In patients with uncomplicated essential hypertension, cardiac output remains within normal ranges and intravascular volume is normal or low, assuming the presence of a sufficient Windkessel effect ...and usual resistance and compliance calculations. However, mean circulatory pressure is elevated in these patients. In addition, vascular resistance is augmented, and most importantly, the viscoelasticity of the cardiovascular system is substantially impaired. Such considerations are essential to understanding the mechanisms behind carotid-femoral arterial stiffness, a major risk factor in individuals with hypertension. Arterial stiffness, measured from pulse wave velocity, is substantially increased in hypertension even independently of blood pressure levels. Structural vascular changes and endothelial dysfunction are consistently associated with vessel impairments in animal models of hypertension. Increased arterial stiffness has a major effect on pulse pressure (the difference between systolic and diastolic blood pressure), wave reflections, kidney function, and above all, cardiovascular risk. This increased cardiovascular risk is particularly deleterious in patients with hypertension and/or type 2 diabetes mellitus, who are at risk of both renal and cardiovascular events. In this Review, we discuss the importance of arterial stiffness in the diagnosis and management of hypertension and the need for new approaches for the treatment of hypertension in patients with or without diabetes and/or renal impairment.
The prospects for using fiber optical parametric amplifiers (OPAs) in optical communication systems are reviewed. Phase‐insensitive amplifiers (PIAs) and phase‐sensitive amplifiers (PSAs) are ...considered. Low‐penalty amplification at/or near 1 Tb/s has been achieved, for both wavelength‐ and time‐division multiplexed formats. High‐quality mid‐span spectral inversion has been demonstrated at 0.64 Tb/s, avoiding electronic dispersion compensation. All‐optical amplitude regeneration of amplitude‐modulated signals has been performed, while PSAs have been used to demonstrate phase regeneration of phase‐modulated signals. A PSA with 1.1‐dB noise figure has been demonstrated, and preliminary wavelength‐division multiplexing experiments have been performed with PSAs. 512 Gb/s have been transmitted over 6,000 km by periodic phase conjugation. Simulations indicate that PIAs could reach data rate x reach products in excess of 14,000 Tb/s × km in realistic wavelength‐division multiplexed long‐haul networks. Technical challenges remaining to be addressed in order for fiber OPAs to become useful for long‐haul communication networks are discussed.
The prospects for using fiber optical parametric amplifiers in optical communication systems are reviewed. All‐optical amplitude or phase regeneration can be performed. A PSA with 1.1 dB noise figure has been demonstrated. 512 Gb/s have been transmitted over 6,000 km by periodic phase conjugation. Simulations indicate the potential for transmitting multi‐Tb/s signals over thousands of kilometres. Technical challenges are discussed.
From 2007 to 2013, the globally averaged mole fraction of methane in the atmosphere increased by 5.7 ± 1.2 ppb yr−1. Simultaneously, δ13CCH4 (a measure of the 13C/12C isotope ratio in methane) has ...shifted to significantly more negative values since 2007. Growth was extreme in 2014, at 12.5 ± 0.4 ppb, with a further shift to more negative values being observed at most latitudes. The isotopic evidence presented here suggests that the methane rise was dominated by significant increases in biogenic methane emissions, particularly in the tropics, for example, from expansion of tropical wetlands in years with strongly positive rainfall anomalies or emissions from increased agricultural sources such as ruminants and rice paddies. Changes in the removal rate of methane by the OH radical have not been seen in other tracers of atmospheric chemistry and do not appear to explain short‐term variations in methane. Fossil fuel emissions may also have grown, but the sustained shift to more 13C‐depleted values and its significant interannual variability, and the tropical and Southern Hemisphere loci of post‐2007 growth, both indicate that fossil fuel emissions have not been the dominant factor driving the increase. A major cause of increased tropical wetland and tropical agricultural methane emissions, the likely major contributors to growth, may be their responses to meteorological change.
Plain Language Summary
Atmospheric methane, which is a powerful greenhouse gas, is increasing rapidly. In the 20th century, methane growth was primarily driven by emissions from fossil fuel sources, such as the natural gas industry and coal mining. Then, in the early years of the 21st century, came a period of stability in methane. However, since 2007, growth has resumed, with especially strong growth in 2014. Evidence from carbon isotopes implies that the primary cause of the new growth is an increase in biogenic emissions, probably from wetlands and also agricultural sources, such as rice fields and cattle. The evidence presented in this research study, from a wide range of measurement sites both in the northern and southern hemispheres, suggests increased tropical emissions, for example from tropical wetlands, may be a principal cause of the global rise in methane. Contributions to the growth may also come from agricultural sources and perhaps some fossil fuel emissions also.
Key Points
Atmospheric methane is growing rapidly
Isotopic evidence implies that the growth is driven by biogenic sources
Growth is dominated by tropical sources
Atmospheric methane grew very rapidly in 2014 (12.7 ± 0.5 ppb/year), 2015 (10.1 ± 0.7 ppb/year), 2016 (7.0 ± 0.7 ppb/year), and 2017 (7.7 ± 0.7 ppb/year), at rates not observed since the 1980s. The ...increase in the methane burden began in 2007, with the mean global mole fraction in remote surface background air rising from about 1,775 ppb in 2006 to 1,850 ppb in 2017. Simultaneously the 13C/12C isotopic ratio (expressed as δ13CCH4) has shifted, now trending negative for more than a decade. The causes of methane's recent mole fraction increase are therefore either a change in the relative proportions (and totals) of emissions from biogenic and thermogenic and pyrogenic sources, especially in the tropics and subtropics, or a decline in the atmospheric sink of methane, or both. Unfortunately, with limited measurement data sets, it is not currently possible to be more definitive. The climate warming impact of the observed methane increase over the past decade, if continued at >5 ppb/year in the coming decades, is sufficient to challenge the Paris Agreement, which requires sharp cuts in the atmospheric methane burden. However, anthropogenic methane emissions are relatively very large and thus offer attractive targets for rapid reduction, which are essential if the Paris Agreement aims are to be attained.
Plain Language Summary
The rise in atmospheric methane (CH4), which began in 2007, accelerated in the past 4 years. The growth has been worldwide, especially in the tropics and northern midlatitudes. With the rise has come a shift in the carbon isotope ratio of the methane. The causes of the rise are not fully understood, and may include increased emissions and perhaps a decline in the destruction of methane in the air. Methane's increase since 2007 was not expected in future greenhouse gas scenarios compliant with the targets of the Paris Agreement, and if the increase continues at the same rates it may become very difficult to meet the Paris goals. There is now urgent need to reduce methane emissions, especially from the fossil fuel industry.
Key Points
Atmospheric methane is rising; its carbon isotopic ratio has become more depleted in C‐13
The possible causes of the change include an increase in emissions, with changing relative proportions of source inputs, or a decline in methane destruction, or both
If this rise continues, there are significant consequences for the UN Paris Agreement
Context. Asteroseismology allows us to probe stellar interiors. In the case of red giant stars, conditions in the stellar interior are such as to allow for the existence of mixed modes, consisting in ...a coupling between gravity waves in the radiative interior and pressure waves in the convective envelope. Mixed modes can thus be used to probe the physical conditions in red giant cores. However, we still need to identify the physical mechanisms that transport angular momentum inside red giants, leading to the slow-down observed for red giant core rotation. Thus large-scale measurements of red giant core rotation are of prime importance to obtain tighter constraints on the efficiency of the internal angular momentum transport, and to study how this efficiency changes with stellar parameters. Aims. This work aims at identifying the components of the rotational multiplets for dipole mixed modes in a large number of red giant oscillation spectra observed by Kepler. Such identification provides us with a direct measurement of the red giant mean core rotation. Methods. We compute stretched spectra that mimic the regular pattern of pure dipole gravity modes. Mixed modes with the same azimuthal order are expected to be almost equally spaced in stretched period, with a spacing equal to the pure dipole gravity mode period spacing. The departure from this regular pattern allows us to disentangle the various rotational components and therefore to determine the mean core rotation rates of red giants. Results. We automatically identify the rotational multiplet components of 1183 stars on the red giant branch with a success rate of 69% with respect to our initial sample. As no information on the internal rotation can be deduced for stars seen pole-on, we obtain mean core rotation measurements for 875 red giant branch stars. This large sample includes stars with a mass as large as 2.5 M⊙, allowing us to test the dependence of the core slow-down rate on the stellar mass. Conclusions. Disentangling rotational splittings from mixed modes is now possible in an automated way for stars on the red giant branch, even for the most complicated cases, where the rotational splittings exceed half the mixed-mode spacing. This work on a large sample allows us to refine previous measurements of the evolution of the mean core rotation on the red giant branch. Rather than a slight slow-down, our results suggest rotation is constant along the red giant branch, with values independent of the mass.
Retinoic acid–related orphan receptor (ROR)-γt, the master transcription factor of the Th17 subset of CD4+ Th cells, is a promising target for treating a host of autoimmune diseases. RORγt plays a ...vital role in the pathogenesis of inflammatory bowel diseases—Crohn disease and ulcerative colitis—caused by untoward reactivity of the immune system to the components of the intestinal microbiome. The mammalian intestinal tract is a highly complex and compartmentalized organ with specialized functions, and is a privileged site for the generation of both peripherally induced regulatory CD4+ T cells (Tregs) and effector Th17 cells. As Th17 cells can be proinflammatory in nature, the equilibrium between effector Th17 and Treg cells is crucial for balancing intestinal homeostasis and inflammation. Recent findings suggest that RORγt, in addition to Th17 cells, is also expressed in peripherally induced, colonic regulatory CD4+ T cells. Therefore, RORγt is expressed in both effector and regulatory subsets of CD4+ T cells in the intestine. The present review discusses the role of RORγt in cellular and molecular differentiation of Th17 and Treg, and examines how targeting RORγt in inflammatory bowel disease therapy could influence the development of these two diverse subsets of immune cells with opposing functions.
Purpose
Due to the increasing demand for intensive care unit (ICU) treatment, and to improve quality and efficiency of care, there is a need for adequate and efficient clinical decision-making. The ...advancement of artificial intelligence (AI) technologies has resulted in the development of prediction models, which might aid clinical decision-making. This systematic review seeks to give a contemporary overview of the current maturity of AI in the ICU, the research methods behind these studies, and the risk of bias in these studies.
Methods
A systematic search was conducted in Embase, Medline, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases to identify eligible studies. Studies using AI to analyze ICU data were considered eligible. Specifically, the study design, study aim, dataset size, level of validation, level of readiness, and the outcomes of clinical trials were extracted. Risk of bias in individual studies was evaluated by the Prediction model Risk Of Bias ASsessment Tool (PROBAST).
Results
Out of 6455 studies identified through literature search, 494 were included. The most common study design was retrospective 476 studies (96.4% of all studies) followed by prospective observational 8 (1.6%) and clinical 10 (2%) trials. 378 (80.9%) retrospective studies were classified as high risk of bias. No studies were identified that reported on the outcome evaluation of an AI model integrated in routine clinical practice.
Conclusion
The vast majority of developed ICU-AI models remain within the testing and prototyping environment; only a handful were actually evaluated in clinical practice. A uniform and structured approach can support the development, safe delivery, and implementation of AI to determine clinical benefit in the ICU.
Context. The solar-like pulsator HD 49385 was observed with the CoRoT⋆ satellite over a period of 137 days. The analysis of its oscillation spectrum yielded precise estimates of the mode frequencies ...over nine radial orders and distinguished some unusual characteristics, such as some modes outside the identified ridges in the échelle diagram and that the curvature of the ℓ = 1 ridge differs significantly from that of the ℓ = 0 ridge. Aims. We search for stellar models that can reproduce the peculiar features of the oscillation spectrum of HD 49385. After showing that they can be accounted for only by a low-frequency ℓ = 1 avoided crossing, we investigate the information provided by the mixed modes about the structure of the core of HD 49385. Methods. We propose a toy-model to study the case of avoided crossings with a strong coupling between the p-mode and g-mode cavities in order to establish the presence of mixed modes in the spectrum of HD 49385. We then show that traditional optimization techniques are ill-suited to stars with mixed modes in avoided crossing. We propose a new approach to the computation of grids of models that we apply to HD 49385. Results. The detection of mixed modes leads us to establish the post-main-sequence status of HD 49385. The mixed mode frequencies suggest that there is a strong coupling between the p-mode and g-mode cavities. As a result, we show that the amount of core overshooting in HD 49385 is either very small (0 < αov < 0.05) or moderate (0.18 < αov < 0.20). The mixing length parameter is found to be significantly lower than the solar one (αCGM = 0.55 ± 0.04 compared to the solar value α⊙ = 0.64). Finally, we show that the revised solar abundances of Asplund ensure closer agreement with the observations than the classical ones of Grevesse & Noels. At each step, we investigate the origin and meaning of these seismic diagnostics in terms of the physical structure of the star. Conclusions. The subgiant HD 49385 is the first star for which a thorough modeling has been attempted to reproduce all the properties of an avoided crossing. It has provided the opportunity to show that the study of the coupling between the cavities in these stars can provide valuable insight into open questions such as core overshooting, the efficiency of convection, and the abundances of heavy elements in stars.
Abstract
BACKGROUND
Arterial stiffness—typically assessed from non-invasive measurement of pulse wave velocity along a straight portion of the vascular tree between the right common carotid and ...femoral arteries—is a reliable predictor of cardiovascular risk in patients with essential hypertension.
METHODS
We reviewed how carotid-femoral pulse wave velocity increases with age and is significantly higher in hypertension (than in age- and gender-matched individuals without hypertension), particularly when hypertension is associated with diabetes mellitus.
RESULTS
From the elastic aorta to the muscular peripheral arteries of young healthy individuals, there is a gradual but significant increase in stiffness, with a specific gradient. This moderates the transmission of pulsatile pressure towards the periphery, thus protecting the microcirculatory network. The heterogeneity of stiffness between the elastic and muscular arteries causes the gradient to disappear or be inversed with aging, particularly in long-standing hypertension.
CONCLUSIONS
In hypertension therefore, pulsatile pressure transmission to the microcirculation is augmented, increasing the potential risk of damage to the brain, the heart, and the kidney. Furthermore, elevated pulse pressure exacerbates end-stage renal disease, particularly in older hypertensive individuals. With increasing age, the elastin content of vessel walls declines throughout the arterial network, and arterial stiffening increases further due to the presence of rigid wall material such as collagen, but also fibronectin, proteoglycans, and vascular calcification. Certain genes, mainly related to angiotensin and/or aldosterone, affect this aging process and contribute to the extent of arterial stiffness, which can independently affect both forward and reflected pressure waves.
In patients with both hypertension and type II diabetes, the systolic blood pressure (SBP) increases linearly with age, while that of diastolic blood pressure (DBP) declines curvilinearly as early as ...age 45, all suggesting the development of increased arterial stiffness. Increased stiffness is an important, independent, and significant risk predictor in subjects with hypertension and diabetes. In patients with both diseases, stiffness assessed at the same mean arterial pressure (MAP) was significantly higher in diabetic patients. Arterial stiffness is related to age, heart rate (HR), and MAP, but in diabetic patients, it also related to diabetes duration and insulin treatment (IT). In the metabolic syndrome (MetSyn), diabetes also acts on the small arteries through capillary rarefaction to reduce the effective length of the arterial tree, increases the reflected pulse wave and thus the pulse pressure (PP). These studies indicate that diabetes and hypertension additively contribute to increased pulsatility and suggest that any means to reduce stiffness would be beneficial in these conditions.
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