Real-Time Detection of Gas-Phase Organohalogens from Aqueous Photochemistry Using Orbitrap Mass Spectrometry

SSCI-VIDE+CARE+MRT:CEM:SPR:CGOInternational audienceMarine short-lived halogenated compounds, emitted from algae, phytoplankton, and other marine biota, significantly affect both the troposphere and the stratosphere. Here, we show that such compounds might also be photochemically produced through photosensitized reactions in surface water. Gas-phase products were detected and identified by high-resolution mass spectrometry, more particularly by means of an atmospheric pressure chemical ionization source coupled to an Orbitrap mass spectrometer. Under simulated solar irradiation, halogenated organic compounds were produced and detected in the gas phase when a proxy of dissolved organic matter, i.e., 4-benzoylbenzoic acid, was excited into its triplet state. We present a mechanism explaining the formation of a variety of such halogenated compounds. These photochemical reactions take place at the air/sea interface and are, therefore, a potential source of short-lived halogenated compounds in the atmosphere, participating in the tropospheric halogen cycle

Sedimentology and stratigraphy of the type section of the Pennsylvanian Boss Point Formation, Joggins Fossil Cliffs, Nova Scotia, Canada

The 1125-m-thick type section of the Pennsylvanian Boss Point Formation is well exposed along the shore of the Bay of Fundy in Nova Scotia. We provide the first comprehensive account of the entirety of this formation, which comprises nearly one-third of the stratigraphic thickness of the Joggins Fossil Cliffs UNESCO World Heritage Site. The basal Chignecto Bay Member (0–91.5 m) is composed of redbeds, single-storey channel bodies with northerly paleoflow, and thin palustrine limestones. The middle Ward Point Member (91.5–951.7 m) contains up to 16 megacycles composed of alternations between thick packages of braided fluvial sandstone and fine-grained deposits. Although regional studies of the Boss Point Formation suggest that the fine-grained deposits are largely composed of lacustrine sediments, these intervals consist largely of poorly drained and well-drained floodplain deposits in the type section. The facies variations and southeast-directed paleoflow in the Ward Point Member record modest uplift associated with the growth of the salt-cored Minudie Anticline. The North Reef Member (951.7–1125 m) is composed of redbeds and two distinctive multistorey channel bodies. This uppermost member records a shift to more arid, oxidizing conditions, was the precursor to a major phase of salt withdrawal, and represents a transition to the overlying Little River Formation. The sedimentological framework, revised stratigraphy, and detailed measured section and map will provide a foundation for future study of this remarkable Pennsylvanian exposure

Fat intake modifies vascular responsiveness and receptor expression of vasoconstrictors: Implications for diet-induced obesity

Objective: Angiotensin II (Ang II), endothelin-1 (ET-1) and reactive oxygen species (ROS) have been implicated in the development of pathologic changes associated with obesity including hypertension and atherosclerosis. The aim of this study was to investigate the effects of dietary fat content on vasoreactivity and receptor expression at the level of gene and protein expression. Methods: C57BL/6 mice were fed diets of normal (Control, 12.3% kcal from fat), high (HF, 41% kcal from fat) and very high (VHF, 58% kcal from fat) fat content for 15weeks. Glucose tolerance tests were performed, and aortic rings were exposed to ET-1 (0.01-300nM) and Ang II (100nM) in the presence of l-nitro-arginine-methyl ester (l-NAME; 300μM). Gene and protein expressions of angiotensin and endothelin receptors were examined by real-time PCR and immunoblotting, respectively. The effects of diet on responses to acetylcholine (ACh 0.1-300μM), in the absence or presence of l-NAME, and to exogenous ROS/·OH were also investigated. Results: Both high fat diets similarly impaired glucose tolerance (P<0.05). Increasing dietary fat augmented contractions to Ang II in a step-wise manner (P<0.05). Conversely, increasing dietary fat had no effect on contractions to ET-1. Exposure to ROS/·OH resulted in a rapid vasodilation that was markedly augmented in a step-wise manner with increasing dietary fat (P<0.05). Endothelium-dependent relaxation to ACh was unaffected whereas vasoconstriction to high concentrations of ACh was enhanced in VHF animals (P<0.05 vs. control). Gene expression of the AT1B receptor was increased in the aorta of VHF mice, and aortic ETA receptor protein expression was increased after both high fat diets. Conclusions: These findings demonstrate that changes in dietary fat intake modulate vascular reactivity in response to Ang II and ROS, as well as expression of vascular angiotensin and endothelin receptors. Dietary fat intake may thereby directly affect cardiovascular ris

A four-month gatifloxacin-containing regimen for treating tuberculosis.

BACKGROUND: Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control. This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis. METHODS: We conducted a noninferiority, randomized, open-label, controlled trial involving patients 18 to 65 years of age with smear-positive, rifampin-sensitive, newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries. A standard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin (400 mg per day) was substituted for ethambutol during the intensive phase and was continued, along with rifampin and isoniazid, during the continuation phase. The primary efficacy end point was an unfavorable outcome (treatment failure, recurrence, or death or study dropout during treatment) measured 24 months after the end of treatment, with a noninferiority margin of 6 percentage points, adjusted for country. RESULTS: A total of 1836 patients were assigned to the 4-month regimen (experimental group) or the standard regimen (control group). Baseline characteristics were well balanced between the groups. At 24 months after the end of treatment, the adjusted difference in the risk of an unfavorable outcome (experimental group [21.0%] minus control group [17.2%]) in the modified intention-to-treat population (1356 patients) was 3.5 percentage points (95% confidence interval, -0.7 to 7.7). There was heterogeneity across countries (P=0.02 for interaction, with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal) and in baseline cavitary status (P=0.04 for interaction) and body-mass index (P=0.10 for interaction). The standard regimen, as compared with the 4-month regimen, was associated with a higher dropout rate during treatment (5.0% vs. 2.7%) and more treatment failures (2.4% vs. 1.7%) but fewer recurrences (7.1% vs. 14.6%). There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen. CONCLUSIONS: Noninferiority of the 4-month regimen to the standard regimen with respect to the primary efficacy end point was not shown. (Funded by the Special Program for Research and Training in Tropical Diseases and others; ClinicalTrials.gov number, NCT00216385.)

Efficacy of a loading dose of IV salbutamol in children with severe acute asthma admitted to a PICU:a randomized controlled trial

The optimal dose regimen for intravenous (IV) treatment in children with severe acute asthma (SAA) is still a matter of debate. We assessed the efficacy of adding a salbutamol loading dose to continuous infusion with salbutamol in children admitted to a pediatric intensive care unit (PICU) with SAA. This multicentre, placebo-controlled randomized trial in the PICUs of four tertiary care children’s hospitals included children (2–18 years) with SAA admitted between 2017 and 2019. Children were randomized to receive either a loading dose IV salbutamol (15 mcg/kg, max. 750 mcg) or normal saline while on continuous salbutamol infusion. The primary outcome was the asthma score (Qureshi) 1 h after the intervention. Analysis of covariance models was used to evaluate sensitivity to change in asthma scores. Serum concentrations of salbutamol were obtained. Fifty-eight children were included (29 in the intervention group). Median baseline asthma score was 12 (IQR 10–13) in the intervention group and 11 (9–12) in the control group (p = 0.032). The asthma score 1 h after the intervention did not differ significantly between the groups (p = 0.508, β-coefficient = 0.283). The median increase in salbutamol plasma levels 10 min after the intervention was 13 μg/L (IQR 5–24) in the intervention group and 4 μg/L (IQR 0–7) in the control group (p = 0.001). Side effects were comparable between both groups. Conclusion: We found no clinical benefit of adding a loading dose IV salbutamol to continuous infusion of salbutamol, in children admitted to the PICU with SAA. Clinically significant side effects from the loading dose were not encountered.What is Known:• Pediatric asthma guidelines struggle with an evidence-based approach for the treatment of SAA beyond the initial steps of oxygen suppletion, repetitive administration of inhaled β2-agonists, and systemic steroids.• During an SAA episode, effective delivery of inhaled drugs is unpredictable due to severe airway obstruction.What is New:• This study found no beneficial effect of an additional loading dose IV salbutamol in children admitted to the PICU.• This study found no clinically significant side effects from the loading dose

Current management of limited-stage SCLC and CONVERT trial impact:Results of the EORTC Lung Cancer Group survey

Objectives: The CONVERT trial showed that twice-daily (BD) concurrent chemoradiotherapy should continue tobe considered the standard of care in localised LS-SCLC. A survey was conducted to assess the impact of theCONVERT trial in clinical practice and to identify any relevant research questions for future trials in this setting.Methods and materials: An EORTC Group online survey of LS-SCLC practice was distributed to the EORTC LCGand to members of several European thoracic oncology societies between April and December 2018.Results: 198 responses were analysed. The majority of respondents (88%, n=174) were aware of the CONVERTtrial. Radiation oncologists comprised 56% of all respondents. Once-daily (OD) radiotherapy is still the mostcommonly used regimen, however the use of concurrent BD radiotherapy increased after the publication ofCONVERT (n=59/186, 32% prior to and n=78/187, 42% after the publication, p=0.053). The main reasonsfor not implementing BD after the CONVERT publication were logistical issues (n=88, 44%), inconvenience forpatients (n=56, 28%), and the absence of a statistical survival difference between the two arms in CONVERT(n=38, 19%). Brain MRI was used by 28% during staging but more than half (60%) of the respondents did notroutinely image the brain during follow-up. The main research questions of interest in LS-SCLC were 1) integratingnovel targeted therapies-immunotherapies (n=160, 81%), 2) PCI (+/- hippocampal sparing) vs. MRIsurveillance (n=140, 71%) and, 3) biomarker driven trials (n=92, 46%).Conclusion: Once daily radiotherapy (60–66 Gy in 30–33 fractions) remains the most prescribed radiotherapyfractionation, despite the findings suggested by the CONVERT trial.info:eu-repo/semantics/publishe

The Use of Single-Sided NMR to Study Moisture Behaviour in an Activated Carbon Fibre/Phenolic Composite

Nuclear Magnetic Resonance (NMR) has been shown to be a useful technique to study the form and content of water in polymer composites. Composites using activated carbon fibres with phenolic resin have complex water absorption behaviour which would benefit from such investigation; however, the presence of the conductive fibres can make NMR problematic. In this study, single-sided NMR has been successfully used on such material by developing a method for sample-to-sample compensation for the effect of conductivity. Transverse relaxation curves showed water to be primarily in two states in the resin, corresponding to "bound" and "mobile" molecules. In addition, two much less bound states were identified in the composite, associated firstly with water adsorbed on to the fibre surface and secondly with clusters of water molecules moving more freely within the fibre pores

Excess years of life lost to COVID-19 and other causes of death by sex, neighbourhood deprivation, and region in England and Wales during 2020: A registry-based study

BackgroundDeaths in the first year of the Coronavirus Disease 2019 (COVID-19) pandemic in England and Wales were unevenly distributed socioeconomically and geographically. However, the full scale of inequalities may have been underestimated to date, as most measures of excess mortality do not adequately account for varying age profiles of deaths between social groups. We measured years of life lost (YLL) attributable to the pandemic, directly or indirectly, comparing mortality across geographic and socioeconomic groups.Methods and findingsWe used national mortality registers in England and Wales, from 27 December 2014 until 25 December 2020, covering 3,265,937 deaths. YLLs (main outcome) were calculated using 2019 single year sex-specific life tables for England and Wales. Interrupted time-series analyses, with panel time-series models, were used to estimate expected YLL by sex, geographical region, and deprivation quintile between 7 March 2020 and 25 December 2020 by cause: direct deaths (COVID-19 and other respiratory diseases), cardiovascular disease and diabetes, cancer, and other indirect deaths (all other causes). Excess YLL during the pandemic period were calculated by subtracting observed from expected values. Additional analyses focused on excess deaths for region and deprivation strata, by age-group. Between 7 March 2020 and 25 December 2020, there were an estimated 763,550 (95% CI: 696,826 to 830,273) excess YLL in England and Wales, equivalent to a 15% (95% CI: 14 to 16) increase in YLL compared to the equivalent time period in 2019. There was a strong deprivation gradient in all-cause excess YLL, with rates per 100,000 population ranging from 916 (95% CI: 820 to 1,012) for the least deprived quintile to 1,645 (95% CI: 1,472 to 1,819) for the most deprived. The differences in excess YLL between deprivation quintiles were greatest in younger age groups; for all-cause deaths, a mean of 9.1 years per death (95% CI: 8.2 to 10.0) were lost in the least deprived quintile, compared to 10.8 (95% CI: 10.0 to 11.6) in the most deprived; for COVID-19 and other respiratory deaths, a mean of 8.9 years per death (95% CI: 8.7 to 9.1) were lost in the least deprived quintile, compared to 11.2 (95% CI: 11.0 to 11.5) in the most deprived. For all-cause mortality, estimated deaths in the most deprived compared to the most affluent areas were much higher in younger age groups, but similar for those aged 85 or over. There was marked variability in both all-cause and direct excess YLL by region, with the highest rates in the North West. Limitations include the quasi-experimental nature of the research design and the requirement for accurate and timely recording.ConclusionsIn this study, we observed strong socioeconomic and geographical health inequalities in YLL, during the first calendar year of the COVID-19 pandemic. These were in line with long-standing existing inequalities in England and Wales, with the most deprived areas reporting the largest numbers in potential YLL

Preclinical Assessment of Bacteriophage Therapy against Experimental Acinetobacter baumannii Lung Infection

Respiratory infections caused by multidrug-resistant Acinetobacter baumannii are difficult to treat and associated with high mortality among critically ill hospitalized patients. Bacteriophages (phages) eliminate pathogens with high host specificity and efficacy. However, the lack of appropriate preclinical experimental models hampers the progress of clinical development of phages as therapeutic agents. Therefore, we tested the efficacy of a purified lytic phage, vB_AbaM_Acibel004, against multidrug-resistant A. baumannii clinical isolate RUH 2037 infection in immunocompetent mice and a human lung tissue model. Sham- and A. baumannii-infected mice received a single-dose of phage or buffer via intratracheal aerosolization. Group-specific differences in bacterial burden, immune and clinical responses were compared. Phage-treated mice not only recovered faster from infection-associated hypothermia but also had lower pulmonary bacterial burden, lower lung permeability, and cytokine release. Histopathological examination revealed less inflammation with unaffected inflammatory cellular recruitment. No phage-specific adverse events were noted. Additionally, the bactericidal effect of the purified phage on A. baumannii was confirmed after single-dose treatment in an ex vivo human lung infection model. Taken together, our data suggest that the investigated phage has significant potential to treat multidrug-resistant A. baumannii infections and further support the development of appropriate methods for preclinical evaluation of antibacterial efficacy of phages