Publications by authors named "Tim Wu"

26 Publications

  • Page 1 of 1

Burden of Behavioral Health Comorbidities on Outpatient Health Care Utilization by Active Duty Service Members With a First Documented mTBI.

Mil Med 2021 01;186(Suppl 1):567-571

National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD 20889, USA.

Objective: More than 280,000 Active Duty Service Members (ADSMs) sustained a mild traumatic brain injury (mTBI) between 2000 and 2019 (Q3). Previous studies of veterans have shown higher utilization of outpatient health clinics by veterans diagnosed with mTBI. Additionally, veterans with mTBI and comorbid behavioral health (BH) conditions such as post-traumatic stress disorder, depression, and substance use disorders have significantly higher health care utilization than veterans diagnosed with mTBI alone. However, few studies of the relationship between mTBI, health care utilization, and BH conditions in the active duty military population currently exist. We examined the proportion of ADSMs with a BH diagnosis before and after a first documented mTBI and quantified outpatient utilization of the Military Health System in the year before and following injury.

Materials And Methods: Retrospective analysis of 4,901,840 outpatient encounters for 39,559 ADSMs with a first documented diagnosis of mTBI recorded in the Department of Defense electronic health record, subsets of who had a BH diagnosis. We examined median outpatient utilization 1 year before and 1 year after mTBI using Wilcoxon signed rank test, and the results are reported with an effect size r. Outpatient utilization is compared by BH subgroups.

Results: Approximately 60% of ADSMs experience a first mTBI with no associated BH condition, but 17% of men and women are newly diagnosed with a BH condition in the year following mTBI. ADSMs with a history of a BH condition before mTBI increased their median outpatient utilization from 23 to 35 visits for men and from 32 to 42 visits for women. In previously healthy ADSMs with a new BH condition following mTBI, men more than tripled median utilization from 7 to 24 outpatient visits, and women doubled utilization from 15 to 32 outpatient visits.

Conclusions: Behavioral health comorbidities affect approximately one-third of ADSMs following a first mTBI, and approximately 17% of previously healthy active duty men and women will be diagnosed with a new BH condition in the year following a first mTBI. Post-mTBI outpatient health care utilization is highly dependent on the presence or absence of BH condition and is markedly higher is ADSMs with a BH diagnosis in the year after a first documented mTBI.
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http://dx.doi.org/10.1093/milmed/usaa320DOI Listing
January 2021

Long-Term Arterial Remodeling After Bioresorbable Scaffold Implantation 4-Year Follow-up of Quantitative Coronary Angiography, Histology and Optical Coherence Tomography.

Cardiovasc Eng Technol 2020 Dec 27;11(6):636-645. Epub 2020 Oct 27.

Department of Cardiology, The Dongguan Affiliated Hospital of Jinan University, Binhaiwan Central Hospital of Dongguan, Dongguan, China.

Purpose: Our previous studies have confirmed the safety and efficacy of the novel fully bioresorbable PLLA scaffold (PowerScaffold®) at 12 months implantation. In the present study, the scaffold absorption and coronary vessel remodeling at 4 years were evaluated.

Methods: After PowerScaffold® were implanted into 13 coronary arteries of 6 miniature pigs, quantitative coronary angiography (QCA) was performed at 15 days and 4 years follow-up to measure the mean lumen diameter (MLD), late lumen loss (LLL), and % stenosis of the coronary arteries. Optical coherence tomography (OCT) was performed to obtain the strut footprints at 4 years before euthanization for histological analysis. In addition, 2 PowerScaffold® were implanted into 2 miniature pigs for 2 years as supplementary data. All stented arteries were dissected and stained with HE, Masson, EVG, and Alcian blue to observe struts, cells, fibrinoid, elastin, and proteoglycans, respectively.

Results: There were no significant differences in MLD, LLL and % stenosis in stented coronary arteries between 15 days and 4 years by QCA. At 4 years, most strut sites were indiscernible and replaced by extracellular matrix and connective tissue by histology. Both strut/vessel wall interaction and strut coverage were shown 100% by OCT.

Conclusion: At 4 years, the scaffold struts were completely embedded into vessel wall and mostly replaced by regenerated tissue. There was no sign of in-stent stenosis in all stented arteries.
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http://dx.doi.org/10.1007/s13239-020-00495-7DOI Listing
December 2020

Development of an aviation-style computerized checklist displayed on a tablet computer for improving handoff communication in the post-anesthesia care unit.

J Clin Monit Comput 2020 May 13. Epub 2020 May 13.

Department of Anesthesiology and Pain Medicine, University of Washington, 1959 NE Pacific Street, AA-117B, Box 356540, Seattle, WA, 98195-6540, USA.

Critical patient care information is often omitted or misunderstood during handoffs, which can lead to inefficiencies, delays, and sometimes patient harm. We implemented an aviation-style post-anesthesia care unit (PACU) handoff checklist displayed on a tablet computer to improve PACU handoff communication. We developed an aviation-style computerized checklist system for use in procedural rooms and adapted it for tablet computers to facilitate the performance of PACU handoffs. We then compared the proportion of PACU handoff items communicated before and after the implementation of the PACU handoff checklist on a tablet computer. A trained observer recorded the proportion of PACU handoff information items communicated, any resistance during the performance of the checklist, the type of provider participating in the handoff, and the time required to perform the handoff. We also obtained these patient outcomes: PACU length of stay, respiratory events, post-operative nausea and vomiting, and pain. A total of 209 PACU handoffs were observed before and 210 after the implementation of the tablet-based PACU handoff checklist. The average proportion of PACU handoff items communicated increased from 49.3% (95% CI 47.7-51.0%) before checklist implementation to 72.0% (95% CI 69.2-74.9%) after checklist implementation (p < 0.001). A tablet-based aviation-style handoff checklist resulted in an increase in PACU handoff items communicated, but did not have an effect on patient outcomes.
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http://dx.doi.org/10.1007/s10877-020-00521-yDOI Listing
May 2020

Structural optimization and finite element analysis of poly-l-lactide acid coronary stent with improved radial strength and acute recoil rate.

