Classification of multi-class motor imagery with a novel hierarchical SVM algorithm for brain–computer interfaces

Pattern classification algorithm is the crucial step in developing brain–computer interface (BCI) applications. In this paper, a hierarchical support vector machine (HSVM) algorithm is proposed to address an EEG-based four-class motor imagery classification task. Wavelet packet transform is employed to decompose raw EEG signals. Thereafter, EEG signals with effective frequency sub-bands are grouped and reconstructed. EEG feature vectors are extracted from the reconstructed EEG signals with one versus the rest common spatial patterns (OVR-CSP) and one versus one common spatial patterns (OVO-CSP). Then, a two-layer HSVM algorithm is designed for the classification of these EEG feature vectors, where “OVO” classifiers are used in the first layer and “OVR” in the second layer. A public dataset (BCI Competition IV-II-a)is employed to validate the proposed method. Fivefold cross-validation results demonstrate that the average accuracy of classification in the first layer and the second layer is 67.5 ± 17.7% and 60.3 ± 14.7%, respectively. The average accuracy of the classification is 64.4 ± 16.7% overall. These results show that the proposed method is effective for four-class motor imagery classification.     

Micromotion-induced strain fields influence early stages of repair at bone–implant interfaces

Implant loading can create micromotion at the bone–implant interface. The interfacial strain associated with implant micromotion could contribute to regulating the tissue healing response. Excessive micromotion can lead to fibrous encapsulation and implant loosening. Our objective was to characterize the influence of interfacial strain on bone regeneration around implants in mouse tibiae. A micromotion system was used to create strain under conditions of (1) no initial contact between implant and bone and (2) direct bone–implant contact. Pin- and screw-shaped implants were subjected to displacements of 150 or 300 μm for 60 cycles per day for 7 days. Pin-shaped implants placed in five animals were subjected to three sessions of 150 μm displacement per day, with 60 cycles per session. Control implants in both types of interfaces were stabilized throughout the healing period. Experimental strain analyses, microtomography, image-based displacement mapping, and finite element simulations were used to characterize interfacial strain fields. Calcified tissue sections were prepared and Goldner trichrome stained to evaluate the tissue reactions in higher and lower strain regions. In stable implants bone formation occurred consistently around the implants. In implants subjected to micromotion bone regeneration was disrupted in areas of high strain concentrations (e.g. >30%), whereas lower strain values were permissive of bone formation. Increasing implant displacement or number of cycles per day also changed the strain distribution and disturbed bone healing. These results indicate that not only implant micromotion but also the associated interfacial strain field contributes to regulating the interfacial mechanobiology at healing bone–implant interfaces.     

Methods for quantification of pore–voltage sensor interaction in CaV1.2

Voltage sensors (VSs) initiate the pore opening and closure in voltage-gated ion channels. Here, we propose a technique for estimation of the equilibrium constant of the up- and downward VS movements and rate constants of pore transitions from macroscopic current kinetics. Bell-shaped voltage dependence of the activation/deactivation time constants and Bolzmann distributions of Ca_V1.2 activation were analyzed in terms of a circular four-state (rest, activated, open, deactivated) channel model: both dependencies uniquely constrain the model parameters. Neutralization of gating charges in IS4 or IIS4 only slightly affects the equilibrium constant of VS transition while affecting simultaneously the rate constants of pore opening and closure. The application of our technique revealed that pore mutations on IS6–IVS6 segments induce pronounced shifts of the VS equilibrium between the resting (down) and activated (up) position. Analyzing a channelopathy mutation highlighted that the leftward shift of the activation curve induced by I781T on IIS6 is only partially (35 %) caused by a destabilization of the channel pore but predominantly (65 %) by a shifted VS equilibrium towards activation. The algorithm proposed for CaV1.2 may be applicable for calculating rate constants from macroscopic current kinetics in other voltage-gated ion channels.     

Discrimination of left and right leg motor imagery for brain–computer interfaces

This article reports on a study to identify electroencephalography (EEG) signals with potential to provide new BCI channels through mental motor imagery (MMI). Leg motion was assessed to see if left and right leg MMI could be discriminated in the EEG. The study also explored simultaneous observation of leg movement as a means to enhance MMI evoked EEG signals. The results demonstrate that MMI of the left and right leg produce a contralateral preponderance of EEG alpha band desynchronization, which can be spatially discriminated. This suggests that lower extremity MMI could provide signals for additional BCI channels. The study also shows that movement imitation enhances alpha band desynchronization during MMI, and might provide a useful aid in the identification and training of BCI signals.     

Development of a bovine collagen–apatitic calcium phosphate cement for potential fracture treatment through vertebroplasty

The aim of this study was to examine the potential of incorporating bovine fibres as a means of reinforcing a typically brittle apatite calcium phosphate cement for vertebroplasty. Type I collagen derived from bovine Achilles tendon was ground cryogenically to produce an average fibre length of 0.96 ± 0.55 mm and manually mixed into the powder phase of an apatite-based cement at 1, 3 or 5 wt.%. Fibre addition of up to 5 wt.% had a significant effect (P ? 0.001) on the fracture toughness, which was increased by 172%. Adding ?1 wt.% bovine collagen fibres did not compromise the compressive properties significantly, however, a decrease of 39–53% was demonstrated at ?3 wt.% fibre loading. Adding bovine collagen to the calcium phosphate cement reduced the initial and final setting times to satisfy the clinical requirements stated for vertebroplasty. The cement viscosity increased in a linear manner (R² = 0.975) with increased loading of collagen fibres, such that the injectability was found to be reduced by 83% at 5 wt.% collagen loading. This study suggests for the first time the potential application of a collagen-reinforced calcium phosphate cement as a viable option in the treatment of vertebral fractures, however, issues surrounding efficacious cement delivery need to be addressed.     

The Development of a PC Based Platform for Experimental Data Management

FOREWORD　　The Polygraph System we are using in our lab was produced by Nihon Konden.And most of the institutes in our country use this kind of instrument in their re-search work. Though the analogue part of the system still possesses satisfactoryfunctions,its ink- jet paper recorder is not convenient for the saving,examining andanalysis of the experimental data.With our newly developed platform,the analogueoutput signals from the Polygraph System can be digitized,saved,processed,dis-pl…     

Epigenetic Analysis of Neurocognitive Development at 1 year of Age in a Community-Based Pregnancy Cohort

Multiple studies show that molecular genetic changes and epigenetic modifications affect the risk of cognitive disability or impairment. However, the role of epigenetic variation in cognitive development of neurotypical young children remains largely unknown. Using data from a prospective, community-based study of mother-infant pairs, we investigated the association of DNA methylation patterns in neonatal umbilical cord blood with cognitive and language development at 1 year of age. No CpG loci achieved genome-wide significance, although a small number of weakly suggestive associations with Bayley-III Receptive Communication scales were noted. While umbilical cord blood is a convenient resource for genetic analyses of birth outcomes, our results do not provide conclusive evidence that its use for DNA methylation profiling yields epigenetic markers that are directly related to postnatal neurocognitive outcomes at 1 year of age.     

Are Doppler studies a useful method of assessing neovascularization in human Achilles tendinopathy? A systematic review and suggestions for optimizing machine settings

Achilles tendinopathy describes a painful condition. The symptoms include localized swelling and tenderness, and the condition is often associated with altered tendon structure and neovascularization. Doppler ultrasound has been used in Achilles neovascularization and despite the lack of standardization and machine settings, recent research has demonstrated a potential relationship between pathology and the presence of neovascularization. This paper is a systematic review of the published studies which have used Doppler ultrasound in the assessment of Achilles neovascularization, and a prospective study to suggest a degree of optimization for future studies.     

Development of a highly sensitive biotin–streptavidin enzyme-linked immunosorbent assay for detecting diethyl phthalate based on a specific polyclonal antibody

An indirect competitive biotin–streptavidin enzyme-linked immunosorbent assay (BA-ELISA) has been established for the determination of diethyl phthalate (DEP) in wine samples. A highly sensitive and specific polyclonal antibody (pAb-DEP) targeting DEP was prepared. Under optimized conditions, good linearity was achieved within a range of 0.021–9.512 μg·L^?1. The limit of detection (IC₁₀) was 0.0079 μg·L^?1 and the median inhibitory concentration (IC₅₀) was 0.443 μg·L^?1. Besides, the BA-ELISA was highly selective, with low cross-reactivity values with DEP analogs (below 5%). Finally, the concentrations of DEP in wine samples ranged from 5.93 μg·L^?1 to 59.15 μg·L^?1 by BA-ELISA. Satisfactory recoveries (89.19–112.33%) and variation coefficient values (5.81–9.43%) were successfully obtained. The consistency between the results of BA-ELISA and gas chromatography–mass spectrometry (GC–MS) was 97.48%, which further confirmed that the proposed BA-ELISA immunoassay is reliable, rapid, sensitive, and accurate for monitoring DEP in wine samples.     

