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Effect of itraconazole on the pharmacokinetics of faldaprevir in healthy subjects.

Pharmazie 2021 May;76(5):189-194

Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.

Faldaprevir (FDV), a substrate of CYP3A/P-glycoprotein (P-gp), is a selective inhibitor of the hepatitis C virus (HCV) NS3/4 protease. FDV is currently under clinical development for application in interferon-free treatment regimens for patients with chronic HCV infection. Understanding the drug-drug interaction potential of FDV is critical, as certain drug combinations may facilitate the more rapid achievement of steady-state-that is, the ideal drug concentration and balanced metabolic cycle of absorption and elimination that optimize drug efficacy. Read More

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Reliability-based tolerance redesign of mechanical assemblies using Jacobian-Torsor model.

Sci Prog 2021 Apr-Jun;104(2):368504211013227

School of Mechanical Engineering and Automation, Northeastern University, Shenyang, China.

The purpose of this paper is to present a new method to redesign dimensional and geometric tolerances of mechanical assemblies at a lower cost and with higher reliability. A parametric Jacobian-Torsor model is proposed to conduct tolerance analysis of mechanical assembly. A reliability-based tolerance optimization model is established. Read More

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Advanced Biophysical Model to Capture Channel Variability for EQS Capacitive HBC.

IEEE Trans Biomed Eng 2021 Apr 19;PP. Epub 2021 Apr 19.

Human Body Communication (HBC) has come up as a promising alternative to traditional radio frequency (RF) Wireless Body Area Network (WBAN) technologies. This is essentially due to HBC providing a broadband communication channel with enhanced signal security in the physical layer due to lower radiation from the human body as compared to its RF counterparts. An in-depth understanding of the mechanism for the channel loss variability and associated biophysical model needs to be developed before electro-quasistatic (EQS) HBC can be used more frequently in WBAN consumer and medical applications. Read More

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Correlation of the human pubic symphysis surface with age-at-death: a novel quantitative method based on a bandpass filter.

Int J Legal Med 2021 Apr 15. Epub 2021 Apr 15.

Department of Legal Medicine, Toxicology and Physical Anthropology, University of Granada, Parque Tecnológico de La Salud, Av. de la Investigación, 11, 18016, Granada, Spain.

Age-at-death estimation from skeletal remains typically utilizes the roughness of pubic symphysis articular surfaces. This study presents a new quantitative method adapting a tool from geometric morphometrics, bandpass filtering of partial warp bending energy to extract only age-related changes of the surfaces. The study sample consisted of 440 surface-scanned symphyseal pubic bones from men between 14 and 82 years of age, which were landmarked with 102 fixed and surface semilandmarks. Read More

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Pharmacokinetic comparison between a fixed-dose combination of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg and a corresponding loose combination of fimasartan/amlodipine 60/25 mg and hydrochlorothiazide 25 mg in healthy subjects.

Transl Clin Pharmacol 2021 Mar 22;29(1):53-64. Epub 2021 Mar 22.

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea.

For the treatment of hypertension, fixed-dose combinations (FDCs) of antihypertensive drugs can provide complementary benefits from improved compliance and cost-effectiveness compared with loose combinations of corresponding drugs. A new FDC of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg is undergoing clinical development. A randomized, open-label, single-dose, 3-period, 3-sequence, partially replicated crossover phase 1 study was conducted to compare the pharmacokinetics (PKs) between the FDC of fimasartan/amlodipine/hydrochlorothiazide 60/10/25 mg and a loose combination of a dual-combination FDC (fimasartan/amlodipine 60/10 mg) and hydrochlorothiazide 25 mg. Read More

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Phononic Crystals Applied to Localised Surface Haptics.

IEEE Trans Haptics 2021 Apr 12;PP. Epub 2021 Apr 12.

Metamaterials are solid lattices with periodicitiescommensurate with desired wavelengths. Their geometric fea-tures can endow the bulk material with unusual properties suchas, inter alia, negative indices of refraction or unique absorbingqualities. Mesoscale metamaterials can be designed to causethe occurence of phononic crystals in the ultrasonic domain. Read More

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A random parameter negative binomial model for signalized intersection accidents in Seoul, Korea.

