Bistable systems with stochastic noise: Virtues and limits of effective one-dimensional Langevin equations

The understanding of the statistical properties and of the dynamics of multistable systems is gaining more and more importance in a vast variety of scientific fields. This is especially relevant for the investigation of the tipping points of complex systems. Sometimes, in order to understand the time series of given observables exhibiting bimodal distributions, simple one-dimensional Langevin models are fitted to reproduce the observed statistical properties, and used to investing-ate the projected dynamics of the observable. This is of great relevance for studying potential catastrophic changes in the properties of the underlying system or resonant behaviours like those related to stochastic resonance-like mechanisms. In this paper, we propose a framework for encasing this kind of studies, using simple box models of the oceanic circulation and choosing as observable the strength of the thermohaline circulation. We study the statistical properties of the transitions between the two modes of operation of the thermohaline circulation under symmetric boundary forcings and test their agreement with simplified one-dimensional phenomenological theories. We extend our analysis to include stochastic resonance-like amplification processes. We conclude that fitted one-dimensional Langevin models, when closely scrutinised, may result to be more ad-hoc than they seem, lacking robustness and/or well-posedness. They should be treated with care, more as an empiric descriptive tool than as methodology with predictive power

Asymmetry and uncertainties in biogeophysical climate-vegetation feedback over a range of CO2 forcings

Climate–vegetation feedback has the potential to significantly contribute to climate change, but little is known about its range of uncertainties. Here, using an Earth system model of intermediate complexity we address possible uncertainties in the strength of the biogeophysical climate–vegetation feedback using a single-model multi-physics ensemble. Equilibrium experiments with halving (140 ppm) and doubling (560 ppm) of CO2 give a contribution of the vegetation–climate feedback to global temperature change in the range −0.3 to −0.1 °C and −0.1 to 0.2 °C, respectively. There is an asymmetry between warming and cooling, with a larger, positive vegetation–climate feedback in the lower CO2 climate. Hotspots of climate–vegetation feedback are the boreal zone, the Amazon rainforest and the Sahara. Albedo parameterization is the dominant source of uncertainty in the subtropics and at high northern latitudes, while uncertainties in evapotranspiration are more relevant in the tropics. We analyse the separate impact of changes in stomatal conductance, leaf area index and vegetation dynamics on climate and we find that different processes are dominant in lower and higher CO2 worlds. The reduction in stomatal conductance gives the main contribution to temperature increase for a doubling of CO2, while dynamic vegetation is the dominant process in the CO2 halving experiments. Globally the climate–vegetation feedback is rather small compared to the sum of the fast climate feedbacks. However, it is comparable to the amplitude of the fast feedbacks at high northern latitudes where it can contribute considerably to polar amplification. The uncertainties in the climate–vegetation feedback are comparable to the multi-model spread of the fast climate feedbacks

SDF1 Gene Variation Is Associated with Circulating SDF1 alpha Level and Endothelial Progenitor Cell Number-The Bruneck Study

BACKGROUND: Stromal cell-derived factor-1 (SDF1) and its receptor CXC chemokine receptor 4 (CXCR4) play a critical role in progenitor cell homing, mobilization and differentiation. It would be interesting to assess the predictive value of SDF-1alpha level for EPC number, and to ascertain whether there is a relationship between SDF1 gene variation, plasma SDF-1alpha level, and the number and function of circulating EPCs. We also tested whether EPC number and function was related to CXCR4 gene variation. METHODOLOGY AND PRINCIPAL FINDINGS: We genotyped a cohort of individuals who participated in the Bruneck Study for single nucleotide polymorphisms (SNPs) in the SDF1 and CXCR4 genes, and measured blood SDF1alpha level as well as EPC number and function. SDF1alpha levels were correlated with age, gender, alcohol consumption, circulating reticulocyte numbers, and concentrations of matrix metalloproteinase-9, C-reactive protein, cystatin C, fibrinogen and homocytein. In blood samples taken in 2005, EPC number was inversely associated with SDF1alpha level (p<0.001). EPC number in 2005 was also inversely associated with SDF1alpha level in 2000 (p = 0.009), suggesting a predictive value of plasma SDF1alpha level for EPC number. There was an association between the SDF1 gene rs2297630 SNP A/A genotype, increased SDF1alpha level (p = 0.002) and lower EPC number (p = 0.006). CONCLUSIONS: Our data indicate that a SDF1 gene variation (rs2297630) has an influence on SDF1alpha level and circulating EPC number, and that plasma SDF1alpha level is a predictor of EPC number

Association of serum-soluble heat shock protein 60 with carotid atherosclerosis: clinical significance determined in a follow-up study

BACKGROUND AND PURPOSE: Previous work has shown that soluble heat shock protein 60 (HSP60; sHSP60), present in circulating blood, is associated with carotid atherosclerosis. In the current evaluation, we tested the hypothesis that sHSP60 levels are associated with the progression of carotid arteriosclerosis, prospectively. METHODS: The association of sHSP60 with early atherogenesis (5-year development and progression of nonstenotic carotid plaques) was investigated as part of the population-based prospective Bruneck Study. The current study focused on the follow-up period between 1995 and 2000 and, thus, included 684 subjects. RESULTS: sHSP60 levels measured in 1995 and 2000 were highly correlated (r=0.40; P<0.001), indicating consistency over a 5-year period. Circulating HSP60 levels were significantly correlated with antilipopolysaccharide and anti-HSP60 antibodies. It was also elevated in subjects with chronic infection (top quintile group of HSP60, among subjects with and without chronic infection: 23.8% versus 17.0%; P=0.003 after adjustment for age and sex). HSP60 levels were significantly associated with early atherogenesis, both in the entire population (multivariate odds ratio, for a comparison between quintile group V versus I+II: 2.0 [1.2 to 3.5] and the subgroup free of atherosclerosis at the 1995 baseline: 3.8 [1.6 to 8.9]). The risk of early atherogenesis was additionally amplified when high-sHSP60 and chronic infection were present together. CONCLUSIONS: Our study provides the first prospective data confirming an association between high levels of sHSP60 and early carotid atherosclerosis. This possibly indicates an involvement of sHSP60 in activating proinflammatory processes associated with early vessel pathology

Mid-Pleistocene transition in glacial cycles explained by declining CO2 and regolith removal

Variations in Earth's orbit pace the glacial-interglacial cycles of the Quaternary, but the mechanisms that transform regional and seasonal variations in solar insolation into glacial-interglacial cycles are still elusive. Here, we present transient simulations of coevolution of climate, ice sheets, and carbon cycle over the past 3 million years. We show that a gradual lowering of atmospheric CO2 and regolith removal are essential to reproduce the evolution of climate variability over the Quaternary. The long-term CO2 decrease leads to the initiation of Northern Hemisphere glaciation and an increase in the amplitude of glacial-interglacial variations, while the combined effect of CO2 decline and regolith removal controls the timing of the transition from a 41,000- to 100,000-year world. Our results suggest that the current CO2 concentration is unprecedented over the past 3 million years and that global temperature never exceeded the preindustrial value by more than 2°C during the Quaternary

The role of CO2 decline for the onset of Northern Hemisphere glaciation

The Pliocene–Pleistocene Transition (PPT), from around 3.2 to 2.5 million years ago (Ma), represented a major shift in the climate system and was characterized by a gradual cooling trend and the appearance of large continental ice sheets over northern Eurasia and North America. Paleo evidence indicates that the PPT was accompanied and possibly caused by a decrease in atmospheric CO2, but the temporal resolution of CO2 reconstructions is low for this period of time and uncertainties remain large. Therefore, instead of applying existent CO2 reconstructions we solved an ‘inverse’ problem by finding a schematic CO2 concentration scenario that allows us to simulate the temporal evolution of key climate characteristics in agreement with paleoclimate records. To this end, we performed an ensemble of transient simulations with an Earth system model of intermediate complexity from which we derived a best guess transient CO2 scenario for the interval from 3.2 to 2.4 Ma that gives the best fit between the simulated and reconstructed benthic δ18O and global sea surface temperature evolution. Our data-constrained CO2 scenarios are consistent with recent CO2 reconstructions and suggest a gradual CO2 decline from 375–425 to 275–300 ppm, between 3.2 and 2.4 Ma. In addition to a gradual decline, the best fit to paleoclimate data requires the existence of pronounced CO2 variability coherent with the 41-kyr (1 kyr = 1000 years) obliquity cycle. In our simulations the long-term CO2 decline is accompanied by a relatively abrupt intensification of Northern Hemisphere glaciation at around 2.7 Ma. This is the result of a threshold behaviour of the ice sheets response to gradual CO2 decrease and orbital forcing. The simulated Northern Hemisphere ice sheets during the early Pleistocene glacial cycles reach a maximum volume equivalent to a sea level drop of about 40 m. Both ice volume and benthic δ18O are dominated by 41-kyr cyclicity. Our simulations suggest that before 2.7 Ma Greenland was ice free during summer insolation maxima and only partly ice covered during periods of minimum summer insolation. A fully glaciated Greenland comparable to its present-day ice volume is modelled only during glacial maxima after 2.7 Ma and more continuously after 2.5 Ma

Mid-Pleistocene transition in glacial cycles explained by declining CO2and regolith removal

Variations in Earth’s orbit pace the glacial-interglacial cycles of the Quaternary, but the mechanisms that transform regional and seasonal variations in solar insolation into glacial-interglacial cycles are still elusive. Here, we present transient simulations of coevolution of climate, ice sheets, and carbon cycle over the past 3 million years. We show that a gradual lowering of atmospheric CO2 and regolith removal are essential to reproduce the evolution of climate variability over the Quaternary. The long-term CO2 decrease leads to the initiation of Northern Hemisphere glaciation and an increase in the amplitude of glacial-interglacial variations, while the combined effect of CO2 decline and regolith removal controls the timing of the transition from a 41,000- to 100,000-year world. Our results suggest that the current CO2 concentration is unprecedented over the past 3 million years and that global temperature never exceeded the preindustrial value by more than 2°C during the Quaternary

Breastfeeding Is Associated With a Reduced Maternal Cardiovascular Risk:Systematic Review and Meta-Analysis Involving Data From 8 Studies and 1 192 700 Parous Women

BACKGROUND: Breastfeeding has been robustly linked to reduced maternal risk of breast cancer, ovarian cancer, and type 2 diabetes. We herein systematically reviewed the published evidence on the association of breastfeeding with maternal risk of cardiovascular disease (CVD) outcomes. METHODS AND RESULTS: Our systematic search of PubMed and Web of Science of articles published up to April 16, 2021, identified 8 relevant prospective studies involving 1 192 700 parous women (weighted mean age: 51.3 years at study entry, 24.6 years at first birth; weighted mean number of births: 2.3). A total of 982 566 women (82%) reported having ever breastfed (weighted mean lifetime duration of breastfeeding: 15.6 months). During a weighted median follow‐up of 10.3 years, 54 226 CVD, 26 913 coronary heart disease, 30 843 stroke, and 10 766 fatal CVD events were recorded. In a random‐effects meta‐analysis, the pooled multivariable‐adjusted hazard ratios comparing parous women who ever breastfed to those who never breastfed were 0.89 for CVD (95% CI, 0.83–0.95; I(2)=79.4%), 0.86 for coronary heart disease (95% CI, 0.78–0.95; I(2)=79.7%), 0.88 for stroke (95% CI, 0.79–0.99; I(2)=79.6%), and 0.83 for fatal CVD (95% CI, 0.76–0.92; I(2)=47.7%). The quality of the evidence assessed with the Grading of Recommendations Assessment, Development, and Evaluation tool ranged from very low to moderate, which was mainly driven by high between‐studies heterogeneity. Strengths of associations did not differ by mean age at study entry, median follow‐up duration, mean parity, level of adjustment, study quality, or geographical region. A progressive risk reduction of all CVD outcomes with lifetime durations of breastfeeding from 0 up to 12 months was found, with some uncertainty about shapes of associations for longer durations. CONCLUSIONS: Breastfeeding was associated with reduced maternal risk of CVD outcomes

Opioid-blunted cortisol response to stress is associated with increased negative mood and wanting of social reward

Animal research suggests a central role of the μ-opioid receptor (MOR) system in regulating affiliative behaviors and in mediating the stress-buffering function of social contact. However, the neurochemistry of stress-related social contact seeking in humans is still poorly understood. In a randomized, double-blind, between-subjects design, healthy female volunteers (N = 80) received either 10 mg of the µ-opioid agonist morphine sulfate, or a placebo. Following a standardized psychosocial stress induction, participants engaged in a social reward task, in which the motivation to obtain skin-to-skin social touch and the hedonic reactions elicited by such touch were assessed. Morphine prevented the increase of salivary cortisol typically observed following acute stress exposure. Notably, this altered HPA axis responsivity was associated with increased negative affect in response to psychosocial stress, and with enhanced subjective wanting of highly rewarding social contact. These findings provide novel evidence on the effect of exogenous opioids administration on the reactions to psychosocial stress and point to a state-dependent regulation of social motivation

Circulating MicroRNA-122 Is Associated With the Risk of New-Onset Metabolic Syndrome and Type 2 Diabetes

MicroRNA-122 (miR-122) is abundant in the liver and involved in lipid homeostasis, but its relevance to the long-term risk of developing metabolic disorders is unknown. We therefore measured circulating miR-122 in the prospective population-based Bruneck Study (n = 810; survey year 1995). Circulating miR-122 was associated with prevalent insulin resistance, obesity, metabolic syndrome, type 2 diabetes, and an adverse lipid profile. Among 92 plasma proteins and 135 lipid subspecies quantified with mass spectrometry, it correlated inversely with zinc-α-2-glycoprotein and positively with afamin, complement factor H, VLDL-associated apolipoproteins, and lipid subspecies containing monounsaturated and saturated fatty acids. Proteomics analysis of livers from antagomiR-122–treated mice revealed novel regulators of hepatic lipid metabolism that are responsive to miR-122 inhibition. In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT, n = 155), 12-month atorvastatin reduced circulating miR-122. A similar response to atorvastatin was observed in mice and cultured murine hepatocytes. Over up to 15 years of follow-up in the Bruneck Study, multivariable adjusted risk ratios per one-SD higher log miR-122 were 1.60 (95% CI 1.30–1.96; P < 0.001) for metabolic syndrome and 1.37 (1.03–1.82; P = 0.021) for type 2 diabetes. In conclusion, circulating miR-122 is strongly associated with the risk of developing metabolic syndrome and type 2 diabetes in the general population