Problems in FMD eradication : a way forward?

The authors would like to acknowledge the support of the Wellcome Trust (eGrantsref. No. 8048) and Biotechnology and Biological Sciences Research Council (BBSRC; Grants BB/K003801/1 and BB/L004526/1).Foot and Mouth Disease Virus (FMDV) is one of the most commonly reported OIE-listed pathogens. FMDV is one of the most contagious mammalian viruses known to man: the virus is endemic in many developing countries causing substantial economic loses and the restriction of international trade in animals/animal products. The virus infects domestic animals (cattle, pigs, sheep, goats), but also a wide range of wild-life species, the latter forming reservoirs of disease. The need to diagnose FMDV infections (serotype/strain identification) and vaccine production/testing requires expensive, high disease security/containment facilities. Chemically inactivated (‘killed’) vaccines have been available for decades, but the huge genetic diversity of this virus (7 serotypes with 1000s of subtypes) and the need to periodically re-vaccinate animals to maintain protective levels of antibodies argue for the development of new vaccines. Indeed, in the early 1990s, on the basis of a cost-benefit analysis, the European Union replaced the policy of routine vaccination using the inactivated vaccine with disease control via mass-slaughter of infected and surrounding susceptible animals (plus vaccination in extremis). For various reasons mass-slaughter is unacceptable in many developing countries so in their case vaccination, in one form or another, is the only way forward. In the past few years there have been exciting developments in the production of new types of vaccine and many hold great prospects for improving disease control, but the thesis of this paper is that only the development of a new type of vaccine – live, attenuated, FMDV strains, offers the prospect of eradicating FMDV.Publisher PDFPeer reviewe

Expression and immunogenicity of secreted forms of bovine ephemeral fever virus glycoproteins applied to subunit vaccine development

This study was support by grants from the Taiwan Ministry of Science and Technology (MOST-106-2911-I-020-501; MOST-107-2313-B-020-011-MY3) and the UK Biotechnology and Biological Sciences Research Council (BB/P025080/1).Aims  Vaccines for bovine ephemeral fever virus (BEFV) are available but are difficult to produce, expensive, or suffer from genetic instability. Therefore, we designed constructs encoding C-terminally truncated forms (transmembrane anchoring region deleted) of glycoproteins G and GNS such that they were secreted from the cell into the media to achieve high-level antigen expression, correct glycosylation pattern, and enable further simple purification with the V5 epitope tag. Methods and Results  In this study, synthetic biology was employed to create membrane-bound and secreted forms of G and GNS glycoprotein. Mammalian cell culture was employed as an antigen expression platform, and the secreted forms of G and GNS protein were easily purified from media by using a highly effective, single-step method. The V5 epitope tag was genetically fused to the C-termini of the proteins, enabling detection of the antigen through immunoblotting and immunomicroscopy. Our data demonstrated that the C-terminally truncated form of the G glycoprotein was efficiently secreted from cells into the cell media. Moreover, the immunogenicity was confirmed in mice test. Conclusions  The immuno-dot blots showed that the truncated G glycoprotein was present in the total cell extract, and was clearly secreted into the media, consistent with the western blotting data and live-cell images. Our strategy presented the expression of secreted, epitope-tagged, forms of the BEFV glycoproteins such that appropriately glycosylated forms of BEFV G protein was secreted from the BHK-21 cells. This indicates that high-level expression of secreted G glycoprotein is a feasible strategy for large-scale production of vaccines and improving vaccine efficacy. Significance and Impact of the Study The antigen expression strategy designed in this study can produce high-quality recombinant protein and reduce the amount of antigen used in the vaccine.PostprintPeer reviewe

Using routine clinical and administrative data to produce a dataset of attendances at Emergency Departments following self-harm

Background: Self-harm is a significant public health concern in the UK. This is reflected in the recent addition to the English Public Health Outcomes Framework of rates of attendance at Emergency Departments (EDs) following self-harm. However there is currently no source of data to measure this outcome. Routinely available data for inpatient admissions following self-harm miss the majority of cases presenting to services. Methods: Using the Clinical Record Interactive Search system, the electronic health records (EHRs) used in four EDs were linked to Hospital Episode Statistics to create a dataset of attendances following self-harm. This dataset was compared with an audit dataset of ED attendances created by manual searching of ED records. The proportion of total cases detected by each dataset was compared. Results: There were 1932 attendances detected by the EHR dataset and 1906 by the audit. The EHR and audit datasets detected 77 and 76 of all attendances respectively and both detected 82 of individual patients. There were no differences in terms of age, sex, ethnicity or marital status between those detected and those missed using the EHR method. Both datasets revealed more than double the number of self-harm incidents than could be identified from inpatient admission records. Conclusions: It was possible to use routinely collected EHR data to create a dataset of attendances at EDs following self-harm. The dataset detected the same proportion of attendances and individuals as the audit dataset, proved more comprehensive than the use of inpatient admission records, and did not show a systematic bias in those cases it missed. © 2015 Polling et al

Factors associated with use of psychiatric intensive care and seclusion in adult inpatient mental health services

Aims.Within acute psychiatric inpatient services, patients exhibiting severely disturbed behaviour can be transferred to a psychiatric intensive care unit (PICU) and/or secluded in order to manage the risks posed to the patient and others. However, whether specific patient groups are more likely to be subjected to these coercive measures is unclear. Using robust methodological and statistical techniques, we aimed to determine the demographic, clinical and behavioural predictors of both PICU and seclusion.Methods.Data were extracted from an anonymised database comprising the electronic medical records of patients within a large South London mental health trust. Two cohorts were derived, (1) a PICU cohort comprising all patients transferred from general adult acute wards to a non-forensic PICU ward between April 2008 and April 2013 (N = 986) and a randomly selected group of patients admitted to general adult wards within this period who were not transferred to PICU (N = 994), and (2) a seclusion cohort comprising all seclusion episodes occurring in non-forensic PICU wards within the study period (N = 990) and a randomly selected group of patients treated in these wards who were not secluded (N = 1032). Demographic and clinical factors (age, sex, ethnicity, diagnosis, admission status and time since admission) and behavioural precursors (potentially relevant behaviours occurring in the 3 days preceding PICU transfer/seclusion or random sample date) were extracted from electronic medical records. Mixed effects, multivariable logistic regression analyses were performed with all variables included as predictors.Results.PICU cases were significantly more likely to be younger in age, have a diagnosis of bipolar disorder and to be held on a formal section compared with patients who were not transferred to PICU; female sex and longer time since admission were associated with lower odds of transfer. With regard to behavioural precursors, the strongest predictors of PICU transfer were incidents of physical aggression towards others or objects and absconding or attempts to abscond. Secluded patients were also more likely to be younger and legally detained relative to non-secluded patients; however, female sex increased the odds of seclusion. Likelihood of seclusion also decreased with time since admission. Seclusion was significantly associated with a range of behavioural precursors with the strongest associations observed for incidents involving restraint or shouting.Conclusions.Whilst recent behaviour is an important determinant, patient age, sex, admission status and time since admission also contribute to risk of PICU transfer and seclusion. Alternative, less coercive strategies must meet the needs of patients with these characteristics

Geospatial information infrastructures

Manual of Digital Earth / Editors: Huadong Guo, Michael F. Goodchild, Alessandro Annoni .- Springer, 2020 .- ISBN: 978-981-32-9915-3Geospatial information infrastructures (GIIs) provide the technological, semantic,organizationalandlegalstructurethatallowforthediscovery,sharing,and use of geospatial information (GI). In this chapter, we introduce the overall concept and surrounding notions such as geographic information systems (GIS) and spatial datainfrastructures(SDI).WeoutlinethehistoryofGIIsintermsoftheorganizational andtechnologicaldevelopmentsaswellasthecurrentstate-of-art,andreflectonsome of the central challenges and possible future trajectories. We focus on the tension betweenincreasedneedsforstandardizationandtheever-acceleratingtechnological changes. We conclude that GIIs evolved as a strong underpinning contribution to implementation of the Digital Earth vision. In the future, these infrastructures are challengedtobecomeflexibleandrobustenoughtoabsorbandembracetechnological transformationsandtheaccompanyingsocietalandorganizationalimplications.With this contribution, we present the reader a comprehensive overview of the field and a solid basis for reflections about future developments

Institutions, Human Capital, and Development

In this article, we revisit the relationship among institutions, human capital, and development. We argue that empirical models that treat institutions and human capital as exogenous are misspecified, both because of the usual omitted variable bias problems and because of differential measurement error in these variables, and that this misspecification is at the root of the very large returns of human capital, about four to five times greater than that implied by micro (Mincerian) estimates, found in the previous literature. Using cross-country and cross-regional regressions, we show that when we focus on historically determined differences in human capital and control for the effect of institutions, the impact of institutions on long-run development is robust, whereas the estimates of the effect of human capital are much diminished and become consistent with micro estimates. Using historical and cross-country regression evidence, we also show that there is no support for the view that differences in the human capital endowments of early European colonists have been a major factor in the subsequent institutional development of former colonies.Comisión Nacional de Investigación Ciencia y Tecnología (Chile) (CONICYT/Programa de Investigación Asociativa (project SOC1102))United States. Army Research Office (ARO MURI W911NF-12-1-0509

FMDV replicons encoding green fluorescent protein are replication competent

The study of replication of viruses that require high bio-secure facilities can be accomplished with less stringent containment using non-infectious 'replicon' systems. The FMDV replicon system (pT7rep) reported by Mclnerney et al. (2000) was modified by the replacement of sequences encoding chloramphenicol acetyl-transferase (CAT) with those encoding a functional L proteinase (Lpro) linked to a bi-functional fluorescent/antibiotic resistance fusion protein (green fluorescent protein/puromycin resistance, [GFP-PAC]). Cells were transfected with replicon-derived transcript RNA and GFP fluorescence quantified. Replication of transcript RNAs was readily detected by fluorescence, whilst the signal from replication-incompetent forms of the genome was >2-fold lower. Surprisingly, a form of the replicon lacking the Lpro showed a significantly stronger fluorescence signal, but appeared with slightly delayed kinetics. Replication can, therefore, be quantified simply by live-cell imaging and image analyses, providing a rapid and facile alternative to RT-qPCR or CAT assays

The passive surveillance of ticks using companion animal electronic health records

Ticks represent a large global reservoir of zoonotic disease. Current surveillance systems can be time and labour intensive. We propose that the passive surveillance of companion animal electronic health records (EHRs) could provide a novel methodology for describing temporal and spatial tick activity. A total of 16 58 857 EHRs were collected over a 2-year period (31 March 2014 and 29 May 2016) from companion animals attending a large sentinel network of 192 veterinary clinics across Great Britain (the Small Animal Veterinary Surveillance Network - SAVSNET). In total, 2180 EHRs were identified where a tick was recorded on an animal. The relative risk of dogs presenting with a tick compared with cats was 0·73 (95% confidence intervals 0·67-0·80). The highest number of tick records were in the south central regions of England. The presence of ticks showed marked seasonality with summer peaks, and a secondary smaller peak in autumn for cats; ticks were still being found throughout most of Great Britain during the winter. This suggests that passive surveillance of companion animal EHRs can describe tick activity temporally and spatially in a large cohort of veterinary clinics across Great Britain. These results and methodology could help inform veterinary and public health messages as well as increase awareness of ticks and tick-borne diseases in the general population

In-patient treatment in functional and sectorised care: patient satisfaction and length of stay.

BACKGROUND: Debate exists as to whether functional care, in which different psychiatrists are responsible for in- and out-patient care, leads to better in-patient treatment as compared with sectorised care, in which the same psychiatrist is responsible for care across settings. Aims To compare patient satisfaction with in-patient treatment and length of stay in functional and sectorised care. METHOD: Patients with an ICD-10 diagnosis of psychotic, affective or anxiety/somatoform disorders consecutively admitted to an adult acute psychiatric ward in 23 hospitals across 11 National Health Service trusts in England were recruited. Patient satisfaction with in-patient care and length of stay (LoS) were compared (trial registration ISRCTN40256812). RESULTS: In total, 2709 patients were included, of which 1612 received functional and 1097 sectorised care. Patient satisfaction was significantly higher in sectorised care (β = 0.54, 95% CI 0.35-0.73, P<0.001). This difference remained significant when adjusting for locality and patient characteristics. LoS was 6.9 days shorter for patients in sectorised care (β = -6.89, 95% CI -11.76 to -2.02, P<0.001), but this difference did not remain significant when adjusting for clustering by hospital (β = -4.89, 95% CI -13.34 to 3.56, P = 0.26). CONCLUSIONS: This is the first robust evidence that patient satisfaction with in-patient treatment is higher in sectorised care, whereas findings for LoS are less conclusive. If patient satisfaction is seen as a key criterion, sectorised care seems preferable. Declarations of interest None.European Commission 7th Framework Programme. Grant agreement number 602645