Management of multiple drug-resistant tuberculosis

AbstractThere has been a worldwide increase in multiple drug-resistant tuberculosis (MDR-TB) which has in the past been associated with a poor prognosis. In the U.K., about half of the cases live in the London area and we have set out to obtain further information on their treatment and outcome. We examined the risk factors, drug resistance, drug treatment, sputum conversion, and outcome in patients with MDR-TB at three hospitals in South London and diagnosed during the period June 1995–January 1999. Human Immunodeficiency Virus (HIV)-positive patients were excluded. There were 760 patients resident in Lambeth, Southwark and Lewisham Health Authority (LSLHA) who were notified as tuberculosis (TB) during the time period and who were of negative or unknown HIV status. (The population of LSLHA is approx. 750 000.) There was a total of 13 patients with MDR-TB, known or presumed to be HIV negative. Their median age was 28 years (range 15–53); nine (69%) were born outside the U.K. and 11 had pulmonary disease; they had organisms resistant to a median of two first-line drugs (range 2–4) and to a median of four of all drugs tested (range 2–10). They received treatment with a median of six drugs (range 3–9). Eight were followed up for at least 3 years (range 3–6) after the completion of treatment; at their last assessment none had features of active TB and all were sputum negative (smear and culture). Two returned to their countries of origin during treatment; they were sputum negative at that time. Two patients are well and continue on treatment in the U.K. One patient (known HIV negative) died following treatment failure. In conclusion, we obtained disease-free survival in eight cases of MDR-TB, known or presumed to be HIV negative and followed up for 3 years or more. The prognosis for patients treated at specialised centres is good (and better than is generally believed). We describe a new protocol for the detection and management of MDR-TB

All-optical versus electro-optical quantum-limited feedback

All-optical feedback can be effected by putting the output of a source cavity through a Faraday isolator and into a second cavity which is coupled to the source cavity by a nonlinear crystal. If the driven cavity is heavily damped, then it can be adiabatically eliminated and a master equation or quantum Langevin equation derived for the first cavity alone. This is done for an input bath in an arbitrary state, and for an arbitrary nonlinear coupling. If the intercavity coupling involves only the intensity (or one quadrature) of the driven cavity, then the effect on the source cavity is identical to that which can be obtained from electro-optical feedback using direct (or homodyne) detection. If the coupling involves both quadratures, this equivalence no longer holds, and a coupling linear in the source amplitude can produce a nonclassical state in the source cavity. The analogous electro-optic scheme using heterodyne detection introduces extra noise which prevents the production of nonclassical light. Unlike the electro-optic case, the all-optical feedback loop has an output beam (reflected from the second cavity). We show that this may be squeezed, even if the source cavity remains in a classical state.Comment: 21 pages. This is an old (1994) paper, but one which I thought was worth posting because in addition to what is described in abstract it has: (1) the first formulation (to my knowledge) of quantum trajectories for an arbitrary (i.e. squeezed, thermal etc.) broadband bath; (2) the prediction of a periodic modification to the detuning and damping of an oscillator for the simplest sort of all-optical feedback (i.e. a mirror) as seen in the recent experiment "Forces between a Single Atom and Its Distant Mirror Image", P. Bushev et al, Phys. Rev. Lett. 92, 223602 (2004

Creating number states in the micromaser using feedback

We use the quantum theory of feedback developed by Wiseman and Milburn [Phys. Rev. Lett. 70, 548 (1993)] and Wiseman [Phys. Rev. A 49, 2133 (1994)] to investigate the photon-number noise properties of the micromaser with direct detection feedback. We find that the feedback can significantly reduce the amount of noise in the photon number. Under the right conditions the feedback locks the systems onto a number state. As opposed to other schemes in the past [P. Meystre, Opt. Lett. 12, 669 (1987); J. Krause, M. O. Scully, and H. Walther, Phys. Rev. A 36, 4547 (1987)], we can fix the number states to which the system evolves. We also simulate the micromaser using the quantum-trajectories method and show that these results agree with the quantum theory of feedback. We show that the noise of quantum island states [P. Bogar, J. A. Bergou, and M. Hillary, Phys. Rev. A 50, 754 (1994)] can be significantly reduced by the feedback

Continuous Quantum Measurement and the Quantum to Classical Transition

While ultimately they are described by quantum mechanics, macroscopic mechanical systems are nevertheless observed to follow the trajectories predicted by classical mechanics. Hence, in the regime defining macroscopic physics, the trajectories of the correct classical motion must emerge from quantum mechanics, a process referred to as the quantum to classical transition. Extending previous work [Bhattacharya, Habib, and Jacobs, Phys. Rev. Lett. {\bf 85}, 4852 (2000)], here we elucidate this transition in some detail, showing that once the measurement processes which affect all macroscopic systems are taken into account, quantum mechanics indeed predicts the emergence of classical motion. We derive inequalities that describe the parameter regime in which classical motion is obtained, and provide numerical examples. We also demonstrate two further important properties of the classical limit. First, that multiple observers all agree on the motion of an object, and second, that classical statistical inference may be used to correctly track the classical motion.Comment: 12 pages, 4 figures, Revtex