Development and standardization of a reading test for brain‐damaged patients

We conducted 2 studies to assess the psychometric properties and clinical utility of a reading test, the Iowa‐Chapman Reading Test (ICRT), which was developed as a means of measuring reading capacities in patients with brain damage. We first collected normative data from 101 adults, then applied the test to 145 patients with focal cortical brain damage. Forty‐two patients performed defectively on the test, with impairments being evident in connection with a variety of different brain regions. Most important, nearly all (89%) of the 64 patients with lingering complaints of reading difficulties performed below expectations on the ICRT, despite generally normal performances on other standard reading tests. The results indicate that the ICRT provides an economical and sensitive index of reading and in particular, chronic subtle weaknesses in reading that are evident to the patient but not detected by many conventional tests.     

Utilization of a sol–gel method for encapsulation of doxorubicin

The sol-gel pre-doping method was used to encapsulate doxorubicin in silica gels and optimum conditions of preparation of drug-loaded gel were established, ensuring both reproducible and effective results of quantitative encapsulation of doxorubicin and its gradual but complete release. Doxorubicin was encapsulated in polysiloxane polymers using the method based on sol-gel encapsulation without a catalyst, with an acid catalyst (HCl) and a base catalyst (NH₃). The time of gelation of the gel loaded with doxorubicin, encapsulation efficiency of the drug and the degree of release of the drug from the gel are all affected by the kind of catalyst (acidic or basic) or its absence at the gel preparation stage, and the temperature of the gelation process. The time of sol gelation when using the NH₃ or HCl catalyst was 9 days at 21°C, 2 days at 30°C and 1.5 days at 37°C, while for the gel prepared without a catalyst it was 90 days at 21°C, 75 days at 30°C and 70 days at 37°C. The efficiency of doxorubicin encapsulation was 99.5 ± 0.5% (w/w) for acid-catalyzed gel, 98.9 ± 1.01% (w/w) for base-catalyzed gel and 86.4 ± 11.6% (w/w) for non-catalyzed gel. A 100% (w/w) release of doxorubicin by diffusion through pores was found only in the case of base-catalyzed gel after a 140-h incubation time. For acid-catalyzed gel and non-catalyzed gel, the total amounts of released doxorubicin after 140 h of incubation were 3-5% (w/w) and 9-11% (w/w), respectively. The stability of doxorubicin encapsulated in the three kinds of gel matrices was found to be improved compared to the stability of a free form of the drug in solution.     

Improving the performance of poly(3,4-ethylenedioxythiophene) for brain–machine interface applications

Conducting polymers, especially poly(3,4-ethylenedioxythiophene) (PEDOT) based materials, are important for developing highly sensitive and microscale neural probes. In the present work, we show that the conductivity and stability of PEDOT can be significantly increased by switching the widely used counter anion poly(styrenesulfonate) (PSS) to the smaller tetrafluoroborate (TFB) anion during the electrodeposition of the polymer. Time-dependent impedance measurements of polymer modified implantable microwires were conducted in physiological buffer solutions under accelerated aging conditions and the relative stability of PEDOT:PSS and PEDOT:TFB modified microwires was compared over time. This study was also extended to carbon nanotube (CNT) incorporated PEDOT:PSS which, according to some reports, is claimed to enhance the stability and electrical performance of the polymer. However, no noticeable difference was observed between PEDOT:PSS and CNT:PEDOT:PSS in our measurements. At the biologically relevant frequency of 1 kHz, PEDOT:TFB modified microwires exhibit approximately one order of magnitude higher conductivity and demonstrate enhanced stability over both PEDOT:PSS and CNT:PEDOT:PSS modified microwires. In addition, PEDOT:TFB is not neurotoxic and we show the proof-of-concept for both in vitro and in vivo neuronal recordings using PEDOT:TFB modified microelectrode arrays and chronic electrodes, respectively. Our findings suggest that PEDOT:TFB is a promising conductive polymer coating for the recording of neural activities.     

Development of a 3D workspace shoulder assessment tool incorporating electromyography and an inertial measurement unit—a preliminary study

Traditional shoulder range of movement (ROM) measurement tools suffer from inaccuracy or from long experimental setup times. Recently, it has been demonstrated that relatively low-cost wearable inertial measurement unit (IMU) sensors can overcome many of the limitations of traditional motion tracking systems. The aim of this study is to develop and evaluate a single IMU combined with an electromyography (EMG) sensor to monitor the 3D reachable workspace with simultaneous measurement of deltoid muscle activity across the shoulder ROM. Six volunteer subjects with healthy shoulders and one participant with a ‘frozen’ shoulder were recruited to the study. Arm movement in 3D space was plotted in spherical coordinates while the relative EMG intensity of any arm position is presented graphically. The results showed that there was an average ROM surface area of 27291 ± 538 deg² among all six healthy individuals and a ROM surface area of 13571 ± 308 deg² for the subject with frozen shoulder. All three sections of the deltoid show greater EMG activity at higher elevation angles. Using such tools enables individuals, surgeons and physiotherapists to measure the maximum envelope of motion in conjunction with muscle activity in order to provide an objective assessment of shoulder performance in the voluntary 3D workspace.

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Graphical abstract The aim of this study is to develop and evaluate a single IMU combined with an electromyography (EMG) sensor to monitor the 3D reachable workspace with simultaneous measurement of deltoid muscle activity across the shoulder ROM. The assessment tool consists of an IMU sensor, an EMG sensor, a microcontroller and a Bluetooth module. The assessment tool was attached to subjects arm. Individuals were instructed to move their arms with the elbow fully extended. They were then asked to provide the maximal voluntary elevation envelope of the arm in 3D space in multiple attempts starting from a small movement envelope going to the biggest possible in four consecutive circuits. The results showed that there was an average ROM surface area of 27291 ± 538 deg2 among all six healthy individuals and a ROM surface area of 13571 ± 308 deg2 for the subject with frozen shoulder. All three sections of the deltoid show greater EMG activity at higher elevation angles. Using such tools enables individuals, surgeons and physiotherapists to measure the maximum envelope of motion in conjunction with muscle activity in order to provide an objective assessment of shoulder performance in the voluntary 3D workspace.

     

Kinetic analysis of a human chorionic gonadotropin-β epitope–paratope interaction

Kinetics of protein–protein or ligand–ligate interaction has predominantly been studied by optical spectroscopy (particularly fluorescence) and surface plasmon resonance biosensors. Almost all such studies are based on association kinetics between ligand–ligate and suffer from certain methodological and interpretational limitations. Therefore, kinetic analyses of dissociation data of such interactions become indispensable. In the present investigation, the radiolabeled human chorionic gonadotropin-β (¹²⁵IhCGβ) was employed as a probe and nitrocellulose (NC) as a solid support to immobilize monoclonal antibody (MAb) G₁G₁₀.1. The NC–G₁G₁₀.1–¹²⁵IhCGβ complex (NC_com) was prepared and the dissociation of radiolabeled hCGβ was carried out in the presence of excess unlabeled ligate. From the experimental dissociation data under varying ionic strength, dissociation constants (k_{? 1}), association constants (k₊₁) and affinity constants (k_a) were calculated. The values obtained were utilized in exploring the amino acid residues constituting an epitopic region of hCGβ involved in interaction with the complementary paratope on MAb G₁G₁₀.1. Kinetic data of the present study supported our recently published findings [using single step-solid phase radioimmunoassay (SS-SPRIA)] that the core region of hCGβ epitope consists of Arg (94,95) and Asp (99) while a Lys (104) and a His (106) are in proximity to the core epitopic region. Based on the results of present investigation, we conclude that dissociation kinetics coupled with SS-SPRIA unequivocally provides considerable insight into the study of ligand–ligate interactions and epitope analysis.     

Development of a TaqMan Multiplex PCR Assay for Detection of Plasmid-Mediated AmpC β-Lactamase Genes

A multiplex, real-time TaqMan assay was designed to identify clinical isolates carrying plasmid-mediated ampC genes. The specificity and sensitivity of this assay were 100% when testing characterized AmpC/non-AmpC-producing isolates and randomly selected clinical isolates. This is a rapid assay that can be performed in a clinical microbiology laboratory.     

