Development and Evaluation of Self-Microemulsifying Drug Delivery System for Improving Oral Absorption of Poorly Water-Soluble Olaparib.

The purpose of this study is to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) to improve the oral absorption of poorly water-soluble olaparib. Through the solubility test of olaparib in various oils, surfactants and co-surfactants, pharmaceutical excipients were selected. Self-emulsifying regions were identified by mixing the selected materials at various ratios, and a pseudoternary phase diagram was constructed by synthesizing these results. The various physicochemical properties of microemulsion incorporating olaparib were confirmed by investigating the morphology, particle size, zeta potential, drug content and stability. In addition, the improved dissolution and absorption of olaparib were also confirmed through a dissolution test and a pharmacokinetic study. An optimal microemulsion was generated in the formulation of Capmul® MCM 10%, Labrasol® 80% and PEG 400 10%. The fabricated microemulsions were well-dispersed in aqueous solutions, and it was also confirmed that they were maintained well without any problems of physical or chemical stability. The dissolution profiles of olaparib were significantly improved compared to the value of powder. Associated with the high dissolutions of olaparib, the pharmacokinetic parameters were also greatly improved. Taken together with the results mentioned above, the microemulsion could be an effective tool as a formulation for olaparib and other similar drugs.

Automated machine learning (AutoML)-based surface registration methodology for image-guided surgical navigation system.

BACKGROUND: Although the surface registration technique has the advantage of being relatively safe and the operation time is short, it generally has the disadvantage of low accuracy. PURPOSE: This research proposes automated machine learning (AutoML)-based surface registration to improve the accuracy of image-guided surgical navigation systems. METHODS: The state-of-the-art surface registration concept is that first, using a neural network model, a new point-cloud that matches the facial information acquired by a passive probe of an optical tracking system (OTS) is extracted from the facial information obtained by computerized tomography. Target registration error (TRE) representing the accuracy of surface registration is then calculated by applying the iterative closest point (ICP) algorithm to the newly extracted point-cloud and OTS information. In this process, the hyperparameters used in the neural network model and ICP algorithm are automatically optimized using Bayesian optimization with expected improvement to yield improved registration accuracy. RESULTS: Using the proposed surface registration methodology, the average TRE for the targets located in the sinus space and nasal cavity of the soft phantoms is 0.939 ± 0.375 mm, which shows 57.8% improvement compared to the average TRE of 2.227 ± 0.193 mm calculated by the conventional surface registration method (p < 0.01). The performance of the proposed methodology is evaluated, and the average TREs computed by the proposed methodology and the conventional method are 0.767 ± 0.132 and 2.615 ± 0.378 mm, respectively. Additionally, for one healthy adult, the clinical applicability of the AutoML-based surface registration is also presented. CONCLUSION: Our findings showed that the registration accuracy could be improved while maintaining the advantages of the surface registration technique.

Traction Performance Evaluation of the Electric All-Wheel-Drive Tractor.

This study aims to design, develop, and evaluate the traction performance of an electric all-wheel-drive (AWD) tractor based on the power transmission and electric systems. The power transmission system includes the electric motor, helical gear reducer, planetary gear reducer, and tires. The electric system consists of a battery pack and charging system. An engine-generator and charger are installed to supply electric energy in emergency situations. The load measurement system consists of analog (current) and digital (battery voltage and rotational speed of the electric motor) components using a controller area network (CAN) bus. A traction test of the electric AWD tractor was performed towing a test vehicle. The output torques of the tractor motors during the traction test were calculated using the current and torque curves provided by the motor manufacturer. The agricultural work performance is verified by comparing the torque and rpm (T-N) curve of the motor with the reduction ratio applied. The traction is calculated using torque and specifications of the wheel, and traction performance is evaluated using tractive efficiency (TE) and dynamic ratio (DR). The results suggest a direction for the improvement of the electric drive system in agricultural research by comparison with the conventional tractor through the analysis of the agricultural performance and traction performance of the electric AWD tractor.

Weakly Supervised Crop Area Segmentation for an Autonomous Combine Harvester.