Int J Inj Contr Saf Promot 2021 Apr 9:1-11. Epub 2021 Apr 9.

Department of Transportation Engineering and Department of Smart Cities, University of Seoul, Seoul, Korea.

A variety of statistical models were generally considered to better understand the relationship between crash occurrences and diverse factors. However, most of statistical models adapted fixed parameters which cannot incorporate time variation or sement-specific effects. To relieve this problem, this study focuses on a traffic accident frequency model using a random parameter negative binomial approach. Read More

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Assessment of Registration Methods for Thermal Infrared and Visible Images for Diabetic Foot Monitoring.

Sensors (Basel) 2021 Mar 24;21(7). Epub 2021 Mar 24.

IACTEC Medical Technology Group, Instituto de Astrofísica de Canarias (IAC), 38205 San Cristóbal de La Laguna, Spain.

This work presents a revision of four different registration methods for thermal infrared and visible images captured by a camera-based prototype for the remote monitoring of diabetic foot. This prototype uses low cost and off-the-shelf available sensors in thermal infrared and visible spectra. Four different methods (Geometric Optical Translation, Homography, Iterative Closest Point, and Affine transform with Gradient Descent) have been implemented and analyzed for the registration of images obtained from both sensors. Read More

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Spatial Transformer for 3D Point Clouds.

IEEE Trans Pattern Anal Mach Intell 2021 Apr 1;PP. Epub 2021 Apr 1.

Deep neural networks can efficiently process 3D point clouds. At each point convolution layer, local features can be learned from local neighborhoods of point clouds. These features are combined together for further processing to extract the semantic information encoded in the point cloud. Read More

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Degenerate isostable reduction for fixed-point and limit-cycle attractors with defective linearizations.

Dan Wilson

Phys Rev E 2021 Feb;103(2-1):022211

Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, Tennessee 37996, USA.

Isostable coordinates provide a convenient framework for understanding the transient behavior of dynamical systems with stable attractors. These isostable coordinates are often used to characterize the slowest decaying eigenfunctions of the Koopman operator; by neglecting the rapidly decaying Koopman eigenfunctions a reduced order model can be obtained. Existing work has focused primarily on nondegenerate isostable coordinates, that is, isostable coordinates that are associated with eigenvalues that have identical algebraic and geometric multiplicities. Read More

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February 2021

When does Wenzel's extension of Young's equation for the contact angle of droplets apply? A density functional study.

J Chem Phys 2020 May;152(19):194707

Institut für Physik, Johannes Gutenberg Universität Mainz, 55099 Mainz, Germany.

The contact angle of a liquid droplet on a surface under partial wetting conditions differs for a nanoscopically rough or periodically corrugated surface from its value for a perfectly flat surface. Wenzel's relation attributes this difference simply to the geometric magnification of the surface area (by a factor r), but the validity of this idea is controversial. We elucidate this problem by model calculations for a sinusoidal corrugation of the form z(y) = Δ cos(2πy/λ), for a potential of short range σ acting from the wall on the fluid particles. Read More

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Effects of Molecular Properties on Adsorption of Six-Carbon VOCs by Activated Carbon in a Fixed Adsorber.

ACS Omega 2021 Mar 18;6(8):5825-5835. Epub 2021 Feb 18.

Department of Chemical and Materials Engineering, National Ilan University, No. 1, Section 1, Shennong Road, Yilan City, Yilan County, Taiwan 260, ROC.

Gravimetric adsorption equipment with a microbalance was used to measure the adsorption of volatile organic compounds (VOCs) by activated carbon from 288 to 313 K. VOCs [-hexane, cyclohexane, 1-hexene, 2-methylpentane, 3-methylpentane, 2,2-dimethylbutane, acetone, butanone, and 2-pentanone (Pentan-2-one)] were used as adsorbates in the adsorption system. Considering the geometric barrier, the critical diameter, and the boiling point, the adsorption capacities for six-carbon (C) alkane isomers decrease in the order of -hexane, 3-methylpentane, and 2-methylpentane. Read More

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Formation Tracking Control for Multi-Agent Networks with Fixed Time Convergence via Terminal Sliding Mode Control Approach.

