Thinning leads to calving-style changes at Bowdoin Glacier, Greenland

This research has been supported by the Alfred and Flora Spälti Fund and the ETH Zurich Foundation (Sun2ice; grant no. ETH-12 16-2); the Swiss National Science Foundation (grant nos. 200021-153179/1 and PP00P2_183719); the SPI Exploratory Grants 2018 awarded to Fabian Walter and Guillaume Jouvet; the Japanese Ministry of Education, Culture, Sports, Science and Technology through the GRENE Arctic Climate Research Project and the Arctic Challenge for Sustainability (ArCS) project; and by NERC (CALISMO: Calving Laws for Ice Sheet Models; grant no. NE/P011365/1).Ice mass loss from the Greenland ice sheet is the largest single contributor to sea level rise in the 21st century. The mass loss rate has accelerated in recent decades mainly due to thinning and retreat of its outlet glaciers. The diverse calving mechanisms responsible for tidewater glacier retreat are not fully understood yet. Since a tidewater glacier's sensitivity to external forcings depends on its calving style, detailed insight into calving processes is necessary to improve projections of ice sheet mass loss by calving. As tidewater glaciers are mostly thinning, their calving styles are expected to change. Here, we study calving behaviour changes under a thinning regime at Bowdoin Glacier, north-western Greenland, by combining field and remote-sensing data from 2015 to 2019. Previous studies showed that major calving events in 2015 and 2017 were driven by hydro-fracturing and melt-undercutting. New observations from uncrewed aerial vehicle (UAV) imagery and a GPS network installed at the calving front in 2019 suggest ungrounding and buoyant calving have recently occurred as they show (1) increasing tidal modulation of vertical motion compared to previous years, (2) absence of a surface crevasse prior to calving, and (3) uplift and horizontal surface compression prior to calving. Furthermore, an inventory of calving events from 2015 to 2019 based on satellite imagery provides additional support for a change towards buoyant calving since it shows an increasing occurrence of calving events outside of the melt season. The observed change in calving style could lead to a possible retreat of the terminus, which has been stable since 2013. We therefore highlight the need for high-resolution monitoring to detect changing calving styles and numerical models that cover the full spectrum of calving mechanisms to improve projections of ice sheet mass loss by calving.Publisher PDFPeer reviewe

Nanomechanical absorption spectroscopy of 2D materials with femtowatt sensitivity

Nanomechanical spectroscopy (NMS) is a recently developed approach to determine optical absorption spectra of nanoscale materials via mechanical measurements. It is based on measuring changes in the resonance frequency of a membrane resonator vs. the photon energy of incoming light. This method is a direct measurement of absorption, which has practical advantages compared to common optical spectroscopy approaches. In the case of two-dimensional (2D) materials, NMS overcomes limitations inherent to conventional optical methods, such as the complications associated with measurements at high magnetic fields and low temperatures. In this work, we develop a protocol for NMS of 2D materials that yields two orders of magnitude improved sensitivity compared to previous approaches, while being simpler to use. To this end, we use mechanical sample actuation, which simplifies the experiment and provides a reliable calibration for greater accuracy. Additionally, the use of low-stress silicon nitride membranes as our substrate reduces the noise-equivalent power to fW , comparable to commercial semiconductor photodetectors. We use our approach to spectroscopically characterize a 2D transition metal dichalcogenide (WS2), a layered magnetic semiconductor (CrPS4), and a plasmonic super-crystal consisting of gold nanoparticles

An innovative ethosuximide granule formulation designed for pediatric use: Comparative pharmacokinetics, safety, tolerability, and palatability profile versus reference syrup.

