137 results on '"Davis TJ"'
Search Results
2. Auditory perception of motor vehicle travel paths.
- Author
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Ashmead DH, Grantham DW, Maloff ES, Hornsby B, Nakamura T, Davis TJ, Pampel F, Rushing EG, Ashmead, Daniel H, Grantham, D Wesley, Maloff, Erin S, Hornsby, Benjamin, Nakamura, Takabun, Davis, Timothy J, Pampel, Faith, and Rushing, Erin G
- Abstract
Objective: These experiments address concerns that motor vehicles in electric engine mode are so quiet that they pose a risk to pedestrians, especially those with visual impairments.Background: The "quiet car" issue has focused on hybrid and electric vehicles, although it also applies to internal combustion engine vehicles. Previous research has focused on detectability of vehicles, mostly in quiet settings. Instead, we focused on the functional ability to perceive vehicle motion paths.Method: Participants judged whether simulated vehicles were traveling straight or turning, with emphasis on the impact of background traffic sound.Results: In quiet, listeners made the straight-or-turn judgment soon enough in the vehicle's path to be useful for deciding whether to start crossing the street. This judgment is based largely on sound level cues rather than the spatial direction of the vehicle. With even moderate background traffic sound, the ability to tell straight from turn paths is severely compromised. The signal-to-noise ratio needed for the straight-or-turn judgment is much higher than that needed to detect a vehicle.Conclusion: Although a requirement for a minimum vehicle sound level might enhance detection of vehicles in quiet settings, it is unlikely that this requirement would contribute to pedestrian awareness of vehicle movements in typical traffic settings with many vehicles present.Application: The findings are relevant to deliberations by government agencies and automobile manufacturers about standards for minimum automobile sounds and, more generally, for solutions to pedestrians' needs for information about traffic, especially for pedestrians with sensory impairments. [ABSTRACT FROM AUTHOR]- Published
- 2012
3. Alcohol's actions on neuronal nicotinic acetylcholine receptors.
- Author
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Davis TJ and de Fiebre CM
- Abstract
Although it has been known for many years that alcoholism and tobacco addiction often co-occur, relatively little information is available on the biological factors that regulate the co-use and abuse of nicotine and alcohol. In the brain, nicotine acts at several different types of receptors collectively known as nicotinic acetylcholine receptors (nAChRs). Alcohol also acts on at least some of these receptors, enhancing the function of some nAChR subtypes and inhibiting the activity of others. Chronic alcohol and nicotine administration also lead to changes in the numbers of nAChRs. Natural variations (i.e., polymorphisms) in the genes encoding different nAChR subunits may be associated with individual differences in the sensitivity to some of alcohol's and nicotine's effects. Finally, at least one subtype of nAChR may help protect cells against alcohol-induced neurotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2006
4. The natural history of acute, isolated, nonoperatively treated posterior cruciate ligament injuries: a prospective study.
- Author
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Shelbourne KD, Davis TJ, and Patel DV
- Abstract
We sought to determine prospectively the natural history of acute, isolated, nonoperatively treated posterior cruciate ligament injuries in athletically active patients. The study population consisted of 133 patients (average age, 25.2 years at time of injury). All patients completed a subjective questionnaire each year for an average of 5.4 years (range, 2.3 to 11.4). Sixty-eight of the 133 patients returned to the clinic for long-term follow-up evaluation. Objectively, physical examination revealed no change in laxity from initial injury to follow-up. No correlation was found between radiographic joint space narrowing and grade of laxity. The mean modified Noyes knee score was 84.2 points, the mean Lysholm score was 83.4, and the mean Tegner activity score was 5.7. Patients with greater laxity did not have worse subjective scores. No correlation was found between subjective knee scores and time from injury. Regardless of the amount of laxity, half of the patients returned to the same sport at the same or higher level, one-third returned to the same sport at a lower level, and one-sixth did not return to the same sport. Results of this study suggest that athletically active patients with acute isolated posterior cruciate ligament tears treated nonoperatively achieved a level of objective and subjective knee function that was independent of the grade of laxity. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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5. Evaluation of knee stability before and after participation in a functional sports agility program during rehabilitation after anterior cruciate ligament reconstruction.
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Shelbourne KD and Davis TJ
- Abstract
We sought to determine whether participation in a functional sports agility program as early as 4 weeks after anterior cruciate ligament reconstruction with autogenous patellar tendon graft would affect objective knee stability in 603 patients. The rehabilitation program prescribed a functional sports agility program at a mean of 5.1 +/- 1.0 weeks postoperatively when full knee hyperextension, knee flexion to 120 degrees, and quadriceps muscle strength of 60% of the normal leg had been achieved. The patients had KT-1000 arthrometer testing before beginning the program and at subsequent follow-up after they had performed the sport activity. The mean manual maximum KT-1000 arthrometer difference was 1.9 +/- 1.3 mm at initial testing and 1.9 +/- 1.2 mm at follow-up testing. The frequency distribution of the KT-1000 arthrometer scores revealed that 92.7% of patients at initial testing and 93.2% of patients at follow-up testing had displacement difference of 3 mm or less. The results of this study show that functional sports agility programs during the early rehabilitation period after anterior cruciate ligament reconstruction with a correctly placed autogenous patellar tendon graft do not cause a change in graft stability. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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6. The relationship between intercondylar notch width of the femur and the incidence of anterior cruciate ligament tears: a prospective study.
- Author
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Shelbourne KD, Davis TJ, and Klootwyk TE
- Abstract
For 714 consecutive patients who underwent autogenous patellar tendon graft anterior cruciate ligament reconstructions we intraoperatively measured intercondylar notch width. We prospectively recorded height, weight, sex, and which patients subsequently tore their contralateral anterior cruciate ligament or the 10-mm autograft. The patients were divided into two groups based on notch width (group 1, < or = 15 mm; group 2, > or = 16mm. The mean notch width was 13.9 +/- 2.2 mm for women and 15.9 +/- 2.5 mm for men. There was no statistically significant difference in notch width between height groups for women or men. Analysis showed that, with height and weight as covariates, women had statistically significantly narrower notches than men. Twenty-three of 388 patients in group 1 and 4 of 326 patients in group 2 tore their contralateral anterior cruciate ligaments. Within groups, no statistically significant differences in contralateral tear rates existed between men and women. Once the men and women had reconstructions with equally sized 10-mm autografts, there was no difference in graft tear rate between groups or between men and women. Our results show that patients with narrower notches have a higher incidence of tearing their contralateral anterior cruciate ligament. After reconstruction with a 10-mm autograft, the incidence of graft rupture is the same for men and women. [ABSTRACT FROM AUTHOR]
- Published
- 1998
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7. Effects of Constraining Postural Sway During Upper-Limb Precision Aiming Task Practice in Individuals with Stroke.
- Author
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Schwab-Farrell SM, Mayr R, Davis TJ, Riley MA, and Silva PL
- Abstract
Individuals post-stroke commonly demonstrate alterations in motor behavior with regard to both task performance and the motor strategies used in pursuit of task goals. We evaluated whether constraining postural sway (motor strategy) during practice would affect upper-limb precision aiming performance (task performance) and postural control adaptations. Adults with stroke stood on a force plate while immersed in a virtual scene displaying an anterior target. Participants aimed to position a virtual laser pointer (via handheld device) in the target. Participants then completed practice trials involving aiming at a lateral target. For this practice session, participants were randomized to either (a) a "constraint" group wherein they received physical constraint to limit postural sway, or (b) a "no-constraint" group. Task performance and postural control were assessed before and after practice, and transfer to another upper-limb task was evaluated. After practice, both groups improved paretic upper-limb performance. For the target task, the no-constraint group showed task-sensitive changes in postural control. The constraint group showed no changes in postural control. At transfer, the constraint group increased postural sway. Constraining postural sway after stroke should be carefully considered with the recognition that postural sway arises from exploratory movements involved in the discovery of adaptable motor solutions.
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- 2024
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8. Rapid inverse design of metasurfaces with an asymmetric transfer function for all-optical image processing using a mode matching model.
- Author
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Priscilla N, Wesemann L, Clark L, Sulejman SB, Rickett J, Davis TJ, and Roberts A
- Abstract
Metasurfaces have recently emerged as an ultra-compact solution to perform all-optical image processing, including phase contrast imaging. Most metasurfaces used in imaging processing applications operate over a restricted numerical aperture. This limitation imposes constraints on the discernible features that can be effectively visualized and consequently leads to the appearance of undesirable artifacts. Engineering a metasurface that exhibits an asymmetric linear optical transfer function over a relatively large numerical aperture, while maintaining a strong contrast, has proven to be a challenge. In this study, we present a novel approach to designing relatively high numerical aperture and contrast nonlocal metasurfaces (up to a numerical aperture of around 0.5 and an intensity contrast of approximately 50%) with unit cells consisting of several plasmonic nanorods through the use of a rapid, quasi-analytic mode-matching technique, coupled with an optimization algorithm. The combination of these methods facilitates the rapid conceptualization of nonintuitive arrangements of metallic nanoparticles, specifically tailored to perform phase contrast imaging. These designs hold substantial promise in the development of ultra-compact imaging systems.
