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Carotid intima media thickness (cIMT) is a biomarker of subclinical atherosclerosis and a predictor of future cardiovascular events. Identifying associations between gene expression levels and cIMT may provide insight to atherosclerosis etiology. Here, we use two approaches to identify associations between mRNA levels and cIMT: differential gene expression analysis in whole blood and S-PrediXcan. We used microarrays to measure genome-wide whole blood mRNA levels of 5647 European individuals from four studies. We examined the association of mRNA levels with cIMT adjusted for various potential confounders. Significant associations were tested for replication in three studies totaling 3943 participants. Next, we applied S-PrediXcan to summary statistics from a cIMT genome-wide association study (GWAS) of 71 128 individuals to estimate the association between genetically determined mRNA levels and cIMT and replicated these analyses using S-PrediXcan on an independent GWAS on cIMT that included 22 179 individuals from the UK Biobank. mRNA levels of TNFAIP3, CEBPD and METRNL were inversely associated with cIMT, but these associations were not significant in the replication analysis. S-PrediXcan identified associations between cIMT and genetically determined mRNA levels for 36 genes, of which six were significant in the replication analysis, including TLN2, which had not been previously reported for cIMT. There was weak correlation between our results using differential gene expression analysis and S-PrediXcan. Differential expression analysis and S-PrediXcan represent complementary approaches for the discovery of associations between phenotypes and gene expression. Using these approaches, we prioritize TNFAIP3, CEBPD, METRNL and TLN2 as new candidate genes whose differential expression might modulate cIMT.

From the early 2000s onward, scientists, politicians, and intellectuals have presented the South African gene pool as a new archive for the new nation, suggesting a non-racial unity in diversity through common human origins. In this discourse, population genomics and genetic ancestry allude to metaphors of shared kinship to overcome the legacies of race. However, a focus on the underlying practices of measuring and classification reveals how the genomic archive is implicated in the history of apartheid and its racialized subjectivities. Similarly, individual interpretations of genetic ancestry show that race is constantly brought forth in this archival process. The genomic archive interweaves measuring practices in the sciences with the politics of social and biographical experience—a relationship that is at the heart of genetic genealogies.

In this paper I explore the nexus of slavery, diaspora, and citizenship through the close examination of the complex negotiations of “diasporic citizenship” in Ghana. Over the past 25 years, Ghana ...

Psychosocial and biological factors influence the perception of physical changes during pregnancy. Some pregnant women present to the obstetric emergency department (ED) with diverse symptoms not requiring urgent medical action. These visits result in over-consultation, tying up resources and inflating health care expenses. This study outlines factors associated with multiple ED visits during pregnancy, measures the prevalence of anxiety and depression, and explores the choice of maternity clinic for delivery aiming to elucidate options for care strategies. This prospective, cross-sectional, questionnaire-based bicentric study was performed in the obstetric outpatient departments of two university hospitals in Germany and recruited pregnant women between 12/2016 and 11/2017. The questionnaire included socio-demographics, obstetric history, anxiety (GAD-7), depression (PHQ-9), and health status (WHO-5, SF-12). This analysis included 496 women and showed that women with numerous ED visits were significantly younger (p

Although herbivory is widespread among mammals, few species have adopted a strategy of dietary specialization. Feeding on a single plant species often exposes herbivores to high doses of plant secondary metabolites (PSMs), which may exceed the animal's detoxification capacities. Theory predicts that specialists will have unique detoxification mechanisms to process high levels of dietary toxins. To evaluate this hypothesis, we compared liver microsomal metabolism of a juniper specialist, Neotoma stephensi (diet >85% juniper), to a generalist, N. albigula (diet ≤30% juniper). Specifically, we quantified the concentration of a key detoxification enzyme, cytochrome P450 2B (CYP2B) in liver microsomes, and the metabolism of α-pinene, the most abundant terpene in the juniper species consumed by the specialist woodrat. In both species, a 30% juniper diet increased the total CYP2B concentration (2-3×) in microsomes and microsomal α-pinene metabolism rates (4-fold). In N. stephensi, higher levels of dietary juniper (60% and 100%) further induced CYP2B and increased metabolism rates of α-pinene. Although no species-specific differences in metabolism rates were observed at 30% dietary juniper, total microsomal CYP2B concentration was 1.7× higher in N. stephensi than in N. albigula (p

Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. Methods: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. Results: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci ( TTN , CAND2 , SCN10A , PITX2 , CAV1 , SYNPO2L , SOX5 , TBX5, MYH6, RPL3L ). The top variants at known sarcomere genes ( TTN, MYH6 ) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A ) were associated with longer PWD but lower AF risk. Conclusions: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.

Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes.Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

What have affirmative action policies, categorization of care needs, plastic surgery, forensic identification of dead bodies and age assessments of refugees in common? They all determine recognitio...

The city of Bulawayo has had water problems since its establishment. This is partly due to the semi-arid climate within which it is situated, but also to rising levels of demand that have not been met with adequate supply. There are many disagreements among various stakeholders around ownership and management of water infrastructure. Between 2005 and 2015, two waves of protests occurred that had a profound impact on citizen-state relations at both the national and local levels of government. The first wave, 2005–2008, was supported by local city authorities as well as residents. They directed their protest at the ruling government’s decision to effectively transfer the management and ownership of the city’s water resources to a central government agency, the Zimbabwe National Water Authority (ZINWA). The transfer to that agency was part of a national program supposedly meant to improve water provision in the country’s cities and towns. However, the residents of Bulawayo and other cities that were run by the opposition regarded this decision about a common good – water – as a paternalistic assault on their political autonomy. In the end, these protests were successful, and Bulawayo remained the only city in control of its water resources. A few years later, the second wave of protests, 2011–2015, took a different turn. This time, people directed their protest at the City of Bulawayo and its decision to privatize the common good by introducing prepaid water meters. Again, the city’s rationale for the intended changes in the water management system was, purportedly, to improve supply and access. Yet, the residents of Bulawayo fiercely rejected this intervention, this time framing their protests in the language of indignation and need. This chapter critically engages the shifting political subjectivities of protesters in relation to national and local authorities in Bulawayo. By rethinking the notion of water as a common good, it also critically engages the concept of the moral economy as a lens of interpreting the ways in which the citizens in Bulawayo perceive and engage with the state.

Background DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. Results We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data. Conclusions Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.

BACKGROUND: Recent genome-wide association studies (GWASs) identified the first genetic loci associated with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The next step is to use these results to increase our understanding of the biological mechanisms involved. Most of the identified variants likely influence gene regulation. The aim of the current study is to shed light on the mechanisms underlying the genetic signals and prioritize genes by integrating GWAS results with gene expression and DNA methylation (DNAm) levels.METHODS: We applied summary-data-based Mendelian randomization to integrate ADHD and ASD GWAS data with fetal brain expression and methylation quantitative trait loci, given the early onset of these disorders. We also analyzed expression and methylation quantitative trait loci datasets of adult brain and blood, as these provide increased statistical power. We subsequently used summary-data-based Mendelian randomization to investigate if the same variant influences both DNAm and gene expression levels.RESULTS: We identified multiple gene expression and DNAm levels in fetal brain at chromosomes 1 and 17 that were associated with ADHD and ASD, respectively, through pleiotropy at shared genetic variants. The analyses in brain and blood showed additional associated gene expression and DNAm levels at the same and additional loci, likely because of increased statistical power. Several of the associated genes have not been identified in ADHD and ASD GWASs before.CONCLUSIONS: Our findings identified the genetic variants associated with ADHD and ASD that likely act through gene regulation. This facilitates prioritization of candidate genes for functional follow-up studies.

Publisher's version (útgefin grein), The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease., We provide all investigator and study-specific acknowledgements in Supplementary Note 1, and funding sources in Supplementary Note 2.

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The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality1,2. We performed multi-ancestry (N=293,051) and European only (N=271,570) genome-wide association (GWAS) meta-analyses for the PR interval, discovering 210 loci of which 149 are novel. Variants at all loci nearly doubled the percentage of heritability explained, from 33.5% to 62.6%. We observed enrichment for genes involved in cardiac muscle development/contraction and the cytoskeleton highlighting key regulation processes for atrioventricular conduction. Additionally, 19 novel loci harbour genes underlying inherited monogenic heart diseases suggesting the role of these genes in cardiovascular pathology in the general population. We showed that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease risk, including distal conduction disease, AF, atrioventricular pre-excitation, non-ischemic cardiomyopathy, and coronary heart disease. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.

