Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters











Database
Language
Publication year range
1.
Physiol Meas ; 41(5): 054002, 2020 06 19.
Article in English | MEDLINE | ID: mdl-32259798

ABSTRACT

OBJECTIVE: Smartphone devices may enable out-of-clinic assessments in chronic neurological diseases. We describe the Draw a Shape (DaS) Test, a smartphone-based and remotely administered test of Upper Extremity (UE) function developed for people with multiple sclerosis (PwMS). This work introduces DaS-related features that characterise UE function and impairment, and aims to demonstrate how multivariate modelling of these metrics can reliably predict the 9-Hole Peg Test (9HPT), a clinician-administered UE assessment in PwMS. APPROACH: The DaS Test instructed PwMS and healthy controls (HC) to trace predefined shapes on a smartphone screen. A total of 93 subjects (HC, n = 22; PwMS, n = 71) contributed both dominant and non-dominant handed DaS tests. PwMS subjects were characterised as those with normal (nPwMS, n = 50) and abnormal UE function (aPwMS, n = 21) with respect to their average 9HPT time (≤ or > 22.7 (s), respectively). L 1-regularization techniques, combined with linear least squares (OLS, IRLS), or non-linear support vector (SVR) or random forest (RFR) regression were investigated as functions to map relevant DaS features to 9HPT times. MAIN RESULTS: It was observed that average non-dominant handed 9HPT times were more accurately predicted by DaS features (r 2 = 0.41, [Formula: see text] 0.05; MAE: 2.08 ± 0.34 (s)) than average dominant handed 9HPTs (r 2 = 0.39, [Formula: see text] 0.05; MAE: 2.32 ± 0.43 (s)), using simple linear IRLS ([Formula: see text] 0.01). Moreover, it was found that the Mean absolute error (MAE) in predicted 9HPTs was comparable to the variability of actual 9HPT times within HC, nPwMS and aPwMS groups respectively. The 9HPT however exhibited large heteroscedasticity resulting in less stable predictions of longer 9HPT times. SIGNIFICANCE: This study demonstrates the potential of the smartphone-based DaS Test to reliably predict 9HPT times and remotely monitor UE function in PwMS.


Subject(s)
Diagnostic Techniques and Procedures/instrumentation , Multiple Sclerosis/diagnosis , Multiple Sclerosis/physiopathology , Smartphone , Upper Extremity/physiopathology , Adult , Female , Humans , Male , Regression Analysis
2.
J Pharm Biomed Anal ; 154: 57-65, 2018 May 30.
Article in English | MEDLINE | ID: mdl-29533859

ABSTRACT

Previously we have introduced two SPR-based assay principles (dual-binding assay and bridging assay), which allow the determination of two out of three possible interaction parameters for bispecific molecules within one assay setup: two individual interactions to both targets, and/or one simultaneous/overall interaction, which potentially reflects the inter-dependency of both individual binding events. However, activity and similarity are determined by comparing report points over a concentration range, which also mirrors the way data is generated by conventional ELISA-based methods So far, binding kinetics have not been specifically considered in generic approaches for activity assessment. Here, we introduce an improved slope-ratio model which, together with a sensorgram comparison based similarity assessment, allows the development of a detailed, USP-conformal ligand binding assay using only a single sample concentration. We compare this novel analysis method to the usual concentration-range approach for both SPR-based assay principles and discuss its impact on data quality and increased sample throughput.


Subject(s)
Chemistry, Pharmaceutical/methods , Models, Chemical , Surface Plasmon Resonance/methods , Angiopoietin-2/chemistry , Antibodies, Bispecific/chemistry , Enzyme-Linked Immunosorbent Assay , Ligands , Protein Binding , Vascular Endothelial Growth Factor A/chemistry
3.
J Pharm Biomed Anal ; 132: 141-147, 2017 Jan 05.
Article in English | MEDLINE | ID: mdl-27721070

ABSTRACT

The increasing complexity of novel biotherapeutics such as bispecific antibodies or fusion proteins raises new challenges for functional characterization. When compared to standard antibodies, two individual interactions and the inter-dependency of binding events need to be considered for bispecific antibodies. We have previously described an SPR-based assay setup, which enables us to assess the binding activity of a bivalent-bispecific molecule to both targets simultaneously and - in addition to one individual target - in a single setup. However, there might be some pitfalls when applying the bridging assay, e.g. change of antigen activity upon immobilization. Therefore, we have developed an alternative SPR-based assay principle, which allows the individual assessment of both targets in solution. Comparison of data between the assays showed that simultaneous binding can be calculated based on both individual readouts, and revealed a good correlation. Hence, both SPR-based assay principles allow a "full" functional analysis of a bispecific CrossMab in only one assay. The assay principles can be qualified and enable an efficient drug development.


Subject(s)
Biological Assay/methods , Surface Plasmon Resonance/methods , Angiopoietin-2/chemistry , Antibodies, Bispecific/chemistry , Biosensing Techniques , Drug Design , Humans , Immunoglobulin Fragments/chemistry , Ligands , Linear Models , Protein Binding , Reference Values , Reproducibility of Results , Vascular Endothelial Growth Factor A/chemistry
4.
J Pharm Biomed Anal ; 102: 144-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25277666

ABSTRACT

Surface plasmon resonance (SPR) is increasingly applied in drug discovery, early development and production. However, there are remarkably few reports describing the application of SPR in a regulated environment. Here, we describe a novel SPR-based assay, which enables us to assess the binding activity of a bivalent-bispecific anti-Ang-2/anti-VEGF antibody to both targets in a single setup. Validation of the assay revealed a high level of precision, accuracy, linearity and specificity. Upon analysis of temperature stressed samples it could be shown that firstly, the assay is able to indicate function-loss and secondly, it allows the parallel analysis of an additional interaction. Therefore, the described assay is highly suitable for quality assessment of the Ang-2/VEGF CrossMab. Additionally, the use of SPR in the context of assay development and routine use in a GMP environment is discussed.


Subject(s)
Angiopoietin-2/metabolism , Antibodies, Bispecific/metabolism , Vascular Endothelial Growth Factor A/metabolism , Dose-Response Relationship, Drug , Humans , Models, Immunological , Surface Plasmon Resonance
SELECTION OF CITATIONS
SEARCH DETAIL