Effect of Tibial Component Misalignment on the Lower Limb Joint Kinematics During Squat.

The component orientation of the total knee replacement is critical to surgical outcomes. There have been many studies focused on knee movement for different component rotations. However, the effect of component misalignment on a dynamic movement, especially which requires high knee flexion, is not widely studied. The aim of this study is to investigate the effect of tibial component misalignment on a squat motion by predictive simulation. Squat motions with different replacement component alignments were predicted by formulating an optimal control problem. The result indicates that component misalignment on coronal and horizontal planes reduces peak joint flexion angles and the external rotation on the horizontal plane has the most negative impact. Misalignment in external rotation resulted in the greatest reduction of peak joint flexion angles. The simulation was validated by comparison with experimental data, which showed a high level of correlation with the predicted motion.Clinical relevance- The predictive simulation presented in this study can predict the dynamic post-surgery movement of TKR. It has the potential to help surgeons and clinicians at the preoperative planning stage.

Stretchable anisotropic conductive film (S-ACF) for electrical interfacing in high-resolution stretchable circuits.

In stretchable electronics, high-resolution stretchable interfacing at a mild temperature is considered as a great challenge and has not been achieved yet. This study presents a stretchable anisotropic conductive film (S-ACF) that can electrically connect high-resolution stretchable circuit lines to other electrodes whether they are rigid, flexible, or stretchable. The key concepts of this study are (i) high-resolution (~50 µm) but low-contact resistance (0.2 ohm in 0.25 mm2) interfacing by periodically embedding conductive microparticles in thermoplastic film, (ii) low-temperature interfacing through the formation of chemical bonds between the S-ACF and the substrates, (iii) economical interfacing by selectively patterning the S-ACF, and (iv) direct interfacing of chips by using the adhesion of the thermoplastic matrix. We integrate light-emitting diodes on the patterned S-ACF and demonstrate stable light operation at large biaxial areal stretching (εxy = 70%).

Development of a Web-Based Ensemble Machine Learning Application to Select the Optimal Size of Posterior Chamber Phakic Intraocular Lens.

Purpose: Selecting the optimal lens size by predicting the postoperative vault can reduce complications after implantation of an implantable collamer lens with a central-hole (ICL with KS-aquaport). We built a web-based machine learning application that incorporated clinical measurements to predict the postoperative ICL vault and select the optimal ICL size. Methods: We applied the stacking ensemble technique based on eXtreme Gradient Boosting (XGBoost) and a light gradient boosting machine to pre-operative ocular data from two eye centers to predict the postoperative vault. We assigned the Korean patient data to a training (N = 2756 eyes) and internal validation (N = 693 eyes) datasets (prospective validation). Japanese patient data (N = 290 eyes) were used as an independent external dataset from different centers to validate the model. Results: We developed an ensemble model that showed statistically better performance with a lower mean absolute error for ICL vault prediction (106.88 µm and 143.69 µm in the internal and external validation, respectively) than the other machine learning techniques and the classic ICL sizing methods did when applied to both validation datasets. Considering the lens size selection accuracy, our proposed method showed the best performance for both reference datasets (75.9% and 67.4% in the internal and external validation, respectively). Conclusions: Applying the ensemble approach to a large dataset of patients who underwent ICL implantation resulted in a more accurate prediction of vault size and selection of the optimal ICL size. Translational Relevance: We developed a web-based application for ICL sizing to facilitate the use of machine learning calculators for clinicians.

Development of a rabbit monocyte activation test as an alternative to the rabbit pyrogen test and its application in the analysis of plasma-derived products.

The rabbit pyrogen test (RPT) is a safety test conducted as a part of mandatory requirements of regulatory agencies. RPT is currently performed for routine quality control (QC) by manufacturers and for national lot release of biological products, such as plasma-derived products. However, RPT involves the use of many rabbits, counter to the international efforts to minimize the use of animals in research. Furthermore, pyrogen amount cannot be discerned from the test results and the results may be considerably affected by various factors. Therefore, a need exists for substituting RPT with in vitro assays. As a viable alternative to RPT, we here established a rabbit monocyte activation test (RMAT) based on the human MAT in the European Pharmacopoeia. RMAT uses rabbit peripheral blood mononuclear cells as the source of monocytes instead of live animals. The test detected endotoxin, lipoteichoic acid, peptidoglycan, and zymosan with high sensitivity, showing high correlation with the in vivo RPT results. The results of RMAT and RPT testing of non-pyrogenic plasma-derived products were also consistent. Furthermore, RMAT showed satisfactory recovery rates in an interference test with product samples and spiked-in pyrogens. We conclude that RMAT could replace the existing RPT for routine QC.

Standardization of the first Korean national reference standard for snake (Gloydius brevicaudus) antivenom.

