Are generic immunosuppressants safe and effective? Clinical experience is reassuring and regulation is strict, now we need definitive evidence

Increasing use of generic drugs is essential to maintain comprehensive and equitable healthcare, given current pressure on budgets through, for instance, ageing populations. Initiatives among health authorities to promote generic prescribing include educational initiatives (which in the United Kingdom has resulted in high levels of prescribing of international non-proprietary name (INN) drugs in over 80% of all prescriptions), compulsory generic substitution in pharmacies, and patients paying extra “out of pocket” expenses for a proprietary drug.[1-3] Concerns remain, however, about generic prescribing or compulsory substitution in certain drugs and drug classes, including lithium, theophyllines, some anti-epileptic drugs, and the immunosuppressants evaluated in the linked study by Molnar and colleagues (doi:10.1136/bmj.h3163)

Twisted duality of the CAR-Algebra

We give a complete proof of the twisted duality property M(q)'= Z M(q^\perp) Z* of the (self-dual) CAR-Algebra in any Fock representation. The proof is based on the natural Halmos decomposition of the (reference) Hilbert space when two suitable closed subspaces have been distinguished. We use modular theory and techniques developed by Kato concerning pairs of projections in some essential steps of the proof. As a byproduct of the proof we obtain an explicit and simple formula for the graph of the modular operator. This formula can be also applied to fermionic free nets, hence giving a formula of the modular operator for any double cone.Comment: 32 pages, Latex2e, to appear in Journal of Mathematical Physic

First Order Relativistic Three-Body Scattering

Relativistic Faddeev equations for three-body scattering at arbitrary energies are formulated in momentum space and in first order in the two-body transition-operator directly solved in terms of momentum vectors without employing a partial wave decomposition. Relativistic invariance is incorporated within the framework of Poincare invariant quantum mechanics, and presented in some detail. Based on a Malfliet-Tjon type interaction, observables for elastic and break-up scattering are calculated up to projectile energies of 1 GeV. The influence of kinematic and dynamic relativistic effects on those observables is systematically studied. Approximations to the two-body interaction embedded in the three-particle space are compared to the exact treatment.Comment: 26 pages, 13 figure

Protein phosphatase 1-dependent bidirectional synaptic plasticity controls ischemic recovery in the adult brain

Protein kinases and phosphatases can alter the impact of excitotoxicity resulting from ischemia by concurrently modulating apoptotic/survival pathways. Here, we show that protein phosphatase 1 (PP1), known to constrain neuronal signaling and synaptic strength (Mansuy et al., 1998; Morishita et al., 2001), critically regulates neuroprotective pathways in the adult brain. When PP1 is inhibited pharmacologically or genetically, recovery from oxygen/glucose deprivation (OGD) in vitro, or ischemia in vivo is impaired. Furthermore, in vitro, inducing LTP shortly before OGD similarly impairs recovery, an effect that correlates with strong PP1 inhibition. Conversely, inducing LTD before OGD elicits full recovery by preserving PP1 activity, an effect that is abolished by PP1 inhibition. The mechanisms of action of PP1 appear to be coupled with several components of apoptotic pathways, in particular ERK1/2 (extracellular signal-regulated kinase 1/2) whose activation is increased by PP1 inhibition both in vitro and in vivo. Together, these results reveal that the mechanisms of recovery in the adult brain critically involve PP1, and highlight a novel physiological function for long-term potentiation and long-term depression in the control of brain damage and repair

Topological doping of repulsive Hubbard models

The spin configuration induced by single holes and hole pairs doped into stoichiometric, antiferromagnetic cuprates is considered. Unrestricted Hartree-Fock calculations for the three-band Hubbard model are employed to study spin-polaron and vortex-like (meron) solutions. Meron solutions for a single hole are found to be metastable with higher energy than spin polarons. We observe that the meron solution shifts from site-centered to bond-centered as the interaction is increased. Meron-antimeron solutions for hole pairs are found to be unstable. The results are in agreement with earlier findings for the one-band Hubbard model. However, we find that the Hubbard interaction of the one-band model has to be chosen similar to the one of the three-band model to obtain comparable results, not of the order of the charge-transfer gap, as previously expected.Comment: 7 pages, 6 figure

Generalized Particle Statistics in Two-Dimensions: Examples from the Theory of Free Massive Dirac Field

In the framework of algebraic quantum field theory we analyze the anomalous statistics exhibited by a class of automorphisms of the observable algebra of the two-dimensional free massive Dirac field, constructed by fermionic gauge group methods. The violation of Haag duality, the topological peculiarity of a two-dimensional space-time and the fact that unitary implementers do not lie in the global field algebra account for strange behaviour of statistics, which is no longer an intrinsic property of sectors. Since automorphisms are not inner, we exploit asymptotic abelianness of intertwiners in order to construct a braiding for a suitable $C^*$-tensor subcategory of End($\mathscr{A}$). We define two inequivalent classes of path connected bi-asymptopias, selecting only those sets of nets which yield a true generalized statistics operator.Comment: 24 page

Doping dependence of the Neel temperature in Mott-Hubbard antiferromagnets: Effect of vortices

The rapid destruction of long-range antiferromagnetic order upon doping of Mott-Hubbard antiferromagnetic insulators is studied within a generalized Berezinskii-Kosterlitz-Thouless renormalization group theory in accordance with recent calculations suggesting that holes dress with vortices. We calculate the doping-dependent Neel temperature in good agreement with experiments for high-Tc cuprates. Interestingly, the critical doping where long-range order vanishes at zero temperature is predicted to be xc ~ 0.02, independently of any energy scales of the system.Comment: 4 pages with 3 figures included, minor revisions, to be published in PR

Time delay for one-dimensional quantum systems with steplike potentials

This paper concerns time-dependent scattering theory and in particular the concept of time delay for a class of one-dimensional anisotropic quantum systems. These systems are described by a Schr\"{o}dinger Hamiltonian $H = -\Delta + V$ with a potential $V(x)$ converging to different limits $V_{\ell}$ and $V_{r}$ as $x \to -\infty$ and $x \to +\infty$ respectively. Due to the anisotropy they exhibit a two-channel structure. We first establish the existence and properties of the channel wave and scattering operators by using the modern Mourre approach. We then use scattering theory to show the identity of two apparently different representations of time delay. The first one is defined in terms of sojourn times while the second one is given by the Eisenbud-Wigner operator. The identity of these representations is well known for systems where $V(x)$ vanishes as $|x| \to \infty$ ($V_\ell = V_r$). We show that it remains true in the anisotropic case $V_\ell \not = V_r$, i.e. we prove the existence of the time-dependent representation of time delay and its equality with the time-independent Eisenbud-Wigner representation. Finally we use this identity to give a time-dependent interpretation of the Eisenbud-Wigner expression which is commonly used for time delay in the literature.Comment: 48 pages, 1 figur

Projective Hilbert space structures at exceptional points

A non-Hermitian complex symmetric 2x2 matrix toy model is used to study projective Hilbert space structures in the vicinity of exceptional points (EPs). The bi-orthogonal eigenvectors of a diagonalizable matrix are Puiseux-expanded in terms of the root vectors at the EP. It is shown that the apparent contradiction between the two incompatible normalization conditions with finite and singular behavior in the EP-limit can be resolved by projectively extending the original Hilbert space. The complementary normalization conditions correspond then to two different affine charts of this enlarged projective Hilbert space. Geometric phase and phase jump behavior are analyzed and the usefulness of the phase rigidity as measure for the distance to EP configurations is demonstrated. Finally, EP-related aspects of PT-symmetrically extended Quantum Mechanics are discussed and a conjecture concerning the quantum brachistochrone problem is formulated.Comment: 20 pages; discussion extended, refs added; bug correcte

Spintronic magnetic anisotropy

An attractive feature of magnetic adatoms and molecules for nanoscale applications is their superparamagnetism, the preferred alignment of their spin along an easy axis preventing undesired spin reversal. The underlying magnetic anisotropy barrier --a quadrupolar energy splitting-- is internally generated by spin-orbit interaction and can nowadays be probed by electronic transport. Here we predict that in a much broader class of quantum-dot systems with spin larger than one-half, superparamagnetism may arise without spin-orbit interaction: by attaching ferromagnets a spintronic exchange field of quadrupolar nature is generated locally. It can be observed in conductance measurements and surprisingly leads to enhanced spin filtering even in a state with zero average spin. Analogously to the spintronic dipolar exchange field, responsible for a local spin torque, the effect is susceptible to electric control and increases with tunnel coupling as well as with spin polarization.Comment: 6 pages with 4 figures + 26 pages of Supplementary Informatio