Cryogenic probe for low-noise, high-frequency electronic measurements.

The design and performance of a low-noise, modular cryogenic probe, which is applicable to a wide range of measurements over a broad range of working frequencies, temperatures, and magnetic fields, is presented. The design of the probe facilitates the exchange of sample holders and sample-stage amplifiers, which, combined with its characteristic low transmission and reflection loss, make this design suitable for high precision or low sensitivity measurements. The specific example of measuring the shot noise of magnetic tunnel junctions is discussed. We highlight various design characteristics chosen specifically to expand the applicability of the probe to measurement techniques such as nuclear magnetic resonance.

Thermal Interferometry of Anyons in Spin Liquids.

Aharonov-Bohm interferometry is the most direct probe of anyonic statistics in the quantum Hall effect. The technique involves oscillations of the electric current as a function of the magnetic field and is not applicable to Kitaev spin liquids and other systems without charged quasiparticles. Here, we establish a novel protocol, involving heat transport, for revealing fractional statistics even in the absence of charged excitations, as is the case in quantum spin liquids. Specifically, we demonstrate that heat transport in Kitaev spin liquids through two distinct interferometer's geometries, Fabry-Perot and Mach-Zehnder, exhibit drastically different behaviors. Therefore, we propose the use of heat transport interferometry as a probe of anyonic statistics in charge insulators.

First principles calculations of the electric field gradient tensors of Ba2NaOsO6, a Mott insulator with strong spin orbit coupling.

We present first principles calculations of the electrostatic properties of Ba2NaOsO6 (BNOO), a 5d1 Mott insulator with strong spin orbit coupling (SOC) in its low temperature quantum phases. In light of recent NMR experiments showing that BNOO develops a local octahedral distortion that is accompanied by the emergence of an electric field gradient (EFG) and precedes the formation of long range magnetic order (Lu et al 2017 Nat. Commun. 8 14407, Liu et al 2018 Phys. Rev. B 97 224103; Liu et al 2018 Physica B 536 863), we calculated BNOO's EFG tensor for several different model distortions. The local orthorhombic distortion that we identified as most strongly agreeing with experiment corresponds to a Q2 distortion mode of the Na-O octahedra, in agreement with conclusions given in (Liu et al 2018 Phys. Rev. B 97 224103). Furthermore, we found that the EFG is insensitive to the type of underlying magnetic order. By combining NMR results with first principles modeling, we have thus forged a more complete understanding of BNOO's structural and magnetic properties, which could not be achieved based upon experiment or theory alone.

Application of surface coil in nuclear magnetic resonance studies of physical properties of quasi-2D materials.

We conduct a comprehensive set of tests of performance of surface coils used for nuclear magnetic resonance (NMR) study of quasi-2-dimensional samples. We report 115In and 31P NMR measurements on InP, semi-conducting thin substrate samples. Surface coils of both zig-zag meander-line and concentric spiral geometries were used. We compare reception sensitivity and signal-to-noise ratio of the NMR signal obtained by using surface-type coils to that obtained by standard solenoid-type coils. As expected, we find that surface-type coils provide better sensitivity for NMR study of thin film samples. Moreover, we compare the reception sensitivity of different types of the surface coils. We identify the optimal geometry of the surface coils for a given application and/or direction of the applied magnetic field.

Magnetism and local symmetry breaking in a Mott insulator with strong spin orbit interactions.

Study of the combined effects of strong electronic correlations with spin-orbit coupling (SOC) represents a central issue in quantum materials research. Predicting emergent properties represents a huge theoretical problem since the presence of SOC implies that the spin is not a good quantum number. Existing theories propose the emergence of a multitude of exotic quantum phases, distinguishable by either local point symmetry breaking or local spin expectation values, even in materials with simple cubic crystal structure such as Ba2NaOsO6. Experimental tests of these theories by local probes are highly sought for. Our local measurements designed to concurrently probe spin and orbital/lattice degrees of freedom of Ba2NaOsO6 provide such tests. Here we show that a canted ferromagnetic phase which is preceded by local point symmetry breaking is stabilized at low temperatures, as predicted by quantum theories involving multipolar spin interactions.

[Pulmonary hypertension associated with left heart disease: recommendations of the Cologne Consensus Conference 2016]. / Pulmonale Hypertonie bei Linksherzerkrankungen: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more common forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern because of limited ressources and the need to base treatments on scientific evidence. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, representing an unmet need of targeted PH therapies. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, several working groups were initiated, one of which was specifically dedicated to PH associated with left heart disease. This article summarizes the results and recommendations of this working group.

