Sub-pm/Hz\mathrm{\mathbf{\sqrt{\rm Hz}}} non-reciprocal noise in the LISA backlink fiber

The future space-based gravitational wave detector Laser Interferometer Space Antenna (LISA) requires bidirectional exchange of light between its two optical benches on board of each of its three satellites. The current baseline foresees a polarization-maintaining single-mode fiber for this backlink connection. Phase changes which are common in both directions do not enter the science measurement, but differential ("non-reciprocal") phase fluctuations directly do and must thus be guaranteed to be small enough. We have built a setup consisting of a Zerodur$^{\rm TM}$ baseplate with fused silica components attached to it using hydroxide-catalysis bonding and demonstrated the reciprocity of a polarization-maintaining single-mode fiber at the 1 pm/$\sqrt{\textrm{Hz}}$ level as is required for LISA. We used balanced detection to reduce the influence of parasitic optical beams on the reciprocity measurement and a fiber length stabilization to avoid nonlinear effects in our phase measurement system (phase meter). For LISA, a different phase meter is planned to be used that does not show this nonlinearity. We corrected the influence of beam angle changes and temperature changes on the reciprocity measurement in post-processing

Real-time phasefront detector for heterodyne interferometers

We present a real-time differential phasefront detector sensitive to better than 3 mrad rms, which corresponds to a precision of about 500 pm. This detector performs a spatially resolving measurement of the phasefront of a heterodyne interferometer, with heterodyne frequencies up to approximately 10 kHz. This instrument was developed as part of the research for the LISA Technology Package (LTP) interferometer, and will assist in the manufacture of its flight model. Due to the advantages this instrument offers, it also has general applications in optical metrology

Right Heart Remodeling in Patients with End-Stage Alcoholic Liver Cirrhosis: Speckle Tracking Point of View

BACKGROUND: Data regarding cardiac remodeling in patients with alcoholic liver cirrhosis are scarce. We sought to investigate right atrial (RA) and right ventricular (RV) structure, function, and mechanics in patients with alcoholic liver cirrhosis. METHODS: This retrospective cross-sectional investigation included 67 end-stage cirrhotic patients, who were referred for evaluation for liver transplantation and 36 healthy controls. All participants underwent echocardiographic examination including strain analysis, which was performed offline. RESULTS: RV basal diameter and RV thickness were significantly higher in patients with cirrhosis. Conventional parameters of the RV systolic function were similar between the observed groups. Global, endocardial, and epicardial RV longitudinal strains were significantly lower in patients with cirrhosis. Active RA function was significantly higher in cirrhotic patients than in controls. The RA reservoir and conduit strains were significantly lower in cirrhotic patients, while there was no difference in the RA contractile strain. Early diastolic and systolic RA strain rates were significantly lower in cirrhotic patients than in controls, whereas there was no difference in the RA late diastolic strain rate between the two groups. Transaminases and bilirubin correlated negatively with RV global longitudinal strain and RV-free wall strain in patients with end-stage liver cirrhosis. The Model for End-stage Liver Disease (MELD) score, predictor of 3-month mortality, correlated with parameters of RV structure and systolic function, and RA active function in patients with end-stage liver cirrhosis. CONCLUSIONS: RA and RV remodeling is present in patients with end-stage liver cirrhosis even though RV systolic function is preserved. Liver enzymes, bilirubin, and the MELD score correlated with RV and RA remodeling

Left ventricular clefts - incidental finding or pathologic sign of Wilson's disease?

Background: Wilson’s disease is an inherited autosomal recessive multi-systemic disorder characterized by reduced excretion and consequently excessive accumulation of copper in different organs, such as the heart. Results: In a prospective controlled trial, which is the largest to date, we evaluated 61 patients with Wilson’s disease, age- and sex-matched to 61 healthy patients, for cardiac manifestation using cardiac magnetic resonance imaging. Patients were under stable disease and had no signs of heart failure at the time of examination. We detected a left ventricular cleft, an invagination penetrating more than 50% wall thickness of the adjoining compact myocardium in diastole, in 20% of the patients (12 out of 61) compared to 5% among control patients (3 out of 61, p = 0.013). No correlation between the incidence of cleft and a certain genotype of Wilson’s disease was found. All described cases were incidental findings and none of the patients showed other signs of cardiac involvement. Conclusions: To conclude, the results of this study suggests that the increased occurrence of left ventricular clefts is due to Wilson’s disease. Large studies with a long observation period are needed for further evaluation

Measurement of the non-reciprocal phase noise of a polarization maintaining single-mode optical fiber

Polarization maintaining single-mode optical fibers are key components in the interferometry of the Laser Interferometer Space Antenna (LISA). LISA's measurement principle relies on the availability of space qualified fibers of this type which influence the phase of light with a wavelength of 1064 nm passing in opposite directions through them with differences smaller than 6 prad/. We present a measurement scheme suitable to sense these non-reciprocal phase changes, as well as results obtained using this setup on samples of commercially available fibers. The experimental setup for the fiber characterization consists of a quasi-monolithic interferometer which constitutes a representative cut-out of the local interferometry on-board LISA concerning the fiber. Several noise sources are identified and improvements to the setup are presented to overcome them. The noise level achieved using this setup is between approximately 40 prad/ and 400 prad/ in the frequency range between 1 mHz and 1 Hz. It is also verified that this noise level is limited by the setup and not introduced by the fiber.DLR/50 OQ 060

Digital laser frequency control and phase stabilization loops for a high precision space-borne metrology system

We report on the design, implementation and characterization of fully digital control loops for laser frequency stabilization, differential phase-locking and performance optimization of the optical metrology system on-board the LISA Pathfinder space mission. The optical metrology system consists of a laser with modulator, four Mach-Zehnder interferometers, a phase-meter and a digital processing unit for data analysis. The digital loop design has the advantage of easy and flexible controller implementation and loop calibration, automated and flexible locking and resetting, and improved performance over analogue circuitry. Using the practical ability of our system to modulate the laser frequency allows us to accurately determine the open loop transfer function and other system properties. Various noise sources and their impact on system performance are investigated in detail.Comment: 10 pages, 7 figures; draft only, for edited version see journal lin

Variations in local calcium signaling in adjacent cardiac myocytes of the intact mouse heart detected with two-dimensional confocal microscopy

Dyssynchronous local Ca release within individual cardiac myocytes has been linked to cellular contractile dysfunction. Differences in Ca kinetics in adjacent cells may also provide a substrate for inefficient contraction and arrhythmias. In a new approach we quantify variation in local Ca transients between adjacent myocytes in the whole heart. Langendorff-perfused mouse hearts were loaded with Fluo-8 AM to detect Ca and Di-4-ANEPPS to visualize cell membranes. A spinning disc confocal microscope with a fast camera allowed us to record Ca signals within an area of 465 μm by 315 μm with an acquisition speed of 55 fps. Images from multiple transients recorded at steady state were registered to their time point in the cardiac cycle to restore averaged local Ca transients with a higher temporal resolution. Local Ca transients within and between adjacent myocytes were compared with regard to amplitude, time to peak and decay at steady state stimulation (250 ms cycle length). Image registration from multiple sequential Ca transients allowed reconstruction of high temporal resolution (2.4 ± 1.3 ms) local CaT in 2D image sets (N = 4 hearts, n = 8 regions). During steady state stimulation, spatial Ca gradients were homogeneous within cells in both directions and independent of distance between measured points. Variation in CaT amplitudes was similar across the short and the long side of neighboring cells. Variations in TAU and TTP were similar in both directions. Isoproterenol enhanced the CaT but not the overall pattern of spatial heterogeneities. Here we detected and analyzed local Ca signals in intact mouse hearts with high temporal and spatial resolution, taking into account 2D arrangement of the cells. We observed significant differences in the variation of CaT amplitude along the long and short axis of cardiac myocytes. Variations of Ca signals between neighboring cells may contribute to the substrate of cardiac remodeling

Long‐term effects of Na+/Ca2+ exchanger inhibition with ORM‐11035 improves cardiac function and remodelling without lowering blood pressure in a model of heart failure with preserved ejection fraction

