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Avascular necrosis (AVN) of the bones remains a major clinical challenge. Fractures in the talus, the scaphoid, and the neck of the femur are especially challenging to heal due to the low blood vessel network and the lack of collateral blood supply. These fractures are associated with high rates of nonunion and increased infections that require repeated operations. Conventional treatments by autografting or allografting bone replacement and synthetic bone implants have limitations, including the invasiveness of operative procedures, tissue supply insufficiency, and the risk of host rejection. The advancement in tissue engineering has revealed the potential of stem cells as restorative agents for bone injuries. The administration of mesenchymal stem cells (MSCs) into the talus, the scaphoid, and the neck of the femur could produce enhanced osteogenesis via the manipulation of MSC culture conditions. In this study, we used hydroxyapatite as the nanomaterial, and hypoxic milieu to enhance MSC differentiation capacity into the osteogenic lineage, allowing for more rapid and efficient bone cell replacement treatment. Our results demonstrate 1% oxygen and 12.5 μg/mL of hydroxyapatite (HAP) as the optimal conditions to incorporate the osteogenic medium for the osteogenic induction of MSCs. We also established a proof of concept that the addition of HAP and hypoxic conditions could augment the osteoinductive capacity of MSCs. We also developed an accurate mathematical model to support future bone cell replacement therapy.

Mesenchymal stem cells (MSCs) transplantation seems to be a promising new therapy for diabetic wound healing (DWH), and currently, arrays of MSCs from various sources ranging from umbilical, adipose to dental sources are available as a treatment modality for this disease. However, it now appears that only a fraction of transplanted cells actually assimilate and survive in host tissues suggesting that the major mechanism by which stem cells participate in tissue repair are most likely related to their secretome level. These include a wide range of growth factors, cytokines, and chemokines, which can be found from the conditioned medium (CM) used to culture the cells. Basic studies and preclinical work confirm that the therapeutic effect of CMs are comparable with the application of stem cells. This review describes in detail the wound healing process in diabetes and the cellular and biological factors that influence the process. Subsequently, through a comprehensive literature search of studies related to wound healing in diabetics, we aim to provide an overview of scientific merits of using MSCs-CM in the treatment of diabetic wound as well as the significant caveats, which restricts its potential use in clinical set-ups. To our best knowledge, this is one of the first review papers that collect the importance of stem cells as an alternative treatment to the DWH. We anticipate that the success of this treatment will have a significant clinical impact on diabetic wounds.

The second (H2) and third (H3) harmonic generations in surface acoustic wave (SAW) resonators based on the YZ-cut LiNbO 3 operating in both longitudinal leaky SAW (LLSAW) mode and Rayleigh SAW mode were investigated and compared. For the Rayleigh SAW mode, the patterns and trends of nonlinearly excited harmonics in the YZ-cut LiNbO 3 were the same as those of 128° YX LiNbO 3 except that the peaks of nonlinear harmonic responses in YZ-cut LiNbO 3 were denser than the latter. However, for the YZ-cut LiNbO 3 LLSAW resonators, the peaks of the nonlinear harmonic responses would be 20 to 30 dBm lower than those in the Rayleigh SAW resonators. For the YZ-cut LiNbO 3 LLSAW resonators, we found that the quasi-periodic peaks in the nonlinear harmonics response would disappear at a substrate thickness of 500 μm. Results showed that the nonlinear harmonic generation concerns in SAW filters and duplexers may be substantially reduced by the use of longitudinal leaky SAW based on YZ-cut LiNbO 3 .

Interleukin-17A (IL-17A) produced by Th17 cells, contributes to the pathogenesis of various autoimmune diseases by stimulating the release of cytokines and chemokines and its regulation. Anti-IL-17A antibody which blocks the function of IL-17A has been proved to be an effective treatment of autoimmune disease. The aim of our study was to generate a potential humanized anti-IL-17A therapeutic monoclonal antibody (mAb) through a comprehensive panel of in vitro and in vivo biological activity studies, as well as physicochemical characterization. HZD37-5, a humanized monoclonal antibody specifically recognizing N78 loci of IL-17A, binds to human and rhesus monkeys, blocks IL-17 induced signal transduction and the release of IL-6, IL-8, CXCL-1 and G-GSF. In an in vivo efficacy mouse model, HZD37-5 significantly inhibited human IL-17A induced-keratinocyte chemoattractant (KC) secretion in a dose-dependent manner. The pharmacokinetics (PK) study result of HZD37-5 in rhesus monkeys indicated that HZD37-5 had favorable PK characteristics with limited distribution (78.0–78.8 ml/kg), slow elimination (5.00–6.45 ml/day/kg), long half-life (9.1–10.7 days) and high bioavailability (103%) following a single IV or SC dose at 1.5 mg/kg. These findings provided a comprehensive preclinical characterization of HZD37-5 and supported that it may be developed as a potential therapeutic for the treatment of autoimmune diseases, including psoriasis, psoriatic arthritis, axial spondyloarthritis, etc.

Purpose: To report a case series of seven eyes (six patients) with severe limbal stem cell failure who underwent cultivated oral mucosa epithelium transplantation (COMET) in preparation for corneal transplant surgery and assess the change in visual acuity postoperatively. Design: Case series. Methods: A retrospective analysis of an interventional case series of six patients with severe limbal stem cell deficiency who underwent COMET between 2012 and 2015 was performed. Six eyes had COMET followed by corneal transplant, and one eye had corneal transplant preceding COMET. The change in the visual acuity after operation was evaluated. Results: A total of six patients with seven eyes were studied. All of them had severe ocular surface disease with limbal stem cell deficiency (LSCD) secondary to chemical injury (five eyes), SJS (one eye), and severe ocular rosacea (one eye). Four eyes had improvements in visual acuity, two of which achieved best corrected visual acuity (BCVA) of 6/12. Conclusion: The use of COMET helps to optimize the ocular surface in severe LSCD for further corneal transplant surgeries. It has helped to improve the graft uptake and subsequent visual improvement, especially in chronic chemical burn cases.

The use of antidiabetic agents which control glycemic levels in the blood and simultaneously inhibit oxidative stress is an important strategy in the prevention of Diabetes Mellitus and its complications. In our previous study, malabaricone C (3) and its dimer, giganteone A (5) exhibited significant DPPH free radical scavenging activities which were lower than the activity of the positive control, ascorbic acid. These compounds were evaluated for their α-glucosidase inhibitory activities at different concentrations (0.02–2.5 mM) in the present study. Compounds 3 (IC50 59.61 µM) and 5 (IC50 39.52 µM) were identified as active alpha-glucosidase inhibitors, each respectively being 24 and 37 folds more potent than the standard inhibitor, acarbose. Based on the molecular docking studies, compounds 3 and 5 docked into the active site of the α-glucosidase enzyme, forming mainly hydrogen bonds in the active site.

The pathogenesis involving non-alcoholic fatty liver disease (NAFLD) in the context of chronic HBV (CHB) virus infection requires to be understood for developing improved modalities of diagnosis and treatment. We retrospectively investigated the association between NAFLD and CHB virus infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between years 2013 and 2016, we studied 455 subjects in the current investigation. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the hepatitis B virus (HBV) viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. We found that there was a high concurrence of NAFLD among patients with CHB virus infection. The presence of metabolic syndrome and chronic inflammation in CHB virus-infected patients were two independent factors that led to the progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components.

The Safe City Programme was launched one and a half-decade ago in Malaysia as one of the National Key Result Areas (NKRAs) strategy to curb crimes. However, the crime rates, in particular in Kuala Lumpur (KL), have shown little evidence of abating. Little is understood of the actual challenges facing the programme. Therefore, questions have been raised and many researchers are attracted to focus on this scenario. Thus, this study aimed to assess local players’ views of the challenges facing the safe city programme in KL and to provide a framework for the prevention strategies. The research involved qualitative in-depth interviews with key players in the area of safe city, crime experts and officials, and community heads. Themes and a framework were formulated through thematic analysis. The results showed that the understanding of a safe city programme could be differentiated through the lens of sustainability and resilience challenges, as well as their levels of prevention. Thus, the grey area of tertiary prevention strategies could be identified and strengthened.

The heterostructures made of magnetostrictive and piezoelectric layers have been recently investigated for the application of magnetic sensors and antenna. In this paper we investigate the possibility of FeGaB thin film on quartz crystal substrate with different orientations of quartz layer. Response of magnetic FeGaB/AlN nanoplate resonator under RF magnetic excitation was simulated by finite element program COMSOL. The results were compared with available experiment and confirmed the validity of available material properties of FeGaB thin film and current simulation method. Quartz/FeGaB composite resonator structures based on different modes of vibration were studied. Quartz/FeGaB resonator based on in-plane extensional modes was found to have a large magnetoelectric coupling effect. These findings can be used to design RF magnetic sensors based on Quartz/FeGaB bilayer plate.

Background. Mesenchymal stem cells (MSCs) express growth factors and other cytokines that stimulate repair and control the immune response. MSCs are also immunoprivileged with low risk of rejection. Umbilical cord-derived MSCs (UCMSCs) are particularly attractive as an off-the-shelf allogeneic treatment in emergency medical conditions. We aim to determine the safety and efficacy of intravenous allogeneic infusion of UCMSCs (CLV-100) by Cytopeutics® (Selangor, Malaysia) in healthy volunteers, and to determine the effective dose at which an immunomodulatory effect is observed. Methodology. Umbilical cord samples were collected after delivery of full-term, healthy babies with written consent from both parents. All 3 generations (newborn, parents, and grandparents) were screened for genetic mutations, infections, cancers, and other inherited diseases. Samples were transferred to a certified Good Manufacturing Practice laboratory for processing. Subjects were infused with either low dose (LD, 65 million cells) or high dose (HD, 130 million cells) of CLV-100 and followed up for 6 months. We measured cytokines using ELISA including anti-inflammatory cytokines interleukin 1 receptor antagonist (IL-1RA), interleukin 10 (IL-10), pro-/anti-inflammatory cytokine interleukin 6 (IL-6), and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α). Results. 11 healthy subjects (LD, n = 5 ; HD, n = 6 ; mean age of 55 ± 13 years) were recruited. All subjects tolerated the CLV-100 infusion well with no adverse reaction throughout the study especially in vital parameters and routine blood tests. At 6 months, the HD group had significantly higher levels of anti-inflammatory markers IL1-RA ( 705 ± 160 vs. 306 ± 36 pg / mL ; p = 0.02 ) and IL-10 ( 321 ± 27 vs. 251 ± 28 pg / m L; p = 0.02 ); and lower levels of proinflammatory marker TNF-α ( 74 ± 23 vs. 115 ± 15 pg / mL ; p = 0.04 ) compared to LD group. Conclusion. Allogeneic UCMSCs CLV-100 infusion is safe and well-tolerated in low and high doses. Anti-inflammatory effect is observed with a high-dose infusion.

The effect of pretilt and twisted angle on twisted nematic liquid crystal filter (TNLCF) is studied theoretically and experimentally in this paper, based on the birefringence and distortion characteristic of twisted nematic liquid crystal, the output performance of TNLCF has been analyzed through numerical simulation firstly, then the corresponding experiment results verify the correctness of the simulation results, which show that the output performance of TNLCF is indeed related to pretilt angle and twisted angle of liquid crystal–with the increasing of the twisted angle the central wavelength of TNLCF will shift to the long wavelength, with the increasing of pretilt angle for the top glass substrate and the decreasing of pretilt angle for the bottom glass substrate the central wavelength of TNLCF will shift to the short wavelength, and if the pretilt angle of the bottom glass substrate is increased and the pretilt angle of the top glass substrate is reduced at the same time in some certain value or otherwise the shift trend of the central wavelength will be not evident. These results will offer an important reference value for the design and application of TNLCF as we believe.

We report on a 32-MHz quartz temperature compensated crystal oscillator (TCXO) fully integrated with commercial CMOS electronics and vacuum packaged at wafer level using a low-temperature MEMS-after quartz process. The novel quartz resonator design provides for stress isolation from the CMOS substrate, thereby yielding classical AT-cut f/T profiles and low hysteresis which can be compensated to±0.2 parts per million over temperature using on-chip third-order compensation circuitry. The TCXO operates at low power of 2.5 mW and can be thinned to as part of the wafer-level eutectic encapsulation. Full integration with large state-of-the-art CMOS wafers is possible using carrier wafer techniques.

Identification of causative organisms of clinically suspected microbial keratitis is very important so that appropriate targeted antimicrobial treatment can be offered to patients. The current routine method of corneal scraping specimens on to multiple agar culture plates for microbiological study is not really providing encouraging result. Our trial of modified technique of using BACTEC broth for three clinically suspected microbial keratitis cases worked 100% to identify the causative organisms in cases of microbial keratitis.

Blindness and vision impairment are caused by irremediable retinal degeneration in affected individuals worldwide. Cell therapy for a retinal replacement can potentially rescue their vision, specifically for those who lost the light sensing photoreceptors in the eye. As such, well-characterized retinal cells are required for the replacement purposes. Stem cell-based therapy in photoreceptor and retinal pigment epithelium transplantation is well received, however, the drawbacks of retinal transplantation is the limited clinical protocols development, insufficient number of transplanted cells for recovery, the selection of potential stem cell sources that can be differentiated into the target cells, and the ability of cells to migrate to the host tissue. Dental pulp stem cells (DPSC) belong to a subset of mesenchymal stem cells, and are recently being studied due to its high capability of differentiating into cells of the neuronal lineage. In this review, we look into the potential uses of DPSC in treating retinal degeneration, and also the current data supporting its application.

Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration.

Recent research work on the theoretical and experimental possibilities of acoustically actuated MEMS RF magnetoelectric antennas using piezoelectric-magnetostrictive multilayers have been published, for example in ref. [1], [2]. A mechanism of electromagnetic-acoustic coupling was achieved in the composite ferromagnetic/piezoelectric heterostructure. The magnetostrictive thin film provided the function of converting the RF magnetic signal to acoustic vibration of the composite resonator while the piezoelectric body realized the transduction of acoustic wave to electric signal. In this paper, we proposed a novel MEMS RF FeGaB/Quartz receiver sensor where FeGaB had a relatively stronger piezomagnetic coefficient compared to other ferromagnetic materials such as nickel. The quartz resonator had the advantages of high Q, low resistance, and high frequency-temperature stability. Experiments were set up to measure the remnant magnetization state of FeGaB thin film deposited on AT- and SC-cut quartz wafers. Consistent comparison results were obtained between the simulated and measured magnetization curves of FeGaB thin films. A 10 MHz AT-cut quartz resonator coated with 200-nm-thick FeGaB layer was fabricated and tested. The frequency response of a similar uncoated quartz resonator was also tested so that the difference between the responses of coated and uncoated resonator respectively could yield a qualitative view of the magnetic field response. A special setup of experiments were taken to reduce the electric field effect of the RF signal. The simulated frequency responses of the coated and uncoated resonators showed trends that were consistent with the experimental results.

Retinal disorders account for a large proportion of ocular disorders that can lead to visual impairment or blindness, and yet our limited knowledge in the pathogenesis and choice of appropriate animal models for new treatment modalities may contribute to ineffective therapies. Although genetic in vivo models are favored, the variable expressivity and penetrance of these heterogeneous disorders can cause difficulties in assessing potential treatments against retinal degeneration. Hence, an attractive alternative is to develop a chemically-induced model that is both cost-friendly and standardizable. Sodium iodate is an oxidative chemical that is used to simulate late stage retinitis pigmentosa and age-related macular degeneration. In this study, retinal degeneration was induced through systemic administration of sodium iodate (NaIO3) at varying doses up to 80 mg/kg in Sprague-Dawley rats. An analysis on the visual response of the rats by electroretinography (ERG) showed a decrease in photoreceptor function with NaIO3 administration at a dose of 40 mg/kg or greater. The results correlated with the TUNEL assay, which revealed signs of DNA damage throughout the retina. Histomorphological analysis also revealed extensive structural lesions throughout the outer retina and parts of the inner retina. Our results provided a detailed view of NaIO3-induced retinal degeneration, and showed that the administration of 40 mg/kg NaIO3 was sufficient to generate disturbances in retinal function. The pathological findings in this model reveal a degenerating retina, and can be further utilized to develop effective therapies for RPE, photoreceptor, and bipolar cell regeneration.

Background: In view of the importance of chronic HBV (CHB) infection and the global burden of non-alcoholic fatty liver disease (NAFLD), it is imperative to understand the potential interplay between the two diseases. Methods: Here, we retrospectively investigated the association between NAFLD and CHB infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between year 2013 and 2016, we studied 449 subjects in the current investigation. Findings: CAP and LSM scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the HBV viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. Interpretations: Together, we found that there was a high concurrence of NAFLD among patients with CHB. The presence of metabolic syndrome and chronic inflammation in CHB patients were two independent factors that led to progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components. Plasma markers of liver steatosis and fibrosis progression are key to development of cell-targeted therapies exploiting specific molecular pathways. Funding Statement: This work was supported by a grant from the Frontier Research Grant (FRG), FG019-17AFR to Mohamed Rosmawati and Xiamen University Malaysia Research Funding (XMUMRF), XMUMRF/2018-C2/ILAB/0001. Marie Larsson is supported by the Swedish Research Council, the Swedish Physicians against AIDS Research Foundation; VINNMER for Vinnova, Linkoping University Hospital Research Fund, ALF Grants Region Ostergotland, FORSS. Declaration of Interests: The authors declare no conflicts interest. Ethics Approval Statement: The medical records of patients were extracted from the hospital database using patients’ unique hospital registration number. This study was approved by the Medical Ethics Committee of the University Malaya Medical Centre (MEC-938.42).

Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions.

This case report aims to share the successful management of Epithelial Downgrowth (ED) which occurred following persistent wound leak, after Removal of Silicone Oil (ROSO) via the anterior chamber. A teenage male with history of high myopia underwent bilateral phacoemulsification and implantation of Multifocal Intraocular Lens (MFIOLs). Four months later, he complained of left eye floaters and blurring of vision. Fundus showed left vitreous haemorrhage with lens subluxation. Left 23 gauge pars plana vitrectomy revealed multiple retinal tears. Endolaser and gas injection with MFIOL repositioning was done. Retinal redetachment and MFIOL subluxation occurred six weeks postoperatively. Revision vitrectomy with silicone oil and explantation of MFIOL was performed rendering left eye aphakic. Four months later, he underwent ROSO via a superior corneal incision. Positive Seidels was seen two weeks post-ROSO and resuturing was performed. Unfortunately, advancing ED was noted at the superior cornea. One month after ROSO, scleral fixated IOL implantation with manual removal of ED and intracameral injection of 5-fluorouracil (5-FU) were performed. Twelve months postoperatively, cornea remained clear with a pinhole vision of 6/7.5 and retina was flat. In conclusion, wound leak after ROSO via the anterior chamber in aphakic individuals may predispose to ED. Key to treatment of this sight threatening condition is thoughtful anterior segment examination. Manual removal of the membrane combined with 5-FU injection during secondary lens implantation surgery is an effective treatment.

Aim or Purpose: To evaluate the use of autologous bone marrow derived mesenchymal stem cells (BM-MSCs) to treat cornea stromal defect in a rabbit model. Methods: A non-randomized interventional controlled animal study involving twenty one adult New Zealand white rabbits. Corneal deep lamellar dissections were created in three groups of rabbits and treated accordingly. Group I; Autologous bone marrow derived MSCs with autologous fibrin and human amniotic membrane. Group II; Autologous fibrin with human amniotic membrane without MSCs. Group III; No treatment. Clinical outcome was evaluated by corneal re-epithelization, corneal opacity, corneal thickness and histology. Results: BM-MSCs were successfully isolated from bone marrow of seven rabbits based on the adherence property of the cells to the plastic of the cell culture plate. At day 60 corneal thicknesses was significantly thicker in Group I. The localization of PKH26 labeled BM-MSCs showed an increase in cell density at the transplanted site, proving its role in cornea stromal regeneration. Although the cornea clarity was not achieved in this study, we believe that cornea stromal remodeling requires many months to years to regain its original optical quality. Conclusion: Locally transplanted BM-MSCs may be a useful source for cornea stromal regeneration. The use of autologous BM-MSCs offers a promising option for treating corneal disorder without the risk of immune-rejection and calcification.

