Protocolized Brain Oxygen Optimization in Subarachnoid Hemorrhage.

Brain tissue hypoxia (P <sub>bt</sub> O <sub>2</sub> < 20 mmHg) is common after subarachnoid hemorrhage (SAH) and associated with poor outcome. Recent data suggest that brain oxygen optimization is feasible and reduces the time spent with P <sub>bt</sub> O <sub>2</sub> < 20 mmHg from 45 to 16% in patients with severe traumatic brain injury. Here, we intended to quantify the brain tissue hypoxia burden despite implementation of a protocolized treatment approach in poor-grade SAH patients and to identify the simultaneous occurrence of pathologic values potentially amenable to treatment. We present a bi-centric observational cohort study including 100 poor-grade SAH patients admitted to two tertiary care centers who underwent multimodal brain monitoring and were managed with a P <sub>bt</sub> O <sub>2</sub> -targeted protocolized approach. P <sub>bt</sub> O <sub>2</sub> optimization (≥ 20 mmHg) included a stepwise neuro-intensive care approach, aiming to prevent low cerebral perfusion pressure (CPP), and blood hemoglobin, and to keep normocapnia, normoxemia, and normothermia. Based on routine blood gas analysis, hemoglobin, PaCO <sub>2,</sub> and PaO <sub>2</sub> data were matched to 2-h averaged data of continuous CPP, P <sub>bt</sub> O <sub>2</sub> , core temperature, and to hourly cerebral microdialysis (CMD) samples over the first 11 days. Patients had a Glasgow Coma Scale of 3 (IQR 3-4) and were 58 years old (IQR 48-66). Overall incidence of brain tissue hypoxia was 25%, which was not different between both sites despite differences in the treatment approach. During brain tissue hypoxia, episodes of CPP < 70 mmHg (27%), PaCO <sub>2</sub> < 35 mmHg (19%), PaO <sub>2</sub> < 80 mmHg (14%), Hb < 9 g/dL (11%), metabolic crisis (CMD-lactate/pyruvate ratio > 40, and CMD-glucose < 0.7 mmol/L; 7%), and temperature > 38.3 °C (4%) were common. Our results demonstrate that brain tissue hypoxia remains common despite implementation of a P <sub>bt</sub> O <sub>2</sub> -targeted therapy in poor-grade SAH patients, suggesting room for further optimization

The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections : current knowledge and new perspectives

ACKNOWLEDGEMENTS: We thank our friends and colleagues in the medical mycology, fungal immunology and microbiota fields for many thought-provoking discussions. FUNDING: We received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie action, Innovative Training Network: FunHoMic; grant N° 812969. CdE received funding from the French Government ‘Investissement d’Avenir’ program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases, ANR-10-LABX-62-IBEID), the Agence Nationale de la Recherche (ERA-Net Infect-ERA, FUNCOMPATH, ANR-14-IFEC-0004), the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507). SLL and CdE received funding from the Swiss National Science Foundation (Sinergia program, #CRSII5_173863). BIOASTER received funding from the French Government ‘Investissement d’Avenir’ program (Grant No. ANR-10-AIRT-03). MSG was supported by a Humboldt Research Fellowship for Postdoctoral Researchers by the Alexander von Humboldt-Foundation and the Deutsche Forschungsgemeinschaft (DFG) Emmy Noether Program (project no. 434385622 / GR 5617/1-1). BH was supported by the Deutsche Forschungsgemeinschaft (DFG) project Hu 532/20-1, project C1 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” - HDM-FUN (Grant Agreement 847507), the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (215599/Z/19/Z). IDJ was supported by the Deutsche orschungsgemeinschaft (DFG) project C5 within the Collaborative Research Centre (CRC)/Transregio 124 FungiNet and the Balance of the Microverse Cluster under Germany´s Excellence Strategy – EXC 2051 – Project-ID 390713860, the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC and the Wellcome Trust (Grant 215599/Z/19/Z). CM received funding from the the Instituto de Salud Carlos III/FEDER. MGN was supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. CAM was supported by EU Horizon2020 consortium “Host-Directed Medicine in invasive FUNgal infections” -HDM-FUN (Grant Agreement 847507) and the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology (097377/Z/11/Z). AWW receives core funding support from the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS). AJPB was supported by a programme grant from the UK Medical Research Council (MR/M026663/1) and by the Medical Research Council Centre for Medical Mycology at the University of Exeter (MR/N006364/1).Peer reviewedPublisher PD

Evidence for α\alpha-particle condensation in nuclei from the Hoyle state deexcitation

The fragmentation of quasi-projectiles from the nuclear reaction $^{40}$Ca+$^{12}$C at 25 MeV/nucleon was used to produce excited states candidates to $\alpha$-particle condensation. Complete kinematic characterization of individual decay events, made possible by a high-granularity 4$\pi$ charged particle multi-detector, reveals that 7.5$\pm$4.0% of the particle decays of the Hoyle state correspond to direct decays in three equal-energy $\alpha$-particles.Comment: Phys. Lett. B, in pres

A colour-excess extinction map of the southern Galactic disc from the VVV and GLIMPSE surveys

Published versionAn improved high-resolution and deep AKs foreground dust extinction map is presented for the Galactic disc area within 295° ≲ l ≲ 350°, −1.0° ≲ b ≲ +1.0°. At some longitudes the map reaches up to |b| ∼ 2.25°, for a total of ∼148 deg2. The map was constructed via the Rayleigh–Jeans colour excess (RJCE) technique based on deep near-infrared (NIR) and mid-infrared (MIR) photometry. The new extinction map features a maximum bin size of 1', and relies on NIR observations from the Two Micron All-Sky Survey (2MASS) and new data from ESO’s Vista Variables in the Vía Láctea (VVV) survey, in concert with MIR observations from the Galactic Legacy Infrared Mid-Plane Survey Extraordinaire. The VVV photometry penetrates ∼4 mag fainter than 2MASS, and provides enhanced sampling of the underlying stellar populations in this heavily obscured region. Consequently, the new results supersede existing RJCE maps tied solely to brighter photometry, revealing a systematic underestimation of extinction in prior work that was based on shallower data. The new high-resolution and large-scale extinction map presented here is readily available to the community through a web query interface

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiwavelength observations of a TeV-Flare from W comae

We report results from an intensive multiwavelength campaign on the intermediate-frequency-peaked BL Lacertae object W Com (z = 0.102) during a strong outburst of very high energy gamma-ray emission in 2008 June. The very high energy gamma-ray signal was detected by VERITAS on 2008 June 7-8 with a flux F(>200 GeV) =(5.7 0.6) × 10-11 cm-2 s -1, about three times brighter than during the discovery of gamma-ray emission from W Com by VERITAS in 2008 March. The initial detection of this flare by VERITAS at energies above 200 GeV was followed by observations in high-energy gamma rays (AGILE; E γ≥ 100 MeV), X-rays (Swift and XMM-Newton), and at UV, and ground-based optical and radio monitoring through the GASP-WEBT consortium and other observatories. Here we describe the multiwavelength data and derive the spectral energy distribution of the source from contemporaneous data taken throughout the flare. © 2009. The American Astronomical Society. All rights reserved

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Parasitological and immunological effects induced by immunization of Mandrillus sphinx against the human filarial Loa loa using infective stage larvae irradiated at 40 krad

Six mandrills were immunized with 150 Loa loa infective stage larvae (L3) irradiated with 40 Krad, and challenged with 100 L3, 60 days after initial vaccination. The parasitological outcome of this immunization was compared to results from six mandrills infected with normal L3. No clear association was seen between vaccination and microfilaremia until day 245 when a significant drop in the level of microfilaria occured in vaccinated compared to infected animals (5 vs 10 mf/ml; p = 0.012). A one-year follow-up of the humoral immune response showed a strong adult, microfilariae (Mf) and L3 specific IgG response, with distinct profiles for each extract. In immunized animal a significant decrease in antibody level was systematically observed between days 90-145 for the anti-L3 and anti-adult IgG. However, in the same group anti-Mf antibody levels that peaked around 160-175 days post-challenge, were inversely correlated with the decrease in Mf density between day 200 and day 386. These results suggest that immunization with irradiated L3 using these specific conditions may affect the appearance of Mf