Application of Global Burden of Animal Diseases methods at country level: experiences of the Ethiopia case study.

Animals play a central role in human livelihoods and welfare. Animal diseases have a great impact on the benefits humans derive from animals and can also pose a risk to human health. Better control of animal diseases generates wider societal benefits, including reducing the climate and ecological impacts of livestock and improving animal welfare. To better understand the scale of investment justified for the control and prevention of animal disease, the wide-ranging impacts of disease on animal production and health must be measured. The Global Burden of Animal Diseases (GBADs) programme is quantifying animal disease burden from the local to global levels. The GBADs programme includes country case studies for national- and local-level analysis. Ethiopia is the first case study country in which GBADs methods have been applied. GBADs'Ethiopia case study consists of three activity areas: i) stakeholder engagement; ii) livestock disease burden estimation, including data collection, analytics, evidence generation and communication; and iii) capacity building in animal health economics. At the start of the case study, various stakeholder communication platforms were used to familiarise stakeholders with GBADs and engage their support in various ways, including data access, and, through this engagement, to ensure the programme tools and outputs were relevant and useful to their needs. Existing data were retrieved from multiple sources and used to estimate disease burden. This process involved multiple steps, including estimation of biomass and economic value, the Animal Health Loss Envelope (farm-level disease burden), wider economic impacts and attribution of the disease burden to different levels of causes. This was carried out for major livestock species (cattle, sheep, goats and poultry) in Ethiopia. Capacity building on animal health economics was carried out for GBADs end users to increase competence in utilising animal health economic evidence, including GBADs outputs. This article documents experiences of the implementation of these activities in the GBADs Ethiopia case study.

Les animaux représentent une part substantielle des moyens de subsistance et contribuent de manière essentielle au bien-être humain. Les bénéfices que l'humanité peut retirer des animaux sont toutefois compromis par les maladies animales, qui font aussi peser un risque sur la santé publique. Les avantages sociétaux d'un meilleur contrôle des maladies animales dépassent la portée strictement sanitaire et recouvrent notamment l'atténuation de l'impact climatique et environnemental des animaux d'élevage et l'amélioration du bien-être animal. Pour mieux appréhender l'échelle des investissements requis pour contrôler et prévenir les maladies animales, il convient de mesurer les impacts très divers de ces maladies sur la production et la santé animales. Le programme " Impact mondial des maladies animales " (GBADs) procède actuellement à la quantification de la charge des maladies animales, du niveau local au niveau mondial. Il comprend aussi des études de cas conduites dans des pays choisis pour une analyse à l'échelle nationale, voire locale. L'Ethiopie est le premier pays à avoir fait l'objet d'une étude de cas nationale reprenant les méthodes du GBADs. L'étude comportait trois volets d'activités : i) la mobilisation des parties prenantes ; ii) l'estimation de la charge des maladies chez les animaux d'élevage, notamment la collecte de données, leur analyse, l'apport d'éléments probants et la communication ; et iii) le renforcement des capacités en économie de la santé animale. Au lancement de l'étude, plusieurs plateformes de communication professionnelles ont été utilisées pour mieux faire connaître le GBADs aux différents acteurs et solliciter leur soutien de diverses manières, en particulier en termes d'accès aux données, et pour s'assurer, grâce à cette mobilisation, que les outils et les résultats du programme étaient pertinents pour eux et répondaient à leurs besoins. Les données existantes ont été recueillies auprès de multiples sources et ont permis d'estimer la charge sanitaire. Ce processus comportait plusieurs étapes, dont l'estimation de la biomasse et de la valeur économique, la définition de l'enveloppe des pertes sanitaires animales (charge sanitaire à l'échelle des exploitations), l'appréciation des effets économiques au sens large et la répartition de la charge sanitaire en fonction des niveaux des causes attribuées. Les analyses portaient sur les principales espèces d'animaux d'élevage (bovins, ovins, caprins et volailles) en Ethiopie. Des activités de renforcement des capacités en économie de la santé animale ont été proposées aux utilisateurs finaux du GBADs afin de les former à l'utilisation des preuves économiques en santé animale. Les auteurs expliquent comment s'est déroulée la mise en oeuvre de ces activités lors de l'étude du GBADs conduite en Ethiopie.

