Author: "Hilliard D" / Language: english - Searchworks@Jio Institute Digital Library Search Results

71 results on '"Hilliard D"'

1. Towards axial heterostructures with atomically-sharp interfaces in self-catalyzed nanowires

Author: Hilliard, D., Tauchnitz, T., Hübner, R., Schneider, H., Helm, M., and Dimakis, E.
Abstract: Axial heterostructures have diverse functionality in electronic and optoelectronic devices. Implementing such systems in freestanding semiconducting nanowires further broadens the scope of potential applications, for example: distributed Bragg reflectors, high-efficiency light-emitting diodes, and quantum dot heterostructures. The challenge, however, lies in reducing the compositional grading effect of the constituent heterostructure materials across the interfaces in nanowires grown in vapor-liquid-solid mode. Here, our previously developed nanowire growth technique called droplet-confined alternate pulsed-epitaxy [1] (an adaptation of conventional molecular beam epitaxy), which grants precise control over the axial growth rate and droplet composition, is employed to grow Al(x)Ga(1-x)As axial insertions in self-catalyzed GaAs nanowires. A full nanowire with six insertions is shown in Figure 1 (top). High-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) and nanowire growth models are utilized to gain an understanding of the compositional grading mechanism and its dependence on the growth temperature (TG), the nanowire radius (RNW), and the amount of supplied Al. Figure 1 (bottom) is an example HAADF-STEM image showing two atomically resolved Al(x)Ga(1-x)As insertions embedded in a zincblende GaAs nanowire, whereas Figure 2 shows the extracted Al-content (x) axial profiles for three selected insertions with different TG and RNW (the same amount of supplied Al). We show that lower TG and/or smaller RNW result in sharper interfaces, with a more profound improvement for the AlxGa1-xAs-to-GaAs interface. In the best case, almost symmetric insertions with interface thicknesses of only 2 – 3 monolayers are achieved, approaching the absolute limit of atomically sharp interfaces. Thermodynamics, kinetics, and nanowire geometry are all factors considered during the formation of our Al(x)Ga(1-x)As insertions. Using two existing heterostructure growth models [2, 3] to fit our experimental data we can extract valuable quantitative information regarding the interface characteristics. Our results show for the first time that not only TG, but also size effects, i.e. a decreasing RNW, play a large role in the thermodynamic stability at the liquid-solid interface, setting previously unknown limitations on the maximum attainable interface sharpness. These findings and their implications will be discussed in detail. The functionality of our insertions is successfully tested via their employment as axial barriers in quantum dot nanowire heterostructures. By growing the quantum dot heterostructure at 350 °C, consequently sharpening the quantum dot interfaces, we observe a one order of magnitude decrease in quantum dot emission linewidth (Figure 3) in comparison to a similar system grown at 550 °C. 1. Balaghi et al., Nano Lett. 16, 4032 (2016) 2. Luna et al., Phys. Rev. Lett. 109, 126101 (2012) 3. Priante et al., Nano Lett. 16, 1917 (2016)
Published: 2022

2. Enhancing the interface sharpness of axial heterostructures in self-catalyzed nanowires

Author: Hilliard, D., Tauchnitz, T., Hübner, R., Schneider, H., Helm, M., and Dimakis, E.
Abstract: Axial heterostructures have diverse functionality in electronic and optoelectronic devices. Implementing such systems in freestanding semiconducting nanowires further broadens the scope of potential applications, for example: distributed Bragg reflectors, high-efficiency light-emitting diodes, and quantum dot heterostructures. The challenge, however, lies in reducing the compositional grading effect of the constituent heterostructure materials across the interfaces in nanowires grown in vapor-liquid-solid mode. Here, our previously developed nanowire growth technique called droplet-confined alternate pulsed-epitaxy [1] (an adaptation of conventional molecular beam epitaxy), which grants precise control over the axial growth rate and droplet composition, is employed to grow Al(x)Ga(1-x)As axial insertions in self-catalyzed GaAs nanowires. High-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) and nanowire growth models are utilized to gain an understanding of the compositional grading mechanism and its dependence on the growth temperature (TG), the nanowire radius (RNW), and the amount of supplied Al. Figure 1 (a) is an example HAADF-STEM image showing two Al(x)Ga(1-x)As insertions embedded in a zincblende GaAs nanowire, whereas Figure 1 (b) shows the extracted Al-content (x) axial profiles for three selected insertions with different TG and RNW (the same amount of supplied Al). We show that lower TG and/or smaller RNW result in sharper interfaces, with a more profound improvement for the AlxGa1-xAs-to-GaAs interface. In the best case, almost symmetric insertions with interface thicknesses of only 2 – 3 monolayers are achieved, approaching the absolute limit of atomically sharp interfaces. The fitting of our experimental data with existing heterostructure growth models [2, 3] is suggestive of different mechanisms behind the compositional grading of the two interfaces and will be discussed in detail. The functionality of our insertions is successfully tested via their employment as axial barriers in quantum dot nanowire heterostructures. By growing the quantum dot heterostructure at 350 °C, consequently sharpening the quantum dot interfaces, we observe a one order of magnitude decrease in quantum dot emission linewidth (Figure 1 (c)) in comparison to a similar system grown at 550 °C. [1] Balaghi et al., Nano Lett. 16, 4032 (2016) [2] Luna et al., Phys. Rev. Lett. 109, 126101 (2012) [3] Priante et al., Nano Lett. 16, 1917 (2016)
Published: 2022

3. The Origin of Lay Control of Public Education in Memphis, Tennessee

Author: Hilliard, D. Moss
Published: 1946

4. Historical Development of Grades and Departments in the Public Schools of Memphis, Tennessee

Author: Hilliard, D. Moss
Published: 1946

5. Complex quantum dots in III-As nanowires

Author: Hilliard, D., Tauchnitz, T., Hübner, R., Schneider, H., Helm, M., and Dimakis, E.
Subjects: Nanowire, Condensed Matter::Materials Science, Quantum dot, Interface, Condensed Matter::Mesoscopic Systems and Quantum Hall Effect, Superlattice, Strain
Abstract: Single quantum dots embedded in the core of freestanding semiconductor nanowires grown directly on Si offer a novel and promising scheme for the realization of on-demand sources of single photons or entangled photon pairs in quantum technology systems. Here, we have investigated the growth mechanism and optical properties of axial quantum dots embedded in GaAs nanowires grown in self-catalyzed vapor-liquid-solid mode while demonstrating the tuneabilty of their emission energy across a wide range of wavelengths with the potential for telecom band access. We have incorporated GaAs complex quantum dots inside GaAs/In(x)Al(1-x)As and GaAs/Al(x)Ga(1-x)As core/shell nanowires grown via our nanowire growth technique called droplet-confined alternate pulsed-epitaxy (DCAPE)[1] (an adaptation of conventional molecular beam epitaxy (MBE)), which grants precise control over the axial growth rate and droplet composition. Using a combination of conventional MBE and DCAPE the growth of highly symmetrical quantum dots, as little as 10 nm in diameter and just a few nanometers in height, were made possible. Strong axial confinement was achieved in the form of a double axial heterostructure by incorporating two Al(x)Ga(1-x)As/Al(y)Ga(1-y)As short-period superlattices separated by a thin GaAs segment (figure 1(a)). The complexity of our quantum dots is derived from the unique possibility of using different ternary alloys for the axial and radial confinement. By introducing a latticed mismatched ternary alloy shell as the radial barrier (In(x)Al(1-x)As), we demonstrated controlled hydrostatic strain induced redshifts of the highly polarized quantum dot emission energy by adjusting the In content of the shell. For 39% In we measured a redshift in the quantum dot emission of 320 meV, from an unstrained quantum dot reference (Al(x)Ga(1-x)As shell), as shown by the photoluminescence measurements in figure 1 (b). To optimize the emission quality, the compositional grading effect of the constituent superlattice materials across the interfaces must be addressed. High-angle annular dark-field scanning transmission electron microscopy, energy-dispersive X-ray spectroscopy, and nanowire growth models were utilized to gain an understanding of the compositional grading mechanism at the quantum dot/superlattice interface. We found that interfacial sharpness increases significantly by reducing the superlattice growth temperature and nanowire radius. Notwithstanding, limitations in what can be achieved ensue and possible strategies to overcome them will be presented. [1] Balaghi et al., Nano Lett. 16, 4032 (2016)
Published: 2021

