Gas‐phase activation of CO2 by chloride tagged metal atoms, ClM− (M=Mg, Zn), has been investigated by mass spectrometry and high‐level quantum chemistry. Both metals activate CO2 with significant ...bending of the CO2 moiety to form complexes with the general formula ClM,CO2−. The structure of the metal–CO2 complex depends on the method of formation, and the energy landscapes and reaction dynamics have been probed by collisional induced dissociation and thermal ion molecule reactions with isotopically labeled species. Having established these structural relationships, the gas‐phase reactivity of ClM(κ2‐O2C)− with acetaldehyde (here considered a carbohydrate mimic) was then studied. Formation of lactate and enolate‐pyruvate complexes are observed, showing that CO2 fixation by C−C bond formation takes place. For M=Zn, even formation of free pyruvate (C3H3O3−) is observed. Implications of the observed CO2 reactivity for the electrochemical conversion of carbon dioxide, and to biochemical and artificial photosynthesis is briefly discussed. Detailed potential energy diagrams obtained by the quantum chemical calculations offer models consistent with experimental observation.
Activating CO2: Anionic chloride tagged complexes of magnesium and zinc, ClM− (M=Mg, Zn), can bind and activate CO2 to form complexes of the form ClMCO2−. It is demonstrated that complexes of this kind, ClM(κ2‐O2C)−, are carbon nucleophiles that can add to C=O bonds. Addition to CO2 results in carbonate and oxalate complexes, whereas addition to acetaldehyde results in lactate complexes and free pyruvate (see scheme).
A magnesium complex incorporating a novel metal–CO2 binding motif is spectroscopically identified. Here we show with the help of infrared photodissociation spectroscopy that the complex exists solely ...in the ClMg(η2‐O2C)− form. This bidentate double oxygen metal–CO2 coordination has previously not been observed in neutral nor in charged unimetallic complexes. The antisymmetric CO2 stretching mode in ClMg(η2‐O2C)− is found at 1128 cm−1, which is considerably redshifted from the corresponding mode in bare CO2 at 2349 cm−1, suggesting that the CO2 moiety has a considerable negative charge (∼1.8 e−). We also employed electronic structure calculations and kinetic analysis to support the interpretation of the experimental results.
Bidentate coordination of CO2: An anionic complex of MgCl− and CO2, ClMgCO2−, is formed upon electrospray ionization followed by collision‐induced dissociation. With the help of infrared photodissociation spectroscopy it is shown that the complex exists solely in the double oxygen‐bound ClMg(η2‐O2C)− form, a type of CO2 coordination not previously seen in unimetallic complexes.
82Rb PET is commonly performed using the same injected activity in all patients, resulting in lower image quality in larger patients. This study compared 82Rb dosing with exponential vs proportional ...functions of body weight on the standardization of myocardial perfusion image (MPI) quality.
Two sequential cohorts of N = 60 patients were matched by patient weight. Rest and dipyridamole stress 82Rb PET was performed using 0.1 MBq·kg−2 exponential and 9 MBq·kg−1 proportional dosing. MPI scans were compared qualitatively with visual image quality scoring (IQS) and quantitatively using the myocardium-to-blood contrast-to-noise ratio (CNR) and blood background signal-to-noise ratio (SNR) as a function of body weight.
Average (min–max) patient body weight was 81 ± 18 kg (46–137 kg). Proportional dosing resulted in decreasing CNR, SNR, and visual IQS with increasing body weight (P < 0.05). Exponential dosing eliminated the weight-dependent decreases in these image quality metrics that were observed in the proportional dosing group.
82Rb PET dosing as an exponential (squared) function of body weight produced consistent stress perfusion image quality over a wide range of patient weights. Dramatically lower doses can be used in lighter patients, with the equivalent population dose shifted toward the heavier patients to standardize diagnostic image quality.
To determine rates of surgical site infection (SSI) with and without an abdominal closure protocol for gynecologic oncology patients undergoing abdominal hysterectomy.
Consecutive patients were ...identified using CPT codes who underwent total abdominal hysterectomy by gynecologic oncologists at a tertiary care center from January 1, 2015 to December 31, 2019, and stratified by use of the abdominal closure protocol. Demographic, perioperative, and pathologic variables were collected. Fisher's exact and Chi squared tests were used for categorical variables, logistic regression and student t-tests for continuous variables. Multiple logistic regression was used to analyze the relationships between these variables, use of the closure protocol, and development of SSI.
739 patients were included over the study period (n = 393 pre-implementation, n = 346 post-implementation of the abdominal closure protocol,). Baseline demographics including ASA score, BMI, diabetes, and smoking were similar between these groups (P = 0.14–0.94). The rate of SSI within 30 days was 5.9% (23/393) in the pre-protocol group and 8.1% (28/346) under the abdominal closure protocol (P = 0.25). On univariate analysis, factors associated with SSI were BMI >40, diabetes, bowel resection, ASA score 3 or 4, hypertension, and contaminated wound class (uOR 2.31–4.09). On multivariate analysis BMI >40, diabetes, and bowel resection remained independent risk factors (aOR 2.27–2.99), with the closure protocol not achieving significance (aOR 1.43, 95% CI 0.79–2.59). There were no potentially high-risk sub-groups in whom the closing protocol showed benefit.
The abdominal closure protocol in isolation did not decrease SSI in those undergoing TAH by a gynecologic oncologist.
•An abdominal closure protocol in isolation did not decrease the rate of SSI during oncologic total abdominal hysterectomy.•SSI rates after hysterectomy remain high, further research into alternative methods to decrease the rates of SSI are needed.•Institutions which already implemented other SSI reduction bundle steps may forego the addition of a separate closing tray.
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, ...the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutières syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in ∼8370 patients with SLE and ∼7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P=0.0008, OR=1.73, 95% CI=1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P=2.99E-13, OR=5.2, 95% CI=3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis.
•TAS used as bioreinforcing agent in recycled PP-PE blends without a compatibilizer.•Addition of 30%wt loading of TAS resulted in HDT of 10 °C above the neat polymer.•TAS under these conditions did ...not enhance polymer crystallinity.•TAS increased modulus but decreased toughness, elongation, and strength.
The present study revealed that torrefied almond shells (TAS) can be used as a bio-reinforcing agent for recycled polypropylene-polyethylene (PP-PE) blends without requiring a compatibilizer. Torrefaction of almond shells was performed to increase their hydrophobicity and provide good interfacial adhesion between matrix and filler. PP-PE samples blended with TAS were prepared using 3 different size ranges (sieved between mesh sizes of 100 and 120, 60 and 70, 35 and 45) and 7 different weight percent (%wt) loadings (0, 5, 10, 20, 30, 40, and 50). An increase in TAS loading resulted in an increase in flexural and tensile moduli, but a decrease in strength, elongation, and toughness. The effect of particle size and %wt loading on the heat deflection temperature (HDT) and crystallinity of PP-PE biocomposites were analyzed by thermo-mechanical analysis (TMA) and differential scanning calorimetry (DSC), respectively. HDT increased with higher TAS loading and with smaller particle size. The maximum observed increase was 10 °C at 30%wt loading of the small particles compared to neat PP-PE. The results for these biocomposites show that they can be potential candidates for consumer plastic applications.
We estimate a model that summarizes the yield curve using latent factors (specifically, level, slope, and curvature) and also includes observable macroeconomic variables (specifically, real activity, ...inflation, and the monetary policy instrument). Our goal is to provide a characterization of the dynamic interactions between the macroeconomy and the yield curve. We find strong evidence of the effects of macro variables on future movements in the yield curve and evidence for a reverse influence as well. We also relate our results to the expectations hypothesis.
Metformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in observational studies. We aimed to evaluate the efficacy of oral metformin for slowing ...geographic atrophy (GA) progression.
Parallel-group, multicenter, randomized phase II clinical trial.
Participants aged ≥ 55 years without diabetes who had GA from atrophic AMD in ≥ 1 eye.
We enrolled participants across 12 clinical centers and randomized participants in a 1:1 ratio to receive oral metformin (2000 mg daily) or observation for 18 months. Fundus autofluorescence imaging was obtained at baseline and every 6 months.
The primary efficacy endpoint was the annualized enlargement rate of the square root-transformed GA area. Secondary endpoints included best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit.
Of 66 enrolled participants, 34 (57 eyes) were randomized to the observation group and 32 (53 eyes) were randomized to the treatment group. The median follow-up duration was 13.9 and 12.6 months in the observation and metformin groups, respectively. The mean ± standard error annualized enlargement rate of square root transformed GA area was 0.35 ± 0.04 mm/year in the observation group and 0.42 ± 0.04 mm/year in the treatment group (risk difference = 0.07 mm/year, 95% confidence interval = -0.05 to 0.18 mm/year;
= 0.26). The mean ± standard error decline in BCVA was 4.8 ± 1.7 letters/year in the observation group and 3.4 ± 1.1 letters/year in the treatment group (
= 0.56). The mean ± standard error decline in LLVA was 7.3 ± 2.5 letters/year in the observation group and 0.8 ± 2.2 letters/year in the treatment group (
= 0.06). Fourteen participants in the metformin group experienced nonserious adverse events related to metformin, with gastrointestinal side effects as the most common. No serious adverse events were attributed to metformin.
The results of this trial as conducted do not support oral metformin having effects on reducing the progression of GA. Additional placebo-controlled trials are needed to explore the role of metformin for AMD, especially for earlier stages of the disease.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Background Preterm delivery remains the leading cause of perinatal mortality. Risk factors and biomarkers have traditionally failed to identify the majority of preterm deliveries. Objective To ...develop and validate a mass spectrometry–based serum test to predict spontaneous preterm delivery in asymptomatic pregnant women. Study Design A total of 5501 pregnant women were enrolled between 170/7 and 286/7 weeks gestational age in the prospective Proteomic Assessment of Preterm Risk study at 11 sites in the United States between 2011 and 2013. Maternal blood was collected at enrollment and outcomes collected following delivery. Maternal serum was processed by a proteomic workflow, and proteins were quantified by multiple reaction monitoring mass spectrometry. The discovery and verification process identified 2 serum proteins, insulin-like growth factor–binding protein 4 (IBP4) and sex hormone–binding globulin (SHBG), as predictors of spontaneous preterm delivery. We evaluated a predictor using the log ratio of the measures of IBP4 and SHBG (IBP4/SHBG) in a clinical validation study to classify spontaneous preterm delivery cases (<370/7 weeks gestational age) in a nested case-control cohort different from subjects used in discovery and verification. Strict blinding and independent statistical analyses were employed. Results The predictor had an area under the receiver operating characteristic curve value of 0.75 and sensitivity and specificity of 0.75 and 0.74, respectively. The IBP4/SHBG predictor at this sensitivity and specificity had an odds ratio of 5.04 for spontaneous preterm delivery. Accuracy of the IBP4/SHBG predictor increased using earlier case-vs-control gestational age cutoffs (eg, <350/7 vs ≥350/7 weeks gestational age). Importantly, higher-risk subjects defined by the IBP4/SHBG predictor score generally gave birth earlier than lower-risk subjects. Conclusion A serum-based molecular predictor identifies asymptomatic pregnant women at risk of spontaneous preterm delivery, which may provide utility in identifying women at risk at an early stage of pregnancy to allow for clinical intervention. This early detection would guide enhanced levels of care and accelerate development of clinical strategies to prevent preterm delivery.
PDF
