Enhanced Characterization of Drug Metabolism and the Influence of the Intestinal Microbiome: A Pharmacokinetic, Microbiome, and Untargeted Metabolomics Study.

Determining factors that contribute to interindividual and intra-individual variability in pharmacokinetics (PKs) and drug metabolism is essential for the optimal use of drugs in humans. Intestinal microbes are important contributors to variability; however, such gut microbe-drug interactions and the clinical significance of these interactions are still being elucidated. Traditional PKs can be complemented by untargeted mass spectrometry coupled with molecular networking to study the intricacies of drug metabolism. To show the utility of molecular networking on metabolism we investigated the impact of a 7-day course of cefprozil on cytochrome P450 (CYP) activity using a modified Cooperstown cocktail and assessed plasma, urine, and fecal data by targeted and untargeted metabolomics and molecular networking in healthy volunteers. This prospective study revealed that cefprozil decreased the activities of CYP1A2, CYP2C19, and CYP3A, decreased alpha diversity and increased interindividual microbiome variability. We further demonstrate a relationship between the loss of microbiome alpha diversity caused by cefprozil and increased drug and metabolite formation in fecal samples. Untargeted metabolomics/molecular networking revealed several omeprazole metabolites that we hypothesize may be metabolized by both CYP2C19 and bacteria from the gut microbiome. Our observations are consistent with the hypothesis that factors that perturb the gut microbiome, such as antibiotics, alter drug metabolism and ultimately drug efficacy and toxicity but that these effects are most strongly revealed on a per individual basis

Stabilizing the intensity of a wave amplified by a beam of particles

The intensity of an electromagnetic wave interacting self-consistently with a beam of charged particles as in a free electron laser, displays large oscillations due to an aggregate of particles, called the macro-particle. In this article, we propose a strategy to stabilize the intensity by re-shaping the macro-particle. This strategy involves the study of the linear stability (using the residue method) of selected periodic orbits of a mean-field model. As parameters of an additional perturbation are varied, bifurcations occur in the system which have drastic effect on the modification of the self-consistent dynamics, and in particular, of the macro-particle. We show how to obtain an appropriate tuning of the parameters which is able to strongly decrease the oscillations of the intensity without reducing its mean-value

Simulation and Experimental Validation of a Misaligned Rotor in Journal Bearings using Different Levels of Detail

In this contribution, a given test rig of a rotor system with journal bearing is validated by using simulation models with different levels of detail. A special focus is placed on the misalignment between rotor and bearing axis. It is shown, how to consider misalignment in the numeric calculation of the bearing forces as well as in the modeling of the rotor system. With a model of the LAVAL rotor, the misalignment in the test rig is identified by measuring and simulating relative equilibrium positions of the rotor in the bearing at different rotational speeds. A measured rotor orbit due to unbalance is used to compare simulation results of different complex rotor models and discuss their accuracy and efficiency

Prediction of Instability in Rotor-Seal Systems using Forward Whirl Magnetic Bearing Excitation

To separate different fluids and pressure levels in high-speed turbomachinery or pumps, mostly contactless seals are used. The leakage flow inside the seal gap applies forces to the vibrating rotor system in deflectional and tangential directions, that are dependent on the rotational speed. Above a speed limit, mainly tangential seal forces can lead to self-excited vibrations and, ultimately, rotor instability. This is similar to the “oil whip” phenomenon in journal bearings. To predict the speed limit, two methods are shown and compared: Simulations based on the bulk flow assumptions and an experimental method. To demonstrate the application, a test rig is used. The experimental method uses measured transfer functions, utilizing an active magnetic bearing for forward whirl excitation in the safe operational range. The speed limit can be predicted by analyzing and extrapolating the vibrational behavior of the rotor-seal system

Advancing Pharmacist Collaborative Care within Academic Health Systems.

