Gravitational Lensing at Millimeter Wavelengths

With today's millimeter and submillimeter instruments observers use gravitational lensing mostly as a tool to boost the sensitivity when observing distant objects. This is evident through the dominance of gravitationally lensed objects among those detected in CO rotational lines at z>1. It is also evident in the use of lensing magnification by galaxy clusters in order to reach faint submm/mm continuum sources. There are, however, a few cases where millimeter lines have been directly involved in understanding lensing configurations. Future mm/submm instruments, such as the ALMA interferometer, will have both the sensitivity and the angular resolution to allow detailed observations of gravitational lenses. The almost constant sensitivity to dust emission over the redshift range z=1-10 means that the likelihood for strong lensing of dust continuum sources is much higher than for optically selected sources. A large number of new strong lenses are therefore likely to be discovered with ALMA, allowing a direct assessment of cosmological parameters through lens statistics. Combined with an angular resolution <0.1", ALMA will also be efficient for probing the gravitational potential of galaxy clusters, where we will be able to study both the sources and the lenses themselves, free of obscuration and extinction corrections, derive rotation curves for the lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on "Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be published by Springer-Verlag 2002. Paper with full resolution figures can be found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g

Affective Man-Machine Interface: Unveiling human emotions through biosignals

As is known for centuries, humans exhibit an electrical profile. This profile is altered through various psychological and physiological processes, which can be measured through biosignals; e.g., electromyography (EMG) and electrodermal activity (EDA). These biosignals can reveal our emotions and, as such, can serve as an advanced man-machine interface (MMI) for empathic consumer products. However, such a MMI requires the correct classification of biosignals to emotion classes. This chapter starts with an introduction on biosignals for emotion detection. Next, a state-of-the-art review is presented on automatic emotion classification. Moreover, guidelines are presented for affective MMI. Subsequently, a research is presented that explores the use of EDA and three facial EMG signals to determine neutral, positive, negative, and mixed emotions, using recordings of 21 people. A range of techniques is tested, which resulted in a generic framework for automated emotion classification with up to 61.31% correct classification of the four emotion classes, without the need of personal profiles. Among various other directives for future research, the results emphasize the need for parallel processing of multiple biosignals

Effects of omecamtiv mecarbil on symptoms and health-related quality of life in patients with chronic heart failure: results from the COSMIC-HF study

Background: Chronic HF with reduced ejection fraction (HFrEF) impairs health related quality of life (HRQL). Omecamtiv mecarbil, a novel activator of cardiac myosin, improves left ventricular systolic function and remodeling and reduces natriuretic peptides. We sought to evaluate the effect of omecamtiv mecarbil on symptoms and HRQL in patients with chronic HFrEF and elevated natriuretic peptides enrolled in the COSMIC-HF trial. Methods: Patients (n = 448) were randomized 1:1:1 to placebo, 25 mg of omecamtiv mecarbil twice daily (OM 25 mg), or to pharmacokinetically-guided dose titration (OM-PK) for 20 weeks. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was administered to assess HRQL at baseline, 16 weeks, and 20 weeks. The primary scores of interest were the Total Symptom Score (TSS), Physical Limitation Scale (PLS), and Clinical Summary Score (CSS). Results: Mean change in score from baseline to 20 weeks for the TSS was 5.0 (95%CI: 1.8-8.1) for placebo, 6.6(95%CI: 3.4-9.8) for OM 25 mg (p = 0.32 vs placebo), and 9.9 (95%CI: 6.7-13.0) for OM-PK (p = 0.03 vs placebo); for the PLS, it was 3.1 for placebo (95%CI: -0.3-6.6), 6.0 (95%CI: 3.1-8.9) for OM 25 mg (p=0.12), and 4.3 (95%CI: 0.7-7.9) for OM-PK (p=0.42); for the CSS, it was 4.1 (95%CI: 1.4-6.9) for placebo, 6.3 (95%CI: 3.6-9.0) for OM 25 mg (p=0.19), and 7.0 (95%CI: 4.1-10.0) for OM-PK (p=0.14). Differences between omecamtiv mecarbil and placebo were greater in patients who were more symptomatic at baseline. Conclusions: HRQL as measured by the TSS improved in patients with HFrEF assigned to omecamtiv mecarbil (OM-PK group) relative to placebo. Ongoing trials are prospectively testing whether omecamtiv mecarbil improves symptoms and HRQL in HFrEF

Ultrasound imaging of congestion in heart failure – examinations beyond the heart

Congestion, related to pressures and/or fluid overload, plays a central role in the pathophysiology, presentation and prognosis of heart failure and is an important therapeutic target. While symptoms and physical signs of fluid overload are required to make a clinical diagnosis of heart failure, they lack both sensitivity and specificity, which might lead to diagnostic delay and uncertainty. Over the last decades, new ultrasound methods for the detection of elevated intracardiac pressures and/or fluid overload have been developed that are more sensitive and specific, thereby enabling earlier and more accurate diagnosis and facilitating treatment strategies. Accordingly, we considered that a state‐of‐the‐art review of ultrasound methods for the detection and quantification of congestion was timely, including imaging of the heart, lungs (B‐lines), kidneys (intrarenal venous flow), and venous system (inferior vena cava and internal jugular vein diameter)

Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial

Aims: Both left ventricular (LV) and left atrial (LA) dysfunction and remodelling contribute to adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Danicamtiv is a novel, cardiac myosin activator that enhances cardiomyocyte contraction. Methods and results: We studied the effects of danicamtiv on LV and LA function in non‐clinical studies (ex vivo : skinned muscle fibres and myofibrils; in vivo : dogs with heart failure) and in a randomized, double‐blind, single‐ and multiple‐dose phase 2a trial in patients with stable HFrEF (placebo, n = 10; danicamtiv, n = 30; 50–100 mg twice daily for 7 days). Danicamtiv increased ATPase activity and calcium sensitivity in LV and LA myofibrils/muscle fibres. In dogs with heart failure, danicamtiv improved LV stroke volume (+10.6 mL, P &lt; 0.05) and LA emptying fraction (+10.7%, P &lt; 0.05). In patients with HFrEF (mean age 60 years, 25% women, ischaemic heart disease 48%, mean LV ejection fraction 32%), treatment‐emergent adverse events, mostly mild, were reported in 17 patients (57%) receiving danicamtiv and 4 patients (40%) receiving placebo. Danicamtiv (at plasma concentrations ≥2000 ng/mL) increased stroke volume (up to +7.8 mL, P &lt; 0.01), improved global longitudinal (up to −1.0%, P &lt; 0.05) and circumferential strain (up to −3.3%, P &lt; 0.01), decreased LA minimal volume index (up to −2.4 mL/m2, P &lt; 0.01) and increased LA function index (up to 6.1, P &lt; 0.01), when compared with placebo. Conclusions: Danicamtiv was well tolerated and improved LV systolic function in patients with HFrEF. A marked improvement in LA volume and function was also observed in patients with HFrEF, consistent with pre‐clinical findings of direct activation of LA contractility

Star Formation and Dynamics in the Galactic Centre

The centre of our Galaxy is one of the most studied and yet enigmatic places in the Universe. At a distance of about 8 kpc from our Sun, the Galactic centre (GC) is the ideal environment to study the extreme processes that take place in the vicinity of a supermassive black hole (SMBH). Despite the hostile environment, several tens of early-type stars populate the central parsec of our Galaxy. A fraction of them lie in a thin ring with mild eccentricity and inner radius ~0.04 pc, while the S-stars, i.e. the ~30 stars closest to the SMBH (<0.04 pc), have randomly oriented and highly eccentric orbits. The formation of such early-type stars has been a puzzle for a long time: molecular clouds should be tidally disrupted by the SMBH before they can fragment into stars. We review the main scenarios proposed to explain the formation and the dynamical evolution of the early-type stars in the GC. In particular, we discuss the most popular in situ scenarios (accretion disc fragmentation and molecular cloud disruption) and migration scenarios (star cluster inspiral and Hills mechanism). We focus on the most pressing challenges that must be faced to shed light on the process of star formation in the vicinity of a SMBH.Comment: 68 pages, 35 figures; invited review chapter, to be published in expanded form in Haardt, F., Gorini, V., Moschella, U. and Treves, A., 'Astrophysical Black Holes'. Lecture Notes in Physics. Springer 201

Moral courage in the workplace: moving to and from the desire and decision to act

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72135/1/j.1467-8608.2007.00484.x.pd

Serum potassium and outcomes in heart failure with preserved ejection fraction: a post-hoc analysis of the PARAGON-HF trial

Introduction: The relationship between serum potassium concentration and outcomes in patients with heart failure and preserved ejection fraction (HFpEF) is not well‐established. Aims: To explore the association between serum potassium and clinical outcomes in the PARAGON‐HF trial in which 4822 patients with HFpEF were randomised to treatment with sacubitril/valsartan or valsartan. Methods: The relationship between serum potassium concentrations and the primary study composite outcome of total (first and recurrent) heart failure hospitalisations and cardiovascular death was analysed. Hypo‐, normo‐, and hyperkalaemia were defined as serum potassium &lt;4 mmol/l, 4‐5 mmol/l and &gt;5 mmol/l, respectively. Both screening and time‐updated potassium (categorical and continuous spline‐transformed) were studied. Results: Patient mean age was 73 years and 52% were women. Patients with higher baseline potassium more often had an ischaemic aetiology and diabetes and MRA treatment. Compared with normokalaemia, both time‐updated (but not screening) hypo‐ and hyperkalaemia were associated with a higher risk of the primary outcome: adjusted HR (95%CI) for hypokalaemia=1.55 (1.30‐1.85); p&lt;0.001 and for hyperkalaemia=1.21 (1.02‐1.44); p=0.025. Hypokalaemia had a stronger association with a higher risk of all‐cause, cardiovascular and non‐cardiovascular death than hyperkalaemia. The association of hypokalaemia with increased risk of all‐cause and cardiovascular death was most marked in participants with impaired kidney function (interactionP&lt;0.05). Serum potassium did not significantly differ between sacubitril/valsartan and valsartan throughout the follow‐up. Conclusions: Both hypo‐ and hyperkalaemia were associated with heart failure hospitalisation but only hypokalaemia was associated with mortality, especially in the context of renal impairment. Hypokalaemia was as strongly associated with death from non‐cardiovascular causes as with cardiovascular death. Collectively, these findings suggest that potassium disturbances are a more of a marker of HFpEF severity rather than a direct cause of death