A multi-center naturalistic study of a newly designed 12-sessions group psychoeducation program for patients with bipolar disorder and their caregivers

Background: Psychoeducation (PE) for bipolar disorder (BD) has a first-line recommendation for the maintenance treatment phase of BD. Formats vary greatly in the number of sessions, whether offered individually or in a group, and with or without caregivers attending. Due to a large variation in formats in the Netherlands, a new program was developed and implemented in 17 outpatient clinics throughout the country. The current study investigated the feasibility of a newly developed 12-sessions PE group program for patients with BD and their caregivers in routine outpatient practice and additionally explored its effectiveness. Methods: Participants in the study were 108 patients diagnosed with BD, 88 caregivers and 35 course leaders. Feasibility and acceptance of the program were investigated by measures of attendance, and evaluative questionnaires after session 12. Preliminary treatment effects were investigated by pre- and post-measures on mood symptoms, attitudes towards BD and its treatment, levels of self-management, and levels of expressed emotion. Results: There was a high degree of satisfaction with the current program as reported by patients, caregivers, and course leaders. The average attendance was high and 83% of the patients and 75% of the caregivers completed the program. Analyses of treatment effects suggest positive effects on depressive symptoms and self-management in patients, and lower EE as experienced by caregivers. Conclusions: This compact 12-sessions psychoeducation group program showed good feasibility and was well accepted by patients, caregivers, and course leaders. Preliminary effects on measures of self-management, expressed emotions, and depressive symptoms were promising. After its introduction it has been widely implemented in mental health institutions throughout the Netherlands

Detection of increased pyruvate dehydrogenase flux in the human heart during adenosine stress test using hyperpolarized [1-13C]pyruvate cardiovascular magnetic resonance imaging

BACKGROUND: Hyperpolarized (HP) [1-(13)C]pyruvate cardiovascular magnetic resonance (CMR) imaging can visualize the uptake and intracellular conversion of [1-(13)C]pyruvate to either [1-(13)C]lactate or (13)C-bicarbonate depending on the prevailing metabolic state. The aim of the present study was to combine an adenosine stress test with HP [1-(13)C]pyruvate CMR to detect cardiac metabolism in the healthy human heart at rest and during moderate stress. METHODS: A prospective descriptive study was performed between October 2019 and August 2020. Healthy human subjects underwent cine CMR and HP [1-(13)C]pyruvate CMR at rest and during adenosine stress. HP [1-(13)C]pyruvate CMR images were acquired at the mid-left-ventricle (LV) level. Semi-quantitative assessment of first-pass myocardial [1-(13)C]pyruvate perfusion and metabolism were assessed. Paired t-tests were used to compare mean values at rest and during stress. RESULTS: Six healthy subjects (two female), age 29 ± 7 years were studied and no adverse reactions occurred. Myocardial [1-(13)C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2 ± 2.8 to 2.7 ± 1.3 s, p = 0.02. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (k(PL)) for lactate increased from 11 ± 9 *10(–3) to 20 ± 10 * 10(–3) s(−1), p = 0.04. The pyruvate oxidation rate (k(PB)) increased from 4 ± 4 *10(–3) to 12 ± 7 *10(–3) s(−1), p = 0.008. This increase in carbohydrate metabolism was positively correlated with heart rate (R(2) = 0.44, p = 0.02). CONCLUSIONS: Adenosine stress testing combined with HP [1-(13)C]pyruvate CMR is feasible and well-tolerated in healthy subjects. We observed an increased pyruvate oxidation during cardiac stress. The present study is an important step in the translation of HP [1-(13)C]pyruvate CMR into clinical cardiac imaging. Trial registration EUDRACT, 2018-003533-15. Registered 4th of December 2018, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-003533-1

2001-GT-XXXX Boundary Layer Development in the BR710 and BR715 LP Turbines - The Implementation of High Lift and Ultra High Lift Concepts

ABSTRACT This paper describes a detailed study into the unsteady boundary layer behaviour in two high lift and one ultra high lift Rolls-Royce Deutschland LP turbines. The objectives of the paper are to show that high lift and ultra high-lift concepts have been successfully incorporated into the design of these new LP turbine profiles. Measurements from surface mounted hot film sensors were made in full size, cold flow test rigs at the altitude test facility at Stuttgart University. The LP turbine blade profiles are thought to be state of the art in terms of their lift and design philosophy. The two high lift profiles represent slightly different styles of velocity distribution. The first high-lift profile comes from a two stage LP turbine (the BR710 cold-flow, high-lift demonstrator rig). The second high-lift profile tested is from a three-stage machine (the BR715 LPT rig). The ultra-high lift profile measurements come from a redesign of the BR715 LP turbine: this is designated the BR715UHL LP turbine. This ultra high-lift profile represents a 12% reduction in blade numbers compared to the original BR715 turbine. The results from NGV2 on all of the turbines show "classical" unsteady boundary layer behaviour. The measurements from NGV3 (of both the BR715 and BR715UHL turbines) are more complicated, but can still be broken down into classical regions of wake-induced transition, natural transition and calming. The wakes from both upstream rotors and NGVs interact in a complicated manner, affecting the suction surface boundary layer of NGV3. This has important implications for the prediction of the flows on blade rows in multistage environments

