Summary
Viral infections can be fatal because of the direct cytopathic effects of the virus or the induction of a strong, uncontrolled inflammatory response. Virus and host intrinsic characteristics ...strongly modulate the outcome of viral infections. Recently we determined the circumstances under which enhanced replication of virus within the lymphoid tissue is beneficial for the outcome of a disease. This enforced viral replication promotes anti‐viral immune activation and, counterintuitively, accelerates virus control. In this review we summarize the mechanisms that contribute to enforced viral replication.
Antigen‐presenting cells and CD169+ macrophages exhibit enforced viral replication after infection with the model viruses lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus (VSV). Ubiquitin‐specific peptidase 18 (Usp18), an endogenous type I interferon blocker in CD169+ macrophages, has been identified as a proviral gene, as are B cell activating factor (BAFF) and carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1). Lymphotoxins (LT) strongly enhance viral replication in the spleen and lymph nodes. All these factors modulate splenic architecture and thereby promote the development of CD169+ macrophages. Tumor necrosis factor alpha (TNF‐α) and nuclear factor kappa‐light‐chain‐enhancer of activated B cell signaling (NF‐κB) have been found to promote the survival of infected CD169+ macrophages, thereby similarly promoting enforced viral replication.
Association of autoimmune disease with infections is evident from (1) autoimmune phenomena described during a chronic virus infection; (2) onset of autoimmune disease simultaneous to viral infections; and (3) experimental evidence. Involvement of virus infection during onset of type I diabetes is strongly evident. Epstein–Bar virus (EBV) infection was discussed to be involved in the pathogenesis of systemic lupus erythematosus.
In conclusion, several mechanisms promote viral replication in secondary lymphatic organs. Identifying such factors in humans is a challenge for future studies.
Viral infections can be fatal because of the direct cytopathic effects of the virus or the induction of a strong, uncontrolled inflammatory response. Recently we determined the circumstances under which enhanced replication of virus within the lymphoid tissue is beneficial for the outcome of a disease. This enforced viral replication promotes anti‐viral immune activation and, counterintuitively, accelerates virus control.
Fentanyl is one of the most frequently administered intraoperative drugs and may increase the risk of postoperative respiratory complications (PRCs).
We performed a pre-specified analysis of 145 735 ...adult non-cardiac surgical cases under general anaesthesia. Using multivariable logistic regression, we evaluated the association of intraoperative fentanyl dose and PRCs within 3 days after surgery (defined as reintubation, respiratory failure, pneumonia, pulmonary oedema, or atelectasis). We examined effect modification by patient characteristics, surgical site, and anaesthetics used.
PRCs within 3 days after surgery occurred in 18 839 (12.9%) patients. In comparison with high intraoperative fentanyl doses median: 3.85; inter-quartile range (IQR): 3.42–4.50 μg kg−1, quartile 4 (Q4), low intraoperative fentanyl dose median: 0.80, IQR: 0.00–1.14 μg kg−1, quartile 1 (Q1) was significantly associated with lower odds of PRCs Q1 vs Q4: 10.9% vs 16.2%; adjusted odds ratio (aOR) 0.79; 95% confidence intervals (CI) 0.75–0.84; P<0.001; adjusted absolute risk difference (aARD) −1.7%. This effect was augmented by thoracic surgery (P for interaction <0.001; aARD −6.2%), high doses of inhalation anaesthetics (P for interaction=0.016; aARD −2.2%) and neuromuscular blocking agents (NMBAs) (P for interaction=0.001; aARD −3.4%). Exploratory analysis demonstrated that compared with no fentanyl, low-dose fentanyl was associated with lower rates of PRCs (decile 2 vs decile 1: aOR 0.82, CI 0.75–0.89, P<0.001).
Intraoperative low-dose fentanyl (about 60–120 μg for a 70 kg patient) was associated with lower risk of postoperative respiratory complications compared with both no fentanyl and high-dose fentanyl. Beneficial effects of low-dose fentanyl were magnified in specific patient subgroups.
NCT03198208.
The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital ...readmission.
We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors.
Compared with low intraoperative opioid dosing quintile 1, median (inter-quartile range): 8 (4–9) mg morphine equivalents, exposure to high-dose opioids during surgery quintile 5: 32 (27–41) equivalents is an independent predictor of 30-day readmission odds ratio (OR) 1.15 (95% confidence interval 1.07–1.24); P<0.001. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose–response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0–2 vs 3–30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors.
High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery.
Precision measurements of nuclear
β
decay are among the most sensitive methods to probe beyond standard model (BSM) physics in the neutrino sector. In particular, momentum conservation between the ...emitted decay products in the final state is sensitive to any new physics that couples to the neutrino mass. One way to observe these momentum recoil effects experimentally is through high-precision measurements of nuclear electron capture (EC) decay where the final state only contains the neutrino and a recoiling atom. The Beryllium Electron capture in Superconducting Tunnel junctions (BeEST) experiment precisely measures the eV-scale radiation that follows the radioactive decay of
7
Be implanted into sensitive superconducting tunnel junction (STJ) quantum sensors. STJs are ideally suited for measurements of this type due to their high resolution at the low recoil energies in EC decay, and their high-rate counting capabilities. We present the motivation for the BeEST experiment and describe the various phases of the project.
A
bstract
We study the phenomenology of a hypercharge-zero SU (2) triplet scalar whose existence is motivated by two-step electroweak symmetry-breaking. We consider both the possibility that the ...triplets are stable and contribute to the dark matter density, or that they decay via mixing with the standard model Higgs boson. The former is constrained by disappearing charged track searches at the LHC and by dark matter direct detection experiments, while the latter is constrained by existing multilepton collider searches. We find that a two-step electroweak phase transition involving a stable triplet with a negative quadratic term is ruled out by direct detection searches, while an unstable triplet with a mass less than 230 GeV is excluded at 95% confidence level.
We analyze star formation in the nuclei of nine Seyfert galaxies at spatial resolutions down to 0.085", corresponding to length scales of order 10 pc in most objects. Our data were taken mostly with ...the near-infrared adaptive optics integral field spectrograph SINFONI. The stellar light profiles typically have size scales of a few tens of parsecs. In two cases there is unambiguous kinematic evidence for stellar disks on these scales. In the nuclear regions there appear to have been recent, but no longer active, starbursts in the last 10-300 Myr. The stellar luminosity is less than a few percent of the AGN in the central 10 pc, whereas on kiloparsec scales the luminosities are comparable. The surface stellar luminosity density follows a similar trend in all the objects, increasing steadily at smaller radii up to similar to 10 super(13) L unk kpc super(-2) in the central few parsecs, where the mass surface density exceeds 10 super(4) M unk pc super(-2). The intense starbursts were probably Eddington limited and hence inevitably short lived, implying that the starbursts occur in multiple short bursts. The data hint at a delay of 50-100 Myr between the onset of star formation and subsequent fueling of the black hole. We discuss whether this may be a consequence of the role that stellar ejecta could play in fueling the black hole. While a significant mass is ejected by OB winds and supernovae, their high velocity means that very little of it can be accreted. On the other hand, winds from AGB stars ultimately dominate the total mass loss, and they can also be accreted very efficiently because of their slow speeds.
Location information from long-duration super-pressure balloons flying in the Southern Hemisphere lower stratosphere during 2014 as part of X Project Loon are used to assess the quality of a number ...of different reanalyses including National Centers for Environmental Prediction Climate Forecast System version 2 (NCEP-CFSv2), European Centre for Medium-Range Weather Forecasts (ERA-Interim), NASA Modern Era Retrospective-Analysis for Research and Applications (MERRA), and the recently released MERRA version 2. Balloon GPS location information is used to derive wind speeds which are then compared with values from the reanalyses interpolated to the balloon times and locations. All reanalysis data sets accurately describe the winds, with biases in zonal winds of less than 0.37 m s−1 and meridional biases of less than 0.08 m s−1. The standard deviation on the differences between Loon and reanalyses zonal winds is latitude-dependent, ranging between 2.5 and 3.5 m s−1, increasing equatorward. Comparisons between Loon trajectories and those calculated by applying a trajectory model to reanalysis wind fields show that MERRA-2 wind fields result in the most accurate simulated trajectories with a mean 5-day balloon–reanalysis trajectory separation of 621 km and median separation of 324 km showing significant improvements over MERRA version 1 and slightly outperforming ERA-Interim. The latitudinal structure of the trajectory statistics for all reanalyses displays marginally lower mean separations between 15 and 35° S than between 35 and 55° S, despite standard deviations in the wind differences increasing toward the equator. This is shown to be related to the distance travelled by the balloon playing a role in the separation statistics.
Introduction
This study explores the uses of microcalorimetry to detect Mycobacterium tuberculosis (TB) in sputum. Microcalorimetry measures metabolic heat evolution during cellular proliferation of ...tuberculosis (TB) and is considered as a possible alternative to conventional diagnostic tools.
Objectives
To compare the time to detection (TTD) from the BACTEC™ MGIT™ 960 and the calScreener™ calorimetric system.
Methods
Sixty‐four sputa samples were selected from patients with confirmed pulmonary tuberculosis. Those sample were then decontaminated and analysed using calorimetry and BACTEC MGIT 960 system.
Results
The incubation period until detection of M. tuberculosis in the sample was 8·5 ± 3·7 days for the MGIT system and 10·1 ± 4·1 days (mean ± SD) for calorimetry.
Conclusions
The microincubations in the 48‐well format calScreener offers potential for rapid and accurate diagnostic of TB in different samples. Although TTD from calorimetry is still longer than with the MGIT, our findings suggest that several improvements are possible. Still, the instrument is ideal for continuous, real‐time analysis of net metabolic heat release of limited sample numbers.
Significance and Impact of the Study
Our result emphasizes that with further optimization, calorimetry can become an alternative detection method for tuberculosis.
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