Abstract
Financial sector wages have increased extraordinarily over the last decades. We address two potential explanations for this increase: (1) rising demand for talent and (2) firms sharing rents ...with their employees. Matching administrative data of Swedish workers, which include unique measures of individual talent, with financial information on their employers, we find no evidence that talent in finance improved, neither on average nor at the top. The increase in relative finance wages is present across talent and education levels, which together can explain at most 20% of it. In contrast, rising financial sector profits that are shared with employees account for up to half of the relative wage increase. The limited labour supply response may partly be explained by the importance of early-career entry and social connections in finance. Our findings alleviate concerns about “brain drain” into finance but suggest that finance workers have captured rising rents over time.
Hypercholesterolemia is a major risk factor for cardiovascular diseases, increasing the incidence of myocardial infarction and death. Statin-induced lowering of low-density lipoprotein cholesterol ...(LDL-C) reduces cardiovascular morbidity and mortality. However, many individuals treated with statins do not achieve their target levels of LDL-C, and thus, LDL-associated residual risk remains. Gain-of-function mutations of the proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with hypercholesterolemia and increased risk of cardiovascular events. Conversely, loss-of-function mutations are linked to low plasma LDL-C levels and a reduction of cardiovascular risk without known unwanted effects on individual health. Experimental studies have revealed that PCSK9 reduces the hepatic uptake of LDL-C by increasing the endosomal and lysosomal degradation of LDL receptors (LDLR). Low intracellular cholesterol levels in response to statin treatment activate the sterol regulatory element-binding protein-2 (SREBP-2), resulting in coexpression of LDLR and PCSK9. Although this self-regulatory mechanism contributes to maintain cholesterol homeostasis preventing excessive cholesterol uptake, it may limit the therapeutic effect of statins. A number of clinical studies have demonstrated that inhibition of PCSK9 alone and in addition to statins potently reduces serum LDL-C concentrations. Moreover, experimental studies indicate that PCSK9 might accelerate atherosclerosis by promoting inflammation, endothelial dysfunction, and hypertension by mechanisms independent of the LDLR. Further research is needed to characterize the potential therapeutic and to rule out unwanted off-target effects of PCSK9 inhibition. In this review we elucidate the role of PCSK9 in lipid homeostasis, highlight the impact of PCSK9 on atherosclerosis, and summarize current therapeutic strategies targeting PCSK9.
Silica nanoparticles (NPs) embedded in atactic polystyrene (PS) are simulated using coarse-grained (CG) potentials obtained via iterative Boltzmann inversion (IBI). The potentials are parametrized ...and validated on polystyrene of 2 kDa (i.e., chains containing 20 monomers). It is shown that the CG potentials are transferable between different systems. The structure of the polymer chains is strongly influenced by the NP. Layering, chain expansion, and preferential orientation of segments as well as of entire chains are found. The extent of the structural perturbation depends on the details of the system: bare NPs vs NPs grafted with PS chains, grafting density (0, 0.5, and 1 chains/nm2), length of the grafted chains (2 and 8 kDa), and the matrix chains (2–20 kDa). For example, there is a change in the swelling state for the grafted corona (8 kDa, 1 chains/nm2), when the matrix polymer is changed from 2 to > 8 kDa. This phenomenon, sometimes called “wet brush to dry brush transition”, is in good agreement with neutron scattering investigations. Another example is the behavior of the radius of gyration of free polymer chains close to the NP. Short chains expand compared to the bulk, whereas chains whose unperturbed radius of gyration is larger than that of the NP contract.
Summary Remodelling is a response of the myocardium and vasculature to a range of potentially noxious haemodynamic, metabolic, and inflammatory stimuli. Remodelling is initially functional, ...compensatory, and adaptive but, when sustained, progresses to structural changes that become self-perpetuating and pathogenic. Remodelling involves responses not only of the cardiomyocytes, endothelium, and vascular smooth muscle cells, but also of interstitial cells and matrix. In this Review we characterise the remodelling processes in atherosclerosis, vascular and myocardial ischaemia–reperfusion injury, and heart failure, and we draw attention to potential avenues for innovative therapeutic approaches, including conditioning and metabolic strategies.
OBJECTIVE:--To assess whether sex differences exist in the effective control and medication treatment intensity of cardiovascular disease (CVD) risk factors. RESEARCH DESIGN AND METHODS--We performed ...a cross-sectional analysis including 44,893 patients with type 2 diabetes (51% women). End points included uncontrolled CVD risk factors (LDL cholesterol >=130 mg/dl, systolic blood pressure SBP >=140 mmHg, and A1C >=8%) and the intensity of medical management in patients with uncontrolled CVD risk factors. Multiple-adjusted odds ratios were calculated after stratification for the presence of CVD (present in 39% of the patients). RESULTS:--Women with CVD were less likely to have SBP, LDL cholesterol, and A1C controlled and less likely to receive intensive lipid-lowering treatment. Women without CVD were less likely than men to have LDL cholesterol controlled with no differences in SBP or A1C control. CONCLUSIONS:--Women with diabetes and CVD have poorer control of important modifiable risk factors than men and receive less intensified lipid-lowering treatment.
We cast the acceleration of the dynamics of coarse-grained polymer models, or, conversely, the decrease in monomer friction in terms of excess entropy differences between different coarse-grained ...resolutions. From a simple bead–spring model of unentangled polymers in a melt, we systematically derive two coarse-grained models of different resolutions, for which exact excess entropies are obtained through a carefully carried out two-step thermodynamic integration. We found that the excess entropy differences between the coarser and finer models correlated well with the logarithm of the ratio of dynamical properties quantifying the acceleration upon changing the model resolution. Moreover, we have considered how well the two-body approximation to the excess entropy is correlated and also the scaling of the excess entropy in the analysis. Our results indicate that the acceleration brought about by coarse-graining can be understood in terms of excess entropy differences for unentangled polymers also. The correlations presented in this work may open new possibilities to a posteriori correct the coarse-graining dynamics by a simple route.
