Diurnal variation of midlatitudinal NO3 column abundance over table mountain facility, California

The column abundance of NO3 was measured over Table Mountain Facility, CA (34.4° 117.7° W) from May 2003 through September 2004, using lunar occultation near full moon with a grating spectrometer. The NO 3 column retrieval was performed with the differential optical absorption spectroscopy (DOAS) technique using both the 623 and 662 nm NO 3 absorption bands. Other spectral features such as Fraunhofer lines and absorption from water vapor and oxygen were removed using solar spectra obtained at different airmass factors. We observed a seasonal variation, with nocturnally averaged NO3 columns between 5-7 × 1013 molec cm-2 during October through March, and 5-22 × 10 13 molec cm-2 during April through September. A subset of the data, with diurnal variability vastly different from the temporal profile obtained from one-dimensional stratospheric model calculations, clearly has boundary layer contributions; this was confirmed by simultaneous long-path DOAS measurements. However, even the NO3 columns that did follow the modeled time evolution were often much larger than modeled stratospheric partial columns constrained by realistic temperatures and ozone concentrations. This discrepancy is attributed to substantial tropospheric NO3 in the free troposphere, which may have the same time dependence as stratospheric NO 3

Compartmentalized Intracellular Click Chemistry with Biodegradable Polymersomes

Polymersome nanoreactors that can be employed as artificial organelles have gained much interest over the past decades. Such systems often include biological catalysts (i.e., enzymes) so that they can undertake chemical reactions in cellulo. Examples of nanoreactor artificial organelles that acquire metal catalysts in their structure are limited, and their application in living cells remains fairly restricted. In part, this shortfall is due to difficulties associated with constructing systems that maintain their stability in vitro, let alone the toxicity they impose on cells. This study demonstrates a biodegradable and biocompatible polymersome nanoreactor platform, which can be applied as an artificial organelle in living cells. The ability of the artificial organelles to covalently and non-covalently incorporate tris(triazolylmethyl)amine-Cu(I) complexes in their membrane is shown. Such artificial organelles are capable of effectively catalyzing a copper-catalyzed azide-alkyne cycloaddition intracellularly, without compromising the cells’ integrity. The platform represents a step forward in the application of polymersome-based nanoreactors as artificial organelles

Eye Size and Shape in Relation to Refractive Error in Children:A Magnetic Resonance Imaging Study

Purpose: The purpose of this study was to determine the association between eye shape and volume measured with magnetic resonance imaging (MRI) and optical biometry and with spherical equivalent (SE) in children. Methods: For this study, there were 3637 10-year-old children from a population-based birth-cohort study that underwent optical biometry (IOL-master 500) and T2-weighted MRI scanning (height, width, and volume). Cycloplegic refractive error was determined by automated refraction. The MRI images of the eyes were segmented using an automated algorithm combining atlas registration with voxel classification. Associations among optical biometry, anthropometry, MRI measurements, and RE were tested using Pearson correlation. Differences between refractive error groups were tested using ANOVA. Results: The mean volume of the posterior segment was 6350 (±680) mm3. Myopic eyes (SE ≤ -0.5 diopters [D]) had 470 mm3 (P &lt; 0.001) and 970 mm3 (P &lt; 0.001) larger posterior segment volume than emmetropic and hyperopic eyes (SE ≥ +2.0D), respectively. The majority of eyes (77.1%) had an oblate shape, but 47.4% of myopic eyes had a prolate shape versus 3.9% of hyperopic eyes. The correlation between SE and MRI-derived posterior segment length (r -0.51, P &lt; 0.001) was stronger than the correlation with height (r -0.30, P &lt; 0.001) or width of the eye (r -0.10, P &lt; 0.001). Conclusions: In this study, eye shape at 10 years of age was predominantly oblate, even in eyes with myopia. Of all MRI measurements, posterior segment length was most prominently associated with SE. Whether eye shape predicts future myopia development or progression should be investigated in longitudinal studies.</p

Eye Size and Shape in Relation to Refractive Error in Children:A Magnetic Resonance Imaging Study

Purpose: The purpose of this study was to determine the association between eye shape and volume measured with magnetic resonance imaging (MRI) and optical biometry and with spherical equivalent (SE) in children. Methods: For this study, there were 3637 10-year-old children from a population-based birth-cohort study that underwent optical biometry (IOL-master 500) and T2-weighted MRI scanning (height, width, and volume). Cycloplegic refractive error was determined by automated refraction. The MRI images of the eyes were segmented using an automated algorithm combining atlas registration with voxel classification. Associations among optical biometry, anthropometry, MRI measurements, and RE were tested using Pearson correlation. Differences between refractive error groups were tested using ANOVA. Results: The mean volume of the posterior segment was 6350 (±680) mm3. Myopic eyes (SE ≤ -0.5 diopters [D]) had 470 mm3 (P &lt; 0.001) and 970 mm3 (P &lt; 0.001) larger posterior segment volume than emmetropic and hyperopic eyes (SE ≥ +2.0D), respectively. The majority of eyes (77.1%) had an oblate shape, but 47.4% of myopic eyes had a prolate shape versus 3.9% of hyperopic eyes. The correlation between SE and MRI-derived posterior segment length (r -0.51, P &lt; 0.001) was stronger than the correlation with height (r -0.30, P &lt; 0.001) or width of the eye (r -0.10, P &lt; 0.001). Conclusions: In this study, eye shape at 10 years of age was predominantly oblate, even in eyes with myopia. Of all MRI measurements, posterior segment length was most prominently associated with SE. Whether eye shape predicts future myopia development or progression should be investigated in longitudinal studies.</p

Population Pharmacokinetic Modelling of Intravenous Immunoglobulin Treatment in Patients with Guillain–Barré Syndrome

BACKGROUND AND OBJECTIVE: Intravenous immunoglobulin (IVIg) at a standard dosage is the treatment of choice for Guillain–Barré syndrome. The pharmacokinetics, however, is highly variable between patients, and a rapid clearance of IVIg is associated with poor recovery. We aimed to develop a model to predict the pharmacokinetics of a standard 5-day IVIg course (0.4 g/kg/day) in patients with Guillain–Barré syndrome. METHODS: Non-linear mixed-effects modelling software (NONMEM(®)) was used to construct a pharmacokinetic model based on a model-building cohort of 177 patients with Guillain–Barré syndrome, with a total of 589 sequential serum samples tested for total immunoglobulin G (IgG) levels, and evaluated on an independent validation cohort that consisted of 177 patients with Guillain–Barré syndrome with 689 sequential serum samples. RESULTS: The final two-compartment model accurately described the daily increment in serum IgG levels during a standard IVIg course; the initial rapid fall and then a gradual decline to steady-state levels thereafter. The covariates that increased IgG clearance were a more severe disease (as indicated by the Guillain–Barré syndrome disability score) and concomitant methylprednisolone treatment. When the current dosing regimen was simulated, the percentage of patients who reached a target ∆IgG > 7.3 g/L at 2 weeks decreased from 74% in mildly affected patients to only 33% in the most severely affected and mechanically ventilated patients (Guillain–Barré syndrome disability score of 5). CONCLUSIONS: This is the first population-pharmacokinetic model for standard IVIg treatment in Guillain–Barré syndrome. The model provides a new tool to predict the pharmacokinetics of alternative regimens of IVIg in Guillain–Barré syndrome to design future trials and personalise treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40262-022-01136-z

Dynamics and prognostic value of serum neurofilament light chain in Guillain-Barré syndrome

Background: Neurofilament light chain (NfL) is a biomarker for axonal damage in several neurological disorders. We studied the longitudinal changes in serum NfL in patients with Guillain-Barré syndrome (GBS) in relation to disease severity, electrophysiological subtype, treatment response, and prognosis. Methods: We included patients with GBS who participated in a double-blind, randomised, placebo-controlled trial that evaluated the effects of a second course of intravenous immunoglobulin (IVIg) on clinical outcomes. Serum NfL levels were measured before initiation of treatment and at one, two, four, and twelve weeks using a Simoa HD-X Analyzer. Serum NfL dynamics were analysed using linear mixed-effects models. Logistic regression was employed to determine the associations of serum NfL with clinical outcome and the prognostic value of serum NfL after correcting for known prognostic markers.Findings: NfL levels were tested in serum from 281 patients. Serum NfL dynamics were associated with disease severity and electrophysiological subtype. Strong associations were found between high levels of serum NfL at two weeks and inability to walk unaided at four weeks (OR = 1.74, 95% CI = 1.27–2.45), and high serum NfL levels at four weeks and inability to walk unaided at 26 weeks (OR = 2.79, 95% CI = 1.72–4.90). Baseline serum NfL had the most significant prognostic value for ability to walk, independent of known predictors of outcome. The time to regain ability to walk unaided was significantly longer for patients with highest serum NfL levels at baseline (p = 0.0048) and week 2 (p &lt; 0.0001). No differences in serum NfL were observed between patients that received a second IVIg course vs. IVIg and placebo.Interpretation: Serum NfL levels are associated with disease severity, axonal involvement, and poor outcome in GBS. Serum NfL potentially represents a biomarker to monitor neuronal damage in GBS and an intermediate endpoint to evaluate the effects of treatment. </p

Fusidic acid cream in the treatment of impetigo in general practice: double blind randomised placebo controlled trial

OBJECTIVE: To test the hypothesis that fusidic acid would not increase the treatment effect of disinfecting with povidone-iodine alone in children with impetigo. DESIGN: Randomised placebo controlled trial. SETTING: General practices in Greater Rotterdam. PARTICIPANTS: 184 children aged 0-12 years with impetigo. MAIN OUTCOME MEASURES: Clinical cure and bacterial cure after one week. RESULTS: After one week of treatment 55% of the patients in the fusidic acid group were clinically cured compared with 13% in the placebo group (odds ratio 12.6, 95% confidence interval 5.0 to 31.5, number needed to treat 2.3). After two weeks and four weeks the differences in cure rates between the two groups had become smaller. More children in the placebo group were non-compliant (12 v 5) and received extra antibiotic treatment (11 v 3), and more children in the placebo group reported adverse effects (19 v 7). Staphylococcus aureus was found in 96% of the positive cultures; no strains were resistant to fusidic acid. CONCLUSIONS: Fusidic acid is much more effective than placebo (when both are given in combination with povidone-iodine shampoo) in the treatment of impetigo. Because of the low rate of cure and high rate of adverse events in the placebo group, the value of povidone-iodine in impetigo can be questioned

Development and external validation of preoperative clinical prediction models for postoperative outcomes including preoperative aerobic fitness in patients approaching elective colorectal cancer surgery

Introduction: Preoperative aerobic fitness is associated with postoperative outcomes after elective colorectal cancer (CRC) surgery. This study aimed to develop and externally validate two clinical prediction models incorporating a practical test to assess preoperative aerobic fitness to distinguish between patients with and without an increased risk for 1) postoperative complications and 2) a prolonged time to in-hospital recovery of physical functioning after elective colorectal cancer (CRC) surgery. Materials and methods: Models were developed using prospective data from 256 patients and externally validated using prospective data of 291 patients. Postoperative complications were classified according to Clavien-Dindo. The modified Iowa level of assistance scale (mILAS) was used to determine time to postoperative in-hospital physical recovery. Aerobic fitness, age, sex, body mass index, American Society of Anesthesiologists (ASA) classification, neoadjuvant treatment, surgical approach, tumour location, and preoperative haemoglobin level were potential predictors. Areas under the curve (AUC), calibration plots, and Hosmer-Lemeshow tests evaluated predictive performance. Results: Aerobic fitness, sex, age, ASA, tumour location, and surgical approach were included in the final models. External validation of the model for complications and postoperative recovery presented moderate to fair discrimination (AUC 0.666 (0.598–0.733) and 0.722 (0.651–0.794), respectively) and good calibration. High sensitivity and high negative predictive values were observed in the lower predicted risk categories (&lt;40 %). Conclusion: Both models identify patients with and without an increased risk of complications or a prolonged time to in-hospital physical recovery. They might be used for improving patient-tailored preoperative risk assessment and targeted and cost-effective application of prehabilitation interventions.</p

Direct stenting with the Bx VELOCITY balloon-expandable stent mounted on the Raptor rapid exchange delivery system versus predilatation in a European randomized Trial: the VELVET trial.

Abstract AIMS: This study examined the six-month angiographic results of direct coronary stenting, and compared the nine-month safety, efficacy and cost of this strategy versus stenting after balloon predilatation. METHODS: In phase I of VELVET, 122 patients (mean age = 62.3 +/- 10.1 years, 77% male, 11% with diabetes) with angina pectoris or myocardial ischemia resulting from a single de novo 51% to 95% coronary stenosis underwent direct stenting. The endpoints of phase I included angiographic findings and rates of major adverse cardiac events up to six months of follow-up. In phase II, 401 patients (mean age = 61.3 +/- 10.8 years, 79% male, 16% with diabetes) with angina pectoris or documented myocardial ischemia resulting from single or multiple, de novo or restenotic, coronary lesions were randomized between direc