Resonances in a spring-pendulum: algorithms for equivariant singularity theory

A spring-pendulum in resonance is a time-independent Hamiltonian model system for formal reduction to one degree of freedom, where some symmetry (reversibility) is maintained. The reduction is handled by equivariant singularity theory with a distinguished parameter, yielding an integrable approximation of the Poincaré map. This makes a concise description of certain bifurcations possible. The computation of reparametrizations from normal form to the actual system is performed by Gröbner basis techniques.

The Elliptic Billiard: Subtleties of Separability

Some of the subtleties of the integrability of the elliptic quantum billiard are discussed. A well known classical constant of the motion has in the quantum case an ill-defined commutator with the Hamiltonian. It is shown how this problem can be solved. A geometric picture is given revealing why levels of a separable system cross. It is shown that the repulsions found by Ayant and Arvieu are computational effects and that the method used by Traiber et al. is related to the present picture which explains the crossings they find. An asymptotic formula for the energy-levels is derived and it is found that the statistical quantities of the spectrum P(s) and \Delta(L) have the form expected for an integrable system.Comment: 10 pages, LaTeX, 3 Figures (postscript). Submitted to European Journal of Physic

Subtherapeutic triazole concentrations as result of a drug-drug interaction with lumacaftor/ivacaftor

Lumacaftor/ivacaftor (Orkambi®, LUM/IVA) is indicated for the treatment of cystic fibrosis (CF) patients aged ≥ 2 years with homozygous F580del mutation in the CFTR gene. Triazole fungal agents are used to treat fungal disease in CF. The use of triazoles is limited by pharmacokinetic challenges, such as drug-drug interactions. The most notable drug-drug interaction between triazoles and LUM/IVA is due to strong induction of CYP3A4 and UGT by LUM. In this real-world retrospective observational study, we described the effect of LUM/IVA on the trough concentration of triazoles. Concomitant use of LUM/IVA with itraconazole, posaconazole or voriconazole resulted in subtherapeutic triazole levels in 76% of the plasma samples. In comparison, in patients with triazole agents without LUM/IVA only 30.6% of the plasma samples resulted in subtherapeutic concentrations. Subtherapeutic plasma concentrations of triazoles should be considered in CF patients on LUM/IVA and further research is warranted for other dosing strategies and alternative antifungal therapy.</p

Subtherapeutic triazole concentrations as result of a drug-drug interaction with lumacaftor/ivacaftor

Lumacaftor/ivacaftor (Orkambi®, LUM/IVA) is indicated for the treatment of cystic fibrosis (CF) patients aged ≥ 2 years with homozygous F580del mutation in the CFTR gene. Triazole fungal agents are used to treat fungal disease in CF. The use of triazoles is limited by pharmacokinetic challenges, such as drug-drug interactions. The most notable drug-drug interaction between triazoles and LUM/IVA is due to strong induction of CYP3A4 and UGT by LUM. In this real-world retrospective observational study, we described the effect of LUM/IVA on the trough concentration of triazoles. Concomitant use of LUM/IVA with itraconazole, posaconazole or voriconazole resulted in subtherapeutic triazole levels in 76% of the plasma samples. In comparison, in patients with triazole agents without LUM/IVA only 30.6% of the plasma samples resulted in subtherapeutic concentrations. Subtherapeutic plasma concentrations of triazoles should be considered in CF patients on LUM/IVA and further research is warranted for other dosing strategies and alternative antifungal therapy.</p

New Results for Diffusion in Lorentz Lattice Gas Cellular Automata

New calculations to over ten million time steps have revealed a more complex diffusive behavior than previously reported, of a point particle on a square and triangular lattice randomly occupied by mirror or rotator scatterers. For the square lattice fully occupied by mirrors where extended closed particle orbits occur, anomalous diffusion was still found. However, for a not fully occupied lattice the super diffusion, first noticed by Owczarek and Prellberg for a particular concentration, obtains for all concentrations. For the square lattice occupied by rotators and the triangular lattice occupied by mirrors or rotators, an absence of diffusion (trapping) was found for all concentrations, except on critical lines, where anomalous diffusion (extended closed orbits) occurs and hyperscaling holds for all closed orbits with {\em universal} exponents ${\displaystyle{d_f = \frac{7}{4}}}$ and ${\displaystyle{\tau = \frac{15}{7}}}$. Only one point on these critical lines can be related to a corresponding percolation problem. The questions arise therefore whether the other critical points can be mapped onto a new percolation-like problem, and of the dynamical significance of hyperscaling.Comment: 52 pages, including 18 figures on the last 22 pages, email: [email protected]

