4D In-Situ Microscopy of Aerosol Filtration in a Wall Flow Filter

The transient nature of the internal pore structure of particulate wall flow filters, caused by the continuous deposition of particulate matter, makes studying their flow and filtration characteristics challenging. In this article we present a new methodology and first experimental demonstration of time resolved in-situ synchrotron micro X-ray computed tomography (micro-CT) to study aerosol filtration. We directly imaged in 4D (3D plus time) pore scale deposits of TiO2 nanoparticles (nominal mean primary diameter of 25 nm) with a pixel resolution of 1.6 μm. We obtained 3D tomograms at a rate of ∼1 per minute. The combined spatial and temporal resolution allows us to observe pore blocking and filling phenomena as they occur in the filter’s pore space. We quantified the reduction in filter porosity over time, from an initial porosity of 0.60 to a final porosity of 0.56 after 20 min. Furthermore, the penetration depth of particulate deposits and filtration rate was quantified. This novel image-based method offers valuable and statistically relevant insights into how the pore structure and function evolves during particulate filtration. Our data set will allow validation of simulations of automotive wall flow filters. Evolutions of this experimental design have potential for the study of a wide range of dry aerosol filters and could be directly applied to catalysed automotive wall flow filters

TH17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity

Acting in concert with TGF-b, IL-6 signaling induces Th17 cell development by programming Th17-related genes via STAT3. A role for IL-6 signaling beyond the inductive phase of Th17 cell development has not been defined, as IL-23 signaling downstream of Th17 cell induction also activates STAT3 and is thought responsible for Th17 cell maintenance. Here, we find that IL-6 signaling is required for both induction and maintenance of Th17 cells; IL-6Ra–deficient Th17 cells rapidly lost their Th17 phenotype and did not cause disease in two models of colitis. Cotransfer of WT Th17 cells with IL-6Ra–deficient Th17 cells induced colitis but was unable to rescue phenotype loss of the latter. High IL-6 in the colon promoted classic, or cis, rather than trans receptor signaling that was required for maintenance of Th17 cells. Thus, ongoing classic IL6 signaling underpins the Th17 program and is required for Th17 cell maintenance and function

Carbon uptake and distribution in Spark Plasma Sintering (SPS) processed Sm(Co, Fe, Cu, Zr)z

Spark Plasma Sintering (SPS) rapidly consolidates high-melting point powders between carbon dies, but carbon can pose a risk for many materials. Carbon uptake in SPS and conventional, pressure-less sintered (CS) Sm(Co, Fe, Cu, Zr)z has been analysed using Electron Probe Micro-Analysis (EPMA) to produce high-detail elemental distribution maps. Field's metal was used as mounting material to avoid introducing carbon into the samples. The distribution maps show high surface carbon levels in the SPS-processed Sm(Co, Fe, Cu, Zr)z to a depth of 10 μm. Much less carbon was observed in CS Sm(Co, Fe, Cu, Zr)z. Furthermore, elemental carbon analysis (LECO-C) confirmed carbon was most abundant at the surface in SPS-processed Sm(Co, Fe, Cu, Zr)z but also at higher levels internally, when compared to the CS sample. It is inferred that the carbon contamination is due to the contact between the powder and the graphite die/paper at elevated temperatures during SPS process. The measured levels of carbon in the SPS-processed sample are not expected to significantly impact the magnetic properties of Sm(Co, Fe, Cu, Zr)z. These results may have implications for other powder materials processed by SPS with properties sensitive to carbon

Stereotactic ablative body radiotherapy in patients with oligometastatic cancers:a prospective, registry-based, single-arm, observational, evaluation study

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is increasingly being used to treat oligometastatic cancers, but high-level evidence to provide a basis for policy making is scarce. Additional evidence from a real-world setting is required. We present the results of a national study of patients with extracranial oligometastases undergoing SABR, representing the largest dataset, to our knowledge, on outcomes in this population so far. METHODS: In 2015, National Health Service (NHS) England launched a Commissioning through Evaluation scheme that funded a prospective, registry-based, single-arm, observational, evaluation study of patients with solid cancer and extracranial oligometastases treated with SABR. Prescribed doses ranged from 24-60 Gy administered in three to eight fractions. The study was done at 17 NHS radiotherapy centres in England. Patients were eligible for the scheme if aged 18 years or older with confirmed primary carcinoma (excluding haematological malignancies), one to three extracranial metastatic lesions, a disease-free interval from primary tumour development to metastases of longer than 6 months (with the exception of synchronous colorectal liver metastases), a WHO performance status of 2 or lower, and a life expectancy of at least 6 months. The primary outcome was overall survival at 1 year and 2 years from the start of SABR treatment. The study is now completed. FINDINGS: Between June 15, 2015, and Jan 30, 2019, 1422 patients were recruited from 17 hospitals in England. The median age of the patients was 69 years (IQR 62-76), and the most common primary tumour was prostate cancer (406 [28·6%] patients). Median follow-up was 13 months (IQR 6-23). Overall survival was 92·3% (95% CI 90·5-93·9) at 1 year and 79·2% (76·0-82·1) at 2 years. The most common grade 3 adverse event was fatigue (28 [2·0%] of 1422 patients) and the most common serious (grade 4) event was increased liver enzymes (nine [0·6%]). Notreatment-related deaths were reported. INTERPRETATION: In patients with extracranial oligometastatic cancer, use of SABR was associated with high overall survival and low toxicity. 'The study findings complement existing evidence from a randomised, phase 2 trial, and represent high-level, real-world evidence supporting the use of SABR in this patient cohort, with a phase 3 randomised, controlled trial to confirm these findings underway. Based on the selection criteria in this study, SABR was commissioned by NHS England in March, 2020, as a treatment option for patients with oligometastatic disease. FUNDING: NHS England Commissioning through Evaluation scheme

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status