Los animales desempeñan un papel fundamental en los medios de subsistencia y el bienestar humanos. En este sentido, las enfermedades animales tienen un gran impacto en los beneficios que los humanos obtienen de los animales y también pueden suponer un riesgo para la salud humana. Un mejor control de las enfermedades animales genera beneficios sociales más amplios, como la reducción del impacto climático y ecológico de la ganadería y la mejora del bienestar animal. Para comprender mejor la magnitud de la inversión justificada para el control y la prevención de las enfermedades animales, es preciso medir las amplias repercusiones de las enfermedades en la producción y la sanidad animal. El programa sobre el impacto global de las enfermedades animales (GBADs) cuantifica el impacto de las enfermedades animales desde el nivel local hasta el mundial. El programa GBADs incluye estudios de casos por países a fin de realizar un análisis a escala nacional y local. Etiopía es el primer país en el que se han aplicado los métodos del GBADs. El estudio de caso del GBADs en dicho país se divide en tres áreas de actividad: i) la participación de las partes interesadas; ii) la estimación del impacto de las enfermedades del ganado, incluida la recopilación de datos, el análisis, la generación de pruebas y la comunicación; y iii) el desarrollo de capacidades en el ámbito de la economía de la sanidad animal. Al inicio del estudio de caso, se utilizaron diversas plataformas de comunicación con las partes interesadas para familiarizarlas con el GBADs y recabar su apoyo a través de diversas vías, entre las que se incluía el acceso a los datos, y, mediante esta colaboración, garantizar que las herramientas y los resultados del programa fueran pertinentes y útiles para sus necesidades. Se obtuvieron datos de diversas fuentes que se utilizaron para estimar el impacto de las enfermedades. Este proceso implicó múltiples pasos, incluida la estimación de la biomasa y el valor económico, la cartera de pérdidas en sanidad animal (impacto de las enfermedades a nivel de explotación), los impactos económicos más amplios y la atribución del impacto de las enfermedades a diferentes categorías de causas. Esto se llevó a cabo para las principales especies ganaderas (bovinos, ovinos, caprinos y aves de corral) en Etiopía. Se realizaron actividades de capacitación en economía de la sanidad animal para los usuarios finales con el fin de aumentar su competencia en la utilización de los datos económicos sobre sanidad animal, incluidos los resultados del GBADs. Este artículo documenta las experiencias de la puesta en práctica de estas actividades en el estudio de caso del GBADs en Etiopía.

Outcomes of patients with exomphalos and associated congenital heart diseases.

INTRODUCTION: Exomphalos is an anterior abdominal wall defect resulting in herniation of contents into the umbilical cord. Severe associated chromosomal anomalies and congenital heart disease (CHD) are known to influence mortality, but it is not clear which cardiac anomalies have the greatest impact on survival. METHODS: We performed a retrospective review of the treatment and outcome of patients with exomphalos over a 30-year period (1990-2020), with a focus on those with the combination of exomphalos major and major CHD (EMCHD). RESULTS: There were 123 patients with exomphalos identified, 59 (48%) had exomphalos major (ExoMaj) (defect > 5 cm or containing liver), and 64 (52%) exomphalos minor (ExoMin). In the ExoMaj group; 17% had major CHD (10/59), M:F 28:31, 29% premature (< 37 weeks, 17/59) and 14% had low birth-weight (< 2.5 kg, 8/59). In the ExoMin group; 9% had major CHD (6/64), M:F 42:22, 18% premature and 10% had low birth-weight. The 5-year survival was 20% in the EMCHD group versus 90% in the ExoMaj with minor or no CHD [p < 0.0001]. Deaths in the EMCHD had mainly right heart anomalies and all of them required mechanical ventilation (MV) for pulmonary hypoplasia prior to cardiac intervention. In contrast, survivors did not require mechanical ventilation prior to cardiac intervention. CONCLUSION: EMCHD is associated with high mortality. The most significant finding was high mortality in those with right heart anomalies in combination with pulmonary hypoplasia, especially if pre-intervention mechanical ventilation is required.

The fingerprint of a flow: wrinkle patterns in nonuniform coatings on pre-stretched soft foundations.

We study the wrinkle patterns obtained when applying a thin polymeric film on a uniaxially prestretched soft foundation. The film is coated onto a substrate where it drains under the action of gravity, thereby introducing a continuous variation in its thickness. We first study the fluid mechanics component of the problem and derive the coating profile as a function of the curing properties of the polymeric solution. Upon polymerization, the prestretch is released and yields the formation of wrinkles, which are arranged in organized patterns, including fractals. We study a variety of scenarios depending on the relative orientation of the gradient of film thickness and the stretching direction. In particular, we characterize and rationalize the distribution of singular events in our problem where wrinkles merge to allow a variation of the average value of the wrinkle wavelength across the sample.

Precision medicine for suicidality: from universality to subtypes and personalization.

Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies. Such markers may reflect and/or be a proxy for the core biology of suicide. We were successful in this endeavor, using a comprehensive stepwise approach, leading to a wealth of findings. Steps 1, 2 and 3 were discovery, prioritization and validation for tracking suicidality, resulting in a Top Dozen list of candidate biomarkers comprising the top biomarkers from each step, as well as a larger list of 148 candidate biomarkers that survived Bonferroni correction in the validation step. Step 4 was testing the Top Dozen list and Bonferroni biomarker list for predictive ability for suicidal ideation (SI) and for future hospitalizations for suicidality in independent cohorts, leading to the identification of completely novel predictive biomarkers (such as CLN5 and AK2), as well as reinforcement of ours and others previous findings in the field (such as SLC4A4 and SKA2). Additionally, we examined whether subtypes of suicidality can be identified based on mental state at the time of high SI and identified four potential subtypes: high anxiety, low mood, combined and non-affective (psychotic). Such subtypes may delineate groups of individuals that are more homogenous in terms of suicidality biology and behavior. We also studied a more personalized approach, by psychiatric diagnosis and gender, with a focus on bipolar males, the highest risk group. Such a personalized approach may be more sensitive to gender differences and to the impact of psychiatric co-morbidities and medications. We compared testing the universal biomarkers in everybody versus testing by subtypes versus personalized by gender and diagnosis, and show that the subtype and personalized approaches permit enhanced precision of predictions for different universal biomarkers. In particular, LHFP appears to be a strong predictor for suicidality in males with depression. We also directly examined whether biomarkers discovered using male bipolars only are better predictors in a male bipolar independent cohort than universal biomarkers and show evidence for a possible advantage of personalization. We identified completely novel biomarkers (such as SPTBN1 and C7orf73), and reinforced previously known biomarkers (such as PTEN and SAT1). For diagnostic ability testing purposes, we also examined as predictors phenotypic measures as apps (for suicide risk (CFI-S, Convergent Functional Information for Suicidality) and for anxiety and mood (SASS, Simplified Affective State Scale)) by themselves, as well as in combination with the top biomarkers (the combination being our a priori primary endpoint), to provide context and enhance precision of predictions. We obtained area under the curves of 90% for SI and 77% for future hospitalizations in independent cohorts. Step 5 was to look for mechanistic understanding, starting with examining evidence for the Top Dozen and Bonferroni biomarkers for involvement in other psychiatric and non-psychiatric disorders, as a mechanism for biological predisposition and vulnerability. The biomarkers we identified also provide a window towards understanding the biology of suicide, implicating biological pathways related to neurogenesis, programmed cell death and insulin signaling from the universal biomarkers, as well as mTOR signaling from the male bipolar biomarkers. In particular, HTR2A increase coupled with ARRB1 and GSK3B decreases in expression in suicidality may provide a synergistic mechanistical corrective target, as do SLC4A4 increase coupled with AHCYL1 and AHCYL2 decrease. Step 6 was to move beyond diagnostics and mechanistical risk assessment, towards providing a foundation for personalized therapeutics. Items scored positive in the CFI-S and subtypes identified by SASS in different individuals provide targets for personalized (psycho)therapy. Some individual biomarkers are targets of existing drugs used to treat mood disorders and suicidality (lithium, clozapine and omega-3 fatty acids), providing a means toward pharmacogenomics stratification of patients and monitoring of response to treatment. Such biomarkers merit evaluation in clinical trials. Bioinformatics drug repurposing analyses with the gene expression biosignatures of the Top Dozen and Bonferroni-validated universal biomarkers identified novel potential therapeutics for suicidality, such as ebselen (a lithium mimetic), piracetam (a nootropic), chlorogenic acid (a polyphenol) and metformin (an antidiabetic and possible longevity promoting drug). Finally, based on the totality of our data and of the evidence in the field to date, a convergent functional evidence score prioritizing biomarkers that have all around evidence (track suicidality, predict it, are reflective of biological predisposition and are potential drug targets) brought to the fore APOE and IL6 from among the universal biomarkers, suggesting an inflammatory/accelerated aging component that may be a targetable common denominator.

Veterinary and human vaccine evaluation methods.

Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines.

First Report of Grapevine leafroll-associated virus-2 and -3 in Texas Vineyards.

Grapevine leafroll disease (GLD), caused by the grapevine leafroll-associated viruses (GLRaVs, family Closteroviridae) is an important disease in all grapevine-growing regions of the world (2). It negatively affects vine vigor, fruit yield, and grape quality (e.g., sugar accumulation) (3). Typical disease symptoms include downward rolling of grape leaves accompanied by interveinal reddening in red-fruited varieties and interveinal chlorosis in white-fruited varieties (2). The state of Texas currently has over 275 commercial vineyards and acreage under grape production is expanding. Currently, there is limited information on the presence of either GLRaV-2 (genus Closterovirus) or GLRaV-3 (genus Ampelovirus) in this state. During the 2012 season, 19 individual, symptomatic grapevines (13 cv. Lenoir and 6 cv. Blanc du Bois) were sampled (14 petioles per vine) from one vineyard site in Richards, TX. Total nucleic acid was extracted from the samples as described before (5) and tested by RT-PCR using species specific primers to amplify a 334-bp fragment of the HSP70h gene of GLRaV-2 (L2 F: 5'-ATAATTCGGCGTACATCCCCACTT-3' and U2 R: 5'-GCCCTCCGCGCAACTAATGACAG-3') (1) and a 541-bp fragment of the HSP70h gene of GLRaV-3 (LC1 F: 5'-CGCTAGGGCTGTGGAAGTATT-3' and LC2 R: 5'-GTTGTCCCGGGTACCAGATAT-3') (4). Samples were also subjected to triple (TAS) and double (DAS) antibody sandwich ELISA for GLRaV-2 and GLRaV-3 using commercially available antibody test kits (AC Diagnostics, Fayetteville, AR). Five samples tested positive for GLRaV-2 and one for GLRaV-3, all from the variety Lenoir with no incidences of mixed infection. In addition to the RT-PCR and ELISA, the presence of GLRaV-2 and GLRaV-3 was confirmed by direct sequencing of select RT-PCR products, which was purified using the QIAquick PCR Purification kit (Qiagen Inc., CA). The sequencing took place at the Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA. GLRaV-2 isolate TX12 (GenBank Accession No. KF417612) and GLRaV-3 isolate TX9 (KJ545571) shared 85 to 100% and 94 to 100% nucleotide identity and 74 to 100% and 82 to 100% amino acid identity, respectively, with previously reported isolates from around the world. All samples tested negative for GLRaV-1, -4, -4 strain 5, and -4 strain 9 (4), suggesting that some of the symptomatic vines may have a different disease or abiotic disorder, such as a nutrient deficiency. To our knowledge, this is the first report of GLRaV-2 and GLRaV-3 in the state of Texas. References: (1) N. Bertazzon and E. Angelini. J. Plant Pathol. 86:283, 2004. (2) M. Fuchs et al. Plant Dis. 93:395, 2009. (3) L. Kovacs et al. Am. J. Enol. Vitic. 52:254, 2001. (4) F. Osman et al. J. Virol. Methods. 141:22, 2007. (5) A. Rowhani et al. Proc. ICVG (Adelaide). 13:82, 2000.

Prevalence and risk factors for gingivitis in a cohort of UK companion cats aged up to 6 years.

OBJECTIVES: Prospectively collected data were used to estimate the prevalence of gingivitis in a cohort of companion cats aged up to 6 years and to investigate factors associated with the risk of gingivitis in cats aged 3 to 4 years. MATERIALS AND METHODS: Data were obtained from a longitudinal study of domestic cats (the Bristol Cats Study), using owner-completed questionnaires and veterinary surgeon-completed oral health scores. Prevalence estimates of veterinary-reported gingivitis for cats aged up to 6 years old (n = 1534) were calculated for different age groups. Cat signalment, diet and dental care were assessed for association with gingivitis in cats aged 3 to 4 years (n = 317) using univariable and multiple logistic regression. RESULTS: The prevalence of gingivitis increased with age and ranged from 24.5% (<12 months old) to 56.3% (5 to 6 years old). Odds of gingivitis in cats aged 3 to 4 years were higher in cats fed a wet only or mixed wet/dry diet compared to dry only (odds ratio: 2.7; 95% confidence interval: 1.4 to 5.1), cats not reported to hunt compared to reported hunters (odds ratio: 2.1; 95% confidence interval: 1.0 to 4.2), cats reported to dribble whilst being stroked at age 6 months compared to reported non-dribblers (odds ratio: 3.2; 95% confidence interval: 1.3 to 8.4) and cats with orange variants in their coat colour compared to non-orange cats (odds ratio: 2.3; 95% confidence interval: 1.0 to 5.3). CLINICAL SIGNIFICANCE: These results will help veterinary surgeons identify cats that may be at a greater risk of gingivitis and provide an evidence base to inform dietary and oral healthcare recommendations aimed at promoting gingival health in cats.

Non-invasive cardiac output monitoring with electrical velocimetry after cardiac surgery in infants.

INTRODUCTION: Low cardiac output following cardiac surgery is a major determinant of outcome that may be improved by early detection, yet there are no widely accepted methods for its measurement in young children. We evaluated the feasibility of the routine use of electrical velocimetry, a non-invasive technique providing continuous measurement of cardiac output, in infants in the early postoperative period. METHODS: With ethical approval and parental consent, infants undergoing cardiac surgery were recruited. The ICON electrical velocimetry monitor was attached on admission to the intensive care unit (ICU) and remained for up to 24h. RESULTS: A total of 15 infants were recruited, median age 3 months (interquartile range (IQR) 0.5-7.5) and weight 4.8kg (IQR 3.9-7.1), undergoing various operations. Cardiac index had a weak correlation with arterial lactate (r=-0.24, p=0.02) and no correlation with blood pressure, central venous pressure or arteriovenous oxygen difference. Data were recorded for a median of 19h (range 5-24), with lead detachment or movement artefact the most common causes of data loss. There was marked minute-to-minute variability, with 25% of consecutive measurements having >5% variability. CONCLUSION: Cardiac index measured by electrical velocimetry in infants in the early postoperative period is impaired by frequent data loss and marked intrapatient variability. Our feasibility study suggests that it is unsuitable for use as a routine monitoring tool in the setting of postsurgical ICU care.

Animal production food safety: priority pathogens for standard setting by the World Organisation for Animal Health.

In this short study, expert opinion and a literature review were used to identify the pathogens that should be prioritised by the World Organisation for Animal Health (OIE) for the development of future standards for animal production food safety. Prioritisation was based on a pathogen's impact on human health and amenability to control using on-farm measures. As the OIE mandate includes alleviation of global poverty, the study focused on developing countries and those with 'in-transition' economies. The regions considered were Eastern Europe, Asia, the Middle East, Africa and South America. Salmonella (from species other than poultry) and pathogenic Escherichia coli were considered to be top priorities. Brucella spp., Echinococcus granulosus and Staphylococcus aureus were also mentioned by experts. As Salmonella, and to a lesser extent pathogenic E. coli, can be controlled by on-farm measures, these pathogens should be considered for prioritisation in future standard setting. On-farm control measures for Brucella spp. will be addressed in 2010-2011 in a review of the OLE Terrestrial Animal/Health Code chapter on brucellosis. In Africa, E. granulosus, the causative agent of hydatidosis, was estimated to have the greatest impact of all pathogens that could potentially be transmitted by food (i.e. via contamination). It was also listed for the Middle East and thought to be of importance by both South American experts consulted. Taenia saginata was thought to be of importance in South America and Africa and by one expert in the Middle East.

Survey of the characteristics of cats owned by households in the UK and factors affecting their neutered status.

Data were collected on 1260 cats owned by a random sample of UK households in 2007, by means of telephone questionnaires, which were completed by 33 per cent of the households contacted. Cats were owned by 26 per cent of these households, 42 per cent of which owned more than one cat. The owners of 622 female cats reported a total of 110 unplanned litters of kittens. Excluding cats with an unknown neutered status 92 per cent of the cats aged six months or more were neutered, but only 66 per cent of the cats aged six to 12 months were neutered. Multivariable logistic regression, based on data collected for one randomly selected cat aged four months or more in each cat-owning household, was used to identify factors affecting the cats' neutered status. Analysis of 48 sexually entire cats and 501 neutered cats showed that cats aged 10 months or more, with indoor access, that had been vaccinated within the last year or were currently registered with a veterinary practice, were more likely to be neutered than cats aged less than 10 months, without indoor access, that had been vaccinated more than one year ago or were not registered with a veterinary practice.

Fluid dynamic induced break-up during volcanic eruptions.

Determining whether magma fragments during eruption remains a seminal challenge in volcanology. There is a robust paradigm for fragmentation of high viscosity, silicic magmas, however little is known about the fragmentation behaviour of lower viscosity systems-the most abundant form of volcanism on Earth and on other planetary bodies and satellites. Here we provide a quantitative model, based on experiments, for the non-brittle, fluid dynamic induced fragmentation of low viscosity melts. We define the conditions under which extensional thinning or liquid break-up can be expected. We show that break-up, both in our experiments and natural eruptions, occurs by both viscous and capillary instabilities operating on contrasting timescales. These timescales are used to produce a universal break-up criterion valid for low viscosity melts such as basalt, kimberlite and carbonatite. Lastly, we relate these break-up instabilities to changes in eruptive behaviour, the associated natural hazard and ultimately the deposits formed.

