Oral and Intravenous Amoxicillin Dosing Recommendations in Neonates: A Pooled Population Pharmacokinetic Study.

BACKGROUND: There is a lack of evidence on oral amoxicillin pharmacokinetics and exposure in neonates with possible serious bacterial infection (pSBI). We aimed to describe amoxicillin disposition following oral and intravenous administration and to provide dosing recommendations for preterm and term neonates treated for pSBI. METHODS: In this pooled-population pharmacokinetic study, 3 datasets were combined for nonlinear mixed-effects modeling. In order to evaluate amoxicillin exposure following oral and intravenous administration, pharmacokinetic profiles for different dosing regimens were simulated with the developed population pharmacokinetic model. A target of 50% time of the free fraction above the minimal inhibitory concentration (MIC) with an MICECOFF of 8 mg/L (to cover gram-negative bacteria such as Escherichia coli) was used. RESULTS: The cohort consisted of 261 (79 oral, 182 intravenous) neonates with a median (range) gestational age of 35.8 weeks (range, 24.9-42.4) and bodyweight of 2.6 kg (range, 0.5-5). A 1-compartment model with first-order absorption best described amoxicillin pharmacokinetics. Clearance (L/h/kg) in neonates born after 30 weeks' gestation increased with increasing postnatal age (PNA day 10, 1.25-fold; PNA day 20, 1.43-fold vs PNA day 3). Oral bioavailability was 87%. We found that a twice-daily regimen of 50 mg/kg/day is superior to a 3- or 4-times daily schedule in the first week of life for both oral and intravenous administration. CONCLUSIONS: This pooled population pharmacokinetic description of intravenous and oral amoxicillin in neonates provides age-specific dosing recommendations. We conclude that neonates treated with oral amoxicillin in the first weeks of life reach adequate amoxicillin levels following a twice-daily dosing regimen. Oral amoxicillin therapy could therefore be an adequate, cost-effective, and more patient-friendly alternative for neonates worldwide.

Precision Heart Rate Estimation Using a PPG Sensor Patch Equipped with New Algorithms of Pre-Quality Checking and Hankel Decomposition.

A new method for accurately estimating heart rates based on a single photoplethysmography (PPG) signal and accelerations is proposed in this study, considering motion artifacts due to subjects' hand motions and walking. The method comprises two sub-algorithms: pre-quality checking and motion artifact removal (MAR) via Hankel decomposition. PPGs and accelerations were collected using a wearable device equipped with a PPG sensor patch and a 3-axis accelerometer. The motion artifacts caused by hand movements and walking were effectively mitigated by the two aforementioned sub-algorithms. The first sub-algorithm utilized a new quality-assessment criterion to identify highly noise-contaminated PPG signals and exclude them from subsequent processing. The second sub-algorithm employed the Hankel matrix and singular value decomposition (SVD) to effectively identify, decompose, and remove motion artifacts. Experimental data collected during hand-moving and walking were considered for evaluation. The performance of the proposed algorithms was assessed using the datasets from the IEEE Signal Processing Cup 2015. The obtained results demonstrated an average error of merely 0.7345 ± 8.1129 beats per minute (bpm) and a mean absolute error of 1.86 bpm for walking, making it the second most accurate method to date that employs a single PPG and a 3-axis accelerometer. The proposed method also achieved the best accuracy of 3.78 bpm in mean absolute errors among all previously reported studies for hand-moving scenarios.

External temperature sensor assisted a new low power photoplethysmography readout system for accurate measurement of the bio-signs.