- Published
- 2024
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9. Entropy as a Window Into Behavioral Phase Transitions: Unveiling Contextual Dynamics in Affordance-Based Reaching.
- Author
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Cooper DS, Moreira TS, and Davis TJ
- Subjects
- Humans, Male, Female, Adult, Young Adult, Biomechanical Phenomena physiology, Goals, Movement physiology, Entropy, Psychomotor Performance physiology
- Abstract
Prior work has demonstrated the presence of hysteresis effects in the control of affordance-guided behavior, in that behavioral transitions around a critical action boundary vary with directions of change in said action boundary. To date, research on this topic has overlooked the influence of the global context on these phenomena. We employ an affordance-based reaching task, whereby participants were asked to move a target to a goal by passing through one of two apertures (size variable or size constant). It was found that the direction of change in the size of the variable aperture influenced the point of behavioral transitions, and this effect interacted with the location of a given goal. In addition, we considered fluctuations in the entropy of participants' reach trajectories as a window into the nature of the behavioral phase transitions. Differences in the structure of entropy were found depending on the direction of change in the size variable aperture. These results are discussed in light of a dynamical systems approach, and recommendations for future work are made.
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- 2024
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10. A Prospective, Longitudinal Study of Caregiver-Reported Adaptive Skills and Function of Individuals with HNRNPH2 -related Neurodevelopmental Disorder.
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Davis TJ, Salazar R, Beenders S, Boehme A, LaMarca NM, and Bain JM
- Abstract
Objectives: This study presents a cohort of individuals in a natural history study with de novo pathogenic missense variants in HNRNPH2 causative of HNRNPH2 -related neurodevelopmental disorder (NDD) to describe individuals' adaptive functional abilities., Methods: We measured adaptive function using the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) and the Vineland Adaptive Behavior Scale (VABS-III). Results were compared using inferential statistics and regression analysis., Results: Sixty-seven individuals carried known pathogenic or likely pathogenic variants in HNRNPH2 . Thirty-five participants (2.89-42.04 years, 83% female) and caregivers completed PEDI-CAT assessments with 25 of these participants completing the VABS-III. Sixteen, three and two participants completed a follow-up PEDI-CAT assessment at one, two and three years respectively. Individuals had mean normative scores less than age-matched peers across all domains on both PEDI-CAT and VABS-III measures, with 91% participants < 5
th percentile on both the PEDI- CAT and VABS-III. Verbal and ambulatory participants had significantly higher PEDI-CAT scores across all domains, using both raw and normative data. There was no significant change in PEDI-CAT scores over 3 years., Conclusions: Overall scores, both raw and normative, are low across all individuals with HNRNPH2 -related NDD using both the PEDI-CAT and VABS-III. PEDI-CAT normative scores do not likely represent the clinical variability, but raw scores may be able to capture functional variability. In a small sample, longitudinal data from the PEDI-CAT domain scores demonstrate stability in performance at 3 years. Trial Registration : ClinicalTrials.gov NCT03492060., Competing Interests: Competing InterestsThe authors declare that they have no competing interests., (© The Author(s) 2023, corrected publication 2024.)- Published
- 2024
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11. Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas.
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Chu F, Cao J, Liu J, Yang H, Davis TJ, Kuang SQ, Cheng X, Zhang Z, Karri S, Vien LT, Bover L, Sun R, Vega F, Green M, Davis RE, and Neelapu SS
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- Humans, Neoplasm Recurrence, Local drug therapy, T-Lymphocytes, Antibodies, Monoclonal metabolism, Receptors, Chimeric Antigen, Lymphoma, B-Cell drug therapy
- Abstract
Background: Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance. Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen, widely expressed in most B-cell lymphomas., Methods: We generated a novel anti-CD79b monoclonal antibody by hybridoma method. The specificity of the antibody was determined by testing against isogenic cell lines with human CD79b knock-in or knock-out. A single-chain variable fragment derived from the monoclonal antibody was used to make a panel of CD79b-targeting CAR molecules containing various hinge, transmembrane, and co-stimulatory domains. These were lentivirally transduced into primary T cells and tested for antitumor activity in in vitro and in vivo B-cell lymphoma models., Results: We found that the novel anti-CD79b monoclonal antibody was highly specific and bound only to human CD79b and no other cell surface protein. In testing the various CD79b-targeting CAR molecules, superior antitumor efficacy in vitro and in vivo was found for a CAR consisting CD8α hinge and transmembrane domains, an OX40 co-stimulatory domain, and a CD3ζ signaling domain. This CD79b CAR specifically recognized human CD79b-expressing lymphoma cell lines but not CD79b knock-out cell lines. CD79b CAR T cells, generated from T cells from either healthy donors or patients with lymphoma, proliferated, produced cytokines, degranulated, and exhibited robust cytotoxic activity in vitro against CD19
+ and CD19- lymphoma cell lines and patient-derived lymphoma tumors relapsing after prior CD19 CAR T-cell therapy. Furthermore, CD79b CAR T cells were highly efficient at eradicating pre-established lymphoma tumors in vivo in three aggressive lymphoma xenograft models, including two cell line-derived xenografts and one patient-derived xenograft. Notably, these CAR T cells did not demonstrate any significant tonic signaling activity or markers of exhaustion., Conclusion: Our results indicated that this novel CD79b CAR T-cell therapy product has robust antitumor activity against B-cell lymphomas. These results supported initiation of a phase 1 clinical trial to evaluate this product in patients with relapsed or refractory B-cell lymphomas., Competing Interests: Competing interests: FC has intellectual property related to cell therapy. JC has intellectual property related to cell therapy. JL has intellectual property related to cell therapy. FV receives research support from Allogene and Geron corporation. SSN received research support from Kite/Gilead, BMS, Allogene, Precision Biosciences, Adicet Bio, and Sana Biotechnology; served as Advisory Board Member/Consultant for Kite/Gilead, Merck, Sellas Life Sciences, Athenex, Allogene, Incyte, Adicet Bio, BMS, Bluebird Bio, Fosun Kite, Sana Biotechnology, Caribou, Astellas Pharma, Morphosys, Janssen, Chimagen, ImmunoACT, Orna Therapeutics, Takeda, and Synthekine; has stock options from Longbow Immunotherapy; and has intellectual property related to cell therapy., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2023
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12. Heterogeneous cardiac sympathetic innervation gradients promote arrhythmogenesis in murine dilated cardiomyopathy.
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Dajani AJ, Liu MB, Olaopa MA, Cao L, Valenzuela-Ripoll C, Davis TJ, Poston MD, Smith EH, Contreras J, Pennino M, Waldmann CM, Hoover DB, Lee JT, Jay PY, Javaheri A, Slavik R, Qu Z, and Ajijola OA
- Subjects
- Humans, Mice, Animals, Heart, Myocardium, Arrhythmias, Cardiac diagnostic imaging, Catecholamines, Cardiomyopathy, Dilated diagnostic imaging
- Abstract
Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We hypothesized that this counterintuitive finding is explained by heterogeneous loss of sympathetic nerves in the failing heart. In a murine model of dilated cardiomyopathy (DCM), delayed PET imaging of sympathetic nerve density using the catecholamine analog [11C]meta-Hydroxyephedrine demonstrated global hypoinnervation in ventricular myocardium. Although reduced, sympathetic innervation in 2 distinct DCM models invariably exhibited transmural (epicardial to endocardial) gradients, with the endocardium being devoid of sympathetic nerve fibers versus controls. Further, the severity of transmural innervation gradients was correlated with VAs. Transmural innervation gradients were also identified in human left ventricular free wall samples from DCM versus controls. We investigated mechanisms underlying this relationship by in silico studies in 1D, 2D, and 3D models of failing and normal human hearts, finding that arrhythmogenesis increased as heterogeneity in sympathetic innervation worsened. Specifically, both DCM-induced myocyte electrical remodeling and spatially inhomogeneous innervation gradients synergistically worsened arrhythmogenesis. Thus, heterogeneous innervation gradients in DCM promoted arrhythmogenesis. Restoration of homogeneous sympathetic innervation in the failing heart may reduce VAs.
- Published
- 2023
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13. Ultrafast Time Dynamics of Plasmonic Fractional Orbital Angular Momentum.
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Bauer T, Davis TJ, Frank B, Dreher P, Janoschka D, Meiler TC, Meyer Zu Heringdorf FJ, Kuipers L, and Giessen H
- Abstract
The creation and manipulation of optical vortices, both in free space and in two-dimensional systems such as surface plasmon polaritons (SPPs), has attracted widespread attention in nano-optics due to their robust topological structure. Coupled with strong spatial confinement in the case of SPPs, these plasmonic vortices and their underlying orbital angular momentum (OAM) have promise in novel light-matter interactions on the nanoscale with applications ranging from on-chip particle manipulation to tailored control of plasmonic quasiparticles. Until now, predominantly integer OAM values have been investigated. Here, we measure and analyze the time evolution of fractional OAM SPPs using time-resolved two-photon photoemission electron microscopy and near-field optical microscopy. We experimentally show the field's complex rotational dynamics and observe the beating of integer OAM eigenmodes at fractional OAM excitations. With our ability to access the ultrafast time dynamics of the electric field, we can follow the buildup of the plasmonic fractional OAM during the interference of the converging surface plasmons. By adiabatically increasing the phase discontinuity at the excitation boundary, we track the total OAM, leading to plateaus around integer OAM values that arise from the interplay between intrinsic and extrinsic OAM., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)
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- 2023
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14. Modelling structural colour from helicoidal multi-layer thin films with natural disorder.
- Author
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Davis TJ, Ospina-Rozo L, Stuart-Fox D, and Roberts A
- Abstract
A coupled mode theory based on Takagi-Taupin equations describing electromagnetic scattering from distorted periodic arrays is applied to the problem of light scattering from beetles. We extend the method to include perturbations in the permittivity tensor to helicoidal arrays seen in many species of scarab beetle and optically anisotropic layered materials more generally. This extension permits analysis of typical dislocations arising from the biological assembly process and the presence of other structures in the elytra. We show that by extracting structural information from transmission electron microscopy data, including characteristic disorder parameters, good agreement with spectral specular and non-specular reflectance measurements is obtained.
- Published
- 2023
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15. Mosquito surveillance on U.S military installations as part of a Japanese encephalitis virus detection program: 2016 to 2021.
- Author
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Olson MF, Brooks C, Kakazu A, Promma P, Sornjai W, Smith DR, and Davis TJ
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- Humans, Animals, Swine, Sus scrofa, Mosquito Vectors, Encephalitis Virus, Japanese, Encephalitis, Japanese diagnosis, Encephalitis, Japanese epidemiology, Encephalitis, Japanese veterinary, Military Personnel, Culex, Aedes
- Abstract
Japanese encephalitis virus (JEV) continues to circulate throughout Southeast Asia and the Western Pacific where approximately 3 billion people in 24 countries are at risk of infection. Surveillance targeting the mosquito vectors of JEV was conducted at four military installations on Okinawa, Japan, between 2016 and 2021. Out of a total of 10,426 mosquitoes from 20 different species, zero were positive for JEV. The most abundant mosquito species collected were Aedes albopictus (36.4%) followed by Culex sitiens (24.3%) and Armigeres subalbatus (19%). Statistically significant differences in mosquito species populations according to location were observed. Changes in land use over time appear to be correlated with the species and number of mosquitoes trapped in each location. JEV appears to be absent from mosquito populations on Okinawa, but further research on domestic pigs and ardeid birds is warranted., Competing Interests: We have no conflicts of interest to disclose., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
- Published
- 2023
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16. Modulation of Cathodoluminescence by Surface Plasmons in Silver Nanowires.
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Liu ACY, Davis TJ, Coenen T, Hari S, Voortman LM, Xu Z, Yuan G, Ballard PM, Funston AM, and Etheridge J
- Abstract
The waveguide modes in chemically-grown silver nanowires on silicon nitride substrates are observed using spectrally- and spatially-resolved cathodoluminescence (CL) excited by high-energy electrons in a scanning electron microscope. The presence of a long-range, travelling surface plasmon mode modulates the coupling efficiency of the incident electron energy into the nanowires, which is observed as oscillations in the measured CL with the point of excitation by the focused electron beam. The experimental data are modeled using the theory of surface plasmon polariton modes in cylindrical metal waveguides, enabling the complex mode wavenumbers and excitation strength of the long-range surface plasmon mode to be extracted. The experiments yield insight into the energy transfer mechanisms between fast electrons and coherent oscillations in surface charge density in metal nanowires and the relative amplitudes of the radiative processes excited in the wire by the electron., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)
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- 2023
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17. Precision aiming performance with the paretic upper limb is associated with center of pressure patterns in individuals with chronic stroke.
- Author
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Schwab SM, Mayr R, Davis TJ, Silva PL, and Riley MA
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- Adult, Humans, Cross-Sectional Studies, Upper Extremity, Movement, Postural Balance, Stroke complications, Stroke diagnosis, Stroke Rehabilitation
- Abstract
Background: Individuals with stroke commonly demonstrate upper-limb sensorimotor impairments. Upper-limb tasks occur against a background level of postural control and thus require a flexible postural control system to facilitate performance. Anterior precision aiming tasks, for example, benefit from lower medial-lateral (ML) center of pressure (COP) fluctuations (where increased fluctuations erode performance) relative to anterior-posterior (AP) fluctuations (where increased fluctuations do not strongly influence performance). After stroke, individuals may compensate for upper-limb impairments by increasing trunk movement which increases overall COP fluctuations and thus may make it more difficult to modulate COP in a task-sensitive manner., Research Question: Do upper-limb task demands modulate COP movement patterns after stroke?, Methods: In this cross-sectional study, adults with chronic stroke (n = 23) and unilateral upper-limb impairments were immersed in a virtual environment displaying an anterior target. Participants aimed to maintain the position of a virtual laser pointer (via handheld controller) in the target with each hand. COP was concurrently recorded. Mixed effects models and correlations were used to detect differences in COP patterns between limbs and movement planes and evaluate associations between task performance and COP patterns, respectively., Results: Participants showed greater COP standard deviation and regularity in the AP compared to the ML direction. The magnitude of difference between AP and ML COP metrics was greater using the nonparetic limb. Task performance was moderately and positively associated with task-sensitive COP patterns (i.e., higher AP:ML ratios of COP metrics) using the paretic upper limb. Participants consistently demonstrated high levels of task performance and task-sensitive COP movement patterns using the nonparetic limb., Significance: Impairments in postural control after stroke may be related to the upper limb used. It is important to recognize the role of directional COP variability and regularity in the context of a task goal after stroke., Competing Interests: Declaration of Competing Interest The authors have no declarations of interest to report., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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18. Thin film notch filters as platforms for biological image processing.
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Sulejman SB, Priscilla N, Wesemann L, Lee WSL, Lou J, Hinde E, Davis TJ, and Roberts A
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- Humans, Image Processing, Computer-Assisted methods, Optical Phenomena
- Abstract
Many image processing operations involve the modification of the spatial frequency content of images. Here we demonstrate object-plane spatial frequency filtering utilizing the angular sensitivity of a commercial spectral bandstop filter. This approach to all-optical image processing is shown to generate real-time pseudo-3D images of transparent biological and other samples, such as human cervical cancer cells. This work demonstrates the potential of non-local, non-interferometric approaches to image processing for uses in label-free biological cell imaging and dynamical monitoring., (© 2023. The Author(s).)
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- 2023
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19. Homing tasks performed using variations of crawling gait patterns reveal a role for attention in podokinetic path integration.
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Harrison SJ and Davis TJ
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- Humans, Walking, Locomotion, Leg, Task Performance and Analysis, Biomechanical Phenomena, Gait, Movement Disorders
- Abstract
Self-motion can be perceived via podokinetic information, that is, based upon the movements of the legs during legged locomotion. This information can be integrated in order to perceive a path of travel through the environment (i.e., via podokinetic path integration). Two types of podokinetic information have been distinguished by analyzing the patterns of bias that result from manipulating the gait patterns used in direct-route homing tasks. Each type of podokinetic information has been associated specific groupings of gaits that support equivalent perceptual measurements of self-motion. Specifically, gaits are grouped if they can be varied across the outbound and inbound phases of a homing task (e.g., walking outbound and jogging inbound) and the accuracy of homing task performances does not differ from matched-gait control conditions. Recently, it was theorized that different types of podokinetic information are related to the differences in the kinematic form of limb motions in these groupings of gaits. Here we test an alternative hypothesis, namely that attention plays a role in selecting the type of podokinetic information. In three experiments, we manipulated the crawling gait patterns used in direct-route homing tasks. Consistent with our hypotheses, we observe that self-motion is equivalently measured via crawling movement patterns that (1) have distinct kinematic forms, but that similarly direct participants' attention onto controlling the swing phase trajectories of their arms, and (2) have distinct inter-limb coordination patterns (i.e., pace vs. trot), but do not require attention to be specifically focused upon swing phase arm trajectories., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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20. The efficacy and safety of a shortened duration of antimicrobial therapy for group A Streptococcus bacteremia.