Ethosuximide, the first-line therapy for childhood absence epilepsy, is currently formulated as a syrup (Zarontin®, Pfizer) with a bitter taste and high sugar content, poorly adapted to children, and a ketogenic diet. The collaborative European FP7 project KIEKIDS aimed at developing an innovative sugar-free, tasteless formulation convenient for pediatric use. This dual Phase-I study evaluated two granule formulations based on lipid multiparticulate (LMP) technology. Two panels of 6 healthy adult volunteers underwent a randomized, placebo-controlled, partly blinded, 3-way cross-over trial, comparing ethosuximide granules A or B with placebo granules and syrup at single 10 mg/kg doses. Corresponding plasma pharmacokinetic profiles of ethosuximide were compared, along with palatability, safety, and tolerability. The LMP granule A proved suboptimal due to bitterness and adherence to beaker walls, while the optimized granule B revealed excellent palatability, similar to placebo granules, and low adherence to glass. The relative bioavailability of granules A versus syrup, based on dose-normalized C <sub>max</sub> and AUC <sub>0-∞</sub> was 93.7% [90% CI: 76.3-115.1] and 96.1% [91.0-101.5], respectively. For granules B it was 87.6% [81.6-94.0] and 92.5% [88.5-96.6], respectively, with slightly delayed t <sub>max</sub> of 0.75 h [0.5-4.05] compared to syrup 0.5 h [0.3-0.8]. Tolerability visual analog scales revealed a trend for statistically non-significant improvement versus syrup at peak (30 min) for transient dizziness (both granules), fatigue (granules A), and anxiety (granules B). The innovative ethosuximide granule formulation B achieves a suitable profile for pediatric use, being sugar-free, tasteless, bioequivalent, and well-tolerated while enabling precise adjustment to body weight

Changes in the Diagnosis of Stroke and Cardiovascular Conditions in Primary Care During First 2 COVID-19 Waves in the Netherlands

BACKGROUND AND OBJECTIVES: Although there is evidence of disruption in acute cerebrovascular and cardiovascular care during the coronavirus disease 2019 (COVID-19) pandemic, its downstream effect in primary care is less clear. We investigated how the pandemic affected utilization of cerebrovascular and cardiovascular care in general practices (GPs) and determined changes in GP-recorded diagnoses of selected cerebrovascular and cardiovascular outcomes. METHODS: From electronic health records of 166,929 primary care patients aged 30 or over within the Rotterdam region, the Netherlands, we extracted the number of consultations related to cerebrovascular and cardiovascular care, and first diagnoses of selected cerebrovascular and cardiovascular risk factors (hypertension, diabetes, lipid disorders), conditions, and events (angina, atrial fibrillation, TIA, myocardial infarction, stroke). We quantified changes in those outcomes during the first COVID-19 wave (March–May 2020) and thereafter (June–December 2020) by comparing them to the same period in 2016–2019. We also estimated the number of potentially missed diagnoses for each outcome. RESULTS: The number of GP consultations related to cerebrovascular and cardiovascular care declined by 38% (0.62, 95% confidence interval 0.56–0.68) during the first wave, as compared to expected counts based on prepandemic levels. Substantial declines in the number of new diagnoses were observed for cerebrovascular events: 37% for TIA (0.63, 0.41–0.96) and 29% for stroke (0.71, 0.59–0.84), while no significant changes were observed for cardiovascular events (myocardial infarction [0.91, 0.74–1.14], angina [0.77, 0.48–1.25]). The counts across individual diagnoses recovered following June 2020, but the number of GP consultations related to cerebrovascular and cardiovascular care remained lower than expected throughout the June to December period (0.93, 0.88–0.98). DISCUSSION: While new diagnoses of acute cardiovascular events remained stable during the COVID-19 pandemic, diagnoses of cerebrovascular events declined substantially compared to prepandemic levels, possibly due to incorrect perception of risk by patients. These findings emphasize the need to improve symptom recognition of cerebrovascular events among the general public and to encourage urgent presentation despite any physical distancing measures

Do-It-Yourself Preoperative High-Resolution Ultrasound-Guided Flap Design of the Superficial Circumflex Iliac Artery Perforator Flap (SCIP)

The superficial circumflex iliac artery perforator (SCIP) flap is a well-documented, thin, free tissue flap with a minimal donor site morbidity, and has the potential to become the new method for resurfacing moderate-size skin defects. The aim of this study is to describe an easy, reliable, systematic, and standardized approach for preoperative SCIP flap design and perforator characterization, using color-coded duplex sonography (CCDS). A list of customized settings and a straightforward algorithm are presented, which are easily applied by an operator with minimal experience. Specific settings for SCIP flap perforator evaluation were investigated and tested on 12 patients. Deep and superficial superficial circumflex iliac artery (SCIA) branches, along with their corresponding perforators and cutaneous veins, were marked individually with a permanent marker and the anatomy was verified intraoperatively. From this, a simplified procedure for preoperative flap design of the SCIP flap was developed. Branches could be localized and evaluated in all patients. A preoperative structured procedure for ultrasonically guided flap design of the SCIP flap is described. A 100% correlation between the number and emergence points of the branches detected by preoperative CCDS mapping and the intraoperative anatomy was found

Sequencing and Analysis of the Mediterranean Amphioxus (Branchiostoma lanceolatum) Transcriptome

BACKGROUND: The basally divergent phylogenetic position of amphioxus (Cephalochordata), as well as its conserved morphology, development and genetics, make it the best proxy for the chordate ancestor. Particularly, studies using the amphioxus model help our understanding of vertebrate evolution and development. Thus, interest for the amphioxus model led to the characterization of both the transcriptome and complete genome sequence of the American species, Branchiostoma floridae. However, recent technical improvements allowing induction of spawning in the laboratory during the breeding season on a daily basis with the Mediterranean species Branchiostoma lanceolatum have encouraged European Evo-Devo researchers to adopt this species as a model even though no genomic or transcriptomic data have been available. To fill this need we used the pyrosequencing method to characterize the B. lanceolatum transcriptome and then compared our results with the published transcriptome of B. floridae. RESULTS: Starting with total RNA from nine different developmental stages of B. lanceolatum, a normalized cDNA library was constructed and sequenced on Roche GS FLX (Titanium mode). Around 1.4 million of reads were produced and assembled into 70,530 contigs (average length of 490 bp). Overall 37% of the assembled sequences were annotated by BlastX and their Gene Ontology terms were determined. These results were then compared to genomic and transcriptomic data of B. floridae to assess similarities and specificities of each species. CONCLUSION: We obtained a high-quality amphioxus (B. lanceolatum) reference transcriptome using a high throughput sequencing approach. We found that 83% of the predicted genes in the B. floridae complete genome sequence are also found in the B. lanceolatum transcriptome, while only 41% were found in the B. floridae transcriptome obtained with traditional Sanger based sequencing. Therefore, given the high degree of sequence conservation between different amphioxus species, this set of ESTs may now be used as the reference transcriptome for the Branchiostoma genus

Free exopolysaccharide from Mycoplasma mycoides subsp. mycoides possesses anti-inflammatory properties

In this study we explored the immunomodulatory properties of highly purified free galactan, the soluble exopolysaccharide secreted by Mycoplasma mycoides subsp. mycoides (Mmm). Galactan was shown to bind to TLR2 but not TLR4 using HEK293 reporter cells and to induce the production of the anti-inflammatory cytokine IL-10 in bovine macrophages, whereas low IL-12p40 and no TNF-α, both pro-inflammatory cytokines, were induced in these cells. In addition, pre-treatment of macrophages with galactan substantially reduced lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines TNF- and IL-12p40 while increasing LPS-induced secretion of immunosuppressive IL-10. Also, galactan did not activate naïve lymphocytes and induced only low production of the Th1 cytokine IFN-γ in Mmm-experienced lymphocytes. Finally, galactan triggered weak recall proliferation of CD4+ T lymphocytes from contagious bovine pleuropneumonia-infected animals despite having a positive effect on the expression of co-stimulatory molecules on macrophages. All together, these results suggest that galactan possesses anti-inflammatory properties and potentially provides Mmm with a mechanism to evade host innate and adaptive cell-mediated immune responses. (Résumé d'auteur

Cloning whole bacterial genomes in yeast

Most microbes have not been cultured, and many of those that are cultivatable are difficult, dangerous or expensive to propagate or are genetically intractable. Routine cloning of large genome fractions or whole genomes from these organisms would significantly enhance their discovery and genetic and functional characterization. Here we report the cloning of whole bacterial genomes in the yeast Saccharomyces cerevisiae as single-DNA molecules. We cloned the genomes of Mycoplasma genitalium (0.6 Mb), M. pneumoniae (0.8 Mb) and M. mycoides subspecies capri (1.1 Mb) as yeast circular centromeric plasmids. These genomes appear to be stably maintained in a host that has efficient, well-established methods for DNA manipulation

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions