To catch and reverse a quantum jump mid-flight.

In quantum physics, measurements can fundamentally yield discrete and random results. Emblematic of this feature is Bohr's 1913 proposal of quantum jumps between two discrete energy levels of an atom1. Experimentally, quantum jumps were first observed in an atomic ion driven by a weak deterministic force while under strong continuous energy measurement2-4. The times at which the discontinuous jump transitions occur are reputed to be fundamentally unpredictable. Despite the non-deterministic character of quantum physics, is it possible to know if a quantum jump is about to occur? Here we answer this question affirmatively: we experimentally demonstrate that the jump from the ground state to an excited state of a superconducting artificial three-level atom can be tracked as it follows a predictable 'flight', by monitoring the population of an auxiliary energy level coupled to the ground state. The experimental results demonstrate that the evolution of each completed jump is continuous, coherent and deterministic. We exploit these features, using real-time monitoring and feedback, to catch and reverse quantum jumps mid-flight-thus deterministically preventing their completion. Our findings, which agree with theoretical predictions essentially without adjustable parameters, support the modern quantum trajectory theory5-9 and should provide new ground for the exploration of real-time intervention techniques in the control of quantum systems, such as the early detection of error syndromes in quantum error correction.

Bright Sub-Poissonian Light through Intrinsic Feedback and External Control.

Balancing nonlinear gain and loss automatically generates sub-Poissonian light, through negative feedback, when the gain is significantly reduced (increased) by the addition (subtraction) of a single photon. We show that micromaser trapping states can provide the necessary feedback in the presence of photon loss and, with the addition of external parametric control, realize a photon number on the order of 100 and a Mandel Q parameter of -0.998, i.e., number squeezing of 27 dB.

Radical Chain Reduction of CCl4 Initiated by Illumination of SPEEK Solutions.

Efficient reduction of CCl4 took place upon exposure to 350-nm photons of aqueous solutions containing sulfonated poly(ether etherketone) (SPEEK) as a sensitizer and either poly(vinyl alcohol) (PVA) or HCO2H/HCO2- buffer. The photoreaction formed chloride ions whose concentration increased linearly with time in solutions free of O2, whereas slower reductions occurred in the presence of air. Utilization of formate buffer as the H-atom donor yielded photoreactions at least 10 times faster than those in the presence of PVA and generated CHCl3 as another reaction product. The quantum yield of chloride ion formation, ø(Cl-), was found to be a function of both the SPEEK concentration and concentration of formate buffer. Whereas the quantum efficiency increased steadily with decreasing solution acidity, a drastic surge in the reaction rate occurred in neutral solutions. ø(Cl-) first increased rapidly to a maximum value exceeding 1 at pH 7.3 and then decreased thereafter. The dependence of r(Cl-) on (I0)1/2, where I0 is the light intensity, and the occurrence of postirradiation formation of Cl- through the reduction of CCl4 in the dark are further evidence that the photoreaction proceeded by a chain process. Several of the kinetic features were rationalized by means of a mechanism involving the α-hydroxy radicals of SPEEK and •CCl3 as chain carriers.

PSINET: Assisting HIV Prevention Amongst Homeless Youth by Planning Ahead.

Homeless youth are prone to Human Immunodeficiency Virus (HIV) due to their engagement in high risk behavior such as unprotected sex, sex under influence of drugs, etc. Many non-profit agencies conduct interventions to educate and train a select group of homeless youth about HIV prevention and treatment practices and rely on word-of-mouth spread of information through their social network. Previous work in strategic selection of intervention participants does not handle uncertainties in the social network's structure and evolving network state, potentially causing significant shortcomings in spread of information. Thus, we developed PSINET, a decision support system to aid the agencies in this task. PSINET includes the following key novelties: (i) it handles uncertainties in network structure and evolving network state; (ii) it addresses these uncertainties by using POMDPs in influence maximization; and (iii) it provides algorithmic advances to allow high quality approximate solutions for such POMDPs. Simulations show that PSINET achieves ~60% more information spread over the current state-of-the-art. PSINET was developed in collaboration with My Friend's Place (a drop-in agency serving homeless youth in Los Angeles) and is currently being reviewed by their officials.

Whole exome sequencing in a patient with uniparental disomy of chromosome 2 and a complex phenotype.

Whole exome sequencing and chromosomal microarrays are two powerful technologies that have transformed the ability of researchers to search for potentially causal variants in human disease. This study combines these tools to search for causal variants in a patient found to have maternal uniparental isodisomy of chromosome 2. This subject has a complex phenotype including skeletal and renal dysplasia, immune deficiencies, growth failure, retinal degeneration and ovarian insufficiency. Eighteen non-synonymous, rare homozygous variants were identified on chromosome 2. Additionally, five genes with compound heterozygous mutations were detected on other chromosomes that could lead to a disease phenotype independent of the uniparental disomy found in this case. Several candidate genes with potential connection to the phenotype are described but none are definitively proven to be causal. This study highlights the potential for detection of a large number of candidate genes using whole exome sequencing complicating interpretation in both the research and clinical settings. Forums must be created for publication and sharing of detailed phenotypic and genotypic reports to facilitate further biological discoveries and clinical counseling.

Stationary inversion of a two level system coupled to an off-resonant cavity with strong dissipation.

We present an off-resonant excitation scheme that realizes pronounced stationary inversion in a two level system. The created inversion exploits a cavity-assisted two-photon resonance to enhance the multiphoton regime of nonlinear cavity QED and survives even in a semiconductor environment, where the cavity decay rate is comparable to the cavity-dot coupling rate. Exciton populations of greater than 0.75 are obtained in the presence of realistic decays and pure dephasing. Quantum trajectory simulations and master equation calculations help elucidate the underlying physics and delineate the limitations of a simplified rate equation model. Experimental signatures of inversion and multiphoton cavity QED are predicted in the fluorescence intensity and second-order correlation function measured as a function of drive power.

A new approach to scoring systems to improve identification of acute medical admissions that will require critical care.

Removal of the intensive care unit (ICU) at the Vale of Leven Hospital mandated the identification and transfer out of those acute medical admissions with a high risk of requiring ICU. The aim of the study was to develop triaging tools that identified such patients and compare them with other scoring systems. The methodology included a retrospective analysis of physiological and arterial gas measurements from 1976 acute medical admissions produced PREEMPT-1 (PRE-critical Emergency Medical Patient Triage). A simpler one for ambulance use (PREAMBLE-1 [PRE-Admission Medical Blue-Light Emergency]) was produced by the addition of peripheral oxygen saturation to a modification of MEWS (Modified Early Warning Score). Prospective application of these tools produced a larger database of 4447 acute admissions from which logistic regression models produced PREEMPT-2 and PREAMBLE-2, which were then compared with the original systems and seven other early warning scoring systems. Results showed that in patients with arterial gases, the area under the receiver operator characteristic curve was significantly higher in PREEMPT-2 (89·1%) and PREAMBLE-2 (84.4%) than all other scoring systems. Similarly, in all patients, it was higher in PREAMBLE-2 (92·4%) than PREAMBLE-1 (88·1%) and the other scoring systems. In conclusion, risk of requiring ICU can be more accurately predicted using PREEMPT-2 and PREAMBLE-2, as described here, than by other early warning scoring systems developed over recent years.

Observation of ground-state quantum beats in atomic spontaneous emission.

We report ground-state quantum beats in spontaneous emission from a continuously driven atomic ensemble. Beats are visible only in an intensity autocorrelation and evidence spontaneously generated coherence in radiative decay. Our measurement realizes a quantum eraser where a first photon detection prepares a superposition and a second erases the "which path" information in the intermediate state.

Hb M Dothan [beta 25/26 (B7/B8)/(GGT/GAG-->GAG//Gly/Glu-->Glu]; a new mechanism of unstable methemoglobin variant and molecular characteristics.

A new unstable beta globin chain variant associated with methemoglobin (Met-Hb) phenotype was found in a Caucasian infant. Molecular analysis of the beta globin gene using polymerase chain reaction (PCR) amplification and sequencing led to the detection of a new in frame deletion in exon-1. Direct sequencing of the PCR product revealed a 3 bp deletion (-GTG) between codons 25/26, which resulted in the loss of a single amino acid (-Gly). We propose that this newly discovered unstable M-hemoglobin (M-Hb) variant, named Hb Dothan [GGT/GAG-->GAG//Gly/Glu-->Glu], is caused by a shift in the amino acid sequence and altered packing of the B and E helices during beta globin synthesis, and also changes the orientation of the critical proximal and distal histidine in the F and E helices respectively. Phenotype/Genotype features and molecular characteristics of this new beta chain are presented in this communication.

Candoxatril, a neutral endopeptidase inhibitor: efficacy and tolerability in essential hypertension.

OBJECTIVE: To examine the efficacy and tolerability of the neutral endopeptidase inhibitor, candoxatril (UK 79,300) as monotherapy in essential hypertension. DESIGN: Double-blind, placebo-controlled, parallel-group study of 28 days' duration. SETTING: Three hospital outpatient departments participating in the Glasgow Blood Pressure Clinic (Glasgow, UK). PATIENTS: Forty patients with essential hypertension with diastolic blood pressure 95-114 mmHg after a 2-4 week placebo run-in period. INTERVENTIONS: Twenty-eight days' treatment with candoxatril 200 mg twice daily or matching placebo capsules. MAIN OUTCOME MEASURES: Changes in supine and erect blood pressure, and volunteered side effects during double-blind treatment. RESULTS: When measured at the end of the dose interval, the fall in supine blood pressure following candoxatril was not significantly greater than that after placebo. Compared with placebo, a significant effect for candoxatril was seen only for systolic blood pressure in the erect posture; the fall in erect diastolic blood pressure attributable to candoxatril was insignificant. Median plasma atrial natriuretic peptide concentration increased in candoxatril-treated patients and decreased in the placebo group. No stimulation of the renin-aldosterone axis was seen. There was a non-significant trend towards greater urinary excretion of cyclic guanosine monophosphate after candoxatril. Mean plasma concentration of candoxatril at (UK 73,967--the active metabolite of candoxatril) reached a peak of 1010 +/- 437 ng/ml after acute dosing, and 1328 +/- 405 ng/ml after chronic dosing; time to maximum concentration was 2 h in each case. Candoxatril was well-tolerated; numbers of adverse events did not differ between active treatment and placebo. CONCLUSIONS: Although atrial natriuretic peptide levels were significantly increased, candoxatril 200 mg twice daily for 28 days did not produce a clinically relevant fall in blood pressure. Our results cast some doubt upon the role of neutral endopeptidase inhibition in the treatment of unselected hypertensive patients.

Normal mode oscillation in the presence of inhomogeneous broadening.

We investigate effects of inhomogeneous broadening of excitons on normal mode oscillation in semiconductor microcavities using a coupled oscillator model. We show that inhomogeneous broadening can drastically alter the coherent oscillatory energy exchange process even in regimes where normal mode splitting remains nearly unchanged. The depth, frequency, and phase of normal mode oscillations of excitons at a given energy within the inhomogeneous distribution depend strongly on the energy separation between the exciton and the normal mode resonance. In addition, for an inhomogeneous broadened system, pronounced oscillations in the intensity of the optical field or the total induced optical polarization no longer imply a similar oscillatory coherent energy exchange between excitons and cavity photons.

The UCLA population studies of chronic obstructive respiratory disease. 5. Agreement and disagreement of tests in identifying abnormal lung function.