This study presents an external temperature sensor assisted a new low power, time-interleave, wide dynamic range, and low DC drift photoplethysmography (PPG) signal acquisition system to obtain the accurate measurement of various bio signs in real-time. The designed chip incorporates a 2-bit control programmable transimpedance amplifier (TIA), a high order filter, a 3:8 programmable gain amplifier (PGA) and 2 × 2 organic light-emitting diode (OLED) driver. Temperature sensor is used herein to compensate the adverse effect of low-skin-temperature on the PPG signal quality. The analog front-end circuit is implemented in the integrated chip with chip area of 2008 µm × 1377 µm and fabricated via TSMC T18 process. With the standard 1.8 V, the experimental result shows that the measured current sensing range is 20 nA-100 uA. The measured dynamic range of the designed readout circuit is 80 dB. The estimated signal to noise ratio is 60 dB@1 uA, and the measured input referred noise is 60.2 pA/Hz½. The total power consumption of the designed chip is 31.32 µW (readout) + 1.62 mW (OLED driver@100% duty cycle). The non-invasive PPG sensor is applied to the wrist artery of the 40 healthy subjects for sensing the pulsation of the blood vessel. The experimental results show that for every 1 °C decrease in mean ambient temperature tends to 0.06 beats/min, 0.125 mmHg and 0.063 mmHg increase in hear rate (HR), systolic (SBP) and diastolic (DBP), respectively. Similarly, for every 1 °C increase in mean ambient temperature tends to 0.13 beats/min, 0.601 mmHg and 0.121 mmHg increase in HR, SBP and DBP, respectively. The measured accuracy and standard error for the HR estimation are 96%, and - 0.022 ± 2.589 beats/minute, respectively. The oxygen stauration (SpO2) measurement results shows that the mean absolute percentage error is less than 5%. The resultant errors for the SBP and DBP measurement are - 0.318 ± 5.19 mmHg and - 0.5 ± 1.91 mmHg, respectively.

Machine Learning Classification for Assessing the Degree of Stenosis and Blood Flow Volume at Arteriovenous Fistulas of Hemodialysis Patients Using a New Photoplethysmography Sensor Device.

The classifier of support vector machine (SVM) learning for assessing the quality of arteriovenous fistulae (AVFs) in hemodialysis (HD) patients using a new photoplethysmography (PPG) sensor device is presented in this work. In clinical practice, there are two important indices for assessing the quality of AVF: the blood flow volume (BFV) and the degree of stenosis (DOS). In hospitals, the BFV and DOS of AVFs are nowadays assessed using an ultrasound Doppler machine, which is bulky, expensive, hard to use, and time consuming. In this study, a newly-developed PPG sensor device was utilized to provide patients and doctors with an inexpensive and small-sized solution for ubiquitous AVF assessment. The readout in this sensor was custom-designed to increase the signal-to-noise ratio (SNR) and reduce the environment interference via maximizing successfully the full dynamic range of measured PPG entering an analog-digital converter (ADC) and effective filtering techniques. With quality PPG measurements obtained, machine learning classifiers including SVM were adopted to assess AVF quality, where the input features are determined based on optical Beer-Lambert's law and hemodynamic model, to ensure all the necessary features are considered. Finally, the clinical experiment results showed that the proposed PPG sensor device successfully achieved an accuracy of 87.84% based on SVM analysis in assessing DOS at AVF, while an accuracy of 88.61% was achieved for assessing BFV at AVF.

A Portable, Wireless Photoplethysomography Sensor for Assessing Health of Arteriovenous Fistula Using Class-Weighted Support Vector Machine.

A portable, wireless photoplethysomography (PPG) sensor for assessing arteriovenous fistula (AVF) by using class-weighted support vector machines (SVM) was presented in this study. Nowadays, in hospital, AVF are assessed by ultrasound Doppler machines, which are bulky, expensive, complicated-to-operate, and time-consuming. In this study, new PPG sensors were proposed and developed successfully to provide portable and inexpensive solutions for AVF assessments. To develop the sensor, at first, by combining the dimensionless number analysis and the optical Beer Lambert's law, five input features were derived for the SVM classifier. In the next step, to increase the signal-noise ratio (SNR) of PPG signals, the front-end readout circuitries were designed to fully use the dynamic range of analog-digital converter (ADC) by controlling the circuitries gain and the light intensity of light emitted diode (LED). Digital signal processing algorithms were proposed next to check and fix signal anomalies. Finally, the class-weighted SVM classifiers employed five different kernel functions to assess AVF quality. The assessment results were provided to doctors for diagonosis and detemining ensuing proper treatments. The experimental results showed that the proposed PPG sensors successfully achieved an accuracy of 89.11% in assessing health of AVF and with a type II error of only 9.59%.

Control Design and Digital Implementation of a Fast 2-Degree-of-Freedom Translational Optical Image Stabilizer for Image Sensors in Mobile Camera Phones.

This study presents design, digital implementation and performance validation of a lead-lag controller for a 2-degree-of-freedom (DOF) translational optical image stabilizer (OIS) installed with a digital image sensor in mobile camera phones. Nowadays, OIS is an important feature of modern commercial mobile camera phones, which aims to mechanically reduce the image blur caused by hand shaking while shooting photos. The OIS developed in this study is able to move the imaging lens by actuating its voice coil motors (VCMs) at the required speed to the position that significantly compensates for imaging blurs by hand shaking. The compensation proposed is made possible by first establishing the exact, nonlinear equations of motion (EOMs) for the OIS, which is followed by designing a simple lead-lag controller based on established nonlinear EOMs for simple digital computation via a field-programmable gate array (FPGA) board in order to achieve fast response. Finally, experimental validation is conducted to show the favorable performance of the designed OIS; i.e., it is able to stabilize the lens holder to the desired position within 0.02 s, which is much less than previously reported times of around 0.1 s. Also, the resulting residual vibration is less than 2.2-2.5 µm, which is commensurate to the very small pixel size found in most of commercial image sensors; thus, significantly minimizing image blur caused by hand shaking.

The 5-HT5A receptor regulates excitability in the auditory startle circuit: functional implications for sensorimotor gating.

Here we applied behavioral testing, pharmacology, and in vivo electrophysiology to determine the function of the serotonin 5-HT5A receptor in goldfish startle plasticity and sensorimotor gating. In an initial series of behavioral experiments, we characterized the effects of a selective 5-HT5A antagonist, SB-699551 (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), on prepulse inhibition of the acoustic startle response. Those experiments showed a dose-dependent decline in startle rates in prepulse conditions. Subsequent behavioral experiments showed that SB-699551 also reduced baseline startle rates (i.e., without prepulse). To determine the cellular mechanisms underlying these behaviors, we tested the effects of two distinct selective 5-HT5A antagonists, SB-699551 and A-843277 (N-(2,6-dimethoxybenzyl)-N'[4-(4-fluorophenyl)thiazol-2-yl]guanidine), on the intrinsic membrane properties and synaptic sound response of the Mauthner cell (M-cell), the decision-making neuron of the startle circuit. Auditory-evoked postsynaptic potentials recorded in the M-cell were similarly attenuated after treatment with either 5-HT5A antagonist (SB-699551, 26.41 ± 3.98% reduction; A-843277, 17.52 ± 6.24% reduction). This attenuation was produced by a tonic (intrinsic) reduction in M-cell input resistance, likely mediated by a Cl(-) conductance, that added to the extrinsic inhibition produced by an auditory prepulse. Interestingly, the effector mechanisms underlying neural prepulse inhibition itself were unaffected by antagonist treatment. In summary, these results provide an in vivo electrophysiological characterization of the 5-HT5A receptor and its behavioral relevance and provide a new perspective on the interaction of intrinsic and extrinsic modulatory mechanisms in startle plasticity and sensorimotor gating.

Mechanical Properties, Microstructure, and Actuation Behavior of Wire Arc Additive Manufactured Nitinol: Titanium Bimetallic Structures.

Nitinol (NiTi) is well known for its corrosion resistance, shape memory effect, superelasticity, and biocompatibility, whereas Titanium (Ti) is well known for its high specific strength, corrosion resistance, and biocompatibility. The bimetallic joint of NiTi and Ti is required for applications that require tailored properties at different locations within the same component, as well as to increase design flexibility while reducing material costs. However, because of the formation of brittle intermetallic phases, connecting NiTi and Ti is difficult. In the present study, a systematic experimental investigation is carried out to develop NiTi-Ti bimetallic joint using wire arc additive manufacturing (WAAM) for the first time and to evaluate its microstructure, mechanical properties, martensitic transformation, and actuation behavior in the as-built condition. The defect-free joint is obtained through WAAM and microstructural studies indicate the formation of intermetallics at the NiTi-Ti interface leading to higher microhardness values (600 HV). Shape recovery behavior and phase transformation temperature were also enhanced in comparison to NiTi. An improved actuation and bending angle recovery is observed in comparison with NiTi. The present study lays the way for the use of WAAM in the construction of NiTi and Ti bimetallic structures for engineering and medicinal applications.

A Fast FPGA Hardware Accelerator for Remote Heart Rate Detection Based on RGB Vision.

A fast hardware accelerator is created by this work via field programmable gate array (FPGA) to estimate heart rate (HR) through the video recorded by a RGB camera based on the technology of remote photoplethysmography (rPPG). The method of rPPG acquires physiological signals of a human body by analyzing the subtle color changes on the surface of the human skin. The hardware implementation of rPPG to estimate HR is proposed herein to aim for a much faster calculation speed than software for a number of applications, like heart failure pre-warning of an in-action athlete and drowsiness detection of a driver. In this accelerator, ICA (Independent Component Analysis) is used to recover the blood volume pulse from the raw signals of remote PPG, and then obtain the heart rate value. The architecture of the hardware circuit is described in Verilog HDL and verified by Quartus II, and also implemented in an Altera DE10-Standard FPGA board, which consists of image capture, heart rate algorithm and image display. A TRDB-D5M camera is utilized for image capture. Two experiments were conducted with image collecting duration of 16 seconds and 8 seconds respectively, and the commercial device Omron HEM-6111 was used as the golden value. The proposed system achieves an accuracy in (ME ± 1.96SD) of -0.76 ± 5.09 and -0.70 ± 8.71 bpm in the short periods of 16-second and 8-second versions, respectively, which outperforms all the reported prior works in combined computation time and accuracy.

Predicting Blood Pressures for Pregnant Women by PPG and Personalized Deep Learning.

Blood pressure (BP) is predicted by this effort based on photoplethysmography (PPG) data to provide effective pre-warning of possible preeclampsia of pregnant women. Towards frequent BP measurement, a PPG sensor device is utilized in this study as a solution to offer continuous, cuffless blood pressure monitoring frequently for pregnant women. PPG data were collected using a flexible sensor patch from the wrist arteries of 194 subjects, which included 154 normal individuals and 40 pregnant women. Deep-learning models in 3 stages were built and trained to predict BP. The first stage involves developing a baseline deep-learning BP model using a dataset from common subjects. In the 2nd stage, this model was fine-tuned with data from pregnant women, using a 1-Dimensional Convolutional Neural Network (1D-CNN) with Convolutional Block Attention Module (CBAMs), followed by bi-directional Gated Recurrent Units (GRUs) layers and attention layers. The fine-tuned model results in a mean error (ME) of -1.40 ± 7.15 (standard deviation, SD) for systolic blood pressure (SBP) and -0.44 (ME) ± 5.06 (SD) for diastolic blood pressure (DBP). At the final stage is the personalization for individual pregnant women using transfer learning again, enhancing further the model accuracy to -0.17 (ME) ± 1.45 (SD) for SBP and 0.27 (ME) ± 0.64 (SD) for DBP showing a promising solution for continuous, non-invasive BP monitoring in precision by the proposed 3-stage of modeling, fine-tuning and personalization.

How a broken vertebra can lead to a fatal hemorrhage: a case report.

BACKGROUND: Unintentional falls are common among the elderly and given the expected increase of the aging population, these falls contribute to a high number of admissions to the emergency department. Relatively low-energy trauma mechanisms can lead to serious injuries in the elderly, with contributing factors being comorbidities, medication use and degenerative abnormalities. CASE PRESENTATION: A 94-year-old female suffered an unintentional fall at home. Upon arrival of the ambulance at her house she was hemodynamically stable and mobilized to the gurney with assistance. During primary survey at the emergency department, her blood pressure and oxygen saturation decreased, she was not able to move her legs anymore and lost consciousness. A full-body CTA was performed, which showed a fracture through the vertebral body of L2 with significant dislocation and a large active bleeding of the corpus, extending to the retroperitoneum and the epidural space. Despite resuscitation, her vital signs deteriorated and given the severe abnormalities on CTA, it was decided to discontinue further treatment, after which she deceased. The performed CTA and an x-ray from 2016 suggested diffuse idiopathic skeletal hyperostosis, which might have contributed to the severity and instability of the vertebral fracture. Mobilization after the fall might have increased the dislocation of the fracture. The use of oral anticoagulants worsened the subsequent bleeding and the extension to the epidural space caused the paralysis of the legs. CONCLUSIONS: It is important to be aware of the possible serious consequences of unintentional falls in the elderly population and to provide strict immobilization of the spinal column until proper imaging.

