Search results for: Sung Chan Kim
Commenced in January 2007
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Paper Count: 430

Search results for: Sung Chan Kim

10 Possible Involvement of DNA-methyltransferase and Histone Deacetylase in the Regulation of Virulence Potential of Acanthamoeba castellanii

Authors: Yi H. Wong, Li L. Chan, Chee O. Leong, Stephen Ambu, Joon W. Mak, Priyadashi S. Sahu

Abstract:

Background: Acanthamoeba is a free-living opportunistic protist which is ubiquitously distributed in the environment. Virulent Acanthamoeba can cause fatal encephalitis in immunocompromised patients and potential blinding keratitis in immunocompetent contact lens wearers. Approximately 24 species have been identified but only the A. castellanii, A. polyphaga and A. culbertsoni are commonly associated with human infections. Until to date, the precise molecular basis for Acanthamoeba pathogenesis remains unclear. Previous studies reported that Acanthamoeba virulence can be diminished through prolonged axenic culture but revived through serial mouse passages. As no clear explanation on this reversible pathogenesis is established, hereby, we postulate that the epigenetic regulators, DNA-methyltransferases (DNMT) and histone-deacetylases (HDAC), could possibly be involved in granting the virulence plasticity of Acanthamoeba spp. Methods: Four rounds of mouse passages were conducted to revive the virulence potential of the virulence-attenuated Acanthamoeba castellanii strain (ATCC 50492). Briefly, each mouse (n=6/group) was inoculated intraperitoneally with Acanthamoebae cells (2x 105 trophozoites/mouse) and incubated for 2 months. Acanthamoebae cells were isolated from infected mouse organs by culture method and subjected to subsequent mouse passage. In vitro cytopathic, encystment and gelatinolytic assays were conducted to evaluate the virulence characteristics of Acanthamoebae isolates for each passage. PCR primers which targeted on the 2 members (DNMT1 and DNMT2) and 5 members (HDAC1 to 5) of the DNMT and HDAC gene families respectively were custom designed. Quantitative real-time PCR (qPCR) was performed to detect and quantify the relative expression of the two gene families in each Acanthamoeba isolates. Beta-tubulin of A. castellanii (Genbank accession no: XP_004353728) was included as housekeeping gene for data normalisation. PCR mixtures were also analyzed by electrophoresis for amplicons detection. All statistical analyses were performed using the paired one-tailed Student’s t test. Results: Our pathogenicity tests showed that the virulence-reactivated Acanthamoeba had a higher degree of cytopathic effect on vero cells, a better resistance to encystment challenge and a higher gelatinolytic activity which was catalysed by serine protease. qPCR assay showed that DNMT1 expression was significantly higher in the virulence-reactivated compared to the virulence-attenuated Acanthamoeba strain (p ≤ 0.01). The specificity of primers which targeted on DNMT1 was confirmed by sequence analysis of PCR amplicons, which showed a 97% similarity to the published DNA-methyltransferase gene of A. castellanii (GenBank accession no: XM_004332804.1). Out of the five primer pairs which targeted on the HDAC family genes, only HDAC4 expression was significantly difference between the two variant strains. In contrast to DNMT1, HDAC4 expression was much higher in the virulence-attenuated Acanthamoeba strain. Conclusion: Our mouse passages had successfully restored the virulence of the attenuated strain. Our findings suggested that DNA-methyltransferase (DNMT1) and histone deacetylase (HDAC4) expressions are associated with virulence potential of Acanthamoeba spp.

Keywords: acanthamoeba, DNA-methyltransferase, histone deacetylase, virulence-associated proteins

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9 Comparisons of Drop Jump and Countermovement Jump Performance for Male Basketball Players with and without Low-Dye Taping Application

Authors: Chung Yan Natalia Yeung, Man Kit Indy Ho, Kin Yu Stan Chan, Ho Pui Kipper Lam, Man Wah Genie Tong, Tze Chung Jim Luk

Abstract:

Excessive foot pronation is a well-known risk factor of knee and foot injuries such as patellofemoral pain, patellar and Achilles tendinopathy, and plantar fasciitis. Low-Dye taping (LDT) application is not uncommon for basketball players to control excessive foot pronation for pain control and injury prevention. The primary potential benefits of using LDT include providing additional supports to medial longitudinal arch and restricting the excessive midfoot and subtalar motion in weight-bearing activities such as running and landing. Meanwhile, restrictions provided by the rigid tape may also potentially limit functional joint movements and sports performance. Coaches and athletes need to weigh the potential benefits and harmful effects before making a decision if applying LDT technique is worthwhile or not. However, the influence of using LDT on basketball-related performance such as explosive and reactive strength is not well understood. Therefore, the purpose of this study was to investigate the change of drop jump (DJ) and countermovement jump (CMJ) performance before and after LDT application for collegiate male basketball players. In this within-subject crossover study, 12 healthy male basketball players (age: 21.7 ± 2.5 years) with at least 3-year regular basketball training experience were recruited. Navicular drop (ND) test was adopted as the screening and only those with excessive pronation (ND ≥ 10mm) were included. Participants with recent lower limb injury history were excluded. Recruited subjects were required to perform both ND, DJ (on a platform of 40cm height) and CMJ (without arms swing) tests in series during taped and non-taped conditions in the counterbalanced order. Reactive strength index (RSI) was calculated by using the flight time divided by the ground contact time measured. For DJ and CMJ tests, the best of three trials was used for analysis. The difference between taped and non-taped conditions for each test was further calculated through standardized effect ± 90% confidence intervals (CI) with clinical magnitude-based inference (MBI). Paired samples T-test showed significant decrease in ND (-4.68 ± 1.44mm; 95% CI: -3.77, -5.60; p < 0.05) while MBI demonstrated most likely beneficial and large effect (standardize effect: -1.59 ± 0.27) in LDT condition. For DJ test, significant increase in both flight time (25.25 ± 29.96ms; 95% CI: 6.22, 44.28; p < 0.05) and RSI (0.22 ± 0.22; 95% CI: 0.08, 0.36; p < 0.05) were observed. In taped condition, MBI showed very likely beneficial and moderate effect (standardized effect: 0.77 ± 0.49) in flight time, possibly beneficial and small effect (standardized effect: -0.26 ± 0.29) in ground contact time and very likely beneficial and moderate effect (standardized effect: 0.77 ± 0.42) in RSI. No significant difference in CMJ was observed (95% CI: -2.73, 2.08; p > 0.05). For basketball players with pes planus, applying LDT could substantially support the foot by elevating the navicular height and potentially provide acute beneficial effects in reactive strength performance. Meanwhile, no significant harmful effect on CMJ was observed. Basketball players may consider applying LDT before the game or training to enhance the reactive strength performance. However since the observed effects in this study could not generalize to other players without excessive foot pronation, further studies on players with normal foot arch or navicular height are recommended.

Keywords: flight time, pes planus, pronated foot, reactive strength index

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8 Poly (3,4-Ethylenedioxythiophene) Prepared by Vapor Phase Polymerization for Stimuli-Responsive Ion-Exchange Drug Delivery

Authors: M. Naveed Yasin, Robert Brooke, Andrew Chan, Geoffrey I. N. Waterhouse, Drew Evans, Darren Svirskis, Ilva D. Rupenthal

Abstract:

