Higgs Mode and Magnon Interactions in 2D Quantum Antiferromagnets from Raman Scattering

We present a theory for Raman scattering on 2D quantum antiferromagnets. The microscopic Fleury-Loudon Hamiltonian is expressed in terms of an effective $O(3)$ - model. Well within the N\'eel ordered phase, the Raman spectrum contains a two-magnon and a two-Higgs contribution, which are calculated diagramatically. The vertex functions for both the Higgs and magnon contributions are determined from a numerical solution of the corresponding Bethe-Salpeter equation. Due to the momentum dependence of the Raman vertex in the relevant $B_{1g}+E_{2g}$ symmetry, the contribution from the Higgs mode is strongly suppressed. Except for intermediate values of the Higgs mass, it does not show up as separate peak in the spectrum but gives rise to a broad continuum above the dominant contribution from two-magnon excitations. The latter give rise to a broad, asymmetric peak at $\omega\simeq 2.44\, J$, which is a result of magnon-magnon interactions mediated by the Higgs mode. The full Raman spectrum is determined completely by the antiferromagnetic exchange coupling $J$ and a dimensionless Higgs mass. Experimental Raman spectra of undoped cuprates turn out to be in very good agreement with the theory only with inclusion of the Higgs contribution. They thus provide a clear signature of the presence of a Higgs mode in spin one-half 2D quantum antiferromagnets.Comment: 12 pages, 15 figure

Multiple testing for SNP-SNP interactions

Most genetic diseases are complex, i.e. associated to combinations of SNPs rather than individual SNPs. In the last few years, this topic has often been addressed in terms of SNP-SNP interaction patterns given as expressions linked by logical operators. Methods for multiple testing in high-dimensional settings can be applied when many SNPs are considered simultaneously. However, another less well-known multiple testing problem arises within a fixed subset of SNPs when the logic expression is chosen optimally. In this article, we propose a general asymptotic approach for deriving the distribution of the maximally selected chi-square statistic in various situations. We show how this result can be used for testing logic expressions - in particular SNP-SNP interaction patterns - while controlling for multiple comparisons. Simulations show that our method provides multiple testing adjustment when the logic expression is chosen such as to maximize the statistic. Its benefit is demonstrated through an application to a real dataset from a large population-based study considering allergy and asthma in KORA. An implementation of our method is available from the Comprehensive R Archive Network (CRAN) as R package 'SNPmaxsel'

Self-consistent Hartree-Fock approach to many-body localization

In this work, we develop a self-consistent Hartree-Fock approach to theoretically study the far-from-equilibrium quantum dynamics of interacting fermions, and apply this approach to explore the onset of many-body localization (MBL) in these systems. We investigate the dynamics of a state with a nonequilibrium density profile; we find that at weak disorder the density profile equilibrates rapidly, whereas for strong disorder it remains frozen on the accessible timescales. We analyze this behavior in terms of the Hartree-Fock self-energy. At weak disorder the self-energy fluctuates strongly and can be interpreted as a self-consistent noise process. By contrast, at strong disorder the self-energy evolves with a few coherent oscillations which cannot delocalize the system. Accordingly, the non-equilibrium site-resolved spectral function shows a broad spectrum at weak disorder and sharp spikes at strong disorder. Our Hartree-Fock theory incorporates spatial fluctuations and rare-region effects. As a consequence, we find subdiffusive relaxation in random systems; but, when the system is subjected to weak quasi-periodic potentials, the subdiffusive response ceases to exist, as rare region effects are absent in this case. This self-consistent Hartree-Fock approach can be regarded as a relatively simple theory that captures much of the MBL phenomenology.Comment: 11 pages, 10 figures, Added references and expanded discussion