The relative sensitivity and specificity of symptoms, spirometry, the flow-volume (FV) curve, the single-breath nitrogen test (SBNT), and specific airway conductance (SGaw) were estimated by cross comparison of these tests with the FEV1/FVC ratio and other tests in 1,201 residents of Los Angeles. Spirometry and the flow-volume curve were estimated to be the most sensitive, yet reasonably specific composite measures, and FEV1/FVC and V75 to be the most sensitive individual indices. Among current smokers, FEV1/FVC was more frequently abnormal (23 percent) than FEF25-75% (16 percent), showed higher concordance with an abnormal FEF25-75% (88 percent), and identified a greater percentage of individuals as abnormal when the FEF25-75% was normal (9 percent) than vice versa. SGaw and SBNT showed a poor concordance with FEV1/FVC and identified more individuals as abnormal who had a normal FEV1/FVC. Although the proportion of current smokers with productive cough was relatively high (26 percent), none of the function tests showed a reasonable concordance with this symptom. These findings suggest that: 1) spirometry, the flow-volume curve, V75 and FEV1/FVC are relatively sensitive and specific indicators of respiratory impairment; 2) spirometry and the FV curve provide similar but not completely overlapping information; 3) SGaw and SBNT yield different (or less specific) information than the other tests; and 4) effects of cigarette smoking identified by productive cough are different from those identified by other tests.

Effects of atenolol withdrawal in patients on triple antihypertensive therapy.

The objective of this study was to examine the contribution of beta-blockade to antihypertensive treatment regimens including an angiotensin converting enzyme inhibitor or a calcium antagonist. The effects on BP control, adverse events, and plasma active renin concentration of removing atenolol from standard triple therapy (bendrofluazide and atenolol together with captopril or nifedipine) were assessed in a double-blind, randomised, parallel-group study, of eight weeks' duration in 46 patients from the Glasgow Blood Pressure Clinic. Blood pressures rose in patients randomised to placebo-atenolol compared with those who continued active-atenolol although the difference did not achieve statistical significance. However, the proportion of patients with controlled blood pressure (supine systolic BP < 140 mmHg plus supine diastolic BP < 95 mmHg) fell from 31% to 0% over the study period in patients given placebo-atenolol. There was a trend for BP control to deteriorate most when atenolol was withdrawn from nifedipine treated patients, but the 95% confidence intervals for the difference from captopril-treated patients were wide. Few side-effects were seen and these did not differ quantitatively between the study groups. Plasma active renin concentration was initially higher in captopril-treated patients, and increased on withdrawal of atenolol in both groups. Our findings suggest that beta-blockers make a clinically relevant contribution to treatment regimens including angiotensin converting enzyme inhibitors or calcium antagonists when given as part of standard triple antihypertensive therapy.

Comparison of captopril, hydralazine and nifedipine as third drug in hypertensive patients.

The antihypertensive, biochemical and adverse effects of captopril, hydralazine, nifedipine and placebo were compared in 160 patients with BP inadequately controlled by atenolol 100 mg daily plus bendrofluazide 5 mg daily. Treatments were given for up to 12 weeks. Beta-blocker and thiazide were continued unchanged. All three active drugs reduced supine BP relative to placebo; mean BP changes attributable to active treatment (95% confidence intervals): captopril 13.4/10.3 mmHg (0.6/4.0 to 26.2/16.6), hydralazine 15.0/10.0 mmHg (1.7/3.4 to 28.3/16.6), nifedipine 16.8/8.1 mmHg (4.0/1.8 to 29.6/14.4). There were no significant differences between the agents. Results for erect BP were similar. Target BP (< 140/95 mmHg) was achieved more frequently on captopril (33%), hydralazine (29%) and nifedipine (17%) than on placebo (10%). Compared with the other treatments captopril increased serum potassium concentration (P = 0.01), and hydralazine reduced serum cholesterol concentration (median changes: captopril -0.2 mmol/l, hydralazine -0.8 mmol/l, nifedipine -0.2 mmol/l, and placebo +0.2 mmol/l, P < 0.001). Overall, side-effects did not differ significantly between the groups; withdrawals resulting from adverse reactions: captopril 15%, hydralazine 24%, nifedipine 22%, and placebo 3% (chi 2 = 8.2, P = 0.04). Captopril, hydralazine and nifedipine did not differ significantly in efficacy and tolerability when added to atenolol and bendrofluazide. However, there were trends in favour of captopril, on which drug the highest proportion of patients had their BP controlled and the lowest proportion were withdrawn because of side-effects. Thus, of the drugs tested, captopril appears to be the best option as third drug in hypertension.

Quenching of singlet molecular oxygen (1O2) by azide anion in solvent mixtures.

The azide ion is a strong physical quencher of singlet molecular oxygen (1O2) and is frequently employed to show involvement of 1O2 in oxidation processes. Rate constants (k(q)) for the quenching of 1O2 by azide are routinely used as standards to calculate k(q) values for quenching by other substrates. We have measured k(q) for azide in solvent mixtures containing deuterium oxide (D2O), acetonitrile (MeCN), 1,4-dioxane, ethanol (EtOH), propylene carbonate (PC), or ethylene carbonate (EC), mixtures commonly used for many experimental studies. The rate constants were calculated directly from 1O2 phosphorescence lifetimes observed after laser pulse excitation of rose bengal (RB), used to generate 1O2. In aqueous mixtures with MeCN and carbonates, the rate constant increased nonlinearly with increasing volume of organic solvent in the mixtures. k(q) was 4.78 x 10(8) M(-1) s(-1) in D2O and increased to 26.7 x 10(8) and 27.7 x 10(8) M(-1) s(-1) in 96% MeCN and 97.7% EC/PC, respectively. However, in EtOH/D2O mixtures, k(q) decreased with increasing alcohol concentration. This shows that a higher solvent polarity increases the quenching efficiency, which is unexpectedly decreased by the proticity of aqueous and alcohol solvent mixtures. The rate constant values increased with increasing temperature, yielding a quenching activation energy of 11.3 kJ mol(-1) in D2O. Our results show that rate constants in most solvent mixtures cannot be derived reliably from k(q) values measured in pure solvents by using a simple additivity rule. We have measured the rate constants with high accuracy, and they may serve as a reliable reference to calculate unknown k(q) values.

Lower fat intake as a predictor of initial and sustained weight loss in obese subjects consuming an otherwise ad libitum diet.

OBJECTIVE: To determine what predicts initial and sustained weight loss in subjects consuming a reduced-fat diet ad libitum and the relationship between achieved level of fat intake and weight loss. DESIGN: Placebo arm of a randomized, controlled trial of a weight-loss drug (dexfenfluramine) in the context of an ad libitum, reduced-fat diet. SUBJECTS: Thirty-nine subjects (initial mean body mass index +/- standard deviation = 34.9 +/- 3.4; body mass index is calculated as kg/m2) from the placebo group who completed the 9-month study. INTERVENTION: Dietary assessment and education (month 0) followed by monthly meetings during the single intervention of reducing fat intake (months 1 through 6); one follow-up at 9 months. MAIN OUTCOME MEASURES: Initial weight loss (first 3 months) and sustained weight loss (over 9-month period). STATISTICS: Dietary intake, body size, exercise levels, age, and gender were included in multiple regression linear models of initial and sustained weight loss if they were significant independent predictors. RESULTS: Greater initial weight loss was associated with a greater decrease in fat intake and a lower achieved fat intake at 3 months. Greater sustained weight loss was associated with a lower achieved fat intake, a higher baseline waist circumference, and higher moderate-intensity exercise levels (months 3 and 6). Weight loss occurred in all subjects who reported a fat intake of 40 g/day or less. APPLICATIONS: The obese persons most likely to achieve and sustain weight loss on an ad libitum, reduced-fat diet are those who can substantially reduce fat intake, those with high initial levels of abdominal fat, and those who undertake regular moderate-intensity exercise. A target of less than 40 g fat per day might be an appropriate goal to ensure weight loss, but dietary underreporting and the difficulty of sustaining very-low-fat intakes need to be considered.

Antibody to Coxsackie B virus in diagnosing postviral fatigue syndrome.

OBJECTIVE: To study the association between coxsackie B virus infection and the postviral fatigue syndrome and to assess the immunological abnormalities associated with the syndrome. DESIGN: Case-control study of patients with the postviral fatigue syndrome referred by local general practitioners over one year. SETTING: General practitioner referrals in Dunbartonshire, Scotland. PATIENTS: 254 Patients referred with the postviral fatigue syndrome (exhaustion, myalgia, and other symptoms referable to postviral fatigue syndrome of fairly recent onset--that is, several months) and age and sex matched controls obtained from same general practitioner; 11 patients were rejected because of wrong diagnoses, resolution of symptoms, and refusal to participate, leaving 243 patients and matched controls. MAIN OUTCOME MEASURES: Detailed questionnaire (patients and controls) and clinical examination (patients) and blind analysis of blood sample at entry and after six months for determination of coxsackie B virus IgM and IgG antibodies and other variables (including lymphocyte protein synthesis, lymphocyte subsets, and immune complexes). RESULTS: Percentage positive rates for coxsackie B virus IgM at entry were 24.4% for patients and 22.6% for controls and for coxsackie B virus IgG 56.2% and 55.3% respectively; there were no significant differences between different categories of patients according to clinical likelihood of the syndrome nor any predictive value in a fourfold rise or fall in the coxsackie B virus IgG titre in patients between entry and review at six months. The rates of positive antibody test results in patients and controls showed a strong seasonal variation. Of the numerous immunological tests performed, only a few detected significant abnormalities; in particular the mean value for immune complex concentration was much higher in 35 patients and 35 controls compared with the normal range and mean value for total IgM was also raised in 227 patients and 35 controls compared with the normal range. CONCLUSIONS: Serological tests available for detecting coxsackie B virus antibodies do not help diagnose the postviral fatigue syndrome. Percentage positive rates of the antibodies in patients simply reflect the background in the population as probably do the raised concentrations of total IgM and immune complexes.

Aspirin and bile acid induced gastric mucosal damage: protection by prostaglandins and antacids.

The importance of bile acids in causing gastric mucosal haemorrhage and the protective effect of prostaglandins and antacids has been studied in a series of studies using an animal model. Bile acids alone did not damage the gastric mucosa, but conjugated bile acids together with aspirin and hydrochloric acid may cause gastric mucosal haemorrhage. The prostaglandin analogue 15(R)15-methyl-E2 methyl ester protected the gastric mucosa against damage caused by conjugated bile acids together with aspirin or hydrochloric acid. Gastric mucosal protection was also achieved with antacids, but this effect appeared to be mainly on the aspirin rather than on the bile acid component of the damage. Bile acid binding, if it did occur, did not prevent the bile acid from increasing aspirin-induced gastric mucosal damage.

Onset of a quantum phase transition with a trapped ion quantum simulator.

A quantum simulator is a well-controlled quantum system that can follow the evolution of a prescribed model whose behaviour may be difficult to determine. A good example is the simulation of a set of interacting spins, where phase transitions between various spin orders can underlie poorly understood concepts such as spin liquids. Here we simulate the emergence of magnetism by implementing a fully connected non-uniform ferromagnetic quantum Ising model using up to 9 trapped (171)Yb(+) ions. By increasing the Ising coupling strengths compared with the transverse field, the crossover from paramagnetism to ferromagnetic order sharpens as the system is scaled up, prefacing the expected quantum phase transition in the thermodynamic limit. We measure scalable order parameters appropriate for large systems, such as various moments of the magnetization. As the results are theoretically tractable, this work provides a critical benchmark for the simulation of intractable arbitrary fully connected Ising models in larger systems.