Is feline foamy virus really apathogenic?

Feline foamy virus (FFV) is a retrovirus commonly found in cats. It is generally thought to be apathogenic, making it a suitable candidate as a gene therapy vector. However, there have been reports of association of FFV with chronic progressive arthritis and a cofactor effect with feline immunodeficiency virus. This study investigated experimental FFV infection and whether this was associated with signs of disease. Eight young specific pathogen free cats were inoculated intramuscularly with FFV. The cats were examined twice weekly and blood and pharyngeal samples were taken. Haematology, biochemistry and FFV quantitative polymerase chain reaction (qPCR) were performed. Tissue samples were also collected throughout the six month period. FFV was initially detected by qPCR in the blood within the first two weeks of infection and viraemia persisted throughout the study. Two peaks of viraemia were observed, at day 20 (80-170FFU/ml blood) and day 155 (332-415FFU/ml blood). FFV was also consistently detected in oropharyngeal samples after day 36. Anti-FFV IgG was detected in all cats by ELISA; antibody levels had an early peak around day 35 and then increased again following the second rise in circulating viral load. All cats remained clinically normal, except for one cat with an unrelated gingivitis. None of the cats developed pyrexia. The biochemical profile and blood cell counts remained within normal limits except for one cat with a persistent eosinophilia. Initial fluctuations in white cell counts settled within three weeks and did not deviate outside of the normal ranges. All tissue samples contained FFV DNA; lymphoreticular tissues, salivary gland and lung had the highest viral loads. Although there were no gross pathological lesions on post mortem examination, histologically a mild glomerulonephritis and a moderate interstitial pneumonia were observed in all cats. We conclude that during the six month period of infection, although cats appeared clinically normal, histopathological changes were observed in the lungs and kidneys. Further investigation of the significance of these changes is warranted before FFV is developed as a vector for gene delivery.

Opinions of veterinarians about the age at which kittens should be neutered.

The mean age recommended by veterinary practices for neutering kittens is 22.6 weeks, with only 28 per cent of veterinarians considering it appropriate to neuter 12- to 16-week-old kittens. Multivariable logistic regression was used to identify variables associated with veterinarians' opinion that 12 to 16 weeks is an appropriate age at which to neuter kittens. Significant risk factors included time since graduation, perception of the problem of there being too many unwanted domestic cats and their practice's policy on the recommended neutering age. Veterinarians who thought that neutering eight- to 11-week-old rescue kittens before homing was justified and veterinarians who had neutered 12- to 16-week-old domestic kittens within the previous year were more likely to consider that neutering 12- to 16-week-old kittens was appropriate. Veterinarians who thought that surgical complications, anaesthetic complications and lower urinary tract disease were, or might be, more likely to occur in kittens neutered at 12 to 16 weeks than in those neutered at six months of age, were significantly less likely to think that neutering 12- to 16-week-old kittens was appropriate.

Spatter matters - distinguishing primary (eruptive) and secondary (non-eruptive) spatter deposits.

Spatter is a common pyroclastic product of hawaiian fountaining, which typically forms vent-proximal ramparts or cones. Based on textural characteristics and field relations of spatter from the 1969 Mauna Ulu eruption of Kilauea, Hawai'i, three spatter types were identified: (1) Primary spatter deposited as spatter ramparts and isolated cones during the peak of episode 1; (2) Late-stage spatter comprising dense, small volume, vent proximal deposits, formed at the end of episode 1; (3) Secondary spatter preserved in isolated mounds around tectonic ground cracks that we interpret to have formed by the disruption of overlying lava. We propose that not all spatter deposits are evidence of primary magmatic fountaining. Rather, deposits can be "secondary" in nature and associated with lava drain-back, disruption, and subsequent ejection from tectonic cracks. Importantly, these secondary pyroclastic deposits are difficult to distinguish from primary eruptive features based on field relations and bulk clast vesicularity alone, allowing for the potential misinterpretation of eruption vents, on Earth and in remotely sensed planetary data, thereby misinforming hazard maps and probabilistic assessments. Here, we show that vesicle number density provides a statistically-robust metric by which to discriminate primary and secondary spatter, supporting accurate identification of eruptive vents.

Ash production by attrition in volcanic conduits and plumes.

Tephra deposits result from explosive volcanic eruption and serve as indirect probes into fragmentation processes operating in subsurface volcanic conduits. Primary magmatic fragmentation creates a population of pyroclasts through volatile-driven decompression during conduit ascent. In this study, we explore the role that secondary fragmentation, specifically attrition, has in transforming primary pyroclasts upon transport in volcanic conduits and plumes. We utilize total grain size distributions from a suite of natural and experimentally produced tephra to show that attrition is likely to occur in all explosive volcanic eruptions. Our experimental results indicate that fine ash production and surface area generation is fast (<15 min) thereby rapidly raising the fractal dimension of tephra deposits. Furthermore, a new metric, the Entropy of Information, is introduced to quantify the degree of attrition (secondary fragmentation) from grain size data. Attrition elevates fine ash production which, in turn, has consequences for eruption column stability, tephra dispersal, aggregation, volcanic lightening generation, and has concomitant effects on aviation safety and Earth's climate.

Foot-and-Mouth Disease Impact on Smallholders - What Do We Know, What Don't We Know and How Can We Find Out More?

Foot-and-mouth disease (FMD) endemic regions contain three-quarters of the world's FMD susceptible livestock and most of the world's poor livestock keepers. Yet FMD impact on smallholders in these regions is poorly understood. Diseases of low mortality can exert a large impact if incidence is high. Modelling and field studies commonly find high FMD incidence in endemic countries. Sero-surveys typically find a third of young cattle are sero-positive, however, the proportion of sero-positive animals that developed disease, and resulting impact, are unknown. The few smallholder FMD impact studies that have been performed assessed different aspects of impact, using different approaches. They find that FMD impact can be high (>10% of annual household income). However, impact is highly variable, being a function of FMD incidence and dependency on activities affected by FMD. FMD restricts investment in productive but less FMD-resilient farming methods, however, other barriers to efficient production may exist, reducing the benefits of FMD control. Applying control measures is costly and can have wide-reaching negative impacts; veterinary-cordon-fences may damage wildlife populations, and livestock movement restrictions and trade bans damage farmer profits and the wider economy. When control measures are ineffective, farmers, society and wildlife may experience the burden of control without reducing disease burden. Foot-and-mouth disease control has benefitted smallholders in South America and elsewhere. Success takes decades of regional cooperation with effective veterinary services and widespread farmer participation. However, both the likelihood of success and the full cost of control measures must be considered. Controlling FMD in smallholder systems is challenging, particularly when movement restrictions are hard to enforce. In parts of Africa this is compounded by endemically infected wildlife and limited vaccine performance. This paper reviews FMD impact on smallholders in endemic countries. Significant evidence gaps exist and guidance on the design of FMD impact studies is provided.

Risk factors for road traffic accidents in cats up to age 12†months that were registered between 2010 and 2013 with the UK pet cat cohort ('Bristol Cats').

Road traffic accidents (RTAs) are a common cause of death and injury in domestic cats, and a concern to many owners. This study assessed potential risk factors for RTAs in cats up to 12 months of age within a UK cat cohort known as 'The Bristol Cats study'. Data were obtained from three questionnaires, completed by cat owners when their cats were approximately 8-16 weeks old, 6 months old and 12 months old. Information was gathered regarding environmental conditions, cat characteristics and owner management factors. Univariable and multivariable logistic regression models were used to assess associations between these factors and RTAs. Of 1264 eligible study cats, 49 (3.9 per cent) had been involved in an RTA, of which 71.4 per cent (35/49) were known to result in fatal injuries. Rural locations were associated with a higher odds of RTAs than towns, cities or suburban locations. An increased odds of an RTA was also associated with cats that were reported by their owners to hunt at the roadside, as well as cats whose owners classified the road by their house as being a 'long straight section of road'. No significant associations were found between coat colour, breed, sex or neuter status and the odds of an RTA.

Early-life risk factors identified for owner-reported feline overweight and obesity at around two years of age.

