Reactions to messages about smoking, vaping and COVID-19: Two national experiments

Introduction The pace and scale of the COVID-19 pandemic, coupled with ongoing efforts by health agencies to communicate harms, have created a pressing need for data to inform messaging about smoking, vaping, and COVID-19. We examined reactions to COVID-19 and traditional health harms messages discouraging smoking and vaping. Methods Participants were a national convenience sample of 810 US adults recruited online in May 2020. All participated in a smoking message experiment and a vaping message experiment, presented in a random order. In each experiment, participants viewed one message formatted as a Twitter post. The experiments adopted a 3 (traditional health harms of smoking or vaping: Three harms, one harm, absent) × 2 (COVID-19 harms: one harm, absent) between-subjects design. Outcomes included perceived message effectiveness (primary) and constructs from the Tobacco Warnings Model (secondary: Attention, negative affect, cognitive elaboration, social interactions). Results Smoking messages with traditional or COVID-19 harms elicited higher perceived effectiveness for discouraging smoking than control messages without these harms (all p <0.001). However, including both traditional and COVID-19 harms in smoking messages had no benefit beyond including either alone. Smoking messages affected Tobacco Warnings Model constructs and did not elicit more reactance than control messages. Smoking messages also elicited higher perceived effectiveness for discouraging vaping. Including traditional harms in messages about vaping elicited higher perceived effectiveness for discouraging vaping (p <0.05), but including COVID-19 harms did not. Conclusions Messages linking smoking with COVID-19 may hold promise for discouraging smoking and may have the added benefit of also discouraging vaping

Detection of the blazar S4 0954+65 at very-high-energy with the MAGIC telescopes during an exceptionally high optical state

The very high energy (VHE ¿ 100 GeV) -ray MAGIC observations of the blazar S4 0954+65, were triggered by an exceptionally high flux state of emission in the optical. This blazar has a disputed redshift of z = 0.368 or z ¿ 0.45 and an uncertain classification among blazar subclasses. The exceptional source state described here makes for an excellent opportunity to understand physical processes in the jet of S4 0954+65 and thus contribute to its classification. Methods. We investigated the multiwavelength (MWL) light curve and spectral energy distribution (SED) of the S4 0954+65 blazar during an enhanced state in February 2015 and have put it in context with possible emission scenarios. We collected photometric data in radio, optical, X-ray, and ¿-ray. We studied both the optical polarization and the inner parsec-scale jet behavior with 43 GHz data. Results. Observations with the MAGIC telescopes led to the first detection of S4 0954+65 at VHE. Simultaneous data with Fermi-LAT at high energy ¿-ray(HE, 100 MeV < E < 100 GeV) also show a period of increased activity. Imaging at 43 GHz reveals the emergence of a new feature in the radio jet in coincidence with the VHE flare. Simultaneous monitoring of the optical polarization angle reveals a rotation of approximately 100. Conclusions. The high emission state during the flare allows us to compile the simultaneous broadband SED and to characterize it in the scope of blazar jet emission models. The broadband spectrum can be modeled with an emission mechanism commonly invoked for flat spectrum radio quasars (FSRQs), that is, inverse Compton scattering on an external soft photon field from the dust torus, also known as external Compton. The light curve and SED phenomenology is consistent with an interpretation of a blob propagating through a helical structured magnetic field and eventually crossing a standing shock in the jet, a scenario typically applied to FSRQs and low-frequency peaked BL Lac objects (LBL). © ESO 2018.The financial support of the German BMBF and MPG, the Italian INFN and INAF, the Swiss National Fund SNF, the ERDF under the Spanish MINECO (FPA2015-69818-P, FPA2012-36668, FPA2015-68378-P, FPA2015-69210-C6-2-R, FPA2015-69210-C6-4-R, FPA2015-69210-C6-6-R, AYA2015-71042-P, AYA2016-76012-C3-1-P, ESP2015-71662-C2-2-P, CSD2009-00064), and the Japanese JSPS and MEXT is gratefully acknowledged. This work was also supported by the Spanish Centro de Excelencia “Severo Ochoa” SEV-2012-0234 and SEV-2015-0548, and Unidad de Excelencia “María de Maeztu” MDM-2014-0369, by the Croatian Science Foundation (HrZZ) Project IP-2016-06-9782 and the University of Rijeka Project 13.12.1.3.02, by the DFG Collaborative Research Centers SFB823/C4 and SFB876/C3, the Polish National Research Centre grant UMO-2016/22/M/ST9/00382 and by the Brazilian MCTIC, CNPq, and FAPERJ. IA acknowledges support by a Ramón y Cajal grant of the Ministerio de Economía, Industria y Competitividad (MINECO) of Spain. The research at the IAA–CSIC was supported in part by the MINECO through grants AYA2016–80889–P, AYA2013–40825–P, and AYA2010–14844, and by the regional government of Andalucía through grant P09–FQM–4784.Peer Reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells

AbstractDystrophic skeletal muscle cells from Duchenne muscular dystrophy (DMD) patients and mdx mice exhibit elevated cytosolic Ca2+ concentrations ([Ca2+]c). Pretreatment of mdx myotubes for 6–12 days with creatine (20 mM) decreased the elevation in [Ca2+]c induced by either high extracellular Ca2+ concentrations or hypo-osmotic stress to control levels. 45Ca2+ influx measurements suggest that creatine lowered [Ca2+]c by stimulating sarcoplasmic reticulum Ca2+-ATPase. Creatine pretreatment increased levels of phosphocreatine but not ATP. Furthermore, myotube formation and survival were significantly enhanced by creatine pretreatment. Therefore, creatine supplementation may be useful for treatment of DMD

Erythropoietin stimulates proliferation and interferes with differentiation of myoblasts.

Erythropoietin (Epo) is required for the production of mature red blood cells. The requirement for Epo and its receptor (EpoR) for normal heart development and the response of vascular endothelium and cells of neural origin to Epo provide evidence that the function of Epo as a growth factor or cytokine to protect cells from apoptosis extends beyond the hematopoietic lineage. We now report that the EpoR is expressed on myoblasts and can mediate a biological response of these cells to treatment with Epo. Primary murine satellite cells and myoblast C2C12 cells, both of which express endogenous EpoR, exhibit a proliferative response to Epo and a marked decrease in terminal differentiation to form myotubes. We also observed that Epo stimulation activates Jak2/Stat5 signal transduction and increases cytoplasmic calcium, which is dependent on tyrosine phosphorylation. In erythroid progenitor cells, Epo stimulates induction of transcription factor GATA-1 and EpoR; in C2C12 cells, GATA-3 and EpoR expression are induced. The decrease in differentiation of C2C12 cells is concomitant with an increase in Myf-5 and MyoD expression and inhibition of myogenin induction during differentiation, altering the pattern of expression of the MyoD family of transcription factors during muscle differentiation. These data suggest that, rather than acting in an instructive or specific mode for differentiation, Epo can stimulate proliferation of myoblasts to expand the progenitor population during differentiation and may have a potential role in muscle development or repair

The role of soils in regulation and provision of blue and green water

The United Nations Sustainable Development Goal 6 aims for clean water and sanitation for all by 2030, through eight subgoals dealing with four themes: (i) water quantity and availability, (ii) water quality, (iii) finding sustainable solutions and (iv) policy and governance. In this opinion paper, we assess how soils and associated land and water management can help achieve this goal, considering soils at two scales: local soil health and healthy landscapes. The merging of these two viewpoints shows the interlinked importance of the two scales. Soil health reflects the capacity of a soil to provide ecosystem services at a specific location, taking into account local climate and soil conditions. Soil is also an important component of a healthy and sustainable landscape, and they are connected by the water that flows through the soil and the transported sediments. Soils are linked to water in two ways: through plant-available water in the soil (green water) and through water in surface bodies or available as groundwater (blue water). In addition, water connects the soil scale and the landscape scale by flowing through both. Nature-based solutions at both soil health and landscape-scale can help achieve sustainable future development but need to be embedded in good governance, social acceptance and economic viability