Using spectral domain optical coherence tomography (SD-OCT) the retina can be segmented automatically to visualize all retinal layers. In glaucoma chronically elevated intraocular pressure leads to a ...decline of retinal ganglion cells (RGC) which changes retinal architecture. The goal of these analyses was to gain insight into the changes induced by glaucoma within all macular layers using SD-OCT within a closely circumscribed glaucoma cohort.
SD-OCT measurements with automated retinal layer segmentation were performed in both eyes of primary open-angle glaucoma patients with a defined monocular absolute visual field scotoma in the central 10° of the visual field and in an age-matched healthy control group. Thickness of single retinal layers and entire retina were compared with special attention to the localization of the visual field scotoma in the glaucomatous eyes.
30 eyes of 15 glaucoma patients and 15 eyes of 15 healthy controls were included in this study. Statistical significant thickness differences were detected in the control group between superior and inferior retina for the retinal nerve fiber layer (RNFL), the outer plexiform layer (OPL) and the outer nuclear layer (ONL). In the glaucoma group thickness differences between worse and less affected eyes in the RNFL, the ganglion cell layer (GCL) and the inner plexiform layers (INL) were found. Comparison between healthy and diseased eyes revealed significant thickness differences in the RNFL, GCL, IPL and total retinal thickness but not the outer retinal layers.
Comparison between SD-OCT measurements of the macula between healthy and glaucomatous eyes in a closely circumscribed disease stage showed a pronounced disease impact on the inner but not the outer retina. These results provide evidence that GCL and IPL thickness seem to be good measures to discriminate between affected and unaffected eyes in testing for glaucoma.
Oxidative stress is causally linked to the progression of heart failure, and mitochondria are critical sources of reactive oxygen species in failing myocardium. We previously observed that in heart ...failure, elevated cytosolic Na(+) (Na(+)(i)) reduces mitochondrial Ca(2+) (Ca(2+)(m)) by accelerating Ca(2+) efflux via the mitochondrial Na(+)/Ca(2+) exchanger. Because the regeneration of antioxidative enzymes requires NADPH, which is indirectly regenerated by the Krebs cycle, and Krebs cycle dehydrogenases are activated by Ca(2+)(m), we speculated that in failing myocytes, elevated Na(+)(i) promotes oxidative stress.
We used a patch-clamp-based approach to simultaneously monitor cytosolic and mitochondrial Ca(2+) and, alternatively, mitochondrial H(2)O(2) together with NAD(P)H in guinea pig cardiac myocytes. Cells were depolarized in a voltage-clamp mode (3 Hz), and a transition of workload was induced by beta-adrenergic stimulation. During this transition, NAD(P)H initially oxidized but recovered when Ca(2+)(m) increased. The transient oxidation of NAD(P)H was closely associated with an increase in mitochondrial H(2)O(2) formation. This reactive oxygen species formation was potentiated when mitochondrial Ca(2+) uptake was blocked (by Ru360) or Ca(2+) efflux was accelerated (by elevation of Na(+)(i)). In failing myocytes, H(2)O(2) formation was increased, which was prevented by reducing mitochondrial Ca(2+) efflux via the mitochondrial Na(+)/Ca(2+) exchanger.
Besides matching energy supply and demand, mitochondrial Ca(2+) uptake critically regulates mitochondrial reactive oxygen species production. In heart failure, elevated Na(+)(i) promotes reactive oxygen species formation by reducing mitochondrial Ca(2+) uptake. This novel mechanism, by which defects in ion homeostasis induce oxidative stress, represents a potential drug target to reduce reactive oxygen species production in the failing heart.
We have extended a recently developed multichain slip-spring approach to polymer solutions. The method is based on the dissipative particle dynamics (DPD). Entanglements are mimicked by the inclusion ...of slip-springs that connect polymer beads, slide along their contour, and are created/destroyed at chain ends. The required average number of slip-springs in polymer melts can be adjusted by the chemical potential. In solutions, we assume that the chemical potential and the friction of slip-springs are constant regardless of the polymer volume fraction. We have evaluated the proposed method by a comparison with experimental data. For this purpose, we have performed dynamic viscoelastic measurements for polystyrene/tricresyl phosphate solutions. The linear viscoelastic spectra are in reasonable agreement including the plateau modulus given that the comparison is made for a reduced frequency normalized by the Rouse time. The dependence of the slip-spring friction and the chemical potential of slip-springs on the polymer volume fraction may be considered for further improvement of the model.
Abstract Resting heart rate is central to cardiac output and is influenced by changes occurring in numerous diseases. It predicts longevity and cardiovascular diseases, and current evidence suggests ...that it is also an important marker of outcome in cardiovascular disease, including heart failure. Beta-blockers improve outcomes in heart failure; however, they have effects outside reducing heart rate. Ivabradine has demonstrated efficacy in reducing rehospitalizations and mortality in heart failure and in improving exercise tolerance and reducing angina attacks in patients with coronary artery disease, whereas selective heart rate reduction may also prove to be beneficial in therapeutic areas outside those in which ivabradine has already demonstrated clinical efficacy. This review provides an update on the associations between heart rate and cardiovascular outcomes in various conditions, the experimental effects of heart rate reduction with ivabradine, and the potential new indications in cardiovascular disease.
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