6. Al(x)Ga(1-x)As /Al(y)Ga(1-y)As axial short-period superlattices in self-catalyzed nanowires

Author: Hilliard, D., Tauchnitz, T., Hübner, R., Schneider, H., Helm, M., and Dimakis, E.
Subjects: Nanowire, Condensed Matter::Materials Science, Quantum dot, Interface, Condensed Matter::Mesoscopic Systems and Quantum Hall Effect, Superlattice, Strain
Abstract: Shrt abstract: Using our nanowire growth technique called droplet-confined alternate pulsed-epitaxy, which provides precise control over the axial growth rate and droplet composition, the growth mechanism of self-catalyzed GaAs epitaxial nanowires containing AlxGa1-xAs/AlyGa1-yAs axial short-period superlattices, was systematically examined. Significant increases in interfacial abruptness were confirmed by reducing the nanowire diameter and superlattice growth temperature. Additionally, we found that an unstable droplet contact angle impacts the superlattice growth rate considerably. The unique versatility of our short-period superlattices was tested by using them as axial barriers for GaAs quantum dot heterostructures embedded in nanowires. Furthermore, encapsulating the nanowire in lattice-mismatched shells operating as radial barriers, we demonstrated the tuneabilty of the quantum dot emission energy via strain engineering. Long abstract Short-period superlattices have diverse functionality in electronic and optoelectronic devices. Implementing such systems as axial heterostructures in freestanding semiconducting nanowires further broadens the scope of potential applications, for example: distributed Bragg reflectors, high-efficiency light-emitting diodes, and quantum dot heterostructures. The challenge, however, lies in reducing the compositional grading effect of the constituent superlattice materials across the interfaces in nanowires grown in self-catalyzed vapor-liquid-solid mode. Here, our previously developed nanowire growth technique called droplet-confined alternate pulsed-epitaxy[1] (an adaptation of conventional molecular beam epitaxy), which grants precise control over the axial growth rate and droplet composition, was employed to grow Al(x)Ga(1-x)As/Al(y)Ga(1-y)As axial superlattices in self-catalyzed GaAs nanowires with diameters as thin as 20 nm. High-angle annular dark-field scanning transmission electron microscopy (figure 1(a)), energy-dispersive X-ray spectroscopy, and growth models were utilized to gain an understanding of the compositional grading mechanism. By varying several growth parameters involving growth temperature, nanowire diameter, and droplet contact angle, the link between them and the superlattice characteristics was explored. We found that interfacial abruptness increases significantly by reducing the superlattice growth temperature and nanowire radius. Moreover, we studied the impact of an unstable contact angle on the superlattice growth rate, showing good agreement with analytical growth models and demonstrating the importance of growth rate stability in obtaining reproducible Al contents across successive superlattice periods. We confirmed with monolayer resolution, controlled Al contents in a wide compositional range and superlattice period widths of just a few monolayers (figure 1 (b)). The quality of our short-period superlattices was successfully tested via their employment as axial barriers in quantum dot nanowire heterostructures (figure 1 (c)). Additionally, by introducing a lattice-mismatched ternary alloy shell as the radial barrier (In(x)Al(1-x)As in this case), we demonstrated controlled strain-induced redshifts of the quantum dot emission energy by adjusting the In content of the shell. For 39% In, we measured a redshift in the quantum dot emission of 180 meV as shown by the photoluminescence measurements in figure 1 (d). Notwithstanding, limitations in what can be accomplished are present and possible strategies to overcome them will be presented. [1] Balaghi et al., Nano Lett. 16, 4032 (2016)
Published: 2021

7. Tunable Magnetic Vortex Dynamics in Ion-Implanted Permalloy Disks

Author: Ramasubramanian, L., Kákay, A., Fowley, C., Yildirim, O., Matthes, P., Sorokin, S., Titova, A., Hilliard, D., Böttger, R., Hübner, R., Gemming, S., Schulz, S. E., Kronast, F., Makarov, D., Faßbender, J., Deac, A. M., and Publica
Subjects: frequency tunability, ion implantation, reduced saturation magnetisation, vortex dynamics, electrical detection
Abstract: Nanoscale, low-phase noise, tunable transmitter-receiver links are key for enabling the progress of wireless communi-cation. We demonstrate that vortex-based spin-torque nano-oscillators, which are intrinsically low-noise devices due to their topologically-protected magnetic structure, can achieve frequency tunability when submitted to local ion im-plantation. In the experiments presented here, the gyrotropic mode is excited with spin-polarized alternating currents and anisotropic magnetoresistance measurements yield discreet frequencies from a single device. Indeed, chromium-implanted regions of permalloy disks exhibit different saturation magnetisation than the surrounding, non-irradiated areas, and thus different resonance frequency, corresponding to the specific area where the core is gyrating. Our study proves that such devices can be fabricated without the need of further lithographical steps, suggesting ion irradiation can be a viable and cost-effective fabrication method for densely-packed networks of oscillators.
Published: 2020

8. Dipeptidyl Peptidase-4 Inhibitors Administered in Combination With Metformin Result in an Additive Increase in the Plasma Concentration of Active GLP-1

Author: Migoya, E M, Bergeron, R, Miller, J L, Snyder, R NK, Tanen, M, Hilliard, D, Weiss, B, Larson, P, Gutierrez, M, Jiang, G, Liu, F, Pryor, K A, Yao, J, Zhu, L, Holst, J J, Deacon, C, Herman, G, Thornberry, N, Amatruda, J, Williams-Herman, D, Wagner, J A, and SinhaRoy, R
Published: 2010
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9. Multiple-Dose Pharmacodynamics and Pharmacokinetics of Anacetrapib, a Potent Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Healthy Subjects

Author: Krishna, R, Bergman, A J, Jin, B, Fallon, M, Cote, J, Van Hoydonck, P, Laethem, T, Gendrano, I N, III, Van Dyck, K, Hilliard, D, Laterza, O, Snyder, K, Chavez-Eng, C, Lutz, R, Chen, J, Bloomfield, D M, De Smet, M, Van Bortel, L M, Gutierrez, M, Al-Huniti, N, Dykstra, K, Gottesdiener, K M, and Wagner, J A
Published: 2008
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10. Optimizing dose selection using population PK/FD modeling and simulation for the cholesteryl ester transfer protein (CETP) inhibitor MK-0859 in healthy subjects: 8

Author: Bergman, A., Dykstra, K., Al-Huniti, N., Fallon, M., Lute, R., Chavez-Eng, C., Jin, B., Hartford, A., Cote, J., Hilliard, D., Laethem, T., Van Hoydonck, P., Snyder, K., Van Dyck, K., Stone, J., Lasseter, K. C., Van Bortel, L., Wagner, J., and Krishna, R.
Published: 2008

11. Pharmacokinetics, Pharmacodynamics, and Safety of a Prostaglandin D2 Receptor Antagonist

Author: Lai, E, Wenning, L A, Crumley, T M, De Lepeleire, I, Liu, F, de Hoon, J N, Van Hecken, A, Depré, M, Hilliard, D, Greenberg, H, OʼNeill, G, Metters, K, Gottesdiener, K G, and Wagner, J A
Published: 2008
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12. DEMONSTRATION OF SPECIFIC COX-2 INHIBITION BY MK-966 IN HUMANS WITH SUPRATHERAPEUTIC DOSES.

Author: Van Hecken, A., Depré, M., Ehrich, E., De Lepeleire, I., Hilliard, D., Porras, A., Wong, P., Buntinx, A., Gertz, B. J., and De Schepper, P. J.
Published: 1999

13. Ion Irradiation Induced Cobalt/Cobalt Oxide Heterostructures: From Materials to Devices

Author: Hilliard, D., Yildirim, O., Fowley, C., Arekapudi, S. S. P. K., Cansever, H., Böttger, R., Hlawacek, G., Hellwig, O., Lindner, J., Faßbender, J., and Deac, A. M.
Subjects: displacement, bias, irradiation, magnetic, removal, exchange, cobalt oxide, oxygen removal, reduction, perpencular, anisotropy, magnetization, cobalt, oxygen reduction, Co3O4, ferromagnetic, ion beam, antiferromagnetic, ion, oxygen, CoO, proton, paramagnetic
Abstract: The demand on high data transfer and storage capacities requires smaller devices to transmit or save data. Forming well-defined ferromagnetic and electrically conducting volumes within a non-magnetic and insulating matrix in the dimensions of several nanometers can pave a way to the production of such small devices. It has been demonstrated that the reduction of oxygen in Co₃O₄/Pd multilayers is possible via local proton irradiation resulting in ferromagnetic and conducting Co embedded in a nonmagnetic and insulating Co₃O₄ matrix [1]. However, the physical mechanism behind the ion irradiation-induced oxide reduction was not addressed clearly. There are two possible mechanisms suggested to play a role behind this oxide reduction. The first one is the chemical reduction of oxygen by reacting with implanted H+ ions, while the second possible mechanism is atomic displacements induced by ion irradiation. To address this issue, we analysed cobalt oxide thin films after irradiation with H+ and Ne+ ions at different doses. The irradiation parameters for Ne+ were chosen to give the same displacements per atom (dpa) as that of H+ which is required to reduce cobalt oxide. We also confined irradiated areas on the films in the range of microns to submicron, in order to ascertain the lateral distribution of oxygen after irradiation. We prepared single layer films of CoO (6-12nm) and Co₃O₄ (10nm) capped with Pt protection layers. Broad-beam H+ irradiations were performed at 0.3 keV for ion doses ranging from 10¹⁵ to 10¹⁷ ions/cm² on unpatterned films. After irradiation the films were characterized structurally and magnetically and compared to un-irradiated films. Extended films showed approximately 7% of the Co bulk metal saturation magnetization (MS) after irradiation at a dose of 5 x 10¹⁶ ions/cm² (fig. 1a inset). The increase is more pronounced with Co₃O₄ than CoO (fig. 1a). A sample was also prepared with a striped irradiation mask of 40 μm pitch. These films showed a higher magnetization after irradiation at lower doses as compared to unpatterned films, 0.14 MA/m for a dose of 10¹⁶ ions/cm² (striped) as opposed to 0.025 MA/m (extended) for a dose of 10¹⁷ ions/cm². Figure 1 (b) shows the effect of stripe width (0.5, 5, 10, 20 μm) on the resulting magnetization after H+ irradiation at the same energy with a dose of 10¹⁷ ions/cm². No clear correlation between stripe width and MS was seen in either oxide phase for stripes down to 0.5 μm. However, the CoO sample with 0.5 μm stripes and a thinner oxide thickness of 6 nm (gold line) as opposed to 12 nm exhibited larger MS after irradiation, indicating oxygen displacements occur in the first few nanometers of the oxide. We also performed 5 keV Ne+ irradiations with the helium-ion microscope (HIM) varying the ion dose from 10¹⁴ to 10¹⁶ ions/cm². After Ne+ irradiations magnetic force microscopy (MFM) images were taken along with a topography image in the remnant state (fig. 2). Starting from the ion dose of 5x10¹⁴ ions/cm², a magnetic contrast could be observed by MFM, suggesting that oxygen atoms were successfully removed locally by reducing paramagnetic CoO to ferromagnetic Co. The formation of topographical bubbles was observed upon increasing the ion dose from 10¹⁵ ions/cm² to 10¹⁶ ions/cm². The lateral and horizontal sizes of the observed bubbles show a clear dependence on the ion dose with a narrow size distribution. In conclusion, our results show that, oxygen removal by means of H+ irradiation is more efficient in Co₃O₄ films as opposed to CoO. Additionally, although there is little dependence of the resulting Ms on the pitch of the stripes (in the range of 0.5 - 20 μm), the use of a stripe mask has a more pronounced effect on the oxygen removal process as compared to the irradiations on extended films. Therefore, the physical mechanism behind the ion-irradiation induced oxide reduction process cannot purely be a chemical reaction between oxygen and hydrogen. As an outlook, the lateral size and spacing of the ferromagnetic regions generated by H+ irradiation is only limited by the resolution of EBL. This method and the successful formation of ferromagnetic regions upon Ne+ irradiation using the HIM can be exploited to print smaller, closer and synchronized contacts for nanocontact spin torque oscillators.
Published: 2018

14. Ion Irradiation Induced Cobalt/Cobalt Oxide Heterostructures: From Materials to Devices

Author: Hilliard, D., Yildirim, O., Fowley, C., Kanth Arekapudi, S. S. P. K., Cansever, H., Böttger, R., Hlawacek, G., Hellwig, O., Lindner, J., Fassbender, J., Deac, A. M., and Perzanowski, M.
Subjects: Condensed Matter::Materials Science, Ion irradiation, Oxygen reduction, Ferromagnetic, Cobalt oxide
Abstract: Spintronic devices are often patterned from continuous films into micro- or nanostructures. Fabrication of those nano-devices is self-limited and depends on the lateral resolution of the chosen fabrication method. Ion irradiation offers an alternative route to introduce smaller magnetic patterns limited by the size of the ion beam. Irradiation of oxide materials can cause chemical reduction and lead to the local formation of metallic species. By using the oxide family of ferromagnets (e.g., Fe, Ni and Co), reduction leads to the formation of ferromagnetic and conducting volumes limited by the size of the ion irradiated area that are embedded into a non-magnetic and insulating matrix. On the other hand, the physical mechanism behind ion irradiation-induced oxide reduction could not be explained. Therefore, our studies focus on ion (H, He, Ne, O) irradiated cobalt-oxide (CoO or Co3O4) systems in order to explain the physics behind the process. Also, the knowledge is being exploited to tune exchange-bias direction, prepare nano contacts for synchronized spin torque oscillators, and to form topographically stabilized magnetic skyrmions.
Published: 2017

15. Race Walkers Quicken Their Pace by Tuning In, Not Stepping Out.

Author: Clingman, Joy M. and Hilliard, D. Vanessa
Subjects: WALKING (Sports), SPORT walking training, ATHLETES, HUMAN locomotion, DISSOCIATION (Psychology), WALKING
Abstract: This study examined the effects of attentional focus on race walking performance. Sixteen experienced race walkers, eight males and eight females, were randomly assigned to walk four separate half-mile segments on a quarter-mile track under specific sets of instructions. Two sets of instructions were externally oriented and two were internally oriented. The internally oriented instructions included a set asking the subjects to focus on cadence (the number of steps taken in a designated period of time) and a set asking them to focus on stride length (the distance covered in a single step). The externally oriented instructions asked subjects to use a dissociative strategy. Although no overall difference was found between internal and external focus, results indicated that the focus on cadence was superior to both the external focus, p<.05, and a focus on stride length, p<.05. No significant differences between the stride length focus and the external focus were found. These results are discussed in terms of the importance of using an internal focus that is beneficial. [ABSTRACT FROM AUTHOR]
Published: 1990
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16. LETTERS.

Author: GIRONDELOT, HENRI, FERMAUD, RUTH WHIPPLE, GREENE, ALVIN C., PATTON, PRICE A., FRY, MEREDITH W., SCHULZ JR., WILLIAM, ROLLINS, KENNETH B., LOWANCE, WILLIAM F., BEEBE, LUCIUS, HOUSTLE JR., ARCH E., COOK, HILLIARD D., MORRISON, ROBERT L., FITCH, JOHN, BAKER, WILLIAM C., SIMMONS, RALPH, LITTLEFIELD, JEAN TYLER, COBB, NED I., GROSS, NATHAN K., PAUL, LORRAINE B., and CHEEVER, C. E.
Subjects: FINANCIAL counseling, INTERNATIONAL relations, FINANCIAL planning, WEALTH management services
Published: 1956

17. Radar Cross Section measurements of small Unmanned Air Vehicle Systems in non-cooperative field environments.

Author: To, L., Bati, A., and Hilliard, D.
Published: 2009

18. Utilization of compact range collimator for Radar Cross-Section measurements.

Author: Hilliard, D., Mensa, D., and Oh, K.
Published: 2009

19. Performance of an Automated High Accuracy Phase Measurement System.

Author: Stein, S., Glaze, D., Levine, J., Gray, J., Hilliard, D., Howe, D., and Erb, L.
Published: 1982
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20. Pharmacokinetics, Pharmacodynamics, and Safety of a Prostaglandin D2 Receptor Antagonist.

Author: Lai, E., Wenning, L. A., Crumley, T. M., De Lepeleire, I., Liu, F., de Hoon, J. N., Van Hecken, A., Depré, M., Hilliard, D., Greenberg, H., O'Neill, G., Metters, K., Gottesdiener, K. G., and Wagner, J. A.
Subjects: PHARMACOKINETICS, PHARMACODYNAMICS, PHYSIOLOGICAL effects of chemicals, THERAPEUTICS, SAFETY
Abstract: Laropiprant is a selective antagonist of the prostaglandin D2 (PGD2) receptor subtype 1 (DP1). Three double-blind, randomized, placebo-controlled studies evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of laropiprant in healthy male volunteers. Single doses up to 900 mg and multiple doses up to 450 mg were generally well tolerated. Laropiprant exhibited dose-proportional pharmacokinetics. Oral absorption is rapid (Tmax=0.8–2.0 h) and the terminal half-life is approximately 12–18 h. The pharmacokinetics of laropiprant was not affected by food. Single doses of 6 mg and higher were effective in suppressing PGD2-induced cyclic AMP accumulation in platelets, demonstrating laropiprant target engagement with DP1. Laropiprant has detectable off-target antagonist effects at the thromboxane A2 receptor but no clinically significant effect on collagen-induced platelet aggregation or bleeding times with multiple doses up to 200 mg.Clinical Pharmacology & Therapeutics (2008); 83, 6, 840–847 doi:10.1038/sj.clpt.6100345 [ABSTRACT FROM AUTHOR]
Published: 2008
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21. Pharmacokinetics and Pharmacodynamic Effects of the Oral DPP-4 Inhibitor Sitagliptin in Middle-Aged Obese Subjects.

Author: Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan AG, Lasseter K, Dilzer S, Blum R, and Wagner JA
Abstract: Sitagliptin (MK-0431) is an oral, potent, and selective dipeptidyl peptidase-IV (DPP-4) inhibitor developed for the treatment of type 2 diabetes. This multicenter, randomized, double-blind, placebo-controlled study examined the pharmacokinetic and pharmacodynamic effects of sitagliptin in obese subjects. Middle-aged (45-63 years), nondiabetic, obese (body mass index: 30-40 kg/m(2)) men and women were randomized to sitagliptin 200 mg bid (n = 24) or placebo (n = 8) for 28 days. Steady-state plasma concentrations of sitagliptin were achieved within 2 days of starting treatment, and >90% of the dose was excreted unchanged in urine. Sitagliptin treatment led to approximately 90% inhibition of plasma DPP-4 activity, increased active glucagon-like peptide-1 (GLP-1) levels by 2.7-fold (P < .001), and decreased post-oral glucose tolerance test glucose excursion by 35% (P < .050) compared to placebo. In nondiabetic obese subjects, treatment with sitagliptin 200 mg bid was generally well tolerated without associated hypoglycemia and led to maximal inhibition of plasma DPP-4 activity, increased active GLP-1, and reduced glycemic excursion. [ABSTRACT FROM AUTHOR]
Published: 2006

22. Anxiety reduction in competitive running as a function of success.

Author: Clingman, Joy M. and Hilliard, D. Vanessa
Subjects: *PSYCHOLOGY of athletes, *ANXIETY
Abstract: Examines the relationship between competition and anxiety in adult athletes. Use of the State-Trait Anxiety Inventory; Interactions between success and anxiety; Results in male and female athletes.
Published: 1994

23. Chemotherapy of non-small cell lung carcinoma guided by an in vitro drug resistance assay measuring total tumour cell kill.

Author: Wilbur, DW, Camacho, ES, Hilliard, DA, Dill, PL, Weisenthal, LM, Wilbur, D W, Camacho, E S, Hilliard, D A, Dill, P L, and Weisenthal, L M
Published: 1992
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24. Automated High-Accuracy Phase Measurement System.

Author: Stein, S., Glaze, D., Levine, J., Gray, J., Hilliard, D., Howe, D., and Erb, L. A.
Published: 1983
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25. The Measurement of Radioactivity in Solution.

Author: Solomon, A. K. and Estes, Hilliard D.
Published: 1948
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26. Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study

Author: Elovitz Michal A, Gomez Ricardo, Kusanovic Juan P, Srinivas Sindhu, York Timothy P, Hilliard DaShaunda D, Hill Lori D, Romero Roberto, and Strauss Jerome F
Subjects: Internal medicine, RC31-1245, Genetics, QH426-470
Abstract: Abstract Background Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate gene. Furthermore, ERAP2 expression is altered in first trimester placentas of women destined to develop preeclampsia. Methods A case-control design was used to test for associations between two SNPs in ERAP2, rs2549782 and rs17408150, and preeclampsia status in 1103 Chilean maternal-fetal dyads and 1637 unpaired African American samples (836 maternal, 837 fetal). Results We found that the fetal minor allele (G) of rs2549782 was associated with an increased risk for preeclampsia in the African American population (P = 0.009), but not in the Chilean population. We found no association between rs17408150 and risk for preeclampsia in the Chilean population. Association between rs17408150 and risk for preeclampsia was not tested in the African American population due to the absence of the minor allele in this population. Conclusions We report an association between fetal ERAP2 and preeclampsia in an African American population. In conjunction with previous studies, which have found maternal associations with this gene in an Australian/New Zealand population and a Norwegian population, ERAP2 has now been associated with preeclampsia in three populations. This provides strong evidence that ERAP2 plays a role in the development of preeclampsia.
Published: 2011
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27. Surface wave scattering on a drone air vehicle.