MicroRNA-Analyse bei Zwillingen mit und ohne angeborenem Herzfehler

Angeborenene Herzfehler (AHF) gehören zu den häufigsten angeborenen Organfehlbildungen des Neugeborenen. Ihre Pathogenese ist bisher weitesgehend ungeklärt. Neben der bereits bekannten genetischen Prädisposition sind dabei in den letzten Jahren die Bedeutung von miRNAs und des gesamten Bereichs der Epigenetik in den Fokus der Forschung gerückt. Das Ziel dieser Arbeit war es, spezifische microRNAs (miRNAs) im Blut von Zwillingen mit AHF zu bestimmen, die im Vergleich zu den herzgesunden Zwillingskindern verändert exprimiert werden. Zwillinge stellen hierfür aufgrund ihrer gleichen oder ähnlichen Genetik eine optimale Untersuchungsgruppe dar. Dabei wurden verschiedene Einflussgrößen wie Art der Schwangerschaftsentstehung, Zygosität und Reife der Zwillinge bei Geburt näher betrachtet. Es handelt sich um eine Pilotstudie, in der im Blut von 19 Zwillingspaaren miRNAAnalysen mithilfe von MicroArrays durchgeführt wurden, die anschließend mittels qRT-PCR validiert wurden. Zusätzlich wurden somatische Daten der Zwillinge und pränatale Daten gesammelt. Die Auswertung zeigte, dass zahlreiche miRNAs in den verschiedenen Vergleichsgruppen signifikant verändert exprimiert werden. Dabei konnten sowohl miRNAs bestimmt werden, die bereits in der Literatur mit dem Vorkommen von AHF assoziiert sind, als auch solche, die in diesem Zusammenhang noch weitesgehend unbeschrieben sind. Bei diesen miRNAs konnten wir neben ihrer Bedeutung bei der Entstehung von AHF auch einen Zusammenhang mit den Risikofaktoren der Frühgeburt, der Schwangerschaftsentstehung durch IVF-Behandlung und der Monozygosität feststellen. In der Zukunft müssen epigenetische Faktoren mittels Genomsequenzierung im Blut der Zwillinge untersucht werden und mit dem miRNA-Expressionsprofil korreliert werden, um mögliche diagnostische Angriffspunkte bestimmen zu können.Congenital heart diseases (CHD) are one of the most common congenital malformations. Their developement is not totally understood up to now. In addition to the already known genetic predisposition, microRNAs (miRNAs) and the whole field of epigenetics have become the focus of research in the last years. The purpose of this study was to determine specific miRNAs in the blood of twins with CHD which are expressed diffenrently compared to their healthy co-twins. Because of their identical or similar genetics, twins represent an optimal study group. Different contributing factors like the way of conception, the maturity of the twins at birth and their zygosity were examined. This is a pilot study in which miRNA expression-levels in the blood of 19 twin pairs were analysed using MicroArray and were validated using qRTPCR. In addition, somatic data of the twins and prenatal data were collected. We could find numerous miRNAs expressed significantly different in the various collectives. Some of them are already known to be associated with CHD, whereas some were largely unknown in the developement of CHD. In addition to the meaning of these miRNAs in the developement of CHD, we could observe a connection between the risk factors prematury, monozygosity and In-vitro fertilisation and the increased occurrence of CHD. In the future, epigenetics need to be investigated in the blood of the twins by genome sequencing and correlation with the expression profiles of miRNAs in order to determine diagnostic targets

Social Conformity in Autism

Humans are extremely susceptible to social influence. Here, we examine whether this susceptibility is altered in autism, a condition characterized by social difficulties. Autistic participants (N=22) and neurotypical controls (N=22) completed a memory test of previously seen words and were then exposed to answers supposedly given by four other individuals. Autistic individuals and controls were as likely to alter their judgements to align with inaccurate responses of group members. These changes reflected both temporary judgement changes (public conformity) and long-lasting memory changes (private conformity). Both groups were more susceptible to answers believed to be from other humans than from computer algorithms. Our results suggest that autistic individuals and controls are equally susceptible to social influence when reporting their memories

Early intravenous magnesium sulfate and its impact on cerebral vasospasm as well as delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a retrospective matched case-control analysis

Introduction Magnesium sulfate (MgSO4) is a potential neuroprotective agent for patients with aneurysmal subarachnoid hemorrhage (aSAH). We analysed the effect of early application of intraoperative intravenous magnesium sulfate (MgSO4) and compared the rate of cerebral vasospasm (CV), delayed cerebral ischemia (DCI) and neurological outcome in two patient cohorts. Material and methods A retrospective matched-pair analysis from patients of a single center in Germany was performed without (group A) and with (group B) MgSO4 application <24 hrs after diagnosis. Pairs were matched according to the known risk factors for DCI and CV (age, Fisher grade, smoking, severity of SAH). Incidence of CV, DCI, and neurological outcome using the modified Rankin Scale (mRS) 3 and 12 months after SAH were recorded. Results 196 patients fulfilled the inclusion criteria. After risk stratification, 48 patients were included in the final analysis (mean±SD age 54.2±8.1yrs, 30 f, 18 m) and were assigned to group A (n=24) or group B (n=24). CV occurred less frequently in group B (33%) than in A (46%). Likewise, DCI was present in 13% (group B) as compared to 42% (group A). After 12 months, 22 patients of group B had a favorable functional outcome (mRS 0 to 3) compared to 15 of group A. Conclusions In this study, the incidence of CV and DCI was lower in patients receiving intravenous MgSO4 within 24 hrs after aneurysmal SAH onset. Favorable functional outcome was more likely in the magnesium group after 12 months of follow-up

Efficacy of Sertraline Plus Placebo or Add-On Celecoxib in Major Depressive Disorder: Macrophage Migration Inhibitory Factor as a Promising Biomarker for Remission After Sertraline-Results From a Randomized Controlled Clinical Trial

