Development and validation of the schedule for the assessment of insight in eating disorders (SAI-ED)

This study examined the reliability, validity and internal structure of the newly developed, interview-based Schedule for the Assessment of Insight in Eating Disorders (SAI-ED) and the relationships of insight with demographic and clinical characteristics in EDs. Ninety-four female patients – 44 with anorexia nervosa (AN) and 50 with bulimia nervosa (BN) – were assessed with SAI-ED. The Brown Assessment of Beliefs Scale was used to evaluate convergent validity of SAI-ED. Hierarchical cluster analysis and multidimensional scaling were used to identify insight components and assess their inter-relationships. The final 8-item SAI-ED demonstrated good psychometric properties. Inter-rater and test-retest reliabilities were high. Three subscales of SAI-ED were identified which measure major insight components: awareness of illness, awareness of symptoms, and treatment engagement. Patients with AN had significant lower score on SAI-ED than patients with BN. Impaired insight was associated with: (a) lower current and lowest lifetime BMI and more severe dietary restrain in AN, (b) illness duration, severity of overall ED symptoms, body-related concerns and obsessionality in BN. Insight is a multidimensional construct in EDs associated with different clinical aspects in AN and BN. The SAI-ED is a valid and reliable tool for the assessment of insight in EDs patients

Sex-Specific Associations Between Trauma Exposure, Pubertal Timing, and Anxiety in Black Children

Recent research has linked early life stress (ELS), such as trauma exposure, with early puberty. Early puberty has also been identified as a risk factor for poor mental health outcomes. However, these two paths have primarily been examined independently. In addition, more studies have examined these associations in girls than boys, and findings for boys remain mixed. We hypothesized that early puberty (relative to peers) would be positively associated with both prior trauma exposure and concurrent anxiety symptoms. We anticipated that these associations might differ by sex. We tested these hypotheses within a cross-sectional sample of 133 8- to 13-year-old Black girls and boys with trauma exposure. The association between trauma and accelerated pubertal timing was sex-specific: it was positive for girls and negative for boys. We stratified subsequent analyses by sex. Regression analyses indicated that early puberty relative to peers predicted more anxiety symptoms for girls but not boys, after accounting for trauma exposure. A statistical mediation analysis indicated that, for girls, the positive association between trauma exposure and anxiety was partially mediated by pubertal timing. These results indicate that trauma exposure may have sex-specific effects on pubertal timing and anxiety risk in Black children. We also found that, for girls, trauma may increase risk for adverse outcomes by prompting earlier puberty, which is linked to higher anxiety. These findings are consistent with cascading effects of trauma across development, and highlight the need for further study of sex-specific mechanisms

Metabonomic Investigation of Liver Profiles of Nonpolar Metabolites Obtained from Alcohol-Dosed Rats and Mice Using High Mass Accuracy MSn Analysis

Alcoholism is a complex disorder that, in man, appears to be genetically influenced, although the underlying genes and molecular pathways are not completely known. Here the intragastric alcohol feeding model in rodents was used together with high mass accuracy LC/MS(n) analysis to assess the metabonomic changes in nonpolar metabolite profiles for livers from control and alcohol treated rats and mice. Ion signals with a peak area variance of less than 30% (based on repeat analysis of a pooled quality control sample analysed throughout the batch) were submitted to multivariate statistical analysis (using principal components analysis, PCA). PCA revealed robust differences between profiles from control and alcohol-treated animals from both species. The major metabolites seen to differ between control and alcohol-treated animals were identified using high accuracy MS(n) data and verified using external search engines (http://www.lipidmaps.org; http://www.hmdb.ca; http://www.genome.jp/kegg/) and authentic standards. The main metabolite classes to show major changes in the alcoholic liver-derived samples were fatty acyls, fatty acid ethyl esters, glycerolipids and phosphatidylethanol homologues. Significant metabolites that were up-regulated by alcohol treatment in both rat and mouse livers included fatty acyls, metabolites such as octadecatrienoic acid and eicosapentaenoic acid, a number of fatty acid ethyl esters such as ethyl arachidonate, ethyl docosahexaenoic acid, ethyl linoleate and ethyl oleate and phosphatidylethanol (PEth) homologues (predominantly PEth 18:0/18:2 and PEth 16:0/18:2; PEth homologues are currently considered as potential biomarkers for harmful and prolonged alcohol consumption in man). A number of glycerophospholipids resulted in both up-regulation (m/z 903.7436 [M+H](+) corresponding to a triglyceride) and down-regulation (m/z 667.5296 [M+H](+) corresponding to a diglyceride). Metabolite profiles were broadly similar in both mouse and rat models. However, there were a number of significant differences in the alcohol-treated group particularly in the marked down-regulation of retinol and free cholesterol in the mouse compared to the rat. Unique markers for alcohol treatment included ethyl docosahexaenoic acid. Metabolites were identified with high confidence using predominantly negative ion MS(n) data for the fatty acyl components to match to www.lipidmaps.org MS and MS/MS databases; interpreting positive ion data needed to take into account possible adduct ions which may confound the identification of other lipid classes. The observed changes in lipid profiles were consistent with alcohol induced liver injury in humans

Methylomic profiles reveal sex-specific differences in leukocyte composition associated with post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a debilitating mental disorder precipitated by trauma exposure. However, only some persons exposed to trauma develop PTSD. There are sex differences in risk; twice as many women as men develop a lifetime diagnosis of PTSD. Methylomic profiles derived from peripheral blood are well-suited for investigating PTSD because DNA methylation (DNAm) encodes individual response to trauma and may play a key role in the immune dysregulation characteristic of PTSD pathophysiology. In the current study, we leveraged recent methodological advances to investigate sex-specific differences in DNAm-based leukocyte composition that are associated with lifetime PTSD. We estimated leukocyte composition on a combined methylation array dataset (483 participants, ∼450 k CpG sites) consisting of two civilian cohorts, the Detroit Neighborhood Health Study and Grady Trauma Project. Sex-stratified Mann-Whitney U test and two-way ANCOVA revealed that lifetime PTSD was associated with significantly higher monocyte proportions in males, but not in females (Holm-adjusted p-val < 0.05). No difference in monocyte proportions was observed between current and remitted PTSD cases in males, suggesting that this sex-specific difference may reflect a long-standing trait of lifetime history of PTSD, rather than current state of PTSD. Associations with lifetime PTSD or PTSD status were not observed in any other leukocyte subtype and our finding in monocytes was confirmed using cell estimates based on a different deconvolution algorithm, suggesting that our sex-specific findings are robust across cell estimation approaches. Overall, our main finding of elevated monocyte proportions in males, but not in females with lifetime history of PTSD provides evidence for a sex-specific difference in peripheral blood leukocyte composition that is detectable in methylomic profiles and that may reflect long-standing changes associated with PTSD diagnosis

Bright triplet excitons in lead halide perovskites

Nanostructured semiconductors emit light from electronic states known as excitons[1]. According to Hund's rules[2], the lowest energy exciton in organic materials should be a poorly emitting triplet state. Analogously, the lowest exciton level in all known inorganic semiconductors is believed to be optically inactive. These 'dark' excitons (into which the system can relax) hinder light-emitting devices based on semiconductor nanostructures. While strategies to diminish their influence have been developed[3-5], no materials have been identified in which the lowest exciton is bright. Here we show that the lowest exciton in quasi-cubic lead halide perovskites is optically active. We first use the effective-mass model and group theory to explore this possibility, which can occur when the strong spin-orbit coupling in the perovskite conduction band is combined with the Rashba effect [6-10]. We then apply our model to CsPbX3 (X=Cl,Br,I) nanocrystals[11], for which we measure size- and composition-dependent fluorescence at the single-nanocrystal level. The bright character of the lowest exciton immediately explains the anomalous photon-emission rates of these materials, which emit 20 and 1,000 times faster[12] than any other semiconductor nanocrystal at room[13-16] and cryogenic[17] temperatures, respectively. The bright exciton is further confirmed by detailed analysis of the fine structure in low-temperature fluorescence spectra. For semiconductor nanocrystals[18], which are already used in lighting[19,20], lasers[21,22], and displays[23], these optically active excitons can lead to materials with brighter emission and enhanced absorption. More generally, our results provide criteria for identifying other semiconductors exhibiting bright excitons with potentially broad implications for optoelectronic devices.Comment: 14 pages and 3 figures in the main text, Methods and extended data 16 pages which include 11 figures, and supporting information 28 page

Experimental validation of a short-term Borehole-to-Ground (B2G) dynamic model

[EN] The design and optimization of ground source heat pump systems require the ability to accurately reproduce the dynamic thermal behavior of the system on a short-term basis, specially in a system control perspective. In this context, modeling borehole heat exchangers (BHEs) is one of the most relevant and difficult tasks. Developing a model that is able to accurately reproduce the instantaneous response of a BHE while keeping a good agreement on a long-term basis is not straightforward. Thus, decoupling the short-term and long-term behavior will ease the design of a fast short-term focused model. This work presents a short-term BHE dynamic model, called Borehole-to-Ground (B2G), which is based on the thermal network approach, combined with a vertical discretization of the borehole. The proposed model has been validated against experimental data from a real borehole located in Stockholm, Sweden. Validation results prove the ability of the model to reproduce the short-term behavior of the borehole with an accurate prediction of the outlet fluid temperature, as well as the internal temperature profile along the U-tube.The present work has been supported by the FP7 European project "Advanced ground source heat pump systems for heating and cooling in Mediterranean climate" (GROUND-MED), and by the "Resource-Efficient Refrigeration And Heat Pump Systems" (EFF-SYS+) program.Ruiz Calvo, F.; Rosa, MD.; Acuña, J.; Corberán Salvador, JM.; Montagud Montalvá, CI. (2015). Experimental validation of a short-term Borehole-to-Ground (B2G) dynamic model. Applied Energy. 140:210-223. https://doi.org/10.1016/j.apenergy.2014.12.002S21022314

Efficacy of rifabutin-based triple therapy as second-line treatment to eradicate helicobacter pylori infection

<p>Abstract</p> <p>Background</p> <p>Rifabutin has been found to be effective in multi-resistant patients after various treatment cycles for Helicobacter pylori (HP) infection, but it has not been analysed as a second-line treatment. Therefore, we seek to compare the effectiveness of a treatment regimen including rifabutin versus conventional quadruple therapy (QT).</p> <p>Methods</p> <p>Open clinical trial, randomised and multi-centre, of two treatment protocols: A) Conventional regime -QT- (omeprazole 20 mg bid, bismuth citrate 120 mg qid, tetracycline 500 mg qid and metronidazole 500 mg tid); B) Experimental one -OAR- (omeprazole 20 mg bid, amoxicillin 1 gr bid, and rifabutin 150 mg bid), both taken orally for 7 days, in patients with HP infection for whom first-line treatment had failed. Eradication was determined by Urea Breath Test (UBT). Safety was determined by the adverse events.</p> <p>Results</p> <p>99 patients were randomised, QT, n = 54; OAR, n = 45. The two groups were homogeneous. In 8 cases, treatment was suspended (6 in QT and 2 in OAR). The eradication achieved, analysed by ITT, was for QT, 38 cases (70.4%), and for OAR, 20 cases (44.4%); p = 0.009, OR = 1.58. Of the cases analysed PP, QT were 77.1%; OAR, 46.5%; p = 0.002. Adverse effects were described in 64% of the QT patients and in 44% of the OAR patients (p = 0.04).</p> <p>Conclusion</p> <p>A 7-day rifabutin-based triple therapy associated to amoxicillin and omeprazole at standard dose was not found to be effective as a second-line rescue therapy. The problem with quadruple therapy lies in the adverse side effects it provokes. We believe the search should continue for alternatives that are more comfortably administered and that are at least as effective, but with fewer adverse side effects.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN81058036</p

Distant delivery of a mindfulness-based intervention for people with Parkinson's disease: the study protocol of a randomised pilot trial

BACKGROUND: Psychological difficulties, especially depression and anxiety, are the most prevalent non-motor symptoms in Parkinson's disease. Pharmacological treatments for these conditions appear relatively ineffective in Parkinson's disease. Mindfulness courses are increasingly popular and recognised as effective for managing emotional states, and there is growing evidence for the effectiveness of mindfulness courses for people with long-term medical conditions. With this exploratory pilot trial, we want to assess the feasibility of the procedures and processes, including recruitment, most appropriate outcome measure(s), acceptability of type and number of measures, potential nocebo effects, and potential effectiveness and cost-effectiveness of a specially adapted distance-delivered mindfulness-based intervention in people affected by Parkinson's disease. METHODS/DESIGN: This is a pilot two-arm randomised parallel group controlled trial. Sixty participants who meet eligibility criteria will be randomly assigned either to an 8-week mindfulness-based intervention group or a wait-list control group. The mindfulness intervention will include 1-h weekly sessions delivered by a health psychologist trained to facilitate mindfulness courses. Participants in both groups will complete standardised questionnaires assessing anxiety, depression, pain, insomnia, fatigue, and daily activities at four time points (baseline, 4, 8, and 20 weeks). The analysis will also consider potential mechanisms of change, such as acceptance, self-compassion, and tolerance of uncertainty, as well as health economic outcomes. Participants' experiences of the mindfulness interventions will be explored via in-depth interviews. DISCUSSION: A mindfulness-based intervention for people with Parkinson's delivered remotely, through Skype group videoconferences, may represent a viable, more accessible, intervention for people with mobility limitations and people who live in rural areas. The trial will provide important information about the feasibility, potential efficacy and cost-effectiveness, and acceptability of the intervention as well as mechanisms of psychosocial adjustment. The results of this pilot trial will help us design a phase III trial to assess efficacy of an online mindfulness-based intervention in Parkinson's disease and evaluate significance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02683330

Bright triplet excitons in caesium lead halide perovskites

Nanostructured semiconductors emit light from electronic states known as excitons. For organic materials, Hund’s rules state that the lowest-energy exciton is a poorly emitting triplet state. For inorganic semiconductors, similar rules predict an analogue of this triplet state known as the ‘dark exciton’. Because dark excitons release photons slowly, hindering emission from inorganic nanostructures, materials that disobey these rules have been sought. However, despite considerable experimental and theoretical efforts, no inorganic semiconductors have been identified in which the lowest exciton is bright. Here we show that the lowest exciton in caesium lead halide perovskites (CsPbX_3, with X = Cl, Br or I) involves a highly emissive triplet state. We first use an effective-mass model and group theory to demonstrate the possibility of such a state existing, which can occur when the strong spin–orbit coupling in the conduction band of a perovskite is combined with the Rashba effect. We then apply our model to CsPbX_3 nanocrystals, and measure size- and composition-dependent fluorescence at the single-nanocrystal level. The bright triplet character of the lowest exciton explains the anomalous photon-emission rates of these materials, which emit about 20 and 1,000 times faster than any other semiconductor nanocrystal at room and cryogenic temperatures, respectively. The existence of this bright triplet exciton is further confirmed by analysis of the fine structure in low-temperature fluorescence spectra. For semiconductor nanocrystals, which are already used in lighting, lasers and displays, these excitons could lead to materials with brighter emission. More generally, our results provide criteria for identifying other semiconductors that exhibit bright excitons, with potential implications for optoelectronic devices

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Funding Information: This work was supported by the National Institute of Mental Health / U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium ), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience . Statistical analyses were carried out on the LISA/Genetic Cluster Computer ( https://userinfo.surfsara.nl/systems/lisa ) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. Funding Information: MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the National Institute of Mental Health/ U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience. Statistical analyses were carried out on the LISA/Genetic Cluster Computer (https://userinfo.surfsara.nl/systems/lisa) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. This material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the U.S. Department of the Army or the Department of Defense. We thank the investigators who comprise the PGC-PTSD working group and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. We thank Mark Zervas for his critical input. Full acknowledgments are in Supplement 1. MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc. RallyPoint Networks, Inc. Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled ?Genotype-guided dosing of opioid agonists,? filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological PsychiatryBackground: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.publishersversionpublishe