Incremental piezoelectric equations for small vibrations superposed on initial deformations are presented. The equations are implemented in COMSOL finite element models (FEA). Equations are validated by comparing the results for the force sensitivity coefficient Kf of a circular quartz plate subjected to a pair of diametrical forces with measured data. The model results show a consistent trend with the experimental results, and the relative difference between our FEA results and Ballato's measured result is about 13%. A detailed study of the acceleration sensitivity of a rectangular AT-cut quartz plate is presented. The plate resonator is fixed along one edge as a cantilever. For AT-cut quartz resonators with the crystal digonal X-axis perpendicular to plate X-axis, the in-plane acceleration sensitivity is found to be negligible compared with the out-of-plane (Y-axis) acceleration sensitivity. For AT-cut quartz resonators with the crystal digonal X-axis parallel to plate X-axis, the Y-axis acceleration sensitivity is found to be rectified, that is the fractional change in frequency is positive with respect to both positive and negative Y-axis accelerations. The Y-axis acceleration sensitivity is small in comparison with the in-plane acceleration sensitivity for small body forces. However, for large body forces, the Y-axis acceleration sensitivity dominates because it increases nonlinearly with the Y-axis acceleration. The resonator rectified acceleration sensitivity is confirmed by phase noise measurements. For reduced acceleration sensitivity, two pairs of electrodes along the plate edges reduce the bending of the plate resonator and subsequently reduce acceleration sensitivity. We present a new method using these edge electrodes in which a dc bias field is employed to control the resonant frequency of resonator subjected to g body forces. A dc bias field with an appropriate dc bias voltage could potentially yield a reduction of acceleration sensitivity in Y-axis direction of about two orders of magnitude.

A general purpose finite element model that yielded directly the nonlinear frequency response of the second harmonic generation in SAW IDT resonators was developed. The model enabled us to study the effects of the nonlinear material constants, voltage drive, duty factor, and IDT geometry on f-2f nonlinear interactions. Specifically we have applied our model to the study of nonlinear frequency response of second harmonic generation in lithium niobate YX-127o SAW IDT resonators. Lithium niobate was chosen because a complete set of its nonlinear material constants was known and published in the literature. A complete set of nonlinear piezoelectric equations along with their material constants for a lithium niobate YX-127o SAW IDT 836 MHz resonator was implemented in a finite element program. Two sets of finite element matrix equations were derived for the fundamental SAW mode and its 2nd harmonic mode, respectively. We demonstrated how two frequency domain interfaces could be coupled together to simulate the f-2f nonlinear interactions. The fundamental Rayleigh SAW mode was excited by a drive voltage at the IDT that in turn generated the 2nd harmonic mode at twice the frequency. A higher voltage drive lead to higher 2f interactions. Effects of the 2nd harmonic generation on the fundamental SAW mode and its Q were observed when the voltage drive was greater than 0.5V. For example, when the drive voltage was 0.1V the fundamental mode was clean. But when the drive voltage was increased to 0.5V the fundamental mode exhibited Q reduction and stronger f-2f interactions were observed, namely, there were stronger interactions of the 2f BAW mode with the f SAW mode. There was an optimal duty factor of 0.4 to 0.5 for the least f-2f interactions. Thinner electrode thickness resulted in stronger f-2f interactions.

The behavior of vibrating crystal plates under the action of external forces was studied. The plates were respectively subjected to diametrical compression force and bending force in different configurations: (a) a clamped cantilever, (b) a cantilever with displaced knife edges, and (c) a dual support mounting with displaced knife edge applied midway between. Finite element models were developed using the theory of small deformations superposed on finite initial deformations in Lagrangian formulation. The model results compared well with the experimental results by Mingins, Ballato, et. al., [3, 4]. For the AT-cut plate, the azimuth Ψ angles of frequency insensitivity due to compressional force were found at Ψ∼65° and 115°. For the plate bending in a clamped cantilever configuration a W-shaped plot of negative frequency deviations was observed when Ψ was varied from 0° to 180°, while the maximum positive frequency deviations occurred at Ψ∼270°. For the plate bending of cantilever with displaced knife edges, the results were similar to the plate bending in a clamped cantilever configuration. For the plate bending of dual support mounting with displaced knife edge applied in midway, the results for Ψ = 0° to 180° were very similar to Ψ = 180° to 360°. By searching out the effects of frequency deviations, optimal angles can be obtained to minimize or eliminate them.

Although nasopharyngeal carcinoma (NPC) is commonly seen in patients from Asia, optic neuropathy is a rare initial presenting symptom of this disease. This is an interventional case report discussing the clinical response of NPC-related optic neuropathy to pulse-steroid therapy. We discuss two patients who initially presented with signs of optic neuropathy. On imaging, a skull-base tumor was noted infiltrating the area of the affected optic nerve. An excision biopsy of the tumor revealed nasopharyngeal carcinoma. Both patients were pulsed with intravenous (IV) methlyprednisolone one gm/day for three days, followed by oral steroids (one mg/kg/BW) with gradual tapering. After two weeks, both showed visual improvement and chemo- and radiation therapy commenced at this time. In these two cases, pulse-steroid therapy did not hinder the chemo- and radiation therapy for nasopharyngeal carcinoma. Steroid therapy brought immediate visual recovery and gradual oral tapering could assist in optimizing visual outcomes for patients with compressive optic neuropathy from nasopharyngeal carcinoma.

Ocular trauma is a topic of unresolved controversies and there are continuous controversial and debatable management strategies for open-globe injuries (OGIs). International classification of ocular trauma proposed almost 15 years ago needs to be reviewed and to be more robust in predicting the outcome in the setting of OGIs. Anterior segment trauma involves controversies related to patching for corneal abrasion, corneal laceration repair, and medical management of hyphema. Timing of cataract surgery and intraocular lens implantation in the setting of trauma is still debated worldwide. There are unresolved issues regarding the management of OGIs involving the posterior segment. Timing of vitrectomy has been and will continue to be debated by proponents of early versus delayed intervention. The use of prophylactic cryotherapy and scleral buckle is still practiced differently throughout the world. The role of intravitreal antibiotics in posterior segment trauma in the absence of infection is still debated. Similarly, the use of vitrectomy versus vitreous tap in the setting of traumatic endophthalmitis is not fully resolved. In optic neuropathy, the role of intravenous methylprednisolone versus conservative management is always debated and still there are no evidence-based guidelines about the beneficial role of pulse steroid therapy. The role of optic canal decompression in the setting of acute traumatic optic neuropathy is also not conclusive. Orbital and adnexal trauma has been shown to adversely affect the outcome of OGI patients but both lids and orbital injury are not taken as preoperative variables in international ocular trauma classification. The timing of intervention in blow-out fracture is still debated. The pediatric age group, owing to the high risk of amblyopia and intraocular inflammation as well as strong vitreoretinal adhesions, has to be managed by different principles. Although the risk of sympathetic ophthalmia is very rare, it is always one of the key debated issues while managing traumatized eyes with no light perception vision. Prospective, controlled clinical studies are not possible in the OGI setting and this article reviews pertinent data regarding these management issues and controversies, and provides recommendations for treatment based on the available published data and the authors' personal experience.

The experimental studies of temperature coefficient of frequency (TCF) of SAW resonators were usually modeled by TCF models first proposed by Bechmann, Ballato and Lukaszeck[1]. These models unfortunately were not frame invariant with regards to the material property tensors of the crystal substrate and metal interdigital transducers (IDTs). Furthermore the models did not have the 3rd order nonlinear elastic constants that were needed to account for the effects of thermal strains from mountings, boundary constraints, and material interfaces. We employed a Lagrangian model of TCF of SAW resonators wherein governing equations for incremental vibrations superposed on thermal strains were implemented in a finite element program. The model used material coordinates referred to a fixed reference frame at a reference temperature, therefore the material property tensors were frame invariant. In addition it had a term that was a product of the 3rd order nonlinear elastic constants and thermoelastic strains. This product could account for the thermoelastic strains from interfacial stresses and boundary conditions. The objective of our study was to provide an accurate and detailed finite element model of the effects of the crystal substrate, metal IDTs, and stack layers on the TCF of SAW resonators. Good comparisons of model results with the experimental results were found for the 1 GHz lithium tantalate YXl 42° shear horizontal SAW resonator. Characterization of the electrode film properties was found to be important, especially when the film thickness was increased from 2000 A to 4000 A.

The acceleration sensitivity and its related problem of force-frequency in quartz resonators were studied. We studied the effects of initial nonlinear strains versus the effects of nonlinear elastic constants on the force-frequency problem of quartz resonators subjected to bending forces. We found that for quartz thickness shear resonators subjected to bending, the force frequency effect could be described primarily by the effects of nonlinear elastic constants with negligible effects from initial nonlinear strains. Since the acceleration sensitivity of quartz resonators is due mainly to bending forces, we proposed a set of simplified equations for these problems which were easier to implement in commercial finite element software.

The langasite crystal has the capability of no phase change at temperatures exceeding 600°C for high temperature applications. Since the material properties of langasite were measured usually at 25 0C as the reference temperature they are no longer accurate at high temperature environments. We employ a Lagrangian formulation to investigate the temperature behavior of thickness vibrations of langasite in a wide temperature range from 25°C to 600°C. The analysis only requires the elastic constants and their effective temperature derivatives of elastic constants and thermal expansion coefficients to predict the material constants at any given temperature. Based on the new values of the elastic constants and thermal expansion coefficients, the zero-valued temperature coefficients of frequency are investigated. The presently identified temperature compensated crystal cuts of the thickness-shear modes of langasite at different temperatures were compared with those at reference temperature and also with some cuts found in the literature.

Richard MH Lee,1 Fook Chang Lam,1 Tassos Georgiou,1 Bobby Paul,1 Kong Yong Then,1 Ioannis Mavrikakis,1 Venkata S Avadhanam,1 Christopher SC Liu1,21Sussex Eye Hospital, Brighton, United Kingdom; 2Tongdean Eye Clinic, Hove, United KingdomAims: To report on the suturing techniques and aspects of postoperative management in penetrating keratoplasty in the United Kingdom.Methods: A postal questionnaire was sent to 137 ophthalmic consultants identified from a Royal College of Ophthalmology database as having a special interest in anterior segment surgery. The questionnaire surveyed surgeon preferences for surgical and suturing technique for penetrating keratoplasty surgery, and the postoperative care of corneal grafts.Results: In all, 68% of questionnaires were completed and returned: 73% of respondents used a Flieringa ring or equivalent, 94% routinely used cardinal sutures, with 50.5% removing them at the end of the procedure. The most common suturing technique for routine penetrating keratoplasty was a single continuous suture (35%). In these cases, a 10/0 nylon suture was used by 89%. Sixty-six percent changed their technique in high-risk cases, 52% used a 3-1-1 knot, and 75% made a distinction between a reef and granny knot, with 76% using a reef. Thirty percent buried the knots within the donor material, and 29% within the host tissue. Twenty-five percent had no routine time for graft suture removal, but 41% removed them between 1 and 2 years post-surgery. After suture removal, 98% used steroids and 88% used topical antibiotics. Thirty-four percent stopped topical steroids before suture removal, with 38% stopping topical steroids more than 3 months prior to suture removal.Conclusion: This survey demonstrates that there is considerable variation in suturing techniques and postoperative care for penetrating keratoplasty. These significant variations in practice need to be considered when interpreting outcomes and research.Keywords: corneal graft, penetrating keratoplasty, anterior segment surgery, cornea, corneal surgery, corneal transplantation

Optical coherence tomography of the peripapillary nerve fibre layer has been used in optic atrophy for identification of axonal loss and for differential diagnosis. In the present study, we aim to evaluate whether the pattern of peripapillary nerve fibre layer thinning, based on the optical coherence tomography normative database, correlates with aetiology in cases of optic atrophy. This retrospective study is approved by the Tan Tock Seng Hospital Ethics Review Board. Consecutive patients with optic atrophy seen in the Neuro-Ophthalmology Clinic between May 2005 and August 2006 were included. The normal eyes of the patients served as controls. All patients underwent imaging using Stratus optical coherence tomography of the peripapillary nerve fibre layer, optic disc photographs and Humphrey perimetry. The aetiology of each case of optic atrophy were made by means other than the optical coherence tomography. Significant nerve fibre layer thinning was defined as a reading in the red quadrant on the Stratus...

We investigate the properties of shear horizontal surface acoustic wave propagation in layered functionally graded piezoelectric material structures loaded with viscous liquid. The piezoelectric material is polarized in the z-direction and the material properties change gradually along the thickness of the layer. Interfacial mechanical conditions are continuity of particle velocity and stress components at the interface. We here assume that the liquid is electrically insulated and its permittivity is much less than that of the piezoelectric material. The solutions of dispersion relations are obtained for insulated liquid with electrically open or shorted conditions by means of transfer matrix method. The effects of the gradient variation of material constants on the phase velocity and attenuation are presented and discussed in detail. The analytical method and the results are useful for the design of the resonators and sensors.

Theoretical analyses and designs of high-Q, quartz thin film resonators are presented. The resonators operate at an ultra-high frequency of 3.4 GHz for application to high-frequency timing devices such as cesium chip-scale atomic clocks. The frequency spectra for the 3.4-GHz thin film quartz resonators, which serve as design aids in selecting the resonator dimensions/configurations for simple electrodes, and ring electrode mesa designs are presented here for the first time. The thin film aluminum electrodes are found to play a major role in the resonators because the electrodes are only one third the thickness and mass of the active areas of the plate resonator. Hence, in addition to the material properties of quartz, the elastic, viscoelastic, and thermal properties of the electrodes are included in the models. The frequency-temperature behavior is obtained for the best resonator designs. To improve the frequency-temperature behavior of the resonators, new quartz cuts are proposed to compensate for the thermal stresses caused by the aluminum electrodes and the mounting supports. Frequency response analyses are performed to determine the Q-factor, motional resistance, capacitance ratio, and other figures of merit. The resonators have Q's of about 3800, resistance of about 1300 to 1400 ohms, and capacitance ratios of 1100 to 2800.

Common piezoelectric resonators such as quartz resonators have a very high Q and ultra stable resonant frequency. However, due to small material nonlinearities in the quartz crystal, the resonator is drive level dependent, that is, the resonator level of activity and its frequency are dependent on the driving, or excitation, voltage. The size of these resonators will be reduced to one fourth of their current sizes in the next few years, but the electrical power which is applied will not be reduced as much. Hence, the applied power to resonator size ratio will be larger, and the drive level dependency may play a role in the resonator designs. We study this phenomenon using the Lagrangian nonlinear stress equations of motion and Piola–Kirchhoff stress tensor of the second kind. Solutions are obtained using COMSOL for the AT-cut, BT-cut, SC-cut and other doubly rotated cut quartz resonators and the results compared well with experimental data. The phenomenon of the drive level dependence is discussed in terms of the voltage drive, electric field, power density and current density. It is found that the drive level dependency is best described in terms of the power density. Experimental results for the AT-, BT- and SC-cut resonators in comparison with our model results are presented. Results for new doubly rotated cuts are presented. The effects of spurious modes, quality factor and air damping on DLD are presented.

The quartz resonator Q with aluminum electrodes was studied with respect to its fundamental thickness shear mode frequency and its viscoelastic, viscopiezoelectric, and viscopiezoelectromagnetic behaviors. The governing equations for viscoelasticity, viscopiezoelectricity, and viscopiezoelectromagnetism were implemented for an AT-cut quartz resonator. To simulate the radiation conditions at infinity for the viscopiezoelectromagnetic model, perfectly matched layers over a surface enclosing the resonator were implemented to absorb all incident electromagnetic radiation. The shape of the radiation spectrum of a 5.6 MHz AT-cut quartz resonator was found to compare relatively well the measured results by Campbell and Weber. The mesa-plate resonator was studied for a frequency range of 1.4 GHz to 3.4 GHz. The resonator Q was determined to be influenced predominantly by the quartz viscoelasticity; however at frequencies greater than 2.3 GHz, the quartz electromagnetic radiation had an increasingly significant effect on the resonator Q. At 3.4 GHz, the electromagnetic radiation accounted for about 14% of the loss in resonator Q. At frequencies less than 2 GHz, the calculated resonator Q compared well with the intrinsic Q(x) provided by the formula Q(x) = 16 x 10(6)/f where f was in MHz. At frequencies higher than 2.3 GHz, the aluminum electrodes had significant effects on the resonator Q. At 3.4 GHz, the electromagnetic radiation loss in the electrodes was an order of magnitude greater than their viscoelastic loss; hence, the vibrating aluminum electrodes became an efficient emitter of electromagnetic waves. The effects of electrical resistance in both the electrodes and quartz were determined to be negligible.

To describe the incidence of neuro-ophthalmic diseases in a multi-ethnic Asian population in Singapore.Prospective study in public hospitals in Singapore. All neuro-ophthalmic cases seen in four public sector hospitals over a 22-month period (September 2002 to June 2004) were identified using a standardized protocol. The 2004 Singapore population was used as a denominator to estimate annual incidence. The prevalence of ischemic risk factors (hypertension, diabetes, and hypercholesterolemia) among cases was compared to population data.A total of 1,356 patients with neuro-ophthalmic diseases were seen during the study period, of which 627 were new incident cases. The overall annual incidence of neuro-ophthalmic diseases was 9.81 per 100,000 (95% confidence interval, 8.80-10.90). The incidence increased with age. After controlling for age, the annual incidence was similar between men (10.75 per 100,000) and women (9.00 per 100,000), but was higher in Chinese (10.33 per 100,000) and Indians (9.34 per 100,000) than in Malays (6.62 per 100,000). The three commonest specific neuro-ophthalmic conditions were abducens nerve palsy (1.27 per 100,000), anterior ischemic optic neuropathy (1.08 per 100,000) and oculomotor nerve palsy (0.91 per 100,000). The incidence of optic neuritis was 0.83 per 100,000. Compared with the Singapore general population, the prevalence of diabetes was significantly higher in people aged 40-59, while the prevalence of hypercholesterolemia was significantly higher in 60-69 year age group.In this study of public hospitals in Singapore, the incidence of neuro-ophthalmic diseases was higher in Chinese and Indians compared to Malays.

The frequency–temperature characteristics of quartz crystal resonators, particularly the frequency stability in a specific temperature range in which the vibration modes are strongly coupled, has been an important requirement in most applications. The analytical work on frequency–temperature relations has been done over the last decades in many aspects, ranging from the fundamental theory for the thermal effect on vibrations of elastic solids to simplified plate equations of a few strongly coupled vibration modes. However, it has been clearly observed that due to complications of the resonator structures such as the presence of a mounting structure and electrodes, simple and analytical solutions will not be able to consider all the factors which will have inevitable and noticeable effects. In this paper, we incorporate the frequency–temperature theory for crystal plates based on the incremental thermal field formulation by Lee and Yong into our finite element analysis implementation, which is then used to analyze the free vibrations of crystal plates with the higher-order Mindlin plate theory. The effect of electrodes on the frequency–temperature relation is also considered. The computational results are compared with experimental ones from actual products. The satisfactory agreement demonstrates the precise prediction of the frequency–temperature behavior and practical applications of the finite element analysis in product modeling and development.

According to ultraviolet (UV) spectroscopic studies, a positive AZ photoresist film thicker than 10 (m can hardly transmit UV lights of wavelengths 200–285 nm. A simple photomask for UV photolithography was prepared using a quartz glass plate coated with a light-obstructing film of positive AZ photoresist, and the quality of the photomask and fidelity of the pattern transferred by the photomask were evaluated. The developed AZ photoresist photomask was used for fabrication of gold microelectrode on polycarbonate (PC) sheets. PC sheetswere exposed to the UV lights emitted from a low-pressure mercury lamp and passed through the photomask. The PC sheets were subjected to selective surface photolysis in the exposed area. After a series of wet chemical reactions, nano gold particles serving as the catalyst for electroless plating were deposited on the irradiated area. Gold microelectrodes were then generated by immersing the selectively activated PC sheet in an electroless gold plating bath for a specific time. Without need for a clean room, the photomasks can be prepared by a chemist in a common chemical laboratory with low-cost materials and simple procedures.