Quantum nature of Gaussian discord : experimental evidence and role of system-environment correlations

L.M. acknowledges Project No. P205/12/0694 of Czech Science Foundation (GACR). N.K. is grateful for the support provided by the A. von Humboldt Foundation. N.Q. and N.K. acknowledge the support from the Scottish Universities Physics Alliance (SUPA) and the Engineering and Physical Sciences Research Council (EPSRC). The project was supported within the framework of the BMBF grant “QuORep” and in the framework of the International Max Planck Partnership (IMPP) with Scottish Universities.We provide experimental evidence of quantum features in bipartite states classified as entirely classical according to a conventional criterion based on the Glauber P function but possessing nonzero Gaussian quantum discord. Their quantum nature is experimentally revealed by acting locally on one part of the discordant state. We experimentally verify and investigate the effect of discord increase under the action of local loss and link it to the entanglement with the environment. Adding an environmental system purifying the state, we unveil the flow of quantum correlations within a global pure system using the Koashi-Winter inequality. For a discordant state generated by splitting a state in which the initial squeezing is destroyed by random displacements, we demonstrate the recovery of entanglement highlighting the role of system-environment correlations.Publisher PDFPeer reviewe

Crystallographic studies of the Escherichia coli quinol-fumarate reductase with inhibitors bound to the quinol-binding site

The quinol-fumarate reductase (QFR) respiratory complex of Escherichia coli is a four-subunit integral-membrane complex that catalyzes the final step of anaerobic respiration when fumarate is the terminal electron acceptor. The membrane-soluble redox-active molecule menaquinol (MQH(2)) transfers electrons to QFR by binding directly to the membrane-spanning region. The crystal structure of QFR contains two quinone species, presumably MQH(2), bound to the transmembrane-spanning region. The binding sites for the two quinone molecules are termed Q(P) and Q(D), indicating their positions proximal Q(P)) or distal (Q(D)) to the site of fumarate reduction in the hydrophilic flavoprotein and iron-sulfur protein subunits. It has not been established whether both of these sites are mechanistically significant. Co-crystallization studies of the E. coli QFR with the known quinol-binding site inhibitors 2-heptyl-4-hydroxyquinoline-N-oxide and 2-[1-(p-chlorophenyl)ethyl] 4,6-dinitrophenol establish that both inhibitors block the binding of MQH(2) at the Q(P) site. In the structures with the inhibitor bound at Q(P), no density is observed at Q(D), which suggests that the occupancy of this site can vary and argues against a structurally obligatory role for quinol binding to Q(D). A comparison of the Q(P) site of the E. coli enzyme with quinone-binding sites in other respiratory enzymes shows that an acidic residue is structurally conserved. This acidic residue, Glu-C29, in the E. coli enzyme may act as a proton shuttle from the quinol during enzyme turnover

Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation

OBJECTIVES: To investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with standard clinic care. DESIGN: Systematic review of current evidence and economic modelling. DATA SOURCES: Major electronic databases were searched up to May 2013. The economic model parameters were derived from the clinical effectiveness review, routine sources of cost data and advice from clinical experts. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) comparing self-monitoring versus standard clinical care in people with different clinical conditions. Self-monitoring included both self-management (patients conducted the tests and adjusted their treatment according to an algorithm) and self-testing (patients conducted the tests, but received treatment recommendations from a clinician). Various point-of-care coagulometers were considered. RESULTS: 26 RCTs (8763 participants) were included. Both self-management and self-testing were as safe as standard care in terms of major bleeding events (RR 1.08, 95% CI 0.81 to 1.45, p=0.690, and RR 0.99, 95% CI 0.80 to 1.23, p=0.92, respectively). Self-management was associated with fewer thromboembolic events (RR 0.51, 95% CI 0.37 to 0.69, p </= 0.001) and with a borderline significant reduction in all-cause mortality (RR 0.68, 95% CI 0.46 to 1.01, p=0.06) than standard care. Self-testing resulted in a modest increase in time in therapeutic range compared with standard care (weighted mean difference, WMD 4.4%, 95% CI 1.71 to 7.18, p=0.02). Total health and social care costs over 10 years were pound7324 with standard care and pound7326 with self-monitoring (estimated quality adjusted life year, QALY gain was 0.028). Self-monitoring was found to have approximately 80% probability of being cost-effective compared with standard care applying a ceiling willingness-to-pay threshold of pound20,000 per QALY gained. Within the base case model, applying the pooled relative effect of thromboembolic events, self-management alone was highly cost-effective while self-testing was not. CONCLUSIONS: Self-monitoring appears to be a safe and cost-effective option. TRIAL REGISTRATION NUMBER: PROSPERO CRD42013004944

Measurement of Exercise Tolerance before Surgery (METS) study: a protocol for an international multicentre prospective cohort study of cardiopulmonary exercise testing prior to major non-cardiac surgery

Introduction: Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors’ subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia.Methods and analysis: The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1?year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30?days after surgery, and the secondary outcome is all-cause death within 1?year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration.Ethics and dissemination: The METS Study has received research ethics board approval at all sites. Participant recruitment began in March 2013, and 1-year follow-up is expected to finish in 2016. Publication of the results of the METS Study is anticipated to occur in 2017.<br/

"The non-ischemic repair" as a safe alternative method for repair of anterior post-infarction VSD

Patient's myocardium with post-infarction ventricular septum defect (VSD) is characterized by severe dysfunction. The "additive ischemia" caused by the operating process of cross-clamp ischemia and reperfusion injury, has a significant aggravation to the myocardium and overall negative impact to patient's outcome. We present a useful, safe and advantageous methodology in order to abolish "the toxic phase" of ischemia-reperfusion which is adopted by most as the "classic repair method" of myocardial protection. This abolition is in our opinion, particularly beneficial in order to reverse postoperatively the Low Cardiac Output Syndrome (LOS) and achieve better short and long term results. By using this method we avoid the aortic occlusion, the use of systematic hypothermia and any cardioplegic arrest. Furthermore, the total cardio-pulmonary bypass (CPB) time is significantly reduced, tissue debridement and stitching is much easier and safer. We think the method is applicable for every anterior and apical case of post-infarction septum rupture. After application of method in 3 patients with anterior post-myocardial infarction VSD, we are convinced that the patient will have a better postoperative haemodynamic condition and therefore a better outcome

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients

Background: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. Methods/design: 2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. Discussion: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. Trial registration: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826Not peer reviewedPublisher PD

A cluster randomised trial of educational messages to improve the primary care of diabetes

<p>Abstract</p> <p>Background</p> <p>Regular laboratory test monitoring of patient parameters offers a route for improving the quality of chronic disease care. We evaluated the effects of brief educational messages attached to laboratory test reports on diabetes care.</p> <p>Methods</p> <p>A programme of cluster randomised controlled trials was set in primary care practices in one primary care trust in England. Participants were the primary care practices' constituent healthcare professionals and patients with diabetes. Interventions comprised brief educational messages added to paper and electronic primary care practice laboratory test reports and introduced over two phases. Phase one messages, attached to Haemoglobin A1c (HbA1c) reports, targeted glycaemic and cholesterol control. Phase two messages, attached to albumin:creatinine ratio (ACR) reports, targeted blood pressure (BP) control, and foot inspection. Main outcome measures comprised practice mean HbA1c and cholesterol levels, diastolic and systolic BP, and proportions of patients having undergone foot inspections.</p> <p>Results</p> <p>Initially, 35 out of 37 eligible practices participated. Outcome data were available for a total of 8,690 patients with diabetes from 32 practices. The BP message produced a statistically significant reduction in diastolic BP (-0.62 mmHg; 95% confidence interval -0.82 to -0.42 mmHg) but not systolic BP (-0.06 mmHg, -0.42 to 0.30 mmHg) and increased the odds of achieving target BP control (odds ratio 1.05; 1.00, 1.10). The foot inspection message increased the likelihood of a recorded foot inspection (incidence rate ratio 1.26; 1.18 to 1.36). The glycaemic control message had no effect on mean HbA1c (increase 0.01%; -0.03 to 0.04) despite increasing the odds of a change in likelihood of HbA1c tests being ordered (OR 1.06; 1.01, 1.11). The cholesterol message had no effect (decrease 0.01 mmol/l, -0.04 to 0.05).</p> <p>Conclusions</p> <p>Three out of four interventions improved intermediate outcomes or process of diabetes care. The diastolic BP reduction approximates to relative reductions in mortality of 3% to 5% in stroke and 3% to 4% in ischaemic heart disease over 10 years. The lack of effect for other outcomes may, in part, be explained by difficulties in bringing about further improvements beyond certain thresholds of clinical performance.</p> <p>Trial Registration</p> <p>Current Controlled Trials, <a href="http://www.controlled-trials.com/ISRCTN2186314">ISRCTN2186314</a>.</p

Using death to one's advantage: HIV modulation of apoptosis

Infection by human immunodeficiency virus (HIV) is associated with an early immune dysfunction and progressive destruction of CD4+ T lymphocytes. This progressive disappearance of T cells leads to a lack of immune control of HIV replication and to the development of immune deficiency resulting in the increased occurrence of opportunistic infections associated with acquired immune deficiency syndrome (AIDS). The HIV-induced, premature destruction of lymphocytes is associated with the continuous production of HIV viral proteins that modulate apoptotic pathways. The viral proteins, such as Tat, Env, and Nef, are associated with chronic immune activation and the continuous induction of apoptotic factors. Viral protein expression predisposes lymphocytes, particularly CD4+ T cells, CD8+ T cells, and antigen-presenting cells, to evolve into effectors of apoptosis and as a result, to lead to the destruction of healthy, non-infected T cells. Tat and Nef, along with Vpu, can also protect HIV-infected cells from apoptosis by increasing anti-apoptotic proteins and down- regulating cell surface receptors recognized by immune system cells. This review will discuss the validity of the apoptosis hypothesis in HIV disease and the potential mechanism(s) that HIV proteins perform in the progressive T cell depletion observed in AIDS pathogenesis. Originally published Leukemia, Vol. 15, No. 3, Mar 200

Acidithiobacillus ferrooxidans metabolism: from genome sequence to industrial applications

<p>Abstract</p> <p>Background</p> <p><it>Acidithiobacillus ferrooxidans </it>is a major participant in consortia of microorganisms used for the industrial recovery of copper (bioleaching or biomining). It is a chemolithoautrophic, γ-proteobacterium using energy from the oxidation of iron- and sulfur-containing minerals for growth. It thrives at extremely low pH (pH 1–2) and fixes both carbon and nitrogen from the atmosphere. It solubilizes copper and other metals from rocks and plays an important role in nutrient and metal biogeochemical cycling in acid environments. The lack of a well-developed system for genetic manipulation has prevented thorough exploration of its physiology. Also, confusion has been caused by prior metabolic models constructed based upon the examination of multiple, and sometimes distantly related, strains of the microorganism.</p> <p>Results</p> <p>The genome of the type strain <it>A. ferrooxidans </it>ATCC 23270 was sequenced and annotated to identify general features and provide a framework for <it>in silico </it>metabolic reconstruction. Earlier models of iron and sulfur oxidation, biofilm formation, quorum sensing, inorganic ion uptake, and amino acid metabolism are confirmed and extended. Initial models are presented for central carbon metabolism, anaerobic metabolism (including sulfur reduction, hydrogen metabolism and nitrogen fixation), stress responses, DNA repair, and metal and toxic compound fluxes.</p> <p>Conclusion</p> <p>Bioinformatics analysis provides a valuable platform for gene discovery and functional prediction that helps explain the activity of <it>A. ferrooxidans </it>in industrial bioleaching and its role as a primary producer in acidic environments. An analysis of the genome of the type strain provides a coherent view of its gene content and metabolic potential.</p

Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study.

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability