Publications by authors named "Karen Hughes"

134 Publications

Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2.

Clin Transl Immunology 2021 5;10(4):e1269. Epub 2021 Apr 5.

School of Chemistry and Molecular Biosciences The University of Queensland St Lucia QLD Australia.

Objectives: Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia).

Methods: A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat.

Results: In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4 and cytotoxic CD8 T cells . In the Syrian hamster challenge model ( = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level.

Conclusion: The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2-8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.
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http://dx.doi.org/10.1002/cti2.1269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021130PMC
April 2021

STOP-sexual violence: evaluation of a community-based nightlife worker awareness raising bystander training programme.

Eur J Public Health 2021 Jan 9. Epub 2021 Jan 9.

IREFREA-ES, Palma de Mallorca, Spain.

Background: Preventing sexual violence in nightlife environments is a pervasive issue across many countries. This study explored the associated impact of a nightlife worker sexual violence awareness raising/bystander training programme (STOP-SV) on trainees' sexual violence myth acceptance and readiness and confidence to intervene.

Methods: : Pre- and post-test (n = 118), and 3-month follow-up (n = 38) trainee surveys were implemented across three countries (Czech Republic, Portugal and Spain). Paired-sample tests examined changes across time-periods in participants' myth acceptance (e.g. unwanted sexual advances are a normal part of a night out), and readiness and confidence to intervene. Multi-nominal regression was used to examine the relationship between the change in pre-to-post-training scores and trainee characteristics.

Results: Compared to pre-training, post-training participants were significantly (P < 0.01) less likely to agree with sexual violence myths, and more likely to be ready and confident to intervene. In bi-variate and multi-variate analyses, we found no significant associations between the change in pre-to-post-training scores and trainee characteristics. Analyses of the small follow-up sub-sample illustrated some positive changes at the post-training and follow-up time-periods (i.e. reduction in sexual violence myth acceptance).

Conclusion: This exploratory study suggests that the STOP-SV training programme was associated with a decrease in trainees' acceptance of sexual violence myths, and an increase in their readiness and confidence to intervene. Our findings support the case for further implementation and evaluation of awareness raising/bystander programmes for nightlife workers that aim to prevent and respond to sexual violence.
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http://dx.doi.org/10.1093/eurpub/ckaa245DOI Listing
January 2021

Uptake of core outcome sets by clinical trialists publishing in major medical journals: Protocol.

HRB Open Res 2020 25;3:53. Epub 2021 Jan 25.

MRC/NIHR Trials Methodology Research Partnership, Department of Biostatistics, University of Liverpool, Liverpool, UK.

Outcome heterogeneity, selective reporting, and choosing outcomes that do not reflect needs and priorities of stakeholders, limit the examination of health intervention effects, particularly in late phase trials. Core outcome sets (COS) are a proposed solution to these issues. A COS is an agreed-upon, standardised set of outcomes that should be measured and reported as a minimum in all trials in a specific area of health or healthcare. COS are intended to increase standardisation of outcome measurement and reporting to better enable comparisons between, and synthesis of findings of trials in a particular health area.  This study will examine late phase trials, published between October 2019 and March 2020 (inclusive), in the following five medical journals: , , , , and . Trials will be examined to determine if they refer to a COS, and whether they use a COS. Trialists for each identified trial will subsequently be contacted to complete an online survey examining trialists' awareness of, and decisions to search for and use a COS. This study will provide important information on uptake of COS by later phase trialists in major medical journals, and the views of these trialists on COS use in trials. These findings will inform approaches to increasing awareness and uptake of COS in future health trials.
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http://dx.doi.org/10.12688/hrbopenres.13109.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919602PMC
January 2021

A systematic review finds Core Outcome Set uptake varies widely across different areas of health.

J Clin Epidemiol 2021 Jan 26;129:114-123. Epub 2020 Sep 26.

MRC North West Hub for Trials Methodology Research, Department of Health Data Science, University of Liverpool, Block F Waterhouse Building, 1-5 Brownlow Street, Liverpool L69 3GL, United Kingdom.

Objective: The aim of our review was to bring together studies that had assessed the uptake of core outcome sets (COS) to explore the level of uptake across different COS and areas of health.

Study Design And Setting: We examined the citations of 337 COS reports to identify studies that had assessed the uptake of a particular COS in randomized controlled trials (RCTs) or systematic reviews (SRs).

Results: We identified 24 studies that had assessed uptake in RCTs and two studies that had assessed uptake in SRs. The studies covered a total of 17/337 (5%) COS. Uptake rates reported for RCTs varied from 0% of RCTs (gout) to 82% RCTs (rheumatoid arthritis) measuring the full COS. Studies that assessed uptake of individual core outcomes showed a wide variation in uptake between the outcomes. Suggested barriers to uptake included lack of validated measures, lack of patient and other key stakeholder involvement in COS development, and lack of awareness of the COS.

Conclusions: Few studies have been undertaken to assess the uptake of COS in RCTs and SRs. Further studies are needed to assess whether COS have been implemented across a wider range of disease categories and to explore the barriers and facilitators to COS uptake.
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http://dx.doi.org/10.1016/j.jclinepi.2020.09.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815247PMC
January 2021

Exploring the health and service utilisation of general practice patients with a history of adverse childhood experiences (ACEs): an observational study using electronic health records.

BMJ Open 2020 09 25;10(9):e036239. Epub 2020 Sep 25.

WHO Collaborating Centre on Investment for Health and Well-being, Public Health Wales, Wrexham, UK.

Objectives: To examine the relationships between adverse childhood experiences (ACEs), chronic health and health service utilisation among a sample of general practice patients.

Design: Cross-sectional observational study using anonymised data from electronic health records for 763 patients.

Setting: Four general practices in northwest England and North Wales.

Outcome Measures: Patient demographic data (age, gender); body mass index; self-reported smoking status; self-reported ACEs; diagnosis of chronic health conditions; current mental health problems; total number of service contacts and repeat medication use in the previous 6 months.

Results: A history of ACEs (experiencing abuse or neglect as a child, and/or growing up in a household characterised by violence, substance use, mental health problems or criminal behaviour) was strongly independently associated with current mental health problems, smoking and chronic obstructive pulmonary disease, showing a dose-response relationship with level of ACE exposure. Medication use and contact were significantly greater among patients with high ACE exposure (≥4 ACEs), compared with those with no ACEs. However, contrary to findings from population studies, health service utilisation was not significantly different for patients with increased ACE exposure (1-3 ACEs) and their ACE-free counterparts.

Conclusions: Findings highlight the contribution ACEs make to unequal distributions of risk to health and well-being and patterns of health service use in the UK.
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http://dx.doi.org/10.1136/bmjopen-2019-036239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520840PMC
September 2020

Assessing the relevance and uptake of core outcome sets (an agreed minimum collection of outcomes to measure in research studies) in Cochrane systematic reviews: a review.

BMJ Open 2020 09 6;10(9):e036562. Epub 2020 Sep 6.

Center for Evidence-based Healthcare, Medizinische Fakultät, Technische Universität Dresden, Dresden, Germany.

Objectives: A core outcome set (COS) is an agreed standardised minimum collection of outcomes that should be measured and reported in research in a specific area of health. Cochrane systematic reviews ('reviews') are rigorous reviews on health-related topics conducted under the auspices of Cochrane. This study examines the use of existing COS to inform the choice of outcomes in Cochrane systematic reviews ('reviews') and investigates the views of the coordinating editors of Cochrane Review Groups (CRGs) on this topic.

Methods: A cohort of 100 recently published or updated Cochrane reviews were assessed for reference to a COS being used to inform the choice of outcomes for the review. Existing COS, published 2 or more years before the review publication, were then identified to assess how often a reviewer could have used a relevant COS if it was available. We asked 52 CRG coordinating editors about their involvement in COS development, how outcomes are selected for reviews in their CRG and their views of the advantages and challenges surrounding the standardisation of outcomes within their CRG.

