Accurately evaluating for a small bowel obstruction using an abdominal radiograph, by a new method: The Bowel-Spine Ratio.

INTRODUCTION: A well-established method does not exist to rule out a small bowel obstruction using an abdominal xray series with significant accuracy. The hypothesis of the study is that the ratio of an average small bowel diameter to lumbar spine diameter over 0.5 is most likely a small bowel obstruction. METHODS: An x-ray abdominal series measurement technique was applied to 41 subjects with a chief complaint of "abdominal pain" as part of a randomized retrospective case review to predict an obstruction v. non obstruction. A total number of 81 abdominal pain subjects with a mean age of 46.7 years were selected with 40 excluded due to normal small bowel gas pattern. The subject's medical information was unknown to the authors when reading their images. The measurement technique involved averaging the largest and smallest small bowel short axis diameters with comparison to the lowest clearly visible lumbar body width. The subjects' medical course as described in the medical chart or subsequent computed tomography scans were used as the referencing standard to determine presence of obstruction vs non-obstruction. RESULTS: This method, called the Bowel-Spine Ratio (BSR), resulted in a sensitivity of 0.882 (0.622-0.979; 95% CI), specificity of 0.957 (0.760-0.998; 95% CI), accuracy of 94.7% (80.9%-99.1%; 95% CI) and a positive likelihood ratio of 21 for predicting a small bowel obstruction. CONCLUSION: The abdominal series Bowel-Spine Ratio is a simple yet effective technique to screen for a small bowel obstruction using limited resources and to avoid unnecessary computed tomography scans with the potential to reduce health care costs. IMPLICATIONS FOR PRACTICE: Clinicians could have increased confidence in utilizing abdominal radiographs to evaluate for small bowel obstruction.

Evaluating changes to home bowel cancer screening kits: an end-user perspective study.

PURPOSE: Many people do not participate in mail-out bowel cancer screening programs due to difficulties using the screening kit. The current study investigated the ways the screening kit could be modified to improve usability. METHODS: 1,109 people evaluated 15 different screening kit modifications. Participants reported on how these kit modifications would affect their screening barriers, their future screening intentions, and how much they would recommend that the modification is made to the current screening kit used the program. All responses were given via an online survey conducted between April and December of 2021. RESULTS: Seventeen percent of previous NBCSP non-participators indicated that a one-sample test would increase their intention to participate. Recommendation ratings demonstrated higher levels of support for modifications that included providing a barcode naming label (M = 9.06, 95% CI [8.81, 9.31]), having a larger diameter opening of the collection tube (M = 8.42, 95% CI [8.10, 8.74]), and highlighting the expiry date on the kit packaging (M = 8.59, 95% CI [8.29, 8.89]). There were lower levels of support for modifications that reduced the size of the packaging the kit is sent in (M = 6.47, 95% CI [6.09, 6.85]), removed branding from kit packaging (M = 5.98, 95% CI [5.57, 6.39]), and removed the information booklet that comes with the screening kit (M = 5.25, 95% CI [4.78, 5.72]). CONCLUSION: These findings highlight multiple ways in which bowel cancer screening kits can be changed to increase usability for invitees of national bowel cancer screening programs. Findings have implications for all screening programs that use immunochemical-based bowel cancer screening kits.

Consensus on the Key Characteristics of Immunotoxic Agents as a Basis for Hazard Identification.

BACKGROUND: Key characteristics (KCs), properties of agents or exposures that confer potential hazard, have been developed for carcinogens and other toxicant classes. KCs have been used in the systematic assessment of hazards and to identify assay and data gaps that limit screening and risk assessment. Many of the mechanisms through which pharmaceuticals and occupational or environmental agents modulate immune function are well recognized. Thus KCs could be identified for immunoactive substances and applied to improve hazard assessment of immunodulatory agents. OBJECTIVES: The goal was to generate a consensus-based synthesis of scientific evidence describing the KCs of agents known to cause immunotoxicity and potential applications, such as assays to measure the KCs. METHODS: A committee of 18 experts with diverse specialties identified 10 KCs of immunotoxic agents, namely, 1) covalently binds to proteins to form novel antigens, 2) affects antigen processing and presentation, 3) alters immune cell signaling, 4) alters immune cell proliferation, 5) modifies cellular differentiation, 6) alters immune cell-cell communication, 7) alters effector function of specific cell types, 8) alters immune cell trafficking, 9) alters cell death processes, and 10) breaks down immune tolerance. The group considered how these KCs could influence immune processes and contribute to hypersensitivity, inappropriate enhancement, immunosuppression, or autoimmunity. DISCUSSION: KCs can be used to improve efforts to identify agents that cause immunotoxicity via one or more mechanisms, to develop better testing and biomarker approaches to evaluate immunotoxicity, and to enable a more comprehensive and mechanistic understanding of adverse effects of exposures on the immune system. https://doi.org/10.1289/EHP10800.