Author: Benson, M., Hilliard, D., Mensa, D., Oh, K., To, L., and Yates, W.
Published: 1993
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28. Luneburg lens antenna with photonic sensors.

Author: Hilliard, D. and Mensa, D.
Published: 1992
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29. LBOVI-A-3.

Author: Stoch, S. A., Tanaka, W. K., Hilliard, D. A., Chappell, D. L., Modur, V. R., Phillips, R. L., Deutsch, P., Abbi, S., Crumley, T. M., Miller, J. L., Lyle, S., Schapiro, B. L., Gottesdiener, K. M., and Wagner, J. A.
Subjects: BIOMARKERS, TESTOSTERONE, PHARMACODYNAMICS, GENE expression, RANDOMIZED controlled trials, PLACEBOS, DRUG side effects
Abstract: Background/aims: To pilot a pharmacodynamic (PD) model of short-term androgen administration that may be used to predict long-term effects of androgen administration in postmenopausal women. The study was specifically designed to identify biomarkers that evaluate early skin response to exogenous androgens. The clinical consequences of androgen administration include hirsutism and acne. Skin biopsies were performed to document morphological changes in the pilosebaceous unit (PSU) and gene expression changes (Taqman and microarray). Functional skin response was gauged by measuring sebum excretion rates (SER).Methods: A double-blind, randomized, placebo-controlled, parallel-group study was conducted in 36 healthy postmenopausal female subjects to identify early biomarkers of androgen administration. Subjects were randomized to receive either 2.5 mg of transdermal testosterone gel (TTG; AndroGel®), 300 μg of TTGtransdermal testosterone gel, or placebo gel, daily for 6 weeks in a 1:1:1 ratio. Skin biopsies were performed to document morphological changes in the pilosebaceous unit (PSU) and gene expression changes (Taqman and microarray). Five-mm skin punch biopsies were obtained from the back of subjects at baseline, after 6 weeks of treatment, and 4 weeks post treatment. Biopsies were analyzed for histological changes characterized by total sebaceous gland volume and sebocyte cell size. Skin biopsies were also analyzed for molecular skin changes using skin Taqman/microarray assays. Measurements of sebum excretion rates (SER) were obtained at baseline and after 6 weeks of treatment.Results: Six weeks of treatment with the 2.5-mg TTGdose of AndroGel® increased sebaceous gland volume on average by 42% (p=0.0410) and sebum excretion rateSER by 52% (p=0.0021) relative to placebo. Microarray and Taqman analyses on skin samples also demonstrated changes in the 2.5-mg TTG AndroGel® group. Histological and molecular findings were noted to be reversible 4 weeks after discontinuing therapy.Analysis of Total Sebaceous Gland Volume (106 μm3) at Week 6 (See Tables 1 and 2)Analysis Results for SER at Week 6Conclusions: TTG treatment is associated with marked increases in sebaceous gland volume and SER, consistent with side effects including hirsutism and acne. Biomarkers sufficiently robust to support using to test for androgen-mediated skin effects in postmenopausal women were identified.Clinical Pharmacology & Therapeutics (2005) 79, P84–P84; doi: 10.1016/j.clpt.2005.12.299 [ABSTRACT FROM AUTHOR]
Published: 2006
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30. Effect of rofecoxib, etoricoxib, celecoxib, and naproxen on urinary excretion of prostanoids in elderly volunteers.

Author: Schwartz, J. I., Vandormael, K., Thach, C., Lasseter, K. C., Holmes, G. B., Miller, J. L., Hreniuk, D., Hilliard, D., Snyder, K. M., Gertz, B. J., and Gottesdiener, K. M.
Published: 2004
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31. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Author: S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. 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Lindsay, M Christoforidou, A Abicht, E Harno, K Cyganek, A Fitchet, S Neelotpol, P Nikishin, P Serradas, J Hinrichsen, M Halvorson, M Chovatia, B Voet, Jinny Willis, E Parretti, M Haslbeck, M Wellard, L Teng, Julio Wainstein, J S Fischer, K. Lalic, D Roggenland, I Gich, R Anwar, Maurizio Cassader, D Serota, X J Li, R J Schotzinger, Vilmundur Gudnason, Björn Zethelius, S A Wootton, W Andrzejewski, R Rezsohazy, R Gao, T Klimentova, T Mazurek, I Bruckner, C Dohrmann, R E James, G daSilva Xavier, Kim S-Y., A Dorca, Stuart J. Pocock, Terri J. Allen, I Giovos, P B Parab, N H Andersen, P Fotinakis, Miriam Cnop, H Lee, Norbert Tennagels, Omorodola I. Abatan, F Ailett, I. Lager, D Manzella, H Hut, Larry A. Distiller, G Lip, Lim S-K., Rong Zhang, T Tsuno, Steen Knudsen, M. Bajardi, Manuel Benito, Dai Sugimoto, Melvin J. Prince, D W Dunstan, D Rankins, K A Majali, G Ozansoy, Isabella Russo, S Uçak, G Annuzzi, R Talar-Wojnarowska, K Lange, S Neugebauer-Baba, Campbell H. Thompson, Eric Renard, P. D. Mountjoy, Z Morrison, Elizabeth A. Davis, Franco Cavallo, C Corvaja, R Antuña, Craig John Currie, H Linnebjerg, He Y-L., A J Palmer, Mariola R. Chacón, H Malinska, M. Jones, R Lichnovská, K Mandes, Paolo Tessari, T Mokhort, A Laina, H. L. Y. Chan, I Schmidt, R Banks, Richard G. IJzerman, L Ksinantova, G Setti, H Vaudry, A Gallo, V Spallone, Chen J-W., Thomas Danne, A Chong, M Hallschmid, S Aczel, S Hulme, N Islam, M Hosoi, P M Ternan, P Di Bartolo, N Bishara, T Shibasaki, Martin A. Osterhoff, Im S-S., M Jecht, T Hamaguchi, S Mattera, K Ways, Elizabeth Northam, U Rajala, Reinhard W. Holl, L Yang, S Panaiotopoulos, K Horvath, R Kluge, Thora B. Bodvarsdottir, Y Dong, Irene Alemanno, C McDougall, Reimar W. Thomsen, M Campbell, W Rabl, John Öhrvik, Yuichiro Yamada, Paola Ungaro, W Benzer, Mike Sampson, Roberto Trevisan, R G Radu, Aas A-M., P E Lobo, Ricardo Scott, S M Son, Josephine M. Forbes, T A Hillier, K L Wyne, Louis L. Nguyen, J Farmer, M H Tan, Kwon H-S., J Yang, L Sandvik, Franco Folli, A K Jenum, M Nguyen, W Pratipanawatr, A L Frederiksen, Rebecca Smith, Lee H-J., A Schäfer, C Manuelli, G S Denver, T Vukovich, B Maceira, K Matsumoto, K. Chokkalingam, Nurcan Üçeyler, P Modi, Timothy M. Morgan, S Mertens, B M Singh, Michaela Riedl, K Iso, C Cucurullo, G. F. Bottazzo, M Calvani, K Hur, J Wetzels, Kazuhiro Takahashi, Y Aso, H Stammer, M G Masding, Fitsum Guebre-Egziabher, J L González-Sánchez, L Armstrong, Alberto Maran, Peter G.F. Swift, S S Popovic, J Starczynski, E Vitacolonna, Luigi Laviola, R W Gelling, Marina Cardellini, D Barilla, Rosa de Diego Martínez, W H Landschulz, Anne Mette Rosenfalck, R K Wong, Kevin E. Schneider, K Peros, Giuseppe Nanni, F Zhang, I Rákóczi, T Iburi, M Nakhjavani, X Q Zhang, S Tournis, Per Lav Madsen, Graham A. Hitman, A. Tura, K Laubner, N D Kostic, Lawrence M. Dolan, R. Sinha Roy, J A Wagner, J. Tuomilehto, J Hauptman, M Abdel-Ghany, D Lacombe, Toralph Ruge, Johannes A Maassen, Triantafyllos Didangelos, K Sasaki, I Argüelles, Klaus Levin, C Popow, Emanuel Christ, R Chetty, L Baillet-Blanco, Jo-Ann Salmon, T Mine, James L. Trevaskis, I Franke, J Gorski, E A Andrianova, A Dayan, A Caballero, Aleksandra Gilis-Januszewska, M Yasujima, Z Kasalová, C.D.A. Stehouwer, F. K. Gorus, G A Nichols, A Glowania, David P. Strachan, P Fredlund, N. F. da Silva, P Reboldi, M Sausbier, K H Groenier, G Stuccio, N Guttman, K R Ahmed, A D Ristic, T Kapellen, J Coutcher, Aldo V. Greco, Oswald Wagner, A Zagayko, Maria Alevizaki, B B Zhang, W F Ferris, Jenny Fredriksson, Lois Jovanovic, J Hänninen, R De Giglio, Kazuo Yagui, O Potterat, P Hamliton, R E Scranton, B Mankovsky, A Stylianou, B Fellström, Abdel-Wahab Yha., M Kitagawa, Katherine L. Baldock, F R Johnson, F Baigts, S D'Addato, F J Sanz, A Mistry, S D Wise, T Pratipanawatr, U R Fölsch, James R.C. Parkinson, Claudia Sommer, C Park, F E Griffiths, M L Martí, R Demirtunc, S Taniguchi, J Lundkvist, T Siegmund, Juan Sztajzel, C Dienesch, F Baumgartner, L Scalone, T M Mckolanis, K Otake, Ullrik Pedersen-Bjergaard, T M Vriesendorp, Michael B. Wheeler, Henry Schmitt, Peter Hovind, S Lange, Stephane Roze, L. Van Gaal, B Klaproth, Anthony E. Civitarese, D Eckland, A Dagar, D F Hopkins, Kari Stefansson, C Gonzalez-Yanes, B Meyboom-de Jong, D. J. Betteridge, K Buhling, M Crepaldi, Ana M. Wägner, L Renna, L Volpe, R McBride, V Corbo, E O Brennesvik, R P Hayes, R Abdollahnia, G Viviani, C F Liew, Francisco Pérez-Bravo, Jeffrey Baron, Brian M. Frier, H H Samira, D Szentendrei, K. J. Schjoedt, W K Waldhäusl, D Gniuli, D Zou, G Tschank, V Urbančič, A L Nolan, Albertini J-P., J Malcomson, M Larbig, C Cheyssac, K Aurich, C M Kesson, S Heller, Maija E. Miettinen, R F Luco, Adrian J. Cameron, Luigi Mattiello, Z. Metelko, X E Zhang, M Parramón, I. G. 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Fuller, Nicholas Katsilambros, Michele Muggeo, Pia Ekbom, Piero Marchetti, V Melki, C Bailleau, H Stavrianos, A D'Errico, Geremia B. Bolli, Amabile Maier, Kelter A-R., Anders Green, Q J Morélis, Steffen Thiel, C Watkins, R C Cheung, A Clark, Elvira Fioriti, N Ari, Nam J-Y., Y Cottin, L G Krinelke, H Al Mohammedi, Simon C. Fleming, C Jones, Z Kerényi, Ahn Y-H., Meile M-J., P Nánási, M Graner, V Canonico, Gangnerau M-N., Hugh R. Taylor, Giovanni Sartore, A. Dejgaard, Carol Kelley, S. Ali, Stéphane Dalle, Jeffrey S. Gonzalez, Elena Šeböková, Alexander Beck, Ingo B. Leibiger, M Rosu, C Pencea, Werner Waldhäusl, Kaltenbacher M-C., R Butzer, S Thore, Adam G. Tabak, Angelo Avogaro, E Standi, Boris Kovatchev, O Bradescu, Patrizia Dentelli, A Fujita, C Verri, R Chlup, Prasad Ydm., S V Hörsten, van der Merwe M-T., D Hilliard, W Klein, D Worthley, M Udvardy, Berit R. 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Liu, H, Jeong, I, Chae, M, Choi, M, Yoo, H, Kim, C, Yun, M, Na, M, Kang, Y, Kong, O, Son, S, Kim, I, Tanaka, N, Hosoi, M, Matsuyama, Y, Fukumoto, M, Yamakita, T, Yoshioka, K, Ishii, T, Sato, T, Fujii, S, Aoki, T, Shibata, T, Mizutani, N, Suzuki, J, Fowelin, J, Samuelsson, P, Brandrup wogsen, G, Okumura, K, Tokmakova, A, Staroverova, D, Antcieferov, M, Shutichina, I, Kuntchevich, G, Vriesendorp, T, Morélis, Q, Legemate, D, Schaper, F, Mainas, E, Gkioulmpasanis, I, Panagiotou, I, Vassilikos, G, Skorda, L, Sidira, M, Christoforidou, M, Alaveras, A, Artikis, V, Evdemon, E, Lechleitner, M, Koch, T, Ebenbichler, C, Sturm, W, Moretti, L, Moruzzo, D, Boldrini, E, Pandolfo, C, Kameyama, M, Iwasa, R, Cho, M, Nam, J, Huh, K, Kaplar, M, Paragh, G, Erdei, A, Csongradi, E, Garai, I, Varga, J, Galuska, L, Udvardy, M, Higa, M, Kaneko, Y, Hiroi, N, Koziarska, D, Nowacki, P, Majkowska, L, Luzniak, P, Wojciechowska luźniak, A, Tushuizen, M, Nieuwland, R, Snoeck, D, Sturk, A, Diamant, M, Aguiar, L, Bahia, L, Villela, N, Laflor, C, Conde, C, Bottino, D, Dorigo, D, Bouskela, E, Pu, S, Luo, Z, Lam, K, Dan, Q, Xu, A, Shen, J, Cheng, K, Xu, J, Thamer, C, Stefan, N, Haap, M, Heller, E, Tschritter, O, De Prado, A, Ortiz, A, Ybarra, J, Gich, I, Pou, J, Ehren, M, Roggenland, D, Reinsen, B, Klein, H, Rittig, K, Stock, J, Kocher, B, Balletshofer, B, Shon, H, Chung, D, Nakatani, Y, Matsuhisa, M, Kaneto, H, Hatazaki, M, Yoshiuchi, K, Katakami, N, Kawamori, D, Ohtoshi, K, Sakamoto, K, Matsuoka, T, Ozawa, K, Ogawa, S, Hori, M, Yamasaki, Y, Zitouni, K, Harry, D, Nourooz zadeh, J, Earle, K, Olesen, P, Franco, L, Corvaja, C, Semplicini, A, Ceylan işık, A, Arı, N, Rösen, P, Lee, I, Park, K, Jung, E, Shin, D, Jo, S, Obuobie, K, Prakash, P, Hanna, F, Lazarus, J, Varadhan, L, Gurushankar, J, James, D, Sheikh, S, Gaede, P, Zou, D, Vilarrasa, N, Perez maraver, M, Mena, E, Perez, D, Setti, G, Buckingham, R, Urbančič, V, Stefanovska, A, Bernjak, A, Ažman juvan, K, Kocijančič, A, Glowania, A, Filters, T, Fosmark, D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
Subjects: 0303 health sciences, medicine.medical_specialty, business.industry, EASD, Endocrinology, Diabetes and Metabolism, Human physiology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Family medicine, Internal Medicine, Medicine, business, 030217 neurology & neurosurgery, 030304 developmental biology
Published: 2004