J Biomed Mater Res B Appl Biomater 2020 10 10;108(7):2754-2764. Epub 2020 Mar 10.

Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials (Ministry of Education), School of Materials Science and Engineering, Shandong University, Jinan, China.

Current poly-l-lactide acid (PLLA) scaffolds have issues of inadequate mechanical strength leading to thrombosis formation. Designing a novel bioabsorbable PLLA stent with a novel structure and improved mechanical property is urgently needed. In this study, stent structure modification and optimization based on bioresorbable vascular scaffold Version 1.1 (BVS 1.1, Abbott Laboratories) were conducted. The mechanical property of the redesigned stent was studied using both computerized finite element analysis and experimental mechanical deformation testing, including radial strength (RS), acute recoil (AR), foreshortening (FS), and bending stiffness (BS). The simulated and experimental results showed that the mechanical properties of the modified structure were significantly improved (modified stent vs. BVS 1.1: RS: 2.25 vs. 1.29 N/mm; AR: 3.03 vs. 4.41%; FS: 1.13 vs. 6.89%; BS: 1.49 vs. 0.72 N mm ).
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http://dx.doi.org/10.1002/jbm.b.34605DOI Listing
October 2020

Long-term clinical safety and efficacy of drug-coated balloon in the treatment of in-stent restenosis: A meta-analysis and systematic review.

Catheter Cardiovasc Interv 2020 08 12;96(2):E129-E141. Epub 2019 Nov 12.

Department of Cardiology, The Dongguan Affiliated Hospital (Dongguan 5th People's Hospital), Jinan University School of Medicine, Dongguan, China.

Objectives: The aim of this study was to evaluate the long-term clinical safety and efficacy of drug-coated balloon (DCB) in the treatment of in-stent restenosis (ISR).

Background: There is a long-term safety issue in peripheral arterial disease patients treated with paclitaxel-coated balloon, this has also raised concerns on DCB in coronary intervention.

Methods: Nine randomized controlled trials (RCTs) and nine observational studies (OSs) were included with a total of 3,782 patients (1,827 in the DCB group, 1,955 in the drug-eluting stent [DES] group) being analyzed. The primary outcome measure-major adverse cardiovascular events (MACEs), target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), cardiac death (CD), stent thrombosis (ST), all-cause death (AD), and coronary angiography outcomes included late lumen loss (LLL), minimum luminal diameter (MLD), diameter stenosis (DS) were analyzed.

Results: DCB treatment significantly reduced the LLL (MD: -0.13; [CI -0.23 to -0.03], p = .01). No difference was found for MLD (MD: -0.1; [CI -0.24 to 0.04], p = .17) and DS% (RR = 0.98 [CI 0.80-1.20], p = .86). There was no significant difference in TLR, TVR, MI, CD, ST, AD, and the overall incidence of MACEs between the two groups up to 3 years follow-up. Subgroup analysis for different type of ISR and DES showed no significant difference in the incidence of endpoints, and there is no difference when considering RCTs or OSs only.

Conclusions: The safety and efficacy of the DCB and DES in the treatment of ISR is comparable at up to 3 years follow-up.
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http://dx.doi.org/10.1002/ccd.28572DOI Listing
August 2020

Inflammation and dysfunction in human aortic endothelial cells associated with poly-l-lactic acid degradation in vitro are alleviated by curcumin.

J Biomed Mater Res A 2019 12 9;107(12):2756-2763. Epub 2019 Sep 9.

Central Laboratory, The Dongguan Affiliated Hospital of Medical College of Jinan University, The Fifth People's Hospital of Dongguan, Dongguan, China.

Poly-l-lactic acid (PLLA) is widely used in clinic, for example, as biodegradable coronary artery stents. However, inflammatory responses in endothelial cells associated with PLLA degradation are relatively undefined. We previously reported inflammation in human aortic endothelial cells (HAEC) in vitro and in vivo. Here, we further assessed inflammatory injury, including cell migration, cell function, and inflammatory cytokines expressed in HAEC treated with PLLA and curcumin by CCK-8, wound healing assay, ELISA, and Western blot. Significant inhibition of cell migration, remarkable dysfunction, and inflammatory responses were found in HAEC treated with PLLA degradation extract, and these effects were alleviated by Cur treatment. These findings indicated that cautious evaluation of biodegradable polymers should be performed, and Cur represents a promising anti-inflammatory agent for alleviating endothelial dysfunction and inflammation caused by PLLA degradation. In addition, Cur should be further studied experimentally in in vivo experiments on animal models as a potential therapeutic to reduce thrombosis of biodegradable polymer stents.
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http://dx.doi.org/10.1002/jbm.a.36778DOI Listing
December 2019

Effect of inflammation on endothelial cells induced by poly-L-lactic acid degradation in vitro and in vivo.

J Biomater Sci Polym Ed 2018 10 8;29(15):1909-1919. Epub 2018 Oct 8.

a Central Laboratory, The Dongguan Affiliated Hospital of Medical College of Jinan University , The Fifth People's Hospital of Dongguan , Dongguan , China.