Scoping health literacy in Latin America.

Studies evaluating the influence of health literacy on patient behavior and outcomes suggest a positive relationship between health literacy and health knowledge, health behaviors, and health status. In Latin American countries, studies assessing health literacy are few, regional, and demonstrate considerable variation, with reported rates of adequate health literacy ranging from 5.0% to 73.3%. In this paper, we examine and explore the state of health literacy and efforts to promote it in Latin America. Key challenges to those efforts include socioeconomic inequality, social/geographic isolation, and cultural-, language-, and policy-related barriers, many of which disproportionately affect indigenous populations and others living in rural areas. Greater use of infographics, videos, and mobile apps may enhance health literacy and patient empowerment, especially when language barriers exist. This paper provides strategies and tools for tailored programming, examples of successful health literacy interventions, and policy recommendations to improve health literacy in Latin America, intending to spur additional discussion and action. Centrally organized collaboration across multiple sectors of society, with community involvement, will enhance health literacy and improve health and well-being across Latin America.

Implementation Evaluation of a Complex Intervention to Improve Timeliness of Care for Veterans with Transient Ischemic Attack.

BACKGROUND: The Protocol-guided Rapid Evaluation of Veterans Experiencing New Transient Neurologic Symptoms (PREVENT) program was designed to address systemic barriers to providing timely guideline-concordant care for patients with transient ischemic attack (TIA). OBJECTIVE: We evaluated an implementation bundle used to promote local adaptation and adoption of a multi-component, complex quality improvement (QI) intervention to improve the quality of TIA care Bravata et al. (BMC Neurology 19:294, 2019). DESIGN: A stepped-wedge implementation trial with six geographically diverse sites. PARTICIPANTS: The six facility QI teams were multi-disciplinary, clinical staff. INTERVENTIONS: PREVENT employed a bundle of key implementation strategies: team activation; external facilitation; and a community of practice. This strategy bundle had direct ties to four constructs from the Consolidated Framework for Implementation Research (CFIR): Champions, Reflecting & Evaluating, Planning, and Goals & Feedback. MAIN MEASURES: Using a mixed-methods approach guided by the CFIR and data matrix analyses, we evaluated the degree to which implementation success and clinical improvement were associated with implementation strategies. The primary outcomes were the number of completed implementation activities, the level of team organization and > 15 points improvement in the Without Fail Rate (WFR) over 1 year. KEY RESULTS: Facility QI teams actively engaged in the implementation strategies with high utilization. Facilities with the greatest implementation success were those with central champions whose teams engaged in planning and goal setting, and regularly reflected upon their quality data and evaluated their progress against their QI plan. The strong presence of effective champions acted as a pre-condition for the strong presence of Reflecting & Evaluating, Goals & Feedback, and Planning (rather than the other way around), helping to explain how champions at the +2 level influenced ongoing implementation. CONCLUSIONS: The CFIR-guided bundle of implementation strategies facilitated the local implementation of the PREVENT QI program and was associated with clinical improvement in the national VA healthcare system. TRIAL REGISTRATION: clinicaltrials.gov: NCT02769338.

Good emergency management practices: a review of the core principles, with a focus on preparedness.