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Nguyen ADK, Smith S, Davis TJ, Yarwood T, and Hanson J
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- Humans, Middle Aged, Aged, Retrospective Studies, Australia, Anti-Bacterial Agents therapeutic use, Bacteremia drug therapy, Streptococcal Infections drug therapy
- Abstract
Objectives: To determine if shorter courses of antibiotic therapy for group A Streptococcus (GAS) bacteremia are associated with excess mortality., Methods: In this retrospective study of consecutive cases of GAS bacteremia in tropical Australia, the duration of antibiotic therapy was correlated with 90-day all-cause mortality., Results: There were 286 episodes of GAS bacteremia; the patients' median (interquartile range) age was 60 (48-71) years and 169/286 (59.1%) patients identified as an Indigenous Australian. There were 227/286 (79.4%) patients with a significant comorbidity. The all-cause 90-day mortality was 16/286 (5.6%); however, 12/16 (81.3%) patients died while still receiving their initial course of antibiotics and only 7/16 (43.8%) deaths were directly attributable to the GAS infection. After excluding patients who died while taking their initial course of antibiotics and those in whom the duration of therapy was uncertain, there was no difference in 90-day mortality between patients receiving ≤5 days of intravenous antibiotics and those receiving longer courses (1/137 [0.7%] vs 3/107 [2.8%], P-value = 0.32) nor in patients receiving ≤10 days of total therapy and those receiving longer courses (1/67 [1.5%] vs 3/178 [1.7%], P-value = 1.0)., Conclusion: Even among patients with significant comorbidity, shorter antibiotic courses for GAS bacteremia are not associated with excess mortality., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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21. Bidirectional Associations Between Physical Activity and Pain Among Older Adults: An Ecological Momentary Assessment Study.
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Davis TJ, Hevel DJ, Dunton GF, and Maher JP
- Subjects
- Humans, Aged, Surveys and Questionnaires, Self Report, Pain, Ecological Momentary Assessment, Exercise
- Abstract
This paper examines the within-day, bidirectional associations between physical activity and self-reported pain among older adults. Older adults (N = 104; range: 60-98 years) participated in a 10-day Ecological Momentary Assessment (EMA) study. Participants received six EMA prompts/day with a single item assessing pain. Participants wore an activPAL monitor measuring step counts. At the within-person level, on occasions when participants took more steps than usual in the 30 min before the EMA prompt, they were more likely to experience pain at the prompt (β^02=0.0003, p < .03). At the between-person level, greater step counts in the 30 min before the EMA prompt, on average, were associated with less pain on occasions when pain was experienced (β^01=-0.0005, p < .04). Pain was not related to subsequent stepping. Bidirectional associations between physical activity and pain were not documented, but physical activity did appear to be related to subsequent pain.
- Published
- 2022
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22. Addressing Missing Data in GC × GC Metabolomics: Identifying Missingness Type and Evaluating the Impact of Imputation Methods on Experimental Replication.
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Davis TJ, Firzli TR, Higgins Keppler EA, Richardson M, and Bean HD
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- Bayes Theorem, Chromatography, Gas, Principal Component Analysis, Reproducibility of Results, Metabolomics methods
- Abstract
Missing data is a significant issue in metabolomics that is often neglected when conducting data preprocessing, particularly when it comes to imputation. This can have serious implications for downstream statistical analyses and lead to misleading or uninterpretable inferences. In this study, we aim to identify the primary types of missingness that affect untargeted metabolomics data and compare strategies for imputation using two real-world comprehensive two-dimensional gas chromatography (GC × GC) data sets. We also present these goals in the context of experimental replication whereby imputation is conducted in a within-replicate-based fashion─the first description and evaluation of this strategy─and introduce an R package MetabImpute to carry out these analyses. Our results conclude that, in these two GC × GC data sets, missingness was most likely of the missing at-random (MAR) and missing not-at-random (MNAR) types as opposed to missing completely at-random (MCAR). Gibbs sampler imputation and Random Forest gave the best results when imputing MAR and MNAR compared against single-value imputation (zero, minimum, mean, median, and half-minimum) and other more sophisticated approaches (Bayesian principal component analysis and quantile regression imputation for left-censored data). When samples are replicated, within-replicate imputation approaches led to an increase in the reproducibility of peak quantification compared to imputation that ignores replication, suggesting that imputing with respect to replication may preserve potentially important features in downstream analyses for biomarker discovery.
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- 2022
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23. Examination of the independent contribution of rheumatic heart disease and congestive cardiac failure to the development and outcome of melioidosis in Far North Queensland, tropical Australia.
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Davies P, Smith S, Wilcox R, Stewart JD, Davis TJ, McKenna K, and Hanson J
- Subjects
- Aged, Australia epidemiology, Humans, Queensland epidemiology, Risk Factors, Heart Failure epidemiology, Melioidosis epidemiology, Rheumatic Heart Disease diagnosis, Rheumatic Heart Disease epidemiology
- Abstract
Background: Patients with rheumatic heart disease (RHD) and congestive cardiac failure (CCF) are believed to have an increased risk of melioidosis and are thought to be more likely to die from the infection. This study was performed to confirm these findings in a region with a high incidence of all three conditions., Principal Findings: Between January 1998 and December 2021 there were 392 cases of melioidosis in Far North Queensland, tropical Australia; 200/392 (51.0%) identified as an Indigenous Australian, and 337/392 (86.0%) had a confirmed predisposing comorbidity that increased risk for the infection. Overall, 46/392 (11.7%) died before hospital discharge; the case fatality rate declining during the study period (p for trend = 0.001). There were only 3/392 (0.8%) with confirmed RHD, all of whom had at least one other risk factor for melioidosis; all 3 survived to hospital discharge. Among the 200 Indigenous Australians in the cohort, 2 had confirmed RHD; not statistically greater than the prevalence of RHD in the local general Indigenous population (1.0% versus 1.2%, p = 1.0). RHD was present in only 1/193 (0.5%) cases of melioidosis diagnosed after October 2016, a period which coincided with prospective data collection. There were 26/392 (6.6%) with confirmed CCF, but all 26 had another traditional risk factor for melioidosis. Patients with CCF were more likely to also have chronic lung disease (OR (95% CI: 4.46 (1.93-10.31), p<0.001) and chronic kidney disease (odds ratio (OR) (95% confidence interval (CI): 2.98 (1.22-7.29), p = 0.01) than those who did not have CCF. Two patients with melioidosis and CCF died before hospital discharge; both were elderly (aged 81 and 91 years) and had significant comorbidity., Conclusions: In this region of tropical Australia RHD and CCF do not appear to be independent risk factors for melioidosis and have limited prognostic utility., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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24. Spaceflight Analogue Culture Enhances the Host-Pathogen Interaction Between Salmonella and a 3-D Biomimetic Intestinal Co-Culture Model.
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Barrila J, Yang J, Franco Meléndez KP, Yang S, Buss K, Davis TJ, Aronow BJ, Bean HD, Davis RR, Forsyth RJ, Ott CM, Gangaraju S, Kang BY, Hanratty B, Nydam SD, Nauman EA, Kong W, Steel J, and Nickerson CA
- Subjects
- Animals, Coculture Techniques, Host-Pathogen Interactions, Humans, Mammals, Salmonella typhimurium genetics, Biomimetics, Space Flight
- Abstract
Physical forces associated with spaceflight and spaceflight analogue culture regulate a wide range of physiological responses by both bacterial and mammalian cells that can impact infection. However, our mechanistic understanding of how these environments regulate host-pathogen interactions in humans is poorly understood. Using a spaceflight analogue low fluid shear culture system, we investigated the effect of Low Shear Modeled Microgravity (LSMMG) culture on the colonization of Salmonella Typhimurium in a 3-D biomimetic model of human colonic epithelium containing macrophages. RNA-seq profiling of stationary phase wild type and Δ hfq mutant bacteria alone indicated that LSMMG culture induced global changes in gene expression in both strains and that the RNA binding protein Hfq played a significant role in regulating the transcriptional response of the pathogen to LSMMG culture. However, a core set of genes important for adhesion, invasion, and motility were commonly induced in both strains. LSMMG culture enhanced the colonization (adherence, invasion and intracellular survival) of Salmonella in this advanced model of intestinal epithelium using a mechanism that was independent of Hfq. Although S . Typhimurium Δ hfq mutants are normally defective for invasion when grown as conventional shaking cultures, LSMMG conditions unexpectedly enabled high levels of colonization by an isogenic Δ hfq mutant. In response to infection with either the wild type or mutant, host cells upregulated transcripts involved in inflammation, tissue remodeling, and wound healing during intracellular survival. Interestingly, infection by the Δ hfq mutant led to fewer transcriptional differences between LSMMG- and control-infected host cells relative to infection with the wild type strain. This is the first study to investigate the effect of LSMMG culture on the interaction between S . Typhimurium and a 3-D model of human intestinal tissue. These findings advance our understanding of how physical forces can impact the early stages of human enteric salmonellosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barrila, Yang, Franco Meléndez, Yang, Buss, Davis, Aronow, Bean, Davis, Forsyth, Ott, Gangaraju, Kang, Hanratty, Nydam, Nauman, Kong, Steel and Nickerson.)
