Sharing responsibility between public and private sectors for the management of aquatic emergency animal diseases.

Aquatic animal disease outbreaks affect both the public (represented by the government) and the private sector (represented by the aquaculture and fisheries industry). However, all too often, the responsibilities and costs of responding to an outbreak may not be shared. Without a mechanism for public and private sectors to work together, the outcomes of an emergency response may not be ideal, or of common benefit to all potentially affected parties. In Australia, a mechanism is being developed for public and private sectors to share the responsibilities and costs of responding to aquatic animal disease outbreaks, through an industry- government aquatic emergency animal disease response agreement. The agreement provides an approach for both public and private sectors to share the responsibilities and costs of responding to a disease outbreak and to coordinate disease prevention activities to reduce their shared risk. The key elements of the agreement include provisions to incentivise faster notification of disease outbreaks, facilitate a faster response, share decision-making and costs (including compensation for affected businesses), clarify the responsibilities of all parties and, most importantly, strengthen risk mitigation activities. This paper describes how the draft agreement has been developed among 18 industry and government parties, how key elements of the agreement may contribute to improved aquatic animal health outcomes, and the principles which could be applied by other OIE Member Countries.

Les foyers de maladies survenant chez les animaux aquatiques affectent aussi bien le secteur public (représenté par les services gouvernementaux) que le secteur privé (représenté par les entreprises de l'aquaculture et de la pêche). Néanmoins, trop souvent ces secteurs ne partagent ni les responsabilités ni les coûts afférents aux interventions consécutives à un foyer. À défaut d'un mécanisme permettant aux secteurs public et privé de travailler ensemble, les résultats de la réponse à une urgence sanitaire risquent de ne pas être optimaux et de ne pas apporter les mêmes bénéfices à l'ensemble des parties potentiellement affectées. L'Australie a mis en place un mécanisme pour que les secteurs public et privé puissent partager les responsabilités et les coûts de la réponse aux foyers de maladies affectant les animaux aquatiques à travers un accord spécifique conclu entre le secteur de l'aquaculture et les instances gouvernementales compétentes. C'est une première mondiale dans le domaine de la gestion de la santé des animaux aquatiques. L'accord porte sur les modalités du partage des responsabilités et des coûts liés à la réponse à un foyer entre les secteurs public et privé ainsi que sur la coordination des activités de prévention sanitaire destinées à réduire les risques communs. Parmi les aspects déterminants de l'accord figurent des dispositions visant à accélérer les notifications des foyers, à faciliter une réponse plus rapide, à partager les processus de décision et les coûts (y compris l'indemnisation des entreprises affectées), à clarifier les responsabilités de chaque partie et, plus important encore, à renforcer les activités d'atténuation du risque. Les auteurs décrivent la mise en œuvre de cet accord, auquel ont pris part 18 instances du secteur privé et gouvernemental ; ils expliquent le rôle des principaux aspects de cet accord dans l'amélioration attendue de la santé des animaux aquatiques et soulignent les principes que d'autres Pays membres de l'OIE pourraient avantageusement appliquer à cette même fin.

Los brotes de enfermedades de los animales acuáticos afectan por un igual al sector público (instancias gubernamentales) y al privado (industria acuícola y pesquera). Ocurre demasiado a menudo, sin embargo, que estos sectores no asuman conjuntamente las responsabilidades y los costos de responder a un brote. En ausencia de un mecanismo para que ambos sectores trabajen de consuno, los resultados de la respuesta a una emergencia quizá no sean los idóneos, o no vayan en beneficio de todas las partes que pueden verse afectadas. En Australia se está instituyendo un mecanismo para que el sector público y el privado compartan las responsabilidades y los costos de la lucha contra brotes infecciosos en los animales acuáticos, mecanismo que reposa en un acuerdo de respuesta de emergencia a enfermedades de los animales acuáticos suscrito entre la industria y el Gobierno. Se trata de una primicia mundial en el ámbito de la gestión de la sanidad acuícola. El acuerdo prevé un método para que ambos sectores asuman en común las responsabilidades y los costos de responder a un brote infeccioso y coordinen sus respectivas actividades de prevención de enfermedades a fin de reducir el riesgo común. Entre los principales elementos del acuerdo hay disposiciones destinadas a incentivar una notificación más rápida de los brotes de enfermedad, facilitar una respuesta más ágil, compartir decisiones y costos (incluidas las indemnizaciones a empresas afectadas), aclarar las responsabilidades que incumben a todas y cada una de las partes y también, aspecto este de suma importancia, potenciar las labores de mitigación del riesgo. Los autores describen el proceso de elaboración del acuerdo entre 18 instancias del mundo empresarial y el sector público, explican cómo sus principales elementos servirán para mejorar los resultados sanitarios en los animales acuáticos y exponen los principios que podrían aplicar otros Países Miembros de la OIE para lograr también mejores resultados en el ámbito de la sanidad acuícola.

A new approach to the management of emerging diseases of aquatic animals.

Since 1970, aquaculture has grown at a rate of between 5% and 10% per annum. It has achieved this by expanding into new areas, farming new (often non-native) species and intensifying production. These features of aquaculture, combined with large-scale movements of animals, have driven disease emergence, with negative consequences for both production and biodiversity. Efforts to improve the management of emerging diseases of aquatic animals must include actions to reduce the rate of disease emergence, enhance disease detection and reporting, and improve responses to prevent disease spread. The rate of disease emergence can be reduced by understanding the underpinning mechanisms and developing measures to mitigate them. The three principal mechanisms of disease emergence, namely, host switching, decreased host immunocompetence and increased pathogen virulence, have many drivers. The most important of these drivers are those that expose susceptible hosts to novel pathogens (e.g. the introduction of non-native hosts, translocation of pathogens, and increased interaction between wild and farmed populations), followed by host switching. Exposure to wild populations can be reduced through infrastructure and management measures to reduce escapes or exclude wild animals (e.g. barrier nets, filtration and closed-confinement technology). A high standard of health management ensures immunocompetence and resistance to putative new pathogens and strains, and thus reduces the rate of emergence. Appropriate site selection and husbandry can reduce the likelihood of pathogens developing increased virulence by preventing their continuous cycling in geographically or temporally linked populations. The under-reporting of emerging aquatic animal diseases constrains appropriate investigation and timely response. At the producer level, employing information and communications technology (e.g. smartphone applications and Cloud computing) to collect and manage data, coupled with a farmer-centric approach to surveillance, could improve reporting. In addition, reporting behaviours must be understood and disincentives mitigated. At the international level, improving the reporting of emerging diseases to the World Organisation for Animal Health allows Member Countries to implement appropriate measures to reduce transboundary spread. Reporting would be incentivised if the global response included the provision of support to low-income countries to, in the short term, control a reported emerging disease, and, in the longer term, develop aquatic animal health services. Early detection and reporting of emerging diseases are only of benefit if Competent Authorities' responses prevent disease spread. Effective responses to emerging diseases are challenging because basic information and tools are often lacking. Consequently, responses are likely to be sub-optimal unless contingency plans have been developed and tested, and decision-making arrangements have been well established.

Depuis les années 1970, l'aquaculture connaît un taux de croissance de 5 % à 10 % par an. Cette croissance a été rendue possible par le développement de nouvelles filières, l'élevage d'espèces nouvelles (et souvent non autochtones) et l'intensification de la production. Ces caractéristiques du secteur, associées à des transferts massifs d'espèces aquatiques ont entraîné l'émergence de maladies nouvelles, avec des effets négatifs aussi bien sur la production que sur la biodiversité. Les efforts d'amélioration de la gestion des maladies émergentes des animaux aquatiques doivent comporter des mesures visant à réduire l'incidence des maladies émergentes, à améliorer la détection et la notification des maladies et à optimiser les réponses déployées en cas de maladies afin d'en prévenir la propagation. Il est possible de réduire le taux d'émergence des maladies dès lors que les mécanismes sous-jacents à leur survenue sont bien compris et que les mesures appropriées sont prises pour les contrecarrer. Les trois principaux mécanismes d'émergence de maladies, à savoir la colonisation de nouveaux hôtes par des agents pathogènes, la baisse de l'immunocompétence des hôtes et la virulence accrue des agents pathogènes ont plusieurs facteurs déclenchants. Parmi ceux-ci, les plus importants sont ceux qui exposent les hôtes sensibles à des agents pathogènes nouveaux (par exemple l'introduction d'espèces hôtes non autochtones, les transferts d'agents pathogènes et les interactions accrues entre les populations sauvages et d'élevage), suivis par la colonisation de nouvelles espèces hôtes par des agents pathogènes. L'exposition aux populations sauvages peut être atténuée au moyen d'infrastructures appropriées et de mesures de gestion visant à limiter les évasions ou à exclure les espèces sauvages (par exemple, filets de retenue, filtration des eaux et technologies de confinement en système fermé). Une gestion sanitaire de haut niveau qualitatif permet de préserver l'immunocompétence et la résistance à de nouveaux agents et souches pathogènes potentiels, réduisant ainsi le taux d'émergence de nouvelles maladies. Une sélection appropriée du site de production et des techniques d'élevage permet de réduire la probabilité que les agents pathogènes puissent acquérir une virulence accrue, en les empêchant de prolonger leur cycle dans des populations spatialement ou temporellement reliées. La sous-déclaration de maladies émergentes des animaux aquatiques limite les possibilités de procéder à des enquêtes appropriées et d'organiser la réponse en temps voulu. Au niveau des producteurs, le niveau de notification peut être amélioré en recourant aux technologies de l'information et de la communication (par exemple les applications sur téléphonie mobile et l'informatique en nuage) pour la collecte et la gestion des données et en leur associant une méthodologie de la surveillance centrée sur l'éleveur. En outre, il est essentiel de comprendre les comportements en matière de notification et d'atténuer les facteurs de dissuasion. Au niveau international, la notification de maladies émergentes à l'Organisation mondiale de la santé animale permet aux Pays membres de mettre en place des mesures appropriées pour réduire leur propagation transfrontalière. Une méthode incitative envisageable pour améliorer la notification consiste à ce que la réponse mondiale prévoie d'apporter aux pays à faible revenu le soutien nécessaire pour que ceux-ci puissent, à court terme, lutter contre chaque maladie émergente notifiée et, à plus long terme, créer des Services nationaux chargés de la santé des animaux aquatiques. La détection précoce et la notification rapide des maladies émergentes ne portent leurs fruits que si les réponses mises en place par les Autorités compétentes empêchent toute propagation de ces maladies. Le déploiement de réponses efficaces en cas de maladie émergente est difficile, car les pays manquent souvent d'informations et d'outils de base. En conséquence, les réponses sont souvent inadéquates, à moins que des plans d'urgence n'aient été élaborés et testés, soutenus par des instruments décisionnels bien établis.

Desde 1970 la acuicultura ha registrado una tasa de crecimiento anual de entre el 5% y el 10%, cosa que ha logrado expandiéndose a nuevos territorios, cultivando nuevas especies (a menudo no autóctonas) e intensificando la producción. Estas características de la acuicultura, combinadas con los desplazamientos a gran escala de animales, han provocado la aparición de enfermedades y su cortejo de efectos negativos sobre la producción y la diversidad biológica. Las iniciativas para gestionar más eficazmente las enfermedades emergentes de los animales acuáticos deben incluir medidas que reduzcan la tasa de aparición de enfermedades, ayuden a detectarlas y notificarlas y mejoren las respuestas destinadas a impedir que se propaguen. La tasa de aparición de enfermedades se puede reducir entendiendo los mecanismos que subyacen al proceso e implantando medidas para contrarrestarlos. Los tres principales de esos mecanismos (a saber, el cambio de hospedador, la menor inmunocompetencia de los organismos hospedadores y la mayor virulencia de los patógenos) resultan de la suma de muchos factores. Los más importantes son aquellos que entrañan la exposición de un hospedador sensible a nuevos patógenos (p.ej. la introducción de hospedadores no autóctonos, el traslado de patógenos y el aumento de las interacciones entre poblaciones salvajes y poblaciones de cultivo) y aquellos que desembocan en un cambio de hospedador. Para reducir los niveles de exposición a poblaciones salvajes se pueden implantar medidas de gestión o de infraestructura que hagan difícil que los animales escapen o los aíslen de la fauna salvaje (como redes de barrera, filtración y tecnología de confinamiento cerrado). Una gestión sanitaria de buena calidad asegura la inmunocompetencia y la resistencia a cepas y patógenos supuestamente nuevos, reduciendo con ello la tasa de aparición de enfermedades emergentes. La selección de emplazamientos apropiados y el uso de métodos de cría convenientes pueden reducir la probabilidad de que los patógenos adquieran mayor virulencia porque evitan la continuidad de sus ciclos reproductivos entre poblaciones conectadas entre sí, ya sea geográfica o temporalmente. La insuficiente notificación de enfermedades emergentes de los animales acuáticos supone un lastre para estudiarlas debidamente y responder a ellas con celeridad. Las soluciones para mejorar los niveles de notificación trabajando desde la propia explotación podrían pasar por el uso de las tecnologías de información y comunicación (como las aplicaciones de teléfono inteligente o la informática «en nube¼) para obtener y gestionar datos, combinado con fórmulas de vigilancia cuya figura central sea el productor. Es preciso además entender los comportamientos ligados al hecho de notificar o no una enfermedad y restar peso a aquellos factores que desincentiven la notificación. A escala internacional, una más eficaz notificación de enfermedades emergentes a la Organización Mundial de Sanidad Animal permite a los Países Miembros aplicar medidas apropiadas para reducir la propagación transfronteriza. Algo que incentivaría la notificación es que entre las medidas mundiales de respuesta estuviera la prestación de apoyo a los países de renta baja para ayudarlos, a corto plazo, a controlar la enfermedad emergente notificada y, a más largo plazo, a dotarse de buenos servicios de sanidad acuícola. La pronta detección y notificación de enfermedades emergentes solo resulta provechosa si la respuesta de las autoridades competentes evita que la enfermedad se propague. Lo que dificulta una respuesta eficaz a las enfermedades emergentes es la frecuente falta de información y herramientas básicas. Lo más probable, por lo tanto, es que las respuestas no sean las idóneas a menos que se tengan elaborados y ensayados planes de emergencia y se tengan bien implantados mecanismos decisorios al respecto.

Introduction: Improved aquatic animal health management is vital to aquaculture's role in global food security.