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

Revealing the reporting disparity: VigiBase highlights underreporting of clozapine in other Western European countries compared to the UK

Background: Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs). Objective: In a 2021 article, the United Kingdom (UK) had >90 % of European clozapine-related fatal outcomes in VigiBase, the World Health Organization's pharmacovigilance database. Two possibly opposing hypotheses could explain this disparity: 1) fewer reported fatal outcomes in other Western European countries mainly reflect underreporting to VigiBase, and 2) the higher number of UK reports reflects higher real relative mortality. Methods: VigiBase reports from clozapine's introduction to December 31, 2022, were studied for ADRs and the top 10 causes of fatal outcomes. The UK was compared with 11 other top reporting Western countries (Germany, Denmark, France, Finland, Ireland, Italy, Netherlands, Norway, Spain, Sweden and Switzerland). Nine countries (except Ireland and Switzerland) were compared after controlling for population and clozapine prescriptions. Results: The UK accounted for 29 % of worldwide clozapine-related fatal outcomes, Germany 2 % and <1 % in each of the other countries. The nonspecific label "death" was the top cause in the world (46 %) and in the UK (33 %). "Pneumonia" was second in the world (8 %), the UK (12 %), Ireland (8 %) and Finland (14 %). Assuming that our corrections for population and clozapine use are correct, other countries underreported only 1-10 % of the UK clozapine fatal outcome number. Conclusions: Different Western European countries consistently underreport to VigiBase compared to the UK, but have different reporting/publishing styles for clozapine-related ADRs/fatal outcomes. Three Scandinavian registries suggest lives are saved as clozapine use increases, but this cannot be studied in pharmacovigilance databases

Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN

Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis

CLIC: a Two-Beam Multi-TeV e±e\pm Linear Collider

The CLIC study of a high-energy (0.5 - 5 TeV), high-luminosity (1034 - 1035 cm-2 sec-1) e+e- linear collider is presented. Beam acceleration using high frequency (30 GHz) normal-conducting structures operating at high accelerating fields (150 MV/m) significantly reduces the length and, in consequence, the cost of the linac. Using parameters derived from general scaling laws for linear colliders, the beam stability is shown to be similar to lower frequency designs in spite of the strong wake-field dependency on frequency. A new cost-effective and efficient drive beam generation scheme for RF power production by the so-called "Two-Beam Acceleration" method is described. It uses a thermionic gun and a fully-loaded normal-conducting linac operating at low frequency (937 MHz) to generate and accelerate the drive beam bunches, and RF multiplication by funnelling in compressor rings to produce the desired bunch structure. Recent 30 GHz hardware developments and CLIC Test Facility (CTF) results are described

The GALEX Ultraviolet Atlas of Nearby Galaxies

We present images, integrated photometry, surface-brightness and color profiles for a total of 1034 nearby galaxies recently observed by the GALEX satellite in its far-ultraviolet (FUV; 1516A) and near-ultraviolet (NUV; 2267A) bands. (...) This data set has been complemented with archival optical, near-infrared, and far-infrared fluxes and colors. We find that the integrated (FUV-K) color provides robust discrimination between elliptical and spiral/irregular galaxies and also among spiral galaxies of different sub-types. Elliptical galaxies with brighter K-band luminosities (i.e. more massive) are redder in (NUV-K) color but bluer in (FUV-NUV) than less massive ellipticals. In the case of the spiral/irregular galaxies our analysis shows the presence of a relatively tight correlation between the (FUV-NUV) color and the total infrared-to-UV ratio. The correlation found between (FUV-NUV) color and K-band luminosity (with lower luminosity objects being bluer than more luminous ones) can be explained as due to an increase in the dust content with galaxy luminosity. The images in this Atlas along with the profiles and integrated properties are publicly available through a dedicated web page at http://nedwww.ipac.caltech.edu/level5/GALEX_Atlas/Comment: 181 pages, 10 figures, accepted for publication in ApJS (abstract abridged

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

A social network analysis of social cohesion in a constructed pride: Implications for ex situ reintroduction of the African Lion (Panthera leo)

Animal conservation practices include the grouping of captive related and unrelated individuals to form a social structure which is characteristic of that species in the wild. In response to the rapid decline of wild African lion (Panthera leo) populations, an array of conservational strategies have been adopted. Ex situ reintroduction of the African lion requires the construction of socially cohesive pride structures prior to wild release. This pilot study adopted a social network theory approach to quantitatively assess a captive pride's social structure and the relationships between individuals within them. Group composition (who is present in a group) and social interaction data (social licking, greeting, play) was observed and recorded to assess social cohesion within a released semi-wild pride. UCINET and SOCPROG software was utilised to represent and analyse these social networks. Results indicate that the pride is socially cohesive, does not exhibit random associations, and the role of socially influential keystone individuals is important for maintaining social bondedness within a lion pride. These results are potentially informative for the structure of lion prides, in captivity and in the wild, and could have implications for captive and wild-founder reintroductions