Protease inhibitor monotherapy for long-term management of HIV infection: a randomised, controlled, open-label, non-inferiority trial

BACKGROUND: Standard-of-care antiretroviral therapy (ART) uses a combination of drugs deemed essential to minimise treatment failure and drug resistance. Protease inhibitors are potent, with a high genetic barrier to resistance, and have potential use as monotherapy after viral load suppression is achieved with combination treatment. We aimed to assess clinical risks and benefits of protease inhibitor monotherapy in long-term clinical use: in particular, the effect on drug resistance and future treatment options. METHODS: In this pragmatic, parallel-group, randomised, controlled, open-label, non-inferiority trial, we enrolled adults (≥18 years of age) positive for HIV attending 43 public sector treatment centres in the UK who had suppressed viral load (<50 copies per mL) for at least 24 weeks on combination ART with no change in the previous 12 weeks and a CD4 count of more than 100 cells per μL. Participants were randomly allocated (1:1) to maintain ongoing triple therapy (OT) or to switch to a strategy of physician-selected ritonavir-boosted protease inhibitor monotherapy (PI-mono); we recommended ritonavir (100 mg)-boosted darunavir (800 mg) once daily or ritonavir (100 mg)-boosted lopinavir (400 mg) twice daily, with prompt return to combination treatment if viral load rebounded. All treatments were oral. Randomisation was with permuted blocks of varying size and stratified by centre and baseline ART; we used a computer-generated, sequentially numbered randomisation list. The primary outcome was loss of future drug options, defined as new intermediate-level or high-level resistance to one or more drugs to which the patient's virus was deemed sensitive at trial entry (assessed at 3 years; non-inferiority margin of 10%). We estimated probability of rebound and resistance with Kaplan-Meier analysis. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISRCTN04857074. FINDINGS: Between Nov 4, 2008, and July 28, 2010, we randomly allocated 587 participants to OT (291) or PI-mono (296). At 3 years, one or more future drug options had been lost in two participants (Kaplan-Meier estimate 0·7%) in the OT group and six (2·1%) in the PI-mono group: difference 1·4% (-0·4 to 3·4); non-inferiority shown. 49 (16·8%) participants in the OT group and 65 (22·0%) in the PI-mono group had grade 3 or 4 clinical adverse events (difference 5·1% [95% CI -1·3 to 11·5]; p=0·12); 45 (six treatment related) and 56 (three treatment related) had serious adverse events. INTERPRETATION: Protease inhibitor monotherapy, with regular viral load monitoring and prompt reintroduction of combination treatment for rebound, preserved future treatment options and did not change overall clinical outcomes or frequency of toxic effects. Protease inhibitor monotherapy is an acceptable alternative for long-term clinical management of HIV infection. FUNDING: National Institute for Health Research

Quantum critical states and phase transitions in the presence of non equilibrium noise

Quantum critical points are characterized by scale invariant correlations and correspondingly long ranged entanglement. As such, they present fascinating examples of quantum states of matter, the study of which has been an important theme in modern physics. Nevertheless very little is known about the fate of quantum criticality under non equilibrium conditions. In this paper we investigate the effect of external noise sources on quantum critical points. It is natural to expect that noise will have a similar effect to finite temperature, destroying the subtle correlations underlying the quantum critical behavior. Surprisingly we find that in many interesting situations the ubiquitous 1/f noise preserves the critical correlations. The emergent states show intriguing interplay of intrinsic quantum critical and external noise driven fluctuations. We demonstrate this general phenomenon with specific examples in solid state and ultracold atomic systems. Moreover our approach shows that genuine quantum phase transitions can exist even under non equilibrium conditions.Comment: 9 pages, 2 figure

Optical Bragg, atom Bragg and cavity QED detections of quantum phases and excitation spectra of ultracold atoms in bipartite and frustrated optical lattices

Ultracold atoms loaded on optical lattices can provide unprecedented experimental systems for the quantum simulations and manipulations of many quantum phases and quantum phase transitions between these phases. However, so far, how to detect these quantum phases and phase transitions effectively remains an outstanding challenge. In this paper, we will develop a systematic and unified theory of using the optical Bragg scattering, atomic Bragg scattering or cavity QED to detect the ground state and the excitation spectrum of many quantum phases of interacting bosons loaded in bipartite and frustrated optical lattices. We show that the two photon Raman transition processes in the three detection methods not only couple to the density order parameter, but also the {\sl valence bond order} parameter due to the hopping of the bosons on the lattice. This valence bond order coupling is very sensitive to any superfluid order or any Valence bond (VB) order in the quantum phases to be probed. These quantum phases include not only the well known superfluid and Mott insulating phases, but also other important phases such as various kinds of charge density waves (CDW), valence bond solids (VBS), CDW-VBS phases with both CDW and VBS orders unique to frustrated lattices, and also various kinds of supersolids. The physical measurable quantities of the three experiments are the light scattering cross sections, the atom scattered clouds and the cavity leaking photons respectively. We analyze respectively the experimental conditions of the three detection methods to probe these various quantum phases and their corresponding excitation spectra. We also address the effects of a finite temperature and a harmonic trap.Comment: REVTEX4-1, 32 pages, 16.eps figures, to Appear in Annals of Physic

Non-equilibrium coherence dynamics in one-dimensional Bose gases

Low-dimensional systems are beautiful examples of many-body quantum physics. For one-dimensional systems the Luttinger liquid approach provides insight into universal properties. Much is known of the equilibrium state, both in the weakly and strongly interacting regime. However, it remains a challenge to probe the dynamics by which this equilibrium state is reached. Here we present a direct experimental study of the coherence dynamics in both isolated and coupled degenerate 1d Bose gases. Dynamic splitting is used to create two 1d systems in a phase coherent state. The time evolution of the coherence is revealed in local phase shifts of the subsequently observed interference patterns. Completely isolated 1d Bose gases are observed to exhibit a universal sub-exponential coherence decay in excellent agreement with recent predictions by Burkov et al. [Phys. Rev. Lett. 98, 200404 (2007)]. For two coupled 1d Bose gases the coherence factor is observed to approach a non-zero equilibrium value as predicted by a Bogoliubov approach. This coupled-system decay to finite coherence is the matter wave equivalent of phase locking two lasers by injection. The non-equilibrium dynamics of superfluids plays an important role in a wide range of physical systems, such as superconductors, quantum-Hall systems, superfluid Helium, and spin systems. Our experiments studying coherence dynamics show that 1d Bose gases are ideally suited for investigating this class of phenomena.Comment: to appear in natur

Basics of Superluminal Signals

The paper elucidates the physical basis of experimental results on superluminal signal velocity. It will be made plausible that superluminal signals do not violate the principle of causality but they can shorten the luminal vacuum time span between cause and effect. This amazing behaviour is based on the property that any physical signal has a finite duration.Comment: 11 pages, 8 figure

A.N. Kolmogorov’s defence of Mendelism

In 1939 N.I. Ermolaeva published the results of an experiment which repeated parts of Mendel’s classical experiments. On the basis of her experiment she concluded that Mendel’s principle that self-pollination of hybrid plants gave rise to segregation proportions 3:1 was false. The great probability theorist A.N. Kolmogorov reviewed Ermolaeva’s data using a test, now referred to as Kolmogorov’s, or Kolmogorov-Smirnov, test, which he had proposed in 1933. He found, contrary to Ermolaeva, that her results clearly confirmed Mendel’s principle. This paper shows that there were methodological flaws in Kolmogorov’s statistical analysis and presents a substantially adjusted approach, which confirms his conclusions. Some historical commentary on the Lysenko-era background is given, to illuminate the relationship of the disciplines of genetics and statistics in the struggle against the prevailing politically-correct pseudoscience in the Soviet Union. There is a Brazilian connection through the person of Th. Dobzhansky

Gap structure in the electron-doped Iron-Arsenide Superconductor Ba(Fe0.92Co0.08)2As2: low-temperature specific heat study

We report the field and temperature dependence of the low-temperature specific heat down to 400 mK and in magnetic fields up to 9 T of the electron-doped Ba(Fe0.92Co0.08)2As2 superconductor. Using the phonon specific heat obtained from pure BaFe2As2 we find the normal state Sommerfeld coefficient to be 18 mJ/mol.K^2 and a condensation energy of 1.27 J/mol. The temperature dependence of the electronic specific heat clearly indicate the presence of the low-energy excitations in the system. The magnetic field variation of field-induced specific heat cannot be described by single clean s- or d-wave models. Rather, the data require an anisotropic gap scenario which may or may not have nodes. We discuss the implications of these results.Comment: New Journal of Physics in press, 10 pages, 5 figure

Quantum Simulation of Antiferromagnetic Spin Chains in an Optical Lattice

Understanding exotic forms of magnetism in quantum mechanical systems is a central goal of modern condensed matter physics, with implications from high temperature superconductors to spintronic devices. Simulating magnetic materials in the vicinity of a quantum phase transition is computationally intractable on classical computers due to the extreme complexity arising from quantum entanglement between the constituent magnetic spins. Here we employ a degenerate Bose gas confined in an optical lattice to simulate a chain of interacting quantum Ising spins as they undergo a phase transition. Strong spin interactions are achieved through a site-occupation to pseudo-spin mapping. As we vary an applied field, quantum fluctuations drive a phase transition from a paramagnetic phase into an antiferromagnetic phase. In the paramagnetic phase the interaction between the spins is overwhelmed by the applied field which aligns the spins. In the antiferromagnetic phase the interaction dominates and produces staggered magnetic ordering. Magnetic domain formation is observed through both in-situ site-resolved imaging and noise correlation measurements. By demonstrating a route to quantum magnetism in an optical lattice, this work should facilitate further investigations of magnetic models using ultracold atoms, improving our understanding of real magnetic materials.Comment: 12 pages, 9 figure

The Top-Dog Index: A New Measurement for the Demand Consistency of the Size Distribution in Pre-Pack Orders for a Fashion Discounter with Many Small Branches

We propose the new Top-Dog-Index, a measure for the branch-dependent historic deviation of the supply data of apparel sizes from the sales data of a fashion discounter. A common approach is to estimate demand for sizes directly from the sales data. This approach may yield information for the demand for sizes if aggregated over all branches and products. However, as we will show in a real-world business case, this direct approach is in general not capable to provide information about each branch's individual demand for sizes: the supply per branch is so small that either the number of sales is statistically too small for a good estimate (early measurement) or there will be too much unsatisfied demand neglected in the sales data (late measurement). Moreover, in our real-world data we could not verify any of the demand distribution assumptions suggested in the literature. Our approach cannot estimate the demand for sizes directly. It can, however, individually measure for each branch the scarcest and the amplest sizes, aggregated over all products. This measurement can iteratively be used to adapt the size distributions in the pre-pack orders for the future. A real-world blind study shows the potential of this distribution free heuristic optimization approach: The gross yield measured in percent of gross value was almost one percentage point higher in the test-group branches than in the control-group branches.Comment: 22 pages, 15 figure

Dynamics of thermochemical plumes: 1. Plume formation and entrainment of a dense layer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94724/1/ggge779.pd