Supergravity description of spacetime instantons

We present and discuss BPS instanton solutions that appear in type II string theory compactifications on Calabi-Yau threefolds. From an effective action point of view these arise as finite action solutions of the Euclidean equations of motion in four-dimensional N=2 supergravity coupled to tensor multiplets. As a solution generating technique we make use of the c-map, which produces instanton solutions from either Euclidean black holes or from Taub-NUT like geometries.Comment: 35 pages, some clarifications adde

Метафорична картина світу та її місце у системі світів

Статья посвящается исследованию понятия метафорической картины мира, целесообразность выделения которой автор объясняет тем, что по аналогии с языковой и концептуальной картинами мира, термин "метафорическая картина мира" содержит информацию о сложной структуре многосмысловых значений, которые в силу своей метафорической природе гармонически объединяются.У статті йдеться про поняття метафоричної картини світу, доцільність виділення якої авторка пояснює тим, що за аналогією до мовної й концептуальної картин світу, термін "метафорична картина світу" вміщує інформацію про складну структуру багатосмислових значень, що завдяки своїй метафоричній природі гармонійно поєднуються.The article deals with the notion of metaphorical world picture connected with the general principle of conceptualization. The term "metaphorical world picture" consists of a complex structure of various meanings harmonically combined due to their metaphorical nature

Differences in Trial and Real-world Populations in the Dutch Castration-resistant Prostate Cancer Registry

__Background:__ Trials in castration-resistant prostate cancer (CRPC) treatment have shown improved outcomes, including survival. However, as trial populations are selected, results may not be representative for the real-world population. The aim of this study was to assess the differences between patients treated in a clinical trial versus standard care during the course of CRPC in a real-world CRPC population. __Design, setting, and participants:__ Castration-resistant Prostate Cancer Registry is a population-based, observational, retrospective registry. CRPC patients from 20 hospitals in the Netherlands have been included from 2010 to 2013. __Outcome measurements and statistical analysis:__ Baseline characteristics, systemic treatment, and overall survival were the main outcomes. Descriptive statistics, multivariate Cox regression, and multiple imputations with the Monte Carlo Markov Chain method were used. __Results and limitations:__ In total, 1524 patients were enrolled of which 203 patients had participated in trials at any time. The median follow-up period was 23 mo. Patients in the trial group were significantly younger and had less comorbidities. Docetaxel treatment was more freque

Improved imputation quality of low-frequency and rare variants in European samples using the ‘Genome of The Netherlands'

Although genome-wide association studies (GWAS) have identified many common variants associated with complex traits, low-frequency and rare variants have not been interrogated in a comprehensive manner. Imputation from dense reference panels, such as the 1000 Genomes Project (1000G), enables testing of ungenotyped variants for association. Here we present the results of imputation using a large, new population-specific panel: the Genome of The Netherlands (GoNL). We benchmarked the performance of the 1000G and GoNL reference sets by comparing imputation genotypes with ‘true' genotypes typed on ImmunoChip in three European populations (Dutch, British, and Italian). GoNL showed significant improvement in the imputation quality for rare variants (MAF 0.05–0.5%) compared with 1000G. In Dutch samples, the mean observed Pearson correlation, r2, increased from 0.61 to 0.71. We also saw improved imputation accuracy for other European populations (in the British samples, r2 improved from 0.58 to 0.65, and in the Italians from 0.43 to 0.47). A combined reference set comprising 1000G and GoNL improved the imputation of rare variants even further. The Italian samples benefitted the most from this combined reference (the mean r2 increased from 0.47 to 0.50). We conclude that the creation of a large population-specific reference is advantageous for imputing rare variants and that a combined reference panel across multiple populations yields the best imputation results

Age in aortic disease:The path towards atrial fibrillation

Background: Aging induces structural remodeling, altering atrial electrogram morphology. Over time, structural and consequently electrical remodeling creates a substrate for atrial fibrillation. In structural heart disease, age-induced remodeling comes on top of a pre-existing degree of structural remodeling due to pressure or volume overload. Objective: Investigate the severity of age-related electrical remodeling in patients undergoing surgery for structural heart disease by utilizing a high resolution epicardial mapping approach. Methods: Five seconds of sinus rhythm were recorded intraoperatively at the right atrium (RA), Bachmann's bundle (BB), the left atrium, and the pulmonary vein area. Potential voltage, low-voltage area (LVA) and conduction velocity (CV) were assessed in all regions. Results: 104 patients were included (62,5 % male, age: 26–84 years) and categorized in three age groups: young-age (age &lt;60 years, n = 40), middle-age (age 60–71 years, n = 33), or old-age (age ≥72 years, n = 31) group. Compared to the young-age group, the old-age group had 1) lower median potential voltages at RA (4.65 [3.53–5.62]mV versus 5.94 [4.86–6.79]mV, p = 0.001) and 2) lower CV at RA (87.86 [82.53–96.67]cm/s versus 94.81 [90.14–98.59]cm/s, p = 0.016) and BB (83.38 [67.72–94.96]cm/s versus 98.84 [86.58–102.90]cm/s, p = 0.005). Conclusions: Age-related electrophysiological changes in patients with structural heart disease include reduction in atrial potential voltages and slowing of CV. These changes were less pronounced in the middle-age group. This indicates that electrical remodeling is a combination of both the underlying heart disease and the aging process. However, the less pronounced changes in the middle-age group may reflect a more gradual progression of age-related remodeling.</p

Issues and recommendations from the OHBM COBIDAS MEEG committee for reproducible EEG and MEG research

The Organization for Human Brain Mapping (OHBM) has been active in advocating for the instantiation of best practices in neuroimaging data acquisition, analysis, reporting and sharing of both data and analysis code to deal with issues in science related to reproducibility and replicability. Here we summarize recommendations for such practices in magnetoencephalographic (MEG) and electroencephalographic (EEG) research, recently developed by the OHBM neuroimaging community known by the abbreviated name of COBIDAS MEEG. We discuss the rationale for the guidelines and their general content, which encompass many topics under active discussion in the field. We highlight future opportunities and challenges to maximizing the sharing and exploitation of MEG and EEG data, and we also discuss how this ‘living’ set of guidelines will evolve to continually address new developments in neurophysiological assessment methods and multimodal integration of neurophysiological data with other data types.Peer reviewe

Restrictive Atrial Dysfunction in Cardiac Amyloidosis: Differences between Immunoglobulin Light Chain and Transthyretin Cardiac Amyloidosis Patients

Background: In cardiac amyloidosis, the prevalence of thromboembolic events and atrial fibrillation is higher in transthyretin amyloidosis compared to immunoglobulin light chain amyloidosis. Therefore, we hypothesize that transthyretin cardiac amyloidosis patients have worse atrial function. Purpose: To explore the left atrial function by conventional ultrasound and strain analysis in immunoglobulin light chain- and transthyretin cardiac amyloidosis patients. Methods: In cardiac amyloidosis patients in our Amyloidosis Expert Center, echocardiographic strain analysis was performed using speckle tracking. Results: The data of 53 cardiac amyloidosis patients (83% male, mean age 70 years) were analyzed. Transthyretin cardiac amyloidosis patients (n = 24, 45%) were older (75 ± 5.6 vs. 65 ± 7.2 years, p < 0.001) and had more left ventricular (LV) hypertrophy than immunoglobulin light chain cardiac amyloidosis patients (n = 29, 55%). However, LV systolic and diastolic function did not differ, nor did left atrial dimensions (LAVI 56(24) vs. 50(31) mL/m 2). Left atrial reservoir strain was markedly lower in transthyretin cardiac amyloidosis (7.4(6.2) vs. 13.6(14.7), p = 0.017). This association was independent of other measurements of the left atrial and ventricular function. Conclusions: Transthyretin cardiac amyloidosis patients had lower left atrial reservoir function compared to immunoglobulin light chain cardiac amyloidosis patients although the left atrial geometry was similar. Interestingly, this association was independent of left atrial- and LV ejection fraction and global longitudinal strain. Further research is warranted to assess the impact of impaired left atrial dysfunction in transthyretin cardiac amyloidosis on atrial fibrillation burden and prognosis

Postoperative Metamorphopsia in Macula-Off Rhegmatogenous Retinal Detachment:Associations with Visual Function, Vision Related Quality of Life, and Optical Coherence Tomography Findings

To evaluate postoperative metamorphopsia in macula-off rhegmatogenous retinal detachment (RRD) and its association with visual function, vision related quality of life, and optical coherence tomography (OCT) findings.45 patients with primary macula-off RRD were included. At 12 months postoperatively, data on metamorphopsia using sine amsler charts (SAC), best corrected visual acuity (BCVA), letter contrast sensitivity, color vision (saturated and desaturated color confusion indexes), critical print size, reading acuity, the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and OCT, were obtained.Metamorphopsia was present in 39 patients (88.6%), with most of them (n = 35, 77.8%) showing only mild metamorphopsia (SAC score = 1). Patients with metamorphopsia had significantly worse postoperative BCVA (p = 0.02), critical print size (p<0.0005), and reading acuity (p = 0.001) compared to patients without metamorphopsia. Other visual function outcomes and NEI-VFQ-25 overall composite score were all also somewhat lower in patients with metamorphopsia, but this did not reach statistical significance. No association with OCT findings was present.The prevalence of postoperative metamorphopsia in macula-off RRD patients is high, however, the degree of metamorphopsia is relatively low. When metamorphopsia is present, visual functions seem to be compromised, while vision related quality of life is only mildly affected

Resolving unknown nucleotides in the IPD-IMGT/HLA database by extended and full-length sequencing of HLA class I and II alleles

In the past, identification of HLA alleles was limited to sequencing the region of the gene coding for the peptide binding groove, resulting in a lack of sequence information in the HLA database, challenging HLA allele assignment software programs. We investigated full-length sequences of 19 HLA class I and 7 HLA class II alleles, and we extended another 47 HLA class I alleles with sequences of 5′ and 3′ UTR regions that were all not yet available in the IPD-IMGT/HLA database. We resolved 8638 unknown nucleotides in the coding sequence of HLA class I and 2139 of HLA class II. Furthermore, with full-length sequencing of the 26 alleles, more than 90 kb of sequence information was added to the non-coding sequences, whereas extension of the 47 alleles resulted in the addition of 5.5 kb unknown nucleotides to the 5′ UTR and &gt; 31.7 kb to the 3′ UTR region. With this information, some interesting features were observed, like possible recombination events and lineage evolutionary origins. The continuing increase in the availability of full-length sequences in the HLA database will enable the identification of the evolutionary origin and will help the community to improve the alignment and assignment accuracy of HLA alleles.</p

Sexual minority youth and depressive symptoms or depressive disorder: A systematic review and meta-analysis of population-based studies

Objective: Research has suggested that sexual minority young people are more likely to have depressive symptoms or depressive disorder, but to date most studies in the field have relied on convenience-based samples. This study overcomes this limitation by systematically reviewing the literature from population-based studies and conducting a meta-analysis to identify whether depressive disorder and depressive symptoms are elevated in sexual minority youth. Method: A systematic review and meta-analysis were conducted and informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to determine if rates of depressive symptoms or depressive disorder differ for sexual minority youth, relative to heterosexual adolescents. MEDLINE, PsycINFO, EMBASE and ERIC databases were searched. Studies reporting depressive symptom data or the prevalence of depressive disorder in population-based samples of adolescents, that included sexual minority youth and heterosexual young people, were included in the review. A meta-analysis was conducted to examine differences between groups. Results: Twenty-three articles met the inclusion criteria. The proportion of sexual minority youth in the studies ranged from 2.3% to 12%. Sexual minority youth reported higher rates of depressive symptoms and depressive disorder (odds ratio = 2.94, pConclusions: There is robust evidence that rates of depressive disorder and depressive symptoms are elevated in sexual minority youth in comparison to heterosexual young people. Despite the elevated risk of depressive symptoms or depressive disorder for sexual minority youth, the treatment for this group of young people has received little attention