[Pulmonary hypertension due to left heart disease: recommendations of the Cologne Consensus Conference 2010]. / Pulmonale Hypertonie bei Linksherzerkrankungen: Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, so that it may be speculated whether selected patients may benefit from targeted PH therapy. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH due to left heart disease. This commentary summarizes the results and recommendations of this working group.

Field evolution of coexisting superconducting and magnetic orders in CeCoIn5.

We present nuclear magnetic resonance (NMR) measurements on the three distinct In sites of CeCoIn5 with a magnetic field applied in the [100] direction. We identify the microscopic nature of the long range magnetic order (LRO) stabilized at low temperatures in fields above 10.2 T while still in the superconducting (SC) state. We infer that the ordered moment is oriented along the c axis and map its field evolution. The study of the field dependence of the NMR shift for the different In sites indicates that the LRO likely coexists with a modulated SC phase, possibly that predicted by Fulde, Ferrell, Larkin, and Ovchinnikov. Furthermore, we discern a field region dominated by strong spin fluctuations where static LRO is absent and propose a revised phase diagram.

A Reusable, Low-profile, Cryogenic Wire Seal.

We describe the design of a reusable Indium wire seal which has a small profile and is leak tight to better than 1x10(-10) std. cc/sec. from room temperature down to approximately mK. The pressure necessary to deform the Indium wire o-ring is provided by a screw-cap mating to threads on the outside of the cylindrical volume to be sealed.

Field dependence of the ground state in the exotic superconductor CeCoIn5: a nuclear magnetic resonance investigation.

We report 115In nuclear magnetic resonance (NMR) measurements in CeCoIn5 at low temperature (T approximately 70 mK) as a function of the magnetic field (H0) from 2 to 13.5 T applied perpendicular to the c axis. A NMR line shift reveals that below 10 T the spin susceptibility increases as sqrt[H0]. We associate this with an increase of the density of states due to the Zeeman and Doppler-shifted quasiparticles extended outside the vortex cores in a d-wave superconductor. Above 10 T a new superconducting state is stabilized, possibly the modulated phase predicted by Fulde, Ferrell, Larkin, and Ovchinnikov. This phase is clearly identified by a strong and linear increase of the NMR shift with the field, before a jump at the first order transition to the normal state.

Observation of spin susceptibility enhancement in the possible Fulde-Ferrell-Larkin-Ovchinnikov state of CeCoIn(5).

We report (115)In nuclear magnetic resonance measurements of the heavy-fermion superconductor CeCoIn(5) in the vicinity of the superconducting critical field H(c2) for a magnetic field applied perpendicular to the c axis. A possible inhomogeneous superconducting state, the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state, is stabilized in this part of the phase diagram. In an 11 T applied magnetic field, we observe clear signatures of the two phase transitions: the higher temperature one to the homogeneous superconducting state and the lower temperature phase transition to a FFLO state. We find that the spin susceptibility in the putative FFLO state is significantly enhanced as compared to the value in a homogeneous superconducting state. The implications of this finding for the nature of the low temperature phase are discussed.

Prognostic value of N-terminal pro-B-type natriuretic peptide for conservatively and surgically treated patients with aortic valve stenosis.

OBJECTIVE: To evaluate the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with aortic stenosis being treated conservatively or undergoing aortic valve replacement (AVR). METHODS: 159 patients were followed up for a median of 902 days. 102 patients underwent AVR and 57 were treated conservatively. NT-proBNP at baseline was raised in association with the degree of severity and of functional status. RESULTS: During follow up 21 patients (13%) died of cardiac causes or required rehospitalisation for decompensated heart failure. NT-proBNP at baseline was higher in patients with an adverse outcome than in event-free survivors (median 623 (interquartile range 204-1854) pg/ml v 1054 (687-2960) pg/ml, p = 0.028). This difference was even more obvious in conservatively treated patients (331 (129-881) pg/ml v 1102 (796-2960) pg/ml, p = 0.002). Baseline NT-proBNP independently predicted an adverse outcome in the entire study group and in particular in conservatively treated patients (area under the curve (AUC) = 0.65, p = 0.028 and AUC = 0.82, p = 0.002, respectively) but not in patients undergoing AVR (AUC = 0.544). At a cut-off value of 640 pg/ml, baseline NT-proBNP was discriminative for an adverse outcome. CONCLUSION: NT-proBNP concentration is related to severity of aortic stenosis and provides independent prognostic information for an adverse outcome. However, this predictive value is limited to conservatively treated patients. Thus, the data suggest that assessing NT-proBNP may have incremental value for selecting the optimal timing of valve replacement.

Release pattern of N-terminal pro B-type natriuretic peptide (NT-proBNP) in acute coronary syndromes.

BACKGROUND: Recently it has been found that BNP and NT-proBNP provide independent prognostic information in patients with acute coronary syndromes (ACS). However, little data are available on the time course of NT-proBNP levels in relation to onset of symptoms. METHODS AND RESULTS: We included 765 patients (236 females, aged 64 +/- 11 years) with an ACS (STEMI 42%, NSTEMI 41%, UAP 17%), who were referred for coronary angiography. NT-proBNP was assessed on admission and the next day. NT-proBNP values were related to the time duration from onset of symptoms until blood drawing with lowest values within 3 h and highest values 24-36 h after onset of symptoms (147 (64-436) pg/ml and 1099 (293-3795) pg/ml, respectively, p < 0.001). Highest values for NT-proBNP on admission were found in patients with NSTEMI compared to patients with STEMI and UAP (912 (310-2258) pg/ml) vs 262 (85-1282) pg/ml) vs 182 (74- 410) pg/ml; p < 0.001), but no difference was present between STEMI and NSTEMI the day after admission (1325 (532-2974) pg/ ml vs 1169 (555-3413) pg/ml; p = 0.676). In contrast NT-proBNP values remained unchanged in UAP (182 (74-410) pg/ml) vs 171 (53-474) pg/ml). CONCLUSION: The time interval from onset of symptoms to first blood collection is an important determinant for NT-proBNP values on admission in patients with an ACS and needs to be considered in clinical practice.

Nickel release, a possible indicator for the duration of antiplatelet treatment, from a nickel cardiac device in vivo: a study in patients with atrial septal defects implanted with an Amplatzer occluder.

UNLABELLED: The present study was undertaken to evaluate the safety and release of nickel after implantation of a nickel device (Amplatzer occluder) in patients with an atrial septal defect (ASD) receiving antiplatelet therapy. METHODS: Blood and urine samples were obtained from 24 patients with ASD before occluder implantation (baseline) and during a 12-month post closure period. Antiplatelet drugs were administered for the initial 6-month period post implantation. The nickel content in the specimens was determined using electrothermal atomic absorption spectroscopy. The clinical, sonographic and magnetic resonance imaging follow-ups were carried out 1 week, 1 month, 6 months and 12 months post implantation. RESULTS: Mean baseline concentrations of nickel in serum and urine were within normal range with values of 0.6 +/- 0.2 microg/l and 3.1 +/- 1.2 microg/l, respectively. During the 6-week post closure period, the time needed for the formation of neointima on the surface of the graft, nickel levels in serum increased up to 5-fold (p < 0.01 versus baseline). Mean concentrations in serum and urine returned to baseline levels within 4-6 months post implantation. All patients showed satisfactory clinical improvements and there was no sonographic evidence of complications. CONCLUSIONS: The initial dissolution of nickel from the Amplatzer occluder is not a specific cardiovascular risk and is temporarily linked to the formation of the non-thrombogenic neointima on the surface of the graft. The antiplatelet drug regimen used (300 mg aspirin + 75 mg clopidogrel daily for 3 months in the initial phase and 100 mg aspirin daily for a further 3 months) appears to cover the period of neointima formation on the nickel device when nickel levels are significantly elevated. However, further studies in a larger number of patients and over a period greater than 12 months are needed to confirm the validity of these conclusions and to formulate definitive recommendations on the duration of the antiplatelet treatment.

Left ventricular adaptation after atrial septal defect closure assessed by increased concentrations of N-terminal pro-brain natriuretic peptide and cardiac magnetic resonance imaging in adult patients.

OBJECTIVE: To determine in an observational study whether N-terminal pro-brain natriuretic peptide (NT-proBNP) is raised in patients with an atrial septal defect (ASD) and whether concentrations change after interventional closure. METHODS: 12 patients (6 men, mean (SD) age 44.4 (18.6) years) with a moderate sized ASD type II (23.3 (4.5) mm, pulmonary to systemic flow ratio 2.1 (0.68)) were investigated. In all patients a magnetic resonance imaging (MRI) study was performed and NT-proBNP was assessed at baseline and early (9 (13) days) and late (138 (64) days) after intervention. RESULTS: Concentrations of NT-proBNP were found to be within the normal range at baseline (median 87 pg/ml, interquartile range 65-181 pg/ml) but increased early after the interventional closure (315 pg/ml, 133-384 pg/ml, p = 0.005 versus baseline). The increase of NT-proBNP was associated with an increase in left ventricular dimensions as assessed by MRI (left ventricular end diastolic volume 104 (27) ml to 118 (27) ml, p = 0.003). Late after ASD closure NT-proBNP returned to baseline concentrations (102 pg/ml, 82-188 pg/ml, p = 0.004 versus early follow up). CONCLUSION: These findings suggest the presence of transitory haemodynamic stress during adaptation of the left ventricle after ASD closure, which may contribute to the understanding of the pathological mechanism of acute heart failure and delayed improvement of exercise capacity after ASD closure.

Influence of the angiotensin converting enzyme inhibitor ramipril on high-sensitivity C-reactive protein (hs-CRP) in patients with documented atherosclerosis.

UNLABELLED: Some medications have been shown to produce reductions in hs-CRP levels after initiating therapy. Whereas the role of the renin-angiotensin system in the inflammatory process has been documented in more detail during the last few years, the impact of an ACE-inhibitor therapy on this process has not been fully understood so far. The aim of this study was to investigate the effect of a therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on hs-CRP plasma concentrations in patients with atherosclerosis. METHODS AND RESULTS: A total of 24 patients were enrolled in this prospective, uncontrolled, open-label multicenter study. Inclusion criteria were documented atherosclerosis, baseline high-sensitivity C-reactive protein between 3 and 12 mg/l, LDL-Cholesterol < or =150 mg/dl and no previous treatment with ACE inhibitors or angiotensin receptor blockers. Ten patients, pretreated with statins, and 10 patients not previously treated with statins were eligible for statistical analysis. Baseline high-sensitivity C-reactive protein was significantly decreased from 3.99+/-1.61 mg/l (mean+/-SD) to 2.72+/-1.19 mg/l (-32%) after 3 months treatment with 10 mg ramipril daily (p=0.0002). The decrease was more pronounced in patients who had not been treated with statins previously (-1.50 mg/l+/-1.44 mg/l) compared to those who were pretreated (-0.90 mg/l+/-0.93 mg/l). CONCLUSIONS: The ACE inhibitor ramipril administered in a daily dose of 10 mg to patients with atherosclerosis reduces the high-sensitivity C-reactive protein concentration. This effect may contribute to cardiovascular risk reduction mediated by ramipril aside from the blood pressure lowering effect.

[Information deficits concerning blood pressure self-measurement]. / Informationsdefizite bei der Blutdruck-Selbstmessung -- Ergebnisse einer Patientenbefragung.

BACKGROUND AND OBJECTIVE: Blood pressure values resulting from measurements by the patients themselves have greater diagnostic and prognostic significance than those measured by the physician, assuming, however, that measurement is taken correctly. As self-measurement of blood pressure has meanwhile become a widespread practice. The question arises to what extent the rules on exact measurement of blood pressure are known to the patient. PATIENTS AND METHODS: The answers to questions on five rules on self-measurement of blood pressure (resting period prior to measurement, time of measurement and intake of morning medication, left or right arm for measurement, level of measuring point and width of cuff) given by 500 hypertensive patients (373 men, 127 women, mean age 59.2 +/- 10.2 years) were evaluated. RESULTS: Three patients only were in the position to answer all five questions correctly. 19 % were unable to give any right answer. Patients showed highest information levels concerning the resting period before measurement. Approximately half of them (51 %) knew that a pause of three minutes has to be kept. Only one in three, however, was familiar with the fact that morning measurement has to be taken prior to the intake of antihypertensives (32 %) choosing the arm that shows higher blood pressure values. 28 % were informed that the measuring point has to lie at the height of the heart. Only 4 % were able to answer the question on the width of the cuff correctly. CONCLUSION: Our findings show that the rules on correct self-measurement of blood pressure are unknown to most of the hypertensive patients. This may be due to the fact that they are insufficiently informed and trained.

[Cardiopulmonary exercise capacity increases after interventional ASD-closure]. / Verbesserung der kardiopulmonalen Belastbarkeit nach interventionellem ASD-Verschluss.

BACKGROUND: In patients with atrial septal defects of the secundum-type (ASD), exercise tolerance is reduced. Generally, ASD closure is recommended in symptomatic patients and in patients with a relevant left-to-right shunt (Qp/Qs > 1.5). Only few data are available concerning objective parameters of cardiopulmonary exercise capacity. The aim of this study was to evaluate exercise capacity as achieved by ergospirometry in adult patients with an ASD at baseline and in the long-term following transcatheter closure. METHODS AND RESULTS: Thirty consecutive patients (8 male; mean age 43.4 years; defect size 23.5 mm; pulmonary-to-systemic flow ratio (Qp/Qs) 1.94) performed exercise testing on a supine bicycle ergometer. At baseline, oxygen consumption at maximal exercise (VO(2) peak) was 14.3 ml/min kg, oxygen consumption at the anaerobic threshold (VO(2)-AT) was 11.2 ml/min/kg and maximal achieved workload was 86 Watt. At one and six months after ASD-closure, there was no relevant increase of the VO(2) peak, the VO(2)-AT or the maximal workload. After 12 months, there was a significant increase of the VO(2) peak (15.1 ml/min/kg, p = 0.049), the VO(2)-AT (13 ml/min/kg, p < 0.001) and the maximal workload (99 Watt, p < 0.01). An increase of the oxygen consumption at the anaerobic threshold (Delta VO(2) AT) could be seen in 24 out of 30 patients and was independent of shunt volume (Q(p)/Q(s) < or = 2, 1.95 ml/ min/kg; Q(p)/Q(s) > 2, 2.13 ml/min/ kg; ns), defect size (defect < or = 24 mm, 2.0 ml/min/kg; defect > 24 mm, 1.5 ml/min/kg; ns), age (age < or = 44 years, 1.97 ml/min/kg; age >44 years, 1.66 ml/min/kg; ns), gender (female 1.56 ml/min/ kg; male 1.91 ml/min/kg; ns) and of the existence of a residual shunt. Highly symptomatic patients had a tendency to have greater benefit from ASD-closure as compared to mildly symptomatic patients (NYHA 0/I 1.85 ml/min/kg; NYHA II 1.5 ml/min/ kg; NYHA III 2.7 ml/min/kg; ns). There was no correlation between shunt volume, shunt size, pulmonal arterial pressure and increase of the oxygen consumption at the anaerobic threshold (Delta VO(2) AT). CONCLUSION: There is no relevant improvement in exercise capacity early (1-6 months) after interventional ASD-closure, but late after ASD-closure (12 months) exercise capacity improves significantly. This improvement can be found in almost all patients independent of gender, age, symptoms, shunt volume and defect size.

Acute and 3-month treatment effects of candesartan cilexetil on hemodynamics, neurohormones, and clinical symptoms in patients with congestive heart failure.

BACKGROUND: This study evaluated the short-term and long-term effects of the angiotensin II type 1 receptor antagonist candesartan cilexetil on hemodynamics, neurohormones, and clinical symptoms in patients with congestive heart failure (CHF). METHODS: In this multicenter, double-blind, parallel-group study, 218 patients with CHF (New York Heart Association class II or III) with impaired left ventricular function (ejection fraction < or =40%) and pulmonary capillary wedge pressure > or =13 mm Hg were randomly assigned to 12 weeks of treatment with placebo (n = 44) or candesartan cilexetil (2 mg [n = 45], 4 mg [n = 46], 8 mg [n = 39], or 16 mg [n = 44]) once daily after a 2-week placebo run-in period. Hemodynamic measurements were performed by right heart catheterization over a 24-hour period after single (day 1) and repeated (3-month) treatment with the study drug. RESULTS: On regression analysis of the time-response curves, single and multiple doses of candesartan cilexetil produced sustained, significant, and dose-dependent reductions in pulmonary capillary wedge pressure (short-term effect P =.036, long-term effect P =.035) and mean pulmonary arterial pressure (short-term effect P =.031, long-term effect P =.042). Systemic vascular resistance showed a trend toward decreasing with dose on short-term and long-term treatments. No consistent changes were seen in cardiac index. Compensatory increases in plasma renin activity and angiotensin II levels with decreases in aldosterone and atrial natriuretic peptide were dose-dependent and significant. Candesartan cilexetil improved clinical symptoms, stabilized patient New York Heart Association status compared with placebo, and was judged to be an efficacious treatment by the investigators. More patients receiving placebo stopped the trial prematurely because of an adverse event than in any candesartan cilexetil group, and there was no excess of deaths in any treatment group. Candesartan was safe and well tolerated at all dosages. CONCLUSIONS: Candesartan cilexetil demonstrated significant short-term and long-term improvements in hemodynamic, neurohormonal, and symptomatic status and was well tolerated in patients with CHF.