Hybrid quantum logic and a test of Bell's inequality using two different atomic isotopes.

Entanglement is one of the most fundamental properties of quantum mechanics, and is the key resource for quantum information processing (QIP). Bipartite entangled states of identical particles have been generated and studied in several experiments, and post-selected or heralded entangled states involving pairs of photons, single photons and single atoms, or different nuclei in the solid state, have also been produced. Here we use a deterministic quantum logic gate to generate a 'hybrid' entangled state of two trapped-ion qubits held in different isotopes of calcium, perform full tomography of the state produced, and make a test of Bell's inequality with non-identical atoms. We use a laser-driven two-qubit gate, whose mechanism is insensitive to the qubits' energy splittings, to produce a maximally entangled state of one (40)Ca(+) qubit and one (43)Ca(+) qubit, held 3.5 micrometres apart in the same ion trap, with 99.8 ± 0.6 per cent fidelity. We test the CHSH (Clauser-Horne-Shimony-Holt) version of Bell's inequality for this novel entangled state and find that it is violated by 15 standard deviations; in this test, we close the detection loophole but not the locality loophole. Mixed-species quantum logic is a powerful technique for the construction of a quantum computer based on trapped ions, as it allows protection of memory qubits while other qubits undergo logic operations or are used as photonic interfaces to other processing units. The entangling gate mechanism used here can also be applied to qubits stored in different atomic elements; this would allow both memory and logic gate errors caused by photon scattering to be reduced below the levels required for fault-tolerant quantum error correction, which is an essential prerequisite for general-purpose quantum computing.

Impact of mismatches in HbA1c vs glucose values on the diagnostic classification of diabetes and prediabetes.

AIMS: To determine whether HbA1c mismatches (HbA1c levels that are higher or lower than expected for the average glucose levels in different individuals) could lead to errors if diagnostic classification is based only on HbA1c levels. METHODS: In a cross-sectional study, 3106 participants without known diabetes underwent a 75-g oral glucose tolerance test (fasting glucose and 2-h glucose) and a 50-g glucose challenge test (1-h glucose) on separate days. They were classified by oral glucose tolerance test results as having: normal glucose metabolism; prediabetes; or diabetes. Predicted HbA1c was determined from the linear regression modelling the relationship between observed HbA1c and average glucose (mean of fasting glucose and 2-h glucose from the oral glucose tolerance test, and 1-h glucose from the glucose challenge test) within oral glucose tolerance test groups. The haemoglobin glycation index was calculated as [observed - predicted HbA1c ], and divided into low, intermediate and high haemoglobin glycation index mismatch tertiles. RESULTS: Those participants with higher mismatches were more likely to be black, to be men, to be older, and to have higher BMI (all P<0.001). Using oral glucose tolerance test criteria, the distribution of normal glucose metabolism, prediabetes and diabetes was similar across mismatch tertiles; however, using HbA1c criteria, the participants with low mismatches were classified as 97% normal glucose metabolism, 3% prediabetes and 0% diabetes, i.e. mostly normal, while those with high mismatches were classified as 13% normal glucose metabolism, 77% prediabetes and 10% diabetes, i.e. mostly abnormal (P<0.001). CONCLUSIONS: Measuring only HbA1c could lead to under-diagnosis in people with low mismatches and over-diagnosis in those with high mismatches. Additional oral glucose tolerance tests and/or fasting glucose testing to complement HbA1c in diagnostic classification should be performed in most individuals.

Resilient Entangling Gates for Trapped Ions.

Constructing a large-scale ion trap quantum processor will require entangling gate operations that are robust in the presence of noise and experimental imperfection. We experimentally demonstrate how a new type of Mølmer-Sørensen gate protects against infidelity caused by heating of the motional mode used during the gate. Furthermore, we show how the same technique simultaneously provides significant protection against slow fluctuations and mis-sets in the secular frequency. Since this parameter sensitivity is worsened in cases where the ions are not ground-state cooled, our method provides a path towards relaxing ion cooling requirements in practical realizations of quantum computing and simulation.

Trapped-Ion Quantum Logic with Global Radiation Fields.

Trapped ions are a promising tool for building a large-scale quantum computer. However, the number of required radiation fields for the realization of quantum gates in any proposed ion-based architecture scales with the number of ions within the quantum computer, posing a major obstacle when imagining a device with millions of ions. Here, we present a fundamentally different approach for trapped-ion quantum computing where this detrimental scaling vanishes. The method is based on individually controlled voltages applied to each logic gate location to facilitate the actual gate operation analogous to a traditional transistor architecture within a classical computer processor. To demonstrate the key principle of this approach we implement a versatile quantum gate method based on long-wavelength radiation and use this method to generate a maximally entangled state of two quantum engineered clock qubits with fidelity 0.985(12). This quantum gate also constitutes a simple-to-implement tool for quantum metrology, sensing, and simulation.

Tackling the burden of the hepatitis C virus in the UK: characterizing and assessing the clinical and economic consequences.

OBJECTIVES: The hepatitis C virus (HCV) remains a significant public health issue. This study aimed to quantify the clinical and economic burden of chronic hepatitis C in the UK, stratified by disease severity, age and awareness of infection, with concurrent assessment of the impact of implementing a treatment prioritization approach. STUDY DESIGN AND METHODS: A previously published back projection, natural history and cost-effectiveness HCV model was adapted to a UK setting to estimate the disease burden of chronic hepatitis C and end-stage liver disease (ESLD) between 1980 and 2035. A published meta-regression analysis informed disease progression, and UK-specific data informed other model inputs. RESULTS: At 2015, prevalence of chronic hepatitis C is estimated to be 241,487 with 22.20%, 33.72%, 17.22%, 16.67% and 10.19% of patients in METAVIR stages F0, F1, F2, F3 and F4, respectively, but is estimated to fall to 193,999 by 2035. ESLD incidence is predicted to peak in 2031. Assuming all patients are diagnosed and treatment is prioritized in F3 and F4 using highly efficacious direct-acting antiviral (DAA) regimens, a 69.85% reduction in ESLD incidence is predicted between 2015 and 2035, and the cumulative discounted medical expenditure associated with the lifetime management of incident ESLD events is estimated to be £1,202,827,444. CONCLUSIONS: The prevalence of chronic hepatitis C is expected to fall in coming decades; however, the ongoing financial burden is expected to be high due to an increase in ESLD incidence. This study highlights the significant costs of managing ESLD that are likely to be incurred without the employment of effective treatment approaches.

Ground-State Cooling of a Trapped Ion Using Long-Wavelength Radiation.

We demonstrate ground-state cooling of a trapped ion using radio-frequency (rf) radiation. This is a powerful tool for the implementation of quantum operations, where rf or microwave radiation instead of lasers is used for motional quantum state engineering. We measure a mean phonon number of n[over ¯]=0.13(4) after sideband cooling, corresponding to a ground-state occupation probability of 88(7)%. After preparing in the vibrational ground state, we demonstrate motional state engineering by driving Rabi oscillations between the |n=0⟩ and |n=1⟩ Fock states. We also use the ability to ground-state cool to accurately measure the motional heating rate and report a reduction by almost 2 orders of magnitude compared with our previously measured result, which we attribute to carefully eliminating sources of electrical noise in the system.

Dehydrative thiolation of allenols: indium vs gold catalysis.

Intermolecular additions of thiols to allenols via formal S(N)2' selectivity to produce functionalized dienes are described. Although this dehydrative reaction was initially developed using gold(I) catalysis, indium(III) proves to be a far superior catalyst in terms of selectivity and substrate scope.

Bacterial expression of human kynurenine 3-monooxygenase: solubility, activity, purification.

Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington's disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification.

Transportable cavity-stabilized laser system for optical carrier frequency transmission experiments.

We report the design and performance of a transportable laser system at 1543 nm, together with its application as the source for a demonstration of optical carrier frequency transmission over 118 km of an installed dark fiber network. The laser system is based around an optical reference cavity featuring an elastic mounting that bonds the cavity to its support, enabling the cavity to be transported without additional clamping. The cavity exhibits passive fractional frequency insensitivity to vibration along the optical axis of 2.0×10(-11) m(-1) s(2). With active fiber noise cancellation, the optical carrier frequency transmission achieves a fractional frequency instability, measured at the user end, of 2.6×10(-16) at 1 s, averaging down to below 3×10(-18) after 20,000 s. The fractional frequency accuracy of the transfer is better than 3×10(-18). This level of performance is sufficient for comparison of state-of-the-art optical frequency standards and is achieved in an urban fiber environment.

In vivo RAF signal transduction as a potential biomarker for sorafenib efficacy in patients with neuroendocrine tumours.

BACKGROUND: Targeted therapies elicit anticancer activity by exerting pharmacodynamic effects on specific molecular targets. Currently, there is limited use of pharmacodynamic assessment to guide drug administration in the routine oncology setting. METHODS: We developed a phosphoshift (pShift) flow cytometry-based test that measures RAF signal transduction capacity in peripheral blood cells, and evaluated it in a phase II clinical trial of oral sorafenib plus low-dose cyclophosphamide in patients with advanced neuroendocrine tumours (NETs), in order to predict clinical course and/or guide individual dose-titration. RESULTS: Twenty-two patients were enrolled. Median progression-free survival (PFS) was 3 months (95% CI 2-10.7), and one patient had a partial response. PFS was longer among five patients who demonstrated an increase in pShift after 7 days of sorafenib compared with those who did not (14.9 months vs 2.8 months; P=0.047). However, pShift did not add value to toxicity-based dose-titration. CONCLUSION: The pharmacodynamic assessment of RAF transduction may identify selected patients with advanced NETs most likely to benefit from the combination of sorafenib plus cyclophosphamide. Further investigation of this test as a potential biomarker is warranted.

Simple manipulation of a microwave dressed-state ion qubit.

Many schemes for implementing quantum information processing require that the atomic states used have a nonzero magnetic moment; however, such magnetically sensitive states of an atom are vulnerable to decoherence due to fluctuating magnetic fields. Dressing an atom with external fields is a powerful method of reducing such decoherence [N. Timoney et al., Nature (London) 476, 185 (2011)]. We introduce an experimentally simpler method of manipulating such a dressed-state qubit, which allows the implementation of general rotations of the qubit, and demonstrate this method using a trapped ytterbium ion.

Haemostatic resuscitation in practice: a descriptive analysis of blood products administered during Operation HERRICK, Afghanistan.

INTRODUCTION: Life-threatening haemorrhage is the leading cause of potentially survivable injury in battlefield casualties. During Operation HERRICK (Afghanistan), mortality rates improved year on year due to a number of advances in trauma care, including haemostatic resuscitation. Blood transfusion practice has not previously been reported in detail during this period. METHODS: A retrospective analysis of blood transfusion at the UK role 3 medical treatment facility (MTF) at Camp Bastion between March 2006 and September 2014 was performed. Data were extracted from two sources: the UK Joint Theatre Trauma Registry (JTTR) and the newly established Deployed Blood Transfusion Database (DBTD). RESULTS: 3840 casualties were transfused 72 138 units of blood and blood products. 2709 adult casualties (71%) were fully linked with JTTR data and were transfused a total of 59 842 units. Casualties received between 1 unit and 264 units of blood product with a median of 13 units per patient. Casualties wounded by explosion required almost twice the volume of blood product transfusion as those wounded by small arms fire or in a motor vehicle collision (18 units, 9 units, and 10 units, respectively). More than half of blood products were transfused within the first 2 hours following arrival at the MTF. There was a trend towards balanced resuscitation with more equal ratios of blood and blood products being used over time. CONCLUSION: This study has defined the epidemiology of blood transfusion practice during Operation HERRICK. The DBTD is the largest combined trauma database of its kind. It will ensure that lessons learnt during this period are defined and not forgotten; it should also allow further research questions to be answered in this important area of resuscitation practice.

Contribution of local regeneration of glucocorticoids to tissue steroid pools.

11ß-Hydroxysteroid dehydrogenase 1 (11ßHSD1) is a drug target to attenuate adverse effects of chronic glucocorticoid excess. It catalyses intracellular regeneration of active glucocorticoids in tissues including brain, liver and adipose tissue (coupled to hexose-6-phosphate dehydrogenase, H6PDH). 11ßHSD1 activity in individual tissues is thought to contribute significantly to glucocorticoid levels at those sites, but its local contribution vs glucocorticoid delivery via the circulation is unknown. Here, we hypothesised that hepatic 11ßHSD1 would contribute significantly to the circulating pool. This was studied in mice with Cre-mediated disruption of Hsd11b1 in liver (Alac-Cre) vs adipose tissue (aP2-Cre) or whole-body disruption of H6pdh. Regeneration of [9,12,12-2H3]-cortisol (d3F) from [9,12,12-2H3]-cortisone (d3E), measuring 11ßHSD1 reductase activity was assessed at steady state following infusion of [9,11,12,12-2H4]-cortisol (d4F) in male mice. Concentrations of steroids in plasma and amounts in liver, adipose tissue and brain were measured using mass spectrometry interfaced with matrix-assisted laser desorption ionisation or liquid chromatography. Amounts of d3F were higher in liver, compared with brain and adipose tissue. Rates of appearance of d3F were ~6-fold slower in H6pdh-/- mice, showing the importance for whole-body 11ßHSD1 reductase activity. Disruption of liver 11ßHSD1 reduced the amounts of d3F in liver (by ~36%), without changes elsewhere. In contrast disruption of 11ßHSD1 in adipose tissue reduced rates of appearance of circulating d3F (by ~67%) and also reduced regenerated of d3F in liver and brain (both by ~30%). Thus, the contribution of hepatic 11ßHSD1 to circulating glucocorticoid levels and amounts in other tissues is less than that of adipose tissue.

A versatile microtomography system to study in situ the failure and fragmentation in geomaterials.

This article describes a microtomography experimental platform enabling in situ micro-mechanical study of failure and fragmentation in geomaterials. The system is based on an original high-pressure triaxial flow cell, which is fully integrated into a custom built microtomography scanner equipped with a laboratory x-ray source. The design of the high-precision mechanical apparatus was informed by the concurrent development of advanced tomographic reconstruction methods based on helical scanning and of algorithms correcting for hardware inaccuracies. This experimental system produces very high-quality 3D images of microstructural changes occurring in rocks undergoing mechanical failure and substantial fragmentation. We present the results of two experiments as case studies to demonstrate the capabilities and versatility of this instrumental platform. These experiments tackle various questions related to the onset of rock failure, the hydromechanical coupling and relaxation mechanisms in fractured rocks, or the fragmentation process in geomaterials such as copper ores.