As a promising candidate, biodegradable Poly-L-lactic Acid (PLLA) has been extensively used in coronary artery stents. In our previous reports, PLLA stents implanted in porcine coronary arteries showed safety without stent thrombosis. However, inflammatory responses were observed, which needed further study. In this study, human aortic endothelial cells (HAEC) were treated with different volume percentages of extract of pre-degraded PLLA (extract of PLLA) in vitro, and the cell growth curve and morphological changes were examined. The expression of inflammatory cytokines such as NF-κB, VEGF and VCAM-1 were also observed by ELISA. In addition, PLLA stent was implanted in porcine coronary artery to examine morphological changes, functional marker eNOS and inflammatory responses. The extract of PLLA caused significant growth inhibition and release of NF-κB, VEGF and VCAM-1 in HAEC with volume percentage-dependence. Although re-endothelialization and expression of eNOS was observed, expression of NF-κB and lymphocytes surrounding PLLA were also found after PLLA stents were implanted in the artery. This study demonstrated the effects of inflammation on endothelial cells induced by PLLA degradation in vitro and showed the inflammation in vivo, suggesting that anti-inflammatory strategy is necessary for PLLA stent implantation in the artery.
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http://dx.doi.org/10.1080/09205063.2018.1517858DOI Listing
October 2018

Six-month evaluation of novel bioabsorbable scaffolds composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles in porcine coronary arteries.

J Biomater Appl 2018 08;33(2):227-233

1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Objective Using coronary angiography and intravascular ultrasound methods to evaluate the performance of the novel fully bioabsorbable scaffold (NFBS) composed of poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) at six-month follow-up by comparing with PLLA scaffolds Methods Twelve PLLA/ACP scaffolds and 12 PLLA scaffolds were implanted into the coronary arteries of 12 miniature pigs. Quantitative coronary angiography (QCA) was used to measure the reference vessel diameter (RVD), mean lumen diameter (MLD) and late lumen loss (LLL). According to IVUS images, we calculated the strut malapposition rate (SMR) at post implantation, strut overlap rate (SOR), reference vessel area (RVA), mean stent area (MSA), mean lumen area (MLA) and luminal patency rate (LPR) at six-month follow-up. The radial strength of the scaffold was evaluated using a catheter tensile testing machine. Results QCA results indicated that, at six month, MLD of PLLA/ACP scaffolds was greater than those of PLLA scaffolds (2.47 ± 0.22 mm vs. 2.08 ± 0.25 mm, P < 0.05); LLL of PLLA/ACP scaffolds was less than those of PLLA scaffolds (0.42 ± 0.20 mm vs. 0.75 ± 0.22 mm, P < 0.05). IVUS results showed the SMR and SOR were all significantly less with the PLLA/ACP scaffolds than the PLLA scaffolds (5.84% ± 3.56% vs. 17.72% ± 4.86%, P < 0.05) (6.17% ± 4.63% vs. 17.65% ± 4.29%, P < 0.05). MSA, MLA and LPR of the PLLA/ACP scaffolds were all greater than those of PLLA scaffolds (6.35 ± 0.45 mm vs. 5.35 ± 0.51 mm, P < 0.05) (4.76 ± 0.46 mm vs. 3.77 ± 0.46 mm, P < 0.05) (78.01% ± 12.29% vs. 61.69% ± 9.76%, P < 0.05). Radial strength of PLLA/ACP scaffold at six month was greater than that of PLLA scaffold (76.33 ± 3.14 N vs. 67.67 ± 3.63 N). Conclusion The NFBS had less stent recoil, better lumen patency rate and greater radial strength than PLLA scaffolds. The results suggest the NFBS scaffolds can maintain the structural strength and functional performance, which are effective for up to six months when implanted in porcine coronary arteries.
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http://dx.doi.org/10.1177/0885328218790332DOI Listing
August 2018

Examining the influence of distal radius orientation on distal radioulnar joint contact using a finite element model.

Int J Numer Method Biomed Eng 2016 11 3;32(11). Epub 2016 Feb 3.

Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.

Distal radius malunion is a problem that is common to distal radius fractures and can affect the contact mechanics of the distal radioulnar joint (DRUJ). The goal of this study was to use a computational model of the DRUJ to investigate the influence distal radius orientation has on its contact mechanics. Detailed, finite element models of the radius and ulna bones were constructed from magnetic resonance imaging data. The orientation of the distal radius was rotated in 2° increments about three orthogonal axes representing dorsal-palmar rotation, radial-ulnar rotation and anteversion-retroversion. A computational model was used to predict joint contact at the DRUJ in each condition. Joint contact was found to be most sensitive to dorsal rotation of the distal radius, while radial and ulnar rotation did not substantially affect joint contact pressure. Slight retroversion was found to lower joint contact pressure. In most cases, more than 6° rotation in a given direction resulted in dislocation of the DRUJ, so that adaptation at the joint would be required to maintain articular contact. The joint contact model implemented in this study allowed the relationship between distal radius orientation and DRUJ contact to be examined systematically, in a way that is difficult to achieve using a cadaver-based approach. The results demonstrated the distal radius displacements most critical for maintaining healthy joint mechanics at the DRUJ. It is important that clinicians consider the influence of distal radius malunion and its treatment on DRUJ mechanics, in addition to its consequences for wrist function and forearm rotation. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/cnm.2766DOI Listing
November 2016

12-Month Coronary Angiography, Intravascular Ultrasound and Histology Evaluation of a Novel Fully Bioabsorbable Poly-L-Lactic Acid/Amorphous Calcium Phosphate Scaffolds in Porcine Coronary Arteries.

J Biomed Nanotechnol 2016 Apr;12(4):743-52

Our previous studies have confirmed the superior biocompatibility of the poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) scaffolds (PowerScaffold) compared to PLLA scaffolds and their similar 6-month radial strength compared with TAXUS stents. In order to conduct further dynamic observations on the performance of the PowerScaffold after 12-month implantation compared with the TAXUS stents. Twenty PowerScaffold and 20 TAXUS were implanted in porcine coronary arteries. At 12-month follow-up, Quantitative Coronary Angiography showed that the stent reference vessel diameter (3.19 ± 0.25 mm vs. 2.75 ± 0.22 mm, p < 0.05), the mean lumen diameter (3.07 ± 0.22 mm vs. 2.70 ± 0.17 mm, p < 0.05) and the late lumen gain (0.45 ± 0.07 mm vs. 0.06 ± 0.06 mm, p < 0.01) were all significantly greater with the PowerScaffold than the TAXUS. As well, Intravascular Ultrasound showed the stent reference vessel area (7.74 ± 0.48 mm2 vs. 6.96 ± 0.51 mm2, p < 0.05), the mean stent area (7.49 ± 0.46 mm2 vs. 6.53 ± 0.47 mm2, p < 0.05) and the mean lumen area (7.22 ± 0.50 mm2 vs. 6.00 ± 0.48 mm2, p < 0.01) were all significantly greater with the PowerScaffold than the TAXUS. The luminal patency rate of the PowerScaffold significantly increased from 72.45 ± 6.84% at 1 month to 93.54 ± 8.15% at 12 months (p < 0.01) while the TAXUS stents were associated with a non-significant decreasing trend (89.44 ± 8.44% vs. 86.53 ± 8.22%). Pathology indicated the average thickness of the struts degraded by 14.25 ± 3.04 μm at 1 month, 23.39 ± 2.45 μm at 6 months and 35.54 ± 2.20 μm at 12 months. Immunohistochemical examination showed that the expression of inflammatory factors NF-κB gradually decreased from 1-month to 12-month (36.79 ± 4.78 vs. 5.79 ± 2.85, P < 0.01). As the late lumen gain of arteries implanted with the PowerScaffold increases over time with the growth of vessels, it effectively reverse the late vascular negative remodeling observed with the TAXUS stents, providing a better option for lumen restoration treatment in clinical practice.
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http://dx.doi.org/10.1166/jbn.2016.2241DOI Listing
April 2016

A finite element model to investigate the effect of ulnar variance on distal radioulnar joint mechanics.

Int J Numer Method Biomed Eng 2017 02 8;33(2). Epub 2016 Jun 8.

Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.

Ulnocarpal impaction syndrome involves excessive loading of the ulnocarpal joint. Ulnar shortening osteotomies are an effective way to reduce ulnocarpal loading but alter contact mechanics at the distal radioulnar joint (DRUJ). This study used a computational model to investigate the relationship between ulnar length and DRUJ mechanics. Detailed, finite element models of the radius and ulna bones were constructed from magnetic resonance imaging data. The length of the ulna bone model was increased and decreased up to 5 mm in 1 mm increments. A computational model was used to predict joint contact at the DRUJ for each ulnar length. Lengthening the ulna caused a slight decrease in DRUJ contact pressure, with a more substantial decrease in contact area. Shortening the ulna caused a substantial increase in contact area, with a smaller increase in DRUJ contact pressure. The location of contact on the radial sigmoid notch changed with 2 mm lengthening and 3 mm shortening. The results of this study demonstrate the sensitivity of DRUJ contact to ulnar length changes, which may explain the DRUJ cartilage degeneration that often follows ulnar osteotomies. The joint contact model implemented in this study allowed the relationship between ulnar length and DRUJ contact to be examined systematically, in a way that is difficult to achieve through cadaveric experimentation. The results confirmed published experimental data showing an increased DRUJ contact pressure with ulnar shortening. It is important that clinicians consider the influence of ulnar osteotomies, not only on ulnocarpal loading but also on DRUJ mechanics. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/cnm.2790DOI Listing
February 2017

6-Month Follow-Up of a Novel Biodegradable Drug-Eluting Stent Composed of Poly-L-Lactic Acid and Amorphous Calcium Phosphate Nanoparticles in Porcine Coronary Artery.

J Biomed Nanotechnol 2015 Oct;11(10):1819-25

Rationale: We reported previously, in porcine coronary arteries, that the novel biodegradable PowerStent Absorb paclitaxel-eluting stent had improved and sustained structural strength and functional performance at one month post-implantation.

Objective: To report the stent performance at 6-month follow-up.

Methods And Results: Six PowerStent Absorb and six TAXUS stents were randomly implanted in the left anterior descending and right coronary arteries of six Tibet miniature pigs. Quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) images were obtained at the time of implantation (T0) and at 6 months (T6). Two animals were sacrificed at T6 for histopathological evaluation. At T6, QCA showed that the mean luminal vascular diameter (mLD) between the PowerStent and the TAXUS stents were similar (2.36 ± 0.38 vs. 2.61 ± 0.31, respectively). Based on the IVUS analysis, the mLD and the mean lumen cross-sectional area (mCSA) in the PowerStent-treated arteries were similar between T0 and T6 (mLD: 2.74 ± 0.13 vs. 2.70 ± 0.20 and mCSA: 6.81 ± 0.62 mm2 vs. 6.68 ± 0.94 mm2). Histopathology showed that the PowerStent stents were well apposed to the vessel wall with no recoil, strut fracture and thrombus formation. The stents were fully covered with a layer of endothelial cells.

