Large Shape Staggering in Neutron-Deficient Bi Isotopes.

The changes in the mean-square charge radius (relative to ^{209}Bi), magnetic dipole, and electric quadrupole moments of ^{187,188,189,191}Bi were measured using the in-source resonance-ionization spectroscopy technique at ISOLDE (CERN). A large staggering in radii was found in ^{187,188,189}Bi^{g}, manifested by a sharp radius increase for the ground state of ^{188}Bi relative to the neighboring ^{187,189}Bi^{g}. A large isomer shift was also observed for ^{188}Bi^{m}. Both effects happen at the same neutron number, N=105, where the shape staggering and a similar isomer shift were observed in the mercury isotopes. Experimental results are reproduced by mean-field calculations where the ground or isomeric states were identified by the blocked quasiparticle configuration compatible with the observed spin, parity, and magnetic moment.

Experimental Evidence for Common Driving Effects in Low-Energy Fission from Sublead to Actinides.

Isotopic distributions of fragments from fission of the neutron-deficient ^{178}Hg nuclide are reported. This experimental observable is obtained for the first time in the region around lead using an innovative approach based on inverse kinematics and the coincidence between the large acceptance magnetic spectrometer VAMOS++ and a new detection arm close to the target. The average fragment N/Z ratio and prompt neutron M_{n} multiplicity are derived and compared with current knowledge from actinide fission. A striking consistency emerges, revealing the unexpected dominant role of the proton subsystem with atomic number between the Z=28 and 50 magic numbers. The origin of nuclear charge polarization in fission and fragment deformation at scission are discussed.

Publisher Correction: The observation of vibrating pear-shapes in radon nuclei.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evolution of Octupole Deformation in Radium Nuclei from Coulomb Excitation of Radioactive

There is sparse direct experimental evidence that atomic nuclei can exhibit stable "pear" shapes arising from strong octupole correlations. In order to investigate the nature of octupole collectivity in radium isotopes, electric octupole (E3) matrix elements have been determined for transitions in ^{222,228}Ra nuclei using the method of sub-barrier, multistep Coulomb excitation. Beams of the radioactive radium isotopes were provided by the HIE-ISOLDE facility at CERN. The observed pattern of E3 matrix elements for different nuclear transitions is explained by describing ^{222}Ra as pear shaped with stable octupole deformation, while ^{228}Ra behaves like an octupole vibrator.

The observation of vibrating pear-shapes in radon nuclei.

There is a large body of evidence that atomic nuclei can undergo octupole distortion and assume the shape of a pear. This phenomenon is important for measurements of electric-dipole moments of atoms, which would indicate CP violation and hence probe physics beyond the Standard Model of particle physics. Isotopes of both radon and radium have been identified as candidates for such measurements. Here, we observed the low-lying quantum states in 224Rn and 226Rn by accelerating beams of these radioactive nuclei. We show that radon isotopes undergo octupole vibrations but do not possess static pear-shapes in their ground states. We conclude that radon atoms provide less favourable conditions for the enhancement of a measurable atomic electric-dipole moment.

Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies.

OBJECTIVE: To conduct a systematic review and meta-analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs). METHOD: The PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random-effects models. RESULT: Eighty-two studies comprising 3212 participants with MDD and 2798 HCs met inclusion criteria. Peripheral levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, IL-10, the soluble IL-2 receptor, C-C chemokine ligand 2, IL-13, IL-18, IL-12, the IL-1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs, whereas interferon-gamma levels were lower in MDD (Hedge's g = -0.477, P = 0.043). Levels of IL-1ß, IL-2, IL-4, IL-8, the soluble IL-6 receptor (sIL-6R), IL-5, CCL-3, IL-17, and transforming growth factor-beta 1 were not significantly altered in individuals with MDD compared to HCs. Heterogeneity was large (I2 : 51.6-97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index). CONCLUSION: Our results further characterize a cytokine/chemokine profile associated with MDD. Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.

Microbial 'old friends', immunoregulation and socioeconomic status.

The immune system evolved to require input from at least three sources that we collectively term the 'old friends': (i) the commensal microbiotas transmitted by mothers and other family members; (ii) organisms from the natural environment that modulate and diversify the commensal microbiotas; and (iii) the 'old' infections that could persist in small isolated hunter-gatherer groups as relatively harmless subclinical infections or carrier states. These categories of organism had to be tolerated and co-evolved roles in the development and regulation of the immune system. By contrast, the 'crowd infections' (such as childhood virus infections) evolved later, when urbanization led to large communities. They did not evolve immunoregulatory roles because they either killed the host or induced solid immunity, and could not persist in hunter-gatherer groups. Because the western lifestyle and medical practice deplete the 'old' infections (for example helminths), immunoregulatory disorders have increased, and the immune system has become more dependent upon microbiotas and the natural environment. However, urbanization maintains exposure to the crowd infections that lack immunoregulatory roles, while accelerating loss of exposure to the natural environment. This effect is most pronounced in individuals of low socioeconomic status (SES) who lack rural second homes and rural holidays. Interestingly, large epidemiological studies indicate that the health benefits of living close to green spaces are most pronounced for individuals of low SES. Here we discuss the immunoregulatory role of the natural environment, and how this may interact with, and modulate, the proinflammatory effects of psychosocial stressors in low SES individuals.

The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D).

Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair fitness-relevant social functioning, whereas theories that suggest that depression is maladaptive fail to account for the high prevalence of depression risk alleles in human populations. These limitations warrant novel explanations for the origin and persistence of depression risk alleles. Accordingly, studies on risk alleles for depression were identified using PubMed and Ovid MEDLINE to examine data supporting the hypothesis that risk alleles for depression originated and have been retained in the human genome because these alleles promote pathogen host defense, which includes an integrated suite of immunological and behavioral responses to infection. Depression risk alleles identified by both candidate gene and genome-wide association study (GWAS) methodologies were found to be regularly associated with immune responses to infection that were likely to enhance survival in the ancestral environment. Moreover, data support the role of specific depressive symptoms in pathogen host defense including hyperthermia, reduced bodily iron stores, conservation/withdrawal behavior, hypervigilance and anorexia. By shifting the adaptive context of depression risk alleles from relations with conspecifics to relations with the microbial world, the Pathogen Host Defense (PATHOS-D) hypothesis provides a novel explanation for how depression can be nonadaptive in the social realm, whereas its risk alleles are nonetheless represented at prevalence rates that bespeak an adaptive function.

MELODIE: a whole-farm model to study the dynamics of nutrients in dairy and pig farms with crops.

In regions of intensive pig and dairy farming, nutrient losses to the environment at farm level are a source of concern for water and air quality. Dynamic models are useful tools to evaluate the effects of production strategies on nutrient flows and losses to the environment. This paper presents the development of a new whole-farm model upscaling dynamic models developed at the field or animal scale. The model, called MELODIE, is based on an original structure with interacting biotechnical and decisional modules. Indeed, it is supported by an ontology of production systems and the associated programming platform DIESE. The biotechnical module simulates the nutrient flows in the different animal, soil and crops and manure sub-models. The decision module relies on an annual optimization of cropping and spreading allocation plans, and on the flexible execution of activity plans for each simulated year. These plans are examined every day by an operational management sub-model and their application is context dependent. As a result, MELODIE dynamically simulates the flows of carbon, nitrogen, phosphorus, copper, zinc and water within the whole farm over the short and long-term considering both the farming system and its adaptation to climatic conditions. Therefore, it is possible to study both the spatial and temporal heterogeneity of the environmental risks, and to test changes of practices and innovative scenarios. This is illustrated with one example of simulation plan on dairy farms to interpret the Nitrogen farm-gate budget indicator. It shows that this indicator is able to reflect small differences in Nitrogen losses between different systems, but it can only be interpreted using a mobile average, not on a yearly basis. This example illustrates how MELODIE could be used to study the dynamic behaviour of the system and the dynamic of nutrient flows. Finally, MELODIE can also be used for comprehensive multi-criterion assessments, and it also constitutes a generic and evolving framework for virtual experimentation on animal farming systems.

Molecular signatures of peripheral blood mononuclear cells during chronic interferon-α treatment: relationship with depression and fatigue.

BACKGROUND: Interferon-alpha (IFN-α) treatment for infectious disease and cancer causes high rates of depression and fatigue, and has been used to investigate the impact of inflammatory cytokines on brain and behavior. However, little is known about the transcriptional impact of chronic IFN-α on immune cells in vivo and its relationship to IFN-α-induced behavioral changes. METHOD: Genome-wide transcriptional profiling was performed on peripheral blood mononuclear cells (PBMCs) from 21 patients with chronic hepatitis C virus (HCV) either awaiting IFN-α therapy (n=10) or at 12 weeks of IFN-α treatment (n=11). RESULTS: Significance analysis of microarray data identified 252 up-regulated and 116 down-regulated gene transcripts. Of the up-regulated genes, 2'-5'-oligoadenylate synthetase 2 (OAS2), a gene linked to chronic fatigue syndrome (CFS), was the only gene that was differentially expressed in patients with IFN-α-induced depression/fatigue, and correlated with depression and fatigue scores at 12 weeks (r=0.80, p=0.003 and r=0.70, p=0.017 respectively). Promoter-based bioinformatic analyses linked IFN-α-related transcriptional alterations to transcription factors involved in myeloid differentiation, IFN-α signaling, activator protein-1 (AP1) and cAMP responsive element binding protein/activation transcription factor (CREB/ATF) pathways, which were derived primarily from monocytes and plasmacytoid dendritic cells. IFN-α-treated patients with high depression/fatigue scores demonstrated up-regulation of genes bearing promoter motifs for transcription factors involved in myeloid differentiation, IFN-α and AP1 signaling, and reduced prevalence of motifs for CREB/ATF, which has been implicated in major depression. CONCLUSIONS: Depression and fatigue during chronic IFN-α administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases.

CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression.

Cytokine-induced activation of indoleamine 2,3-dioxygenase (IDO) catabolizes L-tryptophan (TRP) into L-kynurenine (KYN), which is metabolized to quinolinic acid (QUIN) and kynurenic acid (KA). QUIN and KA are neuroactive and may contribute to the behavioral changes experienced by some patients during exposure to inflammatory stimuli such as interferon (IFN)-alpha. A relationship between depressive symptoms and peripheral blood TRP, KYN and KA during treatment with IFN-alpha has been described. However, whether peripheral blood changes in these IDO catabolites are manifest in the brain and whether they are related to central nervous system cytokine responses and/or behavior is unknown. Accordingly, TRP, KYN, QUIN and KA were measured in cerebrospinal fluid (CSF) and blood along with CSF concentrations of relevant cytokines, chemokines and soluble cytokine receptors in 27 patients with hepatitis C after approximately 12 weeks of either treatment with IFN-alpha (n=16) or no treatment (n=11). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale. IFN-alpha significantly increased peripheral blood KYN, which was accompanied by marked increases in CSF KYN. Increased CSF KYN was in turn associated with significant increases in CSF QUIN and KA. Despite significant decreases in peripheral blood TRP, IFN-alpha had no effect on CSF TRP concentrations. Increases in CSF KYN and QUIN were correlated with increased CSF IFN-alpha, soluble tumor necrosis factor-alpha receptor 2 and monocyte chemoattractant protein-1 as well as increased depressive symptoms. In conclusion, peripheral administration of IFN-alpha activated IDO in concert with central cytokine responses, resulting in increased brain KYN and QUIN, which correlated with depressive symptoms.

Interferon-alpha effects on diurnal hypothalamic-pituitary-adrenal axis activity: relationship with proinflammatory cytokines and behavior.

Interferon (IFN)-alpha has been used to investigate pathways by which innate immune cytokines influence the brain and behavior. Accordingly, the impact of IFN-alpha on diurnal secretion of hypothalamic-pituitary-adrenal (HPA) axis hormones was assessed in 33 patients eligible for treatment with IFN-alpha plus ribavirin for hepatitis C. In addition, the relationship between IFN-alpha-induced HPA axis changes and proinflammatory cytokines and behavior was examined. Plasma ACTH and cortisol as well as tumor necrosis factor (TNF)-alpha, interleukin-6 and their soluble receptors, were measured hourly between 0900 and 2100 hours at baseline and following approximately 12 weeks of either no treatment (n=13) or treatment with IFN-alpha/ribavirin (n=20). Plasma IFN-alpha was also measured at each visit. Depression and fatigue were assessed using the Montgomery-Asberg depression rating scale and the multidimensional fatigue inventory. Compared to no treatment, IFN-alpha/ribavirin administration was associated with significant flattening of the diurnal ACTH and cortisol slope and increased evening plasma ACTH and cortisol concentrations. Flattening of the cortisol slope and increases in evening cortisol were correlated with increases in depression (r=0.38, P<0.05 and r=0.36, P<0.05, respectively) and fatigue (r=0.43, P<0.05 and r=0.49, P<0.01, respectively). No relationship was found between immune and HPA axis measures, although increases in plasma IFN-alpha, TNF-alpha and soluble TNF-alpha receptor2 were independently correlated with behavioral endpoints. These data indicate that chronic exposure to innate immune cytokines may contribute to the altered diurnal HPA axis activity and behavior found in medically ill individuals. However, given the lack of correlation between HPA axis and immune measures, the mechanism by which chronic cytokine exposure influences HPA axis function remains to be determined.

Paroxetine for prevention of depressive symptoms induced by interferon-alpha and ribavirin for hepatitis C.

BACKGROUND: Whether antidepressants prevent depression during interferon-alpha/ribavirin treatment for hepatitis C virus infection has yet to be established. AIM: To investigate the use of paroxetine in a prospective, double-blind, placebo-controlled study for this indication. METHODS: Sixty-one hepatitis C virus-infected patients were randomly assigned to the antidepressant, paroxetine (n = 28), or placebo (n = 33), begun 2 weeks before and continued for 24 weeks during interferon-alpha/ribavirin treatment. Primary endpoints included development of major depression and severity of depressive symptoms measured by the Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: Rates of major depression during the study were low (17%) and did not differ between groups. Nevertheless, using published MADRS cut-off scores, the percent of subjects who met criteria for mild, moderate or severe depression during interferon-alpha/ribavirin therapy was significantly lower in paroxetine- vs. placebo-treated subjects (P = 0.02, Fisher's exact test). Assignment to paroxetine was also associated with significantly reduced depressive symptom severity. This effect was largely accounted for by participants with depression scores above the median (MADRS > 3) at baseline in whom paroxetine was associated with a maximal reduction in MADRS scores of 10.3 (95% CI: 2.1-18.5) compared with placebo at 20 weeks (P < 0.01). Study limitations included a small sample size and high drop-out rate. CONCLUSION: This double-blind, placebo-controlled trial provides preliminary data in support of antidepressant pre-treatment in hepatitis C virus patients with elevated depressive symptoms at baseline.

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice.

Endogenous glucocorticoids restrain proinflammatory cytokine responses to immune challenges such as viral infection. In addition, proinflammatory cytokines induce behavioral alterations including changes in locomotor/exploratory activity. Accordingly, we examined proinflammatory cytokines and open-field behavior in virally infected mice rendered glucocorticoid deficient by adrenalectomy (ADX). Mice were infected with murine cytomegalovirus (MCMV), and open-field behavior (36 h post-infection) and plasma concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 (42 h post-infection) were assessed. Compared to sham-ADX-MCMV-infected animals, ADX-MCMV-infected mice exhibited significant reductions in total distance moved, number of center entries, and time spent in center. These behavioral alterations were accompanied by significantly higher plasma concentrations of TNF-alpha and IL-6, both of which were correlated with degree of behavioral change. To examine the role of TNF-alpha in these behavioral alterations, open-field behavior was compared in wild-type (WT) and TNF-R1-knockout (KO), ADX-MCMV-infected mice. TNF-R1-KO mice exhibited significantly attenuated decreases in number of rearings, number of center entries and time spent in center, but not distance moved, which correlated with plasma IL-6. Given the potential role of brain cytokines in these findings, mRNA expression of TNF-alpha, IL-1 and IL-6 was assessed in various brain regions. Although MCMV induced increases in proinflammatory cytokine mRNA throughout the brain (especially in ADX animals), no remarkable differences were found between WT and TNF-R1-KO mice. These results demonstrate that endogenous glucocorticoids restrain proinflammatory cytokine responses to viral infection and their impact on locomotor/exploratory activity. Moreover, TNF-alpha appears to mediate cytokine-induced changes in open-field behaviors, especially those believed to reflect anxiety.

The neuroimmunology of stress and depression.

This article reviews evidence that shows a bidirectional relationship between the brain and the immune system. As a result of this relationship, mental factors such as stress and depression have been shown to affect immune system functioning, with both immunosuppression and immune activation being reported. Stress and depression also have been associated with worse outcomes in immune-related disorders including cancer and infectious diseases suggesting that stress/depression effects on the immune system are clinically relevant to disease expression. Conversely, several lines of evidence suggest that immune system activation such as during infectious diseases, cancer, and autoimmune disorders is associated with the development of behavioral symptoms similar to those seen in the context of chronic stress or major depression. These findings implicate a role for the immune system in the cause of behavioral disorders in a wide range of medical illnesses. Finally, a paradigm is proposed in which abnormal functioning of either the hypothalamic-pituitary-adrenal (HPA) axis or the inflammatory response system disrupts feedback regulation of both neuroendocrine and immune systems contributing to the development of neuropsychiatric and immunologic disorders.

[Evaluating radiotherapy patients' need for information: a study using a patient information booklet] . / Evaluation des besoins en information des patients suivis en radiothérapie: étude effectuée sur la base du livret de la radiothérapie.

The French Radiotherapy-Oncology Society (SFRO) and the National Trade of Radiotherapists-Oncologists (SNRO) elaborated and published a patient information booklet on radiotherapy, in 1999. This present study appraises the pertinence of the form and substance of this booklet one year after its release. Eight radiotherapy centers participated in this research which evaluated 162 patients at treatment initiation. The conclusions of this study demonstrated the importance of clearly informing patients of their disease, treatment, and the secondary effects of treatment. It is essential to emphasize that 97% of the patients declared that an information booklet is a real necessity, and that the one provided by the SFRO responds to the majority of their concerns. Obtaining technical and practical knowledge resulted in a reassurance about their treatment. The most revealing result is that 87% requested direct communication about their illness, and that cancer be named by this word and not other, evasive terms. Seventy-two percent of the patients requested more information about their cancer, different treatment options, and quality of life issues in an attempt to psychologically prepare themselves to face an illness for which they have little control. Patients refuse to be passive, and claim the right to become 'partners' of the medical teams, concerning their treatment and recovery.

The moon and madness reconsidered.

Belief that the full moon is associated with psychiatric disturbance persists despite 50 years research showing no association. This article traces the historical roots of belief in the power of the moon to cause disorders the mind, especially insanity and epilepsy. Putative mechanisms of lunar action are critiqued. It is proposed that modern findings showing lack of lunar effect can be reconciled with pre-modern beliefs in the moon's power through a mechanism of sleep deprivation. Prior to the advent of modern lighting the moon was a significant source of nocturnal illumination that affected sleep-wake cycle, tending to cause sleep deprivation around the time of full moon. This partial sleep deprivation would have been sufficient to induce mania/hypomania in susceptible bipolar patients and seizures in patients with seizure disorders. The advent of modern lighting attenuated this lunar effect, especially in modern urban areas, where most 20th century studies of lunar effects on the mind have been conducted. The hypothesis presented in this article is open to empirical validation or falsification. Potential tests for the sleep-deprivation hypothesis of lunar action are discussed.