Poly(3,4-ethylenedioxythiophene) (PEDOT) is a robust conducting polymer (CP) exhibiting high conductivity and environmental stability. It can be synthesized by either chemical, electrochemical or vapour phase polymerization (VPP). Dexamethasone sodium phosphate (dexP) is an anionic drug molecule which has previously been loaded onto PEDOT as a dopant via electrochemical polymerisation; however this technique requires conductive surfaces from which polymerization is initiated. On the other hand, VPP produces highly organized biocompatible CP structures while polymerization can be achieved onto a range of surfaces with a relatively straight forward scale-up process. Following VPP of PEDOT, dexP can be loaded and subsequently released via ion-exchange. This study aimed at preparing and characterising both non-porous and porous VPP PEDOT structures including examining drug loading and release via ion-exchange. Porous PEDOT structures were prepared by first depositing a sacrificial polystyrene (PS) colloidal template on a substrate, heat curing this deposition and then spin coating it with the oxidant solution (iron tosylate) at 1500 rpm for 20 sec. VPP of both porous and non-porous PEDOT was achieved by exposing to monomer vapours in a vacuum oven at 40 mbar and 40 °C for 3 hrs. Non-porous structures were prepared similarly on the same substrate but without any sacrificial template. Surface morphology, compositions and behaviour were then characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV) respectively. Drug loading was achieved by 50 CV cycles in a 0.1 M dexP aqueous solution. For drug release, each sample was exposed to 20 mL of phosphate buffer saline (PBS) placed in a water bath operating at 37 °C and 100 rpm. Film was stimulated (continuous pulse of ± 1 V at 0.5 Hz for 17 mins) while immersed into PBS. Samples were collected at 1, 2, 6, 23, 24, 26 and 27 hrs and were analysed for dexP by high performance liquid chromatography (HPLC Agilent 1200 series). AFM and SEM revealed the honey comb nature of prepared porous structures. XPS data showed the elemental composition of the dexP loaded film surface, which related well with that of PEDOT and also showed that one dexP molecule was present per almost three EDOT monomer units. The reproducible electroactive nature was shown by several cycles of reduction and oxidation via CV. Drug release revealed success in drug loading via ion-exchange, with stimulated porous and non-porous structures exhibiting a proof of concept burst release upon application of an electrical stimulus. A similar drug release pattern was observed for porous and non-porous structures without any significant statistical difference, possibly due to the thin nature of these structures. To our knowledge, this is the first report to explore the potential of VPP prepared PEDOT for stimuli-responsive drug delivery via ion-exchange. The produced porous structures were ordered and highly porous as indicated by AFM and SEM. These porous structures exhibited good electroactivity as shown by CV. Future work will investigate porous structures as nano-reservoirs to increase drug loading while sealing these structures to minimize spontaneous drug leakage.

Keywords: PEDOT for ion-exchange drug delivery, stimuli-responsive drug delivery, template based porous PEDOT structures, vapour phase polymerization of PEDOT

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7 Transcriptomic Analysis of Acanthamoeba castellanii Virulence Alteration by Epigenetic DNA Methylation

Authors: Yi-Hao Wong, Li-Li Chan, Chee-Onn Leong, Stephen Ambu, Joon-Wah Mak, Priyasashi Sahu

Abstract:

Background: Acanthamoeba is a genus of amoebae which lives as a free-living in nature or as a human pathogen that causes severe brain and eye infections. Virulence potential of Acanthamoeba is not constant and can change with growth conditions. DNA methylation, an epigenetic process which adds methyl groups to DNA, is used by eukaryotic cells, including several human parasites to control their gene expression. We used qPCR, siRNA gene silencing, and RNA sequencing (RNA-Seq) to study DNA-methyltransferase gene family (DNMT) in order to indicate the possibility of its involvement in programming Acanthamoeba virulence potential. Methods: A virulence-attenuated Acanthamoeba isolate (designation: ATCC; original isolate: ATCC 50492) was subjected to mouse passages to restore its pathogenicity; a virulence-reactivated isolate (designation: AC/5) was generated. Several established factors associated with Acanthamoeba virulence phenotype were examined to confirm the succession of reactivation process. Differential gene expression of DNMT between ATCC and AC/5 isolates was performed by qPCR. Silencing on DNMT gene expression in AC/5 isolate was achieved by siRNA duplex. Total RNAs extracted from ATCC, AC/5, and siRNA-treated (designation: si-146) were subjected to RNA-Seq for comparative transcriptomic analysis in order to identify the genome-wide effect of DNMT in regulating Acanthamoeba gene expression. qPCR was performed to validate the RNA-Seq results. Results: Physiological and cytophatic assays demonstrated an increased in virulence potential of AC/5 isolate after mouse passages. DNMT gene expression was significantly higher in AC/5 compared to ATCC isolate (p ≤ 0.01) by qPCR. si-146 duplex reduced DNMT gene expression in AC/5 isolate by 30%. Comparative transcriptome analysis identified the differentially expressed genes, with 3768 genes in AC/5 vs ATCC isolate; 2102 genes in si-146 vs AC/5 isolate and 3422 genes in si-146 vs ATCC isolate, respectively (fold-change of ≥ 2 or ≤ 0.5, p-value adjusted (padj) < 0.05). Of these, 840 and 1262 genes were upregulated and downregulated, respectively, in si-146 vs AC/5 isolate. Eukaryotic orthologous group (KOG) assignments revealed a higher percentage of downregulated gene expression in si-146 compared to AC/5 isolate, were related to posttranslational modification, signal transduction and energy production. Gene Ontology (GO) terms for those downregulated genes shown were associated with transport activity, oxidation-reduction process, and metabolic process. Among these downregulated genes were putative genes encoded for heat shock proteins, transporters, ubiquitin-related proteins, proteins for vesicular trafficking (small GTPases), and oxidoreductases. Functional analysis of similar predicted proteins had been described in other parasitic protozoa for their survival and pathogenicity. Decreased expression of these genes in si146-treated isolate may account in part for Acanthamoeba reduced pathogenicity. qPCR on 6 selected genes upregulated in AC/5 compared to ATCC isolate corroborated the RNA sequencing findings, indicating a good concordance between these two analyses. Conclusion: To the best of our knowledge, this study represents the first genome-wide analysis of DNA methylation and its effects on gene expression in Acanthamoeba spp. The present data indicate that DNA methylation has substantial effect on global gene expression, allowing further dissection of the genome-wide effects of DNA-methyltransferase gene in regulating Acanthamoeba pathogenicity.

Keywords: Acanthamoeba, DNA methylation, RNA sequencing, virulence

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6 Effect of Chitosan Oligosaccharide from Tenebrio Molitor on Prebiotics

Authors: Hyemi Kim, Jay Kim, Kyunghoon Han, Ra-Yeong Choi, In-Woo Kim, Hyung Joo Suh, Ki-Bae Hong, Sung Hee Han

Abstract:

Chitosan is used in various industries such as food and medical care because it is known to have various functions such as anti-obesity, anti-inflammatory and anti-cancer benefits. Most of the commercial chitosan is extracted from crustaceans. As the harvest rate of snow crabs and red snow crabs decreases and safety issues arise due to environmental pollution, research is underway to extract chitosan from insects. In this study, we used Response Surface Methodology (RSM) to predict the optimal conditions to produce chitosan oligosaccharides from mealworms (MCOS), which can be absorbed through the intestine as low-molecular-weight chitosan. The experimentally confirmed optimal conditions for MCOS production using chitosanase were found to be a substrate concentration of 2.5%, enzyme addition of 30 mg/g and a reaction time of 6 hours. The chemical structure and physicochemical properties of the produced MCOS were measured using MALDI-TOF mass spectra and FTIR spectra. The MALDI-TOF mass spectra revealed peaks corresponding to the dimer (375.045), trimer (525.214), tetramer (693.243), pentamer (826.296), and hexamer (987.360). In the FTIR spectra, commercial chitosan oligosaccharides exhibited a weak peak pattern at 3500-2500 cm-1, unlike chitosan or chitosan oligosaccharides. There was a difference in the peak at 3200~3500 cm-1, where different vibrations corresponding to OH and amine groups overlapped. Chitosan, chitosan oligosaccharide, and commercial chitosan oligosaccharide showed peaks at 2849, 2884, and 2885 cm-1, respectively, attributed to the absorption of the C-H stretching vibration of methyl or methine. The amide I, amide II, and amide III bands of chitosan, chitosan oligosaccharide, and commercial chitosan oligosaccharide exhibited peaks at 1620/1620/1602, 1553/1555/1505, and 1310/1309/1317 cm-1, respectively. Furthermore, the solubility of MCOS was 45.15±3.43, water binding capacity (WBC) was 299.25±4.57, and fat binding capacity (FBC) was 325.61±2.28 and the solubility of commercial chitosan oligosaccharides was 49.04±9.52, WBC was 280.55±0.50, and FBC was 157.22±18.15. Thus, the characteristics of MCOS and commercial chitosan oligosaccharides are similar. The results of investigating the impact of chitosan oligosaccharide on the proliferation of probiotics revealed increased growth in L. casei, L. acidophilus, and Bif. Bifidum. Therefore, the major short-chain fatty acids produced by gut microorganisms, such as acetic acid, propionic acid, and butyric acid, increased within 24 hours of adding 1% (p<0.01) and 2% (p<0.001) MCOS. The impact of MCOS on the overall gut microbiota was assessed, revealing that the Chao1 index did not show significant differences, but the Simpson index decreased in a concentration-dependent manner, indicating a higher species diversity. The addition of MCOS resulted in changes in the overall microbial composition, with an increase in Firmicutes and Verrucomicrobia (p<0.05) compared to the control group, while Proteobacteria and Actinobacteria (p<0.05) decreased. At the genus level, changes in microbiota due to MCOS supplementation showed an increase in beneficial bacteria like lactobacillus, Romboutsia, Turicibacter, and Akkermansia (p<0.0001) while harmful bacteria like Enterococcus, Morganella, Proterus, and Bacteroides (p<0.0001) decreased. In this study, chitosan oligosaccharides were successfully produced under established conditions from mealworms, and these chitosan oligosaccharides are expected to have prebiotic effects, similar to those obtained from crabs.

Keywords: mealworms, chitosan, chitosan oligosaccharide, prebiotics

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5 Optical-Based Lane-Assist System for Rowing Boats

Authors: Stephen Tullis, M. David DiDonato, Hong Sung Park

Abstract:

Rowing boats (shells) are often steered by a small rudder operated by one of the backward-facing rowers; the attention required of that athlete then slightly decreases the power that that athlete can provide. Reducing the steering distraction would then increase the overall boat speed. Races are straight 2000 m courses with each boat in a 13.5 m wide lane marked by small (~15 cm) widely-spaced (~10 m) buoys, and the boat trajectory is affected by both cross-currents and winds. An optical buoy recognition and tracking system has been developed that provides the boat’s location and orientation with respect to the lane edges. This information is provided to the steering athlete as either: a simple overlay on a video display, or fed to a simplified autopilot system giving steering directions to the athlete or directly controlling the rudder. The system is then effectively a “lane-assist” device but with small, widely-spaced lane markers viewed from a very shallow angle due to constraints on camera height. The image is captured with a lightweight 1080p webcam, and most of the image analysis is done in OpenCV. The colour RGB-image is converted to a grayscale using the difference of the red and blue channels, which provides good contrast between the red/yellow buoys and the water, sky, land background and white reflections and noise. Buoy detection is done with thresholding within a tight mask applied to the image. Robust linear regression using Tukey’s biweight estimator of the previously detected buoy locations is used to develop the mask; this avoids the false detection of noise such as waves (reflections) and, in particular, buoys in other lanes. The robust regression also provides the current lane edges in the camera frame that are used to calculate the displacement of the boat from the lane centre (lane location), and its yaw angle. The interception of the detected lane edges provides a lane vanishing point, and yaw angle can be calculated simply based on the displacement of this vanishing point from the camera axis and the image plane distance. Lane location is simply based on the lateral displacement of the vanishing point from any horizontal cut through the lane edges. The boat lane position and yaw are currently fed what is essentially a stripped down marine auto-pilot system. Currently, only the lane location is used in a PID controller of a rudder actuator with integrator anti-windup to deal with saturation of the rudder angle. Low Kp and Kd values decrease unnecessarily fast return to lane centrelines and response to noise, and limiters can be used to avoid lane departure and disqualification. Yaw is not used as a control input, as cross-winds and currents can cause a straight course with considerable yaw or crab angle. Mapping of the controller with rudder angle “overall effectiveness” has not been finalized - very large rudder angles stall and have decreased turning moments, but at less extreme angles the increased rudder drag slows the boat and upsets boat balance. The full system has many features similar to automotive lane-assist systems, but with the added constraints of the lane markers, camera positioning, control response and noise increasing the challenge.

Keywords: auto-pilot, lane-assist, marine, optical, rowing

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4 Effects of Applying Low-Dye Taping in Performing Double-Leg Squat on Electromyographic Activity of Lower Extremity Muscles for Collegiate Basketball Players with Excessive Foot Pronation

Authors: I. M. K. Ho, S. K. Y. Chan, K. H. P. Lam, G. M. W. Tong, N. C. Y. Yeung, J. T. C. Luk

Abstract:

Low-dye taping (LDT) is commonly used for treating foot problems, such as plantar fasciitis, and supporting foot arch for runners and non-athletes patients with pes planus. The potential negative impact of pronated feet leading to tibial and femoral internal rotation via the entire kinetic chain reaction was postulated and identified. The changed lower limb biomechanics potentially leading to poor activation of hip and knee stabilizers, such as gluteus maximus and medius, may associate with higher risk of knee injuries including patellofemoral pain syndrome and ligamentous sprain in many team sports players. It is therefore speculated that foot arch correction with LDT might enhance the use of gluteal muscles. The purpose of this study was to investigate the effect of applying LDT on surface electromyographic (sEMG) activity of superior gluteus maximus (SGMax), inferior gluteus maximus (IGMax), gluteus medius (GMed) and tibialis anterior (TA) during double-leg squat. 12 male collegiate basketball players (age: 21.72.5 years; body fat: 12.43.6%; navicular drop: 13.72.7mm) with at least three years regular basketball training experience participated in this study. Participants were excluded if they had recent history of lower limb injuries, over 16.6% body fat and lesser than 10mm drop in navicular drop (ND) test. Recruited subjects visited the laboratory once for the within-subject crossover study. Maximum voluntary isometric contraction (MVIC) tests on all selected muscles were performed in randomized order followed by sEMG test on double-leg squat during LDT and non-LDT conditions in counterbalanced order. SGMax, IGMax, GMed and TA activities during the entire 2-second concentric and 2-second eccentric phases were normalized and interpreted as %MVIC. The magnitude of the difference between taped and non-taped conditions of each muscle was further assessed via standardized effect90% confidence intervals (CI) with non-clinical magnitude-based inference. Paired samples T-test showed a significant decrease (4.71.4mm) in ND (95% CI: 3.8, 5.6; p < 0.05) while no significant difference was observed between taped and non-taped conditions in sEMG tests for all muscles and contractions (p > 0.05). On top of traditional significant testing, magnitude-based inference showed possibly increase in IGMax activity (small standardized effect: 0.270.44), likely increase in GMed activity (small standardized effect: 0.340.34) and possibly increase in TA activity (small standardized effect: 0.220.29) during eccentric phase. It is speculated that the decrease of navicular drop supported by LDT application could potentially enhance the use of inferior gluteus maximus and gluteus medius especially during eccentric phase in this study. As the eccentric phase of double-leg squat is an important component of landing activities in basketball, further studies on the onset and amount of gluteal activation during jumping and landing activities with LDT are recommended. Since both hip and knee kinematics were not measured in this study, the underlying cause of the observed increase in gluteal activation during squat after LDT is inconclusive. In this regard, the investigation of relationships between LDT application, ND, hip and knee kinematics, and gluteal muscle activity during sports specific jumping and landing tasks should be focused in the future.

Keywords: flat foot, gluteus maximus, gluteus medius, injury prevention

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3 An Innovation Decision Process View in an Adoption of Total Laboratory Automation

Authors: Chia-Jung Chen, Yu-Chi Hsu, June-Dong Lin, Kun-Chen Chan, Chieh-Tien Wang, Li-Ching Wu, Chung-Feng Liu

Abstract:

With fast advances in healthcare technology, various total laboratory automation (TLA) processes have been proposed. However, adopting TLA needs quite high funding. This study explores an early adoption experience by Taiwan’s large-scale hospital group, the Chimei Hospital Group (CMG), which owns three branch hospitals (Yongkang, Liouying and Chiali, in order by service scale), based on the five stages of Everett Rogers’ Diffusion Decision Process. 1.Knowledge stage: Over the years, two weaknesses exists in laboratory department of CMG: 1) only a few examination categories (e.g., sugar testing and HbA1c) can now be completed and reported within a day during an outpatient clinical visit; 2) the Yongkang Hospital laboratory space is dispersed across three buildings, resulting in duplicated investment in analysis instruments and inconvenient artificial specimen transportation. Thus, the senior management of the department raised a crucial question, was it time to process the redesign of the laboratory department? 2.Persuasion stage: At the end of 2013, Yongkang Hospital’s new building and restructuring project created a great opportunity for the redesign of the laboratory department. However, not all laboratory colleagues had the consensus for change. Thus, the top managers arranged a series of benchmark visits to stimulate colleagues into being aware of and accepting TLA. Later, the director of the department proposed a formal report to the top management of CMG with the results of the benchmark visits, preliminary feasibility analysis, potential benefits and so on. 3.Decision stage: This TLA suggestion was well-supported by the top management of CMG and, finally, they made a decision to carry out the project with an instrument-leasing strategy. After the announcement of a request for proposal and several vendor briefings, CMG confirmed their laboratory automation architecture and finally completed the contracts. At the same time, a cross-department project team was formed and the laboratory department assigned a section leader to the National Taiwan University Hospital for one month of relevant training. 4.Implementation stage: During the implementation, the project team called for regular meetings to review the results of the operations and to offer an immediate response to the adjustment. The main project tasks included: 1) completion of the preparatory work for beginning the automation procedures; 2) ensuring information security and privacy protection; 3) formulating automated examination process protocols; 4) evaluating the performance of new instruments and the instrument connectivity; 5)ensuring good integration with hospital information systems (HIS)/laboratory information systems (LIS); and 6) ensuring continued compliance with ISO 15189 certification. 5.Confirmation stage: In short, the core process changes include: 1) cancellation of signature seals on the specimen tubes; 2) transfer of daily examination reports to a data warehouse; 3) routine pre-admission blood drawing and formal inpatient morning blood drawing can be incorporated into an automatically-prepared tube mechanism. The study summarizes below the continuous improvement orientations: (1) Flexible reference range set-up for new instruments in LIS. (2) Restructure of the specimen category. (3) Continuous review and improvements to the examination process. (4) Whether installing the tube (specimen) delivery tracks need further evaluation.

Keywords: innovation decision process, total laboratory automation, health care

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2 Modern Cardiac Surgical Outcomes in Nonagenarians: A Multicentre Retrospective Observational Study

Authors: Laurence Weinberg, Dominic Walpole, Dong-Kyu Lee, Michael D’Silva, Jian W. Chan, Lachlan F. Miles, Bradley Carp, Adam Wells, Tuck S. Ngun, Siven Seevanayagam, George Matalanis, Ziauddin Ansari, Rinaldo Bellomo, Michael Yii

Abstract:

Background: There have been multiple recent advancements in the selection, optimization and management of cardiac surgical patients. However, there is limited data regarding the outcomes of nonagenarians undergoing cardiac surgery, despite this vulnerable cohort increasingly receiving these interventions. This study describes the patient characteristics, management and outcomes of a group of nonagenarians undergoing cardiac surgery in the context of contemporary peri-operative care. Methods: A retrospective observational study was conducted of patients 90 to 99 years of age (i.e., nonagenarians) who had undergone cardiac surgery requiring a classic median sternotomy (i.e., open-heart surgery). All operative indications were included. Patients who underwent minimally invasive surgery, transcatheter aortic valve implantation and thoracic aorta surgery were excluded. Data were collected from four hospitals in Victoria, Australia, over an 8-year period (January 2012 – December 2019). The primary objective was to assess six-month mortality in nonagenarians undergoing open-heart surgery and to evaluate the incidence and severity of postoperative complications using the Clavien-Dindo classification system. The secondary objective was to provide a detailed description of the characteristics and peri-operative management of this group. Results: A total of 12,358 adult patients underwent cardiac surgery at the study centers during the observation period, of whom 18 nonagenarians (0.15%) fulfilled the inclusion criteria. The median (IQR) [min-max] age was 91 years (90.0:91.8) [90-94] and 14 patients (78%) were men. Cardiovascular comorbidities, polypharmacy and frailty, were common. The median (IQR) predicted in-hospital mortality by EuroSCORE II was 6.1% (4.1-14.5). All patients were optimized preoperatively by a multidisciplinary team of surgeons, cardiologists, geriatricians and anesthetists. All index surgeries were performed on cardiopulmonary bypass. Isolated coronary artery bypass grafting (CABG) and CABG with aortic valve replacement were the most common surgeries being performed in four and five patients, respectively. Half the study group underwent surgery involving two or more major procedures (e.g. CABG and valve replacement). Surgery was undertaken emergently in 44% of patients. All patients except one experienced at least one postoperative complication. The most common complications were acute kidney injury (72%), new atrial fibrillation (44%) and delirium (39%). The highest Clavien-Dindo complication grade was IIIb occurring once each in three patients. Clavien-Dindo grade IIIa complications occurred in only one patient. The median (IQR) postoperative length of stay was 11.6 days (9.8:17.6). One patient was discharged home and all others to an inpatient rehabilitation facility. Three patients had an unplanned readmission within 30 days of discharge. All patients had follow-up to at least six months after surgery and mortality over this period was zero. The median (IQR) duration of follow-up was 11.3 months (6.0:26.4) and there were no cases of mortality observed within the available follow-up records. Conclusion: In this group of nonagenarians undergoing cardiac surgery, postoperative six-month mortality was zero. Complications were common but generally of low severity. These findings support carefully selected nonagenarian patients being offered cardiac surgery in the context of contemporary, multidisciplinary perioperative care. Further, studies are needed to assess longer-term mortality and functional and quality of life outcomes in this vulnerable surgical cohort.

