Partial-measurement backaction and nonclassical weak values in a superconducting circuit.

We realize indirect partial measurement of a transmon qubit in circuit quantum electrodynamics by interaction with an ancilla qubit and projective ancilla measurement with a dedicated readout resonator. Accurate control of the interaction and ancilla measurement basis allows tailoring the measurement strength and operator. The tradeoff between measurement strength and qubit backaction is characterized through the distortion of a qubit Rabi oscillation imposed by ancilla measurement in different bases. Combining partial and projective qubit measurements, we provide the solid-state demonstration of the correspondence between a nonclassical weak value and the violation of a Leggett-Garg inequality.

Demonstration of controlled-NOT quantum gates on a pair of superconducting quantum bits.

Quantum computation requires quantum logic gates that use the interaction within pairs of quantum bits (qubits) to perform conditional operations. Superconducting qubits may offer an attractive route towards scalable quantum computing. In previous experiments on coupled superconducting qubits, conditional gate behaviour and entanglement were demonstrated. Here we demonstrate selective execution of the complete set of four different controlled-NOT (CNOT) quantum logic gates, by applying microwave pulses of appropriate frequency to a single pair of coupled flux qubits. All two-qubit computational basis states and their superpositions are used as input, while two independent single-shot SQUID detectors measure the output state, including qubit-qubit correlations. We determined the gate's truth table by directly measuring the state transfer amplitudes and by acquiring the relevant quantum phase shift using a Ramsey-like interference experiment. The four conditional gates result from the symmetry of the qubits in the pair: either qubit can assume the role of control or target, and the gate action can be conditioned on either the 0-state or the 1-state. These gates are now sufficiently characterized to be used in quantum algorithms, and together form an efficient set of versatile building blocks.

[Taperingstrips for paroxetine and venlafaxine]. / Taperingstrips voor paroxetine en venlafaxine.

BACKGROUND: Tapering strips can be used for the gradual reduction of the dose of certain types of drugs such as antidepressants and benzodiazepines. The strips contain a slightly lower dose on each consecutive day. This prevents the withdrawal symptoms still experienced by too many patients and lowers the risk of relapse. AIM: To make tapering strips of antidepressant drugs available for patients in need of a tapering-off procedure. METHOD: The Consensusgroup Tapering studied the literature and consulted with experts to find out whether the plan to make tapering strips of paroxetine and venlafaxine available for patients is feasible. RESULTS: The Cinderella Therapeutic Foundation (www.cinderella-tx.org), a not-for-profit organisation which aims to give patients access to orphan drugs and treatments, wants to make tapering strips of paroxetine and venlafaxine available since these are the two antidepressants that cause the most problems. The process of producing, packaging and checking the tapering doses is iso-certified; each strip is provided with a bar-code and can be followed and traced. Therefore the strips will conform to current safety regulations.In view of the large number of patients taking paroxetine and venlafaxine there is likely to be a considerable demand for tapering strips. CONCLUSION: From a financial, marketing and practical point of view, the introduction of tapering strips is feasable. Patients will derive considerable benefits. The paroxetine strips will be produced first and are expected to be available from December 2013.

[A heterotopic pregnancy]. / Een heterotope zwangerschap.

BACKGROUND: Heterotopic pregnancy is a rare but life-threatening situation. This is a situation where a woman has one or more intrauterine pregnancies and at least one ectopic pregnancy. CASE DESCRIPTION: Heterotopic pregnancy was discovered in a 37-year-old woman during a routine ultrasound check. This pregnancy occurred after intrauterine insemination with ovulation induction. CONCLUSION: Heterotopic pregnancies require early diagnosis and treatment. Physicians should be extra vigilant when a woman has become pregnant after using assisted reproductive techniques, because these techniques increase the probability of heterotopic pregnancy. The symptoms of such pregnancies are similar to the symptoms of extrauterine gravidity. However, confirmed intrauterine gravidity does not exclude the existence of extrauterine gravidity. The diagnosis is based entirely on the transvaginal ultrasound. The intact intrauterine gravidity limits treatment options. Tubectomy is the treatment of first choice, but embryo aspiration could also be a safe method in certain circumstances.

Flow-mediated dilatation in the superficial femoral artery is nitric oxide mediated in humans.

Flow-mediated dilatation (FMD) of the brachial and radial arteries is an important research tool for assessment of endothelial function in vivo, and is nitric oxide (NO) dependent. The leg skeletal muscle vascular bed is an important territory for studies in exercise physiology. However, the role of endothelial NO in the FMD response of lower limb arteries has never been investigated. The purpose of this study was to examine the contribution of NO to FMD in the superficial femoral artery in healthy subjects. Since physical inactivity may affect endothelial function, and therefore NO availability, spinal cord-injured (SCI) individuals were included as a model of extreme deconditioning. In eight healthy men (34 +/- 13 years) and six SCI individuals (37 +/- 10 years), the 5 min FMD response in the superficial femoral artery was assessed by echo-Doppler, both during infusion of saline and during infusion of the NO synthase blocker N(G)-monomethyl-L-arginine (L-NMMA). In a subset of the controls (n = 6), the 10 min FMD response was also examined using the same procedure. The 5 min FMD response in controls (4.2 +/- 0.3%) was significantly diminished during L-NMMA infusion (1.0 +/- 0.2%, P < 0.001). In SCI, L-NMMA also significantly decreased the FMD response (from 8.2 +/- 0.4% during saline to 2.4 +/- 0.5% during L-NMMA infusion). The hyperaemic flow response during the first 45 s after cuff deflation was lower in both groups during infusion of L-NMMA, but the effect of L-NMMA on FMD persisted in both groups after correction for the shear stress stimulus. The 10 min FMD was not affected by L-NMMA (saline: 5.4 +/- 1.6%, L-NMMA: 5.6 +/- 1.5%). Superficial femoral artery FMD in response to distal arterial occlusion for a period of 5 min is predominantly mediated by NO in healthy men and in the extremely deconditioned legs of SCI individuals.

Endothelium-dependent and -independent vasodilation of the superficial femoral artery in spinal cord-injured subjects.

Extreme inactivity of the legs in spinal cord-injured (SCI) individuals does not result in an impairment of the superficial femoral artery flow-mediated dilation (FMD). To gain insight into the underlying mechanism, the present study examined nitric oxide (NO) responsiveness of vascular smooth muscles in controls and SCI subjects. In eight healthy men (34 +/- 13 yr) and six SCI subjects (37 +/- 10 yr), superficial femoral artery FMD response was assessed by echo Doppler. Subsequently, infusion of incremental dosages of sodium nitroprusside (SNP) was used to assess NO responsiveness. Peak diameter was examined on a second day after 13 min of arterial occlusion in combination with sublingual administration of nitroglycerine. Resting and peak superficial femoral artery diameter in SCI subjects were smaller than in controls (P < 0.001). The FMD response in controls (4.2 +/- 0.9%) was lower than in SCI subjects (8.2 +/- 0.9%, P < 0.001), but not after correcting for area under the curve for shear rate (P = 0.35). When expressed as relative change from baseline, SCI subjects demonstrate a significantly larger diameter increase compared with controls at each dose of SNP. However, when expressed as a relative increase within the range of diameter changes [baseline (0%) - peak diameter (100%)], both groups demonstrate similar changes in response to SNP. Changes in diameter during SNP infusion and FMD response are larger in SCI subjects compared with controls. When these results are corrected, superficial femoral artery FMD and NO sensitivity in SCI subjects are not different from those in controls. This illustrates the importance of appropriate data presentation and suggests that, subsequent to structural inward remodeling of conduit arteries as a consequence of extreme physical inactivity, arterial function is normalized.

Endothelial function of young healthy males following whole body resistance training.

Given the increasing emphasis on performance of resistance exercise as an essential component of health, we evaluated, using a prospective longitudinal design, the potential for resistance training to affect arterial endothelial function. Twenty-eight men (23 +/- 3.9 yr old; mean +/- SE) engaged in 12 wk of whole body resistance training five times per week using a repeating split-body 3-day cycle. Brachial endothelial function was measured using occlusion cuff-induced flow-mediated dilation. After occlusion of the forearm for 4.5 min, brachial artery dilation and postocclusion blood flow was measured continuously for 15 and 70 s, respectively. Peak and 10-s postocclusion blood flow, shear rate, and brachial artery flow-mediated dilation (relative and normalized to shear rate) were measured pretraining (Pre), at 6 wk of training (Mid), and at 13 wk of training (Post). Results indicated an increase of mean brachial artery diameter by Mid and Post vs. Pre. Peak and 10-s postocclusion blood flow increased by Mid and remained elevated at Post; however, shear rates were not different at any time point. Relative and normalized flow-mediated dilation was also not different at any time point. This study is the first to show that peripheral arterial remodeling does occur with resistance training in healthy young men. In addition, the increase in postocclusion blood flow may indicate improved resistance vessel function. However, unlike studies involving endurance training, flow-mediated dilation did not increase with resistance training. Thus arterial adaptations with high-pressure loads, such as those experienced during resistance exercise, may be quite different compared with endurance training.

The human amylase-encoding genes amy2 and amy3 are identical to AMY2A and AMY2B.

Inspection of the published nucleotide sequences reveals that the human amylase-encoding genes, amy2 and amy3, must be identical to the genes AMY2A and AMY2B, respectively.

Effects of 18 days of bed rest on leg and arm venous properties.

Venous function may be altered by bed rest deconditioning. Yet the contribution of altered venous compliance to the orthostatic intolerance observed after bed rest is uncertain. The purpose of this study was to assess the effect of 18 days of bed rest on leg and arm (respectively large and small change in gravitational gradients and use patterns) venous properties. We hypothesized that the magnitude of these venous changes would be related to orthostatic intolerance. Eleven healthy subjects (10 men, 1 woman) participated in the study. Before (pre) and after (post) 18 days of 6 degrees head-down tilt bed rest, strain gauge venous occlusion plethysmography was used to assess limb venous vascular characteristics. Leg venous compliance was significantly decreased after bed rest (pre: 0.048 +/- 0.007 ml x 100 ml(-1) x mmHg(-1), post: 0.033 +/- 0.007 ml x 100 ml(-1) x mmHg(-1); P < 0.01), whereas arm compliance did not change. Leg venous flow resistance increased significantly after bed rest (pre: 1.73 +/- 1.08 mmHg x ml(-1) x 100 ml x min, post: 3.10 +/- 1.00 mmHg x ml(-1) x 100 ml x min; P < 0.05). Maximal lower body negative pressure tolerance, which was expressed as cumulative stress index (pressure x time), decreased in all subjects after bed rest (pre: 932 mmHg x min, post: 747 mmHg x min). The decrease in orthostatic tolerance was not related to changes in leg venous compliance. In conclusion, this study demonstrates that after bed rest, leg venous compliance is reduced and leg venous outflow resistance is enhanced. However, these changes are not related to measures of orthostatic tolerance; therefore, alterations in venous compliance do not to play a major role in orthostatic intolerance after 18 days of head-down tilt bed rest.

Development of an on-line coupling of liquid-liquid extraction, normal-phase liquid chromatography and high-resolution gas chromatography producing an analytical marker for the prediction of mutagenicity and carcinogenicity of bitumen and bitumen fumes.

A fast and fully automated system for the determination of polycyclic aromatic compounds (PACs) is described. The system has been developed to produce an analytical 'marker', correlating chemical characteristics (including PAC analysis) with mutagenicity and carcinogenicity. The products of interest are bitumen fumes, bitumen and other (heavy or even residual) oil products, regardless of their boiling range. Dimethyl sulphoxide (DMSO) extractables obtained from a flow-injection analysis (FIA) system are introduced on-line in a normal-phase liquid chromatographic (NPLC) system. Here, the PACs are separated from the DMSO and possible co-extracted heavy residual species. The final step incorporates on-line gas chromatographic analysis of the three-to-six-ring PAC fraction, followed by flame-ionisation detection for quantification. It was demonstrated that data obtained from samples in the distillate lubrication-oil range correlate well with data obtained from the manual DMSO-extraction method standardised by the Institute of Petroleum as IP346.

Aqueous leaching of polycyclic aromatic hydrocarbons from bitumen and asphalt.