Conclusions: At six-month post-implantation, the PowerStent Absorb stents maintained their structural strength and functional performance. The development of restenosis was controlled, no stent thrombosis was observed and the stents were fully re-endothelialized. These results suggest the PowerStent Absorb stent is safe and effective for up to 6 months when implanted in porcine coronary arteries.
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http://dx.doi.org/10.1166/jbn.2015.2102DOI Listing
October 2015

Generating Facial Expressions Using an Anatomically Accurate Biomechanical Model.

IEEE Trans Vis Comput Graph 2014 Nov;20(11):1519-29

This paper presents a computational framework for modelling the biomechanics of human facial expressions. A detailed high-order (Cubic-Hermite) finite element model of the human head was constructed using anatomical data segmented from magnetic resonance images. The model includes a superficial soft-tissue continuum consisting of skin, the subcutaneous layer and the superficial Musculo-Aponeurotic system. Embedded within this continuum mesh, are 20 pairs of facial muscles which drive facial expressions. These muscles were treated as transversely-isotropic and their anatomical geometries and fibre orientations were accurately depicted. In order to capture the relative composition of muscles and fat, material heterogeneity was also introduced into the model. Complex contact interactions between the lips, eyelids, and between superficial soft tissue continuum and deep rigid skeletal bones were also computed. In addition, this paper investigates the impact of incorporating material heterogeneity and contact interactions, which are often neglected in similar studies. Four facial expressions were simulated using the developed model and the results were compared with surface data obtained from a 3D structured-light scanner. Predicted expressions showed good agreement with the experimental data.
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http://dx.doi.org/10.1109/TVCG.2014.2339835DOI Listing
November 2014

Novel biodegradable drug-eluting stent composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles demonstrates improved structural and functional performance for coronary artery disease.

J Biomed Nanotechnol 2014 Jul;10(7):1194-204

Bioabsorbable drug-eluting stents (BDES) offer multiple advantages over a permanent bare metal stent (BMS) for coronary artery disease (CAD). However, current BDES remains two major issues: inferior radial strength and biocompatibility. PowerStent Absorb BDES, fabricated by co-formulating amorphous calcium phosphate (ACP) nanoparticles with poly-L-lactic acid (PLLA/ACP, 98/2, w/w) and 2% Paclitaxel (PAX, w/w) was designed to address these issues. Two cohorts of 6 miniature pigs were each implanted with PLLA/PAX (control, 2% PAX, w/w) or PowerStent Absorb BDES. After 1 month in-vivo study, histological analyses showed significantly reduced restenosis in the PowerStent Absorb BDES cohort relative to the control cohort (44.49 +/- 410.49% vs. 64.47 +/- 16.2%, p < 0.05). Stent recoil (21.57 +/- 5.36% vs. 33.81 +/- 11.49, P < 0.05) and inflammation (3.01 +/- 0.62 vs. 4.07 +/- 0.86, P < 0.01) were also obviously decreased. From in-vitro studies, PLLA/ACP/PAX stent tube maintained significantly greater radial strength than control group during 6 months in-vitro degradation (PLLA/ACP/PAX vs. PLLA/PAX: before hydrolysis: 82.4 +/- 1.9 N vs.74.8 +/- 3.8 N; 6 weeks: 73.9 +/- 1.8 N vs. 68.0 +/- 5.3 N; 3 months: 73.5 +/- 3.4 N vs.67.2 +/- 3.8 N; 6 months: 56.3 +/- 8.1 N vs. 57.5 +/- 4.9 N). Moreover, ACP facilitated the hydrolytic degradation of PLLA compared with control one (62.6% vs. 49.8%), meanwhile, it also increased the crystallinity of PLLA (58.4% vs. 50.7%) at 6 months. From SEM observations, ACP created nanometer pores that enlarge gradually to a micrometer scale as degradation proceeds. The changes of the porosity may result in greatly promoting re-endothelialization.
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http://dx.doi.org/10.1166/jbn.2014.1868DOI Listing
July 2014

Emulating facial biomechanics using multivariate partial least squares surrogate models.

Int J Numer Method Biomed Eng 2014 Nov 6;30(11):1103-20. Epub 2014 May 6.

Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.

A detailed biomechanical model of the human face driven by a network of muscles is a useful tool in relating the muscle activities to facial deformations. However, lengthy computational times often hinder its applications in practical settings. The objective of this study is to replace precise but computationally demanding biomechanical model by a much faster multivariate meta-model (surrogate model), such that a significant speedup (to real-time interactive speed) can be achieved. Using a multilevel fractional factorial design, the parameter space of the biomechanical system was probed from a set of sample points chosen to satisfy maximal rank optimality and volume filling. The input-output relationship at these sampled points was then statistically emulated using linear and nonlinear, cross-validated, partial least squares regression models. It was demonstrated that these surrogate models can mimic facial biomechanics efficiently and reliably in real-time.
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http://dx.doi.org/10.1002/cnm.2646DOI Listing
November 2014

Improved biocompatibility of poly(lactic-co-glycolic acid) orv and poly-L-lactic acid blended with nanoparticulate amorphous calcium phosphate in vascular stent applications.

J Biomed Nanotechnol 2014 Jun;10(6):900-10

Biodegradable polymers used as vascular stent coatings and stent platforms encounter a major challenge: biocompatibility in vivo, which plays an important role in in-stent restenosis (ISR). Co-formulating amorphous calcium phosphate (ACP) into poly(lactic-co-glycolic acid) (PLGA) or poly-L-lactic acid (PLLA) was investigated to address the issue. For stent coating applications, metal stents were coated with polyethylene-co-vinyl acetate/poly-n-butyl methacrylate (PEVA/PBMA), PLGA or PLGA/ACP composites, and implanted into rat aortas for one and three months. Comparing with both PEVA/PBMA and PLGA groups after one month, the results showed that stents coated with PLGA/ACP had significantly reduced restenosis (PLGA/ACP vs. PEVA/PBMA vs. PLGA: 21.24 +/- 2.59% vs. 27.54 +/- 1.19% vs. 32.12 +/- 3.93%, P < 0.05), reduced inflammation (1.25 +/- 0.35 vs. 1.77 +/- 0.38 vs. 2.30 +/- 0.21, P < 0.05) and increased speed of re-endothelialization (1.78 +/- 0.46 vs. 1.17 +/- 0.18 vs. 1.20 +/- 0.18, P < 0.05). After three months, the PLGA/ACP group still displayed lower inflammation score (1.33 +/- 0.33 vs. 2.27 +/- 0.55, P < 0.05) and higher endothelial scores (2.33 +/- 0.33 vs. 1.20 +/- 0.18, P < 0.05) as compared with the PEVA/PBMA group. Moreover, for stent platform applications, PLLA/ACP stent tube significantly reduced the inflammatory cells infiltration in the vessel walls of rabbit iliac arteries relative to their PLLA cohort (NF-kappaB-positive cells: 23.31 +/- 2.33/mm2 vs. 9.34 +/- 1.35/mm2, P < 0.05). No systemic biochemical or pathological evidence of toxicity was found in either PLGA/ACP or PLLA/ACP. The co-formulation of ACP into PLGA and PLLA resulted in improved biocompatibility without systemic toxicity.
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http://dx.doi.org/10.1166/jbn.2014.1856DOI Listing
June 2014

Estimating muscle activation patterns using a surrogate model of facial biomechanics.

Annu Int Conf IEEE Eng Med Biol Soc 2013 ;2013:7172-5

Analyzing the muscle activities that drive the expressive facial gestures can be a useful tool in assessing one's emotional state of mind. Since the skin motion is much easier to measure in comparison to the actual electrical excitation signal of facial muscles, a biomechanical model of the human face driven by these muscles can be a useful tool in relating the geometric information to the muscle activity. However, long computational time often hinders its practicality. The objective of this study was to replace the precise but computationally demanding biomechanical model by a much faster multivariate meta-model (surrogate model), such that a significant speedup (real-time interactive speed) can be achieved and data from the biomechanical model can be practically exploited. Using the proposed surrogate, muscle activation patterns of six key facial expressions were estimated in the iterative fit from the structured-light scanned geometric information.
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http://dx.doi.org/10.1109/EMBC.2013.6611212DOI Listing
September 2015

Randomised trial comparing the recording ability of a novel, electronic emergency documentation system with the AHA paper cardiac arrest record.

Emerg Med J 2014 Oct 29;31(10):833-9. Epub 2013 Jul 29.

Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, USA.

Objective: To evaluate the ability of an electronic system created at the University of Washington to accurately document prerecorded VF and pulseless electrical activity (PEA) cardiac arrest scenarios compared with the American Heart Association paper cardiac arrest record.

Methods: 16 anaesthesiology residents were randomly assigned to view one of two prerecorded, simulated VF and PEA scenarios and asked to document the event with either the paper or electronic system. Each subject then repeated the process with the other video and documentation method. Five types of documentation errors were defined: (1) omission, (2) specification, (3) timing, (4) commission and (5) noise. The mean difference in errors between the paper and electronic methods was analysed using a single factor repeated measures ANOVA model.

Results: Compared with paper records, the electronic system omitted 6.3 fewer events (95% CI -10.1 to -2.5, p=0.003), which represents a 28% reduction in omission errors. Users recorded 2.9 fewer noise items (95% CI -5.3 to -0.6, p=0.003) when compared with paper, representing a 36% decrease in redundant or irrelevant information. The rate of timing (Δ=-3.2, 95% CI -9.3 to 3.0, p=0.286) and commission (Δ=-4.4, 95% CI -9.4 to 0.5, p=0.075) errors were similar between the electronic system and paper, while the rate of specification errors were about a third lower for the electronic system when compared with the paper record (Δ=-3.2, 95% CI -6.3 to -0.2, p=0.037).

Conclusions: Compared with paper documentation, documentation with the electronic system captured 24% more critical information during a simulated medical emergency without loss in data quality.
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http://dx.doi.org/10.1136/emermed-2013-202512DOI Listing
October 2014

On modelling large deformations of heterogeneous biological tissues using a mixed finite element formulation.

Comput Methods Biomech Biomed Engin 2015 29;18(5):477-84. Epub 2013 Jul 29.

a Auckland Bioengineering Institute, The University of Auckland , Level 6, 70 Symonds Street, Auckland , New Zealand.

