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Tick-borne encephalitis (TBE) is a viral disease endemic in Eurasia. The virus is mainly transmitted to humans via ticks and occasionally via the consumption of unpasteurized milk products. The European Centre for Disease Prevention and Control reported an increase in TBE incidence over the past years in Europe as well as the emergence of the disease in new areas. To better understand this phenomenon, we investigated the drivers of TBE emergence and increase in incidence in humans through an expert knowledge elicitation. We listed 59 possible drivers grouped in eight domains and elicited forty European experts to: (i) allocate a score per driver, (ii) weight this score within each domain, and (iii) weight the different domains and attribute an uncertainty level per domain. An overall weighted score per driver was calculated, and drivers with comparable scores were grouped into three terminal nodes using a regression tree analysis. The drivers with the highest scores were: (i) changes in human behavior/activities; (ii) changes in eating habits or consumer demand; (iii) changes in the landscape; (iv) influence of humidity on the survival and transmission of the pathogen; (v) difficulty to control reservoir(s) and/or vector(s); (vi) influence of temperature on virus survival and transmission; (vii) number of wildlife compartments/groups acting as reservoirs or amplifying hosts; (viii) increase of autochthonous wild mammals; and (ix) number of tick species vectors and their distribution. Our results support researchers in prioritizing studies targeting the most relevant drivers of emergence and increasing TBE incidence.

The question of the origin of the hard X-ray/soft gamma-ray emission in Centaurus A (Cen A) persists despite decades of observations. Results from X-ray instruments suggest a jet origin since the implied electron temperature ( kT _e ) would cause runaway pair production in the corona. In contrast, instruments sensitive to soft gamma rays report electron temperatures indicating that a coronal origin may be possible. In this context, we analyzed archival INTEGRAL/IBIS-ISGRI and SPI data and observations from a 2022 Cen A monitoring program. Our analysis did not find any spectral variability. Thus we combined all observations for long-term average spectra, which were fit with a NuSTAR observation to study the 3.5 keV–2.2 MeV spectrum. Spectral fits using a CompTT model found kT _e ∼ 550 keV, near runaway pair production. The spectrum was also well described by a log-parabola to model synchrotron self-Compton emission from the jet. Additionally, a spectral fit with the 12 yr catalog Fermi/LAT spectrum using a log-parabola can explain the data up to ∼3 GeV. Above ∼3 GeV, a power-law excess is present, which has been previously reported in LAT/H.E.S.S. analysis. However, including a coronal spectral component can also describe the data well. In this scenario, the hard X-rays/soft gamma rays are due the corona and the MeV to GeV emission is due to the jet.

Changes in precipitation over the European Alps are investigated with the regional climate model MAR (Modèle Atmosphérique Régional) applied with a 7 km resolution over the period 1903–2010 using the reanalysis ERA-20C as forcing. A comparison with several observational datasets demonstrates that the model is able to reproduce the climatology as well as both the interannual variability and the seasonal cycle of precipitation over the European Alps. The relatively high resolution allows us to estimate precipitation at high elevations. The vertical gradient of precipitation simulated by MAR over the European Alps reaches 33% km−1 (1.21 mm d−1 km−1) in summer and 38 % km−1 (1.15 mm d−1 km−1) in winter, on average, over 1971–2008 and shows a large spatial variability. A significant (p value < 0.05) increase in mean winter precipitation is simulated in the northwestern Alps over 1903–2010, with changes typically reaching 20 % to 40 % per century. This increase is mainly explained by a stronger simple daily intensity index (SDII) and is associated with less-frequent but longer wet spells. A general drying is found in summer over the same period, exceeding 20 % to 30 % per century in the western plains and 40 % to 50 % per century in the southern plains surrounding the Alps but remaining much smaller ( %) and not significant above 1500 m a.s.l. Below this level, the summer drying is explained by a reduction in the number of wet days, reaching 20 % per century over the northwestern part of the Alps and 30 % to 50 % per century in the southern part of the Alps. It is associated with shorter but more-frequent wet spells. The centennial trends are modulated over the last decades, with the drying occurring in the plains in winter also affecting high-altitude areas during this season and with a positive trend of autumn precipitation occurring only over the last decades all over the Alps. Maximum daily precipitation index (Rx1day) takes its highest values in autumn in both the western and the eastern parts of the southern Alps, locally reaching 50 to 70 mm d−1 on average over 1903–2010. Centennial maxima up to 250 to 300 mm d−1 are simulated in the southern Alps, in France and Italy, as well as in the Ticino valley in Switzerland. Over 1903–2010, seasonal Rx1day shows a general and significant increase at the annual timescale and also during the four seasons, reaching local values between 20 % and 40 % per century over large parts of the Alps and the Apennines. Trends of Rx1day are significant (p value < 0.05) only when considering long time series, typically 50 to 80 years depending on the area considered. Some of these trends are nonetheless significant when computed over 1970–2010, suggesting a recent acceleration of the increase in extreme precipitation, whereas earlier periods with strong precipitation also occurred, in particular during the 1950s and 1960s.

IntroductionThe “Renal Risk Score” (RRS) and the histopathological classification have been proposed to predict the risk of end-stage kidney disease (ESKD) in ANCA-associated glomerulonephritis (ANCA-GN). Besides, factors associated with kidney function recovery after ANCA-GN onset remain to be more extensively studied. In the present study, we analyzed the value of the RRS and of the histopathological classification for ESKD prediction. Next, we analyzed factors associated with eGFR change within the first 2 years following ANCA-GN diagnosis.Materials and MethodsWe included patients from the Maine–Anjou ANCA-associated vasculitis registry with at least 6 months of follow-up. The values of ANCA-GN, histopathological classification, and RRS, and the factors associated with eGFR variations between ANCA-GN diagnosis and 2 years of follow-up were assessed.ResultsThe predictive values of the histopathological classification and RRS were analyzed in 123 patients. After a median follow-up of 42 months, 33.3% patients developed ESKD. The predictive value of RRS for ESKD was greater than that of the histopathological classification. Determinants of eGFR variation were assessed in 80/123 patients with complete eGFR measurement. The median eGFR increased from ANCA-GN diagnosis to month 6 and stabilized thereafter. The only factor associated with eGFR variation in our study was eGFR at ANCA-GN diagnosis, with higher eGFR at diagnosis being associated with eGFR loss (p

The discovery of lignins in the coralline red alga Calliarthron tuberculosum raised new questions about the deep evolution of lignin biosynthesis. Here we present the transcriptome of C. tuberculosum supported with newly generated genomic data to identify gene candidates from the monolignol biosynthetic pathway using a combination of sequence similarity-based methods. We identified candidates in the monolignol biosynthesis pathway for the genes 4CL, CCR, CAD, CCoAOMT, and CSE but did not identify candidates for PAL, CYP450 (F5H, C3H, C4H), HCT, and COMT. In gene tree analysis, we present evidence that these gene candidates evolved independently from their land plant counterparts, suggesting convergent evolution of a complex multistep lignin biosynthetic pathway in this red algal lineage. Additionally, we provide tools to extract metabolic pathways and genes from the newly generated transcriptomic and genomic datasets. Using these methods, we extracted genes related to sucrose metabolism and calcification. Ultimately, this transcriptome will provide a foundation for further genetic and experimental studies of calcifying red algae.

Climate model projections have previously been used to compute ice shelf basal melt rates in ice sheet models, but the strategies employed – e.g., ocean input, parameterization, calibration technique, and corrections – have varied widely and are often ad hoc. Here, a methodology is proposed for the calculation of circum-Antarctic basal melt rates for floating ice, based on climate models, that is suitable for ISMIP6, the Ice Sheet Model Intercomparison Project for CMIP6 (6th Coupled Model Intercomparison Project). The past and future evolution of ocean temperature and salinity is derived from a climate model by estimating anomalies with respect to the modern day, which are added to a present-day climatology constructed from existing observational datasets. Temperature and salinity are extrapolated to any position potentially occupied by a simulated ice shelf. A simple formulation is proposed for a basal melt parameterization in ISMIP6, constrained by the observed temperature climatology, with a quadratic dependency on either the nonlocal or local thermal forcing. Two calibration methods are proposed: (1) based on the mean Antarctic melt rate (MeanAnt) and (2) based on melt rates near Pine Island's deep grounding line (PIGL). Future Antarctic mean melt rates are an order of magnitude greater in PIGL than in MeanAnt. The PIGL calibration and the local parameterization result in more realistic melt rates near grounding lines. PIGL is also more consistent with observations of interannual melt rate variability underneath Pine Island and Dotson ice shelves. This work stresses the need for more physics and less calibration in the parameterizations and for more observations of hydrographic properties and melt rates at interannual and decadal timescales.

Abstract Background Roughly 10% of newborns need help to complete the transition of birth. For these infants, international guidelines recommend supporting them using a 4-step procedure (A to D). Step A is an assessment time, which includes eight tasks and finishes by starting the positive pressure ventilation (PPV), if necessary (step B). The guidelines changed in 2015 and the allotted time was raised from 30 to 60 seconds for step A completion. This study aimed to assess if the reduced time constraint in step A could have an impact on 1st-year pediatric residents' performance to complete step A and if could lead to later initiation of step A. Methods Using video recordings of standardized neonatal scenarios over 6 years (3 before the change and 3 after), we assessed the ability of 1st-year pediatric residents of the Paris region to complete step A and initiate PPV in the allotted time in each period. Among the sessions, including at least five scenarios we evaluated all the PPV required scenarios executed for the first time by a dyad of 1st-year pediatric residents. Results Among 52 sessions, we included 104 scenarios (25 sessions and 50 scenarios before the change and 27 sessions and 54 scenarios after). PPV started roughly at 1-minute resuscitation in both periods, but completion of the tasks before PPV-start was significant. Only 12% of the dyad of residents executed the eight tasks before PPV initiation in the first period versus 54% in the second period (p < 0.0001). Additionally, the completion of the eight tasks of step A was significantly better during the second period (6 [6-7] vs. 8 [7-8] p < 0.001). Conclusions: These results could suggest that a reduced time constraint for step A imposed by the new Guidelines was associated with better performance.

Projection of the contribution of ice sheets to sea level change as part of the Coupled Model Intercomparison Project Phase 6 (CMIP6) takes the form of simulations from coupled ice sheet–climate models and stand-alone ice sheet models, overseen by the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6). This paper describes the experimental setup for process-based sea level change projections to be performed with stand-alone Greenland and Antarctic ice sheet models in the context of ISMIP6. The ISMIP6 protocol relies on a suite of polar atmospheric and oceanic CMIP-based forcing for ice sheet models, in order to explore the uncertainty in projected sea level change due to future emissions scenarios, CMIP models, ice sheet models, and parameterizations for ice–ocean interactions. We describe here the approach taken for defining the suite of ISMIP6 stand-alone ice sheet simulations, document the experimental framework and implementation, and present an overview of the ISMIP6 forcing to be used by participating ice sheet modeling groups.

Abstract The use of high temperature superconducting (HTS) radio frequency (RF) coils in Magnetic Resonance Imaging (MRI) greatly improves the signal-to-noise ratio (SNR) in many biomedical applications and particularly in micro-MRI. However, a detailed understanding of the electrical behavior of HTS coils is important in order to optimize their performance through MR experiments. This paper presents a simple and versatile cryogen-free cryostat designed to characterize the RF properties of HTS coils prior to their use in MRI. The cryostat can be used at temperatures from 50 K to 300 K, with a control precision of approximately 3 mK at 70 K, and can measure the RF electrical power transmitted to an HTS coil over a range from 1 μW to 10 W. The quality factor and resonance frequency of the tested HTS coil are determined as a function of the temperature and the power it dissipates. This cryostat also permits the dynamic adjustment of the coil resonance frequency via temperature control. Finally, this study demonstrates that the HTS coil takes less than 12 μs to transit from the superconducting to the dissipative state, which is compatible with MRI requirements.

The response of very-high-elevation glaciated areas on Mont Blanc to climate change has been analysed using observations and numerical modelling over the last 2 decades. Unlike the changes at low elevations, we observe very low glacier thickness changes, of about −2.6 m on average since 1993. The slight changes in horizontal ice flow velocities and submergence velocities suggest a decrease of about 10 % in ice flux and surface mass balance. This is due to less snow accumulation and is consistent with the precipitation decrease observed in meteorological data. Conversely, measurements performed in deep boreholes since 1994 reveal strong changes in englacial temperature reaching a 1.5 ∘C increase at a depth of 50 m. We conclude that at such very high elevations, current changes in climate do not lead to visible changes in glacier thickness but cause invisible changes within the glacier in terms of englacial temperatures. Our analysis from numerical modelling shows that glacier near-surface temperature warming is enhanced by increasing melt frequency at high elevations although the impact on surface mass balance is low. This results in a non-linear response of englacial temperature to currently rising air temperatures. In addition, borehole temperature inversion including a new dataset confirms previous findings of similar air temperature changes at high and low elevations in the Alps.

The ice sheet model intercomparison project for CMIP6 (ISMIP6) effort brings together the ice sheet and climate modeling communities to gain understanding of the ice sheet contribution to sea level rise. ISMIP6 conducts stand-alone ice sheet experiments that use space- and time-varying forcing derived from atmosphere–ocean coupled global climate models (AOGCMs) to reflect plausible trajectories for climate projections. The goal of this study is to recommend a subset of CMIP5 AOGCMs (three core and three targeted) to produce forcing for ISMIP6 stand-alone ice sheet simulations, based on (i) their representation of current climate near Antarctica and Greenland relative to observations and (ii) their ability to sample a diversity of projected atmosphere and ocean changes over the 21st century. The selection is performed separately for Greenland and Antarctica. Model evaluation over the historical period focuses on variables used to generate ice sheet forcing. For stage (i), we combine metrics of atmosphere and surface ocean state (annual- and seasonal-mean variables over large spatial domains) with metrics of time-mean subsurface ocean temperature biases averaged over sectors of the continental shelf. For stage (ii), we maximize the diversity of climate projections among the best-performing models. Model selection is also constrained by technical limitations, such as availability of required data from RCP2.6 and RCP8.5 projections. The selected top three CMIP5 climate models are CCSM4, MIROC-ESM-CHEM, and NorESM1-M for Antarctica and HadGEM2-ES, MIROC5, and NorESM1-M for Greenland. This model selection was designed specifically for ISMIP6 but can be adapted for other applications.

A promising approach for the treatment of nonalcoholic steatohepatitis (NASH) is the inhibition of enhanced hepatic de novo lipogenesis (DNL), which is the synthesis of fatty acids from nonlipid sources. This study assesses three approaches to DNL suppression in a newly developed dietary NASH mouse model: i) dietary intervention (switch from NASH‐inducing diet to normal diet); ii) inhibition of acetyl‐coenzyme A carboxylase (ACC), the enzyme catalyzing the rate‐limiting step in DNL; and iii) activation of farnesoid X receptor (FXR), a major transcriptional regulator of DNL. C57BL/6J mice on a high‐fat diet combined with ad libitum consumption of a fructose–sucrose solution developed several of the liver histologic features seen in human disease, including steatosis, inflammation, and fibrosis, accompanied by elevated fibrosis biomarkers and liver injury enzymes. Obesity and metabolic impairments were associated with increased intestinal permeability and progression to adenoma and hepatocellular carcinoma. All three approaches led to resolution of established NASH with fibrosis in mice; however, some differences were noted, e.g., with respect to the degree of hepatic steatosis attenuation. While ACC inhibition resulted in elevated blood triglycerides and peripheral obesity, FXR activation prevented peripheral obesity in NASH mice. Comparative transcriptome analysis underlined the translatability of the mouse model to human NASH and revealed novel mechanistic insights into differential regulation of lipid, inflammatory, and extracellular matrix pathways by FXR agonism and ACC inhibition. Conclusion: Novel insights are provided on back translation of clinically observed endpoints of DNL inhibition by targeting ACC or FXR, which are promising therapeutic options for the treatment of NASH, in a newly developed diet‐induced NASH mouse model.

Understanding the interannual variability of surface mass balance (SMB) and surface melting in Antarctica is key to quantify the signal-to-noise ratio in climate trends, identify opportunities for multi-year climate predictions and assess the ability of climate models to respond to climate variability. Here we simulate summer SMB and surface melting from 1979 to 2017 using the Regional Atmosphere Model (MAR) at 10 km resolution over the drainage basins of the Amundsen Sea glaciers in West Antarctica. Our simulations reproduce the mean present-day climate in terms of near-surface temperature (mean overestimation of 0.10 ∘C), near-surface wind speed (mean underestimation of 0.42 m s−1), and SMB (relative bias  % over Thwaites glacier). The simulated interannual variability of SMB and melting is also close to observation-based estimates. For all the Amundsen glacial drainage basins, the interannual variability of summer SMB and surface melting is driven by two distinct mechanisms: high summer SMB tends to occur when the Amundsen Sea Low (ASL) is shifted southward and westward, while high summer melt rates tend to occur when ASL is shallower (i.e. anticyclonic anomaly). Both mechanisms create a northerly flow anomaly that increases moisture convergence and cloud cover over the Amundsen Sea and therefore favors snowfall and downward longwave radiation over the ice sheet. The part of interannual summer SMB variance explained by the ASL longitudinal migrations increases westward and reaches 40 % for Getz. Interannual variation in the ASL relative central pressure is the largest driver of melt rate variability, with 11 % to 21 % of explained variance (increasing westward). While high summer SMB and melt rates are both favored by positive phases of El Niño–Southern Oscillation (ENSO), the Southern Oscillation Index (SOI) only explains 5 % to 16 % of SMB or melt rate interannual variance in our simulations, with moderate statistical significance. However, the part explained by SOI in the previous austral winter is greater, suggesting that at least a part of the ENSO–SMB and ENSO–melt relationships in summer is inherited from the previous austral winter. Possible mechanisms involve sea ice advection from the Ross Sea and intrusions of circumpolar deep water combined with melt-induced ocean overturning circulation in ice shelf cavities. Finally, we do not find any correlation with the Southern Annular Mode (SAM) in summer.

Background: HIV drug resistance (HIVDR) testing can assist clinicians in selecting treatments. However, high complexity and cost of genotyping assays limit routine testing in settings where HIVDR prevalence has reached high levels. Methods: The oligonucleotide ligation assay (OLA)-Simple kit was developed for detection of HIVDR against first-line non-nucleoside/nucleoside reverse transcriptase inhibitors and validated on 672 codons (168 specimens) from subtypes A, B, C, D, and AE. The kit uses dry reagents to facilitate assay setup, lateral flow devices for visual HIVDR detections, and in-house software with an interface for guiding users and analyzing results. Findings: HIVDR analysis of specimens by OLA-Simple compared to Sanger sequencing revealed 99.6 ± 0.3% specificity and 98.2 ± 0.9% sensitivity, and compared to high-sensitivity assays, 99.6 ± 0.6% specificity and 86.2 ± 2.5% sensitivity, with 2.6 ± 0.9% indeterminate results. OLA-Simple was performed more rapidly compared to Sanger sequencing (