Development of a Clinically Comprehensive Database and a Simple Procedure for Identification of Molds from Solid Media by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is a powerful tool for the rapid and highly accurate identification of clinical pathogens but has not been utilized extensively in clinical mycology due to challenges in developing an effective protein extraction method and the limited databases available. Here, we developed an alternate extraction procedure and constructed a highly stringent database comprising 294 individual isolates representing 76 genera and 152 species. To our knowledge, this is the most comprehensive clinically relevant mold database developed to date. When challenged with 421 blinded clinical isolates from our institution, by use of the BioTyper software, accurate species-level (score of ≥2.0) and genus-level (score of ≥1.7) identifications were obtained for 370 (88.9%) and 18 (4.3%) isolates, respectively. No isolates were misidentified. Of the 33 isolates (7.8%) for which there was no identification (score of <1.7), 25 were basidiomycetes not associated with clinical disease and 8 were Penicillium species that were not represented in the database. Our library clearly outperformed the manufacturer''s database that was obtained with the instrument, which identified only 3 (0.7%) and 26 (6.2%) isolates at species and genus levels, respectively. Identification was not affected by different culture conditions. Implementation into our routine workflow has revolutionized our mycology laboratory efficiency, with improved accuracy and decreased time for mold identification, eliminating reliance on traditional phenotypic features.     

γ-aminobutyric acid measurement in the human brain at 7 T: Short echo-time or Mescher–Garwood editing

The purposes of the current study were to introduce a Mescher–Garwood (MEGA) semi-adiabatic spin-echo full-intensity localization (MEGA-sSPECIAL) sequence with macromolecule (MM) subtraction and to compare the test–retest reproducibility of γ-aminobutyric acid (GABA) measurements at 7 T using the sSPECIAL and MEGA-sSPECIAL sequences. The MEGA-sSPECIAL editing scheme using asymmetric adiabatic and highly selective Gaussian pulses was used to compare its GABA measurement reproducibility with that of short echo-time (TE) sSPECIAL. Proton magnetic resonance spectra were acquired in the motor cortex (M1) and medial prefrontal cortex (mPFC) using the sSPECIAL (TR/TE = 4000/16 ms) and MEGA-sSPECIAL sequences (TR/TE = 4000/80 ms). The metabolites were quantified using LCModel with unsuppressed water spectra. The concentrations are reported in institutional units. The test–retest reproducibility was evaluated by scanning each subject twice. Between-session reproducibility was assessed using coefficients of variation (CVs), Pearson's r correlation coefficients, and intraclass correlation coefficients (ICCs). Intersequence agreement was evaluated using Pearson's r correlation coefficients and Bland–Altman plots. Regarding GABA measurements by sSPECIAL, the GABA concentrations were 0.92 ± 0.31 (IU) in the M1 and 1.56 ± 0.49 (IU) in the mPFC. This demonstrated strong between-session correlation across both regions (r = 0.81, p < 0.01; ICC = 0.82). The CVs between the two scans were 21.8% in the M1 and 10.2% in the mPFC. On the other hand, the GABA measurements by MEGA-sSPECIAL were 0.52 ± 0.04 (IU) in the M1 and 1.04 ± 0.24 (IU) in the mPFC. MEGA-sSPECIAL demonstrated strong between-session correlation across the two regions (r = 0.98, p < 0.001; ICC = 0.98) and lower CVs than sSPECIAL, providing 4.1% in the M1 and 5.8% in the mPFC. The MEGA-editing method showed better reproducibility of GABA measurements in both brain regions compared with the short-TE sSPECIAL method. Thus it is a more sensitive method with which to detect small changes in areas with low GABA concentrations. In GABA-rich brain regions, GABA measurements can be achieved reproducibly using both methods.     

Development of a balanced experimental–computational approach to understanding the mechanics of proximal femur fractures

The majority of people who sustain hip fractures after a fall to the side would not have been identified using current screening techniques such as areal bone mineral density. Identifying them, however, is essential so that appropriate pharmacological or lifestyle interventions can be implemented.A protocol, demonstrated on a single specimen, is introduced, comprising the following components; in vitro biofidelic drop tower testing of a proximal femur; high-speed image analysis through digital image correlation; detailed accounting of the energy present during the drop tower test; organ level finite element simulations of the drop tower test; micro level finite element simulations of critical volumes of interest in the trabecular bone.Fracture in the femoral specimen initiated in the superior part of the neck. Measured fracture load was 3760 N, compared to 4871 N predicted based on the finite element analysis. Digital image correlation showed compressive surface strains as high as 7.1% prior to fracture. Voxel level results were consistent with high-speed video data and helped identify hidden local structural weaknesses.We found using a drop tower test protocol that a femoral neck fracture can be created with a fall velocity and energy representative of a sideways fall from standing. Additionally, we found that the nested explicit finite element method used allowed us to identify local structural weaknesses associated with femur fracture initiation.