Feedback-control of quantum systems using continuous state-estimation

We present a formulation of feedback in quantum systems in which the best estimates of the dynamical variables are obtained continuously from the measurement record, and fed back to control the system. We apply this method to the problem of cooling and confining a single quantum degree of freedom, and compare it to current schemes in which the measurement signal is fed back directly in the manner usually considered in existing treatments of quantum feedback. Direct feedback may be combined with feedback by estimation, and the resulting combination, performed on a linear system, is closely analogous to classical LQG control theory with residual feedback.Comment: 12 pages, multicol revtex, revised and extende

Sensitivity to measurement perturbation of single atom dynamics in cavity QED

We consider continuous observation of the nonlinear dynamics of single atom trapped in an optical cavity by a standing wave with intensity modulation. The motion of the atom changes the phase of the field which is then monitored by homodyne detection of the output field. We show that the conditional Hilbert space dynamics of this system, subject to measurement induced perturbations, depends strongly on whether the corresponding classical dynamics is regular or chaotic. If the classical dynamics is chaotic the distribution of conditional Hilbert space vectors corresponding to different observation records tends to be orthogonal. This is a characteristic feature of hypersensitivity to perturbation for quantum chaotic systems.Comment: 11 pages, 6 figure

High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial.

BACKGROUND: Vitamin D was used to treat tuberculosis in the pre-antibiotic era, and its metabolites induce antimycobacterial immunity in vitro. Clinical trials investigating the effect of adjunctive vitamin D on sputum culture conversion are absent. METHODS: We undertook a multicentre randomised controlled trial of adjunctive vitamin D in adults with sputum smear-positive pulmonary tuberculosis in London, UK. 146 patients were allocated to receive 2·5 mg vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment. The primary endpoint was time from initiation of antimicrobial treatment to sputum culture conversion. Patients were genotyped for TaqI and FokI polymorphisms of the vitamin D receptor, and interaction analyses were done to assess the influence of the vitamin D receptor genotype on response to vitamin D(3). This trial is registered with ClinicalTrials.gov number NCT00419068. FINDINGS: 126 patients were included in the primary efficacy analysis (62 assigned to intervention, 64 assigned to placebo). Median time to sputum culture conversion was 36·0 days in the intervention group and 43·5 days in the placebo group (adjusted hazard ratio 1·39, 95% CI 0·90-2·16; p=0.14). TaqI genotype modified the effect of vitamin D supplementation on time to sputum culture conversion (p(interaction)=0·03), with enhanced response seen only in patients with the tt genotype (8·09, 95% CI 1·36-48·01; p=0·02). FokI genotype did not modify the effect of vitamin D supplementation (p(interaction)=0·85). Mean serum 25-hydroxyvitamin D concentration at 56 days was 101·4 nmol/L in the intervention group and 22·8 nmol/L in the placebo group (95% CI for difference 68·6-88·2; p<0·0001). INTERPRETATION: Administration of four doses of 2·5 mg vitamin D(3) increased serum 25-hydroxyvitamin D concentrations in patients receiving intensive-phase treatment for pulmonary tuberculosis. Vitamin D did not significantly affect time to sputum culture conversion in the whole study population, but it did significantly hasten sputum culture conversion in participants with the tt genotype of the TaqI vitamin D receptor polymorphism. FUNDING: British Lung Foundation

Multipartite Entanglement and Quantum State Exchange

We investigate multipartite entanglement in relation to the theoretical process of quantum state exchange. In particular, we consider such entanglement for a certain pure state involving two groups of N trapped atoms. The state, which can be produced via quantum state exchange, is analogous to the steady-state intracavity state of the subthreshold optical nondegenerate parametric amplifier. We show that, first, it possesses some 2N-way entanglement. Second, we place a lower bound on the amount of such entanglement in the state using a novel measure called the entanglement of minimum bipartite entropy.Comment: 12 pages, 4 figure

Effect of dissipation and measurement on a tunneling system

We consider a parametrically driven Kerr medium in which the pumping may be sinusoidally varied. It has been previously found that this system exhibits coherent tunneling between two fixed points which can be either enhanced or suppressed by altering the driving frequency and strength. We numerically investigate the dynamics when damping is included. This is done both by solving a master equation and using the quantum-trajectory method. In the latter case it is also possible to model the result of a continuous heterodyne measurement of the cavity output. The dissipation destroys the coherences which give rise to the tunneling, causing the sinusoidal oscillation of the mean to give way to a stochastic jumping between the fixed points, manifested as a random telegraph signal. In the quantum-trajectory picture we show that the coherences responsible for tunneling are an exponentially decreasing function of the signal-to-noise ratio for heterodyne measurements. However, evidence of both the bare tunneling rate and the driving modified tunneling rate are still apparent in the random telegraph signal

Classical dynamics of a two-species Bose-Einstein condensate in the presence of nonlinear maser processes

The stability analysis of a generalized Dicke model, in the semi-classical limit, describing the interaction of a two-species Bose-Einstein condensate driven by a quantized field in the presence of Kerr and spontaneous parametric processes is presented. The transitions from Rabi to Josephson dynamics are identified depending on the relative value of the involved parameters. Symmetry-breaking dynamics are shown for both types of coherent oscillations due to the quantized field and nonlinear optical processes.Comment: 12 pages, 5 figures. Accepted for publication as chapter in "Spontaneous Symmetry Breaking, Self-Trapping, and Josephson Oscillations in Nonlinear Systems