4pi Models of CMEs and ICMEs

Coronal mass ejections (CMEs), which dynamically connect the solar surface to the far reaches of interplanetary space, represent a major anifestation of solar activity. They are not only of principal interest but also play a pivotal role in the context of space weather predictions. The steady improvement of both numerical methods and computational resources during recent years has allowed for the creation of increasingly realistic models of interplanetary CMEs (ICMEs), which can now be compared to high-quality observational data from various space-bound missions. This review discusses existing models of CMEs, characterizing them by scientific aim and scope, CME initiation method, and physical effects included, thereby stressing the importance of fully 3-D ('4pi') spatial coverage.Comment: 14 pages plus references. Comments welcome. Accepted for publication in Solar Physics (SUN-360 topical issue

Female rat sexual behavior is unaffected by perinatal fluoxetine exposure

Serotonin plays an important role in adult female sexual behavior, however little is known about the influence of serotonin during early development on sexual functioning in adulthood. During early development, serotonin acts as neurotrophic factor, while it functions as a modulatory neurotransmitter in adulthood. The occurrence of serotonin release, could thus have different effects on behavioral outcomes, depending on the developmental period in which serotonin is released. Because serotonin is involved in the development of the HPG axis which is required for puberty establishment, serotonin could also alter expression patterns of for instance the estrogen receptor ɑ (ERɑ). The aim of our study was to investigate the effects of increased serotonin levels during early development on adult female rat sexual behavior during the full behavioral estrus in a seminatural environment. To do so, rats were perinatally exposed with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (10 mg/kg FLX) and sexual performance was tested during adulthood. All facets of female sexual behavior between the first and last lordosis (behavioral estrus), and within each copulation bout of the behavioral estrus were analyzed. Besides the length and onset of the behavioral estrus and the sexual behaviors patterns, other social and conflict behavior were also investigated. In addition, we studied the effects of perinatal FLX exposure on ERɑ expression patterns in the medial preoptic nucleus, ventromedial nucleus of the hypothalamus, medial amygdala, bed nucleus of the stria terminalis, and the dorsal raphé nucleus. The results showed that perinatal fluoxetine exposure has no effect on adult female sexual behavior. The behavioral estrus of FLX-females had the same length and pattern as CTR-females. In addition, FLX- and CTR-females showed the same amount of paracopulatory behavior and lordosis, both during the full behavioral estrus and the "most active bout". Furthermore, no differences were found in the display of social and conflict behaviors, nor in ERɑ expression patterns in the brain. We conclude that increases in serotonin levels during early development do not have long-term consequences for female sexual behavior in adulthood.</p

Influencers on the Russian Twitter: Institutions vs. people in the discussion on migrants

With the emergence of discussion platforms like Twitter, the hopes rose that computer-mediated public sphere would become more even in access to discussion than mass-mediatized public sphere of the late 20th century. Scholars have argued that it will eventually form an ‘opinion crossroads’ where conflicts would be discussed by all the parties involved. But today, existing research provides mixed evidence on whether ordinary users, rather than mainstream media and institutional actors, can become influencers in discussions on current issues, e.g. relations between host and migrant communities. We focus on the Twitter discussion about an inter-ethnic conflict in Moscow’s Biryuliovo district in 2013 and aim at defining who were its real influencers by reconstructing the discussion’s web graph, as well as analyzing and juxtaposing its metrics to figures indicating user activity. Our results show that, despite hyperactivity of media accounts, they were largely absent as deliberative influencers, but the place of influencers was occupied by politicized (nationalist and liberal) accounts, rather by eyewitness reporters or public figures.This research has been supported in full by Russian Science Foundation (research grant 16-18-10125)

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

Subcortical volumes across the lifespan: data from 18,605 healthy individuals aged 3-90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.Education and Child Studie

Mechanisms responsible for sympathetic activation by cigarette smoking in humans

Background The presser and tachycardic effects of cigarette smoking are associated with an increase in plasma catecholamines, suggesting the dependence of these effects on adrenergic stimulation. Whether the stimulation occurs at a central or a peripheral level and whether reflex mechanisms are involved is unknown. Methods and Results In nine normotensive healthy subjects (age, 33.0+/-3.5 years, mean+/-SEM), we measured blood pressure (Finapres device), heart rate (ECG), calf blood how and vascular resistance (venous occlusion plethysmography), plasma norepinephrine and epinephrine (high-performance liquid chromatography assay), and postganglionic muscle sympathetic nerve activity (microneurography from the peroneal nerve) while subjects were smoking,a filter cigarette (nicotine content, 1.1 mg) or were in control condition. Cigarette smoking (which raised plasma nicotine measured by highperformance liquid chromatography from 1.0+/-0.9 to 44.2+/-7.1 ng/mL) markedly and significantly increased mean arterial pressure (+13.2+/-2.3%), heart rate (+30.3+/-4.7%), calf vascular resistance (+12.1+/-4.9%), plasma norepinephrine (+34.8+/-7.0%), and plasma epinephrine (+90.5+/-39.0%). In contrast, muscle sympathetic nerve activity showed a marked reduction (integrated activity -31.8+/-5.1%, P<.01). The reduction was inversely related to the increase in mean arterial pressure (r=-.67, P<.05), but the slope of the relation was markedly less (-54.1+/-7.5%, P<.05) than that obtained by intravenous infusion of phenylephrine in absence of smoking. The hemodynamic and neurohumoral changes were still visible 30 minutes after smoking and occurred again on smoking a second cigarette. Sham smoking was devoid of any hemodynamic and neurohumoral effect. Conclusions These data support the hypothesis that in humans the sympathetic activation induced by smoking depends on an increased release and/or a reduced clearance of catecholamines at the neuroeffector junctions. Central sympathetic activity is inhibited by smoking, presumably via a baroreceptor stimulation triggered by the smoking-related presser response. The baroreflex is impaired by smoking, however, indicating that partial inability to reflexly counteract the effect of sympathetic activation is also responsible for the presser response

Mechanisms responsible for sympathetic activation by cigarette smoking in humans

Background The presser and tachycardic effects of cigarette smoking are associated with an increase in plasma catecholamines, suggesting the dependence of these effects on adrenergic stimulation. Whether the stimulation occurs at a central or a peripheral level and whether reflex mechanisms are involved is unknown. Methods and Results In nine normotensive healthy subjects (age, 33.0+/-3.5 years, mean+/-SEM), we measured blood pressure (Finapres device), heart rate (ECG), calf blood how and vascular resistance (venous occlusion plethysmography), plasma norepinephrine and epinephrine (high-performance liquid chromatography assay), and postganglionic muscle sympathetic nerve activity (microneurography from the peroneal nerve) while subjects were smoking,a filter cigarette (nicotine content, 1.1 mg) or were in control condition. Cigarette smoking (which raised plasma nicotine measured by highperformance liquid chromatography from 1.0+/-0.9 to 44.2+/-7.1 ng/mL) markedly and significantly increased mean arterial pressure (+13.2+/-2.3%), heart rate (+30.3+/-4.7%), calf vascular resistance (+12.1+/-4.9%), plasma norepinephrine (+34.8+/-7.0%), and plasma epinephrine (+90.5+/-39.0%). In contrast, muscle sympathetic nerve activity showed a marked reduction (integrated activity -31.8+/-5.1%, P<.01). The reduction was inversely related to the increase in mean arterial pressure (r=-.67, P<.05), but the slope of the relation was markedly less (-54.1+/-7.5%, P<.05) than that obtained by intravenous infusion of phenylephrine in absence of smoking. The hemodynamic and neurohumoral changes were still visible 30 minutes after smoking and occurred again on smoking a second cigarette. Sham smoking was devoid of any hemodynamic and neurohumoral effect. Conclusions These data support the hypothesis that in humans the sympathetic activation induced by smoking depends on an increased release and/or a reduced clearance of catecholamines at the neuroeffector junctions. Central sympathetic activity is inhibited by smoking, presumably via a baroreceptor stimulation triggered by the smoking-related presser response. The baroreflex is impaired by smoking, however, indicating that partial inability to reflexly counteract the effect of sympathetic activation is also responsible for the presser response