Generalized Linear Response Theory for the Full Quantum Work Statistics.

We consider a quantum system driven out of equilibrium via a small Hamiltonian perturbation. Building on the paradigmatic framework of linear response theory (LRT), we derive an expression for the full generating function of the dissipated work. Remarkably, we find that all information about the distribution can be encoded in a single quantity, the standard relaxation function in LRT, thus opening up new ways to use phenomenological models to study nonequilibrium fluctuations in complex quantum systems. Our results establish a number of refined quantum thermodynamic constraints on the work statistics that apply to regimes of perturbative but arbitrarily fast protocols, and do not rely on assumptions such as slow driving or weak coupling. Finally, our approach uncovers a distinctly quantum signature in the work statistics that originates from underlying zero-point energy fluctuations. This causes an increased dispersion of the probability distribution at short driving times, a feature that can be probed in efforts to witness nonclassical effects in quantum thermodynamics.

Quantum Work Statistics at Strong Reservoir Coupling.

Determining the statistics of work done on a quantum system while strongly coupled to a reservoir is a formidable task, requiring the calculation of the full eigenspectrum of the combined system and reservoir. Here, we show that this issue can be circumvented by using a polaron transformation that maps the system into a new frame where weak-coupling theory can be applied. Crucially, this polaron approach reproduces the Jarzynski fluctuation theorem, thus ensuring consistency with the laws of stochastic thermodynamics. We apply our formalism to a system driven across the Landau-Zener transition, where we identify clear signatures in the work distribution arising from a non-negligible coupling to the environment. Our results provide a new method for studying the stochastic thermodynamics of driven quantum systems beyond Markovian, weak-coupling regimes.

Thermodynamic Uncertainty Relation in Slowly Driven Quantum Heat Engines.

Thermodynamic uncertainty relations express a trade-off between precision, defined as the noise-to-signal ratio of a generic current, and the amount of associated entropy production. These results have deep consequences for autonomous heat engines operating at steady state, imposing an upper bound for their efficiency in terms of the power yield and its fluctuations. In the present Letter we analyze a different class of heat engines, namely, those which are operating in the periodic slow-driving regime. We show that an alternative TUR is satisfied, which is less restrictive than that of steady-state engines: it allows for engines that produce finite power, with small power fluctuations, to operate close to reversibility. The bound further incorporates the effect of quantum fluctuations, which reduces engine efficiency relative to the average power and reliability. We finally illustrate our findings in the experimentally relevant model of a single-ion heat engine.

Geometry of Work Fluctuations versus Efficiency in Microscopic Thermal Machines.

When engineering microscopic machines, increasing efficiency can often come at a price of reduced reliability due to the impact of stochastic fluctuations. Here we develop a general method for performing multiobjective optimization of efficiency and work fluctuations in thermal machines operating close to equilibrium in either the classical or quantum regime. Our method utilizes techniques from thermodynamic geometry, whereby we match optimal solutions to protocols parametrized by their thermodynamic length. We characterize the optimal protocols for continuous-variable Gaussian machines, which form a crucial class in the study of thermodynamics for microscopic systems.

Quantum Fluctuations Hinder Finite-Time Information Erasure near the Landauer Limit.

Information is physical but information is also processed in finite time. Where computing protocols are concerned, finite-time processing in the quantum regime can dynamically generate coherence. Here we show that this can have significant thermodynamic implications. We demonstrate that quantum coherence generated in the energy eigenbasis of a system undergoing a finite-time information erasure protocol yields rare events with extreme dissipation. These fluctuations are of purely quantum origin. By studying the full statistics of the dissipated heat in the slow-driving limit, we prove that coherence provides a non-negative contribution to all statistical cumulants. Using the simple and paradigmatic example of single bit erasure, we show that these extreme dissipation events yield distinct, experimentally distinguishable signatures.

Geometric Optimisation of Quantum Thermodynamic Processes.

Differential geometry offers a powerful framework for optimising and characterising finite-time thermodynamic processes, both classical and quantum. Here, we start by a pedagogical introduction to the notion of thermodynamic length. We review and connect different frameworks where it emerges in the quantum regime: adiabatically driven closed systems, time-dependent Lindblad master equations, and discrete processes. A geometric lower bound on entropy production in finite-time is then presented, which represents a quantum generalisation of the original classical bound. Following this, we review and develop some general principles for the optimisation of thermodynamic processes in the linear-response regime. These include constant speed of control variation according to the thermodynamic metric, absence of quantum coherence, and optimality of small cycles around the point of maximal ratio between heat capacity and relaxation time for Carnot engines.

Work Fluctuations in Slow Processes: Quantum Signatures and Optimal Control.

An important result in classical stochastic thermodynamics is the work fluctuation-dissipation relation (FDR), which states that the dissipated work done along a slow process is proportional to the resulting work fluctuations. We show that slowly driven quantum systems violate this FDR whenever quantum coherence is generated along the protocol, and we derive a quantum generalization of the work FDR. The additional quantum terms in the FDR are found to lead to a non-Gaussian work distribution. Fundamentally, our result shows that quantum fluctuations prohibit finding slow protocols that minimize both dissipation and fluctuations simultaneously, in contrast to classical slow processes. Instead, we develop a quantum geometric framework to find processes with an optimal trade-off between the two quantities.

Leggett-Garg Inequalities for Quantum Fluctuating Work.

The Leggett-Garg inequalities serve to test whether or not quantum correlations in time can be explained within a classical macrorealistic framework. We apply this test to thermodynamics and derive a set of Leggett-Garg inequalities for the statistics of fluctuating work done on a quantum system unitarily driven in time. It is shown that these inequalities can be violated in a driven two-level system, thereby demonstrating that there exists no general macrorealistic description of quantum work. These violations are shown to emerge within the standard Two-Projective-Measurement scheme as well as for alternative definitions of fluctuating work that are based on weak measurement. Our results elucidate the influences of temporal correlations on work extraction in the quantum regime and highlight a key difference between quantum and classical thermodynamics.

RESCUE PNEUMATIC RETINOPEXY IN PATIENTS WITH FAILED PRIMARY RETINAL DETACHMENT SURGERY.

PURPOSE: To describe the outcome of a series of patients who underwent pneumatic retinopexy (PR) for recurrent retinal detachment after scleral buckling and vitrectomy. METHODS: This is a retrospective review of 42 consecutive cases who underwent secondary PR after either scleral buckling (n = 22) or vitrectomy (n = 20) between 1995 and 2011. Fisher's exact and nonparametric tests were used for comparison. RESULTS: Hundred percent of patients in the scleral buckle group and 90% of the vitrectomy group were repaired with 1 PR procedure (P = 0.67). The two patients in the vitrectomy group failed because of presumed new breaks and proliferative vitreoretinopathy. The median time between the primary procedure and PR was 8.5 days for the scleral buckle group (interquartile range, 5-55 days) and 31.5 days for the vitrectomy group (interquartile range, 21-52 days) (P = 0.003). Postoperative median visual acuity improved by more than 2 logMAR lines in both the scleral buckle group (P = 0.0008) and the vitrectomy group (P = 0.007), with no difference between groups (P = 0.19). The overall complication rate in our patients was 16%, including transient intraocular pressure rise and development of tears requiring further indirect laser retinopexy within 3 months. None of the patients had vitreous hemorrhage, subretinal gas, or endophthalmitis. CONCLUSION: Rescue PR seems to be a safe and effective method of treating recurrent retinal detachment after both unsuccessful scleral buckling and vitrectomy.

Joint statistics of work and entropy production along quantum trajectories.

In thermodynamics, entropy production and work quantify irreversibility and the consumption of useful energy, respectively, when a system is driven out of equilibrium. For quantum systems, these quantities can be identified at the stochastic level by unravelling the system's evolution in terms of quantum jump trajectories. We here derive a general formula for computing the joint statistics of work and entropy production in Markovian driven quantum systems, whose instantaneous steady states are of Gibbs form. If the driven system remains close to the instantaneous Gibbs state at all times, then we show that the corresponding two-variable cumulant generating function implies a joint detailed fluctuation theorem so long as detailed balance is satisfied. As a corollary, we derive a modified fluctuation-dissipation relation (FDR) for the entropy production alone, applicable to transitions between arbitrary steady states, and for systems that violate detailed balance. This FDR contains a term arising from genuinely quantum fluctuations, and extends an analogous relation from classical thermodynamics to the quantum regime.

The dose in humans at which ICI 118,551 (a selective beta 2-adrenoceptor blocking agent) demonstrates blockade of beta 1-adrenoceptors.

The effects of four single oral doses of ICI 118,551 (a selective beta 2-adrenoceptor blocking agent: doses 10, 20, 50, and 100 mg) have been compared with placebo in five normal, healthy volunteers on some cardiovascular responses to intravenous infusions of dobutamine. Increasing infusions of dobutamine produced reproducible dose-dependent reductions in systolic time intervals and increases in systolic blood pressures, these responses representing positive inotropic effects of dobutamine. These effects of dobutamine were unaffected 2 hours after administration by 10 mg ICI 118,551 and minimally by 20 mg; the 50 mg dose attenuated the systolic time interval effect whereas the 100 mg dose attenuated further the systolic time interval reduction and also the increase in systolic blood pressure. These results allow a conclusion that at unit doses of 50 mg and above, ICI 118,551 will produce demonstrable effects on beta 1-adrenoceptors.

Effect of age and gender on tirilazad pharmacokinetics in humans.

Tirilazad mesylate pharmacokinetics were assessed in 12 young and 12 elderly volunteers (six men and six women per age group). Subjects received single 10-minute intravenous infusions of 1.5 mg/kg and 3.0 mg/kg tirilazad mesylate. Plasma tirilazad mesylate concentrations were determined by HPLC. There were no significant dose effects on clearance, but half-life increased with dose because of assay insensitivity at the lower dose. Mean half-lives were 16.3 +/- 15.5 and 21.4 +/- 12.6 hours for young and elderly subjects, respectively, at the 3.0 mg/kg dose. At the same dose, mean tirilazad mesylate systemic clearance was 0.630 +/- 0.254 and 0.428 +/- 0.090 L/hr/kg, respectively. The decreased clearance in elderly volunteers was primarily attributable to a lower clearance in elderly women relative to young women. The small effect of age on tirilazad clearance is likely to have minimum clinical impact. Tirilazad clearance was approximately 40% higher in young women than in young men. The clinical importance of this observation is unknown.

The actions of a new beta-adrenoceptor blocking drug, ICI 66082, on the rabbit papillary muscle and on the dog heart.

1 The actions of 4-(2-hydroxy-3-isopropylaminopropoxy) phenyl acetamide (ICI 66082), a new beta-adrenoceptor blocking drug, on the twitch response of the isolated papillary muscle of the rabbit and on dP/dt max and free heart rate of a denervated dog heart preparation, are described.2 ICI 66082 (up to 1 mg/ml) did not produce any depression of the twitch response of the rabbit papillary muscle. ICI 66082 antagonized the action of isoprenaline on this preparation at a concentration of 0.01 mug/ml.3 ICI 66082 (0.5-1.0 mg/kg intravenously) reduced the control value of dP/dt max in four dog preparations by a mean value of 529 mmHg/s (s.e. mean +/- 139 mm Hg/s), with no significant change in free heart rate. Antagonism of the effect of isoprenaline on dP/dt max and on free heart rate was demonstrated with ICI 66082 (0.1 mg/kg).4 ICI 66082 (1.0-1.5 mg/kg) produced no significant changes in dP/dt max or in free heart rate in four dogs pretreated with reserpine. A significant reduction (16% of the control value) in dP/dt max was observed with ICI 66082 at a high dose of 40-50 mg/kg.5 It is concluded that ICI 66082 is a competitive antagonist against the actions of isoprenaline on cardiac muscle, has no negative inotropic action (unless the dose exceeds 40 mg/kg) and lacks intrinsic sympathomimetic activity.

The effects of three beta-adrenoceptor blocking drugs on isolated preparations of skeletal and cardiac muscle.

1 The effects of propranolol, oxprenolol and practolol on the isometric twitch responses to electrical stimulation of isolated diaphragm muscles from the rat and of isolated papillary muscles from the rabbit are described.2 Depression of the twitch responses of the diaphragm muscle was produced by propranolol (20 mug/ml), by oxprenolol (100 mug/ml) and by practolol (500 mug/ml).3 Depression of the twitch responses of the papillary muscles was produced by propranolol (20 mug/ml) by oxprenolol (100 mug/ml) and by practolol (200 mug/ml).4 No increase of twitch tension was produced by oxprenolol or practolol on either tissue.5 It is concluded that propranolol, oxprenolol and practolol produce negative inotropic actions on isolated cardiac muscle by a mechanism unrelated to blockade of beta-adrenoceptors and which occurs at doses which are well in excess of those doses required to produce beta-blockade.

Clinical pharmacology of epanolol. Pharmacodynamic aspects.