Animal health emergencies can also have serious socio-economic and public health consequences, including impacts on human health, as well as food security and safety. Therefore, policy-makers and advisers should take an active part in the development of emergency management systems. A formally structured animal health emergency management system sets out, in a systematic way, the elements required to achieve the necessary level of preparedness, and provides for planning and implementation of the appropriate actions to be taken in an emergency. Good emergency management practices, as laid down by the Emergency Management Centre for Animal Health (EMC-AH) of the Food and Agriculture Organization of the United Nations, should incorporate all four phases of an animal health event: peacetime (i.e. before the event occurs), alert, emergency and reconstruction. Five actions are implemented before, during and after an animal health event: prepare, prevent, detect, respond and recover. A strategic action plan can be drafted to schedule the activities required to develop the emergency management system and increase a country's level of preparedness, step by step. The EMC-AH aims to support all components of emergency management at the national, regional and international levels along this progressive pathway for emergency preparedness.

Les urgences en santé animale peuvent avoir de graves conséquences socioéconomiques et de santé publique avec d'importantes répercussions sur la santé humaine, la sécurité alimentaire et la sécurité sanitaire des aliments. De ce fait, les décideurs et les conseillers en matière d'élaboration des politiques devraient participer activement à la conception de systèmes de gestion des urgences. Un système officiel de gestion des urgences en santé animale définit de manière systématique les éléments à mettre en place pour atteindre le niveau requis de préparation et envisage la planification ainsi que la mise en œuvre des interventions qu'il conviendra de mener dans une situation d'urgence. Telle que définie par le Centre de gestion des urgences de santé animale (EMC­AH) de l'Organisation des Nations Unies pour l'alimentation et l'agriculture, une bonne gestion des urgences prend en compte chacune des quatre phases d'un événement zoosanitaire, à savoir : le temps dit « de paix ¼ (c'est-à-dire avant que ne survienne l'événement), l'alerte, l'urgence et la reconstruction. Cinq types d'actions sont mises en œuvre avant, pendant et après l'événement de santé animale : la préparation, la prévention, la détection, la réponse et le rétablissement. Un plan d'action stratégique peut être élaboré, afin de programmer les activités requises pour renforcer le système de gestion des urgences et accroître le niveau de préparation du pays, étape par étape. L'EMC­AH entend soutenir toutes les composantes de la gestion des urgences aux niveaux national, régional et international dans le cadre de cette méthode progressive de préparation aux urgences.

Las emergencias zoosanitarias también pueden tener graves consecuencias socioeconómicas y de salud pública e incidir, entre otros ámbitos, en la salud humana, la seguridad alimentaria y la inocuidad de los alimentos. Por ello los planificadores de políticas y los asesores en la materia deben participar activamente en la instauración de sistemas de gestión de emergencias. Cuando está estructurado oficialmente, un sistema de gestión de emergencias zoosanitarias señala, de manera sistemática, los elementos requeridos para alcanzar el nivel de preparación necesario y prevé los procesos de planificación y aplicación de las pertinentes medidas que deben tomarse en el curso de una emergencia. Las buenas prácticas de gestión de emergencias, tal como las define el Centro de Gestión de Emergencias para la Salud Animal (EMC-AH) de la Organización de las Naciones Unidas para la Alimentación y la Agricultura, deben integrar las cuatro fases de un evento zoosanitario: la etapa de «paz¼ (esto es, antes de que se produzca el evento), la alerta, la emergencia y la reconstrucción. Antes, durante y después de un evento zoosanitario se efectúan cinco tipos de operaciones en que se conjugan otros tantos verbos: prepararse, prevenir, detectar, responder y recuperarse. Las actividades necesarias para establecer el sistema de gestión de emergencias y elevar el nivel de preparación de un país pueden estar programadas, paso a paso, en un plan estratégico de acción redactado al efecto. El EMC-AH tiene por objetivo ayudar a cuantos participan en la gestión de emergencias a nivel nacional, regional e internacional a avanzar por esta senda progresiva de preparación para casos de emergencia.

The protocol-guided rapid evaluation of veterans experiencing new transient neurological symptoms (PREVENT) quality improvement program: rationale and methods.

BACKGROUND: Transient ischemic attack (TIA) patients are at high risk of recurrent vascular events; timely management can reduce that risk by 70%. The Protocol-guided Rapid Evaluation of Veterans Experiencing New Transient Neurological Symptoms (PREVENT) developed, implemented, and evaluated a TIA quality improvement (QI) intervention aligned with Learning Healthcare System principles. METHODS: This stepped-wedge trial developed, implemented and evaluated a provider-facing, multi-component intervention to improve TIA care at six facilities. The unit of analysis was the medical center. The intervention was developed based on benchmarking data, staff interviews, literature, and electronic quality measures and included: performance data, clinical protocols, professional education, electronic health record tools, and QI support. The effectiveness outcome was the without-fail rate: the proportion of patients who receive all processes of care for which they are eligible among seven processes. The implementation outcomes were the number of implementation activities completed and final team organization level. The intervention effects on the without-fail rate were analyzed using generalized mixed-effects models with multilevel hierarchical random effects. Mixed methods were used to assess implementation, user satisfaction, and sustainability. DISCUSSION: PREVENT advanced three aspects of a Learning Healthcare System. Learning from Data: teams examined and interacted with their performance data to explore hypotheses, plan QI activities, and evaluate change over time. Learning from Each Other: Teams participated in monthly virtual collaborative calls. Sharing Best Practices: Teams shared tools and best practices. The approach used to design and implement PREVENT may be generalizable to other clinical conditions where time-sensitive care spans clinical settings and medical disciplines. TRIAL REGISTRATION: clinicaltrials.gov: NCT02769338 [May 11, 2016].

Dissociation and other clinical phenomena in youth with psychogenic non-epileptic seizures (PNES) compared to youth with epilepsy.

PURPOSE: To compare youth with psychogenic non-epileptic seizures (PNES) to youth with epilepsy on demographic and clinical features and the Trauma Symptom Checklist for Children (TSCC). METHOD: A retrospective study of 31 patients; 15 patients with PNES (11 females) and 16 patients with epilepsy (8 females) collected consecutively between 2014-2018. Demographic and clinical information (age of seizure onset, life adversities, individual/family psychiatric history, etc.) were gathered. Scales from the TSCC (Dissociation, Depression, Anxiety) were analyzed. RESULTS: Eleven of the youth with PNES (YPNES) (73%) were female, mean age was 14.3 ± 1.6 years and years of education were 9 ± 1.9. Eight of the youth with epilepsy (YWE) (50%) were females, mean age was 11.9 ± 2.8 years and years of education were 5.6 ± 2.9. All 15 YPNES and over half of their families had comorbid psychological problems whilst rates of personal and family psychiatric histories were much lower in YWE. Well over half of YPNES reported experiencing life adversities while one fourth of YWE reported these types of experiences. Significant differences were observed between YPNES and YWE on TSCC Overt Dissociation (p < 0.003), Dissociation (p < 0.009), and Depression (p < 0.001) scales, with YWE producing lower scores. When the six target variables were condensed into one principal component, the global TSCC score was lower in the epilepsy group, even after adjusting for potential effects age, seizure frequency and intellectual quotient. CONCLUSIONS: The current study's results indicate that YPNES present with comparably higher self-reported symptoms of depression and dissociation than YWE.

Clinical Immunotoxicology.

Assessment of the potential for a test article to have adverse effects on immune function can be difficult in clinical trials due to a relative lack of useful endpoints. It is therefore common to use a weight of evidence approach with nonclinical studies to indicate if there is a cause for concern that the test article has immunotoxic potential. The most commonly used follow-up assay for immunosuppression is the T-dependent antibody response (TDAR). However, final selection of an assay (or assays) to evaluate potential human immunotoxicity depends on the type of findings in nonclinical studies. For example, signs of unintended immunostimulation or immunomodulation may be assessed using specialized assays using human cells. Other factors should also be considered, such as pharmacology of the test article, potential structural similarities with known immunomodulatory agents, and/or pharmacokinetic/drug disposition findings consistent with accumulation of test article/metabolite in immune system tissues. Although evaluation of the potential for a test article to have adverse effects on immune function can be a complex task, established nonclinical models and some clinical endpoints can be useful to determine the safety of products intended for use as human therapeutics.

Clinical Trial Results Summary for Laypersons: A User Testing Study.

OBJECTIVE: To apply "user testing" to maximize readability and acceptability of a Clinical Trial Results Laypersons Summary-a new European requirement. METHODS: "User testing" (using questionnaire and semistructured interview) assessed whether people could find and understand key points. Findings were used to improve content and design, prior to retesting. Participants had a range of levels of health literacy and there was a higher education group. Participants accessed the summary on screen. In round 1 we tested 12 points of information. In round 2 a revised summary addressing round 1 findings was tested, leading to a third final version. RESULTS: In round 1, 2 of 12 points of information did not reach the target and interviews raised further format and content issues (some distracting technical explanations and inability to find or understand the 2 main study purposes). These findings informed revisions for the version tested in round 2, with 2 different points not reaching the target (inclusion criteria relating to duration of seasonal allergies and how researchers found out about participants' symptoms). Identified problems in both rounds were addressed and reflected in the final version. Despite improvements, participants did not consistently understand that summaries were intended for the public, or to only interpret results of single trials in the context of additional trials. All readers, including those with higher education, found the clear and straightforward language acceptable. CONCLUSIONS: Applying "user testing" resulted in a largely health-literate summary suitable for people across a range of backgrounds.

Final results of a multi-institutional phase II trial of reirradiation with concurrent weekly cisplatin and cetuximab for recurrent or second primary squamous cell carcinoma of the head and neck.

Background: The optimal regimen of chemotherapy and reirradiation (re-XRT) for recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We report the final outcomes of a multicenter phase II trial evaluating cetuximab and cisplatin-based chemotherapy concurrent with re-XRT for patients with recurrent HNSCC. Materials and methods: Patients with unresectable recurrent disease or positive margins after salvage surgery arising within a previously irradiated field with KPS ≥ 70 were eligible for this trial. Cetuximab 400 mg/m2 was delivered as a loading dose in week 1 followed by weekly cetuximab 250 mg/m2 and cisplatin 30 mg/m2 concurrent with 6 weeks of intensity-modulated radiotherapy to a dose of 60-66 Gy in 30 daily fractions. Patients who previously received both concurrent cetuximab and cisplatin with radiation or who received radiotherapy less than 6 months prior were ineligible. Results: From 2009 to 2013, 48 patients enrolled on this trial, 2 did not receive any protocol treatment. Of the remaining 46 patients, 34 were male and 12 female, with a median age of 62 years (range 36-85). Treatment was feasible and only 1 patient did not complete the treatment course. Common grade 3 or higher acute toxicities were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%), mucositis (11%) and anorexia (11%). There were no grade 5 acute toxicities. Eight grade 3 late toxicities were observed, four of which were swallowing related. With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4% and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was significantly improved with young age (P = 0.01). OS was not associated with radiation dose, surgery before re-XRT or interval from prior XRT. Conclusions: Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good treatment outcomes for patients with high-risk features. Younger patients had significantly improved OS. ClinicalTrials.Gov Identifier: NCT00833261.

Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition.

Chronic inflammation has been associated with a variety of human cancers including prostate cancer. Interleukin-17 (IL-17) is a critical pro-inflammatory cytokine, which has been demonstrated to promote development of prostate cancer, colon cancer, skin cancer, breast cancer, lung cancer and pancreas cancer. IL-17 promotes prostate adenocarcinoma with a concurrent increase of matrix metalloproteinase 7 (MMP7) expression in mouse prostate. Whether MMP7 mediates IL-17's action and the underlying mechanisms remain unknown. We generated Mmp7 and Pten double knockout (KO) (Mmp7-/-) mouse model and demonstrated that MMP7 promotes prostate adenocarcinoma through induction of epithelial-to-mesenchymal transition (EMT) in Pten-null mice. MMP7 disrupted E-cadherin/ß-catenin complex to upregulate EMT transcription factors in mouse prostate tumors. IL-17 receptor C and Pten double KO mice recapitulated the weak EMT characteristics observed in Mmp7-/- mice. IL-17 induced MMP7 and EMT in human prostate cancer LNCaP, C4-2B and PC-3 cell lines, while small interfering RNA knockdown of MMP7 inhibited IL-17-induced EMT. Compound III, a selective MMP7 inhibitor, decreased development of invasive prostate cancer in Pten single KO mice. In human normal prostates and prostate tumors, IL-17 mRNA levels were positively correlated with MMP7 mRNA levels. These findings demonstrate that MMP7 mediates IL-17's function in promoting prostate carcinogenesis through induction of EMT, indicating IL-17-MMP7-EMT axis as a potential target for developing new strategies in the prevention and treatment of prostate cancer.

International health threats and global early warning and response mechanisms.

The global community continues to incur the high costs of crisis mitigation and emergency response to outbreaks of emerging infectious diseases, such as those caused by the H5N1 highly pathogenic avian influenza virus, Ebola virus, Nipah virus, Zika virus or the Middle East respiratory syndrome coronavirus. These viruses are particularly dangerous in regions associated with poor development indicators and high vulnerability. The drivers of these disease crises include failures in the way that animal diseases are detected and reported and failures in the way in which disease response is implemented by animal health and public health systems. In addition, the lack of a coordinated response hampers disease control efforts. A comprehensive approach for disease prevention, detection and response, however, requires a coordinated and joint effort among governments, communities, donors and international networks to invest effectively in prevention systems that can identify early signals of the emergence, spillover and spread of animal pathogens at the local level. These signals include trade bans, market closures, civil unrest, heavy rains and droughts associated with climate change, and livestock intensification or changes in consumer behaviour. The global community needs to increase its investment in early warning and detection systems that can provide information that enables action to be taken at the national, regional and global levels in the event of an outbreak of a transboundary animal disease (TAD). Like any preventive measure, an early warning system requires financial resources, but these are insignificant when compared to the losses that are avoided. Building a global early warning and effective response system for outbreaks is value for money, as the benefits far outweigh the costs. The goal of the Food and Agriculture Organization of the United Nations (FAO) is to end hunger and poverty, which is a challenging and complex task. Building global capacity to prepare for and respond to TADs is an important element of the FAO's strategic objective to increase the resilience of livelihoods to threats and crises. Each year, livestock, and the people who rely upon them for their livelihoods, are confronted with animal disease and crises. They can strike suddenly, causing obvious illness and death, or emerge insidiously and become well established before becoming apparent. Animal disease emergencies threaten the production of, and access to, food; consequently, one of the FAO's missions is to help countries to prepare for and respond to animal health disasters.

La communauté mondiale continue à supporter le coût élevé de l'atténuation des crises ainsi que des réponses apportées en urgence aux foyers de maladies infectieuses émergentes, par exemple les infections dues au virus H5N1 de l'influenza aviaire hautement pathogène, au virus Ebola, au virus Nipah, au virus Zika ou au coronavirus responsable du syndrome respiratoire du Moyen-Orient. Ces virus sont particulièrement dangereux dans les régions les plus vulnérables et dont les indicateurs de développement sont bas. Les défaillances dans la détection et la notification des maladies animales jouent un rôle déterminant dans ces crises sanitaires, de même que l'incapacité des systèmes de santé animale et publique à mettre en œuvre une réponse sanitaire appropriée. En outre, l'absence de coordination dans les réponses apportées affaiblit les efforts pour lutter contre les maladies. La mise en place d'une méthode de prévention, de détection et de réponse intégrée face aux maladies exige que les gouvernements, les communautés, les donateurs et les réseaux internationaux associent leurs efforts et se concertent afin d'investir efficacement dans des systèmes de prévention capables de détecter à l'échelle locale les tout premiers signes d'émergence d'un agent pathogène chez les animaux, de sa transmission à d'autres espèces et de sa propagation. Parmi ces signes révélateurs on peut citer certaines interdictions d'importer, mais aussi la fermeture des marchés, l'existence de troubles civils, les changements climatiques tels que de fortes précipitations ou une sécheresse prolongée et la modification de certaines tendances en production animale ou du comportement des consommateurs. La communauté mondiale doit investir davantage dans des systèmes d'alerte précoce et de détection afin d'obtenir l'information nécessaire pour prendre des mesures appropriées, à l'échelle nationale, régional et mondiale, en cas d'apparition d'une maladie animale transfrontalière. Comme toute mesure de prévention, les systèmes d'alerte précoce doivent être correctement financés, mais cet effort est insignifiant lorsqu'on le compare aux pertes qu'il permet d'éviter. La création d'un système mondial d'alerte précoce et de réponse en cas de foyers constitue un investissement rentable, qui génère des bénéfices bien supérieurs à ses coûts. L'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO) a pour objectif de mettre un terme à la faim et à la pauvreté dans le monde, ce qui constitue une tâche complexe et difficile. Le renforcement des capacités mondiales de préparation et de réponse en cas de maladies animales transfrontalières est un aspect important des objectifs stratégiques de la FAO visant à accroître la résilience des moyens d'existence face aux crises et aux menaces. Chaque année, le cheptel domestique et les personnes qui en tirent leur subsistance sont confrontés à des maladies animales et à des crises sanitaires. Celles-ci peuvent se déchaîner brutalement et présenter un tableau clair de morbidité et de mortalité, ou bien émerger de manière insidieuse et se propager avant l'apparition de signes manifestes. Puisque la production et l'accès aux denrées alimentaires sont menacés par les catastrophes sanitaires dues aux maladies animales, l'une des missions de la FAO consiste à aider les pays à répondre à ces catastrophes et à s'y préparer.