The application of bitumen in, e.g. asphalt roads, roofs and hydraulic applications will lead to the leaching of compounds from the bitumen/asphalt into the environment. Because polycyclic aromatic hydrocarbons (PAHs) are present in bitumen, static and dynamic leach tests have been performed to study the leaching behaviour of this class of compounds. Nine petroleum bitumens covering a representative range of commercially available products and one asphalt made from one of the bitumens have been tested in a static leach test. The asphalt has been also subjected to a dynamic leach test. The main conclusions are that a 30h dynamic leach test is sufficient to determine the equilibrium concentration that will be reached after bitumen or asphalt has been in contact with the water for more than 3-6 days. As an alternative to performing a leach test, this concentration can be calculated from the PAH concentrations in the bitumen, and their distribution coefficients, as calculated here, or from their aqueous solubilities. The equilibrium PAH concentrations in the leach water from bitumens stay well below the surface water limits that exist in several EEC-countries and are also more than an order of magnitude lower than the current EEC limits for potable water.

[Intra-uterine death caused by fetal akinesia]. / Intra-uteriene sterfte door foetale bewegingsarmoede: het belang van diagnostiek na een vruchtdood.

BACKGROUND: When two successive pregnancies end in intra-uterine fetal death (IUFD), the question of whether it is coincidental or if there is an underlying abnormality arises. Although diagnostic investigations into the underlying cause are not always carried out after IUFD, they are recommended by the professional body. CASE DESCRIPTION: A 28-year-old female attended our gynaecology outpatient clinic for a second opinion following two intra-uterine fetal deaths. Her own treating physician was of the opinion that there was no connection between the two IUFDs. After a multidisciplinary evaluation, the phenotype fetal akinesia deformation sequence (FADS) was diagnosed in both cases. This is a rare, clinically and aetiologically heterogeneous group of disorders. Thereafter the patient and her husband were offered specific pre-conception counseling. CONCLUSION: Every IUFD justifies systemic and multidisciplinary investigation to determine any underlying aetiology such as FADS. This may contribute to better pre-conception advice and prenatal individualised diagnostics in a subsequent pregnancy.

PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis.

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) are at risk of arterial disease. We examined the risk of (non)fatal coronary heart disease (CHD) or stroke in patients with PCOS and ovulatory women without PCOS, and assessed whether obesity might explain a higher risk of CHD or stroke. METHODS: We performed a systematic review and meta-analysis of controlled observational studies. Four definitions of PCOS were considered: World Health Organization type II anovulation, National Institutes of Health criteria, Rotterdam consensus and Androgen-excess criteria. Obesity was defined as BMI > 30 kg/m(2) and/or waist circumference >88 cm. Study quality was assessed using the Newcastle-Ottawa Scale. Primary outcome was fatal/non-fatal CHD or stroke. Definitions of CHD and stroke were based on criteria used by the various authors. The effect measure was the pooled relative risk in a random effects model. Risk ratios and rate ratios were combined here. RESULTS: After identifying 1340 articles, 5 follow-up studies published between 2000 and 2008 were included. The studies showed heterogeneity in design, definitions and quality. In a random effects model the relative risk for CHD or stroke were 2.02 comparing women with PCOS to women without PCOS (95% confidence interval 1.47, 2.76). Pooling the two studies with risk estimates adjusted for BMI showed a relative risk of 1.55 (1.27, 1.89). CONCLUSIONS: This meta-analysis showed a 2-fold risk of arterial disease for patients with PCOS relative to women without PCOS. BMI adjustment did not affect this finding, suggesting the increased risk for cardiovascular events in PCOS is not completely related to a higher BMI in patients with PCOS.

Vascular adaptations to 8-week cycling training in older men.

AIM: Because age-related changes in the large conduit arteries (increased wall thickness, and attenuated arterial compliance and endothelial function) are associated with cardiovascular pathology, prevention is of paramount importance. The effects of endurance training (i.e. walking or cycling) in older humans are assessed in cross-sectional studies, examining the brachial and carotid arteries (supplying non-trained areas). The purpose of this study was to assess the effects of 8-week endurance training in older men on conduit artery characteristics in the trained and non-trained vascular beds. METHODS: In eight healthy sedentary older men (70 +/- 3 years), characteristics of the large conduit arteries [common femoral (CFA), superficial femoral (SFA), carotid (CA), and brachial artery (BA)] were measured before and after 8-week cycling training. Functional [arterial compliance and flow-mediated dilation (FMD)] and structural (diameter and intima-media thickness) conduit artery properties were measured using echo-Doppler. Peak blood flow, representing structural peripheral adaptations, was measured using venous occlusion plethysmography. RESULTS: After training, peak leg blood flow was increased (P < 0.01) and baseline diameter and flow were increased in the CFA (P < 0.05). Cycling training enhanced arterial compliance of the SFA (P = 0.03), but did not affect the FMD (P = 0.32) or the intima-media thickness of the SFA. Exercise training did not alter characteristics of the BA or CA. CONCLUSION: Eight weeks of endurance training in older men altered functional and structural characteristics of the lower extremity vasculature, whereas no changes are reported for the conduit arteries in the non-trained areas (BA or in the CA).