Trastorno depresivo mayor; Tratamiento antiinflamatorio; CitocinaTrastorn depressiu major; Tractament antiinflamatori; CitocinaMajor depressive disorder; Anti-inflammatory treatment; CytokineIntroduction: Previous research delivers strong indications that inflammatory activation leads to treatment resistance in a subgroup of patients with Major Depressive Disorder (MDD). Thus, tailored interventions are needed. The present study aimed to find potential biomarkers that may enable patients to be stratified according to immune activation. Methods: A phase IIa randomized placebo-controlled trial was performed to assess levels of inflammatory compounds in responders/remitters and non-responders/non-remitters to sertraline plus celecoxib (n = 20) and sertraline plus placebo (n = 23). Levels of macrophage migration inhibitory factor, neopterin, and tumor necrosis factor alpha were determined by enzyme-linked immunosorbent assay; response and remission were measured by reduction of the Montgomery Åsberg Depression Rating Scale score. Results: Both treatment groups showed a significant decline in depression symptoms, but no difference was found between groups. A clear pattern emerged only for macrophage migration inhibitory factor: placebo remitters showed significantly lower baseline levels than non-remitters (a similar trend was seen in responders and non-responders) while celecoxib responders showed a trend for higher baseline levels than non-responders. Conclusion: Small subsample sizes are a notable limitation, wherefore results are preliminary. However, the present study provides novel insights by suggesting macrophage migration inhibitory factor as a promising biomarker for treatment choice.This present work was funded by the EU 7th Framework program (grant number EU-FP7-CP-IP-2008-222963/EU-FP7-PEOPLE-2009-IAPP-MarieCurie-286334) and Horizon 2020 (grant number H2020-SC1-2016-2017/H2020-SC1-2017-Two-Stage-RTD). Further, part of this work was supported by the foundation Immunität und Seele. The funders had no role in the study design, data collection and analysis, or decision to publish

Low-grade inflammation as a predictor of antidepressant and anti- inflammatory therapy response in MDD patients: a systematic review of the literature in combination with an analysis of experimental data collected in the EU-MOODINFLAME consortium

Terapia antiinflamatoria; Terapia antidepresiva; InflamaciónAnti-inflammatory therapy; Antidepressant therapy; InflammationTeràpia antiinflamatòria; Teràpia antidepressiva; InflamacióLow-grade inflammation plays a role not only in the pathogenesis of major depressive disorder (MDD) but probably also in the poor responsiveness to regular antidepressants. There are also indications that anti-inflammatory agents improve the outcomes of antidepressants. Aim: To study whether the presence of low-grade inflammation predicts the outcome of antidepressants, anti-inflammatory agents, or combinations thereof. Methods: We carried out a systematic review of the literature on the prediction capability of the serum levels of inflammatory compounds and/or the inflammatory state of circulating leukocytes for the outcome of antidepressant/anti-inflammatory treatment in MDD. We compared outcomes of the review with original data (collected in two limited trials carried out in the EU project MOODINFLAME) on the prediction capability of the inflammatory state of monocytes (as measured by inflammatory gene expression) for the outcome of venlafaxine, imipramine, or sertraline treatment, the latter with and without celecoxib added. Results: Collectively, the literature and original data showed that: 1) raised serum levels of pro-inflammatory compounds (in particular of CRP/IL-6) characterize an inflammatory form of MDD with poor responsiveness to predominately serotonergic agents, but a better responsiveness to antidepressant regimens with a) (add-on) noradrenergic, dopaminergic, or glutamatergic action or b) (add-on) anti-inflammatory agents such as infliximab, minocycline, or eicosapentaenoic acid, showing—next to anti-inflammatory—dopaminergic or lipid corrective action; 2) these successful anti-inflammatory (add-on) agents, when used in patients with low serum levels of CRP/IL-6, decreased response rates in comparison to placebo. Add-on aspirin, in contrast, improved responsiveness in such “non-inflammatory” patients; 3) patients with increased inflammatory gene expression in circulating leukocytes had a poor responsiveness to serotonergic/noradrenergic agents. Conclusions: The presence of inflammation in patients with MDD heralds a poor outcome of first-line antidepressant therapies. Immediate step-ups to dopaminergic or glutamatergic regimens or to (add-on) anti-inflammatory agents are most likely indicated. However, at present, insufficient data exist to design protocols with reliable inflammation parameter cutoff points to guide such therapies, the more since detrimental outcomes are possible of anti-inflammatory agents in “non-inflamed” patients.This study was financially supported by the EU via the MOODINFLAME project (EU-FP7-HEALTH-F2-2008-222963), the PSYCHAID (EU-FP7-PEOPLE-2009-IAPP-MarieCurie-286334), and the MOODSTRATIFICATION project (H2020-EU. 3.1.1., GA754740). NM and GA were additionally supported by the foundation "Immunitat und Seele." The funders had no role in study design, data collection, analysis and interpretation of data, the writing of the report, and the decision to submit the paper for publication

TREatment of ATopic eczema (TREAT) Registry Taskforce: consensus on how and when to measure the core dataset for atopic eczema treatment research registries.

BackgroundComparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling.ObjectivesTo reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE.MethodsProposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey.ResultsA total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined.ConclusionsThis core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers)