Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Diving below the spin-down limit:constraints on gravitational waves from the energetic young pulsar PSR J0537-6910

We present a search for continuous gravitational-wave signals from the young, energetic X-ray pulsar PSR J0537-6910 using data from the second and third observing runs of LIGO and Virgo. The search is enabled by a contemporaneous timing ephemeris obtained using NICER data. The NICER ephemeris has also been extended through 2020 October and includes three new glitches. PSR J0537-6910 has the largest spin-down luminosity of any pulsar and is highly active with regards to glitches. Analyses of its long-term and inter-glitch braking indices provided intriguing evidence that its spin-down energy budget may include gravitational-wave emission from a time-varying mass quadrupole moment. Its 62 Hz rotation frequency also puts its possible gravitational-wave emission in the most sensitive band of LIGO/Virgo detectors. Motivated by these considerations, we search for gravitational-wave emission at both once and twice the rotation frequency. We find no signal, however, and report our upper limits. Assuming a rigidly rotating triaxial star, our constraints reach below the gravitational-wave spin-down limit for this star for the first time by more than a factor of two and limit gravitational waves from the l = m = 2 mode to account for less than 14% of the spin-down energy budget. The fiducial equatorial ellipticity is limited to less than about 3 x 10⁻⁵, which is the third best constraint for any young pulsar

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

XRCC1 polymorphisms and haplotypes in Mexican patients with acute lymphoblastic leukemia

We examined the influence of the Arg194Trp, Arg280His, and Arg399Gln polymorphisms of XRCC1 (X-ray repair cross-complementing group 1) on the development of childhood acute lymphoblastic leukemia (ALL) in 120 ALL patients and 120 controls in Mexico. All of them were genotyped for these polymorphisms, using polymerase chain reaction. No significant differences in allele and genotype frequencies for any polymorphism were observed between patients and controls. Estimation of haplotypes showed the eight expected haplotypes (A-H), seven of which were found in both patients and controls; haplotype A (Arg-Arg-Arg) was the most common, whereas haplotypes F and G were absent in patients and controls, respectively. Haplotype B (Trp-Arg-Arg) was found to be associated with an increased risk of ALL (odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.13-3.37; P = 0.016), particularly in males (OR = 2.65, 95%CI = 1.25-5.63; P = 0.01). Individually, the 194Trp, 280His, and 399Gln alleles were not associated with significantly increased risk for ALL in these Mexican children. �FUNPEC-RP

New World Monkey Aotus nancymae as a Model for Campylobacter jejuni Infection and Immunity

Three groups of six monkeys (Aotus nancymae) each were inoculated intragastrically with increasing doses of Campylobacter jejuni. Infection resulted in fecal colonization (100% of monkeys), dose-related diarrhea, and robust immune responses. Colonization duration and diarrhea rate were reduced upon secondary challenge. A. nancymae may be useful for studying anti-Campylobacter vaccine efficacy

Molecular Assembly of Multi-Wall Carbon Nanotubes with Amino Crown Ether: Synthesis and Characterization

Synthetic methodology and physicochemical characterization of multi-wall carbon nanotubes (MWCNTs) functionalized with a crown ether molecule is reported. The MWCNTs were synthesized by spray pyrolysis technique using toluene as carbon source and ferrocene as catalyst. The nanotubes were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Oxidation of MWCNTs was carried out by 8 h of sonication in a mixture of sulfuric and nitric acid (3:1). The MWCNT-COOH was amidated with 4-aminobenzo-15-crown-5 under mild reaction conditions using N,N'-dicyclohexylcarbodiimide and dimethylaminopyridine as catalyst and dimethylformamide as solvent, at room temperature for 24 h. The amidation product was characterized by scanning electron microscopy, infrared spectroscopy, X-ray photoelectron spectroscopy, atomic force microscopy and a mass spectrometry study to determine the fragmentation pattern being m/z 309, 177 and 149 the most important ions

Physiological plasticity is important for maintaining sugarcane growth under water deficit

The water availability at early phenological stages is critical for crop establishment and sugarcane varieties show differential performance under drought. Herein, we evaluated the relative importance of morphological and physiological plasticity of young sugarcane plants grown under water deficit, testing the hypothesis that high phenotypic plasticity is associated with drought tolerance. IACSP95-5000 is a high yielding genotype and IACSP94-2094 has good performance under water limiting environments. Plants were grown in rhizotrons for 35 days under three water availabilities: high (soil water matric potential [Psi(m)] higher than -20 kPa); intermediate (Psi(m) reached 65 and 90 kPa at the end of experimental period) and low (Psi(m) reached values lower than 150 kPa). Our data revealed that morphological and physiological responses of sugarcane to drought are dependent on genotype and intensity of water deficit. In general, IACSP95-5000 showed higher physiological plasticity given by leaf gas exchange and photochemical traits, whereas IACSP94-2094 showed higher morphological plasticity determined by changes in leaf area (LA) and specific LA. As IACSP94-2094 accumulated less biomass than IACSP95-5000 under varying water availability, it is suggested that high morphological plasticity does not always represent an effective advantage to maintain plant growth under water deficit. In addition, our results revealed that sugarcane varieties face water deficit using distinct strategies based on physiological or morphological changes. When the effectiveness of those changes in maintaining plant growth under low water availability is taken into account, our results indicate that the physiological plasticity is more important than the morphological one in young sugarcane plants8CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP305221/2014-02008/57495-3; 2011/16263-

Physiological Plasticity Is Important for Maintaining Sugarcane Growth under Water Deficit

The water availability at early phenological stages is critical for crop establishment and sugarcane varieties show differential performance under drought. Herein, we evaluated the relative importance of morphological and physiological plasticity of young sugarcane plants grown under water deficit, testing the hypothesis that high phenotypic plasticity is associated with drought tolerance. IACSP95-5000 is a high yielding genotype and IACSP94-2094 has good performance under water limiting environments. Plants were grown in rhizotrons for 35 days under three water availabilities: high (soil water matric potential [Ψm] higher than -20 kPa); intermediate (Ψm reached -65 and -90 kPa at the end of experimental period) and low (Ψm reached values lower than -150 kPa). Our data revealed that morphological and physiological responses of sugarcane to drought are dependent on genotype and intensity of water deficit. In general, IACSP95-5000 showed higher physiological plasticity given by leaf gas exchange and photochemical traits, whereas IACSP94-2094 showed higher morphological plasticity determined by changes in leaf area (LA) and specific LA. As IACSP94-2094 accumulated less biomass than IACSP95-5000 under varying water availability, it is suggested that high morphological plasticity does not always represent an effective advantage to maintain plant growth under water deficit. In addition, our results revealed that sugarcane varieties face water deficit using distinct strategies based on physiological or morphological changes. When the effectiveness of those changes in maintaining plant growth under low water availability is taken into account, our results indicate that the physiological plasticity is more important than the morphological one in young sugarcane plants