This study addresses the issue of modelling material heterogeneity of incompressible bodies. It is seen that when using a mixed (displacement-pressure) finite element formulation, the basis functions used for pressure field may not be able to capture the nonlinearity of material parameters, resulting in pseudo-residual stresses. This problem can be resolved by modifying the constitutive relation using Flory's decomposition of the deformation gradient. A two-parameter Mooney-Rivlin constitutive relation is used to demonstrate the methodology. It is shown that for incompressible materials, the modification does not alter the mechanical behaviour described by the original constitutive model. In fact, the modified constitutive equation shows a better predictability when compared against analytical solutions. Two strategies of describing the material variation (i.e. linear and step change) are explained, and their solutions are evaluated for an ideal two-material interfacing problem. When compared with the standard tied coupling approach, the step change method exhibited a much better agreement because of its ability to capture abrupt changes of the material properties. The modified equation in conjunction with integration point-based material heterogeneity is then used to simulate the deformations of heterogeneous biological structures to illustrate its applications.
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http://dx.doi.org/10.1080/10255842.2013.818662DOI Listing
December 2015

Dermatological complications of circumcision: lesson learned from cases in a pediatric dermatology practice.

Pediatr Dermatol 2013 Sep-Oct;30(5):519-28. Epub 2013 May 20.

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

We discuss 11 cases of boys who presented with dermatologic complications of circumcision in an outpatient pediatric dermatology clinic. A medical practitioner had previously circumcised all patients during the newborn period. The majority of cases were found incidentally during initial thorough dermatologic examination. Late cutaneous complications included penile skin bridge, glandular adhesion of remnant foreskin, concealed penis, and a penile epidermal inclusion cyst. Minor surgical procedures under local anesthesia were performed in all but two cases. These cases should help dermatologists recognize the common late cutaneous complications of male newborn circumcision and provide insight into potential options for early intervention and management.
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http://dx.doi.org/10.1111/pde.12140DOI Listing
April 2014

OpenCMISS: a multi-physics & multi-scale computational infrastructure for the VPH/Physiome project.

Prog Biophys Mol Biol 2011 Oct 7;107(1):32-47. Epub 2011 Jul 7.

Auckland Bioengineering Institute (ABI), The University of Auckland, New Zealand.

The VPH/Physiome Project is developing the model encoding standards CellML (cellml.org) and FieldML (fieldml.org) as well as web-accessible model repositories based on these standards (models.physiome.org). Freely available open source computational modelling software is also being developed to solve the partial differential equations described by the models and to visualise results. The OpenCMISS code (opencmiss.org), described here, has been developed by the authors over the last six years to replace the CMISS code that has supported a number of organ system Physiome projects. OpenCMISS is designed to encompass multiple sets of physical equations and to link subcellular and tissue-level biophysical processes into organ-level processes. In the Heart Physiome project, for example, the large deformation mechanics of the myocardial wall need to be coupled to both ventricular flow and embedded coronary flow, and the reaction-diffusion equations that govern the propagation of electrical waves through myocardial tissue need to be coupled with equations that describe the ion channel currents that flow through the cardiac cell membranes. In this paper we discuss the design principles and distributed memory architecture behind the OpenCMISS code. We also discuss the design of the interfaces that link the sets of physical equations across common boundaries (such as fluid-structure coupling), or between spatial fields over the same domain (such as coupled electromechanics), and the concepts behind CellML and FieldML that are embodied in the OpenCMISS data structures. We show how all of these provide a flexible infrastructure for combining models developed across the VPH/Physiome community.
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http://dx.doi.org/10.1016/j.pbiomolbio.2011.06.015DOI Listing
October 2011

In vitro and in vivo degradation of poly(D, L-lactide-co-glycolide)/amorphous calcium phosphate copolymer coated on metal stents.

J Biomed Mater Res A 2011 Mar 25;96(4):632-8. Epub 2011 Jan 25.

Biomedical Engineering and Biotechnology Doctoral Program, University of Massachusetts, Lowell, Massachusetts 01854, USA.

The purpose of this study was to optimize a novel biodegradable polymer for drug eluting stent (DES) applications. Degradation profiles of different poly(D,L-lactide-co-glycolide)/amorphous calcium phosphate (PLGA/ACP) composites coated on stents were studied both in vitro and in vivo for three months. For the in vitro study, stents were immersed into the phosphate buffered saline (37 °C, pH 7.4) with constant shaking. The polymer weight loss was measured weekly and morphological changes were analyzed. The results demonstrated that approximately 60% of polymer was degraded within the three-month period and there was no significant difference between the different PLGA/ACP composites. However, the composite of 50% PLGA (65/35) with 50% ACP showed a slightly faster degradation rate than other composites. Morphologically, all stent surfaces changed from a micro-porous before degradation to a corrugated solid micro-net-like structure at two months post degradation. Based on in vitro results, 65% PLGA (65/35) with 35% ACP) coated stents were selected and implanted into rat aortas (n = 12) for the in vivo study. Microscopic observation showed that no composite was found on any of the implanted stents at 12 weeks post implantation, which indicated the selected PLGA/ACP composite is desired for DES applications.
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http://dx.doi.org/10.1002/jbm.a.33016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291328PMC
March 2011

Trans-iliac rat aorta stenting: a novel high throughput preclinical stent model for restenosis and thrombosis.

J Surg Res 2011 Mar 9;166(1):e91-5. Epub 2010 Dec 9.

Division of Cardiothoracic Surgery, Brown Medical School, Providence, Rhode Island, USA.

Background: Currently, preclinical stent development requires elaborate large animal models, which are time consuming and expensive. We herein report a high throughput rat aorta stenting model which could provide a rapid and low-cost platform for preclinical stent development.

Methods: A total of 86 metal stents (316L stainless steel 13 mm, VasoTech, Inc.) coated with poly (D, L-lactide-co-glycolide)/amorphous calcium phosphate (PLGA/ACP) copolymer were pre-mounted on 1.5 mm × 15 mm balloon catheters and were implanted into aspirin treated Sprague-Dawley rats (500-700 g) initially using either direct placement in the abdominal aorta (group A, n = 7) or a trans-iliac approach (cut-down, group B, n = 79). The surviving rats were sacrificed at 1, 2, 4, and 12 wk post-implantation and the stented arteries were analyzed histopathologically.

Results: Four rats died in group A and nine rats died in group B within 48 h post-stent implantation (mortality: 57% versus 11%, P < 0.05). All animals that died had stent thrombosis/paralysis with visible thrombus on necropsy. Histologically, neointimal growth peaked at approximately 4 wk post-implantation.

Conclusion: This result suggests that human-sized stents can be successfully implanted into the rat aorta via iliac artery insertion with a significantly higher survival rate than trans-aorta implantation. The model system allows rapid (4-12 wk) assessment of stent biocompatibility with mortality/paralysis used as an indicator of stent thrombosis.
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http://dx.doi.org/10.1016/j.jss.2010.11.882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071592PMC
March 2011

Paclitaxel/sirolimus combination coated drug-eluting stent: in vitro and in vivo drug release studies.

J Pharm Biomed Anal 2011 Mar 10;54(4):807-11. Epub 2010 Nov 10.

Biomedical Engineering and Biotechnology Doctoral Program, University of Massachusetts, Lowell, MA 01854, USA.

Paclitaxel and sirolimus are the two major drugs for the treatment of coronary arterial disease in current drug-eluting stents. The two drugs can effectively inhibit the in-stent restenosis through their independent pathways and show synergistic effect in preventing tumor tissue growth. We hypothesize that the combination of the two drugs in a drug-eluting stent (DES) can also effectively suppress the neointima growth in the stented artery. The present work was focused on the investigation of paclitaxel/sirolimus combination release profiles from a novel biodegradable polymer (poly (D, L-lactide-co-glycolide)/amorphous calcium phosphate, PLGA/ACP) coated stent both in vitro and in vivo. For the in vitro, the drug releasing profiles were characterized by measuring the drug concentration in a drug release medium (Dulbecco's phosphate buffered saline, DPBS, pH 7.4) at predetermined time points. For the in vivo, a rat aorta stenting model was employed. The results showed that both paclitaxel and sirolimus had a two-phase release profile both in vitro and in vivo, which is similar to the drug release profile of their individual coated DESs, and there is no evident of interference between two drugs. The data suggest that paclitaxel and sirolimus can be combined pharmacokinetically in a DES for the treatment of coronary arterial diseases.
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http://dx.doi.org/10.1016/j.jpba.2010.10.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008332PMC
March 2011

Drug-eluting stents.

Int J Clin Exp Med 2010 Jul 15;3(3):192-201. Epub 2010 Jul 15.

Coronary artery disease (CAD) is currently a leading cause of death worldwide. Drug-eluting stents (DESs) have been dominant for the treatment of CAD in the interventional cardiology world owing to their efficacy in significantly reducing restenosis. However, late stage stent thrombosis has become a major concern. Stent platform, drug delivery vehicle and type of drug are three parts of DES and each part affects the performance of the DES. Aiming to provide a clue for the design of future DES, this review focuses on the development of the three major components of DES and their roles in restenosis and thrombosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929945PMC
July 2010

High turnover of ezrin T567 phosphorylation: conformation, activity, and cellular function.

Am J Physiol Cell Physiol 2007 Sep 6;293(3):C874-84. Epub 2007 Jun 6.

241 LSA, Dept. of Molecular and Cell Biology, Univ. of California, Berkeley, CA 94720-3200, USA.

In its dormant state, the membrane cytoskeletal linker protein ezrin takes on a NH(2) terminal-to-COOH terminal (N-C) binding conformation. In vitro evidence suggests that eliminating the N-C binding conformation by Thr(567) phosphorylation leads to ezrin activation. Here, we found for resting gastric parietal cells that the levels of ezrin phosphorylation on Thr(567) are low and can be increased to a small extent ( approximately 40%) by stimulating secretion via the cAMP pathway. Treatment of cells with protein phosphatase inhibitors led to a rapid, dramatic increase in Thr(567) phosphorylation by 400% over resting levels, prompting the hypothesis that ezrin activity is regulated by turnover of phosphorylation on Thr(567). In vitro and in vivo fluorescence resonance energy transfer analysis demonstrated that Thr(567) phosphorylation opens the N-C interaction. However, even in the closed conformation, ezrin localizes to membranes by an exposed NH(2) terminal binding site. Importantly, the opened phosphorylated form of ezrin more readily cosediments with F-actin and binds more tightly to membrane than the closed forms. Furthermore, fluorescence recovery after photobleaching analysis in live cells showed that the Thr567Asp mutant had longer recovery times than the wild type or the Thr567Ala mutant, indicating the Thr(567)-phosphorylated form of ezrin is tightly associated with F-actin and the membrane, restricting normal activity. These data demonstrate and emphasize the functional importance of reversible phosphorylation of ezrin on F-actin binding. A novel model is proposed whereby ezrin and closely associated kinase and phosphatase proteins represent a motor complex to maintain a dynamic relationship between the varying membrane surface area and filamentous actin length.
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http://dx.doi.org/10.1152/ajpcell.00111.2007DOI Listing
September 2007