Machine vision with deep learning is a promising type of automatic visual perception for detecting and segmenting an object effectively; however, the scarcity of labelled datasets in agricultural fields prevents the application of deep learning to agriculture. For this reason, this study proposes weakly supervised crop area segmentation (WSCAS) to identify the uncut crop area efficiently for path guidance. Weakly supervised learning has advantage for training models because it entails less laborious annotation. The proposed method trains the classification model using area-specific images so that the target area can be segmented from the input image based on implicitly learned localization. This way makes the model implementation easy even with a small data scale. The performance of the proposed method was evaluated using recorded video frames that were then compared with previous deep-learning-based segmentation methods. The results showed that the proposed method can be conducted with the lowest inference time and that the crop area can be localized with an intersection over union of approximately 0.94. Additionally, the uncut crop edge could be detected for practical use based on the segmentation results with post-image processing such as with a Canny edge detector and Hough transformation. The proposed method showed the significant ability of using automatic perception in agricultural navigation to infer the crop area with real-time level speed and have localization comparable to existing semantic segmentation methods. It is expected that our method will be used as essential tool for the automatic path guidance system of a combine harvester.

Analysis to determine cost-effectiveness of procalcitonin-guided antibiotic use in adult patients with suspected bacterial infection and sepsis.

PURPOSE: Results of a study incorporating real-world results into a predictive model to assess the cost-effectiveness of procalcitonin (PCT)-guided antibiotic use in intensive care unit patients with sepsis are reported. METHODS: A single-center, retrospective cross-sectional study was conducted to determine whether reductions in antibiotic therapy duration and other care improvements resulting from PCT testing and use of an associated treatment pathway offset the costs of PCT testing. Selected base-case cost outcomes in adults with sepsis admitted to a medical intensive care unit (MICU) were assessed in preintervention and postintervention cohorts using a decision analytic model. Cost-minimization and cost-utility analyses were performed from the hospital perspective with a 1-year time horizon. Secondary and univariate sensitivity analyses tested a variety of clinically relevant scenarios and the robustness of the model. RESULTS: Base-case modeling predicted that use of a PCT-guided treatment algorithm would results in hospital cost savings of $45 per patient and result in a gain of 0.0001 quality-adjusted life-year. After exclusion of patients in the postintervention cohort for PCT test ordering outside of institutional guidelines, the mean inpatient antibiotic therapy duration was significantly reduced in the postintervention group relative to the preintervention group (6.2 days versus 4.9 days, p = 0.04) after adjustment for patient sex and age, Charlson Comorbidity Index score, study period, vasopressor use, and ventilator use. Total annual hospital cost savings of $4,840 were predicted. CONCLUSION: Real-world implementation of PCT-guided antibiotic use may have improved patients' quality of life while decreasing hospital costs in MICU patients with undifferentiated sepsis.

Analysis of sensory system aspects of postural stability during quiet standing in adolescent idiopathic scoliosis patients.

BACKGROUND: The aim of this study was to quantitatively analyze quite standing postural stability of adolescent idiopathic scoliosis (AIS) patients in respect to three sensory systems (visual, vestibular, and somatosensory). METHOD: In this study, we analyzed the anterior-posterior center of pressure (CoP) signal using discrete wavelet transform (DWT) between AIS patients (n = 32) and normal controls (n = 25) during quiet standing. RESULT: The energy rate (∆E EYE %) of the CoP signal was significantly higher in the AIS group than that in the control group at levels corresponding to vestibular and somatosensory systems (p < 0.01). CONCLUSIONS: This implies that AIS patients use strategies to compensate for possible head position changes and spinal asymmetry caused by morphological deformations of the spine through vestibular and somatosensory systems. This could be interpreted that such compensation could help them maintain postural stability during quiet standing. The interpretation of CoP signal during quiet standing in AIS patients will improve our understanding of changes in physical exercise ability due to morphological deformity of the spine. This result is useful for evaluating postural stability before and after treatments (spinal fusion, bracing, rehabilitation, and so on).

