IMPORTANCE: Selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) are prophylactic antibiotic regimens used in intensive care units (ICUs) and ...associated with improved patient outcome. Controversy exists regarding the relative effects of both measures on patient outcome and antibiotic resistance. OBJECTIVE: To compare the effects of SDD and SOD, applied as unit-wide interventions, on antibiotic resistance and patient outcome. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, cluster randomized crossover trial comparing 12 months of SOD with 12 months of SDD in 16 Dutch ICUs between August 1, 2009, and February 1, 2013. Patients with an expected length of ICU stay longer than 48 hours were eligible to receive the regimens, and 5957 and 6040 patients were included in the clinical outcome analysis for SOD and SDD, respectively. INTERVENTIONS: Intensive care units were randomized to administer either SDD or SOD. MAIN OUTCOMES AND MEASURES: Unit-wide prevalence of antibiotic-resistant gram-negative bacteria. Secondary outcomes were day-28 mortality, ICU-acquired bacteremia, and length of ICU stay. RESULTS: In point-prevalence surveys, prevalences of antibiotic-resistant gram-negative bacteria in perianal swabs were significantly lower during SDD compared with SOD; for aminoglycoside resistance, average prevalence was 5.6% (95% CI, 4.6%-6.7%) during SDD and 11.8% (95% CI, 10.3%-13.2%) during SOD (P < .001). During both interventions the prevalence of rectal carriage of aminoglycoside-resistant gram-negative bacteria increased 7% per month (95% CI, 1%-13%) during SDD (P = .02) and 4% per month (95% CI, 0%-8%) during SOD (P = .046; P = .40 for difference). Day 28-mortality was 25.7% and 23.8% during SOD and SDD, respectively (adjusted odds ratio, 0.85 95% CI, 0.77-0.93; P = .001), and this difference was similar between surgical and nonsurgical patients. Intensive care unit–acquired bacteremia occurred in 5.9% and 4.5% of the patients during SOD and SDD, respectively (odds ratio, 0.74 95% CI, 0.63-0.88; P < .001; number needed to treat, 69). CONCLUSIONS AND RELEVANCE: Unit-wide application of SDD and SOD was associated with low levels of antibiotic resistance. Compared with SOD, SDD was associated with lower day-28 mortality, rectal carriage of antibiotic-resistant gram-negative bacteria, and ICU-acquired bacteremia but a more pronounced gradual increase in aminoglycoside-resistant gram-negative bacteria. TRIAL REGISTRATION: trialregister.nl Identifier: NTR1780
The linear and mode-coupled contributions to higher-order anisotropic flow are presented for Au+Au collisions at sNN = 27, 39, 54.4, and 200 GeV and compared to similar measurements for Pb+Pb ...collisions at the Large Hadron Collider (LHC). The coefficients and the flow harmonics' correlations, which characterize the linear and mode-coupled response to the lower-order anisotropies, indicate a beam energy dependence consistent with an influence from the specific shear viscosity (η/s). In contrast, the dimensionless coefficients, mode-coupled response coefficients, and normalized symmetric cumulants are approximately beam-energy independent, consistent with a significant role from initial-state effects. These measurements could provide unique supplemental constraints to (i) distinguish between different initial-state models and (ii) delineate the temperature (T) and baryon chemical potential (μB) dependence of the specific shear viscosity ηs(T,μB).
Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection ...such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited.
In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581.
From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001).
When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry.
US National Institutes of Health.
During the 20th century hunger has become a problem of poverty amidst plenty rather than absolute food scarcity. The question is whether this will remain so or whether the hunger of the poor will ...once more be exacerbated by rising food prices. In this paper we discuss biophysical conditions, social forces and non-linear interactions that may critically influence the global availability of food in the long term. Until 2050, the global demand for primary phytomass for food will more than double, while competing claims to natural resources for other purposes (including biobased non-foods will increase. A sober assessment of the earth's biophysical potential for biomass production, which recognizes competing claims and unavoidable losses, suggests that this is in itself still large enough for accommodating this rising demand. However, the exploitation of this biophysical potential proceeds through technical paradigms that set a relative maximum to food production. In addition, socio-economic mechanisms make the food economy run up against a ceiling even before this maximum is reached. As a consequence, current developments may well entail a new trend change in international markets. These developments include the depletion of land and water reserves, the stagnation of the potential yields of major crops, the rise in energy prices, and the way in which systemic socio-economic factors lead to a strong underutilization of production possibilities in the developing world. Given these conditions, the avoidance of steep rises in food prices may depend on the timely relaxation of socio-economic constraints in developing countries and on timely breakthroughs in sustainable yield increases, biorefinement and non-farm production systems. Myopic expectations make it doubtful whether spontaneous market forces will provide the necessary incentives for this, which may be reason for societal actors to consider the need for more active policies.
The cross section of the 13C(α, n0)16O reaction is needed for nuclear astrophysics and applications to a precision of 10% or better, yet inconsistencies among 50 years of experimental studies ...currently lead to an uncertainty of ≈15%. Here, using a state-of-the-art neutron detection array, we have performed a high resolution differential cross section study covering a broad energy range. These measurements result in a dramatic improvement in the extrapolation of the cross section to stellar energies potentially reducing the uncertainty to ≈5% and resolving long standing discrepancies in higher energy data.
The chiral magnetic wave (CMW) has been theorized to propagate in the deconfined nuclear medium formed in high-energy heavy-ion collisions, and to cause a difference in elliptic flow (v2) between ...negatively and positively charged hadrons. Experimental data consistent with the CMW have been reported by the STAR Collaboration at the Relativistic Heavy Ion Collider (RHIC), based on the charge asymmetry dependence of the pion v2 from Au+Au collisions at $\sqrt{s_{NN}}$ = 27 to 200 GeV. In this comprehensive study, we present the STAR measurements of elliptic flow and triangular flow of charged pions, along with the v2 of charged kaons and protons, as a function of charge asymmetry in Au+Au collisions at $\sqrt{s_{NN}}$ = 27, 39, 62.4 and 200 GeV. The slope parameters extracted from the linear dependence of the v2 difference on charge asymmetry for different particle species are reported and compared in different centrality intervals. In addition, the slopes of v2 for charged pions in small systems, i.e., p+Au and d+Au at $\sqrt{s_{NN}}$ = 200 GeV, are also presented and compared with those in large systems, i.e., Au+Au at $\sqrt{s_{NN}}$ = 200 GeV and U+U at 193 GeV. Our results provide new insights for the possible existence of the CMW, and further constrain the background contributions in heavy-ion collisions at RHIC energies.
A
bstract
We report a new measurement of the production of electrons from open heavy-flavor hadron decays (HFEs) at mid-rapidity (|
y
|
<
0.7) in Au+Au collisions at
s
NN
= 200 GeV. Invariant yields ...of HFEs are measured for the transverse momentum range of 3
.
5
< p
T
<
9 GeV/
c
in various configurations of the collision geometry. The HFE yields in head-on Au+Au collisions are suppressed by approximately a factor of 2 compared to that in
p
+
p
collisions scaled by the average number of binary collisions, indicating strong interactions between heavy quarks and the hot and dense medium created in heavy-ion collisions. Comparison of these results with models provides additional tests of theoretical calculations of heavy quark energy loss in the quark-gluon plasma.
Aims Fetuin-A has been identified as a potent circulating inhibitor of ectopic calcification. We investigated the relationship between baseline fetuin-A serum levels and the rate of progression of ...aortic valve calcification (AVC) in non-dialyzed patients with aortic valve disease (AVD). Methods and results Seventy-seven patients (mean age 70 ± 8 years) with echocardiographically proven AVD were collected. In all patients, serum fetuin-A levels, creatinine, calcium, lipid parameters, and C-reactive protein were measured at baseline. For quantification of AVC progression, all patients underwent multislice spiral computed tomography examinations at baseline and after a mean follow-up of 12.6 ± 1.4 months (range 7–18 months). In a multifactorial analysis of covariance including fetuin-A levels, baseline AVC score, the covariables sex, age, body mass index, C-reactive protein, glomerular filtration rate, serum lipids, diabetes, smoking status, and hypertension, only serum fetuin-A levels significantly predict the progression of AVC (P < 0.001). Post hoc analysis demonstrated that patients with baseline fetuin-A levels lower than the median of the cohort (0.72 g/L) showed a significantly higher increase of AVC scores (34.6 ± 31.4%) than patients with fetuin-A levels larger than the median (10.0 ± 11.2%, P < 0.001) despite comparable baseline AVC scores. In addition, fetuin-A levels were associated with major adverse clinical events (MACE; P = 0.03). Conclusion Serum levels of the calcification inhibitor fetuin-A are associated with the progression of AVC and MACE, independent of the renal function and inflammation.
Background. Cardiovascular morbidity and mortality are massively increased in patients with chronic kidney disease (CKD). Sevelamer hydrochloride has been shown to attenuate cardiovascular ...calcifications in CKD and end-stage renal disease (ESRD) patients. We assessed how sevelamer hydrochloride influences the evolution of serum fetuin-A and other serological factors predicting cardiovascular outcome and survival in haemodialysis patients. Methods. Fifty-seven prevalent haemodialysis patients were included in a three-phase prospective interventional trial (A–B–A design; 8 weeks per phase). Sevelamer was only administered in the middle phase of the study. Within the other two phases, ≥90% of the patients received calcium acetate for phosphate binding. Detailed time courses of serum biochemistries were analysed in order to obtain detailed insight into the influence of sevelamer upon CKD–mineral and bone disorder (MBD) parameters as well as serum fetuin-A, fibroblast growth factor 23 (FGF23) and uraemic toxin levels uric acid, indoxyl sulphate, hippuric acid, indole acetic acid, p-cresol and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF). Results. Forty-one patients finished the three prospective study phases (intention-to-treat analysis). After treatment with sevelamer, serum fetuin-A significantly increased (+21%), showing a delayed increase outlasting the third (non-sevelamer) study period. Total and low-density lipoprotein (LDL) cholesterol levels, as well as serum calcium, decreased significantly. The opposite occurred with albumin, C-reactive protein and intact parathyroid hormone (iPTH). FGF23, uric acid, indoxyl sulphate, hippuric acid, indole acetic acid, CMPF and serum phosphate did not change significantly during sevelamer treatment. In contrast, in parallel to sevelamer treatment, there was a significant rise in serum p-cresol. Conclusions. In haemodialysis patients, treatment with sevelamer over 8 weeks was associated with a delayed yet long-lasting increase in serum fetuin-A levels. Increasing the serum level of fetuin-A, a negative acute-phase protein and systemic calcification inhibitor, might be one of the potential anti-calcification mechanisms of sevelamer. Since we failed to detect a decrease in systemic inflammation and uraemic toxins, the exact mechanisms by which sevelamer treatment affects serum fetuin-A remain to be determined.
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