Epanolol has been shown in animal models to be a selective beta-adrenoceptor partial agonist with agonist activity about 20 to 25% of that of the full agonist isoprenaline. Evidence is presented in this review supporting the conclusion that epanolol has the same pharmacological properties in man and that the agonist activity at the beta-adrenoceptor is less than the activity present in pindolol, but greater than that present in acebutolol. The pharmacodynamic consequences in man of the degree of agonist activity possessed by the beta 1-selective partial agonist epanolol include little reductions at rest in heart rate, blood pressure, various measures of cardiac haemodynamic parameters, peripheral blood flow and renal function. On exercise there is attenuation of the heart rate and systolic blood pressure responses, with less perceived exertion than with atenolol. Evidence is available which shows that attenuation of the tachycardia of exercise persists for 24 hours after a single dose of epanolol 200mg, a dose which retains selectivity for the beta 1-adrenoceptor. This pharmacological profile of epanolol in man suggests that it would be an effective antianginal agent when 200mg once daily is administered. Moreover, its unique profile (compared with other antianginal agents) may make it more tolerable to patients than existing antianginal therapy.

Brain volume estimation from serial section measurements: a comparison of methodologies.

Estimation of brain volume from serial sections typically involves using a rectangular. Cavalieri's, parabolic (Simpson's), or a trapezoidal rule to integrate numerically a curve of cross-sectional area measurements plotted against section number. We practically compare the efficacy of each of these methods using mathematical simulations of regularly- and irregularly-shaped "brain volumes" as well as actual morphometric measures from brain regions. There are no meaningful differences between the various estimates when many sections are used--with fewer sections. Cavalieri's estimator is most accurate. This confirms previous theoretical reports demonstrating the efficiency and accuracy of the Cavalieri estimator of volume, particularly when few sections are analyzed. While the Cavalieri approach provides a better approximation of volume under some circumstances, it requires equally spaced sections. We therefore describe methods for the estimation of brain volume from unequally spaced sections, including an estimator based on the fitting of piece-wise parabolic curves to the data. We outline a series of guidelines for the use of these mathematical rules in the estimation of brain volume from serial sections.

Superiority of ibutilide (a new class III agent) over DL-sotalol in converting atrial flutter and atrial fibrillation. The Ibutilide/Sotalol Comparator Study Group.

OBJECTIVE: To compare the efficacy and safety of a single dose of ibutilide, a new class III antiarrhythmic drug, with that of DL-sotalol in terminating chronic atrial fibrillation or flutter in haemodynamically stable patients. DESIGN: Double blind, randomised study. SETTING: 43 European hospitals. PATIENTS: 308 patients (mean age 60 years, 70% men, 48% with heart disease) with sustained atrial fibrillation (n = 251) or atrial flutter (n = 57) (duration three hours to 45 days) were randomised to three groups to receive a 10 minute infusion of 1 mg ibutilide (n = 99), 2 mg ibutilide (n = 106), or 1.5 mg/kg DL-sotalol (n = 103). Infusion was discontinued at termination of the arrhythmia. MAIN OUTCOME MEASURE: Successful conversion of atrial fibrillation or flutter, defined as termination of arrhythmia within one hour of treatment. RESULTS: Both drugs were more effective against atrial flutter than against atrial fibrillation. Ibutilide was superior to DL-sotalol for treating atrial flutter (70% and 56% v 19%), while the high dose of ibutilide was more effective for treating atrial fibrillation than DL-sotalol (44% v 11%) and the lower dose of ibutilide (44% v 20%, p < 0.01). The mean (SD) time to arrhythmia termination was 13 (7) minutes with 2 mg ibutilide, 19 (15) minutes with 1 mg ibutilide, and 25 (17) minutes with DL-sotalol. In all patients, the duration of arrhythmia before treatment was a predictor of arrhythmia termination, although this was less obvious in the group that received 2 mg ibutilide. This dose converted almost 48% of atrial fibrillation that was present for more than 30 days. Concomitant use of digitalis or nifedipine and prolongation of the QTc interval were not predictive of arrhythmia termination. Bradycardia (6.5%) and hypotension (3.7%) were more common side effects with DL-sotalol. Of 211 patients given ibutilide, two (0.9%) who received the higher dose developed polymorphic ventricular tachycardia, one of whom required direct current cardioversion. CONCLUSION: Ibutilide (given in 1 or 2 mg doses over 10 minutes) is highly effective for rapidly terminating persistent atrial fibrillation or atrial flutter. This new class III drug, under monitored conditions, is a potential alternative to currently available cardioversion options.