Aims: Heart failure with preserved ejection fraction (HFpEF) is increasingly common but there is currently no established pharmacological therapy. We hypothesized that ORM-11035, a novel specific Na+/Ca2+ exchanger (NCX) inhibitor, improves cardiac function and remodelling independent of effects on arterial blood pressure in a model of cardiorenal HFpEF. Methods and results: Rats were subjected to subtotal nephrectomy (NXT) or sham operation. Eight weeks after intervention, treatment for 16 weeks with ORM-11035 (1 mg/kg body weight) or vehicle was initiated. At 24 weeks, blood pressure measurements, echocardiography and pressure–volume loops were performed. Contractile function, Ca2+ transients and NCX-mediated Ca2+ extrusion were measured in isolated ventricular cardiomyocytes. NXT rats (untreated) showed a HFpEF phenotype with left ventricular (LV) hypertrophy, LV end-diastolic pressure (LVEDP) elevation, increased brain natriuretic peptide (BNP) levels, preserved ejection fraction and pulmonary congestion. In cardiomyocytes from untreated NXT rats, early relaxation was prolonged and NCX-mediated Ca2+ extrusion was decreased. Chronic treatment with ORM-11035 significantly reduced LV hypertrophy and cardiac remodelling without lowering systolic blood pressure. LVEDP [14 ± 3 vs. 9 ± 2 mmHg; NXT (n = 12) vs. NXT + ORM (n = 12); P = 0.0002] and BNP levels [71 ± 12 vs. 49 ± 11 pg/mL; NXT (n = 12) vs. NXT + ORM (n = 12); P < 0.0001] were reduced after ORM treatment. LV cardiomyocytes from ORM-treated rats showed improved active relaxation and diastolic cytosolic Ca2+ decay as well as restored NCX-mediated Ca2+ removal, indicating NCX modulation with ORM-11035 as a promising target in the treatment of HFpEF. Conclusion: Chronic inhibition of NCX with ORM-11035 significantly attenuated cardiac remodelling and diastolic dysfunction without lowering systemic blood pressure in this model of HFpEF. Therefore, long-term treatment with selective NCX inhibitors such as ORM-11035 should be evaluated further in the treatment of heart failure

Remote Ischemic Preconditioning Neither Improves Survival nor Reduces Myocardial or Kidney Injury in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI)

BACKGROUND: Peri-interventional myocardial injury occurs frequently during transcatheter aortic valve implantation (TAVI). We assessed the effect of remote ischemic preconditioning (RIPC) on myocardial injury, acute kidney injury (AKIN) and 6-month mortality in patients undergoing TAVI. METHODS: We performed a prospective single-center controlled trial. Sixty-six patients treated with RIPC prior to TAVI were enrolled in the study and were matched to a control group by propensity-score. RIPC was applied to the upper extremity using a conventional tourniquet. Myocardial injury was assessed using high-sensitive troponin-T (hsTnT), and kidney injury was assessed using serum creatinine levels. Data were compared with the Wilcoxon-Rank and McNemar tests. Mortality was analysed with the log-rank test. RESULTS: TAVI led to a significant rise of hsTnT across all patients (p < 0.001). No significant inter-group difference in maximum troponin release or areas-under-the-curve was detected. Medtronic CoreValve and Edwards Sapien valves showed similar peri-interventional troponin kinetics and patients receiving neither valve did benefit from RIPC. AKIN occurred in one RIPC patient and four non-RIPC patients (p = 0.250). No significant difference in 6-month mortality was observed. No adverse events related to RIPC were recorded. CONCLUSION: Our data do not show a beneficial role of RIPC in TAVI patients for cardio- or renoprotection, or improved survival

All-reflective coupling of two optical cavities with 3-port diffraction gratings

The shot-noise limited sensitivity of Michelson-type laser interferometers with Fabry-Perot arm cavities can be increased by the so-called power-recycling technique. In such a scheme the power-recycling cavity is optically coupled with the interferometer's arm cavities. A problem arises because the central coupling mirror transmits a rather high laser power and may show thermal lensing, thermo-refractive noise and photo-thermo-refractive noise. Cryogenic cooling of this mirror is also challenging, and thus thermal noise becomes a general problem. Here, we theoretically investigate an all-reflective coupling scheme of two optical cavities based on a 3-port diffraction grating. We show that power-recycling of a high-finesse arm cavity is possible without transmitting any laser power through a substrate material. The power splitting ratio of the three output ports of the grating is, surprisingly, noncritical