Successful Treatment of Cerebral Toxoplasmosis Using Pyrimethamine Oral Solution Compounded From Inexpensive Bulk Powder.

A price increase of pyrimethamine tablets in the United States has made the life-saving drug difficult to acquire for hospitalized patients who need it most. We report the successful use of a pyrimethamine oral suspension compounded from an economical bulk powder in a patient with acute toxoplasmic encephalitis.

A Novel Detection Model and Its Optimal Features to Classify Falls from Low- and High-Acceleration Activities of Daily Life Using an Insole Sensor System.

In order to overcome the current limitations in current threshold-based and machine learning-based fall detectors, an insole system and novel fall classification model were created. Because high-acceleration activities have a high risk for falls, and because of the potential damage that is associated with falls during high-acceleration activities, four low-acceleration activities, four high-acceleration activities, and eight types of high-acceleration falls were performed by twenty young male subjects. Encompassing a total of 800 falls and 320 min of activities of daily life (ADLs), the created Support Vector Machine model’s Leave-One-Out cross-validation provides a fall detection sensitivity (0.996), specificity (1.000), and accuracy (0.999). These classification results are similar or superior to other fall detection models in the literature, while also including high-acceleration ADLs to challenge the classification model, and simultaneously reducing the burden that is associated with wearable sensors and increasing user comfort by inserting the insole system into the shoe.

Removing Control of Cyclodextrin-Drug Complexes Using High Affinity Molecule.

Nanostructured supramolecular assemblies with hydrophobic cavities are used for improving the solubility, bioavailability, and stability of poorly water soluble drugs. In particular, host-guest inclusion using 2-hydroxypropyl-beta-cyclodextrin (HP-ß-CD) is a typical approach in the pharmaceutical field. In this study, celecoxib (CXB), a cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug (NSAID), was used as the model drug (guest material) and effectively incorporated into HP-ß-CD (host material). After forming a complete complex of HP-ß-CD and CXB, 1-adamantylamine (ADA) was used to allow CXB to be released from the HP-ß-CD in a concentration-dependent manner. This was revealed from Fourier-transform infrared spectroscopy and drug dissolution studies. Notably, the use of ADA, which is a high-affinity guest molecule, with cyclodextrin accelerated the removal of CXB from the host material through the exchange of guest molecules. Taken together, the host-guest based approach using a second guest molecule is useful for regulating on-demand drug release and could therefore be a potential tool for biomedical applications.

Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir System.

The purpose of this study was to develop and evaluate a dry elixir (DE) system for enhancing the dissolution rate and oral bioavailability of celecoxib. DE system has been used for improving solubility, oral bioavailability of poorly water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix are rapidly dissolved due to the co-solvent effect, resting in both an enhanced dissolution and bioavailability. DEs containing celecoxib were prepared by spray-drying method and characterized by morphology, drug/ethanol content, drug crystallinity, dissolution rate and oral bioavailability. The ethanol content and drug content in DE system could be easily altered by controlling the spraydrying conditions. The dissolution profile of celecoxib from DE proved to be much higher than that of celecoxib powder due to the nano-structured matrix, amorphous state and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared with celecoxib powder alone and commercial product (Celebrex®) in rats. In particular, blood concentrations of celecoxib form DE formulation were much greater than those of native celecoxib and market product. The data demonstrate that the DE system could provide an useful solid dosage form to enhance the solubility, dissolution rate and oral bioavailability of celecoxib.

Analysis of Pelvis-Thorax Coordination Patterns of Professional and Amateur Golfers during Golf Swing.

The aim of this research was to quantify the coordination pattern between thorax and pelvis during a golf swing. The coordination patterns were calculated using vector coding technique, which had been applied to quantify the coordination changes in coupling angle (γ) between two different segments. For this, fifteen professional and fifteen amateur golfers who had no significant history of musculoskeletal injuries. There was no significant difference in coordination patterns between the two groups for rotation motion during backswing (p = 0.333). On the other hand, during the downswing phase, there were significant differences between professional and amateur groups in all motions (flexion/extension: professional [γ] = 187.8°, amateur [γ] = 167.4°; side bending: professional [γ] = 288.4°, amateur [γ] = 245.7°; rotation: professional [γ] = 232.0°, amateur [γ] = 229.5°). These results are expected to be a discriminating measure to assess complex coordination of golfers' trunk movements and preliminary study for interesting comparison by golf skilled levels.

How to quantify the transition phase during golf swing performance: Torsional load affects low back complaints during the transition phase.

The transition phase of a golf swing is considered to be a decisive instant required for a powerful swing. However, at the same time, the low back torsional loads during this phase can have a considerable effect on golf-related low back pain (LBP). Previous efforts to quantify the transition phase were hampered by problems with accuracy due to methodological limitations. In this study, vector-coding technique (VCT) method was proposed as a comprehensive methodology to quantify the precise transition phase and examine low back torsional load. Towards this end, transition phases were assessed using three different methods (VCT, lead hand speed and X-factor stretch) and compared; then, low back torsional load during the transition phase was examined. As a result, the importance of accurate transition phase quantification has been documented. The largest torsional loads were observed in healthy professional golfers (10.23 ± 1.69 N · kg-1), followed by professional golfers with a history of LBP (7.93 ± 1.79 N · kg-1), healthy amateur golfers (1.79 ± 1.05 N · kg-1) and amateur golfers with a history of LBP (0.99 ± 0.87 N · kg-1), which order was equal to that of the transition phase magnitudes of each group. These results indicate the relationship between the transition phase and LBP history and the dependency of the torsional load magnitude on the transition phase.

Improved determination of dynamic balance using the centre of mass and centre of pressure inclination variables in a complete golf swing cycle.

Golf requires proper dynamic balance to accurately control the club head through a harmonious coordination of each human segment and joint. In this study, we evaluated the ability for dynamic balance during a golf swing by using the centre of mass (COM)-centre of pressure (COP) inclination variables. Twelve professional, 13 amateur and 10 novice golfers participated in this study. Six infrared cameras, two force platforms and SB-Clinic software were used to measure the net COM and COP trajectories. In order to evaluate dynamic balance ability, the COM-COP inclination angle, COM-COP inclination angular velocity and normalised COM-COP inclination angular jerk were used. Professional golfer group revealed a smaller COM-COP inclination angle and angular velocity than novice golfer group in the lead/trail direction (P < 0.01). In the normalised COM-COP inclination angular jerk, the professional golfer group showed a lower value than the other two groups in all directions. Professional golfers tend to exhibit improved dynamic balance, and this can be attributed to the neuromusculoskeletal system that maintains balance with proper postural control. This study has the potential to allow for an evaluation of the dynamic balance mechanism and will provide useful basic information for swing training and prevention of golf injuries.

Analysis of coordination between thoracic and pelvic kinematic movements during gait in adolescents with idiopathic scoliosis.

PURPOSE: In this research, we investigated the coordination pattern and consistency of coordination between the thorax and pelvis during gait in patients with idiopathic scoliosis. METHODS: Across the study, 69 adolescent girls (controls: 30, patients: 39) participated. All participants were asked to walk 10 m barefoot at a self-selected speed. The walking speed, stride length, and range of motion of the pelvic and thoracic angles were collected using a three-dimensional optical motion analysis system, and the thorax-pelvis coordination was quantified using a vector coding technique. The frequency of four different patterns of coordination (in-phase, anti-phase, pelvis only, and thorax only) and the consistency of coordination including direction and magnitude during the gait cycle of the two groups were investigated. Independent-sample t tests were performed to examine differences between the two groups with regard to coordination patterns and consistency. RESULTS: The patients with idiopathic scoliosis showed significantly higher in-phase and relatively lower anti-phase in the transverse plane compared to controls. Additionally, the pelvis only in the transverse, frontal, and sagittal planes was significantly lower in patients. The consistency of coordination in patients was significantly lower than in controls in direction and magnitude on the transverse and frontal planes. CONCLUSION: From viewpoint of the thorax-pelvis coordination, patients with IS had less gait stability in the trunk than controls.