Global food security and nutrition depend heavily on aquaculture, the continued growth of which is crucial as the world heads towards a human population of at least 9 billion by 2050, while harvests from wild capture will, at best, stabilise at current levels. Thus, a fundamental question is: how can we sustainably increase aquatic food production? It is clear that aquatic animal diseases present a substantial threat and, consequently, aquatic animal health management has a critical role in food security. An ecosystem approach to aquaculture will mitigate impacts on ecosystem services and biodiversity, and provide the necessary resilience to future disease threats, including those exacerbated by climate change. Due to the nature of aquatic production systems, this approach must encompass fisheries and other sectors that share the same resources. Improved aquatic animal health management must be a key component of aquaculture's future. At the national level, public-private partnerships are vital in achieving objectives of common benefit. Improved disease reporting and response is critical in the control of listed and emerging diseases and can only be achieved through government, industry and stakeholder collaboration. Great potential exists to improve biosecurity from the farm to national level, but this will only be achieved through collaboration. Industry cannot develop effective biosecurity without a clear government strategy and support, specifically legislation which provides an effective framework for safe trade. Governments have a key role in creating a regulatory environment that supports effective biosecurity and is attractive to investment; such as one that supports the development and regulatory approval of therapeutics. The improved control of transboundary diseases requires the wider and more consistent implementation of OIE standards, particularly on disease notification. This can only be achieved through improved collaboration between trading partners and by supporting low- and middle-income countries to strengthen their aquatic animal health services. There is incredible potential for aquaculture to continue its rapid growth and increase its contribution to global food security. However, sustainable growth of aquaculture is threatened by both known diseases, which we cannot effectively control, and new diseases, which may become pandemic. Recent pandemics have shown that global production systems are epidemiologically connected and, consequently, aquatic animal diseases present a shared global threat that demands global solidarity. The world now depends on a sustainable future for aquaculture and improved aquatic animal health management is critical to its continued and growing contribution to global food security.

La sécurité alimentaire et nutritionnelle mondiale dépend fortement de l'aquaculture, dont l'impératif de croissance continue est d'autant plus vital que la population mondiale devrait dépasser les 9 milliards d'habitants d'ici 2050, tandis que le produit des captures en mer se maintiendra, dans le meilleur des cas, aux niveaux actuels. Par conséquent, la question fondamentale est celle de savoir comment accroître les capacités de production durable de denrées alimentaires d'origine aquatique. Il est évident que les maladies des animaux aquatiques présentent une menace importante et que la gestion de la santé des animaux aquatiques joue un rôle déterminant pour la sécurité alimentaire. Une approche de l'aquaculture basée sur les écosystèmes permettra d'atténuer l'impact des maladies sur les services écosystémiques et sur la biodiversité et d'assurer la résilience nécessaire vis-à-vis des futures menaces sanitaires, y compris celles que le changement climatique risque d'amplifier. Compte tenu de la nature des systèmes de production aquatique, cette approche doit couvrir la pêche mais aussi d'autres secteurs partageant les mêmes ressources. L'amélioration de la gestion de la santé des animaux aquatiques est donc une composante essentielle de l'avenir de l'aquaculture. À l'échelle nationale, les partenariats public­privé sont déterminants pour la réussite d'objectifs d'intérêt commun. L'amélioration de la notification des maladies et de la réponse qui leur est apportée est essentielle pour lutter contre les maladies listées et émergentes et ne peut se faire qu'avec la collaboration des gouvernements, du secteur lui-même et des parties prenantes. Il y a une grande marge potentielle d'amélioration de la biosécurité en aquaculture, depuis la ferme jusqu'au niveau national, mais elle ne pourra se réaliser qu'en mettant en place une collaboration effective. La filière aquacole ne peut assurer une biosécurité efficace si elle ne dispose pas du soutien stratégique des gouvernements, en particulier sous forme d'une législation apportant un cadre effectif à la sécurité sanitaire des échanges. Le rôle des gouvernements est déterminant en ce qu'ils instaurent un contexte réglementaire propice à la biosécurité et attractif pour les investisseurs, par exemple en soutenant le développement et l'autorisation réglementée de nouveaux agents thérapeutiques. Fondamentalement, l'amélioration de la lutte contre les maladies transfrontalières passe par une mise en œuvre plus large et cohérente des normes de l'OIE, en particulier celles relatives à la notification des maladies. Cela ne peut se faire qu'à travers une meilleure collaboration entre partenaires commerciaux et le soutien apporté aux pays à revenu faible et intermédiaire afin qu'ils puissent renforcer leurs services chargés de la santé des animaux aquatiques. L'aquaculture a un potentiel de croissance énorme et devrait pouvoir contribuer encore plus à la sécurité alimentaire mondiale. Néanmoins, la croissance durable de l'aquaculture est menacée par des maladies connues mais que nous ne savons pas encore maîtriser efficacement, ainsi que par des maladies nouvelles qui risquent de prendre une dimension pandémique. Les pandémies récentes ont montré l'interconnexion des systèmes de production mondiaux au plan épidémiologique et la menace mondiale que représentent les maladies des animaux aquatiques, menace qui nous concerne tous et exige une solidarité planétaire. Le monde dépend désormais de la possibilité pour l'aquaculture d'avoir un avenir durable, de sorte qu'il est vital d'améliorer la gestion des maladies des animaux aquatiques afin que le secteur puisse continuer à renforcer sa participation à la sécurité alimentaire mondiale.