Sensors (Basel) 2021 Feb 18;21(4). Epub 2021 Feb 18.

School of Mathematics, Hefei University of Technology, Hefei 230009, China.

This paper investigates formation tracking control for multi-agent networks with fixed time convergence. The control task is that the follower agents are required to form a prescribed formation within a fixed time and the geometric center of the formation moves in sync with the leader. First, an error system is designed by using the information of adjacent agents and a new control protocol is designed based on the error system and terminal sliding mode control (TSMC). Read More

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February 2021

Driver glare exposure with different vehicle frontlighting systems.

J Safety Res 2021 02 8;76:228-237. Epub 2021 Jan 8.

Departamento de Ingeniería del Transporte, Territorio y Urbanismo, Universidad Politécnica de Madrid, Spain. Electronic address:

Introduction: Highway safety performance at night has received less attention in research than daytime, despite the higher accident rates occurring under night-time conditions. This study presents a procedure to assess the potential hazard for drivers created by headlight glare and its interaction with the geometric design of highways.

Method: The proposed procedure consists of a line-of-sight analysis performed by a geoprocessing model in geographic information systems to determine whether the rays of light that connect headlights and oncoming drivers are obstructed by either the roadway or its roadsides. Read More

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February 2021

Pharmacokinetic Interaction Among Ezetimibe, Rosuvastatin, and Telmisartan.

Clin Pharmacol Drug Dev 2021 Mar 1. Epub 2021 Mar 1.

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

To evaluate the pharmacokinetic interactions among rosuvastatin, ezetimibe, and telmisartan, a randomized, open-label, 3-period, 6-sequence crossover study was conducted in healthy subjects. Subjects received one of the following treatments once daily for 7 days in each period with a 1-week washout: a fixed-dose combination of ezetimibe/rosuvastatin 10/20 mg, telmisartan 80 mg, combination therapy of ezetimibe/rosuvastatin 10/20 mg, or telmisartan 80 mg. Blood samples were collected up to 24 hours postdose at steady state. Read More

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Pharmacokinetic and Pharmacodynamic Comparison of Two Formulations of a Fixed-Dose Combination of Gemigliptin/Rosuvastatin 50/20 mg: A Randomized, Open-Label, Single-Dose, Two-Way Crossover Study.

Drug Des Devel Ther 2021 17;15:651-658. Epub 2021 Feb 17.

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

Purpose: A fixed-dose combination (FDC) of gemigliptin/rosuvastatin 50/20 mg as a monolayer tablet has been used to treat patients with both type 2 diabetes mellitus and dyslipidemia. To improve the stability of the FDC, a new FDC formulation as a bilayer tablet was developed. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the FDC of gemigliptin/rosuvastatin 50/20 mg between the newly developed bilayer tablet and the approved monolayer tablet in healthy subjects. Read More

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February 2021

3D Models Reveal the Influence of Achilles Subtendon Twist on Strain and Energy Storage.

Front Bioeng Biotechnol 2021 5;9:539135. Epub 2021 Feb 5.

Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States.

The Achilles tendon (AT) has complex function in walking, exchanging energy due to loading by the triceps surae muscles. AT structure comprises three subtendons which exhibit variable twist among themselves and between individuals. Our goal was to create 3D finite element (FE) models to explore AT structure-function relationships. Read More

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February 2021

GEUINF: Real-Time Visualization of Indoor Facilities Using Mixed Reality.

Sensors (Basel) 2021 Feb 5;21(4). Epub 2021 Feb 5.

Computer Graphics and Geomatics Group of Jaén, University of Jaén, 23071 Jaén, Spain.

Mixed reality (MR) enables a novel way to visualize virtual objects on real scenarios considering physical constraints. This technology arises with other significant advances in the field of sensors fusion for human-centric 3D capturing. Recent advances for scanning the user environment, real-time visualization and 3D vision using ubiquitous systems like smartphones allow us to capture 3D data from the real world. Read More

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February 2021

Geometric Regularized Hopfield Neural Network for Medical Image Enhancement.