32. Do calorie labels change energy purchased in a simulated online food delivery platform? A multi-arm randomised controlled trial.

Author: Luick M, Bianchi F, Bain F, Bandy L, Doshi P, Hilliard D, Leung J, Mottershaw A, Stuijfzand B, Whitwell-Mak J, Jebb SA, Harper H, and Pechey R
Subjects: Humans, Male, Female, Adult, United Kingdom, Choice Behavior, Middle Aged, Consumer Behavior, Obesity prevention & control, Young Adult, Meals, Food Labeling methods, Energy Intake, Food Preferences
Abstract: Background: As rates of obesity and overweight continue to increase in the UK, calorie labels have been introduced on menus as a policy option to provide information to consumers on the energy content of foods and to enable informed choices. This study tested whether the addition of calorie labels to items in a simulated food delivery platform may reduce the energy content of items selected., Methods: UK adults (n = 8,780) who used food delivery platforms were asked to use the simulated platform as they would in real life to order a meal for themselves. Participants were randomly allocated to a control condition (no calorie labels) or to one of seven intervention groups: (1) large size calorie labels adjacent to the price (LP), (2) large size label adjacent to the product name (LN), (3) small label adjacent to price (SP), (4) small label adjacent to product name (SN), (5) LP with a calorie label switch-off filter (LP + Off), (6) LP with a switch-on filter (LP + On), or, (7) LP with a summary label of the total basket energy content (LP + Sum). Regression analysis assessed the impact of calorie labels on energy content of foods selected compared to the control condition., Results: The mean energy selected in the control condition was 1408 kcal (95%CI: 93, 2719). There was a statistically significant reduction in mean energy selected in five of the seven intervention trial arms (LN labels (-60 kcal, 95%CI: -111, -6), SN (-73, 95%CI: -125, -19), LP + Off (-110, 95%CI: -161, -57), LP + On (-109, 95%CI: -159, -57), LP + Sum (-85 kcal, 95%CI: -137, -30). There was no evidence the other two conditions (LP (-33, 95%CI: -88, 24) and SP (-52, 95%CI: -105, 2)) differed from control. There was no evidence of an effect of any intervention when the analysis was restricted to participants who were overweight or obese., Conclusion: Adding calorie labels to food items in a simulated online food delivery platform reduced the energy content of foods selected in five out of seven labelling scenarios. This study provides useful information to inform the implementation of these labels in a food delivery platform context., (© 2024. The Author(s).)
Published: 2024
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33. At the Limit of Interfacial Sharpness in Nanowire Axial Heterostructures.

Author: Hilliard D, Tauchnitz T, Hübner R, Vasileiadis I, Gkotinakos A, Dimitrakopulos G, Komninou P, Sun X, Winnerl S, Schneider H, Helm M, and Dimakis E
Abstract: As semiconductor devices approach dimensions at the atomic scale, controlling the compositional grading across heterointerfaces becomes paramount. Particularly in nanowire axial heterostructures, which are promising for a broad spectrum of nanotechnology applications, the achievement of sharp heterointerfaces has been challenging owing to peculiarities of the commonly used vapor-liquid-solid growth mode. Here, the grading of Al across GaAs/Al x Ga 1- x As/GaAs heterostructures in self-catalyzed nanowires is studied, aiming at finding the limits of the interfacial sharpness for this technologically versatile material system. A pulsed growth mode ensures precise control of the growth mechanisms even at low temperatures, while a semiempirical thermodynamic model is derived to fit the experimental Al-content profiles and quantitatively describe the dependences of the interfacial sharpness on the growth temperature, the nanowire radius, and the Al content. Finally, symmetrical Al profiles with interfacial widths of 2-3 atomic planes, at the limit of the measurement accuracy, are obtained, outperforming even equivalent thin-film heterostructures. The proposed method enables the development of advanced heterostructure schemes for a more effective utilization of the nanowire platform; moreover, it is considered expandable to other material systems and nanostructure types.
Published: 2024
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34. Tunable Magnetic Vortex Dynamics in Ion-Implanted Permalloy Disks.