Mouse genetic model for antigen-induced airway manifestations of asthma.

Allergic asthma is a genetically complex disease characterized by allergen-specific immunoglobulin (Ig)E, eosinophilic inflammation of the lungs and airway hyper-responsiveness to bronchospasmogenic stimuli. In this study, we compared 13 recombinant congenic (RC) mouse strains in an ovalbumin model of allergic asthma. Different intensities and types of responses are observed throughout the RC strains. Intensities range from resistance to asthma in CcS05, to a very severe bronchoconstrictive reaction upon methacholine challenge for the parental STS strain. All strains show a 'modified' Th2 response except CcS14, which shows a 'true' Th2 response. When data from all strains are pooled, airway reactivity shows significant correlations with the serum Ig levels and the levels of interleukin (IL)-4, IL-5 and IL-13 in the broncho-alveolar lavage (BAL), at low dosage of methacholine (below 25 mg/ml), whereas at high dosage airway reactivity only correlates with BAL neutrophil levels. This indicates that at least two different mechanisms are involved in the airway reactivity to methacholine. None of these correlations can be found in every individual strain, which demonstrates that the asthma traits in this mouse model are genetically dissociated and that the loci can be genetically mapped.

Effect of whole body resistance training on arterial compliance in young men.

The effect of resistance training on arterial stiffening is controversial. We tested the hypothesis that resistance training would not alter central arterial compliance. Young healthy men (age, 23 +/- 3.9 (mean +/- s.e.m.) years; n = 28,) were whole-body resistance trained five times a week for 12 weeks, using a rotating 3-day split-body routine. Resting brachial blood pressure (BP), carotid pulse pressure, carotid cross-sectional compliance (CSC), carotid initima-media thickness (IMT) and left ventricular dimensions were evaluated before beginning exercise (PRE), after 6 weeks of exercise (MID) and at the end of 12 weeks of exercise (POST). CSC was measured using the pressure-sonography method. Results indicate reductions in brachial (61.1 +/- 1.4 versus 57.6 +/- 1.2 mmHg; P < 0.01) and carotid pulse pressure (52.2 +/- 1.9 versus 46.8 +/- 2.0 mmHg; P < 0.01) PRE to POST. In contrast, carotid CSC, beta-stiffness index, IMT and cardiac dimensions were unchanged. In young men, central arterial compliance is unaltered with 12 weeks of resistance training and the mechanisms responsible for cardiac hypertrophy and reduced arterial compliance are either not inherent to all resistance-training programmes or may require a prolonged stimulus.

A laboratory rig for studying aspects of worker exposure to bitumen fumes.

This study was performed to establish which factors related to the hot application of bitumen products are relevant to worker exposure to benzene-soluble matter (as part of the total fume emission) and to the polycyclic aromatic compound (PAH) content of bitumen fume. Because personal exposure measurements in field surveys can be influenced by many uncontrollable variables, a simple laboratory rig was developed in which bitumen fumes can be generated reproducibly under well-controlled conditions. Laboratory results were related to personal exposure measurements during asphalt paving and roofing. A quantitative relationship for predicting the laboratory fume emission was derived, with bitumen volatility and temperature the only variables. The variable part of the equation is termed the fuming index (FI). The FI correlates well with measured personal exposures in asphalt paving and in roofing and can be used to predict average personal exposures during these activities if bitumen volatility, application temperature, and for paving, the asphalt type, are known. The laboratory fumes, generated at a standard temperature of 160 degrees C, are representative for fumes emitted in the temperature range relevant for asphalt paving, those generated at 250 degrees C for roofing. The PAH profiles of the fumes collected as personal samples during asphalt paving and roofing operations were similar to those of the fumes generated in the laboratory from the same bitumen and at the same temperature. Because it produces conditions representative of actual bitumen operations, this laboratory set-up is an excellent tool for assessing bitumens in terms of fuming tendency and PAH emissions/exposures.