EU Institutional Politics of Secrecy and Transparency in Foreign Affairs: A Commentary

International diplomacy has long been regarded as the domain of an elite hand-picked few, instructed and groomed in something considered an art form. Both the secrecy and the pomp have their rational place. Political interventions from regime change through to more standard economic and social challenges cue both subtle and dramatic shifts in relationships and alignments and diplomats must rightly handle such situations with great delicacy. Premature or too much public disclosure about diplomatic exchanges could risk undermining the mutual trust and confidence on which the conduct of international relations and negotiations depends. The question of course concerns the determination of what constitutes 'premature' or 'too much' and who decides the point at which public access can or should occur. We have certainly seen a trend towards greater transparency in foreign affairs in recent times, but this will always remain one of the most sensitive areas for national governments and international organisations. Contributors to this publication pose important questions about transparency in the context of foreign affairs at EU level. The question 'How much is enough?' is particularly pertinent. I welcome the exploration of topics of secrecy and transparency in this thematic issue and look forward to further contributions as the theory and practice of the ideas put forward are developed

Five minutes with the European Ombudsman, Emily O’Reilly: “Citizens need to be honest and empower themselves to reach out to institutions”

The principle of European citizenship was introduced by the Maastricht Treaty and came into force in 1993. To mark the 20th anniversary of European citizenship, 2013 was officially designated the ‘European Year of Citizens’, with the aim of raising awareness about the rights of citizens living across the EU. EUROPP’s Assistant Editor Eri Bertsou spoke to the European Ombudsman, Emily O’Reilly, about the importance of European citizenship, and the wider role of civil society organisations in EU politics

Integrated dataset on acute phase protein response in chicken challenged with Escherichia coli lipopolysaccharide endotoxin

Data herein describe the quantitative changes in the plasma proteome in chickens challenged with lipopolysaccharide (LPS), a bacterial endotoxin known to stimulate the host innate immune system obtained by shotgun quantitative proteomic tandem mass tags approach using high-resolution Orbitrap technology. Statistical and bioinformatic analyses were performed to specify the effect of bacterial endotoxin. Plasma from chicken (N=6) challenged with Escherichia coli (LPS) (2 mg/kg body weight) was collected pre (0 h) and at 12, 24, 48, and 72 h post injection along with plasma from a control group (N=6) challenged with sterile saline. Protein identification and relative quantification were performed using Proteome Discoverer, and data were analysed using R. Gene Ontology terms were analysed by the Cytoscape application ClueGO based on Gallus gallus GO Biological Process database, and refined by REVIGO. Absolute quantification of several acute phase proteins, e.g. alpha-1-acid glycoprotein (AGP), serum amyloid A (SAA) and ovotrensferrin (OVT) was performed by immunoassays to validate the LC-MS results. The data contained within this article are directly related to our research article”Quantitative proteomics using tandem mass tags in relation to the acute phase protein response in chicken challenged with Escherichia coli lipopolysaccharide endotoxin” [1]. The raw mass spectrometric data generated in this study were deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD009399 (http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD009399)

Acute phase proteins and biomarkers for health in chickens

Acute phase proteins (APPs) are proteins synthesised predominantly in the liver, whose plasma concentrations increase (positive APP) or decrease (negative APP) as a result of infection, inflammation, trauma and tissue injury. They also change as a result of the introduction of immunogens such as bacterial lipopolysaccharide (LPS), turpentine and vaccination. While publications on APPs in chickens are numerous, the limited availability of anti-sera and commercial ELISAs has resulted in a lot of information on only a few APPs. Disease is a threat to the poultry industry, as pathogens have the potential to evolve, spread and cause rapid onset of disease that is detrimental to the welfare of birds. Low level, sub-acute disease with non-specific, often undiagnosed causes can greatly affect bird health and growth and impact greatly on productivity and profitability. Developing and validating methods to measure and characterise APPs in chickens will allow these proteins to be used diagnostically for monitoring flock health. Using immune parameters such as APPs that correlate with disease resistance or improvements in production and welfare will allow the use of APPs as selection parameters for breeding to be evaluated. For APPs to be useful parameters on which to evaluate chicken health, information on normal APP concentrations is required. Ceruloplasmin (Cp) and PIT54 concentrations were found to be much lower in healthy birds form commercial production farms than the reported normal values obtained from the literature. These APPs were found to be significantly higher in culled birds from a commercial farm and Cp, PIT54 and ovotransferrin (Ovt) were significantly higher in birds classified as having obvious gait defects. Using quantitative shotgun proteomics to identify the differentially abundant proteins between three pools: highly acute phase (HAP), acute phase (AP) and non-acute phase (NAP), generated data from which a selection of proteins, based on the fold difference between the three pools was made. These proteins were targeted on a individual samples alongside proteins known to be APPs in chickens or other species: serum amyloid A (SAA), C-reactive protein (CRP), Ovt, apolipoprotein A-I (apo-AI), transthyretin (Ttn), haemopexin (Hpx) and PIT54. Together with immunoassay data for SAA, Ovt, alpha-1-acid glycoprotein (AGP) and Cp the results of this research reveal that SAA is the only major APP in chickens. Ovotransferrin and AGP behave as moderate APPs while PIT54 and Cp are minor APPs. Haemopexin was not significantly different between the three acute phase groups. Apolipoprotein AI and Ttn were significantly lower in the HAP and AP groups and as such can be classed as negative APPs. In an effort to identify CRP, multiple anti-sera cross reacting with CRP from other species were used and a phosphorylcholine column known to affinity purify CRP were used. Enriched fractions containing low molecular weight proteins, elutions from the affinity column together with HAP, AP and NAP pooled samples were applied to a Q-Exactive Hybrid Quadrupole–Orbitrap mass spectrometer (Thermo Scientific) for Shotgun analysis and CRP was not identified. It would appear that CRP is not present as a plasma protein constitutively or during an APR in chickens and as such is not an APP in this species. Of the proteins targeted as possible novel biomarkers of the APR in chickens mannan binding lectin associated serine protease-2, α-2-HS-glycoprotein (fetuin) and major facilitator superfamily domain-containing protein 10 were reduced in abundance in the HAP group, behaving as negative biomarkers. Myeloid protein and putative ISG(12)2 were positively associated with the acute phase being significantly higher in the HAP and AP groups. The protein cathepsin D was significantly higher in both HAP and AP compared to the NAP indicating that of all the proteins targeted, this appears to have the most potential as a biomarker of the acute phase, as it was significantly increased in the AP as well as the HAP group. To evaluate APPs and investigate biomarkers of intestinal health, a study using re-used poultry litter was undertaken. The introduction of litter at 12 days of age did not significantly increase any APPs measured using immunoassays and quantitative proteomics at 3, 6 and 10 days post introduction. While no APP was found to be significantly different between the challenged and control groups at anytime point, the APPs AGP, SAA and Hpx did increase over time in all birds. The protein apolipoprotein AIV (apo-AIV) was targeted as a possible APP and because of its reported role in controlling satiety. An ELISA was developed, successfully validated and used to measure apo-AIV in this study. While no significant differences in apo-AIV plasma concentrations between challenged and control groups were identified apo-AIV plasma concentrations did change significantly between certain time points in challenged and control groups. Apoliporotein AIV does not appear to behave as an APP in chickens, as it was not significantly different between acute phase groups. The actin associated proteins villin and gelsolin were investigated as possible biomarkers of intestinal health. Villin was found not to be present in the plasma of chickens and as such not a biomarker target. Gelsolin was found not to be differentially expressed during the acute phase or as a result of intestinal challenge. Finally a proteomic approach was undertaken to investigate gastrocnemius tendon (GT) rupture in broiler chickens with a view of elucidating to and identify proteins associated with risk of rupture. A number of proteins were found to be differentially expressed between tendon pools and further work would enable further detailing of these findings. In conclusion this work has made a number of novel findings and addressed a number of data poor areas. The area of chicken APPs research has stagnated over the last 15 years with publications becoming repetitive and reliant on a small number of immunoassays. This work has sought to characterise the classic APPs in chickens, and use a quantitative proteomic approach to measure and categorise them. This method was also used to take a fresh approach to biomarker identification for both the APR and intestinal health. The development and validation of assays for Ovt and apo-AIV and the shotgun data mean that these proteins can be further characterised in chickens with a view of applying their measurement to diagnostics and selective breeding programs

An immunoturbidimetric assay for bovine haptoglobin

In cattle, the serum protein haptoglobin (Hp) is a major acute phase protein (APP) that rises in concentration over a thousand fold following stimulation by pro-inflammatory cytokines. As such, this APP is a valuable biomarker for infection, inflammation and trauma in cattle. The assay for bovine Hp is becoming more commonplace in clinical pathology and in experimental studies when a biomarker of innate immunity is required. The most widely used assay for Hp utilises its binding to haemoglobin (Hp-Hb binding assay), which at low pH enables the preservation of the native peroxidase activity in the haemoglobin. This assay is used for all species, including species such as dog, cat and pig where the level of Hp is higher in healthy animals of these species than in healthy cattle, and therefore a bovine-specific immunoassay that can be automated would be desirable. Thus, a novel-automated species-specific immunoturbidimetric (IT) assay has been developed. Validation studies showed intra- and inter-assay CVs of below 5% and 9% respectively and a recovery of 99% from samples spiked with bovine Hp and a limit of quantification of 0.033 g/L. The assay is not affected by icterus or lipaemia but had moderate interference from haemoglobin and showed a significant correlation with the Hp-Hb binding assay. This novel IT assay for bovine Hp will allow automated analysis of this important bovine APP to identify changes in the Hp concentration not detectable by current Hp-Hb binding assays. It will enable the incorporation of this assay into herd health assessments, animal welfare analysis and for bovine medicine and research

Point-of-care tests for bovine clinical mastitis: what do we have and what do we need?

Mastitis, inflammation of the bovine mammary gland, is generally caused by intramammary infection with bacteria, and antimicrobials have long been a corner stone of mastitis control. As societal concern about antimicrobial use in animal agriculture grows, there is pressure to reduce antimicrobial use in dairy farming. Point-of-care tests for on-farm use are increasingly available as tools to support this. In this Research Reflection, we consider available culture-dependent and culture-independent tests in the context of ASSURED criteria for low-resource settings, including convenience criteria, scientific criteria and societal criteria that can be used to evaluate test performance. As tests become more sophisticated and sensitive, we may be generating more data than we need. Special attention is given to the relationship between test outcomes and treatment decisions, including issues of diagnostic refinement, antimicrobial susceptibility testing, and detection of viable organisms. In addition, we explore the role of technology, big data and people in improved performance and uptake of point-of-care tests, recognising that societal barriers may limit uptake of available or future tests. Finally, we propose that the 3Rs of reduction, refinement and replacement, which have been used in an animal welfare context for many years, could be applied to antimicrobial use for mastitis control on dairy farms

Tooling-up for infectious disease transmission modelling.

In this introduction to the Special Issue on methods for modelling of infectious disease epidemiology we provide a commentary and overview of the field. We suggest that the field has been through three revolutions that have focussed on specific methodological developments; disease dynamics and heterogeneity, advanced computing and inference, and complexity and application to the real-world. Infectious disease dynamics and heterogeneity dominated until the 1980s where the use of analytical models illustrated fundamental concepts such as herd immunity. The second revolution embraced the integration of data with models and the increased use of computing. From the turn of the century an emergence of novel datasets enabled improved modelling of real-world complexity. The emergence of more complex data that reflect the real-world heterogeneities in transmission resulted in the development of improved inference methods such as particle filtering. Each of these three revolutions have always kept the understanding of infectious disease spread as its motivation but have been developed through the use of new techniques, tools and the availability of data. We conclude by providing a commentary on what the next revoluition in infectious disease modelling may be

Support for my video is support for me: A YouTube scoping review of videos including adolescents with chronic pain

Adolescents with chronic pain report feelings of social isolation, of being different, and lack of understanding from peers. These challenges suggest that these adolescents may not obtain the social support they require. Thus, they may have to find other venues through which to find social support. Adolescents are heavy users of social media as a venue to share experience and obtain information and adolescents with chronic pain may be no different. A scoping review of YouTube was conducted by searching videos using the terms 'youth with chronic pain' and 'teens with chronic pain'. Videos in English, targeting at and including an adolescent with chronic pain were included. All identified videos were screened for eligibility until 20 consecutive videos were excluded. For each included video the first 5 related videos suggested by YouTube were screened for eligibility. This selection process resulted in 18 included videos, with a total of 936 comments. Recurring themes in the videos' comments were identified using qualitative content analysis. Videos content mainly covered multidisciplinary treatment options, alternative treatments and impact of pain on daily life. While a variety of treatment options were discussed, details of treatment content were lacking. Comments reflected the overarching message "you are not alone!" and mainly focused on providing and receiving support, sharing suffering, and revealing the impact of pain on relationships and daily life. Despite potential challenges associated with social media, YouTube may be a promising platform for provision of social support for adolescents with chronic pain

Variations in COVID-19 vaccination uptake among people in receipt of psychotropic drugs: cross-sectional analysis of a national population-based prospective cohort

BackgroundCoronavirus disease 2019 (COVID-19) has disproportionately affected people with mental health conditions.AimsWe investigated the association between receiving psychotropic drugs, as an indicator of mental health conditions, and COVID-19 vaccine uptake.MethodWe conducted a cross-sectional analysis of a prospective cohort of the Northern Ireland adult population using national linked primary care registration, vaccination, secondary care and pharmacy dispensing data. Univariable and multivariable logistic regression analyses investigated the association between anxiolytic, antidepressant, antipsychotic, and hypnotic use and COVID-19 vaccination status, accounting for age, gender, deprivation and comorbidities. Receiving any COVID-19 vaccine was the primary outcome.ResultsThere were 1 433 814 individuals, of whom 1 166 917 received a COVID-19 vaccination. Psychotropic medications were dispensed to 267 049 people. In univariable analysis, people who received any psychotropic medication had greater odds of receiving COVID-19 vaccination: odds ratio (OR) = 1.42 (95% CI 1.41–1.44). However, after adjustment, psychotropic medication use was associated with reduced odds of vaccination (ORadj = 0.90, 95% CI 0.89–0.91). People who received anxiolytics (ORadj = 0.63, 95% CI 0.61–0.65), antipsychotics (ORadj = 0.75, 95% CI 0.73–0.78) and hypnotics (ORadj = 0.90, 95% CI 0.87–0.93) had reduced odds of being vaccinated. Antidepressant use was not associated with vaccination (ORadj = 1.02, 95% CI 1.00–1.03).ConclusionsWe found significantly lower odds of vaccination in people who were receiving treatment with anxiolytic and antipsychotic medications. There is an urgent need for evidence-based, tailored vaccine support for people with mental health conditions

Investigating the uptake, effectiveness and safety of COVID-19 vaccines : protocol for an observational study using linked UK national data

Funding: This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (HDRUK2020.146). EAVE II is funded by the Medical Research Council (MC_PC_19075) and supported by the Scottish Government. This work is supported by BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004). BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. ConCOV is supported by the Medical Research Council (MR/V028367/1); Health Data Research UK (HDR-9006) which receives its funding from the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation (BHF) and the Wellcome Trust; and Administrative Data Research UK which is funded by the Economic and Social Research Council (grant ES/S007393/1).Introduction : The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK. Methods and analysis : We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case–control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations. Ethics and dissemination : We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital’s Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.Publisher PDFPeer reviewe