Reaction of Perfluorooctanoic Acid with Criegee Intermediates and Implications for the Atmospheric Fate of Perfluorocarboxylic Acids

The reaction of perfluorooctanoic acid with the smallest carbonyl oxide Criegee intermediate, CH₂OO, has been measured and is very rapid, with a rate coefficient of (4.9 ± 0.8) × 10^–10 cm³ s^–1, similar to that for reactions of Criegee intermediates with other organic acids. Evidence is shown for the formation of hydroperoxymethyl perfluorooctanoate as a product. With such a large rate coefficient, reaction with Criegee intermediates can be a substantial contributor to atmospheric removal of perfluorocarboxylic acids. However, the atmospheric fates of the ester product largely regenerate the initial acid reactant. Wet deposition regenerates the perfluorocarboxylic acid via condensed-phase hydrolysis. Gas-phase reaction with OH is expected principally to result in formation of the acid anhydride, which also hydrolyzes to regenerate the acid, although a minor channel could lead to destruction of the perfluorinated backbone

Strategies to Maximize Science Data Availability for the GOES-R Series of Satellites

The Geostationary Operational Environmental Satellite-R Series (GOES-R) is the next generation of Untied States geostationary weather satellites. The GOES-R series significantly improves the detection and observation of environmental phenomena that directly affect public safety, protection of property and the economic health and prosperity of the United States and all countries within the western hemisphere. Given the real-time or ''now-casting'' nature of the GOES science gathering mission, any data outage or interruption can reduce warning times or scientific fidelity for critical weather data. GOES-R mission level requirements limit key performance product outages to a total of six hours per year to maximize science data availability. Lower level requirement only allow for 120 minutes of disruption between the spacecraft bus interface to the instruments. This requirement is met using both design features of the satellite and ground system, in addition to operational strategies

Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300

It is well established that the coordinated regulation of activity-dependent gene expression by the histone acetyltransferase (HAT) family of transcriptional coactivators is crucial for the formation of contextual fear and spatial memory, and for hippocampal synaptic plasticity. However, no studies have examined the role of this epigenetic mechanism within the infralimbic prefrontal cortex (ILPFC), an area of the brain that is essential for the formation and consolidation of fear extinction memory. Here we report that a postextinction training infusion of a combined p300/CBP inhibitor (Lys-CoA-Tat), directly into the ILPFC, enhances fear extinction memory in mice. Our results also demonstrate that the HAT p300 is highly expressed within pyramidal neurons of the ILPFC and that the small-molecule p300-specific inhibitor (C646) infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. C646 infused 6 h after extinction had no effect on fear extinction memory, nor did an immediate postextinction training infusion into the prelimbic prefrontal cortex. Consistent with the behavioral findings, inhibition of p300 activity within the ILPFC facilitated long-term potentiation (LTP) under stimulation conditions that do not evoke long-lasting LTP. These data suggest that one function of p300 activity within the ILPFC is to constrain synaptic plasticity, and that a reduction in the function of this HAT is required for the formation of fear extinction memory

Flipping the thinking on equality, diversity, and inclusion. why EDI is essential for the development and progression of the chemical sciences: A case study approach

All learners have a contribution to make to the development of the Chemical Sciences, be that in novel ways to teach, and their perspectives and contexts, but also in research, both in chemical education and the wider Chemical Sciences. Through four case studies, this paper explores interactions with diverse groups and how this has altered perspectives on both teaching and research. The case studies include work with visually impaired adults, a project bringing together First Peoples in Australia with academics to explore old ways (traditional science) and new ways (modern approaches), primary (elementary) school perspectives on teaching science, and a project in South Africa to connect university and township communities. Not only do these case studies demonstrate the immense value these diverse groups bring to our understanding about how to learn, but they also bring new perspectives on how to view and solve chemical problems

Left ventricular remodeling and hypertrophy in patients with aortic stenosis:insights from cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive method for determining left ventricular (LV) mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR.</p> <p>Methods</p> <p>Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening <b>≥</b>13 mm and >1.5-fold the thickness of the opposing myocardial segment.</p> <p>Results</p> <p>Ninety-one patients (61±21 years; 57 male) with aortic stenosis (aortic valve area 0.93±0.32cm2) were recruited. The severity of aortic stenosis was unrelated to the degree (r²=0.012, P=0.43) and pattern (P=0.22) of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02). Six patterns of LV adaption were observed: normal ventricular geometry (n=11), concentric remodeling (n=11), asymmetric remodeling (n=11), concentric hypertrophy (n=34), asymmetric hypertrophy (n=14) and LV decompensation (n=10). Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm) with hypertrophic cardiomyopathy.</p> <p>Conclusions</p> <p>We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Reference Number: NCT00930735</p

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

Improving the diagnosis and treatment of urinary tract infection in young children in primary care:results from the ‘DUTY’ prospective diagnostic cohort study

PURPOSE Up to 50% of urinary tract infections (UTIs) in young children are missed in primary care. Urine culture is essential for diagnosis, but urine collection is often difficult. Our aim was to derive and internally validate a 2-step clinical rule using (1) symptoms and signs to select children for urine collection; and (2) symptoms, signs, and dipstick testing to guide antibiotic treatment. METHODS We recruited acutely unwell children aged under 5 years from 233 primary care sites across England and Wales. Index tests were parent-reported symptoms, clinician-reported signs, urine dipstick results, and clinician opinion of UTI likelihood (clinical diagnosis before dipstick and culture). The reference standard was microbiologically confirmed UTI cultured from a clean-catch urine sample. We calculated sensitivity, specificity, and area under the receiver operator characteristic (AUROC) curve of coefficient-based (graded severity) and points-based (dichotomized) symptom/sign logistic regression models, and we then internally validated the AUROC using bootstrapping. RESULTS Three thousand thirty-six children provided urine samples, and culture results were available for 2,740 (90%). Of these results, 60 (2.2%) were positive: the clinical diagnosis was 46.6% sensitive, with an AUROC of 0.77. Previous UTI, increasing pain/crying on passing urine, increasingly smelly urine, absence of severe cough, increasing clinician impression of severe illness, abdominal tenderness on examination, and normal findings on ear examination were associated with UTI. The validated coefficient- and points-based model AUROCs were 0.87 and 0.86, respectively, increasing to 0.90 and 0.90, respectively, by adding dipstick nitrites, leukocytes, and blood. CONCLUSIONS A clinical rule based on symptoms and signs is superior to clinician diagnosis and performs well for identifying young children for noninvasive urine sampling. Dipstick results add further diagnostic value for empiric antibiotic treatment