Systems training for emotional predictability and problem solving for borderline personality disorder:A systematic review

Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a group treatment program for patients with borderline personality disorder (BPD). The program was intended to be highly accessible, both for patients and therapists. During STEPPS, patients are taught emotion regulation and behavior management skills. This systematic review synthesizes the current empirical status of STEPPS, focusing on research designs, quality of studies, target groups, protocols, and outcome. We selected 20 studies, with three randomized controlled trials. Patients with BPD, subthreshold BPD, and patients with BPD and comorbid antisocial personality disorder were investigated. One study was conducted in adolescents. There were no studies in older adults. Results demonstrated STEPPS to be associated with reduced BPD symptoms, improved quality of life, decreased depressive symptoms, and decreased negative affectivity. Mixed results were found for impulsivity and suicidal behaviors. STEPPS has both been studied as an add-on therapy to patients' ongoing treatment, and, with the addition of individual STEPPS sessions, as a stand-alone treatment. High attrition rates were found in patients attending STEPPS, complicating the generalizability of the results. Although the evidence for STEPPS is promising, further research is needed before firm conclusions can be drawn. Recommendations for future research are discussed

Linking Unserved Energy to Weather Regimes

The integration of renewable energy sources into power systems is expected to increase significantly in the coming decades. This can result in critical situations related to the strong variability in space and time of weather patterns. During these critical situations the power system experiences a structural shortage of energy across multiple time steps and regions, leading to Energy Not Served (ENS) events. Our research explores the relationship between six weather regimes that describe the large scale atmospheric flow and ENS events in Europe by simulating future power systems. Our results indicate that most regions have a specific weather regime that leads to the highest number of ENS events. However, ENS events can still occur during any weather regime, but with a lower probability. In particular, our findings show that ENS events in western and central European countries often coincide with either the positive Scandinavian Blocking (SB+), characterised by cold air penetrating Europe under calm weather conditions from north-eastern regions, or North Atlantic Oscillation (NAO+) weather regime, characterised by westerly flow and cold air in the southern half of Europe. Additionally, we found that the relative impact of one of these regimes reaches a peak 10 days before ENS events in these countries. In Scandinavian and Baltic countries, on the other hand, our results indicate that the relative prevalence of the negative Atlantic Ridge (AR-) weather regime is higher during and leading up to the ENS event.Comment: Rogier H. Wuijts and Laurens P. Stoop contributed equally to this wor

Prenatal smoke exposure induces persistent Cyp2a5 methylation and increases nicotine metabolism in the liver of neonatal and adult male offspring

Prenatal smoke exposure (PSE) is a risk factor for nicotine dependence. One susceptibility gene for nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine and nicotine clearance in the liver. Higher activity of the CYP2A6 enzyme is associated with nicotine dependence, but no research has addressed the PSE effects on the CYP2A6 gene or its mouse homologue Cyp2a5. We hypothesized that PSE affects Cyp2a5 promoter methylation, Cyp2a5 mRNA levels, and nicotine metabolism in offspring. We used a smoke-exposed pregnant mouse model. RNA, DNA, and microsomal protein were isolated from liver tissue of foetal, neonatal, and adult offspring. Enzyme activity, Cyp2a5 mRNA levels, and Cyp2a5 methylation status of six CpG sites within the promoter region were analysed via HPLC, RT-PCR, and bisulphite pyrosequencing. Our data show that PSE induced higher cotinine levels in livers of male neonatal and adult offspring compared to controls. PSE-induced cotinine levels in neonates correlated with Cyp2a5 mRNA expression and promoter methylation at CpG-7 and CpG+45. PSE increased methylation in almost all CpG sites in foetal offspring, and this effect persisted at CpG-74 in male neonatal and adult offspring. Our results indicate that male offspring of mothers which were exposed to cigarette smoke during pregnancy have a higher hepatic nicotine metabolism, which could be regulated by DNA methylation. Given the detected persistence into adulthood, extrapolation to the human situation suggests that sons born from smoking mothers could be more susceptible to nicotine dependence later in life

Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation

Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is associated with nicotine dependence and could be regulated through DNA methylation. In this study we investigated whether PostSE further impaired PreSE-induced effects on nicotine metabolism, along with Cyp2a5, orthologue of CYP2A6, mRNA expression and DNA methylation. Using a mouse model where prenatally smoke-exposed adult offspring were exposed to cigarette smoke for 3 months, enzyme activity, mRNA levels, and promoter methylation of hepatic Cyp2a5 were evaluated. We found that in male offspring, PostSE increased PreSE-induced cotinine levels and Cyp2a5 mRNA expression. In addition, both PostSE and PreSE changed Cyp2a5 DNA methylation in male groups. PreSE however decreased cotinine levels whereas it had no effect on Cyp2a5 mRNA expression or methylation. These adverse outcomes of PreSE and PostSE were most prominent in males. When considered in the context of the human health aspects, the combined effect of prenatal and adolescent smoke exposure could lead to an accelerated risk for nicotine dependence later in life.</p

Cardiac Deletion of Smyd2 Is Dispensable for Mouse Heart Development

Chromatin modifying enzymes play a critical role in cardiac differentiation. Previously, it has been shown that the targeted deletion of the histone methyltransferase, Smyd1, the founding member of the SET and MYND domain containing (Smyd) family, interferes with cardiomyocyte maturation and proper formation of the right heart ventricle. The highly related paralogue, Smyd2 is a histone 3 lysine 4- and lysine 36-specific methyltransferase expressed in heart and brain. Here, we report that Smyd2 is differentially expressed during cardiac development with highest expression in the neonatal heart. To elucidate the functional role of Smyd2 in the heart, we generated conditional knockout (cKO) mice harboring a cardiomyocyte-specific deletion of Smyd2 and performed histological, functional and molecular analyses. Unexpectedly, cardiac deletion of Smyd2 was dispensable for proper morphological and functional development of the murine heart and had no effect on global histone 3 lysine 4 or 36 methylation. However, we provide evidence for a potential role of Smyd2 in the transcriptional regulation of genes associated with translation and reveal that Smyd2, similar to Smyd3, interacts with RNA Polymerase II as well as to the RNA helicase, HELZ

The First Plasmodium vivax Relapses of Life Are Usually Genetically Homologous

In a prospective infant cohort, 21 infants developed Plasmodium vivax malaria during their first year. Twelve of their mothers also had vivax malaria in the corresponding pregnancies or postpartum period. The genotypes of the maternal and infant infections were all different. Eight of the 12 mothers and 9 of the 21 infants had recurrent infections. Relapse parasite genotypes were different to the initial infection in 13 of 20 (65%) mothers compared with 5 of 24 (21%) infants (P = .02). The first P. vivax relapses of life are usually genetically homologous, whereas relapse in adults may result from activation of heterologous latent hypnozoites acquired from previous inoculations

The Climatological Renewable Energy Deviation Index

Here we propose an index to quantify and analyse the impact of climatological variability on the energy system at different timescales. We define the Climatological Renewable Energy Deviation Index (CREDI) as the cumulative anomaly of a renewable resource with respect to its climate over a specific time period of interest. We analyse the index at decadal, annual and (sub-)seasonal timescales using the forthcoming Pan-European Climate Database and consider the starting point and window of analysis for its use at those timescales. The CREDI is meant as an analytical tool for researchers and stakeholders to help them quantify, understand, and explain, the impact of the variability of weather on the energy system across timescales. Improved understanding translates to better assessments of how renewable resources, and the associated risks for energy security, may fare in current and future climatological settings. The practical use of the index is in resource planning. For example transmission system operators may be able to adjust short-term planning to reduce adequacy issues before they occur or combine the index with storyline event selection for improved assessments of climate change related risks

Raloxifene augmentation in men and women with a schizophrenia spectrum disorder:A study protocol

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered

Prescription and Underprescription of Clozapine in Dutch Ambulatory Care

Purpose: To our knowledge, no study has examined in a structured way the extent of underprescription of clozapine in ambulatory patients with Non-Affective Psychotic Disorder (NAPD). In the Netherlands, psychiatric care for such patients is provided by Flexible Assertive Community Treatment (FACT) teams and by early intervention teams. In 20 FACT teams and 3 early intervention teams we assessed the proportion of patients who: use clozapine (type 1 patients), previously used this drug (type 2), have an unfulfilled indication for this drug, by type of indication (type 3), or were at least markedly psychotic, but had not yet received two adequate treatments with other antipsychotic drugs (type 4). We expected to find major differences between teams. To rule out that these differences are caused by differences in severity of psychopathology, we also calculated the proportions of patients who use clozapine given an indication at any time (number of type 1 patients divided by the sum of type 1, 2, and 3 patients). Materials and methods: The nurse practitioner of each team identified the patients already on clozapine. Next, using a highly-structured decision tree, the nurse practitioner and psychiatrist assessed whether the remaining patients had an indication for this drug. Indications were treatment-resistant positive symptoms, tardive dyskinesia, aggression and suicidality. The severity of positive symptoms was determined using the Clinical Global Impression-Schizophrenia Scale (CGI-SCH). Results: In the participating FACT-teams 2,286 NAPD patients were assessed. The range among teams in proportions was: type 1: 8.8-34.7% (mean: 23.0%), type 2: 0-8.2% (mean: 3.5%), type 3: 1.7-15.6% (mean: 6.9%), type 4: 1.8-16.3% (mean: 8.6%). The range in proportions of patients using this drug given an indication was 49.0-90.9% (mean: 68.8%). These figures were lower in early intervention teams. Conclusions: The proportion of patients in FACT-teams who have an unfulfilled indication for clozapine is 6.9%. There were considerable differences between teams with respect to this proportion. Almost a third of the outpatients had at any time an indication for clozapine. If one takes type 4 patients into account, this proportion may be higher

Single crystalline Ge1.xMnx nanowires as building blocks for nanoelectronics

Magnetically doped Si and Ge nanowires have potential application in future nanowire spin-based devices. Here, we report a supercritical fluid method for producing single crystalline Mn-doped Ge nanowires with a Mn-doping concentration of between 0.5−1.0 atomic % that display ferromagnetism above 300 K and a superior performance with respect to the hole mobility of around 340 cm2/Vs, demonstrating the potential of using these nanowires as building blocks for electronic devices