Background
Recent observations suggest a lack of humoral response after SARS-CoV-2 vaccination in multiple sclerosis (MS) patients treated with fingolimod or ocrelizumab
Objectives
To assess ...serological response to SARS-CoV-2 vaccination in MS patients receiving these disease-modifying treatments (DMTs) in a real-life setting.
Methods
Retrospective clinical data collection from MS patients followed at San Raffaele Hospital MS Centre (Milan, Italy). All patients treated with fingolimod or ocrelizumab who had received a complete anti-COVID-19 vaccination course, with no clinical history suggestive of previous SARS-CoV-2 infection and with an available post-vaccination serological assay obtained at least 14 days after vaccination completion were considered for the study.
Results
We collected data from 32 MS patients, 16 treated with fingolimod and 16 receiving ocrelizumab. Among the fingolimod group 10 patients (62.5%) had a positive serological response after vaccination and among ocrelizumab-treated patients a positive serological test was found in six cases (37.5%). No relation between serological response and clinical features (i.e., treatment duration, time between vaccination and last treatment dose, and white blood cells count) was identified.
Conclusions
Our initial real-life experience suggests a variable antibody production in MS patients receiving these DMTs. At present, there are no sufficient data to do not recommend anti-SARS-CoV-2 vaccine in these patients.
Carrera Unified Formulation (CUF) is used to perform free-vibrational analyses of rotating structures. CUF is a hierarchical formulation which offers a procedure to obtain refined structural theories ...that account for variable kinematic description. These theories are obtained by expanding the unknown displacement variables over the beam section axes by adopting Taylor’s expansions of N-order, in which N is a free parameter. Linear case (N=1) permits us to obtain classical beam theories while higher order expansions can lead to three-dimensional description of dynamic response of blades. The Finite Element Method is used to solve the governing equations of rotating blades that are derived in a weak form by means of Hamilton’s Principle. These equations are written in terms of “fundamental nuclei”, which do not vary with the theory order (N). Both flapwise and lagwise motions of isotropic, composite and thin-walled structures are traced. The Coriolis force field is included in the equations. Results are presented in terms of natural frequencies and comparisons with published solutions are provided.
This paper proposes one-dimensional layer-wise theories that make use of higher-order zig-zag functions defined over fictitious/mathematical layers of the cross-sectional area. These advanced ...kinematics enable the computational costs to be reduced while the accuracy of the classical layer-wise theories in which the number of physical and numerical layers coincide, is maintained. Variable kinematics theories have been obtained using piecewise continuous power series expansions of an arbitrary order defined over the whole cross-section of the structure. As in the classical layer-wise approach, the cross-section can be divided into a variable number of mathematical subdomains. The expansion order of each subdomain is therefore an input parameter of the analysis. This feature enables the solution to be refined locally as the kinematics expansion can be enriched over generic regions of the cross-section. The governing equations have been obtained by applying the Principle of Virtual Displacements, along with the Carrera Unified Formulation, and have been solved using the Finite Element method. Numerical simulations have been performed considering laminated and sandwich beams with very low length-to-depth ratio values. Comparisons between the present results and solutions available in the literature have pointed out the advantages of this approach, in terms of accuracy of the displacements, of the stress distributions over the beam cross-section and of the natural frequencies with respect to the classical layer-wise theories.
The San Antonio River Basin (SARB) is an ecologically diverse region in South Texas. The city of San Antonio is located within the basin and is the hub of the North American Free Trade Agreement ...(NAFTA). San Antonio, together with other major metropolitan centers in Texas, has experienced rapid population and economic growth over the last thirty years, which accelerated after the implementation of NAFTA in 1994. To assess the environmental implications of this growth in the SARB, we first conducted a land-change analysis using Landsat images from 1984, 1995, and 2010. Then, we analyzed spatiotemporal changes in ecosystem services across the SARB and within three watersheds in Bexar County where the city of San Antonio is located. To estimate changes in ecosystem service values (ESV) during this period, we combined the results of the land-change analysis with a benefit transfer approach using two sets of widely cited ecosystem-service valuation coefficients published in 1997 and 2014 but we modified the urban coefficient from the 2014 publication for low-density and high-density urban areas. When 1997 coefficients were applied, the ESV in the SARB decreased, on average, by $1.2million/year during 1984–1995 and by $1.8million/year during 1995–2010. The ESV in Bexar County decreased, on average, by $0.5million/year and $0.7million/year during the first and second periods, respectively. When the 2014 coefficients and modified urban value coefficients were applied, the ESV in the SARB decreased, on average, by a 27% more during the first period than when the 1997 coefficients were applied, while, ESV increased during the second period by an average of $2.2million/year. This temporally opposite trend in ESV change did not occur in Bexar County, however. Using the 2014 coefficients, ESV in Bexar County decreased 5 times more during the first period and decreased 2.5 times more during the second period than when 1997 coefficients were applied. The differences in ESV trends resulting from the two sets of coefficients can be explained primarily by the different coefficients assigned to urban spaces ($0/ha/year in the 1997 study and $7005/ha/year in the 2014 study). Our results suggest that the value placed on urban areas in the 2014 publication, taken from a single case study and intended primarily for large urban parks, substantially overestimates the ESV of urban space. In our study areas, applying this value, even only to urban green space, led to the improbable conclusion that urbanization had a positive overall effect on the delivery of ecosystem services. While open spaces in urban areas do provide valuable ecosystem services, it is highly unlikely that their value exceeds those provided by less modified ecosystems. The ability to confidently use value coefficients when applying benefit transfer methods to estimate ESVs demands rigorous assessments of their broad applicability.
•We estimate changes in ecosystem services in the San Antonio River Basin, Texas using two sets of valuation coefficients.•Urban expansion in the San Antonio River Basin occurred mostly at the expense of woodlands/forests.•Ecosystem service values decreased substantially since the North American Free Trade Agreement (NAFTA) was enacted in 1994.•The revised urban coefficient reported in Costanza et al. (2014) is highly overestimated.
A number of refined beam theories are discussed in this paper. These theories were obtained by expanding the unknown displacement variables over the beam section axes by adopting Taylor's ...polynomials, trigonometric series, exponential, hyperbolic and zig-zag functions. The Finite Element method is used to derive governing equations in weak form. By using the Unified Formulation introduced by the first author, these equations are written in terms of a small number of fundamental nuclei, whose forms do not depend on the expansions used. The results from the different models considered are compared in terms of displacements, stress and degrees of freedom (DOFs). Mechanical tests for thick laminated beams are presented in order to evaluate the capability of the finite elements. They show that the use of various different functions can improve the performance of the higher-order theories by yielding satisfactory results with a low computational cost.
•Carrera Unified Formulation permits us to deal with any-order of beam theories with no need for ‘ad hoc’ formulations.•The CUF frameworks allow us to consider generic functions in displacement field.•A variety of new expansions have been considered: trigonometric, exponential, hyperbolic and miscellaneous functions.•Zig-Zag theories have been used in the frameworks of the Carrea Unified Formulation in the composite structures analysis.
In this placebo-controlled, phase 3 trial involving patients with relapsing–remitting multiple sclerosis, oral laquinimod administered once daily reduced the number of clinical relapses and slowed ...disability progression.
Laquinimod is an oral quinoline-3-carboxamide small molecule selected for its efficacy and safety from a pool of 60 quinoline-3-carboxamide derivatives of the parent compound, roquinimex, a drug previously evaluated in phase 2 trials of treatment for multiple sclerosis but withdrawn because of safety concerns.
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Preclinical studies have shown that laquinimod reduces inflammatory cell infiltrates in the central nervous system, decreases demyelination, and prevents axonal loss.
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It is currently in clinical development for the treatment of multiple sclerosis.
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A 36-week, double-blind, placebo-controlled, phase 2 clinical trial showed a significant reduction in the primary end point, the cumulative number of gadolinium-enhancing . . .
A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal ...cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small cross-sectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of “critical mass” of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.
•Methodological challenges encountered in imaging of the spinal cord are presented.•Techniques to overcome these challenges for fMRI and DTI are presented.•Methods for spinal cord MRI (fMRI, DTI, MWF, MTR), MRS, and PET are presented.•Post-processing methods to improve spinal cord MRI are discussed.•We discuss the future directions, and current needs, for spinal cord imaging.
This work investigates the dynamic response of various rotating cylindrical structures using low- and high-fidelity one-dimensional (1D) and two-dimensional (2D) finite element models. The adopted ...mathematical formalism is based on the Carrera Unified Formulation (CUF). CUF offers a procedure to obtain higher-order beam and shell models hierarchically and automatically. These theories are formulated by expanding the unknown variables over the beam cross-section or along the shell thickness. Various beam and shell models can be implemented depending on the choice of the polynomial employed in the expansion. Both Taylor-like and Lagrange polynomials are considered for developing different kinematic models. The linearized equations of motion include the Coriolis and initial stress contributions. Various thick and thin cylinders and disk structures with different boundary conditions are considered. The beam and shell results are compared with analytical and three-dimensional (3D) finite element (FE) solutions from the literature.
In the present work, a shell finite element with a variable kinematic field based on a new zig-zag power function is proposed for the analysis of laminated shell structures. The kinematic field is ...written by using an arbitrary number of continuous piecewise polynomial functions. The polynomial expansion order of a generic subdomain is a combination of zig-zag power functions depending on the shell thickness coordinate. As in the classical layer-wise approach, the shell thickness can be divided into a variable number of mathematical subdomains. The expansion order of each subdomain is an input parameter of the analysis. This feature enables the solution to be locally refined over generic regions of the shell thickness by enriching the kinematic field. The advanced finite shell elements with variable kinematics are formulated in the framework of the Carrera Unified Formulation. The finite element arrays are formulated in terms of fundamental nuclei, which are invariants of the theory approximation order and the modelling technique (Equivalent-Single-Layer, Layer-Wise). In this work, the attention is focused on linear static stress analyses of composite laminated shell structures. The governing equations are obtained by applying the Principle of Virtual Displacements, and they are solved using the Finite Element method. Furthermore, the Mixed Interpolated Tensorial Components (MITC) method is employed to contrast the shear locking phenomenon. Several numerical investigations are carried out to validate and demonstrate the accuracy and efficiency of the present shell element.
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