An Intersecting Loop Model as a Solvable Super Spin Chain

In this paper we investigate an integrable loop model and its connection with a supersymmetric spin chain. The Bethe Ansatz solution allows us to study some properties of the ground state. When the loop fugacity $q$ lies in the physical regime, we conjecture that the central charge is $c=q-1$ for $q$ integer $< 2$. Low-lying excitations are examined, supporting a superdiffusive behavior for $q=1$. We argue that these systems are interesting examples of integrable lattice models realizing $c \leq 0$ conformal field theories.Comment: latex file, 7 page

The effect of intrathecal bupivacaine/morphine on quality of recovery in robot-assisted radical prostatectomy: a randomised controlled trial

Robot-assisted radical prostatectomy causes discomfort in the immediate postoperative period. This randomised controlled trial investigated if intrathecal bupivacaine/morphine, in addition to general anaesthesia, could be beneficial for the postoperative quality of recovery. One hundred and fifty-five patients were randomly allocated to an intervention group that received intrathecal 12.5 mg bupivacaine/300 μg morphine (20% dose reduction in patients > 75 years) or a control group receiving a subcutaneous sham injection and an intravenous loading dose of 0.1 mg.kg−1 morphine. Both groups received standardised general anaesthesia and the same postoperative analgesic regimen. The primary outcome was a decrease in the Quality of Recovery-15 (QoR-15) questionnaire score on postoperative day 1. The intervention group (n = 76) had less reduction in QoR-15 on postoperative day 1; median (IQR [range]) 10% (1–8 [−60% to 50%]) vs. 13% (5–24 [−6% to 50%]), p = 0.019, and used less morphine during the admission; 2 mg (1–7 [0–41 mg]) vs. 15 mg (12–20 [8–61 mg]), p < 0.001. Furthermore, they perceived lower pain scores during exertion; numeric rating scale (NRS) 3 (1–6 [0–9]) vs. 5 (3–7 [0–9]), p = 0.001; less bladder spasms (NRS 1 (0–2 [0–10]) vs. 2 (0–5 [0–10]), p = 0.001 and less sedation; NRS 2 (0–3 [0–10]) vs. 3 (2–6 [0–10]), p = 0.005. Moreover, the intervention group used less rescue medication. Pruritus was more severe in the intervention group; NRS 4 (1–7 [0–10]) vs. 0 (0–1 [0–10]), p = 0.000. We conclude that despite a modest increase in the incidence of pruritus, multimodal pain management with intrathecal bupivacaine/morphine remains a viable option for robot-assisted radical prostatectomy

Thermodynamic formalism for systems with Markov dynamics

The thermodynamic formalism allows one to access the chaotic properties of equilibrium and out-of-equilibrium systems, by deriving those from a dynamical partition function. The definition that has been given for this partition function within the framework of discrete time Markov chains was not suitable for continuous time Markov dynamics. Here we propose another interpretation of the definition that allows us to apply the thermodynamic formalism to continuous time. We also generalize the formalism --a dynamical Gibbs ensemble construction-- to a whole family of observables and their associated large deviation functions. This allows us to make the connection between the thermodynamic formalism and the observable involved in the much-studied fluctuation theorem. We illustrate our approach on various physical systems: random walks, exclusion processes, an Ising model and the contact process. In the latter cases, we identify a signature of the occurrence of dynamical phase transitions. We show that this signature can already be unravelled using the simplest dynamical ensemble one could define, based on the number of configuration changes a system has undergone over an asymptotically large time window.Comment: 64 pages, LaTeX; version accepted for publication in Journal of Statistical Physic