, Python3.7, and Octave (Matlab).

Many historical centres in Europe, including the city centre of Zagreb, feature masonry building aggregates, which developed as the building layout of the city was densified. Adjacent buildings in aggregates often share a structural wall and the building that was constructed second connects to the wall of the first building through a dry joint. When compared to the response of single freestanding buildings, several factors make the seismic response of masonry building aggregates more complex: It is not unusual for adjacent units to have different material properties, area and distribution of openings, roof and floor heights and orientations, and construction details.

A correction to this paper has been published: https://doi.org/10.1617/s11527-021-01653-6

Reinforced concrete (RC) U-shaped walls are a popular construction choice, commonly used to resist the lateral loads from wind and earthquakes. In many buildings, the center of stiffness of a floor is eccentric from the center of mass and the building will therefore undergo some twist. Often, U-shaped walls contribute significantly to the torsional stiffness of the building and the analysis of the structure therefore requires an estimate of the torsional stiffness. This research investigates the dependency of the torsional stiffness of U-shaped walls on the translational displacement demands using experimental evidence and advanced numerical models. The experimental results show that the torsional stiffness decreases with increasing translational displacement. Furthermore, the numerical and experimental results indicate that the torsional stiffness degrades at a similar rate as the translational stiffness of the walls. The rotational stiffness of the wall is smaller when it is centered than when it is subjected to a translation. This effect is attributed to the longitudinal stresses throughout the cross section that are already present due to the imposed flexural displacement. In particular, the compression zone resulting from the translational displacement imposed on the wall stiffens the wall with regard to the twisting. As a result, the effective torsional stiffness increases with increasing axial load ratio. Current codes do not provide reduction factors for the torsional stiffness, but the results show that the reduction factors for the shear stiffness can serve as estimate, albeit they do not capture the dependence on the axial load ratio. (C) 2020 American Society of Civil Engineers.

Background Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia after Alzheimer’s disease (AD) and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets have been previously related to neurodegeneration. They contain microRNAs (miRNAs), and their analysis may provide disease biomarkers. Methods Small RNAs from platelets of DLB patients and controls were analyzed by Next Generation Sequencing (NGS), and miRNAs deregulated in DLB were selected. Expression of these miRNAs was then determined and validated by LNA-based qRT-PCR in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Their predictive diagnostic potential was calculated by ROC curve analysis. miRTarbase and miRGate were used for target prediction. Results We profiled the whole platelet miRNA transcriptome from 7 DLB patients and 7 controls using NGS. Twenty-two selected miRNAs were further validated in independent studies (2017–2019) including DLB (n = 59), AD (n = 28), and PD (n = 24) patients, and control individuals (n = 51). Our results demonstrated downregulated expression levels for hsa-let-7d-5p (fold change 0.14; p = 0.006), hsa-miR-132-5p (0.12; p = 0.0015), hsa-miR-142-3p (0.07; p = 0.00047), hsa-miR-146a-5p (0.07; p = 0.00035), hsa-miR-150-5p (0.10; p = 0.0098), hsa-miR-25-3p (0.13; p = 0.0019) and hsa-miR-26b-5p (0.09; p = 0.0014) in DLB compared to AD. ROC curve for this seven-miRNA biosignature yielded an area under the curve (AUC) of 1. Both hsa-miR-142-3p and hsa-miR-150-5p, were down-regulated in DLB compared to controls (AUC = 0.85). Comparing AD and controls, miRNAs hsa-miR-132-5p, hsa-miR-146a-5p, hsa-miR-25-3p, and hsa-miR-6747-3p were up-regulated in AD (AUC = 0.94); and hsa-miR-128-3p and hsa-miR-139-5p were down-regulated in PD compared to controls (AUC = 0.81). Predictive target analysis identified three disease-specific pathway clusters as a result of platelet-miRNA deregulation. In DLB, pathways related to gene expression and small RNA metabolism; in AD, pathways related to stress response and RNA stress granules; and in PD pathways related to protein phosphorylation, metabolism and degradation were identified. Conclusion A platelet-associated bio-signature composed of 7 miRNAs is highly specific and sensitive for distinguishing DLB from AD.

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia after Alzheimer’s disease (AD) and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a 7-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based bio-signature, which distinguishes DLB from AD.The paper explainedProblemDementia with Lewy bodies (DLB) presents pathological and clinical overlap with both Alzheimer’s (AD) and Parkinson’s disease (PD), which impairs its correct diagnosis. Although numerous papers report peripheral biomarkers for AD, well-established biomarkers for DLB distinguishing it from AD are still missing. Platelet miRNA transcriptome was analyzed in several works, but their putative role as disease biomarkers for neurological disorders has not been assessed. It would be of paramount importance to establish a blood-based bio-signature as a minimally invasive mean for DLB diagnosis, improving differentiation of DLB patients from controls and AD.ResultsOur study revealed that platelet miRNAs might be promising biomarkers for the correct diagnosis of DLB stratifying patients in comparison with overlapping disorders, especially AD, and may help to highlight possible disease-related processes. In this cross-sectional study, which includes 162 individuals (DLB, AD, PD and healthy controls), platelet-associated miRNA content was disease group-specific. Three different miRNA sets together with their predicted targeted pathways were defined.ImpactThis study suggests that platelet miRNA may serve as DLB biomarker allowing the correct diagnosis and stratification in an easily-applied manner in clinical settings, and may help to highlight possible disease-related processes.

The seismic performance of buildings depends critically on the stiffness and strength of storey diaphragms. Whilst for modern reinforced concrete or steel structures the connection between floors and lateral resisting members is often assumed as monolithic, timber floors and ceilings in masonry buildings are susceptible to sliding in their supports. In fact, the anchorage of timber beams in masonry walls and intermediate supports relies partly or totally on a frictional type of resisting mechanism. The present work contributes to characterize this behaviour by presenting the results of an extensive experimental programme with cyclic friction triplet tests between mortar and timber units, and between timber and timber units. These were produced to be representative of connection typologies characteristic of pre-modern and contemporary construction periods. Each test was performed under a constant level of contact pressure, which was increased throughout each series to cover a range of normal forces foreseeable in building connections. Other aspects are also discussed, such as the influence of cumulative loading or velocity. The experimental data is made available for public use (https://doi.org/10.5281/zenodo.3348328).

Equivalent frame models are an effective tool for the seismic assessment of existing masonry structures. Due to their simplicity, these models can be used to perform multiple nonlinear dynamic analyses, accounting explicitly for different sources of modeling and input uncertainty. In the past, equivalent frame models have been used to effectively estimate the global response of buildings whose behavior is dominated by in-plane failure modes of piers and spandrels. The recent development of a three-dimensional macroelement formulation for modeling both the in-plane and out-of-plane response extends the use of equivalent frame models to the additional study of local out-of-plane mechanisms of a building. This work applies the newly developed formulation, implemented in OpenSEES (McKenna et al., 2000), to the modeling of two shaking table tests on a stone masonry building and on a modern mixed concrete-unreinforced masonry structure. Since the approach explicitly accounts for the quality of connections in the building (i.e., wall-to-wall and floor-to-wall connections), specific elements and material models were developed for modeling these connections in an equivalent frame idealization of the three-dimensional structure. Through comparison with the experimental results, the performance of the modeling approach is discussed, and the sensitivity of the response to the major sources of modeling uncertainty (quality of connections, damping model) is assessed. The comparisons show that these new equivalent frame models can capture the onset of out-of-plane failure for historical structures with poor floor-to-wall connections and for modern URM buildings with stiff RC slabs, where the slab can uplift from the URM wall, which leads to changing static and kinematic boundary conditions of the out-of-plane loaded wall. The results further show that 1–2% of damping leads to good agreements with the experimental results if initial stiffness proportional Rayleigh damping is used.

This paper presents a mechanical model for the simulation of reinforced concrete (RC) wall boundary elements with lap splices, which builds on the tension chord model. The model is composed of an assembly of components, each one accounting for a different source of deformation. Namely: (i) an anchorage-slip element accounting for the strain penetration of the longitudinal reinforcement into the foundation; (ii) a basic tension chord element evaluating the response outside the lap splice zone; and (iii) a lap splice element describing the behaviour within the lap splice region. For an imposed global displacement, the model provides the steel and concrete stress and strain distributions, the crack distribution and opening, as well as the global resisting axial force. For spliced members, the ultimate displacement is computed through a semi-empirical relationship providing the average lap splice strain at failure. Validation is carried out against a series of uniaxial cyclic tests on RC wall boundary elements featuring both continuous and spliced reinforcement; different lap splice lengths and confining reinforcement are considered. Overall, a good match is obtained between numerical and experimental results in terms of crack width, rebar strain distribution along the splices and ultimate displacement.

D-A-CH-Mitteilungsblatt [enthalten in: Bauingenieur], 95 (4), ISSN:1434-6591, ISSN:0005-6650

Out-of-plane failure of masonry walls is often responsible for the partial collapse of unreinforced masonry structures. Modeling the out-of-plane response of these walls is therefore key in the assessment of existing buildings. The paper presents a new trilinear model describing the force-displacement response of vertically spanning unreinforced masonry walls subjected to out-of-plane loading. Different factors that affect the response of the walls are captured by the model: the support conditions, the level of applied axial load, the slenderness ratio, and the deformability of the wall. The model is validated against experimental results from shake table tests. The force and displacement parameters of the model are described by analytical expressions that are derived from a mechanical model previously developed for unreinforced masonry. They offer an alternative to existing trilinear models in which corner displacements are mainly defined by empirical relationships.

Lewy body diseases (LBD) include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) and together with Alzheimer’s disease (AD) they show an important neuropathological and clinical overlap. The human alpha- and beta-synuclein genes (SNCA and SNCB) are key factors for the development of Lewy body diseases. Here, we aimed to analyze the genotype distribution of potentially functional SNPs in SNCA and SNCB, perform haplotype analysis for SNCB, and to identify functional insertion and deletion (INDEL) variations within the regulatory region of SNCB which might be responsible for the drastically diminished beta-synuclein levels reported for pure DLB. Thus, we genotyped brain samples from AD, DLB, PD, and healthy controls for two SNCA and four SNCB SNPs. We also analyzed INDEL variations upstream of SNCB, determined SNCB expression levels, and correlated INDEL lengths with expression levels. Applying Fisher’s exact, chi-square, ANOVA tests, and the ΔΔCt method, we found disease-specific genotype distribution of SNCA and SNCB SNPs. Additionally, we identified three INDEL variations upstream of SNCB and showed that the INDEL allele lengths were associated with SNCB expression levels. INDEL alleles associated with low SNCB expression were accumulated in pure DLB. Finally, one major and four minor DLB specific SNCB haplotypes were identified with Haploview and Arlequin. In summary, our study showed that different SNCA and SNCB genotypes are associated with the development of either PD or DLB, and that the frequencies of genotypes associated with low SNCB expression are elevated in DLB.

Introduction: Glucocerebrosidase (GBA) gene variants are associated with the development of the Lewy body disorders (LBD) Parkinson disease (PD) and dementia with Lewy bodies (DLB). Idiopathic REM sleep behavior disorder (IRBD) represents prodromal LBD in most instances. We investigated whether GBA variants are overrepresented in IRBD and if their presence shortens the time to conversion to clinically defined LBD. Methods: All GBA coding exons from 69 polysomnography-confirmed IRBD patients and 84 matched controls were sequenced by the Sanger method. Results: Seven missense variants (E326K, L444P, A446T, A318G, R329C, T369M, N3705) were identified in eight (11.6%) IRBD patients and in one (1.2%) control (P = 0.026). After a mean follow-up of 8.9 3.8 years from IRBD diagnosis, five subjects with GBA variants developed LBD (3 DLB and 2 PD) and three remained disease-free. The risk of developing a LBD was similar in IRBD subjects with GBA variants than in those without variants (log rank test, p = 0.935). Conclusions: In IRBD, GBA variants are 1) more frequent when compared to controls, 2) associated with impending PD and DLB but 3) not indicative of a short-term risk for LBD after IRBD diagnosis. IRBD patients carrying GBA variants could be studied with disease-modifying interventions aiming to restore the GBA metabolic pathway. (C) 2018 Elsevier Ltd. All rights reserved.