Predicting Complete Ground Reaction Forces and Moments During Gait With Insole Plantar Pressure Information Using a Wavelet Neural Network.

In general, three-dimensional ground reaction forces (GRFs) and ground reaction moments (GRMs) that occur during human gait are measured using a force plate, which are expensive and have spatial limitations. Therefore, we proposed a prediction model for GRFs and GRMs, which only uses plantar pressure information measured from insole pressure sensors with a wavelet neural network (WNN) and principal component analysis-mutual information (PCA-MI). For this, the prediction model estimated GRFs and GRMs with three different gait speeds (slow, normal, and fast groups) and healthy/pathological gait patterns (healthy and adolescent idiopathic scoliosis (AIS) groups). Model performance was validated using correlation coefficients (r) and the normalized root mean square error (NRMSE%) and was compared to the prediction accuracy of the previous methods using the same dataset. As a result, the performance of the GRF and GRM prediction model proposed in this study (slow group: r = 0.840-0.989 and NRMSE% = 10.693-15.894%; normal group: r = 0.847-0.988 and NRMSE% = 10.920-19.216%; fast group: r = 0.823-0.953 and NRMSE% = 12.009-20.182%; healthy group: r = 0.836-0.976 and NRMSE% = 12.920-18.088%; and AIS group: r = 0.917-0.993 and NRMSE% = 7.914-15.671%) was better than that of the prediction models suggested in previous studies for every group and component (p < 0.05 or 0.01). The results indicated that the proposed model has improved performance compared to previous prediction models.

Multi-class biological tissue classification based on a multi-classifier: Preliminary study of an automatic output power control for ultrasonic surgical units.

Ultrasonic surgical units (USUs) have the advantage of minimizing tissue damage during surgeries that require tissue dissection by reducing problems such as coagulation and unwanted carbonization, but the disadvantage of requiring manual adjustment of power output according to the target tissue. In order to overcome this limitation, it is necessary to determine the properties of in vivo tissues automatically. We propose a multi-classifier that can accurately classify tissues based on the unique impedance of each tissue. For this purpose, a multi-classifier was built based on single classifiers with high classification rates, and the classification accuracy of the proposed model was compared with that of single classifiers for various electrode types (Type-I: 6 mm invasive; Type-II: 3 mm invasive; Type-III: surface). The sensitivity and positive predictive value (PPV) of the multi-classifier by cross checks were determined. According to the 10-fold cross validation results, the classification accuracy of the proposed model was significantly higher (p<0.05 or <0.01) than that of existing single classifiers for all electrode types. In particular, the classification accuracy of the proposed model was highest when the 3mm invasive electrode (Type-II) was used (sensitivity=97.33-100.00%; PPV=96.71-100.00%). The results of this study are an important contribution to achieving automatic optimal output power adjustment of USUs according to the properties of individual tissues.

Quasi-stiffness of the knee joint in flexion and extension during the golf swing.

Biomechanical understanding of the knee joint during a golf swing is essential to improve performance and prevent injury. In this study, we quantified the flexion/extension angle and moment as the primary knee movement, and evaluated quasi-stiffness represented by moment-angle coupling in the knee joint. Eighteen skilled and 23 unskilled golfers participated in this study. Six infrared cameras and two force platforms were used to record a swing motion. The anatomical angle and moment were calculated from kinematic and kinetic models, and quasi-stiffness of the knee joint was determined as an instantaneous slope of moment-angle curves. The lead knee of the skilled group had decreased resistance duration compared with the unskilled group (P < 0.05), and the resistance duration of the lead knee was lower than that of the trail knee in the skilled group (P < 0.01). The lead knee of the skilled golfers had greater flexible excursion duration than the trail knee of the skilled golfers, and of both the lead and trail knees of the unskilled golfers. These results provide critical information for preventing knee injuries during a golf swing and developing rehabilitation strategies following surgery.

A methodological approach for the biomechanical cause analysis of golf-related lumbar spine injuries.