A Dual-Channel PPG Readout System With Motion-Tolerant Adaptability for OLED-OPD Sensors.

An adaptive PPG (Photoplethysmography) readout system for a dual-channel OLED-OPD flexible sensor is designed and developed with motion artifact (<1Hz) and ambient lighting interference successfully compensated without any additional motion sensors. The compensation is made possible by adopting multi-feedbacks and an additional reference OPD channel to cancel effectively DC drifts. In result, the quality of measured PPG is improved to the level such that long-time, continuous quality monitoring of bio-sign such as heart rate (HR) is possible. The readout is designed with an auto-programmable band-pass trans-impedance amplifier (TIA) of a 100dbΩ gain with a continuous-type DC-current cancellation loop. The rest of the readout consists of a 0.5 Hz low-pass filter, an additional second-order band-pass filter (0.1-10Hz), a difference amplifier, a motion reference channel, an analog multiplexer, a programmable gain amplifier (PGA), a digital control and a programmable DAC-PWM based auto-intensity tuned OLED driver. The readout is fabricated in an area of 9 mm2 via the TSMC 180nm process. The experiment result shows that the developed OLED-OPD readout senses well as small as 1nA current, with a measured dynamic range >90dB (1nA to 100 µA) and input-referred noise of 0.26 nA/√H, with power consumption of 460µW. The DC drift is successfully reduced to 1% of its average. The accuracy for heart rate is 96%.

[Low back pain in daily clinical practice; article for education and training purposes]. / Lagerugpijn.

Low back pain is a very common reason for patient visits to a general practitioner or medical specialist. It is associated with a negative effect on daily living and high costs of care. The differential diagnosis of low back pain is extensive, and usually no specific cause can be identified. In such a case, we speak of non-specific low back pain. In this article, we present practical pointers to recognising specific causes of low back pain and answer some frequently-asked questions regarding the diagnosis and treatment of low back pain.

Assessment of need for hemostatic evaluation in patients taking valproic acid: A retrospective cross-sectional study.

INTRODUCTION: Valproic acid (VPA) is a frequently prescribed anti-epileptic drug. Since its introduction side effects on hemostasis are reported. However, studies show conflicting results, and the clinical relevance is questioned. We aimed to determine the coagulopathies induced by VPA in patients who undergo high-risk surgery. The study results warrant attention to this issue, which might contribute to reducing bleeding complications in future patients. METHODS: Between January 2012 and August 2020, 73 consecutive patients using VPA were retrospectively included. Extensive laboratory hemostatic assessment (including platelet function tests) was performed before elective high-risk surgery. Patient characteristics, details of VPA treatment, and laboratory results were extracted from medical records. RESULTS: 46.6% of the patients using VPA (n = 73) showed coagulopathy. Mainly, platelet function disorder was found (36.4%). Thrombocytopenia was seen in 9.6% of the patients. Data suggested that the incidence of coagulopathies was almost twice as high in children as compared to adults and hypofibrinogenemia was only demonstrated in children. No association was found between the incidence of coagulopathies and VPA dosage (mg/kg/day). CONCLUSION: A considerable number of patients using VPA were diagnosed with coagulopathy, especially platelet function disorder. Further prospective studies are needed to confirm the need for comprehensive laboratory testing before elective high-risk surgery in these patients.

Efficacy and safety of switching from intravenous to oral antibiotics (amoxicillin-clavulanic acid) versus a full course of intravenous antibiotics in neonates with probable bacterial infection (RAIN): a multicentre, randomised, open-label, non-inferiority trial.

BACKGROUND: Switching from intravenous antibiotic therapy to oral antibiotic therapy among neonates is not yet practised in high-income settings due to uncertainties about exposure and safety. We aimed to assess the efficacy and safety of early intravenous-to-oral antibiotic switch therapy compared with a full course of intravenous antibiotics among neonates with probable bacterial infection. METHODS: In this multicentre, randomised, open-label, non-inferiority trial, patients were recruited at 17 hospitals in the Netherlands. Neonates (postmenstrual age ≥35 weeks, postnatal age 0-28 days, bodyweight ≥2 kg) in whom prolonged antibiotic treatment was indicated because of a probable bacterial infection, were randomly assigned (1:1) to switch to an oral suspension of amoxicillin 75 mg/kg plus clavulanic acid 18·75 mg/kg (in a 4:1 dosing ratio, given daily in three doses) or continue on intravenous antibiotics (according to the local protocol). Both groups were treated for 7 days. The primary outcome was cumulative bacterial reinfection rate 28 days after treatment completion. A margin of 3% was deemed to indicate non-inferiority, thus if the reinfection rate in the oral amoxicillin-clavulanic acid group was less than 3% higher than that in the intravenous antibiotic group the null hypothesis would be rejected. The primary outcome was assessed in the intention-to-treat population (ie, all patients who were randomly assigned and completed the final follow-up visit on day 35) and the per protocol population. Safety was analysed in all patients who received at least one administration of the allocated treatment and who completed at least one follow-up visit. Secondary outcomes included clinical deterioration and duration of hospitalisation. This trial was registered with ClinicalTrials.gov, NCT03247920, and EudraCT, 2016-004447-36. FINDINGS: Between Feb 8, 2018 and May 12, 2021, 510 neonates were randomly assigned (n=255 oral amoxicillin-clavulanic group; n=255 intravenous antibiotic group). After excluding those who withdrew consent (n=4), did not fulfil inclusion criteria (n=1), and lost to follow-up (n=1), 252 neonates in each group were included in the intention-to-treat population. The cumulative reinfection rate at day 28 was similar between groups (one [<1%] of 252 neonates in the amoxicillin-clavulanic acid group vs one [<1%] of 252 neonates in the intravenous antibiotics group; between-group difference 0 [95% CI -1·9 to 1·9]; pnon-inferiority<0·0001). No statistically significant differences were observed in reported adverse events (127 [50%] vs 113 [45%]; p=0·247). In the intention-to-treat population, median duration of hospitalisation was significantly shorter in the amoxicillin-clavulanic acid group than the intravenous antibiotics group (3·4 days [95% CI 3·0-4·1] vs 6·8 days [6·5-7·0]; p<0·0001). INTERPRETATION: An early intravenous-to-oral antibiotic switch with amoxicillin-clavulanic acid is non-inferior to a full course of intravenous antibiotics in neonates with probable bacterial infection and is not associated with an increased incidence of adverse events. FUNDING: The Netherlands Organization for Health Research and Development, Innovatiefonds Zorgverzekeraars, and the Sophia Foundation for Scientific Research.

Effectiveness and cost-effectiveness of dynamic bracing versus standard care alone in patients suffering from osteoporotic vertebral compression fractures: protocol for a multicentre, two-armed, parallel-group randomised controlled trial with 12 months of follow-up.

INTRODUCTION: Patients with osteoporosis may suffer from a fracture after minimal trauma. Osteoporotic vertebral compression fractures (OVCFs) are among the most common fractures, often leading to substantial pain. There is a need for evidence-based conservative treatment to aid in the management of OVCFs. The objective of this randomised controlled trial (RCT) is to evaluate the effectiveness and cost-effectiveness of dynamic bracing in addition to standard care for improving quality of life (QoL) in patients suffering from an OVCF. METHODS AND ANALYSIS: Ninety-eight postmenopausal women from two academic and four community hospitals with a recent symptomatic thoracolumbar OVCF will be randomised into either the standard care or dynamic bracing group. In the dynamic bracing group, the Spinova Osteo orthosis will be used in addition to standard care. Standard care comprises pain control with analgesics, physical therapy and osteoporosis medication. The primary outcome parameter is QoL 1 year after inclusion, as measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41). Secondary outcome parameters are pain, pain medication used, functional disability, sagittal spinal alignment, recurrence rate of OVCFs and physical activity in daily life. A trial-based economic evaluation consisting of both cost-effectiveness analysis and cost-utility analysis will be performed based on empirical data obtained in the RCT. A process evaluation will assess the feasibility of dynamic bracing. All outcomes will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee, University Hospital Maastricht and Maastricht University (METC azM/UM) (NL74552.068.20/METC 20-055). Patients will be included only after verification of eligibility and obtaining written informed consent. Results will be disseminated via the Dutch National Osteoporosis Patient Society and via publications and conferences. TRIAL REGISTRATION NUMBER: NL8746.

A new dual-frequency liquid crystal lens with ring-and-pie electrodes and a driving scheme to prevent disclination lines and improve recovery time.

A new liquid crystal lens design is proposed to improve the recovery time with a ring-and-pie electrode pattern through a suitable driving scheme and using dual-frequency liquid crystals (DFLC) MLC-2048. Compared with the conventional single hole-type liquid crystal lens, this new structure of the DFLC lens is composed of only two ITO glasses, one of which is designed with the ring-and-pie pattern. For this device, one can control the orientation of liquid crystal directors via a three-stage switching procedure on the particularly-designed ring-and-pie electrode pattern. This aims to eliminate the disclination lines, and using different drive frequencies to reduce the recovery time to be less than 5 seconds. The proposed DFLC lens is shown effective in reducing recovery time, and then serves well as a potential device in places of the conventional lenses with fixed focus lengths and the conventional LC lens with a single circular-hole electrode pattern.

Long-Term Residual-Mobility and Adjacent Segment Disease After Total Lumbar Disc Replacement.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Total disc replacement (TDR) has been introduced in order to preserve segmental motion and thus reduce adjacent segment disease (ASD) as seen after spinal fusion. However, it is uncertain whether these presumed beneficial effects remain. The aim of this study was to evaluate the long-term incidence of ASD and residual-mobility in relation to clinical outcome. METHODS: A total of 210 patients treated with lumbar TDR for degenerative disc disease were invited for follow-up. ASD was reported in case of severe degeneration in an adjacent disc at latest follow-up, or if an increase in disc degeneration was observed in these adjacent segments as compared to direct postoperative radiographs. Residual-mobility of the TDR was defined as a minimal rotation of 4.6° on flexion-extension radiographs. Patient-reported outcome measures were obtained. RESULTS: Fifty-seven patients (27.1%) were lost to follow-up. In 32 patients (15.3%) a revision by spinal fusion had been performed. In 20 patients this revision had occurred ≥5 years after TDR and were included. Consequently, 141 patients were available for analysis (mean follow-up of 16.7 years). Residual-mobility was noted in 38.0%. No significant associations were observed between residual-mobility and the occurrence of ASD, or with clinical outcome. In addition, ASD and clinical outcome were not related either. CONCLUSIONS: It appears that long-term preservation of motion after TDR is met for only a third of patients. However, residual-mobility is not associated with the occurrence of ASD, and both residual-mobility and ASD do not appear to be related to long-term clinical outcome.

A new low-voltage-driven GRIN liquid crystal lens with multiple ring electrodes in unequal widths.

This work is dedicated to design a novel liquid crystal (LC) lens device with multiple ring electrodes in unequal widths, in order to offer tunability on focusing quality and to lower the level of applied voltage. The number and widths of the multiple ring electrodes are pre-designed and optimized to offer the on-line tunability on individual electrode voltages to render a better refraction index distribution for focusing, as compared to the past hole-type LC lenses. The resulted refractive index distribution is expected to offer similar focusing effects based on the theory of the gradient refraction index (GRIN) lens. The transparent electrodes of this new LC lens are placed at the inner surface of the LC cell to minimize the driving voltages, in results, less than 10 V, for the same level of focusing power and an easy practical operation. A new fabrication process in the wafer level to bury bus lines is developed for generating smooth electrical fields over the lens aperture. In addition, a dielectric layer is coated between electrodes and the LC layer.

Achieving high focusing power for a large-aperture liquid crystal lens with novel hole-and-ring electrodes.

Aiming to equip commercial camera modules, such as the optical imaging systems with a CMOS sensor module in 3 Mega pixels, an ultra thin liquid crystal lens with designed hole-and-ring electrodes is proposed in this study to achieve high focusing power. The LC lens with proposed electrodes improves the central intensity of electric field which leads to better focusing quality. The overall thickness of the LC lens can be as thin as 1.2 mm and the shortest focal length of the 4 mm-aperture lens occurs at 20 cm under an applied voltage of 30 V at 1 KHz. The inner ring electrode requires only 40% of applied voltage of the external hole electrode. The applied voltages for this internal ring and external hole electrodes can simply be realized by a pre-designed parallel resistance pair and a single voltage source. Experiments are conducted for validation and it shows that the designed LC lens owns good image clearness and contrast at the focal plane. The proposed design reduces the thickness of LC lens and is capable of achieving relative higher focusing power than past studies with lower applied voltage.