Obesity is considered the second most common health problem in pet cats in developed countries. This study used prospective data from a longitudinal study of pet cats ('C.L.A.W.S.', www.bristol.ac.uk/vetscience/claws) to identify early-life risk factors for feline overweight/obesity occurring at around two years of age. Data were collected via five owner-completed questionnaires (for cats aged two-six months, six months, 12 months, 18 months and two years respectively) completed between May 2011 and April 2015. Owner-reported body condition scores (BCS) of cats at age two years, assessed using images from the 9-point BCS system (Laflamme, 1997), were categorised into a dichotomous variable: overweight/obese (BCS 6-9) and not overweight (BCS 1-5) and used as the dependent variable. Of the 375 cats with owner-reported BCS, 25.3% were overweight or obese at two years of age. Multivariable logistic regression models were built using stepwise forward-selection. To account for potential hierarchical clustering due to multi-cat households two-level random intercept models were considered but clustering had no impact on the analysis. Models were compared using Wald tests. Six factors were significantly associated with overweight/obesity at two years of age: being overweight or obese at one year of age (OR=10.6, 95%CI 4.4-25.3); owner belief that BCS 7 was the ideal weight (OR=33.2, 95%CI 8.5-129.4), or that BCS represented overweight cats but they would not be concerned if their cat were classified in this category (OR=2.7, 95%CI 1.2-6.2), at questionnaire five completion; vets advising owners that the cat should lose weight, or making no comment on their weight, between one and two years of age (OR=12.1, 95%CI 3.2-44.9 and OR=3.9, 95%CI 1.5-10.3 respectively); owners giving their cat treats when they "felt happy" with them at 18 months of age (OR=2.7, 95%CI 1.0 - 7.3); feeding ≥250g wet food daily between two and six months of age (OR=2.7, 95%CI 1.2-5.9), and feeding dry food as the only or major part (>50%) of the diet at two years of age (OR=2.1, 95%CI 1.0-4.2). These findings have the potential to reduce the current high prevalence of a widespread problem by informing preventive advice, and as such improving the health and welfare of pet cats.

Measurement of cytokine mRNA expression in intestinal biopsies of cats with inflammatory enteropathy using quantitative real-time RT-PCR.

Inflammatory bowel disease (IBD) is a common condition in cats characterised by infiltration of inflammatory cells into the intestinal mucosa. In this study, real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to quantify cytokine messenger RNA (mRNA) expression in intestinal biopsies from cats. Biopsies were collected from seven cats with chronic diarrhoea and histologically confirmed IBD, five cats with chronic diarrhoea due to non-IBD gastrointestinal (GI) disease, and nine clinically normal cats with or without subclinical inflammatory changes in small intestine. Real-time RT-PCR was developed for quantification of mRNA encoding interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-12 (p35 and p40), IL-18, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a 'housekeeper' gene. All real-time PCR efficiencies were>90% (range 90.4-102%) with correlation coefficients >0.99 (range 0.998-1). The results of the study were analyzed on the basis of either clinical presentation or histopathological evidence of intestinal inflammation. The former analysis showed that mRNA encoding IL-10 and TGF-beta (immunoregulatory cytokines), and IL-6, IL-18, TNF-alpha and IL-12 p40 (Th1 and pro-inflammatory cytokines) was significantly higher in clinically normal cats and cats with IBD when compared to cats with other GI diseases. IL-5 mRNA was significantly higher in cats with IBD compared to clinically normal cats. IL-2 mRNA was significantly lower in cats with non-IBD GI disease than in clinically normal cats. Analysis on the basis of histopathological change revealed that cats with intestinal inflammation had significantly more transcription of genes encoding IL-6, IL-10, IL-12p40, TNF-alpha and TGF-beta than those with normal intestinal morphology. The results suggest that immune dysregulation plays a role in feline IBD and that IBD in cats has a complicated pathogenesis with both pro-inflammatory and immunoregulatory features.

Global Foot-and-Mouth Disease Research Update and Gap Analysis: 2 - Epidemiology, Wildlife and Economics.

We assessed knowledge gaps in foot-and-mouth disease (FMD) research, and in this study, we consider (i) epidemiology, (ii) wildlife and (iii) economics. The study took the form of a literature review (2011-2015) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD research. During 2011-2015, modelling studies were dominant in the broad field of epidemiology; however, continued efforts are required to develop robust models for use during outbreaks in FMD-free countries, linking epidemiologic and economics models. More guidance is needed for both the evaluation and the setting of targets for vaccine coverage, population immunity and vaccine field efficacy. Similarly, methods for seroprevalence studies need to be improved to obtain more meaningful outputs that allow comparison across studies. To inform control programmes in endemic countries, field trials assessing the effectiveness of vaccination in extensive smallholder systems should be performed to determine whether FMD can be controlled with quality vaccines in settings where implementing effective biosecurity is challenging. Studies need to go beyond measuring only vaccine effects and should extend our knowledge of the impact of FMD and increase our understanding of how to maximize farmer participation in disease control. Where wildlife reservoirs of virus exist, particularly African Buffalo, we need to better understand when and under what circumstances transmission to domestic animals occurs in order to manage this risk appropriately, considering the impact of control measures on livelihoods and wildlife. For settings where FMD eradication is unfeasible, further ground testing of commodity-based trade is recommended. A thorough review of global FMD control programmes, covering successes and failures, would be extremely valuable and could be used to guide other control programmes.