Metabolites are small molecules involved in cellular metabolism where they act as reaction substrates or products. The term ‘metabolomics’ refers to the comprehensive study of these molecules. The concentrations of metabolites in biological tissues are under genetic control, but this is limited by environmental factors such as diet. In adult mono- and dizygotic twin pairs, we estimated the contribution of genetic and shared environmental influences on metabolite levels by structural equation modeling and tested whether the familial resemblance for metabolite levels is mainly explained by genetic or by environmental factors that are shared by family members. Metabolites were measured across three platforms: two based on proton nuclear magnetic resonance techniques and one employing mass spectrometry. These three platforms comprised 237 single metabolic traits of several chemical classes. For the three platforms, metabolites were assessed in 1407, 1037 and 1116 twin pairs, respectively. We carried out power calculations to establish what percentage of shared environmental variance could be detected given these sample sizes. Our study did not find evidence for a systematic contribution of shared environment, defined as the influence of growing up together in the same household, on metabolites assessed in adulthood. Significant heritability was observed for nearly all 237 metabolites; significant contribution of the shared environment was limited to 6 metabolites. The top quartile of the heritability distribution was populated by 5 of the 11 investigated chemical classes. In this quartile, metabolites of the class lipoprotein were significantly overrepresented, whereas metabolites of classes glycerophospholipids and glycerolipids were significantly underrepresented.

Results of comprehensive particle image velocimetry measurements investigating the dynamics of turbulent jets in a rotating fluid are presented. It is observed that background system rotation induces a time-periodic formation–breakdown cycle of the jets. The flow dynamics associated with this process is studied in detail. It is found that the frequency of the cycle increases linearly with the background rotation rate. The data show that the onset of the breakdown phase and of the reformation phase of the cycle can be characterized in terms of a local Rossby number employing an internal velocity and a length scale of the jet. The critical values for this local Rossby number, for onset of breakdown and reformation, scale linearly with a global Rossby number based on the flow conditions at the source. The analysis of the experimental data suggests centrifugal instability as the potential origin of the formation–breakdown cycle.

In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of ${>}200~\text{TW}$ was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.

Background: Continuous video-EEG (cvEEG) monitoring is the standard of care for diagnosis and management of neonatal seizures. However, it is labour-intensive. We aimed to establish consistency in monitoring of newborns utilising NICU nurses. Methods: Neonatal nurses were trained to apply scalp electrodes, troubleshoot technical issues. Guidelines, checklists and visual training modules were developed. A central network system allowed remote access to the cvEEGs by the epileptologist for timely interpretation and feedback. We compared 100 infants with moderate to severe HIE before and after the training program. Results: 192 cvEEGs were performed. Of the 100 infants compared; time to initiate brain monitoring decreased by average of 31.5 hours, in electrographic seizure detection increased(20% compared to 34% a), seizure clinical misdiagnosis decreased (65% compared to 36% ), and Anti-Seizure burden decreased. Conclusions: Training experienced NICU nurses to set-up, start and monitor cvEEG can decrease the time to initiate cvEEG which may lead to better seizure diagnosis and management.

