Informed consent procedures in patients with an acute inability to provide informed consent : Policy and practice in the CENTER-TBI study

Purpose: Enrolling traumatic brain injury (731) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice. Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries. Results: Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N 426;20%) and deferred consent (N 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%). Conclusions: Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers. (C) 2020 Published by Elsevier Inc.Peer reviewe

Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations. (C) 2020 The Authors. Published by Elsevier Inc.Peer reviewe

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Peer reviewe

Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury

Publisher Copyright: © 2022, The Author(s).Traumatic brain injury (TBI) is frequently associated with neuropsychiatric impairments such as symptoms of post-traumatic stress disorder (PTSD), which can be screened using self-report instruments such as the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). The current study aims to inspect the factorial validity and cross-linguistic equivalence of the PCL-5 in individuals after TBI with differential severity. Data for six language groups (n ≥ 200; Dutch, English, Finnish, Italian, Norwegian, Spanish) were extracted from the CENTER-TBI study database. Factorial validity of PTSD was evaluated using confirmatory factor analyses (CFA), and compared between four concurrent structural models. A multi-group CFA approach was utilized to investigate the measurement invariance (MI) of the PCL-5 across languages. All structural models showed satisfactory goodness-of-fit with small between-model variation. The original DSM-5 model for PTSD provided solid evidence of MI across the language groups. The current study underlines the validity of the clinical DSM-5 conceptualization of PTSD and demonstrates the comparability of PCL-5 symptom scores between language versions in individuals after TBI. Future studies should apply MI methods to other sociodemographic (e.g., age, gender) and injury-related (e.g., TBI severity) characteristics to improve the monitoring and clinical care of individuals suffering from PTSD symptoms after TBI.Peer reviewe

Hexa-X the European 6G Flagship Project

Hexa-X will pave the way to the next generation of wireless networks (Hexa) by explorative research (X). The Hexa-X vision is to connect human, physical, and digital worlds with a fabric of sixth generation (6G) key enablers. The vision is driven by the ambition to contribute to objectives of growth, global sustainability, trustworthiness, and digital inclusion. Key 6G value indicators and use cases are defined against the background of technology push, society and industry pull as well as objectives of technology sovereignty. Key areas of research have been formulated accordingly to include connecting intelligence, network of networks, sustainability, global service coverage, extreme experience, and trustworthiness. Critical technology enablers for 6G are developed in the project including, sub-THz transceiver technologies, accurate stand-alone positioning and radio-based imaging, improved radio performance, artificial intelligence (AI) / machine learning (ML) inspired radio access network (RAN) technologies, future network architectures and special purpose solutions including future ultra-reliable low-latency communication (URLLC) schemes. Besides technology enablers, early trials will be carried out to help assess viability and performance aspects of the key technology enablers. The 6G Hexa-X project is integral part of European and global research effort to help define the best possible next generation of networks

Hexa-X the European 6G Flagship Project

Hexa-X will pave the way to the next generation of wireless networks (Hexa) by explorative research (X). The Hexa-X vision is to connect human, physical, and digital worlds with a fabric of sixth generation (6G) key enablers. The vision is driven by the ambition to contribute to objectives of growth, global sustainability, trustworthiness, and digital inclusion. Key 6G value indicators and use cases are defined against the background of technology push, society and industry pull as well as objectives of technology sovereignty. Key areas of research have been formulated accordingly to include connecting intelligence, network of networks, sustainability, global service coverage, extreme experience, and trustworthiness. Critical technology enablers for 6G are developed in the project including, sub-THz transceiver technologies, accurate stand-alone positioning and radio-based imaging, improved radio performance, artificial intelligence (AI) / machine learning (ML) inspired radio access network (RAN) technologies, future network architectures and special purpose solutions including future ultra-reliable low-latency communication (URLLC) schemes. Besides technology enablers, early trials will be carried out to help assess viability and performance aspects of the key technology enablers. The 6G Hexa-X project is integral part of European and global research effort to help define the best possible next generation of networks

Inframe insertion and splice site variants in MFGE8 associate with protection against coronary atherosclerosis

Publisher Copyright: © 2022. The Author(s).A genome-wide association study identifies MFGE8 as protective against coronary atherosclerosis in European and East Asian populations. Cardiovascular diseases are the leading cause of premature death and disability worldwide, with both genetic and environmental determinants. While genome-wide association studies have identified multiple genetic loci associated with cardiovascular diseases, exact genes driving these associations remain mostly uncovered. Due to Finland's population history, many deleterious and high-impact variants are enriched in the Finnish population giving a possibility to find genetic associations for protein-truncating variants that likely tie the association to a gene and that would not be detected elsewhere. In a large Finnish biobank study FinnGen, we identified an association between an inframe insertion rs534125149 in MFGE8 (encoding lactadherin) and protection against coronary atherosclerosis. This variant is highly enriched in Finland, and the protective association was replicated in meta-analysis of BioBank Japan and Estonian biobank. Additionally, we identified a protective association between splice acceptor variant rs201988637 in MFGE8 and coronary atherosclerosis, independent of the rs534125149, with no significant risk-increasing associations. This variant was also associated with lower pulse pressure, pointing towards a function of MFGE8 in arterial aging also in humans in addition to previous evidence in mice. In conclusion, our results suggest that inhibiting the production of lactadherin could lower the risk for coronary heart disease substantially.Peer reviewe

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis