Accelerating growth of HFC-227ea (1,1,1,2,3,3,3-heptafluoropropane) in the atmosphere

We report the first measurements of 1,1,1,2,3,3,3-heptafluoropropane (HFC-227ea), a substitute for ozone depleting compounds, in air samples originating from remote regions of the atmosphere and present evidence for its accelerating growth. Observed mixing ratios ranged from below 0.01 ppt in deep firn air to 0.59 ppt in the current northern mid-latitudinal upper troposphere. Firn air samples collected in Greenland were used to reconstruct a history of atmospheric abundance. Year-on-year increases were deduced, with acceleration in the growth rate from 0.029 ppt per year in 2000 to 0.056 ppt per year in 2007. Upper tropospheric air samples provide evidence for a continuing growth until late 2009. Furthermore we calculated a stratospheric lifetime of 370 years from measurements of air samples collected on board high altitude aircraft and balloons. Emission estimates were determined from the reconstructed atmospheric trend and suggest that current "bottom-up" estimates of global emissions for 2005 are too high by a factor of three

G6b-B Inhibits Constitutive and Agonist-induced Signaling by Glycoprotein VI and CLEC-2

Platelets play an essential role in wound healing by forming thrombi that plug holes in the walls of damaged blood vessels. To achieve this, platelets express a diverse array of cell surface receptors and signaling proteins that induce rapid platelet activation. In this study we show that two platelet glycoprotein receptors that signal via an immunoreceptor tyrosine-based activation motif (ITAM) or an ITAM-like domain, namely the collagen receptor complex glycoprotein VI (GPVI)-FcR γ-chain and the C-type lectin-like receptor 2 (CLEC-2), respectively, support constitutive (i.e. agonist-independent) signaling in a cell line model using a nuclear factor of activated T-cells (NFAT) transcriptional reporter assay that can detect low level activation of phospholipase Cγ (PLCγ). Constitutive and agonist signaling by both receptors is dependent on Src and Syk family kinases, and is inhibited by G6b-B, a platelet immunoglobulin receptor that has two immunoreceptor tyrosine-based inhibitory motifs in its cytosolic tail. Mutation of the conserved tyrosines in the two immunoreceptor tyrosine-based inhibitory motifs prevents the inhibitory action of G6b-B. Interestingly, the inhibitory activity of G6b-B is independent of the Src homology 2 (SH2)-domain containing tyrosine phosphatases, SHP1 and SHP2, and the inositol 5′-phosphatase, SHIP. Constitutive signaling via Src and Syk tyrosine kinases is observed in platelets and is associated with tyrosine phosphorylation of GPVI-FcR γ-chain and CLEC-2. We speculate that inhibition of constitutive signaling through Src and Syk tyrosine kinases by G6b-B may help to prevent unwanted platelet activation

Advanced Fourier-based Model of Bouncing Loads

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record36th IMAC, A Conference and Exposition on Structural Dynamics 2018Contemporary design guideline pertinent to vibration serviceability of entertaining venues describes bouncing forces as a deterministic and periodic process presentable via Fourier series. However, fitting the Fourier harmonics to a comprehensive database of individual bouncing force records established in this study showed that such a simplification is far too radical, thus leading to a significant loss of information. Building on the conventional Fourier force model, this study makes the harmonics specific to each individual and takes into account imperfections in the bouncing process. The result is a numerical generator of stochastic bouncing force time histories which represent reliably the experimentally recorded bouncing force signals.The authors would like to acknowledge the financial support provided by PRIN 2015-2018 “Identification and monitoring of complex structural systems” and National Natural Science Foundation of China 347 (51478346) and State Key Laboratory for Disaster Reduction of Civil Engineering (SLDRCE14-B-16)

Safety and efficacy of ceftolozane/tazobactam plus metronidazole versus meropenem from a phase 2, randomized clinical trial in pediatric participants with complicated intra-abdominal infection

BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed. METHODS: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (\u3c18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points. RESULTS: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, drug-related AEs occurred in 18.6% and 14.3% and serious AEs occurred in 11.4% and 0% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, respectively. No drug-related serious AEs or discontinuations due to drug-related AEs occurred. Rates of the clinical cure for ceftolozane/tazobactam+metronidazole and meropenem at EOT were 80.0% and 95.2% (difference: -14.3; 95% confidence interval: -26.67 to 4.93) and at TOC were 80.0% and 100.0% (difference: -19.1; 95% confidence interval: -30.18 to -2.89), respectively; 6 of the 14 clinical failures for ceftolozane/tazobactam+metronidazole at TOC were indeterminate responses imputed as failures per protocol. CONCLUSION: Ceftolozane/tazobactam+metronidazole was well tolerated in pediatric participants with cIAI and had a safety profile similar to the established safety profile in adults. In this descriptive efficacy analysis, ceftolozane/tazobactam+metronidazole appeared efficacious

Newly detected ozone-depleting substances in the atmosphere

Ozone-depleting substances emitted through human activitiescause large-scale damage to the stratospheric ozone layer, and influence global climate. Consequently, the production of many of these substances has been phased out; prominent examples are the chlorofluorocarbons (CFCs), and their intermediate replacements, the hydrochlorofluorocarbons (HCFCs). So far, seven types of CFC and six types of HCFC have been shown to contribute to stratospheric ozone destruction 1,2. Here, we report the detection and quantification of a further three CFCs and one HCFC. We analysed the composition of unpolluted air samples collected in Tasmania between 1978 and 2012, and extracted from deep firn snow in Greenland in 2008, using gas chromatography with mass spectrometric detection. Using the firn data, we show that all four compounds started to emerge in the atmosphere in the 1960s. Two of the compounds continue to accumulate in the atmosphere. We estimate that, before 2012, emissions of all four compounds combined amounted to more than 74,000 tonnes. This is small compared with peak emissions of other CFCs in the 1980s of more than one million tonnes each year 2. However, the reported emissions are clearly contrary to the intentions behind the Montreal Protocol, and raise questions about the sources of these gases

Let\u27s talk about antibiotics: A randomised trial of two interventions to reduce antibiotic misuse

BACKGROUND: Children with acute respiratory tract infections (ARTIs) receive ≈11.4 million unnecessary antibiotic prescriptions annually. A noted contributor is inadequate parent-clinician communication, however, efforts to reduce overprescribing have only indirectly targeted communication or been impractical. OBJECTIVES: Compare two feasible (higher vs lower intensity) interventions for enhancing parent-clinician communication on the rate of inappropriate antibiotic prescribing. DESIGN: Multisite, parallel group, cluster randomised comparative effectiveness trial. Data collected between March 2017 and March 2019. SETTING: Academic and private practice outpatient clinics. PARTICIPANTS: Clinicians (n=41, 85% of eligible approached) and 1599 parent-child dyads (ages 1-5 years with ARTI symptoms, 71% of eligible approached). INTERVENTIONS: All clinicians received 20 min ARTI diagnosis and treatment education. Higher intensity clinicians received an additional 50 min communication skills training. All parents viewed a 90 second antibiotic education video. MAIN OUTCOMES AND MEASURES: Inappropriate antibiotic treatment was assessed via blinded medical record review by study clinicians and a priori defined as prescriptions for the wrong diagnosis or use of the wrong agent. Secondary outcomes were revisits, adverse drug reactions (both assessed 2 weeks after the visit) and parent ratings of provider communication, shared decision-making and visit satisfaction (assessed at end of the visit on Likert-type scales). RESULTS: Most clinicians completed the study (n=38, 93%), were doctors (n=25, 66%), female (n=30, 78%) and averaged 8 years in practice. All parent-child dyad provided data for the main outcome (n=855 (54%) male, n=1043 (53%) CONCLUSIONS AND RELEVANCE: Rate of inappropriate prescribing was low in both arms. Clinician education coupled with parent education may be sufficient to yield low inappropriate antibiotic prescribing rates. The absence of a significant difference between groups indicates that communication principles previously thought to drive inappropriate prescribing may need to be re-examined or may not have as much of an impact in practices where prescribing has improved in recent years. TRIAL REGISTRATION NUMBER: NCT03037112

Long-Term Outcome of Otherwise Healthy Individuals with Incidentally Discovered Borderline Thrombocytopenia

BACKGROUND: The long-term outcome of individuals with mild degrees of thrombocytopenia is unknown. METHODS AND FINDINGS: In a prospective study conducted between August 1992 and December 2002, 260 apparently healthy individuals with incidentally discovered platelet counts between 100 × 10(9)/l and 150 × 10(9)/l were monitored for 6 mo to determine whether their condition persisted. The monitoring period was completed in 217 cases, of whom 191 (88%) maintained stable platelet counts. These 191 individuals were included in a long-term follow-up study to gain knowledge of their natural history. With a median time of observation of 64 mo, the thrombocytopenia resolved spontaneously or persisted with no other disorders becoming apparent in 64% of cases. The most frequent event during the study period was the subsequent development of an autoimmune disease. The 10-y probability of developing idiopathic thrombocytopenic purpura (ITP), as defined by platelet counts persistently below 100 × 10(9)/l, was 6.9% (95% confidence interval [CI]: 4.0%–12.0%). The 10-y probability of developing autoimmune disorders other than ITP was 12.0% (95% CI: 6.9%–20.8%). Most of the cases (85%) of autoimmune disease occurred in women. CONCLUSIONS: Healthy individuals with a sustained platelet count between 100 × 10(9)/l and 150 × 10(9)/l have a 10-y probability of developing autoimmune disorders of 12%. Further investigation is required to establish whether this risk is higher than in the general population and whether an intensive follow-up results in an improvement of prognosis

Functional and genetic analysis of regulatory regions of coliphage H-19B: location of shiga-like toxin and lysis genes suggest a role for phage functions in toxin release

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74784/1/j.1365-2958.1998.00890.x.pd

Colours and pigments in late ukiyo-e art works: A preliminary non-invasive study of Japanese woodblock prints to interpret hyperspectral images using in-situ point-by-point diffuse reflectance spectroscopy

Dyes and pigments have been used in traditional Japanese woodblock printings in the ukiyo-e style for several centuries. However, the possible introduction of new European pigments and the extraordinary quality of the works of the later period led to take a keen interest in the analytical study of these ukiyo-e prints manufactured at the end of the 19th century. The present research discusses the analytical results of the series Bijin juni kagetsu (“Beauties in the Twelve Months”) by Shuntei, dated in 1898–1899. Due to the characteristics of this type of artworks, diffuse reflectance spectroscopy (DRS) has been chosen as a portable, non-invasive analytical technique to identify pigments and colorants used in the woodblock prints. The analytical possibilities offered by the in-situ point-by-point DRS as a preliminary tool to better interpret hyperspectral imaging (HSI) data were highlighted. Reflectance spectra of more than 190 points sampled throughout the artwork were recorded between 360 and 740 nm, and characterised. Throughout an statistical classification of the spectral data using unsupervised pattern recognition methods, twenty-two different colour composition was confirmed. These groups of reflectance spectra were then identified according the presence of characteristic maxima, minima and inflection points in every spectrum. Some micro-samples extracted from the pigments still remained in a woodblock (used for a 20th century print) were analysed by FESEM-EDS to better interpret some reflectance spectra. Traditional Japanese pigments (like vermilion, red lead, and indigo) and synthetic materials introduced in the 18th and 19th centuries (Prussian blue, synthetic arsenic sulphides, eosin, and methyl violet or crystal violet) were identified in the Shuntei''s series colours, together with some mixtures of pigments to prepare blue, green, orange and purple. Based on these twenty-two reflectance patterns, the point-by-point spectra make easier the task of interpreting the very complex HSI data, and reduce the time of treatment and interpretation required by HSI