BACKGROUND Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions.OBJECTIVES This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.METHODS Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 +/- 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs.RESULTS Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals.CONCLUSIONS The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms. (C) 2019 by the American College of Cardiology Foundation.

Purpose: Reduction of maternal morbidity and mortality is a major worldwide objective anchored in the millennium goals of the United Nations. To improve fetal and maternal care, a constant attempt to discover groundbreaking technologies is ongoing. One approach is the enhancement of non-invasive fetal ECG devices. Most importantly, acceptance of new technologies by pregnant women is a prerequisite for successful implementation. Methods: This questionnaire-based study conducted at the University Hospital Heidelberg, Germany between May and June 2017 evaluates pregnant women’s attitudes towards a new device for fetal ECG monitoring and its potential home usage. The study population was questioned after exposure to the Parides/Atlantis prototype (Nemo Healthcare, Veldhoven, The Netherlands), whereas the maternal and gestational age-matched control group was left to envision telemedical topics. Results: The prototype and its potential usage in a clinical and telemedical setting was highly accepted, and its comfort and appearance satisfied participants. Its use caused significantly improved telemedical understanding as envision increased (p = 0.0015). Implementation and integration of telemedical devices into antenatal care was significantly preferred by the study group (p = 0.0011), though participants desire more specific features for their personal use. Optional home-based self-monitoring to reduce scheduled doctoral visits (p = 0.0004) as well as self-assessment prior to self-initiated, unscheduled consultation (p < 0.0001) could be affected positively by such a device. Furthermore, it could reduce face-to-face interaction with the care provider (p = 0.0163). Conclusions: The positive feedback on remote self-monitoring might open options for a more “patient as partners” oriented prenatal care in the future. Safety and reliability remain a major issue. More comprehensive studies with new technologies are needed to diligently ensure quality of care. Finally, results for new technologies must be communicated to pregnant women for their acceptance and usage of new devices.

This paper discusses the articulation and complex enactment of postcolonial indigeneity, commonly referred to as Khoesan revivalism in contemporary South Africa. Through a close examination of the “substances of indigeneity,” i.e. body casts, human remains and DNA, it interrogates the partial imbrication of past and present scientific and classificatory practices with contemporary political and affective identifications. It argues that, in this constellation, the indigenous does not signify a stable point of reference or remnant of the past, but rather a subject position that is actively claimed and enacted in the present.

Zusammenfassung Im Mittelpunkt dieses Artikels steht eine populationsgenetische Stichprobe im sudafrikanischen Simon’s Town, die im Rahmen des globalen Genographic Project erhoben wurde. Simon’s Town war wahrend der Apartheid besonders stark von Zwangsumsiedlungen der nicht-weisen Bevolkerung betroffen. Nach 1994 fanden sich einige der ehemaligen BewohnerInnen zum Project Phoenix zusammen, um an das Leben im Ort und die Gewalterfahrung der Vertreibungen zu erinnern. Der genetische Abstammungstest, der in Zusammenarbeit mit dem lokalen Museum organisiert wurde, schloss rhetorisch an das Narrativ von Herkunft, Zugehorigkeit und Diversitat an, das auch pragend fur die Erinnerungspolitik des Phonix-Projekts war. Daruber hinaus reprasentierten die VeranstalterInnen die Studie (und deren Ergebnisse) als Illustration einer „post-racial society“, im Sinne des Slogans der Einheit in der Vielfalt. In meinem Beitrag zeichne ich die zugrundeliegende Identifikationspraktik nach und zeige auf, wie hier die Klassifikati...

SummaryWhile many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear.To identify these effects, we performedcis-andtrans-expressionquantitative trait locus (eQTL) analysis in blood from 31,684 individuals through the eQTLGen Consortium.We observed thatcis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting our ability to usecis-eQTLs to pinpoint causal genes within susceptibility loci.In contrast, trans-eQTLs (detected for 37% of 10,317 studied trait-associated variants) were more informative. Multiple unlinked variants, associated to the same complex trait, often converged on trans-genes that are known to play central roles in disease etiology.We observed the same when ascertaining the effect of polygenic scores calculated for 1,263 genome-wide association study (GWAS) traits. Expression levels of 13% of the studied genes correlated with polygenic scores, and many resulting genes are known to drive these traits.

BackgroundThe demand for fetal monitoring and constant reassurance is high in pregnant women. Consequently, pregnant women use various health apps and are more likely to visit emergency departments due to subjective but nonurgent complaints. However, electronic health (eHealth) and mobile health (mHealth) solutions are rarely used to prevent nonurgent emergency consultations. To implement modern care solutions, a better understanding of the attitudes, fears, and hopes of health care professionals toward eHealth and mHealth is needed. ObjectiveThe aim of this study was to investigate the attitudes of health care professionals in obstetrics toward telemedicine. MethodsA quantitative Web-based survey on health care professionals in obstetrics in Germany was conducted. The participants included nurses, midwives, and physicians of all age groups and job positions working in hospitals that provide various levels of health care. The questionnaire comprised 24 questions about the characteristics of the study population, views about emergency consultations in obstetrics, attitude toward telemedicine, job satisfaction, and sleeping behavior. ResultsIn total, 244 health care professionals participated in the Web-based survey. In general, health care professionals were skeptical (170/233, 72.9%) about the use of telemedicine in obstetrics; however, 55.8% (130/233) recognized its potential. Moreover, 72% (62/86) of physicians were optimistic in using apps for pregnancy monitoring, whereas 36.1% (47/130) of nonphysicians (P

BACKGROUND Pregnancy can be distressing, particularly if expectant mothers are worried about the well-being of their fetus. Consequently, the desire for reassurance and frequent fetal monitoring is often pronounced. Smart wearable devices and telemedicine are promising tools that could assist women in self-monitoring their pregnancy at home, hence disburdening emergency departments (EDs). They present the possibility to clarify the need for urgent care remotely and offer tighter pregnancy monitoring. However, patients’ acceptance of such new technologies for fetal monitoring has not yet been explored extensively. OBJECTIVE This survey aimed to elucidate the attitudes of women toward self-monitoring of their pregnancy using noninvasive electronic devices. The technical details of the proposed devices were not specified. METHODS A cross-sectional multicenter study was conducted at the departments of obstetrics of the University Hospitals of Heidelberg and Leipzig, Germany. All patients seen in the obstetrics clinic who were above 18 years were offered participation. We designed a survey questionnaire including validated instruments covering population characteristics, issues in current and past pregnancies, as well as attitudes toward self-monitoring of pregnancy with smart devices. RESULTS A total of 509 pregnant women with no previous experience in telemedicine participated. Only a small minority of 5.9% (29/493) regarded self-monitoring with wearable devices as an alternative to consulting their physicians. Along these lines, only 7.7% (38/496) strongly believed they would visit the ED less often if such devices were readily available. However, if the procedure were combined with a Web-based telemetric physician consult, 13.5% (66/487) would be highly motivated to use the devices. Furthermore, significantly more women regarded it as an alternative prior to seeing a doctor when they perceived a decline in fetal movements (P CONCLUSIONS Our results point to a skeptical attitude toward pregnancy self-monitoring among pregnant women. Nevertheless, many women are open to using devices for pregnancy monitoring in parallel to consulting their physician. The intention to use such devices several times daily or weekly, expressed by more than half of the participants, highlights the potential of such technologies.

Background: QT interval (QT) genome-wide association studies (GWAS) have identified upwards of 35 common variant loci, including SNPs adjacent to putative transcription elongation factor TCEA3. Transcription elongation control has broad effects on gene expression, the misregulation of which is known to influence cardiac conduction system morphogenesis as well as activation or repression of key regulatory genes. Thus, we hypothesized that a genome-wide gene-gene interaction study of TCEA3 lead SNP rs2298632 would identify novel loci that influence QT. Methods: Using 1000 Genomes imputed data (>20 million SNPs) in n=67,445 participants (69% Caucasian; 18% Hispanic/Latino; 11% African American) from 10 studies, we conducted genome-wide meta-analyses to test for the presence of: interaction effect loci by examining rs2298632xSNP interactions on QT; and joint effect loci by simultaneously examining SNP main effects and rs2298632xSNP interactions on QT. Inverse-variance weighted meta-analysis of genomically controlled ancestry- and study-specific summary effects estimated using multivariable adjusted linear models or generalized estimating equations that incorporated robust standard errors was performed using METAL. SNPs demonstrating evidence of heterogeneity (Cochran’s Q P < 0.05) and SNPs that were infrequent or rare (minor allele frequency [MAF] Results: We identified one genome-wide significant interaction effect locus ( P INT -8 ) at PVT1 (lead SNP: rs4733591; mean MAF = 32%), a long non-coding RNA gene for which previous GWAS identified suggestive associations with left ventricular systolic dysfunction. We also identified four genome-wide significant joint effect loci ( P JOINT -8 ) that mapped within or nearby NUCKS1 (lead SNP: rs823094; MAF = 0.33) , CASR (lead SNP = rs17251221; MAF = 0.13) , ACTBL2 (lead SNP = rs7737409; MAF = 0.22) , and KDM1B (lead SNP = rs34969716; MAF = 0.26) , loci with roles in calcium sensing, regulation of gene expression through histone modification, and tumor suppression. Conclusion: Extension of traditional main effects GWAS to interrogate gene-gene interactions for biologically motivated loci like TCEA3 may help inform the structure and function of genetic pathways underlying complex traits like QT.

BACKGROUND Pregnant women have a high demand for fetal monitoring and reassurance. Consequently, they use a variety of health applications in pregnancy and tend to visit emergency departments for objectively non-urgent consults. However, the potential of electronic Health (eHealth) and mobile Health (mHealth) solutions is clinically hardly used to prevent non-urgent emergency consultations. To implement modern care solutions a better understanding of the attitudes, fears and hopes of health care professionals towards eHealth and mHealth is needed. OBJECTIVE The aim of this study was to investigate the attitudes of health care professionals in obstetrics towards telemedicine. METHODS A quantitative web based survey among health care professionals in Germany was conducted. The participants included nurses, midwives and physicians of all age groups and job positions working in hospitals with various level of care. The questionnaire comprised 24 questions capturing study population characteristics, views about emergency consultations in obstetrics, attitude towards telemedicine, job satisfaction and sleeping behavior. RESULTS 244 health care professionals participated in the online survey. In general, health care professionals are skeptical (72.9%; n=170) about the use of telemedicine in obstetrics, however, 55.8% (n=130) recognize its potential. Physicians are optimistic with 72% (n=62) considering the use of applications (apps) for pregnancy monitoring reasonable by contrast to just 36% (n=47) of non-physicians (P CONCLUSIONS Our study reveals an ambivalent attitude towards telemedicine among health care professionals in obstetrics. Efforts to promote the use of telemedicine should concentrate on nurses and midwives since this group is most skeptical about it in Germany. By contrast, particularly young physicians recognize the potential of apps for patient care and would like to use such technology in pregnancy monitoring.

Background: We developed a novel electrocardiographic marker, T-wave area dispersion (TW-Ad), which measures repolarization heterogeneity by assessing interlead T-wave areas during a single cardiac cycle and tested whether it can identify patients at risk for sudden cardiac death (SCD) in the general population. Methods and Results: TW-Ad was measured from standard digital 12-lead ECG in 5618 adults (46% men; age, 50.9±12.5 years) participating in the Health 2000 Study—an epidemiological survey representative of the Finnish adult population. Independent replication was performed in 3831 participants of the KORA S4 Study (Cooperative Health Research in the Region of Augsburg; 49% men; age, 48.7±13.7 years; mean follow-up, 8.8±1.1 years). During follow-up (7.7±1.4 years), 72 SCDs occurred in the Health 2000 Survey. Lower TW-Ad was univariately associated with SCD (0.32±0.36 versus 0.60±0.19; P P P P P Conclusion: Low TW-Ad, reflecting increased heterogeneity of repolarization, in standard 12-lead resting ECGs is a powerful and independent predictor of SCD in the adult general population.

Atrial fibrillation (AF) affects more than 33 million individuals worldwide 1 and has a complex heritability 2 . We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.