Author: Ramasubramanian L, Kákay A, Fowley C, Yildirim O, Matthes P, Sorokin S, Titova A, Hilliard D, Böttger R, Hübner R, Gemming S, Schulz SE, Kronast F, Makarov D, Fassbender J, and Deac A
Abstract: Nanoscale, low-phase-noise, tunable transmitter-receiver links are key for enabling the progress of wireless communication. We demonstrate that vortex-based spin-torque nano-oscillators, which are intrinsically low-noise devices because of their topologically protected magnetic structure, can achieve frequency tunability when submitted to local ion implantation. In the experiments presented here, the gyrotropic mode is excited with spin-polarized alternating currents and anisotropic magnetoresistance measurements yield discrete frequencies from a single device. Indeed, chromium-implanted regions of permalloy disks exhibit different saturation magnetization than neighboring, non-irradiated areas, and thus different resonance frequency, corresponding to the specific area where the core is gyrating. Our study proves that such devices can be fabricated without the need for further lithographical steps, suggesting ion irradiation can be a viable and cost-effective fabrication method for densely packed networks of oscillators.
Published: 2020
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35. Ion-Irradiation-Induced Cobalt/Cobalt Oxide Heterostructures: Printing 3D Interfaces.

Author: Yıldırım O, Hilliard D, Arekapudi SSPK, Fowley C, Cansever H, Koch L, Ramasubramanian L, Zhou S, Böttger R, Lindner J, Faßbender J, Hellwig O, and Deac AM
Abstract: Interfaces separating ferromagnetic (FM) layers from non-ferromagnetic layers offer unique properties due to spin-orbit coupling and symmetry breaking, yielding effects such as exchange bias, perpendicular magnetic anisotropy, spin-pumping, spin-transfer torques, and conversion between charge and spin currents and vice versa. These interfacial phenomena play crucial roles in magnetic data storage and transfer applications, which require the formation of FM nanostructures embedded in non-ferromagnetic matrices. Here, we investigate the possibility of creating such nanostructures by ion irradiation. We study the effect of lateral confinement on the ion-irradiation-induced reduction of nonmagnetic metal oxides (e.g., antiferro- or paramagnetic) to form ferromagnetic metals. Our findings are later exploited to form three-dimensional magnetic interfaces between Co, CoO, and Pt by spatial-selective irradiation of CoO/Pt multilayers. We demonstrate that the mechanical displacement of O atoms plays a crucial role in the reduction from insulating, non-ferromagnetic cobalt oxides to metallic cobalt. Metallic cobalt yields both perpendicular magnetic anisotropy in the generated Co/Pt nanostructures and, at low temperatures, exchange bias at vertical interfaces between Co and CoO. If pushed to the limit of ion-irradiation technology, this approach could, in principle, enable the creation of densely packed, atomic-scale ferromagnetic point-contact spin-torque oscillator (STO) networks or conductive channels for current-confined-path-based current perpendicular-to-plane giant magnetoresistance read heads.
Published: 2020
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36. Thromboelastogram-Guided Resuscitation for Patients with Traumatic Brain Injury on Novel Anticoagulants.

Author: Hota S, Ng M, Hilliard D, and Burgess J
Subjects: Adult, Aged, Aged, 80 and over, Blood Component Transfusion statistics & numerical data, Brain Injuries, Traumatic diagnostic imaging, Brain Injuries, Traumatic mortality, Female, Humans, Injury Severity Score, Intracranial Hemorrhages diagnostic imaging, Intracranial Hemorrhages mortality, Length of Stay statistics & numerical data, Male, Middle Aged, Retrospective Studies, Tomography, X-Ray Computed, Treatment Outcome, Anticoagulants administration & dosage, Brain Injuries, Traumatic blood, Intracranial Hemorrhages blood, Resuscitation methods, Thrombelastography
Abstract: Traumatic brain injuries in patients on antithrombotic agents carry significant morbidity. Initial therapy is centered around reversal of these agents. The thromboelastogram (TEG) maps the clotting cascade to guide reversal. A retrospective chart review was conducted for 118 patients presenting with a traumatic brain injury while on antithrombotics. Patients were divided between those who received a TEG on arrival and those who did not. The primary endpoint was overall mortality. Secondary endpoints included blood product utilization, and outcomes associated with specific novel anticoagulants. Mortality in the control group was 20.3 per cent compared with 18.5 per cent in the TEG group ( P = 0.81). For less severe injuries, the control group mortality was 3.8 per cent and the TEG group mortality was 8.7 per cent ( P = 0.64). For more severe injuries, mortality in the control versus TEG groups were 31.6 per cent and 25.8 per cent, respectively ( P = 0.73). Blood product utilization was significantly lower in the TEG group ( P = 0.002). Overall mortality was not significantly different between the groups. However, when stratified by severity of injury, mortality was reduced in the TEG-guided group in severely injured patients. Blood product utilization was significantly reduced with TEG-guided reversal. Trauma centers can improve the utilization of blood products in reversal of antithrombotics with the use of TEG.
Published: 2019

37. Noisy galvanic vestibular stimulation modulates spatial memory in young healthy adults.

Author: Hilliard D, Passow S, Thurm F, Schuck NW, Garthe A, Kempermann G, and Li SC
Subjects: Adult, Female, Humans, Male, Middle Aged, Signal-To-Noise Ratio, Young Adult, Electric Stimulation, Healthy Volunteers, Spatial Memory, Vestibule, Labyrinth physiology
Abstract: Hippocampal and striatal circuits play important roles in spatial navigation. These regions integrate environmental information and receive intrinsic afferent inputs from the vestibular system. Past research indicates that galvanic vestibular stimulation (GVS) is a non-invasive technique that modulates hippocampal and striatal activities. There are also evidences for enhanced motor and cognitive functions through GVS. This study extends previous research to investigate whether noisy GVS may improve hippocampal- and striatal-associated aspects of spatial navigation performance. Using a virtual navigation task, we examined effects of noisy GVS on spatial learning and memory. To probe the participants' sensitivity to hippocampal- or striatal-associated spatial information, we either enlarged the virtual environment's boundary or replaced an intra-environmental location cue, respectively. Noisy GVS or sham stimulation was applied online during the learning phase in a within-subject crossover design. The results showed that noisy GVS enhanced spatial learning and the sensitivity foremost to hippocampal-dependent spatial information both in males and females. Individual differences in spatial working memory capacity moderated the effects of GVS, with individuals with lower capacity benefitting more from the stimulation. Furthermore, sex-related differences in GVS effects on the two forms of spatial representations may reflect differences between males and females in preferred spatial strategies.
Published: 2019
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38. Can Statewide Emergency Department, Hospital Discharge, and Violent Death Reporting System Data Be Used to Monitor Burden of Firearm-Related Injury and Death in Rhode Island?

Author: Jiang Y, Ranney ML, Sullivan B, Hilliard D, Viner-Brown S, and Alexander-Scott N
Subjects: Cross-Sectional Studies, Data Science methods, Emergency Service, Hospital, Humans, Patient Discharge statistics & numerical data, Population Surveillance methods, Registries statistics & numerical data, Research Design, Rhode Island epidemiology, Violence statistics & numerical data, Data Science standards, Firearms statistics & numerical data, Registries standards
Abstract: Context: National data on the epidemiology of firearm injuries and circumstances of firearm deaths are difficult to obtain and often are nonreliable. Since firearm injury and death rates and causes can vary substantially between states, it is critical to consider state-specific data sources., Objective: In this study, we illustrate how states can systematically examine demographic characteristics, firearm information, type of wound, toxicology tests, precipitating circumstances, and costs to provide a comprehensive picture of firearm injuries and deaths using data sets from a single state with relatively low rates of firearm injury and death., Design: Cross-sectional study., Setting: Firearm-related injury data for the period 2005-2014 were obtained from the Rhode Island emergency department and hospital discharge data sets; death data for the same period were obtained from the Rhode Island Violent Death Reporting System., Main Outcome Measure: Descriptive statistics were used. Healthcare Cost and Utilization Project cost-to-charge ratios were used to convert total hospital charges to costs., Results: Most firearm-related emergency department visits (55.8%) and hospital discharges (79.2%) in Rhode Island were from assaults; however, most firearm-related deaths were suicides (60.1%). The annual cost of firearm-related hospitalizations was more than $830 000. Most decedents who died because of firearms tested positive for illicit substances. Nearly a quarter (23.5%) of firearm-related homicides were due to a conflict between the decedent and suspect. More than half (59%) of firearm suicide decedents were reported to have had current mental or physical problems prior to death., Conclusions: Understanding the state-specific magnitude and patterns (who, where, factors, etc) of firearm injury and death may help inform local injury prevention efforts. States with similar data sets may want to adopt our analyses. Surveillance of firearm-related injury and death is essential. Dissemination of surveillance findings to key stakeholders is critical in improving firearm injury prevention. States that are not part of the National Violent Death Reporting System (NVDRS) could work with their other data sources to obtain a better picture of violent injuries and deaths to make the best use of resources.
Published: 2019
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39. To Improve Homicide Firearm Information Reporting - Rhode Island State Crime Laboratory.

Author: Jiang Y, Lyons D, Northup JB, Hilliard D, Foss K, Young S, and Viner-Brown S
Subjects: Cause of Death, Firearms classification, Homicide trends, Humans, Population Surveillance methods, Rhode Island, Violence trends, Firearms statistics & numerical data, Homicide statistics & numerical data, Violence statistics & numerical data
Abstract: Information on homicide firearms can be used to help state and local communities understand the problems of violence and decrease injuries and deaths. However, it is difficult to collect these data. To our knowledge, in the public health arena, the National Violent Death Reporting System (NVDRS) is the only system that collects detailed firearm information. The Rhode Island State Crime Laboratory (RISCL) can provide detailed information about the firearms and cartridge cases\bullets involved in firearm deaths. With help from the RISCL, the firearm information related to homicides in Rhode Island has improved dramatically. In 2015, information on caliber/gauge increased by 80%, the firearm type by 50%, the make by 50%, and the model by 20%. By documenting the process of using information from the RISCL, it is hoped that this process can be used as a model by other states when reporting on violent deaths.
Published: 2018

40. Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule.

Author: Witek MA, Aufforth RD, Wang H, Kamande JW, Jackson JM, Pullagurla SR, Hupert ML, Usary J, Wysham WZ, Hilliard D, Montgomery S, Bae-Jump V, Carey LA, Gehrig PA, Milowsky MI, Perou CM, Soper JT, Whang YE, Yeh JJ, Martin G, and Soper SA
Abstract: Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges., Competing Interests: Competing interests: The presented CTC isolation technology is being commercialized by Biofluidica, Inc. S.A.S. and M.L.H. hold equity shares in BioFluidica, Inc. M.A.W. declares conflict of interest as spouse of M.L.H. The remaining authors declare that they have no competing financial interests.
Published: 2017
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41. Controllable growth of vertically aligned graphene on C-face SiC.

Author: Liu Y, Chen L, Hilliard D, Huang QS, Liu F, Wang M, Böttger R, Hübner R, N'Diaye AT, Arenholz E, Heera V, Skorupa W, and Zhou S
Abstract: We investigated how to control the growth of vertically aligned graphene on C-face SiC by varying the processing conditions. It is found that, the growth rate scales with the annealing temperature and the graphene height is proportional to the annealing time. Temperature gradient and crystalline quality of the SiC substrates influence their vaporization. The partial vapor pressure is crucial as it can interfere with further vaporization. A growth mechanism is proposed in terms of physical vapor transport. The monolayer character of vertically aligned graphene is verified by Raman and X-ray absorption spectroscopy. With the processed samples, d 0 magnetism is realized and negative magnetoresistance is observed after Cu implantation. We also prove that multiple carriers exist in vertically aligned graphene.
Published: 2016
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42. Single-dose pharmacokinetics and pharmacodynamics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.

Author: Krishna R, Garg A, Panebianco D, Cote J, Bergman AJ, Van Hoydonck P, Laethem T, Van Dyck K, Chen J, Chavez-Eng C, Archer L, Lutz R, Hilliard D, Snyder K, Jin B, Van Bortel L, Lasseter KC, Al-Huniti N, Dykstra K, Gottesdiener K, and Wagner JA
Subjects: Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Cross-Over Studies, Double-Blind Method, Fasting, Female, Humans, Male, Middle Aged, Obesity, Oxazolidinones administration & dosage, Oxazolidinones pharmacology, Sex Factors, Treatment Outcome, Young Adult, Cholesterol Ester Transfer Proteins antagonists & inhibitors, Dyslipidemias drug therapy, Oxazolidinones pharmacokinetics
Abstract: Aims: Anacetrapib is an orally active and potent inhibitor of CETP in development for the treatment of dyslipidaemia. These studies endeavoured to establish the safety, tolerability, pharmacokinetics and pharmacodynamics of rising single doses of anacetrapib, administered in fasted or fed conditions, and to preliminarily assess the effect of food, age, gender and obesity on the single-dose pharmacokinetics and pharmacodynamics of anacetrapib., Methods: Safety, tolerability, anacetrapib concentrations and CETP activity were evaluated., Results: Anacetrapib was rapidly absorbed, with peak concentrations occurring at approximately 4 h post-dose and an apparent terminal half-life ranging from approximately 9 to 62 h in the fasted state and from approximately 42 to approximately 83 h in the fed state. Plasma AUC and C(max) appeared to increase in a less than approximately dose-dependent manner in the fasted state, with an apparent plateau in absorption at higher doses. Single doses of anacetrapib markedly and dose-dependently inhibited serum CETP activity with peak effects of approximately 90% inhibition at t(max) and approximately 58% inhibition at 24 h post-dose. An E(max) model best described the plasma anacetrapib concentration vs CETP activity relationship with an EC(50) of approximately 22 nm. Food increased exposure to anacetrapib; up to approximately two-three-fold with a low-fat meal and by up to approximately six-eight fold with a high-fat meal. Anacetrapib pharmacokinetics and pharmacodynamics were similar in elderly vs young adults, women vs men, and obese vs non-obese young adults. Anacetrapib was well tolerated and was not associated with any meaningful increase in blood pressure., Conclusions: Whereas food increased exposure to anacetrapib significantly, age, gender and obese status did not meaningfully influence anacetrapib pharmacokinetics and pharmacodynamics.
Published: 2009
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43. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes.

Author: Herman GA, Bergman A, Stevens C, Kotey P, Yi B, Zhao P, Dietrich B, Golor G, Schrodter A, Keymeulen B, Lasseter KC, Kipnes MS, Snyder K, Hilliard D, Tanen M, Cilissen C, De Smet M, de Lepeleire I, Van Dyck K, Wang AQ, Zeng W, Davies MJ, Tanaka W, Holst JJ, Deacon CF, Gottesdiener KM, and Wagner JA
Subjects: Administration, Oral, Adult, Area Under Curve, Cross-Over Studies, Diabetes Mellitus, Type 2 drug therapy, Double-Blind Method, Enzyme Inhibitors administration & dosage, Enzyme Inhibitors pharmacokinetics, Female, Glucagon-Like Peptide 1 blood, Glucose Tolerance Test methods, Humans, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents adverse effects, Hypoglycemic Agents pharmacokinetics, Hypoglycemic Agents therapeutic use, Male, Middle Aged, Placebos, Pyrazines administration & dosage, Pyrazines adverse effects, Pyrazines therapeutic use, Sitagliptin Phosphate, Triazoles administration & dosage, Triazoles adverse effects, Triazoles therapeutic use, Blood Glucose drug effects, Diabetes Mellitus, Type 2 blood, Dipeptidyl-Peptidase IV Inhibitors, Gastric Inhibitory Polypeptide blood, Pyrazines pharmacokinetics, Triazoles pharmacokinetics
Abstract: Context: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated., Objective: The objective of the study was to examine the pharmacodynamics, pharmacokinetics, and tolerability of sitagliptin., Design: This was a randomized, double-blind, placebo-controlled, three-period, single-dose crossover study., Setting: The study was conducted at six investigational sites., Patients: The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents., Interventions: Interventions included sitagliptin 25 mg, sitagliptin 200 mg, or placebo., Main Outcome Measures: Measurements included plasma DPP-4 activity; post-OGTT glucose excursion; active and total incretin GIP levels; insulin, C-peptide, and glucagon concentrations; and sitagliptin pharmacokinetics., Results: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin. Sitagliptin was generally well tolerated, with no hypoglycemic events., Conclusions: In this study in patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitagliptin concentration of 100 nm or greater, and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.
Published: 2006
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44. Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers.

Author: Bergman AJ, Stevens C, Zhou Y, Yi B, Laethem M, De Smet M, Snyder K, Hilliard D, Tanaka W, Zeng W, Tanen M, Wang AQ, Chen L, Winchell G, Davies MJ, Ramael S, Wagner JA, and Herman GA
Subjects: Administration, Oral, Adolescent, Adult, Blood Glucose drug effects, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 drug therapy, Dipeptidyl Peptidase 4 blood, Dose-Response Relationship, Drug, Double-Blind Method, Enzyme-Linked Immunosorbent Assay, Follow-Up Studies, Glucagon-Like Peptide 1 blood, Humans, Insulin-Like Growth Factor Binding Protein 3 blood, Insulin-Like Growth Factor I metabolism, Male, Middle Aged, Pyrazines administration & dosage, Reference Values, Sitagliptin Phosphate, Triazoles administration & dosage, Blood Glucose metabolism, Dipeptidyl Peptidase 4 drug effects, Pyrazines pharmacokinetics, Triazoles pharmacokinetics
Abstract: Background: Dipeptidyl peptidase-IV (DPP-IV) inhibitors represent a new class of oral antihyperglycemic agents. Sitagliptin is an orally active and selective DPP-IV inhibitor currently in Phase III development for the treatment of type 2 diabetes mellitus., Objective: The aim of this study was to assess the pharmacokinetic and pharmacodynamic (PK/PD) properties and tolerability of multiple oral once-daily or twice-daily doses of sitagliptin., Methods: This double-blind, randomized, placebo-controlled,incremental oral-dose study was conducted at SGS Biopharma, Antwerp, Belgium. Healthy, nonsmoking male volunteers aged 18 to 45 years with a creatinine clearance rate of >80 mL/min and normoglycemia and weighing within 15% of their ideal height/weight range were randomly assigned to 1 of 8 treatment groups: sitagliptin 25, 50, 100, 200, or 400 mg or placebo, QD for 10 days; a single dose of sitagliptin 800 mg administered on day 1 followed by 600 mg QD on days 3 to 10; or sitagliptin 300 mg BID for 10 days. For analysis of PK properties, plasma and urine samples were obtained before study drug administration on day 1 and at 0.5, 1, 2, 4, 6, 8, 10, 12, and 16 hours after study drug administration on day 1; before study drug administration on days 2 to 9; and every 24 hours for 96 hours after the last dose on day 10, and analyzed for sitagliptin concentrations. Assays were used to measure inhibition of plasma DPP-IV activity and plasma concentrations of active and total glucagon-like peptide-1 (GLP-1), glucose, and glucagon, and serum concentrations of insulin, C-peptide, insulin-like growth factor-1, and insulin like growth factor binding protein-3. Tolerability was assessed throughout the study using physical examination, including vital sign measurements; 12-lead electrocardiography; and laboratory analysis, including hematology, biochemistry (hepatic aminotransferase and creatine phosphokinase), and urinalysis., Results: Seventy subjects were enrolled (mean age, 32.9 years [range, 18-45 years]; mean weight, 79.7 kg [range, 63.4-97.7 kg]; 8 patients per sitagliptin study group and 14 patients in the control group). In the sitagliptin groups, the plasma concentration-time profiles and principal PK parameters (T(max), C(max), and t((1/2))) were statistically similar at days 1 (single dose) and 10 (steady state). In the groups receiving sitagliptin QD doses, accumulation of sitagliptin was modest (AUC accumulation ratio [day 10/day 1] range, 1.05-1.29), and the apparent terminal elimination t((1/2)) was 11.8 to 14.4 hours. At steady state in the sitagliptin QD groups, the mean proportion of drug excreted unchanged in the urine was approximately 70.6%. Dose-dependent inhibition of plasma DPP-IV activity was apparent, and the pattern of inhibition at steady state (day 10) was statistically similar to that observed on day 1. Day-10 weighted mean inhibition of plasma DPP-IV activity over 24 hours was > or = 80% for doses of > or = 50 mg QD. After a standard meal, active GLP-1 concentrations were significantly increased in the sitagliptin groups by approximately 2-fold compared with that in the control group, a finding consistent with near-maximal acute glucose lowering in preclinical studies. Across doses, no apparent adverse effects, including hypoglycemia, were found or reported., Conclusions: The results from this study in a select population of healthy male volunteers suggest that multiple oral doses of sitagliptin inhibited plasma DPP-IV activity and affected active GLP-1 concentrations in a dose-dependent manner, without producing hypoglycemia. Multiple dosing of sitagliptin exhibited a PK/PD profile consistent with that of a QD regimen and was well tolerated.
Published: 2006
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45. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses.

Author: Herman GA, Stevens C, Van Dyck K, Bergman A, Yi B, De Smet M, Snyder K, Hilliard D, Tanen M, Tanaka W, Wang AQ, Zeng W, Musson D, Winchell G, Davies MJ, Ramael S, Gottesdiener KM, and Wagner JA
Subjects: Administration, Oral, Adolescent, Adult, Analysis of Variance, Area Under Curve, Blood Glucose analysis, C-Peptide blood, Common Cold chemically induced, Dipeptidyl Peptidase 4 blood, Dose-Response Relationship, Drug, Double-Blind Method, Enzyme Inhibitors administration & dosage, Enzyme Inhibitors adverse effects, Eye Diseases chemically induced, Fasting blood, Glucagon-Like Peptide 1 blood, Half-Life, Headache chemically induced, Humans, Insulin blood, Male, Middle Aged, Pyrazines administration & dosage, Pyrazines blood, Sitagliptin Phosphate, Triazoles administration & dosage, Triazoles blood, Dipeptidyl Peptidase 4 metabolism, Enzyme Inhibitors pharmacokinetics, Pyrazines pharmacokinetics, Triazoles pharmacokinetics
Abstract: Background: Sitagliptin (MK-0431 [(2R)-4-oxo-4-(3-[trifluoromethyl]-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7[8H]-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine]) is an orally active, potent, and selective inhibitor of dipeptidyl peptidase IV (DPP-IV) currently in phase III development for the treatment of type 2 diabetes., Methods: Two double-blind, randomized, placebo-controlled, alternating-panel studies evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of sitagliptin (1.5-600 mg) in healthy male volunteers., Results: Sitagliptin was well absorbed (approximately 80% excreted unchanged in the urine) with an apparent terminal half-life ranging from 8 to 14 hours. Renal clearance of sitagliptin averaged 388 mL/min and was largely uninfluenced by the dose administered. The area under the plasma concentration-time curve for sitagliptin increased in an approximately dose-dependent manner and was not meaningfully influenced by food. Single doses of sitagliptin markedly and dose-dependently inhibited plasma DPP-IV activity, with approximately 80% or greater inhibition of DPP-IV activity occurring at 50 mg or greater over a 12-hour period and at 100 mg or greater over a 24-hour period. Compared with placebo, sitagliptin produced an approximately 2-fold increase in postmeal active glucagon-like peptide 1 levels. Sitagliptin was well tolerated and was not associated with hypoglycemia., Conclusions: This study provides proof of pharmacologic characteristics for sitagliptin in humans. By inhibiting plasma DPP-IV activity, sitagliptin increases the postprandial rise in active glucagon-like peptide 1 concentrations without causing hypoglycemia in normoglycemic healthy male volunteers. Sitagliptin possesses pharmacokinetic and pharmacodynamic characteristics that support a once-daily dosing regimen.
Published: 2005
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46. All aspects of sharps injuries need to be addressed.

Author: Hilliard D
Subjects: Humans, Nursing Care standards, Accidents, Occupational prevention & control, Needlestick Injuries prevention & control
Published: 2002

47. Exploring the relationship between cultural values, beliefs, and practices and patient falls: a Middle Eastern study.

Author: Hilliard DJ, Frederick L, Tierney-Gumaer R, and Simpson MJ
Subjects: Accidental Falls prevention & control, Adult, Age Factors, Child, Data Collection, Hospital Bed Capacity, 500 and over, Hospitals, Public standards, Humans, Islam, Nursing Service, Hospital standards, Quality Assurance, Health Care, Risk Factors, Saudi Arabia epidemiology, Socialization, Accidental Falls statistics & numerical data, Cultural Characteristics, Hospitals, Public statistics & numerical data, Inpatients statistics & numerical data, Risk Management, Social Values
Abstract: Patient falls have been a concern in North American healthcare for many years. Studies have examined environmental, clinical, and patient variables for purposes of risk identification and fall reduction, primarily in the context of Western societies. An investigation at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, began in 1993 to determine whether commonly reported risk factors apply to the Saudi patient population and whether cultural values, beliefs, and practices such as the performance of ablution before prayer, fasting during the holy month of Ramadan, and the need for socialization influence the rate of patient falls. The study included all inpatients (N = 379) who fell during a 3-year period.
Published: 1999
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48. Sydney Anglicans and homosexuality.

Author: Hilliard D
Subjects: Civil Rights, Female, Humans, Male, New South Wales, Public Opinion, Christianity psychology, Homosexuality psychology, Social Problems
Abstract: The city of Sydney in Australia has one of the largest gay and lesbian communities in the English-speaking world, while the Anglican Church in Sydney is proud of its reputation as a strong-hold and guardian of conservative evangelicalism. Since the early 1970s the Anglican diocese, in its official statements and pastoral policies, has been strongly opposed to homosexuality and the organized gay movement. In 1973 a report on homosexuality by its Ethics and Social Questions Committee was unusual at the time because it recommended the continuance of legal sanctions against male homosexual behavior. There have been many confrontations between Anglican institutions and Sydney's increasingly confident gay community. This paper examines these tensions, the reasons for the stance of the diocese, and the responses of gay Christian groups such as Cross+Section and AngGays.
Published: 1997
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49. Massage for the seriously mentally ill.

Author: Hilliard D
Subjects: Humans, Massage nursing, Massage psychology, Mental Disorders psychology, Massage methods, Mental Disorders nursing, Psychiatric Nursing methods
Abstract: 1. Some seriously mentally ill clients have unfulfilled needs for safe touch. 2. Flashbacks or provocative behavior have not been triggered by the use of massage in a structured setting. 3. The blending psychiatric skills and therapeutic massage can be an effective stress reducer for inpatients or outpatients who seek safe touch.
Published: 1995
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50. The effect of MK-0591, a novel 5-lipoxygenase activating protein inhibitor, on leukotriene biosynthesis and allergen-induced airway responses in asthmatic subjects in vivo.

Author: Diamant Z, Timmers MC, van der Veen H, Friedman BS, De Smet M, Depré M, Hilliard D, Bel EH, and Sterk PJ
Subjects: 5-Lipoxygenase-Activating Proteins, Administration, Oral, Adult, Asthma metabolism, Asthma physiopathology, Bronchial Hyperreactivity metabolism, Bronchial Hyperreactivity physiopathology, Bronchial Provocation Tests methods, Creatinine urine, Double-Blind Method, Forced Expiratory Volume drug effects, Histamine, Humans, Indoles blood, Leukotrienes analysis, Male, Quinolines blood, Time Factors, Allergens adverse effects, Asthma drug therapy, Bronchial Hyperreactivity drug therapy, Carrier Proteins antagonists & inhibitors, Indoles administration & dosage, Leukotriene Antagonists, Leukotrienes biosynthesis, Membrane Proteins antagonists & inhibitors, Quinolines administration & dosage
Abstract: Background: The 5-lipoxygenase metabolites of arachidonic acid are likely to be involved in the pathophysiology of atopic asthma. We investigated the effect of pretreatment with MK-0591, a novel 5-lipoxygenase activating protein inhibitor, on allergen-induced early asthmatic reactions (EARs) and late asthmatic reactions (LARs), and subsequent airway hyperresponsiveness to histamine., Methods: Eight atopic men with mild to moderate asthma aged 19 to 31 years, (forced expiratory volume in 1 second [FEV1] > or = 67% of predicted value, histamine provocative concentration causing a 20% fall in FEV1 [PC20] < 4 mg/ml) and documented EAR and LAR to house dust mite extract participated in a two-period, double-blind, placebo-controlled, crossover study. During each study period histamine PC20 was measured 2 days before and 1 day after a standardized allergen inhalation challenge test. MK-0591 was administered in 3 oral doses of 250 mg each at 24, 12, and 1.5 hours before inhalation of allergen. Biochemical activity of MK-0591 was determined by calcium ionophore A-23187-stimulated leukotriene (LT)B4 biosynthesis in whole blood ex vivo and by urinary LTE4 excretion. Airway response to allergen was measured by FEV1 (percent fall from baseline). The EAR (0 to 3 hours) and the LAR (3 to 8 hours) were expressed as corresponding areas under the time-response curves., Results: MK-0591 and placebo did not differ in their effects on prechallenge FEV1 (p = 0.10). As compared with the value before pretreatment, MK-0591 blocked LTB4 biosynthesis and LTE4 excretion by a mean of 98% (range, 96% to 99%; p < 0.002) and 87% (range, 84% to 96%; p < 0.046), respectively, from 0 to 24 hours after allergen challenge. Both the EAR and the LAR were significantly reduced after administration of MK-0591 as compared with placebo, with a mean inhibition of 79% (p = 0.011) and 39% (p = 0.040), respectively. Allergen-induced airway hyperresponsiveness was not significantly different between the two pretreatment periods (p = 0.37)., Conclusions: In this study oral MK-0591 prevented leukotriene biosynthesis after allergen challenge in patients with mild to moderate asthma. The results of our study indicate that 5-lipoxygenase products play an important role during the EAR, whereas their contribution to the pathophysiology of the LAR seems to be of less importance.
Published: 1995
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