Estimating NOx emissions of stack plumes using a high-resolution atmospheric chemistry model and satellite-derived NO2 columns

This work contributes to an European Monitoring and Verification Support (MVS) capacity for anthropogenic CO2 emissions. Future satellite instruments that map CO2 and NO2 from space will focus on hot-spot emissions from cities and large point sources, where CO2 emissions are accompanied by emissions of NOx. To use NOx as proxy CO2 emission, information about its atmospheric lifetime and the fraction of NOx present as NO2 is required to interpret NO2 plumes. This paper presents Large Eddy Simulations with atmospheric chemistry of four large point sources world-wide. We find that the chemical evolution of the plumes depends strongly on the amount of NOx that is emitted, next to wind speed and direction. For large NOx emissions the chemistry is pushed in a high-NOx chemical regime over a length of almost 100 km downwind of the stack location. Other plumes with lower NOx emissions show a fast transition to an intermediate NOx chemical regime, with short NOx lifetimes. Simulated NO2 columns mostly agree within 20 % with the TROPOspheric Monitoring Instrument (TROPOMI), signalling that the emissions used in the model were approximately correct. However, variability in the simulations is large, making a one-to-one comparison difficult. We find that wind speed variations should be accounted for in emission estimation methods. Moreover, results indicate that common assumptions about the NO2 lifetime (≈4 hours) and NOx: NO2 ratios (≈1.3) in simplified methods that estimate emissions from NO2 satellite data (e.g. Beirle et al., 2019) need revision

Prevention of Catheter-Related Bacteremia with a Daily Ethanol Lock in Patients with Tunnelled Catheters: A Randomized, Placebo-Controlled Trial

Background: Catheter-related bloodstream infection (CRBSI) results in significant attributable morbidity and mortality. In this randomized, double-blind, placebo-controlled trial, we studied the efficacy and safety of a daily ethanol lock for the prevention of CRBSI in patients with a tunnelled central venous catheter (CVC). Methodology: From 2005 through 2008, each lumen of the CVC of adult hematology patients was locked for 15 minutes per day with either 70%-ethanol or placebo, where after the lock solution was flushed through. As a primary endpoint, the incidence rates of endoluminal CRBSI were compared. Principal Findings: The intent-to-treat analysis was based on 376 patients, accounting for 448 CVCs and 27,745 catheter days. For ethanol locks, the incidence of endoluminal CRBSI per 1000 CVC-days was 0.70 (95%-CI, 0.4-1.3), compared to 1.19 (95% confidence interval, 0.7-1.9) for placebo (incidence rate-ratio, 0.59; 95% confidence interval, 0.27-1.30; P = .19). For endoluminal CRBSI according to the strictest definition (positive hub culture and identical bacterial strain in blood), a 3.6-fold, non-significant, reduction was observed for patients receiving ethanol (2 of 226 versus 7 of 222; P = .103). No lifethreatening adverse events were observed. More patients receiving ethanol discontinued lock-therapy (11 of 226 versus 1 of 222; P = .006) or continued with decreased lock-frequency (10 of 226 versus 0 of 222; P = .002), due to non-severe adverse events. Conclusions: In this study, the reduction in the incidence of endoluminal CRBSI using preventive ethanol locks was nonsignificant, although the low incidence of endoluminal CRBSI precludes definite conclusions. Therefore, the lack of statistical significance may partially reflect a lack of power. Significantly more patients treated with ethanol locks discontinued their prophylactic treatment due to adverse effects, which were non-severe but reasonably ethanol related. Additional studies should be performed in populations with higher incidence of (endoluminal) CRBSI. Alternative sources of bacteremia, like exoluminal CRBSI or microbial translocation during chemotherapy-induced mucositis may have been more important in our patients. Trial Registration: ClinicalTrials.gov NCT00122642

Serial [F-18]-FDHT-PET to predict bicalutamide efficacy in patients with androgen receptor positive metastatic breast cancer

Background: The androgen receptor (AR) is a potential target in metastatic breast cancer (MBC), and 16 beta-[F-18]-fluoro-5 alpha-dihydrotestosterone positron emission tomography ([F-18]-FDHT-PET) can be used for noninvasive visualisation of AR. [F-18]-FDHT uptake reduction during AR-targeting therapy reflects AR occupancy and might be predictive for treatment response. We assessed the feasibility of [F-18]-FDHT-PET to detect changes in AR availability during bicalutamide treatment and correlated these changes with treatment response. Patients and methods: Patients with AR thorn MBC, regardless of oestrogen receptor status, received an [F-18]-FDHT-PET at baseline and after 4-6 weeks bicalutamide treatment. Baseline [F-18]-FDHT uptake was expressed as maximum standardised uptake value. Percentage change in tracer uptake, corrected for background activity (SUVcor), between baseline and follow-up PET scan (% reduction), was assessed per-patient and lesion. Clinical benefit was determined in accordance with Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or clinical evaluation (absence of disease progression for >= 24 weeks). Results: Baseline [F-18]-FDHT-PET in 21 patients detected 341 of 515 lesions found with standard imaging and 21 new lesions. Follow-up [F-18]-FDHT- PET was evaluable in 17 patients with 349 lesions, showing a decrease in median SUVcor from 1.3 to 0.7 per-patient and lesion (P <0.001). Median % reduction per-patient was - 45% and per-lesion -39%. In patients with progressive disease (n Z 11), median % reduction was -30% versus -53% for patients who showed clinical benefit (in accordance with RECIST (n = 3) or clinical evaluation (n = 3); P Z 0.338). Conclusion: In this feasibility study, a bicalutamide-induced reduction in [F-18]-FDHT uptake could be detected by follow-up [F-18]-FDHT-PET in patients with AR thorn MBC. However, this change could not predict bicalutamide response. (C) 2020 The Authors. Published by Elsevier Ltd

Widespread reduction in sun-induced fluorescence from the Amazon during the 2015/2016 El Nino

The tropical carbon balance dominates year-to-year variations in the CO2 exchange with the atmosphere through photosynthesis, respiration and fires. Because of its high correlation with gross primary productivity (GPP), observations of sun-induced fluorescence (SIF) are of great interest. We developed a new remotely sensed SIF product with improved signal-to-noise in the tropics, and use it here to quantify the impact of the 2015/2016 El Nino Amazon drought. We find that SIF was strongly suppressed over areas with anomalously high temperatures and decreased levels of water in the soil. SIF went below its climatological range starting from the end of the 2015 dry season (October) and returned to normal levels by February 2016 when atmospheric conditions returned to normal, but well before the end of anomalously low precipitation that persisted through June 2016. Impacts were not uniform across the Amazon basin, with the eastern part experiencing much larger (10-15%) SIF reductions than the western part of the basin (2-5%). We estimate the integrated loss of GPP relative to eight previous years to be 0.34-0.48 PgC in the three-month period October-November-December 2015. This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Nino on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'

iPSC-based modeling of RAG2 severe combined immunodeficiency reveals multiple T cell developmental arrests

RAG2 severe combined immune deficiency (RAG2-SCID) is a lethal disorder caused by the absence of functional T and B cells due to a differentiation block. Here, we generated induced pluripotent stem cells (iPSCs) from a RAG2-SCID patient to study the nature of the T cell developmental blockade. We observed a strongly reduced capacity to differentiate at every investigated stage of T cell development, from early CD7(-)CD5(-) to CD4(+)CD8(+). The impaired differentiation was accompanied by an increase in CD7(-)CD56(+)CD33(+) natural killer (NK) cell-like cells. T cell receptor D rearrangements were completely absent in RAG2SCID cells, whereas the rare T cell receptor B rearrangements were likely the result of illegitimate rearrangements. Repair of RAG2 restored the capacity to induce T cell receptor rearrangements, normalized T cell development, and corrected the NK cell-like phenotype. In conclusion, we succeeded in generating an iPSC-based RAG2-SCID model, which enabled the identification of previously unrecognized disorder-related T cell developmental roadblocks

Incidental findings on coronary computed tomography in women with selected reproductive disorders

OBJECTIVE: To determine the prevalence of incidental findings (IFs) on coronary computed tomography (CCT) in women aged 45–55 years and previously diagnosed with reproductive disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) or preeclampsia (PE). METHODS: A total of 486 middle-aged women with PCOS (n = 101), POI (n = 97) or a history of PE (n = 288) underwent a CCT as part of a prior prospective study. IFs were categorized by their significance (minor, moderate and major). Follow-up information was collected from patients’ records. To investigate the impact of different field of views (FOVs), a subset of scans was analyzed in full FOV and small FOV. RESULTS: In 96/486 (19.8%) women, one or more IFs were detected, of which 54/486 (11.1%) were classified as moderate/major and 48/486 (9.9%) required follow-up. A moderate/major IF was detected in 16/101 (15.9%) women with PCOS, 13/97 (13.4%) women with POI and 25/288 (8.7%) women with a history of PE. In 78 women with an IF detected in the full FOV, the IF was still visible in 60 (76.9%) women in the small FOV. In the full FOV, 46 women required follow-up, but using the small FOV this was reduced to 30 women. CONCLUSION: Using CCT as a cardiovascular disease screening tool in women with selected reproductive disorders increases the probability of detecting IFs that can cause anxiety and may generate extra costs, but can also reveal clinically relevant findings. Using a small FOV centered around the heart resulted in a lower prevalence of IFs and required less follow-up

Thoracoscopic vs. catheter ablation for atrial fibrillation: long-term follow-up of the FAST randomized trial

Aims: Our objectives were to compare effectiveness and long-term prognosis after epicardial thoracoscopic atrial fibrillation (AF) ablation vs. endocardial catheter ablation, in patients with prior failed catheter ablation or high risk of failure. Methods and results: Patients were randomized to thoracoscopic or catheter ablation, consisting of pulmonary vein isolation with optional additional lines (2007–2010). Patients were reassessed in 2016/2017, and those without documented AF recurrence underwent 7-day ambulatory electrocardiography. The primary rhythm outcome was recurrence of any atrial arrhythmia lasting >30 s. The primary clinical endpoint was a composite of death, myocardial infarction, or cerebrovascular event, analysed with adjusted Cox proportional hazard ratios (HRs). One hundred and 24 patients were randomized with 34% persistent AF and mean age 56 years. Arrhythmia recurrence was common at mean follow-up of 7.0 years, but substantially lower with thoracoscopic ablation: 34/61 (56%) compared with 55/63 (87%) with catheter ablation [adjusted HR 0.40, 95% confidence interval (CI) 0.25–0.64; P < 0.001]. Additional ablation procedures were performed in 8 patients (13%) compared with 31 (49%), respectively (P < 0.001). Eleven patients (19%) were on anti-arrhythmic drugs at end of follow-up with thoracoscopy vs. 24 (39%) with catheter ablation (P = 0.012). There was no difference in the composite clinical outcome: 9 patients (15%) in the thoracoscopy arm vs. 10 patients (16%) with catheter ablation (HR 1.11, 95% CI 0.40–3.10; P = 0.84). Pacemaker implantation was required in 6 patients (10%) undergoing thoracoscopy and 3 (5%) in the catheter group (P = 0.27). Conclusion: Thoracoscopic AF ablation demonstrated more consistent maintenance of sinus rhythm than catheter ablation, with similar long-term clinical event rates

iPSC-Based Modeling of RAG2 Severe Combined Immunodeficiency Reveals Multiple T Cell Developmental Arrests

RAG2 severe combined immune deficiency (RAG2-SCID) is a lethal disorder caused by the absence of functional T and B cells due to a differentiation block. Here, we generated induced pluripotent stem cells (iPSCs) from a RAG2-SCID patient to study the nature of the T cell developmental blockade. We observed a strongly reduced capacity to differentiate at every investigated stage of T cell development, from early CD7−CD5− to CD4+CD8+. The impaired differentiation was accompanied by an increase in CD7−CD56+CD33+ natural killer (NK) cell-like cells. T cell receptor D rearrangements were completely absent in RAG2SCID cells, whereas the rare T cell receptor B rearrangements were likely the result of illegitimate rearrangements. Repair of RAG2 restored the capacity to induce T cell receptor rearrangements, normalized T cell development, and corrected the NK cell-like phenotype. In conclusion, we succeeded in generating an iPSC-based RAG2-SCID model, which enabled the identification of previously unrecognized disorder-related T cell developmental roadblocks.In this article, Mikkers

Density dependent hadron field theory for neutron stars with antikaon condensates

We investigate $K^-$ and $\bar K^0$ condensation in $\beta$-equilibrated hyperonic matter within a density dependent hadron field theoretical model. In this model, baryon-baryon and (anti)kaon-baryon interactions are mediated by the exchange of mesons. Density dependent meson-baryon coupling constants are obtained from microscopic Dirac Brueckner calculations using Groningen and Bonn A nucleon-nucleon potential. It is found that the threshold of antikaon condensation is not only sensitive to the equation of state but also to antikaon optical potential depth. Only for large values of antikaon optical potential depth, $K^-$ condensation sets in even in the presence of negatively charged hyperons. The threshold of $\bar K^0$ condensation is always reached after $K^-$ condensation. Antikaon condensation makes the equation of state softer thus resulting in smaller maximum mass stars compared with the case without any condensate.Comment: 20 pages, 7 figures; final version to appear in Physical Review