In 2017, the second national reference standard (NRS) for Gloydius snake venom was established to replace the first NRS for Gloydius snake venom. In connection with the second venom NRS, a candidate for the first NRS for Gloydius snake antivenom was produced in 2017. In this study, the qualification of the candidate was estimated and the potency was determined by a collaborative study. The potency (anti-lethal titer and anti-hemorrhagic titer) of the candidate was determined by measuring the capability of the antivenom to neutralize the lethal and hemorrhagic effects of the second NRS for Gloydius snake venom, which was calibrated against the regional reference standard for Gloydius snake antivenom established in 2006. Two Korean facilities contributed data from 20 independent assays. Subsequently, one foreign national control research laboratories participated in this collaborative study. The general common potency of the anti-lethal and anti-hemorrhagic titers was obtained from the results of a total of 25 tests performed at three facilities. According to the results of the present study, the candidate preparation showed good quality and is judged to be suitable to serve as the first NRS for Gloydius snake antivenom with the following potency: an anti-lethal titer of 3100 unit (U) (95% confidence interval 2991-3276 U) and anti-hemorrhagic titer of 3000 U (95% confidence interval 2849-3159 U). In conclusion, the first NRS for Gloydius snake antivenom was established in this study. This reference standard will be used routinely for quality control of a snake antivenom product by manufacturer in Korea, which also can be used for national quality control, including a national lot-release test of the snake antivenom product.

A Collaborative Study to Establish the Second Korean National Reference Standard for Snake Venom.

In 2015, a candidate for the second national reference standard (NRS) of Gloydius snake venom was produced to replace the first NRS of Gloydius snake venom. In the present study, the potencies of the candidate were determined by a collaborative study, and the qualification of the candidate was estimated. The potencies of the candidate were determined by measuring the murine lethal titers and lapine hemorrhagic titers of venom against the regional working reference standard (RWRS) for antivenom using the methods described in the previous report for the first NRS of Gloydius snake venom. Three Korean facilities contributed data from a total of 30 independent assays. Subsequently, two foreign national control research laboratories contributed to this collaborative study. The results were calculated using the Reed-Muench method for lethality and determined using a mixed-effects model for hemorrhage. The general common potencies of the lethal and hemorrhagic titers were obtained from the results of the 30 tests performed at three Korean facilities. The results are expressed in micrograms for 1 test dose (TD) with a 95% confidence interval as follows: a lethal titer of 90.13 µg/TD (95% confidence interval = 87.39~92.86 µg) and a hemorrhagic titer of 10.80 µg/TD (95% confidence interval = 10.46~11.14 µg). In addition, the candidate preparation showed good quality evaluation according to the results of the quality estimation of the candidate and is judged to be suitable to serve as the Korean NRS for snake venom. In conclusion, the second NRS of Gloydius snake venom was established in this study and will be used for national quality control, including a national lot release test of Korean antivenom products.

Continuous-wave THz vector imaging system utilizing two-tone signal generation and self-mixing detection.

We propose and demonstrate a continuous-wave vector THz imaging system utilizing a photonic generation of two-tone THz signals and self-mixing detection. The proposed system measures amplitude and phase information simultaneously without the local oscillator reference or phase rotation scheme that is required for heterodyne or homodyne detection. In addition, 2π phase ambiguity that occurs when the sample is thicker than the wavelength of THz radiation can be avoided. In this work, THz signal having two frequency components was generated with a uni-traveling-carrier photodiode and electro-optic modulator on the emitter side and detected with a Schottky barrier diode detector used as a self-mixer on the receiver side. The proposed THz vector imaging system exhibited a 50-dB signal to noise ratio and 0.012-rad phase fluctuation with 100-µs integration time at 325-GHz. With the system, we demonstrate two-dimensional THz phase contrast imaging. Considering the recent use of two-dimensional arrays of Schottky barrier diodes as a THz image sensor, the proposed system is greatly advantageous for realizing a real-time THz vector imaging system due to its simple receiver configuration.

Laminated metamaterial flat lens at millimeter-wave frequencies.

A flat and thin shape is obviously advantageous not only in terms of reducing the volume of a device, but also in handling and using it. Particularly, laminating or stacking flat devices is an intuitive and straightforward way of tailoring performance and functions. Here, we experimentally demonstrated a laminated flat lens for millimeter-wave frequencies that is based on split-ring resonators (SRRs) composed of multiple layers with different and/or identical index profiles and that exhibits characteristics that are linear combinations of those of the individual lenses. Since the characteristics of the lenses of each layer are preserved regardless of the neighbouring layers, the desired functionalities can be easily implemented simply by laminating elementary lenses designed already. When we laminated two lenses designed for bending or focusing incoming waves at 120 GHz, we clearly observed that the outgoing waves collimated and bended as desired.

Compact and stable THz vector spectroscopy using silicon photonics technology.

We present a compact and stable terahertz (THz) vector spectroscopy system using silicon photonics technology. A silicon-based integrated phase control circuit greatly reduces the physical size of the continuous-wave THz spectroscopy system and enhances environmental phase stability. Differential lightwave phase control using two carrier-injection electro-optic modulators enables fast and linear phase sweeps of THz-waves. Using the silicon-photonic circuit, we demonstrate a THz vector spectrometer; the dynamic ranges are 65 and 35 dB at 300 GHz and 1 THz with 1-ms integration time and phase variation is less than ± 10° without thermal packaging.

CW-THz vector spectroscopy and imaging system based on 1.55-µm fiber-optics.

We present a continuous-wave terahertz (THz) vector spectroscopy and imaging system based on a 1.5-µm fiber optic uni-traveling-carrier photodiode and InGaAs photo-conductive receiver. Using electro-optic (EO) phase modulators for THz phase control with shortened optical paths, the system achieves fast vector measurement with effective phase stabilization. Dynamic ranges of 100 dB · Hz and 75 dB · Hz at 300 GHz and 1 THz, and phase stability of 1.5° per minute are obtained. With the simultaneous measurement of absorbance and relative permittivity, we demonstrate non-destructive analyses of pharmaceutical cocrystals inside tablets within a few minutes.

Generation of frequency-modulated sub-terahertz signal using microwave photonic technique.

We present a photonic technique for generating a frequency- modulated sub-terahertz signal for non-destructive or noninvasive sensing and imaging applications. Large frequency deviation was achieved by using optical phase modulation and heterodyne photomixing with an uni-travelling photodetector. The operation principle is theoretically derived and explained. In addition, the generation of 350-GHz frequency- modulated sub-terahertz signal with 6.7-GHz frequency deviation is experimentally demonstrated, and the possibility of frequencies up to 1 THz and wider frequency deviations is discussed.

Analysis of baroreflex sensitivity during undulation pump ventricular assist device support.

The aim of this study was to examine the baroreflex sensitivity (BRS), which involves the autonomic nervous system, in a goat with a chronically implanted undulation pump ventricular assist device (UPVAD). The UPVAD involved transforming the rotation of a brushless DC motor into an undulating motion by a disc attached via a special linking mechanism, and a jellyfish valve in the outflow cannula to prevent diastolic backflow. The pump was implanted into the thoracic cavity of a goat by a left thoracotomy, and the inflow and outflow cannulae were sutured to the apex of the left ventricle and to the descending aorta, respectively. The driving cable was wired percutaneously to an external controller. Electrocardiogram and hemodynamic waveforms were recorded at a sampling frequency of 1 kHz. BRS was determined when awake by the slope of the linear regression of R-R interval against mean arterial pressure changes, which were induced by the administration of methoxamine hydrochloride, both with continuous driving of the UPVAD as well as without assistance. BRS values during the UPVAD support and without assistance were 1.60 +/- 0.30 msec/mm Hg and 0.98 +/- 0.22 msec/mm Hg (n = 5, P < 0.05), respectively. BRS was significantly improved during left ventricular assistance. Therefore, UPVAD support might decrease sympathetic nerve activity and increase parasympathetic nerve activity to improve both microcirculation and organ function.

An all-optical frequency up-converter utilizing four-wave mixing in a semiconductor optical amplifier for sub-carrier multiplexed radio-over-fiber applications.

A novel all-optical frequency up-converter utilizing four-wave mixing (FWM) in a semiconductor optical amplifier (SOA) was proposed and experimentally demonstrated. The frequency up-converter converted an optical intermediate frequency (IF) signal (f(IF) = 2.5 GHz) to an optical radio frequency (RF) signal (f(RF) = 35 and 40 GHz) through mixing with an optical local oscillator (LO) signal (f(LO) = 37.5 GHz). The up-converter showed positive conversion efficiency of 5.77 dB for the optical IF power of -22 dBm and the optical LO power of -13 dBm. This scheme showed broad bandwidths with respect to both LO and IF frequencies. The up-converter showed a phase noise of -84.5 dBc/Hz for the LO frequency of 37.5 GHz (f(LO)) and the offset frequency of 10 kHz after the frequency up-conversion.

Generation of two-mode optical signals with broadband frequency tunability and low spurious signal level.

For continuous millimeter and terahertz-wave applications, a two-mode optical signal generation technique that uses two arrayed waveguide gratings and two optical switch units is presented. In addition to easy and fast operation, this scheme offers broadband frequency tunability and high signal purity with a low spurious mode level. Mode spacing, which corresponds to the frequency of the generated MM/THz-wave signal after photomixing, was successfully swept in the range of 200 ~ 550 GHz and the optical spurious mode suppression ratio higher than 25 dBc was achieved. In addition, spurious modes characteristics were investigated by using second harmonic generation (SHG) autocorrelation methods for several frequencies.