A new methodological approach employing mechanical work (MW) determination and relative portion of its elemental analysis was applied to investigate the biomechanical causes of golf-related lumbar spine injuries. Kinematic and kinetic parameters at the lumbar and lower limb joints were measured during downswing in 18 golfers. The MW at the lumbar joint (LJ) was smaller than at the right hip but larger than the MWs at other joints. The contribution of joint angular velocity (JAV) to MW was much greater than that of net muscle moment (NMM) at the LJ, whereas the contribution of NMM to MW was greater rather than or similar to that of JAV at other joints. Thus, the contribution of JAV to MW is likely more critical in terms of the probability of golf-related injury than that of NMM. The MW-based golf-related injury index (MWGII), proposed as the ratio of the contribution of JAV to MW to that of NMM, at the LJ (1.55) was significantly greater than those at other joints ( < 1.05). This generally corresponds to the most frequent occurrence of golf-related injuries around the lumbar spine. Therefore, both MW and MWGII should be considered when investigating the biomechanical causes of lumbar spine injuries.

Upper torso and pelvis linear velocity during the downswing of elite golfers.

BACKGROUND: During a golf swing, analysis of the movement in upper torso and pelvis is a key step to determine a motion control strategy for accurate and consistent shots. However, a majority of previous studies that have evaluated this movement limited their analysis only to the rotational movement of segments, and translational motions were not examined. Therefore, in this study, correlations between translational motions in the 3 axes, which occur between the upper torso and pelvis, were also examined. METHODS: The experiments were carried out with 14 male pro-golfers (age: 29 ± 8 years, career: 8.2 ± 4.8years) who registered in the Korea Professional Golf Association (KPGA). Six infrared cameras (VICON; Oxford Metrics, Oxford, UK) and SB-Clinc software (SWINGBANK Ltd, Korea) were used to collect optical marker trajectories. The center of mass (CoM) of each segment was calculated based on kinematic principal. In addition, peak value of CoM velocity and the time that each peak occurred in each segment during downswing was calculated. Also, using cross-correlation analysis, the degree of coupling and time lags of peak values occurred between and within segments (pelvis and upper torso) were investigated. RESULTS: As a result, a high coupling strength between upper torso and pelvis with an average correlation coefficient = 0.86 was observed, and the coupling between segments was higher than that within segments (correlation coefficient = 0.81 and 0.77, respectively). CONCLUSIONS: Such a high coupling at the upper torso and pelvis can be used to reduce the degree of motion control in the central nervous system and maintain consistent patterns in the movement. The result of this study provides important information for the development of optimal golf swing movement control strategies in the future.

Formulation and optimization of spray-dried amlodipine solid dispersion for enhanced oral absorption.

OBJECTIVE: To enhance the oral absorption of photosensitive amlodipine free base, which exhibits a slow dissolution rate and low permeability characteristics, an amorphous solid dispersion system was formulated and characterized. MATERIAL AND METHODS: The solid dispersion was prepared by dispersing the amlodipine free base in excess dextrin (1:10 by weight) using a spray-drying technique in the presence of a minimum amount (0.9% w/w) of SLS as an absorption enhancer. The dextrin-based solid dispersion of amlodipine (Amlo-SD) was evaluated in term of formulation, characterization and in vivo absorption study, as well as the spray-drying process was also optimized. RESULTS AND DISCUSSION: The Amlo-SD particles were spherical with a smooth surface and an average particle size of 12.9 µm. Amlodipine was dispersed in an amorphous state and its content remained uniform in the Amlo-SD. The physicochemical stability of the Amlo-SD was maintained at room temperature for 6 months and the photostability was considerably improved. The dissolution of the Amlo-SD was much faster than that of amlodipine at pH 1.2 and 6.8. Amlo-SD produced significantly higher plasma concentrations of amlodipine in rats than amlodipine alone. Amlo-SD with and without SLS provided 2.8- and 2.0-fold increase in AUC, respectively: the difference seems to be attributed to a permeability enhancement effect by SLS. CONCLUSION: The Amlo-SD with SLS system is a potential formulation option for amlodipine.