Bringing the OpenMI to LIFE Progress Report No. 4 - 31st March 2008 – 30th September 2008

The Water Framework Directive demands an integrated approach to water management. This requires the ability to predict how catchment processes will behave and interact in response to the activities of water managers and others. In most contexts, it is not feasible to build a single predictive model that adequately represents all the processes; therefore a means of linking models of individual processes is required. This is met by the FP5 HarmonIT project’s Open Modelling Interface and Environment (the OpenMI). The purpose of this project is to transform the OpenMI from a research output to a sustainable operational Standard. It will build the capacity to use the OpenMI and will demonstrate it under operational conditions. It will also develop, test and demonstrate the future support organisation for the OpenMI. Finally, information about the OpenMI will be disseminated to users

Pilot trial and process evaluation of a multilevel smoking prevention intervention in further education settings

Background: Preventing smoking uptake among young people is a public health priority. Further education (FE) settings provide access to the majority of 16- to 18-year-olds, but few evaluations of smoking prevention interventions have been reported in this context to date. Objectives: To evaluate the feasibility and acceptability of implementing and trialling a new multilevel smoking prevention intervention in FE settings. Design: Pilot cluster randomised controlled trial and process evaluation. Setting: Six UK FE institutions. Participants: FE students aged 16–18 years. Intervention: ‘The Filter FE’ intervention. Staff working on Action on Smoking and Health Wales’ ‘The Filter’ youth project applied existing staff training, social media and youth work resources in three intervention settings, compared with three control sites with usual practice. The intervention aimed to prevent smoking uptake by restricting the sale of tobacco to under-18s in local shops, implementing tobacco-free campus policies, training FE staff to deliver smoke-free messages, publicising The Filter youth project’s online advice and support services, and providing educational youth work activities. Main outcome measures: (1) The primary outcome assessed was the feasibility and acceptability of delivering and trialling the intervention. (2) Qualitative process data were analysed to explore student, staff and intervention team experiences of implementing and trialling the intervention. (3) Primary, secondary and intermediate (process) outcomes and economic evaluation methods were piloted. Data sources: New students at participating FE settings were surveyed in September 2014 and followed up in September 2015. Qualitative process data were collected via interviews with FE college managers (n = 5) and the intervention team (n = 6); focus groups with students (n = 11) and staff (n = 5); and observations of intervention settings. Other data sources were semistructured observations of intervention delivery, intervention team records, ‘mystery shopper’ audits of local shops and college policy documents. Results: The intervention was not delivered as planned at any of the three intervention settings, with no implementation of some community- and college-level components, and low fidelity of the social media component across sites. Staff training reached 28 staff and youth work activities were attended by 190 students across the three sites (< 10% of all eligible staff and students), with low levels of acceptability reported. Implementation was limited by various factors, such as uncertainty about the value of smoking prevention activities in FE colleges, intervention management weaknesses and high turnover of intervention staff. It was feasible to recruit, randomise and retain FE settings. Prevalence of weekly smoking at baseline was 20.6% and was 17.2% at follow-up, with low levels of missing data for all pilot outcomes. Limitations: Only 17% of eligible students participated in baseline and follow-up surveys; the representativeness of student and staff focus groups is uncertain. Conclusions: In this study, FE settings were not a supportive environment for smoking prevention activities because of their non-interventionist institutional cultures promoting personal responsibility. Weaknesses in intervention management and staff turnover also limited implementation. Managers accept randomisation but methodological work is required to improve student recruitment and retention rates if trials are to be conducted in FE settings. Trial registration: Current Controlled Trials ISRCTN19563136. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 5, No. 8. See the NIHR Journals Library website for further project information. It was also funded by the Big Lottery Fund

The Lantern, 2019-2020

Cochlea, Greek for Snail • That Light in the Sky • Overview Effect • The Running Man • Sunset • Rabbits • What Happened While You Were Drunk Last Saturday Night • 21st Century Frankenstein • Passing • I Saw the Veil • Star Crossed • Subtle Hints • Hungry • Basement High • The Night Who Lost Its Stars • Remnants • Nostalgia • I Want to Go to Bed • Wooden Car Blues • Silver Honey • The Breakup • Here\u27s to Losing You • Marfa • Cold Wind Blows • Last Week • 6/12/2019 • These Feather Earrings • Every Piece of White Trash Comes from Somewhere • Color Motion Blur • Song of the Kauai O\u27o • You/Me/Him • Girl in Three Parts • With Anxiety • Foreigner • Eating Your Own Field • Mary Cassatt Sits for a Self Portrait • Thanatourism • Lost in Transportation • Chicken Pot Pie Picture Show • Curses, Foiled Again • From Amelia Goldstein\u27s Movement in Your Words 2019 • At the Altar • More Than Words • Show Me Your Eyes • Ears • The Deflowering • Space • The Tea Bags • Make No Mistake • What Does He Do With the Body?: Four Possibilities • The Story of How I Died, or What the Witches Gave Me • Fortune-Teller • No Thanks • Winter Words • Fluorescent Adolescent • Etiquettical Triptych • Curls and Flower Petals • Being or Falling • Fond Memories • You • All to My City • The Shoreline • Tranquility • Eggs • Burnt • Anthony • Targets • Looking Up • Nebula • Eastern State • Beachhttps://digitalcommons.ursinus.edu/lantern/1188/thumbnail.jp

Spotlight on Differentially Expressed Genes in Urinary Bladder Cancer

INTRODUCTION: We previously identified common differentially expressed (DE) genes in bladder cancer (BC). In the present study we analyzed in depth, the expression of several groups of these DE genes. MATERIALS AND METHODS: Samples from 30 human BCs and their adjacent normal tissues were analyzed by whole genome cDNA microarrays, qRT-PCR and Western blotting. Our attention was focused on cell-cycle control and DNA damage repair genes, genes related to apoptosis, signal transduction, angiogenesis, as well as cellular proliferation, invasion and metastasis. Four publicly available GEO Datasets were further analyzed, and the expression data of the genes of interest (GOIs) were compared to those of the present study. The relationship among the GOI was also investigated. GO and KEGG molecular pathway analysis was performed to identify possible enrichment of genes with specific biological themes. RESULTS: Unsupervised cluster analysis of DNA microarray data revealed a clear distinction in BC vs. control samples and low vs. high grade tumors. Genes with at least 2-fold differential expression in BC vs. controls, as well as in non-muscle invasive vs. muscle invasive tumors and in low vs. high grade tumors, were identified and ranked. Specific attention was paid to the changes in osteopontin (OPN, SPP1) expression, due to its multiple biological functions. Similarly, genes exhibiting equal or low expression in BC vs. the controls were scored. Significant pair-wise correlations in gene expression were scored. GO analysis revealed the multi-facet character of the GOIs, since they participate in a variety of mechanisms, including cell proliferation, cell death, metabolism, cell shape, and cytoskeletal re-organization. KEGG analysis revealed that the most significant pathway was that of Bladder Cancer (p = 1.5×10(-31)). CONCLUSIONS: The present work adds to the current knowledge on molecular signature identification of BC. Such works should progress in order to gain more insight into disease molecular mechanisms

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

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