Int J Biomed Imaging 2021 22;2021:6664569. Epub 2021 Jan 22.

Department of Computer Science, University of South Dakota, Vermillion, SD 57069, USA.

One of the major shortcomings of Hopfield neural network (HNN) is that the network may not always converge to a fixed point. HNN, predominantly, is limited to local optimization during training to achieve network stability. In this paper, the convergence problem is addressed using two approaches: (a) by sequencing the activation of a continuous modified HNN (MHNN) based on the geometric correlation of features within various image hyperplanes via pixel gradient vectors and (b) by regulating geometric pixel gradient vectors. Read More

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January 2021

Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial.

Lancet 2021 02 29;397(10275):682-694. Epub 2021 Jan 29.

Global Research in Infectious Diseases, Rio de Janeiro, Brazil. Electronic address:

Background: As part of the accelerated development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we report a dose-finding and adjuvant justification study of SCB-2019, a protein subunit vaccine candidate containing a stabilised trimeric form of the spike (S)-protein (S-Trimer) combined with two different adjuvants.

Methods: Our study is a phase 1, randomised, double-blind placebo-controlled trial at a specialised clinical trials centre in Australia. We enrolled healthy adult volunteers in two age groups: younger adults (aged 18-54 years) and older adults (aged 55-75 years). Read More

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February 2021

Imaging performance of a high-field in-line magnetic resonance imaging linear accelerator with a patient rotation system for fixed-gantry radiotherapy.

Phys Imaging Radiat Oncol 2020 Oct 18;16:130-133. Epub 2020 Nov 18.

Ingham Institute for Applied Medical Research, 1 Campbell St, Liverpool, NSW 2170, Australia.

This paper describes the imaging performance of a high-field in-line MRI linear accelerator with a patient rotation system in-situ. Signal quality was quantified using signal-to-noise ratio (SNR) and RF uniformity maps. B0-field inhomogeneity was assessed using magnetic field mapping. Read More

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October 2020

Pharmacokinetic effects of proton pump inhibitors on the novel PARP inhibitor fluzoparib: a single-arm, fixed-sequence trial in male healthy volunteers.

Invest New Drugs 2021 Jun 9;39(3):796-802. Epub 2021 Jan 9.

Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Tongzipo Road, Yuelu District, Hunan, Changsha, 410013, People's Republic of China.

Purpose To assess the pharmacokinetic (PK) effect of proton pump inhibitors on the novel poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor fluzoparib, and observe the safety of its co-administration with omeprazole. Patients and methods Sixteen male healthy volunteers (HVs) were enrolled in a single-center, single-arm, open-label, fixed-sequence study. HVs took fluzoparib (100 mg, p. Read More

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Spherical Deformable U-Net: Application to Cortical Surface Parcellation and Development Prediction.

IEEE Trans Med Imaging 2021 Apr 1;40(4):1217-1228. Epub 2021 Apr 1.

Convolutional Neural Networks (CNNs) have achieved overwhelming success in learning-related problems for 2D/3D images in the Euclidean space. However, unlike in the Euclidean space, the shapes of many structures in medical imaging have an inherent spherical topology in a manifold space, e.g. Read More

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Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects.

BMC Pulm Med 2021 Jan 7;21(1):18. Epub 2021 Jan 7.

P-One Clinic, Keikokai Medical Corporation, Tokyo, Japan.

Background: A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler device (IND/GLY/MF) is being developed for treatment of asthma. Read More

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January 2021

A Systematic Approach to Dissection of the Equine Brain-Evaluation of a Species-Adapted Protocol for Beginners and Experts.

Front Neuroanat 2020 18;14:614929. Epub 2020 Dec 18.

Section of Clinical and Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig Maximilians University, Munich, Germany.

Introduction of new imaging modalities for the equine brain have refocused attention on the horse as a natural model for ethological, neuroanatomical, and neuroscientific investigations. As opposed to imaging studies, strategies for equine neurodissection still lack a structured approach, standardization and reproducibility. In contrast to other species, where adapted protocols for sampling have been published, no comparable guideline is currently available for equids. Read More

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December 2020

Causal Geometry.

Entropy (Basel) 2020 Dec 26;23(1). Epub 2020 Dec 26.

Allen Discovery Center, Tufts University, Medford, MA 02155, USA.

Information geometry has offered a way to formally study the efficacy of scientific models by quantifying the impact of model parameters on the predicted effects. However, there has been little formal investigation of causation in this framework, despite causal models being a fundamental part of science and explanation. Here, we introduce causal geometry, which formalizes not only how outcomes are impacted by parameters, but also how the parameters of a model can be intervened upon. Read More

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December 2020

Indirect reduced-order modelling: using nonlinear manifolds to conserve kinetic energy.

Proc Math Phys Eng Sci 2020 Nov 18;476(2243):20200589. Epub 2020 Nov 18.

Department of Mechanical Engineering, University of Bristol, Bristol BS8 1TR, UK.

Nonlinear dynamic analysis of complex engineering structures modelled using commercial finite element (FE) software is computationally expensive. Indirect reduced-order modelling strategies alleviate this cost by constructing low-dimensional models using a static solution dataset from the FE model. The applicability of such methods is typically limited to structures in which (a) the main source of nonlinearity is the quasi-static coupling between transverse and in-plane modes (i. Read More

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November 2020

Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study.

Lancet Oncol 2021 01 21;22(1):85-97. Epub 2020 Dec 21.

Sana Klinikum Offenbach, Offenbach, Germany.

Background: A subcutaneous formulation of pertuzumab and trastuzumab with recombinant human hyaluronidase in one ready-to-use, fixed-dose combination vial (pertuzumab, trastuzumab, and hyaluronidase-zzxf) was approved by the US Food and Drug Administration (FDA) on June 29, 2020. We report the primary analysis of the FeDeriCa study, which was designed to assess the pharmacokinetics, efficacy, and safety of the fixed-dose subcutaneous formulation compared to intravenous pertuzumab plus trastuzumab in patients with HER2-positive early breast cancer in the neoadjuvant-adjuvant setting.

Methods: FeDeriCa, a randomised, open-label, international, multicentre, non-inferiority, phase 3 study, was done across 106 sites in 19 countries. Read More

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January 2021

Quantitative PET Imaging and Clinical Parameters as Predictive Factors for Patients With Cervical Carcinoma: Implications of a Prediction Model Generated Using Multi-Objective Support Vector Machine Learning.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820983804

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Purpose: Quantitative features from pre-treatment positron emission tomography (PET) have been used to predict treatment outcomes for patients with cervical carcinoma. The purpose of this study is to use quantitative PET imaging features and clinical parameters to construct a multi-objective machine learning predictive model.

Materials/methods: Seventy-five patients with stage IB2-IVA disease treated at our institution from 2009-2012 were analyzed. Read More

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December 2020

Using a radiopaque marker with radiography for evaluating colonic transit by geometric center in conscious rats: A novel method.

Auton Neurosci 2021 01 4;230:102760. Epub 2020 Dec 4.

Department of Acupuncture and Moxibustion, Meiji University of Integrative Medicine, Honoda, Hiyoshi-cho, Nantan-shi, Kyoto 629-0392, Japan; Department of Acupuncture and Moxibustion, Faculty of Health Science, Teikyo Heisei University, 2-51-4 Higashi-ikebukuro, Toshima-ku, Tokyo 170-8445, Japan. Electronic address:

This study developed a new method using radiopaque markers under X-ray to measure rat colonic transit by geometric center repeatedly and/or over a time series in the same individually. Additionally, the utility of this method was shown by elucidating the innervation of the autonomic nerve on colonic transit in detail with a pharmacological technique in conscious rats. An in-dwelling silastic cannula was inserted into the cecum and the proximal part was moved through the abdominal wall, where it was fixed to the posterior neck skin. Read More

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January 2021