MODULATION OF STRESS-INDUCED BEHAVIORS THROUGH OREXINERGIC SIGNALING IN THE BASOLATERAL AMYGDALA

Stress initiates behavioral disturbances, which are often seen as symptoms of psychiatric disorders, like post-traumatic stress disorder (PTSD), depression, and anxiety. While stress is involved in the formation of disordered states, only certain individuals are vulnerable to, and therefore experience, these outcomes. Further, females are more likely to be diagnosed with stress-induced psychiatric disorders. Elements within stress neurocircuitry offer insight into differential behavioral outcomes associated with stressful experiences; and the basolateral amygdala (BLA), where pro- and anti-stress signals are integrated, is likely an important mediator in phenotype development. The orexin system, too, while being strongly associated with sleep, motivation, and arousal, is critical for directing stress-induced responses. Produced in the hypothalamus, orexins (OrxA and OrxB) are released into the BLA where they target and activate two receptor subtypes: Orx1R and Orx2R. These receptors are found on different cells within BLA microcircuits, with Orx1R predominantly being localized to glutamatergic neurons and Orx2R having slightly higher expression in GABAergic cells. Pharmacological inhibition of Orx1R in the BLA rescues resilient behavior in stress vulnerable mice, while reducing fear freezing behavior, and promoting social learning. Alternatively, Orx2R inhibition in the BLA upsets fear learning in resilient populations, but enhances social avoidance. Alternatively, activation of Orx2R in BLA cells reduces fear freezing and increases social preference. Female mice exhibit unique behavioral patterns as a result of social stress compared to males, but phenotypic responses are observed when females are administered an Orx2R antagonist. While females have higher Orx2R expression in the BLA compared to males, pharmacological intervention with an Orx2R antagonist reveals even further distinctions within female behavioral phenotypes. Together, these results suggest the orexin system is important for defining behavioral outcomes after stress, and while sexual dimorphism exists in behavior and physiology, orexin receptor activity in the BLA appears to be a critical gating mechanism in both male and female stress-induced phenotype development

Reference Ranges of Left Ventricular Strain Measures by Two-Dimensional Speckle-Tracking Echocardiography in Children: A Systematic Review and Meta-Analysis

BACKGROUND: Establishment of the range of reference values and associated variations of two-dimensional speckle-tracking echocardiography (2DSTE)-derived left ventricular (LV) strain is a prerequisite for its routine clinical adoption in pediatrics. The aims of this study were to perform a meta-analysis of normal ranges of LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) measurements derived by 2DSTE in children and to identify confounding factors that may contribute to variance in reported measures. METHODS: A systematic review was launched in MEDLINE, Embase, Scopus, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library. Search hedges were created to cover the concepts of pediatrics, STE, and left-heart ventricle. Two investigators independently identified and included studies if they reported 2DSTE-derived LV GLS, GCS, or GRS. The weighted mean was estimated by using random effects models with 95% CIs, heterogeneity was assessed using the Cochran Q statistic and the inconsistency index (I(2)), and publication bias was evaluated using the Egger test. Effects of demographic (age), clinical, and vendor variables were assessed in a metaregression. RESULTS: The search identified 2,325 children from 43 data sets. The reported normal mean values of GLS among the studies varied from -16.7% to -23.6% (mean, -20.2%; 95% CI, -19.5% to -20.8%), GCS varied from -12.9% to -31.4% (mean, -22.3%; 95% CI, -19.9% to -24.6%), and GRS varied from 33.9% to 54.5% (mean, 45.2%; 95% CI, 38.3% to 51.7%). Twenty-six studies reported longitudinal strain only from the apical four-chamber view, with a mean of -20.4% (95% CI, -19.8% to -21.7%). Twenty-three studies reported circumferential strain (mean, -20.3%; 95% CI, -19.4% to -21.2%) and radial strain (mean, 46.7%; 95% CI, 42.3% to 51.1%) from the short-axis view at the midventricular level. A significant apex-to-base segmental longitudinal strain gradient (P 94% and P < .001 for each strain measure), which was not explained by age, gender, body surface area, blood pressure, heart rate, frame rate, frame rate/heart rate ratio, tissue-tracking methodology, location of reported strain value along the strain curve, ultrasound equipment, or software. The metaregression showed that these effects were not significant determinants of variations among normal ranges of strain values. There was no evidence of publication bias (P = .40). CONCLUSIONS: This study defines reference values of 2DSTE-derived LV strain in children on the basis of a meta-analysis. In healthy children, mean LV GLS was -20.2% (95% CI, -19.5% to -20.8%), mean GCS was -22.3% (95% CI, -19.9% to -24.6%), and mean GRS was 45.2% (95% CI, 38.3% to 51.7%). LV segmental longitudinal strain has a stable apex-to-base gradient that is preserved throughout maturation. Although variations among different reference ranges in this meta-analysis were not dependent on differences in demographic, clinical, or vendor parameters, age- and vendor-specific referenced ranges were established as well

Mapping Exoplanets

The varied surfaces and atmospheres of planets make them interesting places to live, explore, and study from afar. Unfortunately, the great distance to exoplanets makes it impossible to resolve their disk with current or near-term technology. It is still possible, however, to deduce spatial inhomogeneities in exoplanets provided that different regions are visible at different times---this can be due to rotation, orbital motion, and occultations by a star, planet, or moon. Astronomers have so far constructed maps of thermal emission and albedo for short period giant planets. These maps constrain atmospheric dynamics and cloud patterns in exotic atmospheres. In the future, exo-cartography could yield surface maps of terrestrial planets, hinting at the geophysical and geochemical processes that shape them.Comment: Updated chapter for Handbook of Exoplanets, eds. Deeg & Belmonte. 17 pages, including 6 figures and 4 pages of reference

Greenhushing: the deliberate under communicating of sustainability practices by tourism businesses

Greenhushing selectively communicates fewer pro-sustainability actions by businesses than are practiced; based on a perception of customers’ rights to consumerism. We first studied the gap between the communication of sustainability practices in the audits and websites of 31 small rural tourism businesses in the Peak District National Park (UK). The analysis showed that businesses only communicate 30% of all the sustainability actions practiced. Their websites emphasised customer benefits, using explicit, affective, experiential and active language that legitimises the customers’ hedonistic use of the landscape, while downplaying complex issues and normalising sustainability to reduce customer guilt. Just one website mentioned climate change. We found that greenhushing results from a low moral intensity, masking potentially negative consequences of perceived lower competence, whilst protecting business from more cynical consumers who may interpret their statements as hypocritical. Subsequent textual analysis and interviews were used to understand how communication constitutes these organisations. We propose that greenhushing reshapes and constitutes tourism businesses through their communications. Moreover, greenhushing is a form of public moralisation that adopts communication practices similar to greenwashing, reflecting the social norms expected from a business; however, in this case, located in a moral muteness, rather than moral hypocrisy, that businesses accept but resent

The Need for Laboratory Measurements and Ab Initio Studies to Aid Understanding of Exoplanetary Atmospheres

We are now on a clear trajectory for improvements in exoplanet observations that will revolutionize our ability to characterize their atmospheric structure, composition, and circulation, from gas giants to rocky planets. However, exoplanet atmospheric models capable of interpreting the upcoming observations are often limited by insufficiencies in the laboratory and theoretical data that serve as critical inputs to atmospheric physical and chemical tools. Here we provide an up-to-date and condensed description of areas where laboratory and/or ab initio investigations could fill critical gaps in our ability to model exoplanet atmospheric opacities, clouds, and chemistry, building off a larger 2016 white paper, and endorsed by the NAS Exoplanet Science Strategy report. Now is the ideal time for progress in these areas, but this progress requires better access to, understanding of, and training in the production of spectroscopic data as well as a better insight into chemical reaction kinetics both thermal and radiation-induced at a broad range of temperatures. Given that most published efforts have emphasized relatively Earth-like conditions, we can expect significant and enlightening discoveries as emphasis moves to the exotic atmospheres of exoplanets.Comment: Submitted as an Astro2020 Science White Pape

KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: poor prognosis in patients with KRAS-mutation and bone metastasis

Current guidelines lack comprehensive information on the metastatic site-specific role of KRAS mutation in lung adenocarcinoma (LADC). We investigated the effect of KRAS mutation on overall survival (OS) in this setting. In our retrospective study, 500 consecutive Caucasian metastatic LADC patients with known KRAS mutational status were analyzed after excluding 32 patients with EGFR mutations. KRAS mutation incidence was 28.6%. The most frequent metastatic sites were lung (45.6%), bone (26.2%), adrenal gland (17.4%), brain (16.8%), pleura (15.6%) and liver (11%). Patients with intrapulmonary metastasis had significantly increased KRAS mutation frequency compared to those with extrapulmonary metastases (35% vs 26.5%, p=0.0125). In contrast, pleural dissemination and liver involvement were associated with significantly decreased KRAS mutation incidence (vs all other metastatic sites; 17% (p<0.001) and 16% (p=0.02) vs 33%, respectively). Strikingly, we found a significant prognostic effect of KRAS status only in the bone metastatic subcohort (KRAS-wild-type vs KRAS-mutant; median OS 9.7v 3.7 months; HR, 0.49; 95% CI, 0.31 to 0.79; p =0.003). Our study suggests that KRAS mutation frequency in LADC patients shows a metastatic site dependent variation and, moreover, that the presence of KRAS mutation is associated with significantly worse outcome in bone metastatic cases.(VLID)469049

The Minimal Complexity of Adapting Agents Increases with Fitness

What is the relationship between the complexity and the fitness of evolved organisms, whether natural or artificial? It has been asserted, primarily based on empirical data, that the complexity of plants and animals increases as their fitness within a particular environment increases via evolution by natural selection. We simulate the evolution of the brains of simple organisms living in a planar maze that they have to traverse as rapidly as possible. Their connectome evolves over 10,000s of generations. We evaluate their circuit complexity, using four information-theoretical measures, including one that emphasizes the extent to which any network is an irreducible entity. We find that their minimal complexity increases with their fitness

Planet Eclipse Mapping with Long-Term Baseline Drifts

High precision lightcurves combined with eclipse mapping techniques can reveal the horizontal and vertical structure of a planet's thermal emission and the dynamics of hot Jupiters. Someday, they even may reveal the surface maps of rocky planets. However, inverting lightcurves into maps requires an understanding of the planet, star and instrumental trends because they can resemble the gradual flux variations as the planet rotates (ie. partial phase curves). In this work, we simulate lightcurves with baseline trends and assess the impact on planet maps. Baseline trends can be erroneously modeled by incorrect astrophysical planet map features, but there are clues to avoid this pitfall in both the residuals of the lightcurve during eclipse and sharp features at the terminator of the planet. Models that use a Gaussian process or polynomial to account for a baseline trend successfully recover the input map even in the presence of systematics but with worse precision for the m=1 spherical harmonic terms. This is also confirmed with the ThERESA eigencurve method where fewer lightcurve terms can model the planet without correlations between the components. These conclusions help aid the decision on how to schedule observations to improve map precision. If the m=1 components are critical, such as measuring the East/West hotspot shift on a hot Jupiter, better characterization of baseline trends can improve the m=1 terms' precision. For latitudinal North/South information from the remaining mapping terms, it is preferable to obtain high signal-to-noise at ingress/egress with more eclipses.Comment: AJ, accepted, 22 page

Earth as a Transiting Exoplanet: A Validation of Transmission Spectroscopy and Atmospheric Retrieval Methodologies for Terrestrial Exoplanets

The James Webb Space Telescope (JWST) will enable the search for and characterization of terrestrial exoplanet atmospheres in the habitable zone via transmission spectroscopy. However, relatively little work has been done to use solar system data, where ground truth is known, to validate spectroscopic retrieval codes intended for exoplanet studies, particularly in the limit of high resolution and high signal-to-noise (S/N). In this work, we perform such a validation by analyzing a high S/N empirical transmission spectrum of Earth using a new terrestrial exoplanet atmospheric retrieval model with heritage in Solar System remote sensing and gaseous exoplanet retrievals. We fit the Earth's 2-14 um transmission spectrum in low resolution (R=250 at 5 um) and high resolution (R=100,000 at 5 um) under a variety of assumptions about the 1D vertical atmospheric structure. In the limit of noiseless transmission spectra, we find excellent agreement between model and data (deviations < 10%) that enable the robust detection of H2O, CO2, O3, CH4, N2, N2O, NO2, HNO3, CFC-11, and CFC-12 thereby providing compelling support for the detection of habitability, biosignature, and technosignature gases in the atmosphere of the planet using an exoplanet-analog transmission spectrum. Our retrievals at high spectral resolution show a marked sensitivity to the thermal structure of the atmosphere, trace gas abundances, density-dependent effects, such as collision-induced absorption and refraction, and even hint at 3D spatial effects. However, we used synthetic observations of TRAPPIST-1e to verify that the use of simple 1D vertically homogeneous atmospheric models will likely suffice for JWST observations of terrestrial exoplanets transiting M dwarfs.Comment: 37 pages, 14 figures, 9 tables. Accepted for publication in PS