La nutrición y la seguridad alimentaria del mundo dependen en buena medida de la acuicultura, cuyo continuo crecimiento es esencial cuando el planeta se encamina hacia una población de al menos 9 000 millones de seres humanos para 2050 y cuando la producción resultante de la pesca de captura quedará estancada, en el mejor de los casos, en los niveles actuales. Ello abre un interrogante fundamental: el de cómo incrementar de modo sostenible la producción de alimentos de origen acuático. Está claro que las enfermedades de los animales acuáticos representan una importante amenaza y que, por consiguiente, la gestión de su estado de salud cumple una función básica para la seguridad alimentaria. El hecho de considerar la acuicultura en clave ecosistémica atenuará el impacto de esta actividad sobre los servicios y la diversidad biológica de los ecosistemas y aportará la necesaria resiliencia ante futuras amenazas infecciosas, en particular aquellas que el cambio climático va a exacerbar. Por la propia naturaleza de los sistemas de producción acuícola, esta lógica ecosistémica debe abarcar tanto la pesca como otros sectores que comparten los mismos recursos. Un aspecto clave del porvenir de la acuicultura debe ser una mejor gestión de la sanidad de los animales acuáticos. A escala nacional, las alianzas publicoprivadas son vitales para cumplir una serie de objetivos de interés general. Para combatir las patologías inscritas en las listas, así como las enfermedades emergentes, es fundamental contar con mecanismos más eficaces para notificarlas y responder a ellas, lo que pasa necesariamente por la colaboración entre los poderes públicos, la industria y otras partes interesadas. Hay mucho margen para reforzar la seguridad biológica a todos los niveles, desde el de la explotación hasta el nacional, pero el ingrediente insoslayable para ello es la colaboración. El sector no puede instaurar una seguridad biológica eficaz sin contar con el apoyo y con una estrategia clara de los poderes públicos, y más concretamente sin una legislación que encuadre eficazmente la seguridad del comercio. Los gobiernos tienen una función básica que cumplir estableciendo condiciones reglamentarias que, además de propiciar medidas eficaces de seguridad biológica, atraigan las inversiones, por ejemplo, apoyando los procesos de desarrollo y aprobación reglamentaria de productos terapéuticos. Un factor clave para combatir más eficazmente las enfermedades transfronterizas es una aplicación más extendida y coherente de las normas de la OIE, sobre todo en materia de notificación de enfermedades, lo que pasa necesariamente por una colaboración más estrecha entre socios comerciales y por el apoyo a los países de renta baja y mediana para ayudarlos a fortalecer sus servicios de sanidad de los animales acuáticos. La acuicultura encierra un potencial increíble para seguir creciendo con rapidez y contribuyendo cada vez más a la seguridad alimentaria mundial. Su crecimiento sostenible, empero, está amenazado por las enfermedades, ya se trate de patologías conocidas que no sabemos combatir eficazmente o de nuevas enfermedades que pueden llegar a ser pandémicas. Las últimas pandemias han puesto de relieve que los sistemas productivos mundiales están epidemiológicamente conectados y que por lo tanto las enfermedades de los animales acuáticos constituyen un peligro planetario que a todos amenaza y que exige una respuesta mundial solidaria. El mundo depende ahora de que la acuicultura pueda crecer sosteniblemente en el futuro. En este sentido, una gestión más eficaz de la sanidad acuícola es crucial para que el sector siga contribuyendo, y lo haga cada vez más, a la seguridad alimentaria mundial.

The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Design standards for experimental and field studies to evaluate diagnostic accuracy of tests for infectious diseases in aquatic animals.

Design and reporting quality of diagnostic accuracy studies (DAS) are important metrics for assessing utility of tests used in animal and human health. Following standards for designing DAS will assist in appropriate test selection for specific testing purposes and minimize the risk of reporting biased sensitivity and specificity estimates. To examine the benefits of recommending standards, design information from published DAS literature was assessed for 10 finfish, seven mollusc, nine crustacean and two amphibian diseases listed in the 2017 OIE Manual of Diagnostic Tests for Aquatic Animals. Of the 56 DAS identified, 41 were based on field testing, eight on experimental challenge studies and seven on both. Also, we adapted human and terrestrial-animal standards and guidelines for DAS structure for use in aquatic animal diagnostic research. Through this process, we identified and addressed important metrics for consideration at the design phase: study purpose, targeted disease state, selection of appropriate samples and specimens, laboratory analytical methods, statistical methods and data interpretation. These recommended design standards for DAS are presented as a checklist including risk-of-failure points and actions to mitigate bias at each critical step. Adherence to standards when designing DAS will also facilitate future systematic review and meta-analyses of DAS research literature.

Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease.

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all p<0.05). The calculated concordance-index for the nomogram was 0.73 (concordance indexes of all prognostic factors between 0.54 and 0.6). Based on the nomogram the training cohort was divided into 4 groups and 2-year OS ranged between 24.2% and 76.1% (predicted OS between 30.2% and 78.4%). The nomogram discriminated between risk groups in the two validation cohorts (concordance index 0.68 and 0.67). CONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting. KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

Using the Neptune project to benefit Australian aquatic animal health research.

Diseases of aquatic animals have had, and continue to have, a significant impact on aquatic animal health. In Australia, where fisheries and aquaculture are important industries, aquatic species have been subject to serious disease outbreaks, including pilchard herpesvirus, the cause of one of the largest wild fish kills ever recorded. At the same time, there is a consensus that Australia's parasite fauna are largely unknown, and that aquatic animal health information is difficult to access. Managing aquatic animal diseases is challenging because they may be entirely new, their hosts may be new to aquaculture, and specialist expertise and basic diagnostic tools may be lacking or absent. The Neptune project was created in response to these challenges, and it aims to increase awareness of aquatic animal diseases, improve disease management, and promote communication between aquatic animal health professionals in Australia. The project consists of an online database, a digital microscopy platform containing a whole-slide image library, a community space, and online communications technology. The database contains aquatic animal health information from published papers, government reports, and other sources, while the library contains slides of key diseases both endemic and exotic to Australia. These assets make Neptune a powerful resource for researchers, students, and biosecurity officials.

Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals: Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling.

Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the control of inflammatory responses through their impact on various signaling pathways including the JAK/STAT pathway. Although all SOCS protein family members are identified in teleost fish, their functional properties in non-mammalian vertebrates have not been extensively studied. To gain further insight into SOCS functions in bony fish, we have identified and characterized the Atlantic salmon (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence conservation with their mammalian counterparts and they were ubiquitously expressed. SOCS1 in mammalian species has been recognized as a key negative regulator of interferon (IFN) signaling and recent data for the two model fish Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these functions are conserved from teleost to mammals. In agreement with this we here demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN responses. SOCS1 also inhibited IFNγ-induced nuclear localization of STAT1 and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2 kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS, SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to inhibit IFN-mediated signaling. These results are the first to demonstrate that SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish.

Vitamin E supplementation and lifespan in model organisms.

We have conducted a comprehensive literature review regarding the effect of vitamin E on lifespan in model organisms including single-cell organisms, rotifers, Caenorhabditis elegans, Drosophila melanogaster and laboratory rodents. We searched Pubmed and ISI Web of knowledge for studies up to 2011 using the terms "tocopherols", "tocotrienols", "lifespan" and "longevity" in the above mentioned model organisms. Twenty-four studies were included in the final analysis. While some studies suggest an increase in lifespan due to vitamin E, other studies did not observe any vitamin E-mediated changes in lifespan in model organisms. Furthermore there are several studies reporting a decrease in lifespan in response to vitamin E supplementation. Different outcomes between studies may be partly related to species-specific differences, differences in vitamin E concentrations and the vitamin E congeners administered. The findings of our literature review suggest that there is no consistent beneficial effect of vitamin E on lifespan in model organisms which is consistent with reports in human intervention studies.

Survivin, a target to modulate the radiosensitivity of Ewing's sarcoma.

BACKGROUND AND PURPOSE: Radiotherapy constitutes an essential element in the multimodal therapy of Ewing's sarcoma. Compared to other sarcomas, Ewing tumors normally show a good response to radiotherapy. However, there are consistently tumors with a radioresistant phenotype, and the underlying mechanisms are not known in detail. Here we investigated the association between survivin protein expression and the radiosensitivity of Ewing's sarcoma in vitro. MATERIAL AND METHODS: An siRNA-based knockdown approach was used to investigate the influence of survivin expression on cell proliferation, double-strand break (DSB) induction and repair, apoptosis and colony-forming ability in four Ewing's sarcoma cell lines with and without irradiation. RESULTS: Survivin protein and mRNA were upregulated in all cell lines tested in a dose-dependent manner. As a result of survivin knockdown, STA-ET-1 cells showed reduced cell proliferation, an increased number of radiation-induced DSBs, and reduced repair. Apoptosis was increased by knockdown alone and increased further in combination with irradiation. Colony formation was significantly reduced by survivin knockdown in combination with irradiation. CONCLUSION: Survivin is a radiation-inducible protein in Ewing's sarcoma and its down-regulation sensitizes cells toward irradiation. Survivin knockdown in combination with radiation inhibits cell proliferation, repair, and colony formation significantly and increases apoptosis more than each single treatment alone. This might open new perspectives in the radiation treatment of Ewing's sarcoma.

A combination of lipoic acid plus coenzyme Q10 induces PGC1α, a master switch of energy metabolism, improves stress response, and increases cellular glutathione levels in cultured C2C12 skeletal muscle cells.

Skeletal muscle function largely depend on intact energy metabolism, stress response, and antioxidant defense mechanisms. In this study, we tested the effect of a combined supplementation of α-lipoic acid (LA) plus coenzyme Q10 (Q10) on PPARγ-coactivator α (PGC1α) activity, expression of glutathione-related phase II enzymes and glutathione (GSH) levels in cultured C2C12 myotubes. Supplementation of myotubes with 250 µmol/L LA plus 100 µmol/L Q10 significantly increased nuclear levels of PGC1α, a master switch of energy metabolism and mitochondrial biogenesis. The increase of nuclear PGC1α was accompanied by an increase in PPARγ transactivation, a downstream target of PGC1α, and an increase in mitochondrial transcription factor A mRNA centrally involved in mitochondrial replication and transcription. Furthermore, supplementation of myotubes with LA plus Q10 resulted in an increase of genes encoding proteins involved in stress response, GSH synthesis, and its recycling. In LA-plus-Q10-treated myotubes a significant 4-fold increase in GSH was evident. This increase in GSH was accompanied by increased nuclear Nrf2 protein levels, partly regulating γGCS and GST gene expression. Present data suggest that the combined supplementation of skeletal muscle cells with LA plus Q10 may improve energy homeostasis, stress response, and antioxidant defense mechanisms.

Cyanidin does not affect sulforaphane-mediated Nrf2 induction in cultured human keratinocytes.

There is increasing interest in the gene-regulatory activities of isothiocyanates and flavonoids in human skin. Nrf2 agonists, such as isothiocyanate sulforaphane (SFN), have been shown to promote chemopreventive effects in skin both in vitro and in vivo. Recent data indicate that different secondary plant compounds may either antagonise or enhance SFN-induced Nrf2 activation. We therefore studied the interactions of a flavonoid, cyanidin and the potent Nrf2 inductor SFN in cultured human keratinocytes (HaCaT cells). We observed that cyanidin does not induce the activation of Nrf2 and its target genes, γ-glutamylcysteine synthetase (γGCS), NAD(P)H:quinone oxidoreductase 1 and haem oxygenase-1 in HaCaT cells. Furthermore, SFN-mediated Nrf2 activation and its target gene expression were not further enhanced by the co-application of SFN with cyanidin.

3,3'-Diindolylmethane but not indole-3-carbinol activates Nrf2 and induces Nrf2 target gene expression in cultured murine fibroblasts.

There is increasing interest in the gene-regulatory activity of Brassica vegetable derived phytochemicals such as 3,3'-diindolylmethane (DIM) and indole-3-carbinol (I3C). DIM is formed under acidic conditions by dimerization of I3C. This study compared the Nrf2 activating potential of DIM and I3C in murine fibroblasts (NIH3T3). In contrast to its precursor I3C, DIM induces the transactivation of Nrf2. Furthermore, Nrf2 targets such as HO-1, γGCS and NQO1 were increased on the mRNA and protein levels following DIM treatment. DIM was less potent than sulforaphane (used as positive control) in inducing Nrf2-dependent gene expression. The present data suggest that the dimerization of I3C to DIM increases its Nrf2 inducing activity.

Cellular uptake, stability, visualization by 'Naturstoff reagent A', and multidrug resistance protein 1 gene-regulatory activity of cyanidin in human keratinocytes.

There is increasing interest in the role of anthocyanidins as potential skin protective phytochemicals. However, little is known if and to what extent anthocyanidins are taken up by the human skin. In the present study cellular uptake (as determined by HPLC), stability, and gene-regulatory activity of cyanidin were determined in human HaCaT keratinocytes in culture. Using the fluorescent dye Naturstoff reagent A cyanidin was visualized in order to determine its cellular accumulation via flow cytometry and fluorescence microscopy. Cyanidin was rapidly taken up by HaCaT cells at relatively low concentrations. Following incubation, cellular cyanidin levels decreased time-dependently most likely due to degradation into protocatechuic acid and phloroglucinol aldehyde. Confocal laser scanning microscopy data demonstrated that cyanidin was mainly present in the cytoplasm. Cellular uptake of cyanidin was accompanied by an inhibition of multidrug resistance protein 1 (involved in cellular efflux of flavonoids) mRNA-levels indicating its gene-regulatory activity. Naturstoff reagent A seems to be a promising fluorescent dye to visualize cyanidin in keratinocytes.

Egg-laying patterns and in vivo egg production in the monogenean parasites Heteraxine heterocerca and Benedenia seriolae from Japanese yellowtail Seriola quinqueradiata.

Egg-laying patterns and egg production in Heteraxine heterocerca from the gills and Benedenia seriolae from the skin of Japanese yellowtail Seriola quinqueradiata in Japan were investigated in vivo. Eggs were collected every 3 h from sexually mature H. heterocerca and B. seriolae infecting 3 S. quinqueradiata kept individually over 3 consecutive days and exposed to alternating periods of illumination and darkness (LD 12:12; light on 06.00, light off 18.00) and maintained at 23.8 +/- 0.1 degrees C and 35 ppt salinity. A well-defined egg-laying rhythm was demonstrated for H. heterocerca while B. seriolae was shown torelease eggs continuously. A total of 114,000 H. heterocerca eggs was collected and of these, 45.4 (42.5-49.9)% were collected during the first 3 h period following dark at 18.00 h. A total of 662,857 B. seriolae eggs was collected and these were distributed over each 3 h period ranging from 11.1 to 14.1% of the daily egg output. All eggs extracted from the uterus of each H. heterocerca were joined together forming an 'egg-string'. The contrasting egg-laying patterns of H. heterocerca and B. seriolae suggest that each species makes use of a different infection strategy to infect the same host species, S. quinqueradiata.

National aquatic animal health plans: the Australian experience.

Following a major pilchard (Sardinops sagax) mortality event in 1995, Australia recognised the need for a national approach to aquatic animal health, particularly with respectto disease response. Cooperation between industry and government led to the development of AQUAPLAN, Australia's National Strategic Plan for Aquatic Animal Health. Under AQUAPLAN, institutional arrangements for the national technical response to aquatic animal health emergencies were developed based on existing arrangements for terrestrial animal health. The number and range of Australian Aquatic Veterinary Emergency Plan (AQUAVETPLAN) manuals are rising steadily; these are manuals that outline Australia's approach to national disease preparedness and propose the technical response and control strategies to be activated. Additional resources include standard diagnostic techniques and a disease field identification guide. Simulation exercises provide training to respond to aquatic emergency animal disease events. While resource issues and addressing governance remain priorities for the further implementation of AQUAPLAN, the highest priority is the development of a formal arrangement between governments and private sectors on the response to an aquatic emergency animal disease event.

Pediatric radiation oncology in Germany: a study of availability and application.

BACKGROUND: Radiotherapy plays a pivotal role in many multimodal therapy concepts in pediatric oncology. However, the absolute number of irradiated children is estimated to be quite low. The aim of this study was to evaluate the availability and application of pediatric radiation oncology in Germany. METHOD: In summer 2007, a standardized questionnaire was sent to all radiotherapy facilities in Germany. The questions regarded the structure of the departments, the number of irradiated children each year including the distribution of the different diagnoses, the number of curative treatments, inclusion in study trials, and existence of special contact persons for pediatric radiotherapy as well as technical aspects of irradiation of children. RESULTS: Answers to the questionnaires were obtained from 171 departments (77.4%). Of these, 67 (39%) stated to regularly treat children. These departments treated one to nine children in median each year (<5 children/year: 23 departments; >or=20 children: 15 departments). Most of these children suffered from brain tumors, Hodgkin's disease and acute lymphatic leukemia (ALL). Three-dimensional conformal radiotherapy was the most frequent treatment technique; special techniques like intensity-modulated radiotherapy (IMRT) or brachytherapy were rare. CONCLUSIONS: Due to quite low patient numbers treated in most radiotherapy facilities, individual experiences in pediatric radiation oncology can be assumed to be quite limited. As radiotherapy is part of multimodal therapy approaches in pediatric oncology and children treated with radiotherapy are at special risk for potential side effects, pediatric radiation oncology remains a sophisticated area. Therefore radiotherapy reference-institutions implemented by the therapy optimizing protocols are of fundamental importance.

[Stereotactic body radiotherapy (SBRT) -- an overview under special consideration of SBRT and LITT in the therapy of liver metastases]. / Extrakranielle stereotaktische Radiotherapie (ESRT) - eine Ubersicht unter besonderer Berücksichtigung von ESRT und LITT in der Behandlung von Lebermetastasen.

Stereotactic body radiotherapy (SBRT) is a high dose radiotherapy, the radiation dose is applicated one-time or in a few fractions exactly to the tumor or metastases under maximal separation from the normal tissue. Because of this a major expenditure of medical and technical efforts are necessary, a detailed description of the proceedings is following in the methodic part of this article. Indications of SBRT are especially medical irresectable lung tumors of early stages, primary liver/biliary tumors and pulmonary or liver metastases if there is an oncological benefit for the patients. The side effects are moderate, the local tumor control rate is between 78 to 100 %. Depending on the primary tumor the overall survival is prolonged statistically significant. In the Klinikum Krefeld indications of SBRT vs chemotherapy, LITT or resection are discussed by an interdisciplinary conference of gastroenterologists/oncologists, radiologists, radiooncologists and surgeons. An example of LITT will be shown also.

Effects of the gill monogenean Zeuxapta seriolae (Meserve, 1938) and treatment with hydrogen peroxide on pathophysiology of kingfish, Seriola lalandi Valenciennes, 1833.

Infections by the gill fluke Zeuxapta seriolae are a serious concern for sea cage aquaculture of kingfish, Seriola lalandi. The present study aimed to determine the pathophysiological effects of a progressive infection with Z. seriolae and the effects of treatment with hydrogen peroxide. For the progression of infection study, infected fish were taken from a sea cage farm, treated to remove parasites and then infected by cohabitation with heavily infected fish. Samples were taken at 2-week intervals for 8 weeks. Infection intensity peaked at 4 weeks post-infection (mean intensity 565.9) and the number of mature worms (2 mm fixed length or larger) peaked at 6 weeks post-infection. Attachment of Z. seriolae appeared to cause little localized pathology; however, the occurrence of hyperplastic lamellae increased as the infection progressed. Haemoglobin concentrations were negatively correlated with Z. seriolae intensity and were lower than controls at 4 weeks (35.8% decrease) and 6 weeks (57.4% decrease) post-infection. Blood lactate concentration and plasma osmolality increased throughout the course of infection. For the effect of treatment experiment, groups of infected and non-infected fish were sampled either before or after treatment with hydrogen peroxide. Treated fish from both infected and uninfected groups had increased plasma lactate, osmolality and pH compared with pre-treatment groups. Treatment with hydrogen peroxide appeared to have acute effects on fish health but the magnitude (e.g. lactate, osmolality) and extent of the effects (e.g. haemoglobin) was much less than that caused by chronic infection with Z. seriolae.