Association of Tenofovir Use With Risk of Incident Heart Failure in HIV-Infected Patients.

BackgroundThe antiretroviral medication, tenofovir disoproxil fumarate (TDF), is used by most human immunodeficiency virus-infected persons in the United States despite higher risks of chronic kidney disease. Although chronic kidney disease is a strong risk factor for heart failure (HF), the association of TDF with incident HF is unclear.Methods and resultsWe identified 21 435 human immunodeficiency virus-infected patients in the United States Veterans Health Administration actively using antiretrovirals between 2002 and 2011. We excluded patients with a prior diagnosis of HF. TDF was analyzed categorically (current, past, or never use) and continuously (per year of use). Proportional hazards regression and fully adjusted marginal structural models were used to determine the association of TDF exposure with risk of incident HF after adjustment for demographic, human immunodeficiency virus-related, and cardiovascular risk factors. During follow-up, 438 incident HF events occurred. Unadjusted 5-year event rates for current, past, and never users of TDF were 0.9 (95%CI 0.7-1.1), 1.7 (1.4-2.2), and 4.5 (3.9-5.0), respectively. In fully adjusted analyses, HF risk was markedly lower in current TDF users (HR=0.68; 95%CI 0.53-0.86) compared with never users. Among current TDF users, each additional year of TDF exposure was associated with a 21% lower risk of incident HF (95%CI: 0.68-0.92). When limited to antiretroviral-naive patients, HF risk remained lower in current TDF users (HR=0.53; 95%CI 0.36-0.78) compared to never users.ConclusionsAmong a large national cohort of human immunodeficiency virus-infected patients, TDF use was strongly associated with lower risk of incident HF. These findings warrant confirmation in other populations, both with TDF and the recently approved tenofovir alafenamide fumarate

The order-up-to policy "sweet spot": using proportional controllers to eliminate the bullwhip problem

We develop a discrete control theory model of a stochastic demand pattern with both Auto Regressive and Moving Average (ARMA) components. We show that the bullwhip effect arises when the myopic Order-Up-To (OUT) policy is used. This policy is optimal when the ordering cost is linear. We then derive a set of z-transform transfer functions of a modified policy that allows us to avoid the bullwhip problem by incorporating a proportional controller into the inventory position feedback loop. With this technique, the order variation can be reduced to the same level as the demand variation. However, bullwhip-effect avoidance in our policy always comes at the costs of holding extra inventory. When the ordering cost is piece -wise linear and increasing, we compare the total cost per period under the two types of ordering policies: with and without bullwhip - effect reduction. Numerical examples reveal that the cost saving can be substantial if order variance is reduced using the proportional controller

AtomSim: web-deployed atomistic dynamics simulator

AtomSim, a collection of interfaces for computational crystallography simulations, has been developed. It uses forcefield-based dynamics through physics engines such as the General Utility Lattice Program, and can be integrated into larger computational frameworks such as the Virtual Neutron Facility for processing its dynamics into scattering functions, dynamical functions etc. It is also available as a Google App Engine-hosted web-deployed interface. Examples of a quartz molecular dynamics run and a hafnium dioxide phonon calculation are presented

Phonon anharmonicity and negative thermal expansion in SnSe

The anharmonic phonon properties of SnSe in the Pnma phase were investigated with a combination of experiments and first-principles simulations. Using inelastic neutron scattering (INS) and nuclear resonant inelastic X-ray scattering (NRIXS), we have measured the phonon dispersions and density of states (DOS) and their temperature dependence, which revealed a strong, inhomogeneous shift and broadening of the spectrum on warming. First-principles simulations were performed to rationalize these measurements, and to explain the previously reported anisotropic thermal expansion, in particular the negative thermal expansion within the Sn-Se bilayers. Including the anisotropic strain dependence of the phonon free energy, in addition to the electronic ground state energy, is essential to reproduce the negative thermal expansion. From the phonon DOS obtained with INS and additional calorimetry measurements, we quantify the harmonic, dilational, and anharmonic components of the phonon entropy, heat capacity, and free energy. The origin of the anharmonic phonon thermodynamics is linked to the electronic structure.Comment: 14 pages, 12 figure

Calibration and Irradiation Study of the BGO Background Monitor for the BEAST II Experiment

Beam commissioning of the SuperKEKB collider began in 2016. The Beam Exorcism for A STable experiment II (BEAST II) project is particularly designed to measure the beam backgrounds around the interaction point of the SuperKEKB collider for the Belle II experiment. We develop a system using bismuth germanium oxide (BGO) crystals with optical fibers connecting to a multianode photomultiplier tube (MAPMT) and a field-programmable gate array (FPGA) embedded readout board for monitoring the real-time beam backgrounds in BEAST II. The overall radiation sensitivity of this system is estimated to be $(2.20\pm0.26)\times10^{-12}$ Gy/ADU (analog-to-digital unit) with the standard 10 m fibers for transmission and the MAPMT operating at 700 V. Our $\gamma$-ray irradiation study of the BGO system shows that the exposure of BGO crystals to $^{60}$Co $\gamma$-ray doses of 1 krad has led to immediate light output reductions of 25--40%, and the light outputs further drop by 30--45% after the crystals receive doses of 2--4 krad. Our findings agree with those of the previous studies on the radiation hard (RH) BGO crystals grown by the low thermal gradient Czochralski (LTG Cz) technology. The absolute dose from the BGO system is also consistent with the simulation, and is estimated to be about 1.18 times the equivalent dose. These results prove that the BGO system is able to monitor the background dose rate in real time under extreme high radiation conditions. This study concludes that the BGO system is reliable for the beam background study in BEAST II

Various Correlations in Anisotropic Heisenberg XYZ Model with Dzyaloshinski-Moriya Interaction

Various thermal correlations as well as the effect of intrinsic decoherence on the correlations are studied in a two-qubit Heisenberg XYZ spin chain with the Dzyaloshinski--Moriya (DM) interaction along the z direction, i.e. Dz. It is found that tunable parameter Dz may play a constructive role on the concurrence (C), classical correlation (CC) and quantum discord (QD) in thermal equilibrium while it plays a destructive role on the correlations in the intrinsic decoherence case. The entanglement and quantum discord exhibit collapse and revival under the phase decoherence. With a proper combination of the system parameters, the correlations can effectively be kept at high steady state values despite the intrinsic decoherence.Comment: 4 pages, 4 figure

Advances and Future Challenges in Adenoviral Vector Pharmacology and Targeting

Adenovirus is a robust vector for therapeutic applications, but its use is limited by our understanding of its complex in vivo pharmacology. In this review we describe the necessity of identifying its natural, widespread, and multifaceted interactions with the host since this information will be crucial for efficiently redirecting virus into target cells. In the rational design of vectors, the notion of overcoming a sequence of viral “sinks” must be combined with re-targeting to target populations with capsid as well as shielding the vectors from pre-existing or toxic immune responses. It must also be noted that most known adenoviral pharmacology is deduced from the most commonly used serotypes, Ad5 and Ad2. However, these serotypes may not represent all adenoviruses, and may not even represent the most useful vectors for all purposes. Chimeras between Ad serotypes may become useful in engineering vectors that can selectively evade substantial viral traps, such as Kupffer cells, while retaining the robust qualities of Ad5. Similarly, vectorizing other Ad serotypes may become useful in avoiding immunity against Ad5 altogether. Taken together, this research on basic adenovirus biology will be necessary in developing vectors that interact more strategically with the host for the most optimal therapeutic effect

Pattern manipulation via on-chip phase modulation between orbital angular momentum beams

An integrated approach to thermal modulation of relative phase between two optical vortices with opposite chirality has been demonstrated on a silicon-on-insulator substrate. The device consists of a silicon-integrated optical vortex emitter and a phase controlled 3 dB coupler. The relative phase between two optical vortices can be actively modulated on chip by applying a voltage on the integrated heater. The phase shift is shown to be linearly proportional to applied electrical power, and the rotation angle of the interference pattern is observed to be inversely proportional to topological charge. This scheme can be used in lab-on-chip, communications and sensing applications. It can be intentionally implemented with other modulation elements to achieve more complicated applications