Results: In the cohort of reviews from 2019, 40% (40/100) of reviewers noted problems due to outcome inconsistency across the included studies. In 7% (7/100) of reviews, a COS was referenced in relation to the choice of outcomes for the review. Relevant existing COS could be considered for a review update in 35% of the others (33/93). Most editors who responded (31/36, 86%) thought that COS should definitely or possibly be used to inform the choice of outcomes in a review.

Conclusions: Systematic reviewers are continuing to note outcome heterogeneity but are starting to use COS to inform their reviews. There is potential for greater uptake of COS in Cochrane reviews.
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http://dx.doi.org/10.1136/bmjopen-2019-036562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476465PMC
September 2020

Assessing the relevance and uptake of core outcome sets (an agreed minimum collection of outcomes to measure in research studies) in Cochrane systematic reviews: a review.

BMJ Open 2020 09 6;10(9):e036562. Epub 2020 Sep 6.

Center for Evidence-based Healthcare, Medizinische Fakultät, Technische Universität Dresden, Dresden, Germany.

Objectives: A core outcome set (COS) is an agreed standardised minimum collection of outcomes that should be measured and reported in research in a specific area of health. Cochrane systematic reviews ('reviews') are rigorous reviews on health-related topics conducted under the auspices of Cochrane. This study examines the use of existing COS to inform the choice of outcomes in Cochrane systematic reviews ('reviews') and investigates the views of the coordinating editors of Cochrane Review Groups (CRGs) on this topic.

Methods: A cohort of 100 recently published or updated Cochrane reviews were assessed for reference to a COS being used to inform the choice of outcomes for the review. Existing COS, published 2 or more years before the review publication, were then identified to assess how often a reviewer could have used a relevant COS if it was available. We asked 52 CRG coordinating editors about their involvement in COS development, how outcomes are selected for reviews in their CRG and their views of the advantages and challenges surrounding the standardisation of outcomes within their CRG.

Results: In the cohort of reviews from 2019, 40% (40/100) of reviewers noted problems due to outcome inconsistency across the included studies. In 7% (7/100) of reviews, a COS was referenced in relation to the choice of outcomes for the review. Relevant existing COS could be considered for a review update in 35% of the others (33/93). Most editors who responded (31/36, 86%) thought that COS should definitely or possibly be used to inform the choice of outcomes in a review.

Conclusions: Systematic reviewers are continuing to note outcome heterogeneity but are starting to use COS to inform their reviews. There is potential for greater uptake of COS in Cochrane reviews.
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http://dx.doi.org/10.1136/bmjopen-2019-036562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476465PMC
September 2020

Health and financial burden of adverse childhood experiences in England and Wales: a combined primary data study of five surveys.

BMJ Open 2020 06 7;10(6):e036374. Epub 2020 Jun 7.

1World Health Organization Collaborating Centre on Investment for Health and Well-being, Policy and International Health, Public Health Wales, Wrexham, UK.

Objective: To estimate the health and financial burden of adverse childhood experiences (ACEs) in England and Wales.

Design: The study combined data from five randomly stratified cross-sectional ACE studies. Population attributable fractions (PAFs) were calculated for major health risks and causes of ill health and applied to disability adjusted life years (DALYs), with financial costs estimated using a modified human capital method.

Setting: Households in England and Wales.

Participants: 15 285 residents aged 18-69.

Outcome Measures: The outcome measures were PAFs for single (1 ACE) and multiple (2-3 and ≥4 ACEs) ACE exposure categories for four health risks (smoking, alcohol use, drug use, high body mass index) and nine causes of ill health (cancer, type 2 diabetes, heart disease, respiratory disease, stroke, violence, anxiety, depression, other mental illness); and annual estimated DALYs and financial costs attributable to ACEs.

Results: Cumulative relationships were found between ACEs and risks of all outcomes. For health risks, PAFs for ACEs were highest for drug use (Wales 58.8%, England 52.6%), although ACE-attributable smoking had the highest estimated costs (England and Wales, £7.8 billion). For causes of ill health, PAFs for ACEs were highest for violence (Wales 48.9%, England 43.4%) and mental illness (ranging from 29.1% for anxiety in England to 49.7% for other mental illness in Wales). The greatest ACE-attributable costs were for mental illness (anxiety, depression and other mental illness; England and Wales, £11.2 billion) and cancer (£7.9 billion). Across all outcomes, the total annual ACE-attributable cost was estimated at £42.8 billion. The majority of costs related to exposures to multiple rather than a single ACE (ranging from 71.9% for high body mass index to 98.3% for cancer).

Conclusions: ACEs impose a substantial societal burden in England and Wales. Policies and practices that prevent ACEs, build resilience and develop trauma-informed services are needed to reduce burden of disease and avoidable service use and financial costs across health and other sectors.
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http://dx.doi.org/10.1136/bmjopen-2019-036374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282338PMC
June 2020

Pyrophilous fungi detected after wildfires in the Great Smoky Mountains National Park expand known species ranges and biodiversity estimates.

Mycologia 2020 Jul-Aug;112(4):677-698. Epub 2020 Jun 4.

Department of Plant and Microbial Biology, University of California , Berkeley, California 94520-3102.

Following a late fall wildfire in 2016 in the Great Smoky Mountains National Park, pyrophilous fungi in burn zones were documented over a 2-y period with respect to burn severity and phenology. Nuc rDNA internal transcribed spacer (ITS1-5.8S-ITS2 = ITS) barcodes were obtained to confirm morphological evaluations. Forty-one taxa of Ascomycota and Basidiomycota were identified from burn sites and categorized as fruiting only in response to fire or fruiting enhanced by fire. Twenty-two species of Pezizales (Ascomycota) were among the earliest to form ascomata in severe burn zones, only one of which had previously been documented in the Great Smoky Mountains National Park. Nineteen species of Basidiomycota, primarily Agaricales, were also documented. Among these, only five species (, and ) were considered to be obligate pyrophilous taxa, but fruiting of two additional taxa ( and ) was clearly enhanced by fire. was an early colonizer of severe burn sites and persisted through the winter of 2017 and into spring and summer of 2018, often appearing in close association with seedlings. Fruiting of pyrophilous fungi peaked 4-6 mo post fire then diminished, but some continued to fruit up to 2.5 y after the fire. In all, a total of 27 previously unrecorded taxa were added to the All Taxa Biodiversity Inventory (ATBI) database (~0.9%). Most pyrophilous fungi identified in this study are either cosmopolitan or have a Northern Hemisphere distribution, but cryptic endemic lineages were detected in and . One new combination, var. f. , is proposed.
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http://dx.doi.org/10.1080/00275514.2020.1740381DOI Listing
June 2020

Secret lifestyles of pyrophilous fungi in the genus Sphaerosporella.

Am J Bot 2020 06 4;107(6):876-885. Epub 2020 Jun 4.

School of Integrated Plant Science, Cornell University, 334 Plant Science Building, Ithaca, NY, 14853-5904, USA.

Premise: Pyrophilous fungi form aboveground fruiting structures (ascocarps) following wildfires, but their ecology, natural history, and life cycles in the absence of wildfires are largely unknown. Sphaerosporella is considered to be pyrophilous. This study explores Sphaerosporella ascocarp appearance following a rare 2016 wildfire in the Great Smoky Mountains National Park (GSMNP), compares the timing of ascocarp formation with recovery of Sphaerosporella DNA sequences in soils, and explores the association of Sphaerosporella with post-fire Table Mountain pine (Pinus pungens) seedlings.

Methods: Burned sites in the GSMNP were surveyed for pyrophilous fungal ascocarps over 2 years. Ascocarps, mycorrhizae, and endophyte cultures were evaluated morphologically and by Sanger sequencing of the nuclear ribosomal ITS gene region (fungal barcode; Schoch et al., 2012). DNA from soil cores was subjected to Illumina sequencing.

Results: The timing and location of post-fire Sphaerosporella ascocarp formation was correlated with recovery of Sphaerosporella DNA sequences in soils. Genetic markers (fungal barcode) of Sphaerosporella were also recovered from mycorrhizal root tips and endophyte cultures from seedlings of Pinus pungens.

Conclusions: This study demonstrates that Sphaerosporella species, in the absence of fire, are biotrophic, forming both mycorrhizal and endophytic associations with developing Pinus pungens seedlings and may persist in nature in the absence of wildfire as a conifer symbiont. We speculate that Sphaerosporella may fruit only after the host plant is damaged or destroyed and that after wildfires, deep roots, needle endophytes, or heat-resistant spores could serve as a source of soil mycelium.
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http://dx.doi.org/10.1002/ajb2.1482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384086PMC
June 2020

Public acceptability of public health policy to improve population health: A population-based survey.

Health Expect 2020 08 24;23(4):802-812. Epub 2020 Apr 24.

Policy and International Health Directorate, World Health Organization Collaborating Centre on Investment for Health and Well-being, Public Health Wales, Wrexham, UK.

Background: For public health policies to be effective, it is critical that they are acceptable to the public as acceptance levels impact success rate.

Objective: To explore public acceptance of public health statements and examine differences in acceptability across socio-demographics, health behaviours (physical activity, diet, binge drinking and smoking), health status and well-being.

Method: A cross-sectional survey was conducted with a nationally representative sample (N = 1001) using a random stratified sampling method. Face-to-face interviews were conducted at homes of residents in Wales aged 16+ years. Individuals reported whether they agreed, had no opinion, or disagreed with 12 public health statements.

Results: More than half of the sample were supportive of 10 out of 12 statements. The three statements with the greatest support (>80% agreement) reflected the importance of: a safe and loving childhood to becoming a healthy adult, schools teaching about health, and healthier foods costing less. Individuals who engaged in unhealthy behaviours were less likely to agree with some of the statements (eg 39.8% of binge drinkers agreed alcohol adverts should be banned compared to 57.6% of those who never binge drink; P < .001).

Conclusions: Findings show an appetite for public health policies among the majority of the public. The relationship between supporting policies and engaging in healthy behaviours suggests a feedback loop that is potentially capable of shifting both public opinion and the opportunities for policy intervention. If a nation becomes healthier, this could illicit greater support for stronger policies which could encourage more people to move in a healthier direction.
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http://dx.doi.org/10.1111/hex.13041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495082PMC
August 2020

Understanding the association between self-reported poor oral health and exposure to adverse childhood experiences: a retrospective study.

BMC Oral Health 2020 02 14;20(1):51. Epub 2020 Feb 14.

Public Health Collaborating Unit, School of Health Sciences, College of Human Sciences, Bangor University, Wrexham, LL13 7YP, Wales.

Background: Adverse childhood experiences, including physical, sexual or emotional abuse, can have detrimental impacts on child and adult health. However, little research has explored the impact that such early life experiences have on oral health. This study examines whether experiencing adverse childhood experiences before the age of 18 years is associated with self-reported poor dental health in later life.

Methods: Using stratified random probability sampling, a household survey (N = 5307; age range 18-69 years) was conducted in the South of England (Hertfordshire, Luton and Northamptonshire). Data were collected at participants' homes using face-to-face interviews. Measures included exposure to nine adverse childhood experiences, and two dental outcomes: tooth loss (> 8 teeth lost due to dental caries or damage) and missing or filled teeth (direct or indirect restorations; > 12 missing or filled teeth).

Results: Strong associations were found between exposure to childhood adversity and poor dental health. The prevalence of tooth loss was significantly higher (8.3%) in those with 4+ adverse childhood experiences compared to those who had experienced none (5.0%; p < 0.05). A similar relationship was found for levels of missing or filled teeth (13.4%, 4+ adverse childhood experiences; 8.1%, none; p < 0.001). Exposure to 4+ adverse childhood experiences was associated with a higher level of tooth loss and restorations at any age, compared to individuals who had not experienced adversity. Demographically adjusted means for tooth loss increased with adverse childhood experience count in all age groups, rising from 1.0% (18-29 years) and 13.0% (60-69 years) in those with none, to 3.0% and 26.0%, respectively in those reporting 4+.

Conclusions: Exposure to childhood adversity could be an important predictive factor for poor dental health. As oral health is an important part of a child's overall health status, approaches that seek to improve dental health across the life-course should start with safe and nurturing childhoods free from abuse and neglect. Given the growing role that dental professionals have in identifying violence and abuse, it seems appropriate to raise awareness in the field of dentistry of the potential for individuals to have suffered adverse childhood experiences, and the mechanisms linking childhood adversity to poor dental health.
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http://dx.doi.org/10.1186/s12903-020-1028-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020341PMC
February 2020

Safety, tolerability, pharmacokinetics, and immunogenicity of a human monoclonal antibody targeting the G glycoprotein of henipaviruses in healthy adults: a first-in-human, randomised, controlled, phase 1 study.

Lancet Infect Dis 2020 04 3;20(4):445-454. Epub 2020 Feb 3.

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Background: The monoclonal antibody m102.4 is a potent, fully human antibody that neutralises Hendra and Nipah viruses in vitro and in vivo. We aimed to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of m102.4 in healthy adults.

Methods: In this double-blind, placebo-controlled, single-centre, dose-escalation, phase 1 trial of m102.4, we randomly assigned healthy adults aged 18-50 years with a body-mass index of 18·0-35·0 kg/m to one of five cohorts. A sentinel pair for each cohort was randomly assigned to either m102.4 or placebo. The remaining participants in each cohort were randomly assigned (5:1) to receive m102.4 or placebo. Cohorts 1-4 received a single intravenous infusion of m102.4 at doses of 1 mg/kg (cohort 1), 3 mg/kg (cohort 2), 10 mg/kg (cohort 3), and 20 mg/kg (cohort 4), and were monitored for 113 days. Cohort 5 received two infusions of 20 mg/kg 72 h apart and were monitored for 123 days. The primary outcomes were safety and tolerability. Secondary outcomes were pharmacokinetics and immunogenicity. Analyses were completed according to protocol. The study was registered on the Australian New Zealand Clinical Trials Registry, ACTRN12615000395538.

Findings: Between March 27, 2015, and June 16, 2016, 40 (52%) of 77 healthy screened adults were enrolled in the study. Eight participants were assigned to each cohort (six received m102.4 and two received placebo). 86 treatment-emergent adverse events were reported, with similar rates between placebo and treatment groups. The most common treatment-related event was headache (12 [40%] of 30 participants in the combined m102.4 group, and three [30%] of ten participants in the pooled placebo group). No deaths or severe adverse events leading to study discontinuation occurred. Pharmacokinetics based on those receiving m102.4 (n=30) were linear, with a median half-life of 663·3 h (range 474·3-735·1) for cohort 1, 466·3 h (382·8-522·3) for cohort 2, 397·0 h (333·9-491·8) for cohort 3, and 466·7 h (351·0-889·6) for cohort 4. The elimination kinetics of those receiving repeated dosing (cohort 5) were similar to those of single-dose recipients (median elimination half-time 472·0 [385·6-592·0]). Anti-m102.4 antibodies were not detected at any time-point during the study.

Interpretation: Single and repeated dosing of m102.4 were well tolerated and safe, displayed linear pharmacokinetics, and showed no evidence of an immunogenic response. This study will inform future dosing regimens for m102.4 to achieve prolonged exposure for systemic efficacy to prevent and treat henipavirus infections.

Funding: Queensland Department of Health, the National Health and Medical Research Council, and the National Hendra Virus Research Program.
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http://dx.doi.org/10.1016/S1473-3099(19)30634-6DOI Listing
April 2020

Assessing the impact of a research funder's recommendation to consider core outcome sets.

PLoS One 2019 13;14(9):e0222418. Epub 2019 Sep 13.

MRC North West Hub for Trials Methodology Research, Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.

Background: Core outcome sets (COS) have the potential to reduce waste in research by improving the consistency of outcomes measured in trials of the same health condition. However, this reduction in waste will only be realised through the uptake of COS by clinical trialists. Without uptake, the continued development of COS that are not implemented may add to waste in research. Funders of clinical trials have the potential to have an impact on COS uptake by recommending their use to those applying for funding. The aim of our study was to assess the extent to which applicants followed the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme's recommendation to search for a COS to include in their clinical trial.

Methods And Findings: We examined the outcomes section and detailed project descriptions of all 95 researcher-led primary research applications submitted to the NIHR HTA between January 2012, when the recommendation to search for a COS was included in the guidance for applicants, and December 2015 for evidence that a search for a COS had taken place and rationale for outcome choice in the absence of COS. A survey of applicants was conducted to further explore their use of COS and choice of outcomes with a response rate of 49%. Nine out of 95 applicants (10%) stated in their application that they had searched the COMET (Core Outcome Measures for Effectiveness Trials) Initiative database for a COS and another nine referred to searching for a COS using another method, e.g. a review of the literature. Of the 77 (81%) applicants that did not mention COMET or COS in their application, eight stated in the survey that they had searched the COMET database and ten carried out a search using another method. Some applicants who did not search for a COS gave reasons for their choice of outcomes including taking advice from patients and the public and choosing outcomes used in previous trials.

Conclusion: A funding body can have an impact on COS uptake by encouraging trialists to search for a COS. Funders could take further steps by putting processes in place to prompt applicants to be explicit about searching for COS in their application and notifying the funding board if a search has not taken place. The sources of information used by trialists to make decisions about outcomes in the absence of COS may suggest methods of dissemination for COS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222418PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743767PMC
March 2020

Life course health consequences and associated annual costs of adverse childhood experiences across Europe and North America: a systematic review and meta-analysis.

Lancet Public Health 2019 10 3;4(10):e517-e528. Epub 2019 Sep 3.

Violence and Injury Prevention, World Health Organization Regional Office for Europe, Copenhagen, Denmark.

Background: An increasing number of studies are identifying associations between adverse childhood experiences (ACEs) and ill health throughout the life course. We aimed to calculate the proportions of major risk factors for and causes of ill health that are attributable to one or multiple types of ACE and the associated financial costs.

Methods: In this systematic review and meta-analysis, we searched for studies in which risk data in individuals with ACEs were compared with these data in those without ACEs. We searched six electronic databases (MEDLINE, CINAHL, PsycINFO, Applied Social Sciences Index and Abstracts, Criminal Justice Databases, and the Education Resources Information Center) for quantitative studies published between Jan 1, 1990, and July 11, 2018, that reported risks of health-related behaviours and causes of ill health in adults that were associated with cumulative measures of ACEs (ie, number of ACEs). We included studies in adults in populations that did not have a high risk of ACEs, that had sample sizes of at least 1000 people, and that provided ACE prevalence data. We calculated the pooled RR for risk factors (harmful alcohol use, illicit drug use, smoking, and obesity) and causes of ill health (cancer, diabetes, cardiovascular disease, respiratory disease, anxiety, and depression) associated with ACEs. RRs were used to estimate the population-attributable fractions (PAFs) of risk attributable to ACEs and the disability-adjusted life-years (DALYs) and financial costs associated with ACEs. This study was prospectively registered in PROSPERO (CRD42018090356).

Findings: Of 4387 unique articles found following our initial search, after review of the titles (and abstracts, when the title was relevant), we assessed 880 (20%) full-text articles. We considered 221 (25%) full-text articles for inclusion, of which 23 (10%) articles met all selection criteria for our meta-analysis. We found a pooled prevalence of 23·5% of individuals (95% CI 18·7-28·5) with one ACE and 18·7% (14·7-23·2) with two or more ACEs in Europe (from ten studies) and of 23·4% of individuals (22·0-24·8) with one ACE and 35·0% (31·6-38·4) with two or more ACEs in north America (from nine studies). Illicit drug use had the highest PAFs associated with ACEs of all the risk factors assessed in both regions (34·1% in Europe; 41·1% in north America). In both regions, PAFs of causes of ill health were highest for mental illness outcomes: ACEs were attributed to about 30% of cases of anxiety and 40% of cases of depression in north America and more than a quarter of both conditions in Europe. Costs of cardiovascular disease attributable to ACEs were substantially higher than for most other causes of ill health because of higher DALYs for this condition. Total annual costs attributable to ACEs were estimated to be US$581 billion in Europe and $748 billion in north America. More than 75% of these costs arose in individuals with two or more ACEs.

Interpretation: Millions of adults across Europe and north America live with a legacy of ACEs. Our findings suggest that a 10% reduction in ACE prevalence could equate to annual savings of 3 million DALYs or $105 billion. Programmes to prevent ACEs and moderate their effects are available. Rebalancing expenditure towards ensuring safe and nurturing childhoods would be economically beneficial and relieve pressures on health-care systems.

Funding: World Health Organization Regional Office for Europe.
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http://dx.doi.org/10.1016/S2468-2667(19)30145-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098477PMC
October 2019

Stem cell factor and granulocyte colony-stimulating factor promote brain repair and improve cognitive function through VEGF-A in a mouse model of CADASIL.

Neurobiol Dis 2019 12 31;132:104561. Epub 2019 Jul 31.

Department of Neurosurgery, State University of New York Upstate Medical University, Syracuse, NY 13210, USA. Electronic address:

Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 gene mutation in vascular smooth muscle cells (VSMCs), leading to ischemic stroke and vascular dementia. To date, the pathogenesis of CADASIL remains poorly understood, and there is no treatment that can slow the progression of CADASIL. Using a transgenic mouse model of CADASIL (TgNotch3R90C), this study reveals novel findings for understanding CADASIL pathogenesis that decreased cerebral vascular endothelial growth factor (VEGF/VEGF-A) is linked to reduced cerebral blood vessel density. Reduced endothelial cell (EC) proliferation and angiogenesis are seen in TgNotch3R90C mouse brain-isolated ECs. Decreased dendrites, axons, and synapses in the somatosensory and motor cortex layer 2/3 and in the hippocampal CA1, and reduced neurogenesis in both the subventricular zone and subgranular zone occur in 15-month-old TgNotch3R90C mice. These reductions in neuron structures, synapses, and neurogenesis are significantly correlated to decreased cerebral vasculature in the corresponding areas. Impaired spatial learning and memory in TgNotch3R90C mice are significantly correlated with the reduced cerebral vasculature, neuron structures, and synapses. Repeated treatment of stem cell factor and granulocyte colony-stimulating factor (SCF+G-CSF) at 9 and 10 months of age improves cognitive function, increases cerebral VEGF/VEGF-A, restores cerebral vasculature, and enhances regeneration of neuronal structures, synaptogenesis and neurogenesis in TgNotch3R90C mice. Pretreatment with Avastin, an angiogenesis inhibitor by neutralizing VEGF-A, completely eliminates the SCF+G-CSF-enhanced cognitive function, vascular and neuronal structure regeneration, synaptogenesis and neurogenesis in TgNotch3R90C mice. SCF+G-CSF-enhanced EC proliferation and angiogenesis in TgNotch3R90C mouse brain-isolated ECs are also blocked by Avastin pretreatment. These data suggest that SCF+G-CSF treatment may repair Notch3R90C mutation-damaged brain through the VEGF-A-mediated angiogenesis. This study provides novel insight into the involvement of VEGF/VEGF-A in the pathogenesis of CADASIL and sheds light on the mechanism underlying the SCF+G-CSF-enhanced brain repair in CADASIL.
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http://dx.doi.org/10.1016/j.nbd.2019.104561DOI Listing
December 2019

Subtenon Bupivacaine for Postoperative Pain in Patients Undergoing Pterygium Excision: A Double-Blinded Randomized Control Trial.

Cornea 2019 Aug;38(8):959-963

Department of Ophthalmology, Waikato District Health Board, Hamilton, New Zealand.

Purpose: Patients undergoing primary pterygium excision with autologous conjunctival autograft and human tissue adhesive in New Zealand, currently receive subconjunctival anesthesia with oral postoperative analgesia for pain. Our aim was to investigate the potential added benefit of intraoperative subtenon bupivacaine to this regimen.

Methods: A double-blinded, placebo-controlled, randomized trial was conducted at 2 centers. All patients received topical and subconjunctival anesthesia intraoperatively, with standardized oral analgesia as required postoperatively. Participants were allocated to receive subtenon bupivacaine 0.5% or placebo at the conclusion of surgery. Corneal epithelial defect and conjunctival graft size were recorded. Pain and ocular surface irritation were assessed (Likert scale) immediately postoperatively at 3, 6, 12, 24, and 36 hours. Cumulative oral analgesia consumption (doses) was reported at 24 and 36 hours.

Results: Forty-two patients were randomized with participants evenly matched at baseline. Postoperative pain at all time points ≤24 hours was significantly less (2.4 vs. 1.2; P < 0.04) in the bupivacaine arm with no difference at 36 hours (P = 0.27). Ocular surface irritation was also significantly less at all time points ≤12 hours (4.8 vs. 1.3; P < 0.01) with no difference at 24 hours (P = 0.10). Analgesia consumption was less in the bupivacaine arm at 24 (6.5 vs. 2.5; P < 0.01) and 36 hours (7.6 vs. 3.4; P < 0.01). No complications were observed.

Conclusions: Intraoperative subtenon bupivacaine improves patient comfort after pterygium excision by reducing pain, irritation, and requirement for oral analgesia after surgery.
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http://dx.doi.org/10.1097/ICO.0000000000001973DOI Listing
August 2019

Alcohol's harms to others in Wales, United Kingdom: Nature, magnitude and associations with mental well-being.

Addict Behav Rep 2019 Jun 5;9:100162. Epub 2019 Feb 5.

Policy Research and International Development Directorate, Public Health Wales, Cardiff, UK.

Aim: To explore the nature and magnitude of alcohol's harms to others (AHTOs), and associations with mental well-being.

Methods: Cross-sectional survey implemented amongst 891 randomly selected Welsh residents (aged 18+ years), via computer assisted telephone interviews. Questions established past 12-month experience of nine direct harms resulting from another person's alcohol consumption (e.g. violence) and five linked outcomes (e.g. concern for a child). The source (e.g. partner/stranger) and frequency of the AHTO were collected, and respondents' socio-demographics, drinking behaviours and mental well-being status.

Results: During the past 12 months, 43.5% of respondents had experienced at least one direct harm (45.5% at least one direct harm/linked outcome). In demographically adjusted analyses, the odds of experiencing any direct harm decreased sequentially as age group increased (Adjusted Odds Ratio [AORs]: 1.9 [age 65-74 years] - 4.2 [age 18-34 years]), and was higher amongst binge drinkers (AOR, 1.5, p < 0.05). Associations between age group and suffering the direct harms anxiety, disrupted sleep, feeling threatened, property damage and emotional neglect were found. Experience of feeling threatened was lower amongst females (AOR 0.6, p < 0.05). In demographically adjusted analyses, low mental well-being was higher amongst those who had suffered alcohol-related financial issues (AOR 2.2, p < 0.001), emotional neglect (AOR 2.3, p < 0.01) and property damage (AOR 2.2, p < 0.05).

Conclusion: AHTOs place a large, although unequal burden on adults in Wales. Individuals' drinking patterns are associated with experience of AHTOs. Critically, experience of some harms is associated with low mental well-being.
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http://dx.doi.org/10.1016/j.abrep.2019.100162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542752PMC
June 2019

Ideal, expected and perceived descriptive norm drunkenness in UK nightlife environments: a cross-sectional study.

BMC Public Health 2019 Apr 27;19(1):442. Epub 2019 Apr 27.

Policy and International Health, Public Health Wales, Clwydian House, Wrexham, LL13 7YP, UK.

Background: Drunkenness is common in nightlife environments and studies suggest it can be considered both desirable and normal by nightlife users. We aimed to compare UK nightlife users' ideal levels of drunkenness to their expected drunkenness on a night out and their perceptions of descriptive nightlife norms.

Methods: A cross-sectional survey with nightlife patrons (n = 408, aged 18-35) in three cities. Using a scale from 1 (completely sober) to 10 (very drunk), participants rated: personal drunkenness at survey; expected drunkenness on leaving nightlife; perceived descriptive drunkenness norm in the city's nightlife; and ideal personal drunkenness. Analyses were limited to those who had or were intending to consume alcohol.

Results: Almost half of participants (46.8%) expected to get drunker than their reported ideal level on the night of survey, rising to four fifths of those with the highest levels of expected drunkenness. 77.9% rated typical nightlife drunkenness ≥8 but only 40.9% expected to reach this level themselves and only 23.1% reported their ideal drunkenness as ≥8. Higher expected drunkenness was associated with higher ideal drunkenness, higher perceived drunkenness norm and later expected home time.

Conclusions: Nightlife users' perceptions of typical drunkenness in nightlife settings may be elevated and many of the heaviest drinkers are likely to drink beyond their ideal level of drunkenness. Findings can support emerging work to address cultures of intoxication in nightlife environments and suggest that interventions to correct misperceptions of normal levels of nightlife drunkenness may be of benefit.
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http://dx.doi.org/10.1186/s12889-019-6802-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486975PMC
April 2019

Adverse childhood experiences, childhood relationships and associated substance use and mental health in young Europeans.

Eur J Public Health 2019 08;29(4):741-747

Kiev International Institute of Sociology, Kyiv, Ukraine.

Background: Adverse childhood experiences (ACEs) can increase risks of health-harming behaviours and poor health throughout life. While increases in risk may be affected by resilience resources such as supportive childhood relationships, to date few studies have explored these effects.

Methods: We combined data from cross-sectional ACE studies among young adults (n = 14 661) in educational institutions in 10 European countries. Nine ACE types, childhood relationships and six health outcomes (early alcohol initiation, problem alcohol use, smoking, drug use, therapy, suicide attempt) were explored. Multivariate modelling estimated relationships between ACE counts, supportive childhood relationships and health outcomes.

Results: Almost half (46.2%) of participants reported ≥1 ACE and 5.6% reported ≥4 ACEs. Risks of all outcomes increased with ACE count. In individuals with ≥4 ACEs (vs. 0 ACEs), adjusted odds ratios ranged from 2.01 (95% CIs: 1.70-2.38) for smoking to 17.68 (95% CIs: 12.93-24.17) for suicide attempt. Supportive childhood relationships were independently associated with moderating risks of smoking, problem alcohol use, therapy and suicide attempt. In those with ≥4 ACEs, adjusted proportions reporting suicide attempt reduced from 23% with low supportive childhood relationships to 13% with higher support. Equivalent reductions were 25% to 20% for therapy, 23% to 17% for problem drinking and 34% to 32% for smoking.

Conclusions: ACEs are strongly associated with substance use and mental illness. Harmful relationships are moderated by resilience factors such as supportive childhood relationships. Whilst ACEs continue to affect many children, better prevention measures and interventions that enhance resilience to the life-long impacts of toxic childhood stress are required.
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http://dx.doi.org/10.1093/eurpub/ckz037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660110PMC
August 2019

Megaphylogeny resolves global patterns of mushroom evolution.

Nat Ecol Evol 2019 04 18;3(4):668-678. Epub 2019 Mar 18.

Synthetic and Systems Biology Unit, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.

Mushroom-forming fungi (Agaricomycetes) have the greatest morphological diversity and complexity of any group of fungi. They have radiated into most niches and fulfil diverse roles in the ecosystem, including wood decomposers, pathogens or mycorrhizal mutualists. Despite the importance of mushroom-forming fungi, large-scale patterns of their evolutionary history are poorly known, in part due to the lack of a comprehensive and dated molecular phylogeny. Here, using multigene and genome-based data, we assemble a 5,284-species phylogenetic tree and infer ages and broad patterns of speciation/extinction and morphological innovation in mushroom-forming fungi. Agaricomycetes started a rapid class-wide radiation in the Jurassic, coinciding with the spread of (sub)tropical coniferous forests and a warming climate. A possible mass extinction, several clade-specific adaptive radiations and morphological diversification of fruiting bodies followed during the Cretaceous and the Paleogene, convergently giving rise to the classic toadstool morphology, with a cap, stalk and gills (pileate-stipitate morphology). This morphology is associated with increased rates of lineage diversification, suggesting it represents a key innovation in the evolution of mushroom-forming fungi. The increase in mushroom diversity started during the Mesozoic-Cenozoic radiation event, an era of humid climate when terrestrial communities dominated by gymnosperms and reptiles were also expanding.
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http://dx.doi.org/10.1038/s41559-019-0834-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443077PMC
April 2019

The evidence base for routine enquiry into adverse childhood experiences: A scoping review.

Child Abuse Negl 2019 05 16;91:131-146. Epub 2019 Mar 16.

Public Health Collaborating Unit, College of Human Sciences, BIHMR, Bangor University, Wrexham Technology Park, Wrexham, LL13 7YP, UK; Policy and International Development Directorate, a World Health Organization Collaboration Centre on Investment for Health and Well-being, Public Health Wales, Wrexham, LL13 7YP, UK.

Background: Exposure to adverse childhood experiences (ACEs; e.g., maltreatment, household dysfunction) is associated with a multiplicity of negative outcomes throughout the life course. Consequently, increasing interest is being paid to the application of routine enquiry for ACEs to enable identification and direct interventions to mitigate their harms.

Objective: To explore the evidence base for retrospective routine enquiry in adults for ACEs, including feasibility and acceptability amongst practitioners, service user acceptability and outcomes from implementation.

Methods: A scoping review of the literature was conducted, drawing upon three databases (CINAHL, MEDLINE, PsycINFO) and manual searching and citation tracking. Searches included studies published from 1997 until end of April 2018 examining enquiry into ACEs, or the feasibility/acceptability of such enquiry across any setting. All included studies presented empirical findings, with studies focusing on screening for current adversities excluded.

Results: Searches retrieved 380 articles, of which 15 met the eligibility criteria. A narrative approach to synthesize the data was utilized. Four studies examined practitioner feasibility and/or acceptability of enquiry, three reported service user acceptability and six studies implemented routine ACE enquiry (not mutually exclusive categories). Further, eight studies explored current practice and practitioner attitudes towards ACE enquiry.

Conclusions: Limited literature was found providing evidence for outcomes from enquiry. No studies examined impacts on service user health or service utilization. Few studies explored feasibility or acceptability to inform the application of routine ACE enquiry. The implementation of routine ACE enquiry therefore needs careful consideration. Focus should remain on evaluating developing models of ACE enquiry to advance understanding of its impact.
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http://dx.doi.org/10.1016/j.chiabu.2019.03.007DOI Listing
May 2019

Two additional species of (Euagarics, Basidiomycotina).

MycoKeys 2019 14(45):1-24. Epub 2019 Jan 14.

Ecology & Evolutionary Biology, University of Tennessee, Knoxville, TN 37996-1100 University of Tennessee Knoxville United States of America.

For more than a decade, a combination of molecular phylogenetic analyses and morphological characterisation has led to a renovation of the Omphalotaceae, especially of sensu lato. Numerous new genera have been proposed, but sensu stricto has also seen an accretion of species and species complexes. In this manuscript, two species are added to Gymnopus sensu stricto within Section Androsacei.
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http://dx.doi.org/10.3897/mycokeys.45.29350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351703PMC
January 2019

Does adult alcohol consumption combine with adverse childhood experiences to increase involvement in violence in men and women? A cross-sectional study in England and Wales.

BMJ Open 2018 12 6;8(12):e020591. Epub 2018 Dec 6.

Policy, Research and International Development Directorate, Public Health Wales, Cardiff, UK.

Objectives: To examine if, and to what extent, a history of adverse childhood experiences (ACEs) combines with adult alcohol consumption to predict recent violence perpetration and victimisation.

Design: Representative face-to-face survey (n=12 669) delivered using computer-assisted personal interviewing and self-interviewing.

Setting: Domiciles of individuals living in England and Wales.

Participants: Individuals aged 18-69 years resident within randomly selected locations. 12 669 surveys were completed with participants within our defined age range.

Main Outcome Measures: Alcohol consumption was measured using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and childhood adversity using the short ACEs tool. Violence was measured using questions on perpetration and victimisation in the last 12 months.

Results: Compliance was 55.7%. There were strong positive relationships between numbers of ACEs and recent violence perpetration and victimisation in both sexes. Recent violence was also strongly related to positive AUDIT-C (≥5) scores. In males, heavier drinking and ≥4ACEs had a strong multiplicative relationship with adjusted prevalence of recent violent perpetration rising from 1.3% (95% CIs 0.9% to 1.9%; 0 ACEs, negative AUDIT-C) to 3.6% (95% CIs 2.7% to 4.9%; 0 ACEs, positive AUDIT-C) and 8.5% (95% CI 5.6% to 12.7%; ≥4ACEs, negative AUDIT-C) to 28.3% (95% CI 22.5% to 34.8%; ≥4ACEs, positive AUDIT-C). In both sexes, violence perpetration and victimisation reduced with age independently of ACE count and AUDIT-C status. The combination of young age (18-29 years), ≥4ACEs and positive AUDIT-C resulted in the highest adjusted prevalence for both perpetration and victimisation in males (61.9%, 64.9%) and females (24.1%, 27.2%).

Conclusions: Those suffering multiple adverse experiences in childhood are also more likely to be heavier alcohol users. Especially for males, this combination results in substantially increased risks of violence. Addressing ACEs and heavy drinking together is rarely a feature of public health policy, but a combined approach may help reduce the vast costs associated with both.
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http://dx.doi.org/10.1136/bmjopen-2017-020591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286488PMC
December 2018

Revision of pyrophilous taxa of Pholiota described from North America reveals four species-P. brunnescens, P. castanea, P. highlandensis, and P. molesta.

Mycologia 2018 Nov-Dec;110(6):997-1016. Epub 2018 Nov 27.

a Department of Ecology and Evolutionary Biology , University of Tennessee , Dabney 569, Knoxville , Tennessee 37996-1610.

A systematic reevaluation of North American pyrophilous or "burn-loving" species of Pholiota is presented based on molecular and morphological examination of type and historical collections. Confusion surrounds application of the names P. brunnescens, P. carbonaria, P. castanea, P. fulvozonata, P. highlandensis, P. molesta, and P. subsaponacea, with multiple names applied to a single species and multiple species described more than once. Molecular annotations using nuc rDNA ITS1-5.8S-ITS2 (internal transcribed spacer [ITS] barcode) and RPB2 (RNA polymerase II second largest subunit) are used to aid in application of these names in a phylogenetic context. Based on ITS molecular annotations of 13 types, the following heterotypic synonymies are proposed: P. highlandensis (syn. P. carbonaria and P. fulvozonata); P. molesta (syn. P. subsaponacea); and P. brunnescens (syn. P. luteobadia). In addition, we observed that the species P. castanea, known previously only from the type collection in Tennessee, is found commonly on burned sites near the Gulf Coast and other southeast regions of the United States. Overall, the pyrophilous trait is evolutionarily derived in Pholiota. Endophytic and endolichenic stages were deduced for P. highlandensis, the most widely distributed of the pyrophilous Pholiota. As a result, we introduce the "body snatchers" hypothesis that explains the maintenance of some pyrophilous fungi in ecosystems as endophytes and/or endolichenic fungi. Photographs, taxonomic descriptions, and a dichotomous key to pyrophilous species of Pholiota that occur in North America are presented.
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http://dx.doi.org/10.1080/00275514.2018.1516960DOI Listing
April 2019

Considerations and consequences of allowing DNA sequence data as types of fungal taxa.

Authors:
Juan Carlos Zamora Måns Svensson Roland Kirschner Ibai Olariaga Svengunnar Ryman Luis Alberto Parra József Geml Anna Rosling Slavomír Adamčík Teuvo Ahti M Catherine Aime A Martyn Ainsworth László Albert Edgardo Albertó Alberto Altés García Dmitry Ageev Reinhard Agerer Begoña Aguirre-Hudson Joe Ammirati Harry Andersson Claudio Angelini Vladimír Antonín Takayuki Aoki André Aptroot Didier Argaud Blanca Imelda Arguello Sosa Arne Aronsen Ulf Arup Bita Asgari Boris Assyov Violeta Atienza Ditte Bandini João Luís Baptista-Ferreira Hans-Otto Baral Tim Baroni Robert Weingart Barreto Henry Beker Ann Bell Jean-Michel Bellanger Francesco Bellù Martin Bemmann Mika Bendiksby Egil Bendiksen Katriina Bendiksen Lajos Benedek Anna Bérešová-Guttová Franz Berger Reinhard Berndt Annarosa Bernicchia Alona Yu Biketova Enrico Bizio Curtis Bjork Teun Boekhout David Boertmann Tanja Böhning Florent Boittin Carlos G Boluda Menno W Boomsluiter Jan Borovička Tor Erik Brandrud Uwe Braun Irwin Brodo Tatiana Bulyonkova Harold H Burdsall Bart Buyck Ana Rosa Burgaz Vicent Calatayud Philippe Callac Emanuele Campo Massimo Candusso Brigitte Capoen Joaquim Carbó Matteo Carbone Rafael F Castañeda-Ruiz Michael A Castellano Jie Chen Philippe Clerc Giovanni Consiglio Gilles Corriol Régis Courtecuisse Ana Crespo Cathy Cripps Pedro W Crous Gladstone Alves da Silva Meiriele da Silva Marjo Dam Nico Dam Frank Dämmrich Kanad Das Linda Davies Eske De Crop Andre De Kesel Ruben De Lange Bárbara De Madrignac Bonzi Thomas Edison E Dela Cruz Lynn Delgat Vincent Demoulin Dennis E Desjardin Paul Diederich Bálint Dima Maria Martha Dios Pradeep Kumar Divakar Clovis Douanla-Meli Brian Douglas Elisandro Ricardo Drechsler-Santos Paul S Dyer Ursula Eberhardt Damien Ertz Fernando Esteve-Raventós Javier Angel Etayo Salazar Vera Evenson Guillaume Eyssartier Edit Farkas Alain Favre Anna G Fedosova Mario Filippa Péter Finy Adam Flakus Simón Fos Jacques Fournier André Fraiture Paolo Franchi Ana Esperanza Franco Molano Gernot Friebes Andreas Frisch Alan Fryday Giuliana Furci Ricardo Galán Márquez Matteo Garbelotto Joaquina María García-Martín Mónica A García Otálora Dania García Sánchez Alain Gardiennet Sigisfredo Garnica Isaac Garrido Benavent Genevieve Gates Alice da Cruz Lima Gerlach Masoomeh Ghobad-Nejhad Tatiana B Gibertoni Tine Grebenc Irmgard Greilhuber Bella Grishkan Johannes Z Groenewald Martin Grube Gérald Gruhn Cécile Gueidan Gro Gulden Luis Fp Gusmão Josef Hafellner Michel Hairaud Marek Halama Nils Hallenberg Roy E Halling Karen Hansen Christoffer Bugge Harder Jacob Heilmann-Clausen Stip Helleman Alain Henriot Margarita Hernandez-Restrepo Raphaël Herve Caroline Hobart Mascha Hoffmeister Klaus Høiland Jan Holec Håkon Holien Karen Hughes Vit Hubka Seppo Huhtinen Boris Ivančević Marian Jagers Walter Jaklitsch AnnaElise Jansen Ruvishika S Jayawardena Thomas Stjernegaard Jeppesen Mikael Jeppson Peter Johnston Per Magnus Jørgensen Ingvar Kärnefelt Liudmila B Kalinina Gintaras Kantvilas Mitko Karadelev Taiga Kasuya Ivona Kautmanová Richard W Kerrigan Martin Kirchmair Anna Kiyashko Dániel G Knapp Henning Knudsen Kerry Knudsen Tommy Knutsson Miroslav Kolařík Urmas Kõljalg Alica Košuthová Attila Koszka Heikki Kotiranta Vera Kotkova Ondřej Koukol Jiří Kout Gábor M Kovács Martin Kříž Åsa Kruys Viktor Kučera Linas Kudzma Francisco Kuhar Martin Kukwa T K Arun Kumar Vladimír Kunca Ivana Kušan Thomas W Kuyper Carlos Lado Thomas Læssøe Patrice Lainé Ewald Langer Ellen Larsson Karl-Henrik Larsson Gary Laursen Christian Lechat Serena Lee James C Lendemer Laura Levin Uwe Lindemann Håkan Lindström Xingzhong Liu Regulo Carlos Llarena Hernandez Esteve Llop Csaba Locsmándi Deborah Jean Lodge Michael Loizides László Lőkös Jennifer Luangsa-Ard Matthias Lüderitz Thorsten Lumbsch Matthias Lutz Dan Mahoney Ekaterina Malysheva Vera Malysheva Patinjareveettil Manimohan Yasmina Marin-Felix Guilhermina Marques Rubén Martínez-Gil Guy Marson Gerardo Mata P Brandon Matheny Geir Harald Mathiassen Neven Matočec Helmut Mayrhofer Mehdi Mehrabi Ireneia Melo Armin Mešić Andrew S Methven Otto Miettinen Ana M Millanes Romero Andrew N Miller James K Mitchell Roland Moberg Pierre-Arthur Moreau Gabriel Moreno Olga Morozova Asunción Morte Lucia Muggia Guillermo Muñoz González Leena Myllys István Nagy László G Nagy Maria Alice Neves Tuomo Niemelä Pier Luigi Nimis Nicolas Niveiro Machiel E Noordeloos Anders Nordin Sara Raouia Noumeur Yuri Novozhilov Jorinde Nuytinck Esteri Ohenoja Patricia Oliveira Fiuza Alan Orange Alexander Ordynets Beatriz Ortiz-Santana Leticia Pacheco Ferenc Pál-Fám Melissa Palacio Zdeněk Palice Viktor Papp Kadri Pärtel Julia Pawlowska Aurelia Paz Ursula Peintner Shaun Pennycook Olinto Liparini Pereira Pablo Pérez Daniëls Miquel À Pérez-De-Gregorio Capella Carlos Manuel Pérez Del Amo Sergio Pérez Gorjón Sergio Pérez-Ortega Israel Pérez-Vargas Brian A Perry Jens H Petersen Ronald H Petersen Donald H Pfister Chayanard Phukhamsakda Marcin Piątek Meike Piepenbring Raquel Pino-Bodas Juan Pablo Pinzón Esquivel Paul Pirot Eugene S Popov Orlando Popoff María Prieto Álvaro Christian Printzen Nadezhda Psurtseva Witoon Purahong Luis Quijada Gerhard Rambold Natalia A Ramírez Huzefa Raja Olivier Raspé Tania Raymundo Martina Réblová Yury A Rebriev Juan de Dios Reyes García Miguel Ángel Ribes Ripoll Franck Richard Mike J Richardson Víctor J Rico Gerardo Lucio Robledo Flavia Rodrigues Barbosa Cristina Rodriguez-Caycedo Pamela Rodriguez-Flakus Anna Ronikier Luis Rubio Casas Katerina Rusevska Günter Saar Irja Saar Isabel Salcedo Sergio M Salcedo Martínez Carlos A Salvador Montoya Santiago Sánchez-Ramírez J Vladimir Sandoval-Sierra Sergi Santamaria Josiane Santana Monteiro Hans Josef Schroers Barbara Schulz Geert Schmidt-Stohn Trond Schumacher Beatrice Senn-Irlet Hana Ševčíková Oleg Shchepin Takashi Shirouzu Anton Shiryaev Klaus Siepe Esteban B Sir Mohammad Sohrabi Karl Soop Viacheslav Spirin Toby Spribille Marc Stadler Joost Stalpers Soili Stenroos Ave Suija Stellan Sunhede Sten 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IMA Fungus 2018 Jun 24;9(1):167-175. Epub 2018 May 24.

Museum of Evolution, Uppsala University, Norbyvägen 16, 75236 Uppsala, Sweden.

Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11 International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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http://dx.doi.org/10.5598/imafungus.2018.09.01.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048565PMC
June 2018

Adverse childhood experiences and sources of childhood resilience: a retrospective study of their combined relationships with child health and educational attendance.

BMC Public Health 2018 06 26;18(1):792. Epub 2018 Jun 26.

Policy, Research and International Development Directorate, Public Health Wales, Number 2 Capital Quarter, Tyndall Street, Cardiff, CF10 4BZ, UK.

Background: Adverse childhood experiences (ACEs) including maltreatment and exposure to household stressors can impact the health of children. Community factors that provide support, friendship and opportunities for development may build children's resilience and protect them against some harmful impacts of ACEs. We examine if a history of ACEs is associated with poor childhood health and school attendance and the extent to which such outcomes are counteracted by community resilience assets.

Methods: A national (Wales) cross-sectional retrospective survey (n = 2452) using a stratified random probability sampling methodology and including a boost sample (n = 471) of Welsh speakers. Data collection used face-to-face interviews at participants' places of residence. Outcome measures were self-reported poor childhood health, specific conditions (asthma, allergies, headaches, digestive disorders) and school absenteeism.

Results: Prevalence of each common childhood condition, poor childhood health and school absenteeism increased with number of ACEs reported. Childhood community resilience assets (being treated fairly, supportive childhood friends, being given opportunities to use your abilities, access to a trusted adult and having someone to look up to) were independently linked to better outcomes. In those with ≥4 ACEs the presence of all significant resilience assets (vs none) reduced adjusted prevalence of poor childhood health from 59.8 to 21.3%.

Conclusions: Better prevention of ACEs through the combined actions of public services may reduce levels of common childhood conditions, improve school attendance and help alleviate pressures on public services. Whilst the eradication of ACEs remains unlikely, actions to strengthen community resilience assets may partially offset their immediate harms.
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http://dx.doi.org/10.1186/s12889-018-5699-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020215PMC
June 2018

A map for successful CCNE accreditation.

J Prof Nurs 2018 May - Jun;34(3):182-188. Epub 2017 Sep 21.

Otterbein University, United States. Electronic address:

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http://dx.doi.org/10.1016/j.profnurs.2017.09.003DOI Listing
April 2019

Intragenomic nuclear RNA variation in a cryptic Amanita taxon.

Mycologia 2018 Jan-Feb;110(1):93-103

a Department of Ecology and Evolutionary Biology , University of Tennessee , Knoxville , Tennessee 37919.

Amanita cf. lavendula collections in eastern North America, Mexico, and Costa Rica were found to consist of four cryptic taxa, one of which exhibited consistently unreadable nuclear rDNA ITS1-5.8S-ITS2 (fungal barcode) sequences after ITS1 base 130. This taxon is designated here as Amanita cf. lavendula taxon 1. ITS sequences from dikaryotic basidiomata were cloned, but sequences recovered from cloning did not segregate into distinct haplotypes. Rather, there was a mix of haplotypes that varied among themselves predominantly at 28 ITS positions. Analysis of each of these 28 variable bases showed predominantly two alternate bases at each position. Based on these findings and additional sequence data from the nuclear rDNA 28S, RNA polymerase II subunit 2 (RPB2) and mitochondrial rDNA small subunit (SSU) and 23S genes, we speculate that taxon 1 represents an initial hybridization event between two divergent taxa followed by failure of the ribosomal repeat to homogenize. Homogenization failure may be a result of repeated hybridization between divergent internal transcribed spacer (ITS) types with inadequate time for concerted evolution of the ribosomal repeat or, alternately, a complete failure of the ribosomal homogenization process. To our knowledge, this finding represents the first report of a geographically widespread taxon (Canada, eastern USA, Costa Rica) with apparent homogenization failure across all collections. Findings such as these have implications for fungal barcoding efforts and the application of fungal barcodes in identifying environmental sequences.
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http://dx.doi.org/10.1080/00275514.2018.1427402DOI Listing
December 2018

Drink Less Enjoy More: effects of a multi-component intervention on improving adherence to, and knowledge of, alcohol legislation in a UK nightlife setting.

Addiction 2018 08 23;113(8):1420-1429. Epub 2018 Apr 23.

Policy Research and International Development Directorate, Public Health Wales, Cardiff, UK.

Aims: To estimate the association between implementation of a community-based multi-component intervention (Drink Less Enjoy More) and sales of alcohol to pseudo-intoxicated patrons and nightlife patron awareness of associated legislation.

Design: Cross-sectional pre-intervention and follow-up measurements, including alcohol test purchases (using pseudo-intoxicated patrons) in licensed premises (stratified random sample; 2013, 2015) and a survey with nightlife patrons (convenience sample; 2014, 2015).

Setting: One UK municipality with a large night-time economy.

Participants: Licensed premises (pre = 73; follow-up = 100); nightlife patrons (pre = 214; follow-up = 202).

Intervention: The Drink Less Enjoy More intervention included three interacting components: community mobilization and awareness-raising; responsible bar server training; and active law enforcement of existing legislation prohibiting sales of alcohol to, and purchasing of alcohol for, a person who appears to be alcohol intoxicated: 'intoxicated', herein for economy.

Measurements: The primary outcomes were alcohol service refusal to pseudo-intoxicated patrons and nightlife patron knowledge of alcohol legislation (illegal to sell alcohol to, and purchase alcohol for, intoxicated people), adjusted for potential confounders including characteristics of the area, venue, test purchase and nightlife patron.

Findings: Pre-intervention, 16.4% of alcohol sales were refused, compared with 74.0% at follow-up (P < 0.001). In adjusted analyses, the odds of service refusal were higher at follow-up [adjusted odds ratio (aOR) = 14.63, P < 0.001]. Service refusal was also associated with server gender and patron drunkenness within the venue. Among drinkers, accurate awareness of alcohol legislation was higher at follow-up (sales: pre = 44.5%; follow-up = 66.0%; P < 0.001/purchase: pre = 32.5%; follow-up = 56.0%; P < 0.001). In adjusted analyses, knowledge of legislation was higher at follow-up (sales: aOR = 2.73, P < 0.001; purchasing: aOR = 2.73, P < 0.001). Knowledge of legislation was also associated with participant age (purchasing) and expectations of intoxication (sales).

Conclusion: A community-based multi-component intervention concerning alcohol sales legislation in the United Kingdom (UK) was associated with a reduction in sales of alcohol to pseudo-intoxicated patrons in on-licensed premises in a UK nightlife setting and an improvement in nightlife patron awareness of associated legislation.
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http://dx.doi.org/10.1111/add.14223DOI Listing
August 2018