Introduction Airborne fine particulate matter (diameter <2.5μm; PM2.5) is a leading risk factor for ill health and premature death. Road vehicle technology is decreasing exhaust-derived PM emissions but poorly characterised, unregulated non-exhaust PM persists. This study aimed to characterise the toxicology of brakewear PM2.5 (BWPM) from 4 brakepad types, and roadwear PM, compared to diesel exhaust PM2.5 (DEP).
Methods An alveolar type-II epithelial cell line (ATIIER:KRASv12) was exposed to 3.9-31.6µg/cm2 PM2.5 generated from 4 brake pad types (low-metallic/semi-metallic/non-asbestos organic [NAO]/ceramic), roadwear, or DEP for 2-24h. PM composition was determined by ICP-MS, cytotoxicity by LDH and MTT assays, cytokine release by ELISA, gene expression by RT-qPCR and RNA-Seq, and protein expression by western blot.
Results NAO and ceramic BWPM, enriched in copper and zirconium, exerted greatest increases in cytotoxicity, cytokine release (IL-6: NAO 26-fold, ceramic 20-fold; p<0.05), and oxidative stress-related (HMOX1 – NAO 28-fold, ceramic 26-fold, p<0.001) and metal homeostasis genes (MT1G: NAO 197-fold, ceramic 183-fold; p<0.001), consistently greater than roadwear PM or DEP. Amelioration by copper-chelating tetraethylenepentamine implicated BWPM copper. RNA-Seq showed NAO and ceramic BWPM induced most differentially expressed genes vs. control, related to inflammatory, oxidative stress, heat-shock, and hypoxia responses. Effects on hypoxia signalling were confirmed through HIF1α western blot and HIF-signalling reporter assay.
Conclusions NAO and ceramic BWPM were the most potent across multiple endpoints. Future work will study the relevance of HIF-related responses, which have been implicated in fibrotic lung disease. Understanding source-dependent toxicity may facilitate manufacturing- and healthcare-related mitigation of PM toxicity.
Background As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention. Methods In this prospective, observational study, we did modelling using longitudinal, self-reported data from users of the COVID Symptom Study app in England between March 24, and Sept 29, 2020. Beginning on April 28, in England, the Department of Health and Social Care allocated RT-PCR tests for COVID-19 to app users who logged themselves as healthy at least once in 9 days and then reported any symptom. We calculated incidence of COVID-19 using the invited swab (RT-PCR) tests reported in the app, and we estimated prevalence using a symptom-based method (using logistic regression) and a method based on both symptoms and swab test results. We used incidence rates to estimate the effective reproduction number, R(t), modelling the system as a Poisson process and using Markov Chain Monte-Carlo. We used three datasets to validate our models: the Office for National Statistics (ONS) Community Infection Survey, the Real-time Assessment of Community Transmission (REACT-1) study, and UK Government testing data. We used geographically granular estimates to highlight regions with rapidly increasing case numbers, or hotspots. Findings From March 24 to Sept 29, 2020, a total of 2 873 726 users living in England signed up to use the app, of whom 2 842 732 (98·9%) provided valid age information and daily assessments. These users provided a total of 120 192 306 daily reports of their symptoms, and recorded the results of 169 682 invited swab tests. On a national level, our estimates of incidence and prevalence showed a similar sensitivity to changes to those reported in the ONS and REACT-1 studies. On Sept 28, 2020, we estimated an incidence of 15 841 (95% CI 14 023–17 885) daily cases, a prevalence of 0·53% (0·45–0·60), and R(t) of 1·17 (1·15–1·19) in England. On a geographically granular level, on Sept 28, 2020, we detected 15 (75%) of the 20 regions with highest incidence according to government test data. Interpretation Our method could help to detect rapid case increases in regions where government testing provision is lower. Self-reported data from mobile applications can provide an agile resource to inform policy makers during a quickly moving pandemic, serving as a complementary resource to more traditional instruments for disease surveillance.
Source at https://doi.org/10.2903/j.efsa.2018.5132 . ; The European Commission asked EFSA for a scientific opinion on chronic wasting disease in two parts. Part one, on surveillance, animal health risk‐based measures and public health risks, was published in January 2017. This opinion (part two) addresses the remaining Terms of Reference, namely, 'are the conclusions and recommendations in the EFSA opinion of June 2004 on diagnostic methods for chronic wasting disease still valid? If not, an update should be provided', and 'update the conclusions of the 2010 EFSA opinion on the results of the European Union survey on chronic wasting disease in cervids, as regards its occurrence in the cervid population in the European Union'. Data on the performance of authorised rapid tests in North America are not comprehensive, and are more limited than those available for the tests approved for statutory transmissible spongiform encephalopathies surveillance applications in cattle and sheep. There are no data directly comparing available rapid test performances in cervids. The experience in Norway shows that the Bio‐Rad TeSeE™ SAP test, immunohistochemistry and western blotting have detected reindeer, moose and red deer cases. It was shown that testing both brainstem and lymphoid tissue from each animal increases the surveillance sensitivity. Shortcomings in the previous EU survey limited the reliability of inferences that could be made about the potential disease occurrence in Europe. Subsequently, testing activity in Europe was low, until the detection of the disease in Norway, triggering substantial testing efforts in that country. Available data neither support nor refute the conclusion that chronic wasting disease does not occur widely in the EU and do not preclude the possibility that the disease was present in Europe before the survey was conducted. It appears plausible that chronic wasting disease could have become established in Norway more than a decade ago.
[Context] The Transiting Exoplanet Survey Satellite (TESS) is observing bright known planet-host stars across almost the entire sky. These stars have been subject to extensive ground-based observations, providing a large number of radial velocity measurements. ; AHMJT and MRS have benefited from funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no 803193/BEBOP). Funding for the Stellar Astrophysics Centre is funded by the Danish National Research Foundation (Grant agreement no.: DNRF106). ZÇO, MY, and SÖ acknowledge the Scientific and Technological Research Council of Turkey (TÜB˙TAK:118F352). AS acknowledges support from grants ESP2017-82674-R (MICINN) and 2017-SGR-1131 (Generalitat Catalunya). TLC acknowledges support from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 792848 (PULSATION). This work was supported by FCT/MCTES through national funds (UID/FIS/04434/2019). MD is supported by FCT/MCTES through national funds (PIDDAC) by this grant UID/FIS/04434/2019. MD and MV are supported by FEDER - Fundo Europeu de Desenvolvimento Regional through COMPETE2020 - Programa Operacional Competitividade e Internacionalização by these grants: UID/FIS/04434/2019; PTDC/FIS-AST/30389/2017 & POCI-01-0145-FEDER-030389 & POCI-01-0145-FEDER03038. MD is supported in the form of a work contract funded by national funds through Fundação para a Ciência e Tecnologia (FCT). SM acknowledges support by the Spanish Ministry with the Ramon y Cajal fellowship number RYC-2015-17697. BM and RAG acknowledge the support of the CNES/PLATO grant. DLB and LC acknowledge support from the TESS GI Program under awards 80NSSC18K1585 and 80NSSC19K0385. LGC thanks the support from grant FPI-SO from the Spanish Ministry of Economy and Competitiveness (MINECO) (research project SEV-2015-0548-17-2 and predoctoral contract BES-2017-082610). Funding for the TESS mission is provided by the NASA Explorer Program. Based in part on data acquired at the Anglo-Australian Telescope. We acknowledge the traditional owners of the land on which the AAT stands, the Gamilaraay people, and pay our respects to elders past and present. The data presented herein were in part obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation. The authors wish to recognize and acknowledge the very significant cultural role and reverence that the summit of Maunakea has always had within the indigenous Hawaiian community.
Hydropower -- Lesotho Highlands Water Project: design and layout of underground works for 'Muela Hydropower Project -- Design and construction of the cooling water intake tunnel system for Point Aconi generating station, Nova Scotia -- Comparison of two classification systems as applied to the Alpe Devero tunnel, Italy -- Metro/Rail -- Planning and design of tunnels for the Jubilee Line extension, London -- New St Clair River tunnel, Canada-USA -- Application of NATM to design of underground stations in London Clay -- Water/Waste -- Underground works on Third Nairobi Water Supply Project -- Design and construction of caverns for an underground sewage treatment plant, Hong Kong -- The Snake: a rock tunnel for storing combined sewage water, Stockholm -- Tunnelling on the Penzance and St. Ives sewerage scheme, Cornwall, England -- Tunnel-boring Machines -- Two tunnel-boring machines for Lesotho: a design and case history -- Open TBM tunnelling in complex geology for railroad in Sweden -- Use of sedimentary rock impact indices in evaluation of tunnel-boring machine performance -- Development and performance of tunnel-boring machines on Phase II of the London Water Ring Main -- Environmental Issues -- Environmental planning for the Massachusetts Water Resources Authority's MetroWest water supply tunnel -- Palais Bernheimer in Munich: tunnelling for parking space under a historic building -- Limiting the damage to historic buildings due to tunnelling: experience at the Mansion House, London -- Compensation grouting to limit settlements during tunnelling at Waterloo Station, London -- Ground movement model validation at the Heathrow Express trial tunnel -- Case Histories -- Gjøvik Olympic Mountain Hall, Norway -- Construction of new escalator shaft and passageways at London Underground's Waterloo Station -- Water in TBM drives, Delivery Tunnel South, Lesotho Highlands Water Project -- Tunnel-boring Machines -- CEN safety standards for tunnelling machines and air locks -- Tunnels below waste disposal tips -- Machine tunnelling in the northwest of England -- EPB-shield tunnelling for the Taipei Metro, contract 201A -- TBM drive management by use of computerized systems -- Research -- Long-term measurements of loads on tunnel linings in overconsolidated clay -- Non-destructive investigation of tunnels -- Case Histories -- Design, construction and performance of a 700-m 'cover and cut' tunnel in soft clay, Norway -- Shotcrete in the construction of Pen-Y-Clip tunnel, North Wales -- Face support for a large Mix-Shield in heterogeneous ground conditions -- Design -- Tunnel ring design, development, testing and manufacture for the London Water Ring Main -- Medway tunnel detailed design -- Developments in precast concrete tunnel linings in the United Kingdom -- Case Histories -- Channel tunnel: French undersea crossover design and construction -- Design and construction of Metsovon road tunnel, Greece -- Construction of the 'Passante Ferroviario' link in Milan, Italy, lots 3P, 5P and 6P: excavation by large earth pressure balanced shield with chemical foam injection -- Pen-Y-Clip road tunnel, North Wales: achieving a dry lining through a pervious rock formation -- Hydropower -- Tunnel design in the design and construct context—the Pergau experience, Malaysia -- Serra da Mesa project, Brazil: excavation of shafts and penstocks -- Tunnel Machinery -- Rock cutting with roadheaders -- Increased productivity in construction of civil and mining tunnels through the use of high-capacity tunnel-boring machines and continuous belt conveyor muck haulage.
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WOS: 000469975500005 ; We present the discovery of HD 221416 b, the first transiting planet identified by the Transiting Exoplanet Survey Satellite (TESS) for which asteroseismology of the host star is possible. HD 221416 b (HIP 116158, TOI-197) is a bright (V = 8.2 mag), spectroscopically classified subgiant that oscillates with an average frequency of about 430 mu Hz and displays a clear signature of mixed modes. The oscillation amplitude confirms that the redder TESS bandpass compared to Kepler has a small effect on the oscillations, supporting the expected yield of thousands of solar-like oscillators with TESS 2 minute cadence observations. Asteroseismic modeling yields a robust determination of the host star radius (R-* = 2.943 +/- 0.064 R-circle dot), mass (M-* = 1.212 +/- 0.074 M-circle dot), and age (4.9 +/- 1.1 Gyr), and demonstrates that it has just started ascending the red-giant branch. Combining asteroseismology with transit modeling and radial-velocity observations, we show that the planet is a "hot Saturn" (R-p = 9.17 +/- 0.33 R-circle plus) with an orbital period of similar to 14.3 days, irradiance of F = 343 +/- 24 F-circle plus, and moderate mass (M-p = 60.5 +/- 5.7 M-circle plus) and density (rho(p) = 0.431 +/- 0.062 g cm(-3)). The properties of HD 221416 b show that the host-star metallicity-planet mass correlation found in sub-Saturns (4-8 R-circle plus) does not extend to larger radii, indicating that planets in the transition between sub-Saturns and Jupiters follow a relatively narrow range of densities. With a density measured to similar to 15%, HD 221416 b is one of the best characterized Saturn-size planets to date, augmenting the small number of known transiting planets around evolved stars and demonstrating the power of TESS to characterize exoplanets and their host stars using asteroseismology. ; National Aeronautics and Space Administration through the TESS Guest Investigator Program [80NSSC18K1585]; National Science FoundationNational Science Foundation (NSF) [AST-1717000]; Science and Technology Facilities CouncilScience & Technology Facilities Council (STFC); UK Space Agency; European Social Fund via the Lithuanian Science Council [09.3.3-LMT-K-712-01-0103]; Danish National Research FoundationDanmarks Grundforskningsfond [DNRF106]; FONDECYT projectComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)CONICYT FONDECYT [1171208]; CONICYT projectComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) [BASAL AFB-170002]; Ministry for the Economy, Development, and Tourism's Programa Iniciativa Cientifica Milenio [IC 120009]; FONDECYTComision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)CONICYT FONDECYT [3180246]; Millennium Institute of Astrophysics (MAS); MINECOSpanish Ministry of Economy & Competitiveness [ESP2017-82674-R]; AGAURAgencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGUAR) [SGR2017-1131]; PLATO grant from the CNES; European Research Council under the European Community's Seventh Framework Programme (FP72007-2013) ERC grant [338251]; European Research Council through the SPIRE grant [647383]; FCT (Portugal); FEDER through COMPETE2020 [UID/FIS/04434/2013, POCI-01-0145-FEDER-007672, PTDC/FIS-AST/30389/2017, POCI-01-0145-FEDER-030389]; European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grantEuropean Union (EU) [792848]; European UnionEuropean Union (EU) [664931]; Independent Research Fund Denmark [7027-00096B]; Australian Research CouncilAustralian Research Council; NASANational Aeronautics & Space Administration (NASA) [NNX16AI09G, AS5-26555]; NSFNational Science Foundation (NSF) [AST-1514676]; Australian Research CouncilAustralian Research Council [DP150100250]; ERCEuropean Research Council (ERC) [772293]; Ramon y Cajal fellowshipMinistry of Education and Science, Spain [RYC-2015-17697]; Carlsberg FoundationCarlsberg Foundation [CF17-0760]; HBCSE-NIUS programme; NASA through Hubble Fellowship grants - Space Telescope Science Institute [HST-HF2-51399.001, HST-HF2-51424.001]; Premiale 2015 MITiC; NKFIH [K-115709]; Lendulet Program of the Hungarian Academy of Sciences [LP2018-7/2018]; NASA's Science Mission directorate ; The authors wish to recognize and acknowledge the very significant cultural role and reverence that the summit of Maunakea has always had within the indigenous Hawai'ian community. We are most fortunate to have the opportunity to conduct observations from this mountain. We thank Andrei Tokovinin for helpful information on the Speckle observations obtained with SOAR. D.H. acknowledges support by the National Aeronautics and Space Administration through the TESS Guest Investigator Program (80NSSC18K1585) and by the National Science Foundation (AST-1717000). A.C. acknowledges support by the National Science Foundation under the Graduate Research Fellowship Program. W.J.C., W.H.B., A.M., O.J.H., and G.R.D. acknowledge support from the Science and Technology Facilities Council and UK Space Agency. H.K. and F.G. acknowledge support from the European Social Fund via the Lithuanian Science Council grant No. 09.3.3-LMT-K-712-01-0103. Funding for the Stellar Astrophysics Centre is provided by The Danish National Research Foundation (grant DNRF106). A.J. acknowledges support from FONDECYT project 1171208, CONICYT project BASAL AFB-170002, and by the Ministry for the Economy, Development, and Tourism's Programa Iniciativa Cientifica Milenio through grant IC 120009, awarded to the Millennium Institute of Astrophysics (MAS). R.B. acknowledges support from FONDECYT Post-doctoral Fellowship Project 3180246, and from the Millennium Institute of Astrophysics (MAS). A.M.S. is supported by grants ESP2017-82674-R (MINECO) and SGR2017-1131 (AGAUR). R.A.G. and L.B. acknowledge the support of the PLATO grant from the CNES. The research leading to the presented results has received funding from the European Research Council under the European Community's Seventh Framework Programme (FP72007-2013) ERC grant agreement No. 338251 (StellarAges). S.M. acknowledges support from the European Research Council through the SPIRE grant 647383. This work was also supported by FCT (Portugal) through national funds and by FEDER through COMPETE2020 by these grants: UID/FIS/04434/2013 and POCI-01-0145-FEDER-007672, PTDC/FIS-AST/30389/2017, and POCI-01-0145-FEDER-030389. T.L.C. acknowledges support from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 792848 (PULSATION). E.C. is funded by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 664931. V.S.A. acknowledges support from the Independent Research Fund Denmark (Research grant 7027-00096B). D.S. acknowledges support from the Australian Research Council. S.B. acknowledges NASA grant NNX16AI09G and NSF grant AST-1514676. T.R.W. acknowledges support from the Australian Research Council through grant DP150100250. A.M. acknowledges support from the ERC Consolidator Grant funding scheme (project ASTEROCHRONOMETRY, G.A. n. 772293). S.M. acknowledges support from the Ramon y Cajal fellowship number RYC-2015-17697. M.S.L. is supported by the Carlsberg Foundation (grant agreement No. CF17-0760). A.M. and P.R. acknowledge support from the HBCSE-NIUS programme. J.K.T. and J.T. acknowledge that support for this work was provided by NASA through Hubble Fellowship grants HST-HF2-51399.001 and HST-HF2-51424.001 awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract AS5-26555. T.S.R. acknowledges financial support from Premiale 2015 MITiC (PI B. Garilli).; This project has been supported by the NKFIH K-115709 grant and the Lendulet Program of the Hungarian Academy of Sciences, project No. LP2018-7/2018.; Based on observations made with the Hertzsprung SONG telescope operated on the Spanish Observatorio del Teide on the island of Tenerife by the Aarhus and Copenhagen Universities and by the Instituto de Astrofisica de Canarias. Funding for the TESS mission is provided by NASA's Science Mission directorate. We acknowledge the use of public TESS Alert data from pipelines at the TESS Science Office and at the TESS Science Processing Operations Center. This research has made use of the Exoplanet Follow-up Observation Program website, which is operated by the California Institute of Technology, under contract with the National Aeronautics and Space Administration under the Exoplanet Exploration Program. This paper includes data collected by the TESS mission, which are publicly available from the Mikulski Archive for Space Telescopes (MAST).
Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods: This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index 60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926. Findings: Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16-30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77-0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50-0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80-0·88; p<0·001), and full lockdowns (0·57, 0·54-0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation: Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services.