EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

An ultrahot Neptune in the Neptune desert

About 1 out of 200 Sun-like stars has a planet with an orbital period shorter than one day: an ultrashort-period planet1,2. All of the previously known ultrashort-period planets are either hot Jupiters, with sizes above 10 Earth radii (R⊕), or apparently rocky planets smaller than 2 R⊕. Such lack of planets of intermediate size (the ‘hot Neptune desert’) has been interpreted as the inability of low-mass planets to retain any hydrogen/helium (H/He) envelope in the face of strong stellar irradiation. Here we report the discovery of an ultrashort-period planet with a radius of 4.6 R⊕ and a mass of 29 M⊕, firmly in the hot Neptune desert. Data from the Transiting Exoplanet Survey Satellite3 revealed transits of the bright Sun-like star LTT 9779 every 0.79 days. The planet’s mean density is similar to that of Neptune, and according to thermal evolution models, it has a H/He-rich envelope constituting 9.0−2.9+2.7% of the total mass. With an equilibrium temperature around 2,000 K, it is unclear how this ‘ultrahot Neptune’ managed to retain such an envelope. Follow-up observations of the planet’s atmosphere to better understand its origin and physical nature will be facilitated by the star’s brightness (Vmag = 9.8)

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

Preparation of stable isotope-labeled peripheral cannabinoid receptor CB2 by bacterial fermentation

We developed a bacterial fermentation protocol for production of a stable isotope-labeled cannabinoid receptor CB2 for subsequent structural studies of this protein by nuclear magnetic resonance spectroscopy. The human peripheral cannabinoid receptor was expressed in Escherichia coli as a fusion with maltose binding protein and two affinity tags. The fermentation was performed in defined media comprised of mineral salts, glucose and ^(15)N_2-L-tryptophan to afford incorporation of the labeled amino acid into the protein. Medium, growth and expression conditions were optimized so that the fermentation process produced about 2 mg of purified, labeled CB2/L of culture medium. By performing a mass spectroscopic characterization of the purified CB2, we determined that one of the two ^(15)N atoms in tryptophan was incorporated into the recombinant protein. NMR analysis of ^(15)N chemical shifts strongly suggests that the ^(15)N atoms are located in Trp-indole rings. Importantly, analysis of the peptides derived from the CNBr cleavage of the purified protein confirmed a minimum of 95% incorporation of the labeled tryptophan into the CB2 sequence. The labeled CB2, purified and reconstituted into liposomes at a protein-to-lipid molar ratio of 1:500, was functional as confirmed by activation of cognate G proteins in an in vitro coupled assay. To our knowledge, this is the first reported production of a biologically active, stable isotopelabeled G protein-coupled receptor by bacterial fermentation

Evaluation of MBari puck protocol for interoperable ocean observatories

IEEE-1451[1] and OGC Sensor Web Enablement (OGC SWE)[2] define standard protocols to operate instruments, including methods to calibrate, configure, trigger data acquisition, and retrieve instrument data based on specified temporal and geospatial criteria. These standards also provide standard ways to describe instrument capabilities, properties, and data structures produced by the instrument. These standard operational protocols and descriptions enable observing systems to manage very diverse instruments as well as to acquire, process, and interpret their data in a uniform and automated manner. We refer to this property as “instrument interoperability”. This paper describes integration and evaluation of MBARI PUCK protocol [3] within different observatories including OBSEA [4,5] in Spain, the ESONET test-bed in Germany, and the SmartBay observatory in Canada.Peer Reviewe