Introduction: Online medical education resources are widely used in emergency medicine (EM), but strategies to assess quality remain elusive. We previously derived the Medical Education Translational Resources: Impact and Quality (METRIQ) 8 instrument to evaluate quality in medical education blog posts. Methods: As part of a subsequent validation study (The METRIQ Blog Study), a mixed-methods usability analysis was performed to obtain user feedback on the quality assessment instrument in order to improve its clarity and reliability. Participants in the METRIQ Study were first asked to rate five blog posts using the METRIQ-8 Score. They then evaluated the METRIQ-8 instruments ease of use and likelihood of being recommended to others using a 7-point Likert scale and free text comments. Participants were also asked to flag and comment on items within the score that they felt were unclear. Global usability ratings were summarized using median scores or percent rated unclear. We used ANOVA to test associations between ease of use and demographic factors. A thematic analysis was performed on the comments. Results: 309 EM medical students, residents, and attendings completed the survey. Global ratings were generally very favorable (median 2 [IQR 2-3], with 7 being the lowest score) for ease of use and likelihood of recommendation, and did not vary by participants country of origin, frequency of blog use, or learner level. Participants stated that the score was structured, systematic, and straightforward. They found it useful for junior learners and for guiding blog creation. Four questions in the score (questions 2, 4, 5, and 7) were identified by 10% of subjects to be unclear. Thematic analysis of comments identified suggested four main themes for improving the score: adding clearer definitions with marking rubrics; shortening the 7-point scale; adding items evaluating blog post presentation and utility; and, rephrasing the wording of certain questions for clarity. Conclusion: A mixed methods usability analysis of the METRIQ-8 instrument for assessing blog quality was globally well received by EM medical students, residents, and attendings. Qualitative analyses revealed multiple areas to improve the instruments clarity and usability. The METRIQ score is a promising instrument for evaluating the quality of blogs; further development and testing is needed to improve its utility.

Inland water bodies contain significant amounts of carbon in the form of dissolved inorganic carbon (DIC) derived from a mixture of modern atmospheric and pre-aged sources, which needs to be considered in radiocarbon-based dating and natural isotope tracer studies. While reservoir effects in hardwater lakes are generally considered to be constant through time, a comparison of recent and historical DI14C data from 2013 and 1969 for Lake Constance reveals that this is not a valid assumption. We hypothesize that changes in atmospheric carbon contributions to lake water DIC have taken place due to anthropogenically forced eutrophication in the 20th century. A return to more oligotrophic conditions in the lake led to reoxygenation and enhanced terrigenous organic matter remineralization, contributing to lake water DIC. Such comparisons using DI14C measurements from different points in time enable nonlinear changes in lake water DIC source and signature to be disentangled from concurrent anthropogenically induced changes in atmospheric 14C. In the future, coeval changes in lake dynamics due to climate change are expected to further perturb these balances. Depending on the scenario, Lake Constance DI14C is projected to decrease from the 2013 measured value of 0.856 Fm to 0.54–0.62 Fm by the end of the century.

Lymphatic filariasis is a neglected tropical disease caused by roundworm parasites such as Brugia malayi that spread via a mosquito vector. In vitro culture of these parasites provides controlled conditions to understand parasite biology and provides a cheaper way to screen potential micro- and macrofilaricides. Published studies have used a wide array of approaches and metrics regarding in vitro cultures of B. malayi; as a result, drawing comparisons and identifying the reasons why inability to reproduce outcomes are difficult. This study sought to determine conditions that ensure reproducible outcomes and used evaluation metrics that are easily measured and can be automated to ensure objectivity. We found culturing B. malayi third-stage larvae (L3) in endothelial basal media supplemented with 20% fetal bovine serum and 75 µ m ascorbic acid in a temperature- and humidity-controlled incubator produced better survival and molting rates as well as longer and more motile parasites than previously reported. The benefit of ascorbic acid seemed to be unique to L3 parasites, as the addition of ascorbic acid to adult parasites had no significant impact on survival or motility. The methods reported in this study will help in designing experiments for both parasite behaviour studies and drug screening applications for disease eradication.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

The simple calving laws currently used in ice-sheet models do not adequately reflect the complexity and diversity of calving processes. To be effective, calving laws must be grounded in a sound understanding of how calving actually works. Here, we develop a new strategy for formulating calving laws, using (a) the Helsinki Discrete Element Model (HiDEM) to explicitly model fracture and calving processes, and (b) the continuum model Elmer/Ice to identify critical stress states associated with HiDEM calving events. A range of observed calving processes emerges spontaneously from HiDEM in response to variations in ice-front buoyancy and the size of subaqueous undercuts. Calving driven by buoyancy and melt under-cutting is under-predicted by existing calving laws, but we show that the location and magnitude of HiDEM calving events can be predicted in Elmer/Ice from characteristic stress patterns. Our results open the way to developing calving laws that properly reflect the diversity of calving processes, and provide a framework for a unified theory of the calving process continuum.