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- 2022
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25. Physiology, Lactation
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Pillay J and Davis TJ
- Abstract
The normal physiology of lactation is a process that begins to take effect well before the initial latch of the newborn infant. It requires the breast to change in composition, size, and shape during each stage of female development. Development includes puberty, pregnancy, and lactation. These stages are influenced by a cascade of physiologic changes that are crucial to successful breastfeeding. This article will review the development of the mammary gland (mammogenesis), the process by which the mammary gland develops the ability to secrete milk (lactogenesis), and the process of milk production (lactation)., (Copyright © 2022, StatPearls Publishing LLC.)
- Published
- 2022
26. Neonatal heart transplant outcomes: A single institutional experience.
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Lin Y, Davis TJ, Zorrilla-Vaca A, Wojcik BM, Miyamoto SD, Everitt MD, Campbell DN, Jaggers JJ, and Rajab TK
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- Female, Follow-Up Studies, Graft Rejection epidemiology, Heart Defects, Congenital mortality, Humans, Infant, Newborn, Male, Postoperative Complications epidemiology, Reoperation statistics & numerical data, Retrospective Studies, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Heart Defects, Congenital surgery, Heart Transplantation
- Abstract
Objective: Neonatal orthotopic heart transplantation was introduced in the 1980s as a treatment for complex congenital heart disease. Progress in single-ventricle palliation and biventricular correction has resulted in a decline in neonatal heart transplant volume. However, limited reports on neonatal heart transplants have demonstrated favorable outcomes. We report the long-term outcomes of patients with neonatal heart transplants at our institution spanning nearly 30 years., Methods: A retrospective analysis of neonatal heart transplants and neonates listed for transplant was performed at Children's Hospital Colorado. Primary outcomes were early and late survival. Secondary outcomes were rejection episodes, retransplantation, and development of cardiac allograft vasculopathy or post-transplant lymphoproliferative disease., Results: A total of 21 neonates underwent orthotopic heart transplantation at our institution. Among these, 10 neonates were transplanted from 1991 to 2000, 8 neonates were transplanted from 2001 to 2010, and 3 neonates were transplanted from 2011 to 2020. The average age of these patients was 17 days, and the average weight was 3.43 kg. Early survival was 95.2%. Survival at 1 and 5 years was 85.7% (confidence interval [CI], 61.9%-95.2%) and 75% (CI, 45.6%-85.5%), respectively. Of eligible patients, the 10-year and 20-year survival was 72.2% (CI, 45.1%-85.3%) and 50% (CI, 25.9%-70.1%), respectively., Conclusions: Our institution reports favorable outcomes of neonatal heart transplantation. These results should be considered within the context of outcomes for patients awaiting transplant and the limited donor availability. However, the successful nature of these procedures suggest it may be necessary to reevaluate the indications for neonatal heart transplantation, particularly where risk of mortality and morbidity with palliative or corrective surgery is high., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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27. Structuring Poverty: How Racism Shapes Child Poverty and Child and Adolescent Health.
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Heard-Garris N, Boyd R, Kan K, Perez-Cardona L, Heard NJ, and Johnson TJ
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- Adolescent, Adolescent Health, Child, Ethnicity, Family, Humans, Poverty, United States, Racism
- Abstract
Black, Native, and Latinx populations represent the racial and ethnic groups most impacted by poverty. This unequal distribution of poverty must be understood as a consequence of policy decisions-some that have sanctioned violence and others that have created norms-that continue to shape who has access to power, resources, rights, and protections. In this review, we draw on scholarship from multiple disciplines, including pediatrics, public health, environmental health, epidemiology, social and biomedical science, law, policy, and urban planning to explore the central question-What is the relationship between structural racism, poverty, and pediatric health? We discuss historic and present-day events that are critical to the understanding of poverty in the context of American racism and pediatric health. We challenge conventional paradigms that treat racialized poverty as an inherent part of American society. We put forth a conceptual framework to illustrate how white supremacy and American capitalism drive structural racism and shape the racial distribution of resources and power where children and adolescents live, learn, and play, ultimately contributing to pediatric health inequities. Finally, we offer antipoverty strategies grounded in antiracist practices that contend with the compounding, generational impact of racism and poverty on heath to improve child, adolescent, and family health., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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28. The Effect of Navigation Demand on Decision Making in a Dynamic, Sport-Inspired Virtual Environment.
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Alt JM, Kiefer AW, MacPherson R, Davis TJ, and Silva PL
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- Adolescent, Adult, Female, Humans, Male, Young Adult, Decision Making, Spatial Navigation physiology, Sports physiology, Virtual Reality
- Abstract
Athletes commonly make decisions about the passability of closing gaps when navigating sport environments. This study examined whether increased temporal pressure to arrive at a desired location modifies these decisions. Thirty participants navigated toward a waypoint in a virtual, sport-inspired environment. To do so, they had to decide whether they could pass through closing gaps of virtual humans (and take the shortest route) or steer around them (and take a longer route). The decision boundary of participants who were time pressured to arrive at a waypoint was biased toward end gaps of smaller sizes and was less reliably defined, resulting in a higher number of collisions. Effects of temporal pressure were minimized with experience in the experimental task. Results indicate that temporal pressure affects perceptual-motor processes supporting information pickup and shapes the information-action coupling that drives compliance with navigation demands. Theoretical and practical implications are discussed.
- Published
- 2021
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29. Nanophotonics enhanced coverslip for phase imaging in biology.
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Wesemann L, Rickett J, Song J, Lou J, Hinde E, Davis TJ, and Roberts A
- Abstract
The ability to visualise transparent objects such as live cells is central to understanding biological processes. Here we experimentally demonstrate a novel nanostructured coverslip that converts phase information to high-contrast intensity images. This compact device enables real-time, all-optical generation of pseudo three-dimensional images of phase objects on transmission. We show that by placing unstained human cancer cells on the device, the internal structure within the cells can be clearly seen. Our research demonstrates the significant potential of nanophotonic devices for integration into compact imaging and medical diagnostic devices. The nanophotonics enhanced coverslip (NEC) enables ultra-compact phase imaging of samples placed directly on top of the device. Visualisation of artificial phase objects and unstained biological cells is demonstrated.
- Published
- 2021
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30. The temporospatial epidemiology of rheumatic heart disease in Far North Queensland, tropical Australia 1997-2017; impact of socioeconomic status on disease burden, severity and access to care.
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Kang K, Chau KWT, Howell E, Anderson M, Smith S, Davis TJ, Starmer G, and Hanson J
- Subjects
- Adolescent, Adult, Cost of Illness, Female, Humans, Incidence, Male, Prevalence, Queensland epidemiology, Retrospective Studies, Rheumatic Heart Disease mortality, Rheumatic Heart Disease surgery, Social Class, Young Adult, Health Services Accessibility, Rheumatic Heart Disease epidemiology, Severity of Illness Index
- Abstract
Background: The incidence of rheumatic heart disease (RHD) among Indigenous Australians remains one of the highest in the world. Many studies have highlighted the relationship between the social determinants of health and RHD, but few have used registry data to link socioeconomic disadvantage to the delivery of patient care and long-term outcomes., Methods: A retrospective study of individuals living with RHD in Far North Queensland (FNQ), Australia between 1997 and 2017. Patients were identified using the Queensland state RHD register. The Socio-Economic Indexes for Areas (SEIFA) Score-a measure of socioeconomic disadvantage-was correlated with RHD prevalence, disease severity and measures of RHD care., Results: Of the 686 individuals, 622 (90.7%) were Indigenous Australians. RHD incidence increased in the region from 4.7/100,000/year in 1997 to 49.4/100,000/year in 2017 (p<0.001). In 2017, the prevalence of RHD was 12/1000 in the Indigenous population and 2/1000 in the non-Indigenous population (p<0.001). There was an inverse correlation between an area's SEIFA score and its RHD prevalence (rho = -0.77, p = 0.005). 249 (36.2%) individuals in the cohort had 593 RHD-related hospitalisations; the number of RHD-related hospitalisations increased during the study period (p<0.001). In 2017, 293 (42.7%) patients met criteria for secondary prophylaxis, but only 73 (24.9%) had good adherence. Overall, 119/686 (17.3%) required valve surgery; the number of individuals having surgery increased over the study period (p = 0.02). During the study 39/686 (5.7%) died. Non-Indigenous patients were more likely to die than Indigenous patients (9/64 (14%) versus 30/622 (5%), p = 0.002), but Indigenous patients died at a younger age (median (IQR): 52 (35-67) versus 73 (62-77) p = 0.013). RHD-related deaths occurred at a younger age in Indigenous individuals than non-Indigenous individuals (median (IQR) age: 29 (12-58) versus 77 (64-78), p = 0.007)., Conclusions: The incidence of RHD, RHD-related hospitalisations and RHD-related surgery continues to rise in FNQ. Whilst this is partly explained by increased disease recognition and improved delivery of care, the burden of RHD remains unacceptably high and is disproportionately borne by the socioeconomically disadvantaged Indigenous population., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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31. Getting "Our House" in Order: Re-Building Academic Pediatrics by Dismantling the Anti-Black Racist Foundation.
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Jindal M, Heard-Garris N, Empey A, Perrin EC, Zuckerman KE, and Johnson TJ
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- Child, Humans, Black or African American, Pediatrics
- Published
- 2020
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32. Pseudomonas aeruginosa Volatilome Characteristics and Adaptations in Chronic Cystic Fibrosis Lung Infections.
- Author
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Davis TJ, Karanjia AV, Bhebhe CN, West SB, Richardson M, and Bean HD
- Subjects
- Biomarkers analysis, Chromatography, Gas, Chronic Disease, Humans, Mass Spectrometry, Metabolome, Phenotype, Pseudomonas Infections microbiology, Quality of Life, Volatilization, Adaptation, Physiological, Cystic Fibrosis microbiology, Lung microbiology, Pseudomonas aeruginosa metabolism, Respiratory Tract Infections microbiology, Volatile Organic Compounds analysis
- Abstract
Pseudomonas aeruginosa chronic lung infections in individuals with cystic fibrosis (CF) significantly reduce quality of life and increase morbidity and mortality. Tracking these infections is critical for monitoring patient health and informing treatments. We are working toward the development of novel breath-based biomarkers to track chronic P. aeruginosa lung infections in situ Using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOF-MS), we characterized the in vitro volatile metabolomes ("volatilomes") of 81 P. aeruginosa isolates collected from 17 CF patients over at least a 5-year period of their chronic lung infections. We detected 539 volatiles produced by the P. aeruginosa isolates, 69 of which were core volatiles that were highly conserved. We found that each early infection isolate has a unique volatilome, and as infection progresses, the volatilomes of isolates from the same patient become increasingly dissimilar, to the point that these intrapatient isolates are no more similar to one another than to isolates from other patients. We observed that the size and chemical diversity of P. aeruginosa volatilomes do not change over the course of chronic infections; however, the relative abundances of core hydrocarbons, alcohols, and aldehydes do change and are correlated with changes in phenotypes associated with chronic infections. This study indicates that it may be feasible to track P. aeruginosa chronic lung infections by measuring changes to the infection volatilome and lays the groundwork for exploring the translatability of this approach to direct measurement using patient breath. IMPORTANCE Pseudomonas aeruginosa is a leading cause of chronic lung infections in cystic fibrosis (CF), which are correlated with lung function decline. Significant clinical efforts are therefore aimed at detecting infections and tracking them for phenotypic changes, such as mucoidy and antibiotic resistance. Both the detection and tracking of lung infections rely on sputum cultures, but due to improvements in CF therapies, sputum production is declining, although risks for lung infections persist. Therefore, we are working toward the development of breath-based diagnostics for CF lung infections. In this study, we characterized of the volatile metabolomes of 81 P. aeruginosa clinical isolates collected from 17 CF patients over a duration of at least 5 years of a chronic lung infection. We found that the volatilome of P. aeruginosa adapts over time and is correlated with infection phenotype changes, suggesting that it may be possible to track chronic CF lung infections with a breath test., (Copyright © 2020 Davis et al.)
- Published
- 2020
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33. Discovery and Development of S6821 and S7958 as Potent TAS2R8 Antagonists.
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Fotsing JR, Darmohusodo V, Patron AP, Ching BW, Brady T, Arellano M, Chen Q, Davis TJ, Liu H, Servant G, Zhang L, Williams M, Saganich M, Ditschun T, Tachdjian C, and Karanewsky DS
- Subjects
- Animals, Coffee chemistry, Drug Discovery, Drug Stability, Humans, Hydantoins chemical synthesis, Hydantoins toxicity, Molecular Structure, Pyrazoles chemical synthesis, Pyrazoles toxicity, Rats, Structure-Activity Relationship, Hydantoins pharmacology, Pyrazoles pharmacology, Receptors, Cell Surface antagonists & inhibitors, Receptors, G-Protein-Coupled antagonists & inhibitors, Taste drug effects
- Abstract
In humans, bitter taste is mediated by 25 TAS2Rs. Many compounds, including certain active pharmaceutical ingredients, excipients, and nutraceuticals, impart their bitter taste (or in part) through TAS2R8 activation. However, effective TAS2R8 blockers that can either suppress or reduce the bitterness of these compounds have not been described. We are hereby reporting a series of novel 3-(pyrazol-4-yl) imidazolidine-2,4-diones as potent and selective TAS2R8 antagonists. In human sensory tests, S6821 and S7958 , two of the most potent analogues from the series, demonstrated efficacy in blocking TAS2R8-mediated bitterness and were selected for development. Following data evaluation by expert panels of a number of national and multinational regulatory bodies, including the US, the EU, and Japan, S6821 and S7958 were approved as safe under conditions of intended use as bitter taste blockers.
- Published
- 2020
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34. A Metabolomic Approach for Predicting Diurnal Changes in Cortisol.
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Eshima J, Davis TJ, Bean HD, Fricks J, and Smith BS
- Abstract
Introduction : The dysregulation of cortisol secretion has been associated with a number of mental health and mood disorders. However, diagnostics for mental health and mood disorders are behavioral and lack biological contexts. Objectives : The goal of this work is to identify volatile metabolites capable of predicting changes in total urinary cortisol across the diurnal cycle for long-term stress monitoring in psychological disorders. Methods : We applied comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry to sample the urinary volatile metabolome using an untargeted approach across three time points in a single day for 60 subjects. Results : The finalized multiple regression model includes 14 volatile metabolites and 7 interaction terms. A review of the selected metabolites suggests pyrrole, 6-methyl-5-hepten-2-one and 1-iodo-2-methylundecane may originate from endogenous metabolic mechanisms influenced by glucocorticoid signaling mechanisms. Conclusion : This analysis demonstrated the feasibility of using specific volatile metabolites for the prediction of secreted cortisol across time., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in writing of the manuscript, or in the decision to publish the results.
- Published
- 2020
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35. Longitudinal Associations of the Cystic Fibrosis Airway Microbiome and Volatile Metabolites: A Case Study.
- Author
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Hahn A, Whiteson K, Davis TJ, Phan J, Sami I, Koumbourlis AC, Freishtat RJ, Crandall KA, and Bean HD
- Subjects
- Humans, Metagenomics, RNA, Ribosomal, 16S genetics, Sputum, Cystic Fibrosis, Microbiota
- Abstract
The identification of 16S rDNA biomarkers from respiratory samples to describe the continuum of clinical disease states within persons having cystic fibrosis (CF) has remained elusive. We sought to combine 16S, metagenomics, and metabolomics data to describe multiple transitions between clinical disease states in 14 samples collected over a 12-month period in a single person with CF. We hypothesized that each clinical disease state would have a unique combination of bacterial genera and volatile metabolites as a potential signature that could be utilized as a biomarker of clinical disease state. Taxonomy identified by 16S sequencing corroborated clinical culture results, with the majority of the 109 PCR amplicons belonging to the bacteria grown in clinical cultures ( Escherichia coli and Staphylococcus aureus ). While alpha diversity measures fluctuated across disease states, no significant trends were present. Principle coordinates analysis showed that treatment samples trended toward a different community composition than baseline and exacerbation samples. This was driven by the phylum Bacteroidetes (less abundant in treatment, log
2 fold difference -3.29, p = 0.015) and the genus Stenotrophomonas (more abundant in treatment, log2 fold difference 6.26, p = 0.003). Across all sputum samples, 466 distinct volatile metabolites were identified with total intensity varying across clinical disease state. Baseline and exacerbation samples were rather uniform in chemical composition and similar to one another, while treatment samples were highly variable and differed from the other two disease states. When utilizing a combination of the microbiome and metabolome data, we observed associations between samples dominated Staphylococcus and Escherichia and higher relative abundances of alcohols, while samples dominated by Achromobacter correlated with a metabolomics shift toward more oxidized volatiles. However, the microbiome and metabolome data were not tightly correlated; examining both the metagenomics and metabolomics allows for more context to examine changes across clinical disease states. In our study, combining the sputum microbiome and metabolome data revealed stability in the sputum composition through the first exacerbation and treatment episode, and into the second exacerbation. However, the second treatment ushered in a prolonged period of instability, which after three additional exacerbations and treatments culminated in a new lung microbiome and metabolome., (Copyright © 2020 Hahn, Whiteson, Davis, Phan, Sami, Koumbourlis, Freishtat, Crandall and Bean.)- Published
- 2020
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36. Ultrafast vector imaging of plasmonic skyrmion dynamics with deep subwavelength resolution.
- Author
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Davis TJ, Janoschka D, Dreher P, Frank B, Meyer Zu Heringdorf FJ, and Giessen H
- Abstract
Plasmonic skyrmions are an optical manifestation of topological defects in a continuous vector field. Identifying them requires characterization of the vector structure of the electromagnetic near field on thin metal films. Here we introduce time-resolved vector microscopy that creates movies of the electric field vectors of surface plasmons with subfemtosecond time steps and a 10-nanometer spatial scale. We image complete time sequences of propagating surface plasmons as well as plasmonic skyrmions, resolving all vector components of the electric field and their time dynamics, thus demonstrating dynamic spin-momentum coupling as well as the time-varying skyrmion number. The ability to image linear optical effects in the spin and phase structures of light in the single-nanometer range will allow for entirely novel microscopy and metrology applications., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2020
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37. Monitoring changes in the healthy female metabolome across the menstrual cycle using GC × GC-TOFMS.
- Author
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Eshima J, Ong S, Davis TJ, Miranda C, Krishnamurthy D, Nachtsheim A, Stufken J, Plaisier C, Fricks J, Bean HD, and Smith BS
- Subjects
- Acetone urine, Adolescent, Adult, Biomarkers urine, Carbon Disulfide urine, Female, Humans, Menstrual Cycle urine, Ovulation metabolism, Pentanones urine, Young Adult, Gas Chromatography-Mass Spectrometry methods, Menstrual Cycle metabolism, Metabolome physiology, Metabolomics methods
- Abstract
Urinary metabolomics offers a non-invasive means of obtaining information about the system-wide biological health of a patient. Untargeted metabolomics approaches using one-dimensional gas chromatography (GC) are limited due to the chemical complexity of urine, which poorly detects co-eluting low-abundance analytes. Metabolite detection and identification can be improved by applying comprehensive two-dimensional GC, allowing for the discovery of additional viable biomarkers of disease. In this work, we applied comprehensive two-dimensional GC coupled with time-of-flight mass spectrometry (GC × GC-TOFMS) to the analysis of urine samples collected daily across 28-days from 10 healthy female subjects for a personalized approach to female reproductive health monitoring. Through this analysis, we identified 935 unique volatile metabolites. Two statistical methods, a modified T-statistic and Wilcoxon Rank Sum, were applied to analyze differences in metabolome abundance on ovulation days as compared to non-ovulation days. Four metabolites (2-pentanone, 3-penten-2-one, carbon disulfide, acetone) were identified as statistically significant by the modified T-statistic but not the Rank Sum, after a false-discovery rate of 0.1 was set using a Benjamini-Hochberg correction. Subsequent analyses by boxplot indicated that the putative volatile metabolic biomarkers for fertility are expressed in increased or decreased abundance in urine on the day of ovulation. Individual analysis of metabolome expression across 28-days revealed some subject-specific features, which suggest a potential for long-term, personalized fertility monitoring using metabolomics., (Copyright © 2019. Published by Elsevier B.V.)
- Published
- 2019
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38. Metasurfaces with Asymmetric Optical Transfer Functions for Optical Signal Processing.
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Davis TJ, Eftekhari F, Gómez DE, and Roberts A
- Abstract
Metasurface thin films created from arrays of structured optical elements have been shown to perform spatial filtering of optical signals. To extend their usefulness it is important that the symmetry of their response with changes to the in-plane wave vector k_{p}→-k_{p} can be tailored or even dynamically tuned. In this Letter we use a general theory of metasurfaces constructed from nondiffracting arrays of coupled metal particles to derive the optical transfer function and identify the physical properties essential for asymmetry. We validate our theory experimentally showing how the asymmetric response of a two-dimensional (planar) metasurface can be optically tuned. Our results set the direction for future developments of metasurfaces for optical signal processing.
- Published
- 2019
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39. Advances in the application of comprehensive two-dimensional gas chromatography in metabolomics.
- Author
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Keppler EAH, Jenkins CL, Davis TJ, and Bean HD
- Abstract
Due to excellent separation capacity for complex mixtures of chemicals, comprehensive two-dimensional gas chromatography (GC × GC) is being utilized with increasing frequency for metabolomics analyses. This review describes recent advances in GC × GC method development for metabolomics, organismal sampling techniques compatible with GC × GC, metabolomic discoveries made using GC × GC, and recommendations and best practices for collecting and reporting GC × GC metabolomics data.
- Published
- 2018
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40. Mesoscale surface plasmons: modelling and imaging using near-field scanning optical microscopy.
- Author
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Mayevsky AD, Davis TJ, Ballard PM, Henderson CA, and Funston AM
- Abstract
Meso-scale plasmons are supported by structures with dimensions on the order of tens of plasmon wavelengths. Metal structures at this length-scale are promising for the design and engineering of structures to direct the flow of optical energy and generate high intensity, localized electric fields. The near-field optical properties of mesoscale crystalline gold plates were examined using near-field scanning optical microscopy with a focus on the effects of modifying morphology and excitation conditions. Excitation of surface plasmon polaritons (SPPs) at plate edges and their subsequent propagation and interference as radial waves across the surface results in nodes of enhancement of the near-field on the plate surface at specific positions within the plate. The spatial position of the near-field enhancement may be directed by controlling either, or both, the boundary conditions (plate shape) and polarization of the excitation light.
- Published
- 2018
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41. Optical image processing with metasurface dark modes.
- Author
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Roberts A, Gómez DE, and Davis TJ
- Abstract
Here we consider image processing using the optical modes of metasurfaces with an angle-dependent excitation. These spatially dispersive modes can be used to directly manipulate the spatial frequency content of an incident field, suggesting their use as ultra-compact alternatives for analog optical information processing. A general framework for describing the filtering process in terms of the optical transfer functions is provided. In the case where the relevant mode cannot be excited with a normally incident plane wave (a dark mode), high-pass filtering is obtained. We provide examples demonstrating filtering of both amplitude and pure phase objects.
- Published
- 2018
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42. A cluster phase analysis for collective behavior in team sports.
- Author
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López-Felip MA, Davis TJ, Frank TD, and Dixon JA
- Subjects
- Adolescent, Adult, Cluster Analysis, Decision Making physiology, Humans, Male, Soccer physiology, Young Adult, Cooperative Behavior, Interpersonal Relations, Soccer psychology
- Abstract
Collective behavior can be defined as the ability of humans to coordinate with others through a complex environment. Sports offer exquisite examples of this dynamic interplay, requiring decision making and other perceptual-cognitive skills to adjust individual decisions to the team self-organization and vice versa. Considering players of a team as periodic phase oscillators, synchrony analyses can be used to model the coordination of a team. Nonetheless, a main limitation of current models is that collective behavior is context independent. In other words, players on a team can be highly synchronized without this corresponding to a meaningful coordination dynamics relevant to the context of the game. Considering these issues, the aim of this study was to develop a method of analysis sensitive to the context for evidence-based measures of collective behavior., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
43. Cathodoluminescence as a probe of the optical properties of resonant apertures in a metallic film.
- Author
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Singh K, Panchenko E, Nasr B, Liu A, Wesemann L, Davis TJ, and Roberts A
- Abstract
Here we present the results of an investigation of resonances of azimuthal trimer arrangements of rectangular slots in a gold film on a glass substrate using cathodoluminescence (CL) as a probe. The variation in the CL signal collected from specific locations on the sample as a function of wavelength and the spatial dependence of emission into different wavelength bands provides considerable insight into the resonant modes, particularly sub-radiant modes, of these apertures. By comparing our experimental results with electromagnetic simulations we are able to identify a Fabry-Pérot mode of these cavities as well as resonances associated with the excitation of surface plasmon polaritons on the air-gold boundary. We obtain evidence for the excitation of dark (also known as sub-radiant) modes of apertures and aperture ensembles.
- Published
- 2018
- Full Text
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44. Plasmonic circuit for second-order spatial differentiation at the subwavelength scale.
- Author
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Hwang Y, Davis TJ, Lin J, and Yuan XC
- Abstract
We suggest a plasmonic nanodevice for performing the second-order spatial derivative of light fields. The device consists of five gold nanorods arranged to evanescently couple to each other so that emit cross-polarized output proportional to the second-order differentiation of the incident wave. A theoretical model based on the electrostatic eigenmode analysis is derived and numerical simulations using the finite-difference time-domain methods are provided as supporting evidence. It is shown in both the analytic and numerical methods that the proposed plasmonic circuit performs second-order differentiation of the phase of the incident light field in transmission mode with a subwavelength planar resolution. The resolution of 0.29 λ
-1 is numerically demonstrated for a 20 nm thick circuit at the wavelength of 700 nm. The suggested plasmonic device has potential application in miniaturized systems for all-optical computation.- Published
- 2018
- Full Text
- View/download PDF
45. Spatial Release From Masking in Adults With Bilateral Cochlear Implants: Effects of Distracter Azimuth and Microphone Location.
- Author
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Davis TJ and Gifford RH
- Subjects
- Adult, Aged, Aged, 80 and over, Deafness psychology, Female, Humans, Male, Middle Aged, Psychoacoustics, Cochlear Implants, Deafness rehabilitation, Pattern Recognition, Physiological, Perceptual Masking, Speech Perception
- Abstract
Purpose: The primary purpose of this study was to derive spatial release from masking (SRM) performance-azimuth functions for bilateral cochlear implant (CI) users to provide a thorough description of SRM as a function of target/distracter spatial configuration. The secondary purpose of this study was to investigate the effect of the microphone location for SRM in a within-subject study design., Method: Speech recognition was measured in 12 adults with bilateral CIs for 11 spatial separations ranging from -90° to +90° in 20° steps using an adaptive block design. Five of the 12 participants were tested with both the behind-the-ear microphones and a T-mic configuration to further investigate the effect of mic location on SRM., Results: SRM can be significantly affected by the hemifield origin of the distracter stimulus-particularly for listeners with interaural asymmetry in speech understanding. The greatest SRM was observed with a distracter positioned 50° away from the target. There was no effect of mic location on SRM for the current experimental design., Conclusion: Our results demonstrate that the traditional assessment of SRM with a distracter positioned at 90° azimuth may underestimate maximum performance for individuals with bilateral CIs.
- Published
- 2018
- Full Text
- View/download PDF
46. Imaging the Nonlinear Plasmoemission Dynamics of Electrons from Strong Plasmonic Fields.
- Author
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Podbiel D, Kahl P, Makris A, Frank B, Sindermann S, Davis TJ, Giessen H, Hoegen MH, and Meyer Zu Heringdorf FJ
- Abstract
We use subcycle time-resolved photoemission microscopy to unambiguously distinguish optically triggered electron emission (photoemission) from effects caused purely by the plasmonic field (termed "plasmoemission"). We find from time-resolved imaging that nonlinear plasmoemission is dominated by the transverse plasmon field component by utilizing a transient standing wave from two counter-propagating plasmon pulses of opposite transverse spin. From plasmonic foci on flat metal surfaces, we observe highly nonlinear plasmoemission up to the fifth power of intensity and quantized energy transfer, which reflects the quantum-mechanical nature of surface plasmons. Our work constitutes the basis for novel plasmonic devices such as nanometer-confined ultrafast electron sources as well as applications in time-resolved electron microscopy.
- Published
- 2017
- Full Text
- View/download PDF
47. Combined Electric and Acoustic Stimulation With Hearing Preservation: Effect of Cochlear Implant Low-Frequency Cutoff on Speech Understanding and Perceived Listening Difficulty.
- Author
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Gifford RH, Davis TJ, Sunderhaus LW, Menapace C, Buck B, Crosson J, O'Neill L, Beiter A, and Segel P
- Subjects
- Acoustic Stimulation, Adult, Aged, Electric Stimulation, Female, Hearing, Hearing Aids, Humans, Male, Middle Aged, Noise, Signal-To-Noise Ratio, Software, Cochlear Implants, Speech Perception
- Abstract
Objective: The primary objective of this study was to assess the effect of electric and acoustic overlap for speech understanding in typical listening conditions using semidiffuse noise., Design: This study used a within-subjects, repeated measures design including 11 experienced adult implant recipients (13 ears) with functional residual hearing in the implanted and nonimplanted ear. The aided acoustic bandwidth was fixed and the low-frequency cutoff for the cochlear implant (CI) was varied systematically. Assessments were completed in the R-SPACE sound-simulation system which includes a semidiffuse restaurant noise originating from eight loudspeakers placed circumferentially about the subject's head. AzBio sentences were presented at 67 dBA with signal to noise ratio varying between +10 and 0 dB determined individually to yield approximately 50 to 60% correct for the CI-alone condition with full CI bandwidth. Listening conditions for all subjects included CI alone, bimodal (CI + contralateral hearing aid), and bilateral-aided electric and acoustic stimulation (EAS; CI + bilateral hearing aid). Low-frequency cutoffs both below and above the original "clinical software recommendation" frequency were tested for all patients, in all conditions. Subjects estimated listening difficulty for all conditions using listener ratings based on a visual analog scale., Results: Three primary findings were that (1) there was statistically significant benefit of preserved acoustic hearing in the implanted ear for most overlap conditions, (2) the default clinical software recommendation rarely yielded the highest level of speech recognition (1 of 13 ears), and (3) greater EAS overlap than that provided by the clinical recommendation yielded significant improvements in speech understanding., Conclusions: For standard-electrode CI recipients with preserved hearing, spectral overlap of acoustic and electric stimuli yielded significantly better speech understanding and less listening effort in a laboratory-based, restaurant-noise simulation. In conclusion, EAS patients may derive more benefit from greater acoustic and electric overlap than given in current software fitting recommendations, which are based solely on audiometric threshold. These data have larger scientific implications, as previous studies may not have assessed outcomes with optimized EAS parameters, thereby underestimating the benefit afforded by hearing preservation.
- Published
- 2017
- Full Text
- View/download PDF
48. Luminescence of a Transition Metal Complex Inside a Metamaterial Nanocavity.
- Author
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Connell TU, Earl SK, Ng C, Roberts A, Davis TJ, White JM, Polyzos A, and Gómez DE
- Abstract
Modification of the local density of optical states using metallic nanostructures leads to enhancement in the number of emitted quanta and photocatalytic turnover of luminescent materials. In this work, the fabrication of a metamaterial is presented that consists of a nanowire separated from a metallic mirror by a polymer thin film doped with a luminescent organometallic iridium(III) complex. The large spin-orbit coupling of the heavy metal atom results in an excited state with significant magnetic-dipole character. The nanostructured architecture supports two distinct optical modes and their assignment achieved with the assistance of numerical simulations. The simulations show that one mode is characterized by strong confinement of the electric field and the other by strong confinement of the magnetic field. These modes elicit drastic changes in the emitter's photophysical properties, including dominant nanocavity-derived modes observable in the emission spectra along with significant increases in emission intensity and the total decay rate. A combination of simulations and momentum-resolved spectroscopy helps explain the mechanism of the different interactions of each optical mode supported by the metamaterial with the excited state of the emitter., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
- Full Text
- View/download PDF
49. Short-range surface plasmonics: Localized electron emission dynamics from a 60-nm spot on an atomically flat single-crystalline gold surface.
- Author
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Frank B, Kahl P, Podbiel D, Spektor G, Orenstein M, Fu L, Weiss T, Horn-von Hoegen M, Davis TJ, Meyer Zu Heringdorf FJ, and Giessen H
- Abstract
We experimentally and theoretically visualize the propagation of short-range surface plasmon polaritons using atomically flat single-crystalline gold platelets on silicon substrates. We study their excitation and subfemtosecond dynamics via normal-incidence two-photon photoemission electron microscopy. By milling a plasmonic disk and grating structure into a single-crystalline gold platelet, we observe nanofocusing of the short-range surface plasmon polariton. Localized two-photon ultrafast electron emission from a spot with a smallest dimension of 60 nm is observed. Our novel approach opens the door toward reproducible plasmonic nanofocusing devices, which do not degrade upon high light intensity or heating due to the atomically flat surface without any tips, protrusions, or holes. Our nanofoci could also be used as local emitters for ultrafast electron bunches in time-resolved electron microscopes.
- Published
- 2017
- Full Text
- View/download PDF
50. The Stance Leads the Dance: The Emergence of Role in a Joint Supra-Postural Task.
- Author
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Davis TJ, Pinto GB, and Kiefer AW
- Abstract
Successfully meeting a shared goal usually requires co-actors to adopt complementary roles. However, in many cases, who adopts what role is not explicitly predetermined, but instead emerges as a consequence of the differences in the individual abilities and constraints imposed upon each actor. Perhaps the most basic of roles are leader and follower . Here, we investigated the emergence of "leader-follower" dynamics in inter-personal coordination using a joint supra-postural task paradigm (Ramenzoni et al., 2011; Athreya et al., 2014). Pairs of actors were tasked with holding two objects in alignment (each actor manually controlled one of the objects) as they faced different demands for stance (stable vs. difficult) and control (which actor controlled the larger or smaller object). Our results indicate that when actors were in identical stances, neither led the inter-personal (between actors) coordination by any systematic fashion. Alternatively, when asymmetries in postural demands were introduced, the actor with the more difficult stance led the coordination (as determined using cross-recurrence quantification analysis). Moreover, changes in individual stance difficulty resulted in similar changes in the structure of both intra-personal (individual) and inter-personal (dyadic) coordination, suggesting a scale invariance of the task dynamics. Implications for the study of interpersonal coordination are discussed.
- Published
- 2017
- Full Text
- View/download PDF
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