INTRODUCTION:The scope of pharmacy practice has evolved over the last few decades to focus on the optimization of medication therapy. Despite this positive impact, the lack of reimbursement remains a significant barrier to the implementation of innovative pharmacist practice models. SUMMARY:We describe the successful development, implementation and outcomes of three types of pharmacist collaborative care models: (1) a pharmacist with physician oversight, (2) pharmacist-interprofessional teams and (3) physician-pharmacist teams. The outcome measurement of these pharmacist care models varied from the design phase to patient volume measurement and to comprehensive quality dashboards. All of these practice models have been successfully funded by affiliated health systems or grants. CONCLUSIONS:The expansion of pharmacist services delivered by clinical faculty has several benefits to affiliated health systems: (1) significant improvements in patient care quality, (2) access to experts in specialty areas, and (3) the dissemination of outcomes with national and international recognition, increasing the visibility of the health system

Universal trapping scaling on the unstable manifold for a collisionless electrostatic mode

An amplitude equation for an unstable mode in a collisionless plasma is derived from the dynamics on the two-dimensional unstable manifold of the equilibrium. The mode amplitude $\rho(t)$ decouples from the phase due to the spatial homogeneity of the equilibrium, and the resulting one-dimensional dynamics is analyzed using an expansion in $\rho$. As the linear growth rate $\gamma$ vanishes, the expansion coefficients diverge; a rescaling $\rho(t)\equiv\gamma^2\,r(\gamma t)$ of the mode amplitude absorbs these singularities and reveals that the mode electric field exhibits trapping scaling $|E_1|\sim\gamma^2$ as $\gamma\rightarrow0$. The dynamics for $r(\tau)$ depends only on the phase $e^{i\xi}$ where $d\epsilon_{{k}} /dz=|{\epsilon_{{k}}}|e^{-i\xi/2}$ is the derivative of the dielectric as $\gamma\rightarrow0$.Comment: 11 pages (Latex/RevTex), 2 figures available in hard copy from the Author ([email protected]); paper accepted by Physical Review Letter

Shell Evolution towards Ni 78: Low-Lying States in Cu 77

The level structure of the neutron-rich Cu77 nucleus is investigated through β-delayed γ-ray spectroscopy at the Radioactive Isotope Beam Factory of the RIKEN Nishina Center. Ions of Ni77 are produced by in-flight fission, separated and identified in the BigRIPS fragment separator, and implanted in the WAS3ABi silicon detector array, surrounded by Ge cluster detectors of the EURICA array. A large number of excited states in Cu77 are identified for the first time by correlating γ rays with the β decay of Ni77, and a level scheme is constructed by utilizing their coincidence relationships. The good agreement between large-scale Monte Carlo shell model calculations and experimental results allows for the evaluation of the single-particle structure near Ni78 and suggests a single-particle nature for both the 5/21- and 3/21- states in Cu77, leading to doubly magic Ni78. © 2017 American Physical Society

Motion of rotatory molecular motor and chemical reaction rate

We examine the dependence of the physical quantities of the rotatory molecular motor, such as the rotation velocity and the proton translocation rate, on the chemical reaction rate using the model based only on diffusion process. A peculiar behavior of proton translocation is found and the energy transduction efficiency of the motor protein is enhanced by this behavior. We give a natural explanation that this behavior is universal when certain inequalities between chemical reaction rates hold. That may give a clue to examine whether the motion of the molecular motor is dominated by diffusion process or not.Comment: 12 pages, 8 figure

Detachment of hard ticks (Acari: Ixodidae) from hunted sika deer (Cervus nippon)

Ixodid ticks were collected from 13 sika deer, Cervus n. nippon, shot in the Boso Peninsula in central Japan from late February to early March 1999. Haemaphysalis megaspinosa was the most abundant species of the adults collected, although Haemaphysalis longicornis, H. flava, H. kitaokai, H. cornigera, Ixodes ovatus, and Amblyomma testudinarium were also collected. Males were more abundant than females for H. longicornis, H. megaspinosa, H. flava, and H. kitaokai. Ticks that had inserted their hypostome into its host skin (designated attached) were distinguished from those that were detached and on the host\u27s surface. A greater fraction of males than females of all four species were detached. Females were classified in three feeding stages (engorged, partially engorged, and unfed). More H. longicornis and H. megaspinosa unfed female ticks than engorged and partially-engorged female ticks were collected detached. Our results indicated that H. megaspinosa, H. longicornis, H. flava, and H. kitaokai male ticks detached sooner than female ticks after their host died