Keywords: cardiac surgery, mortality, nonagenarians, postoperative complications

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1 Al2O3-Dielectric AlGaN/GaN Enhancement-Mode MOS-HEMTs by Using Ozone Water Oxidization Technique

Authors: Ching-Sung Lee, Wei-Chou Hsu, Han-Yin Liu, Hung-Hsi Huang, Si-Fu Chen, Yun-Jung Yang, Bo-Chun Chiang, Yu-Chuang Chen, Shen-Tin Yang

Abstract:

AlGaN/GaN high electron mobility transistors (HEMTs) have been intensively studied due to their intrinsic advantages of high breakdown electric field, high electron saturation velocity, and excellent chemical stability. They are also suitable for ultra-violet (UV) photodetection due to the corresponding wavelengths of GaN bandgap. To improve the optical responsivity by decreasing the dark current due to gate leakage problems and limited Schottky barrier heights in GaN-based HEMT devices, various metal-oxide-semiconductor HEMTs (MOS-HEMTs) have been devised by using atomic layer deposition (ALD), molecular beam epitaxy (MBE), metal-organic chemical vapor deposition (MOCVD), liquid phase deposition (LPD), and RF sputtering. The gate dielectrics include MgO, HfO2, Al2O3, La2O3, and TiO2. In order to provide complementary circuit operation, enhancement-mode (E-mode) devices have been lately studied using techniques of fluorine treatment, p-type capper, piezoneutralization layer, and MOS-gate structure. This work reports an Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMT design by using a cost-effective ozone water oxidization technique. The present ozone oxidization method advantages of low cost processing facility, processing simplicity, compatibility to device fabrication, and room-temperature operation under atmospheric pressure. It can further reduce the gate-to-channel distance and improve the transocnductance (gm) gain for a specific oxide thickness, since the formation of the Al2O3 will consume part of the AlGaN barrier at the same time. The epitaxial structure of the studied devices was grown by using the MOCVD technique. On a Si substrate, the layer structures include a 3.9 m C-doped GaN buffer, a 300 nm GaN channel layer, and a 5 nm Al0.25Ga0.75N barrier layer. Mesa etching was performed to provide electrical isolation by using an inductively coupled-plasma reactive ion etcher (ICP-RIE). Ti/Al/Au were thermally evaporated and annealed to form the source and drain ohmic contacts. The device was immersed into the H2O2 solution pumped with ozone gas generated by using an OW-K2 ozone generator. Ni/Au were deposited as the gate electrode to complete device fabrication of MOS-HEMT. The formed Al2O3 oxide thickness 7 nm and the remained AlGaN barrier thickness is 2 nm. A reference HEMT device has also been fabricated in comparison on the same epitaxial structure. The gate dimensions are 1.2 × 100 µm 2 with a source-to-drain spacing of 5 μm for both devices. The dielectric constant (k) of Al2O3 was characterized to be 9.2 by using C-V measurement. Reduced interface state density after oxidization has been verified by the low-frequency noise spectra, Hooge coefficients, and pulse I-V measurement. Improved device characteristics at temperatures of 300 K-450 K have been achieved for the present MOS-HEMT design. Consequently, Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMTs by using the ozone water oxidization method are reported. In comparison with a conventional Schottky-gate HEMT, the MOS-HEMT design has demonstrated excellent enhancements of 138% (176%) in gm, max, 118% (139%) in IDS, max, 53% (62%) in BVGD, 3 (2)-order reduction in IG leakage at VGD = -60 V at 300 (450) K. This work is promising for millimeter-wave integrated circuit (MMIC) and three-terminal active UV photodetector applications.

Keywords: MOS-HEMT, enhancement mode, AlGaN/GaN, passivation, ozone water oxidation, gate leakage

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