La comunidad mundial sigue soportando los elevados costos de las actividades de atenuación de crisis y de respuesta de emergencia ante brotes de enfermedades infecciosas emergentes como los causados por el virus de la influenza aviar altamente patógena H5N1, el del Ébola, el Nipah, el Zika o el coronavirus del síndrome respiratorio de Oriente Medio. Estos virus resultan especialmente peligrosos en regiones que presentan indicadores de desarrollo mediocres y un elevado nivel de vulnerabilidad. Entre los factores que subyacen a estas crisis sanitarias están las deficiencias en la forma de detectar y comunicar estas enfermedades y la inadecuada aplicación de medidas de respuesta por parte de los sistemas de salud pública y sanidad animal. Por añadidura, la ausencia de una respuesta coordinada lastra también las actividades de lucha. Un trabajo integral de prevención y detección de enfermedades y de respuesta a ellas exige sin embargo un esfuerzo coordinado y conjunto de gobiernos, poblaciones, donantes y redes internacionales para invertir eficazmente en sistemas de prevención que sirvan para detectar las señales precoces de aparición, extensión y propagación de patógenos animales a nivel local, señales como prohibiciones comerciales, cierres de mercados, desórdenes civiles, cambios climáticos como lluvias o sequías intensas o modificación de la dinámica de producción ganadera o los patrones de consumo. La comunidad mundial debe invertir en mayor medida en sistemas de alerta y detección rápidas que aporten información que pueda traducirse en acciones de ámbito nacional, regional y mundial en caso de brote de una enfermedad animal transfronteriza. Como toda medida de carácter preventivo, un sistema de alerta rápida requiere recursos económicos, pero su cuantía resulta insignificante en comparación con las pérdidas que se evitan. La construcción de un sistema mundial de alerta rápida y respuesta eficaz en caso de brote ofrece gran rentabilidad, por cuanto los beneficios superan holgadamente los costos. La Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO) persigue el objetivo de poner fin al hambre y la pobreza, empresa harto difícil y compleja. Dotar al mundo de la capacidad de preparación y respuesta ante enfermedades animales transfronterizas es un elemento importante del objetivo estratégico de la FAO de lograr que los medios de sustento gocen de mayor resiliencia ante crisis y amenazas. Cada año, los rebaños de animales domésticos y las personas que dependen de ellos para vivir hacen frente a enfermedades y crisis zoosanitarias, que pueden golpear de forma súbita y extender abiertamente la enfermedad y la muerte o, por el contrario, surgir insidiosamente y arraigar antes de que su presencia resulte patente. Las emergencias zoosanitarias hacen peligrar la producción de alimentos y el acceso a ellos. Una de las misiones de la FAO, por consiguiente, es la de ayudar a los países a prepararse para episodios de catástrofe zoosanitaria y a responder a este tipo de eventos cuando se produzcan.

Linking animal diseases and social instability.

Social instability occurs as a consequence of war, civil strife or natural disasters such as earthquakes, floods and droughts. Animal diseases, including zoonoses, can be both a precursor to social instability and a result of social instability. Coping mechanisms, such as sound policies, trust in government, and robust infrastructure break down at times of civil instability. Such breakdowns often lead to a decline in both public health and the food and agricultural livestock base, thus creating a vicious cycle that involves inadequate nutrition, threatened livelihoods, and fewer opportunities for safe trade. This article is principally a discussion of a theoretical nature on the dynamics between animal diseases and social instability. Based on their experience of working for the Food and Agriculture Organization of the United Nations (FAO), the authors provide numerous examples of the connection between the two, mostly in countries that have fragile environments and are experiencing protracted crises. Disease has a direct and immediate effect on a community, but, in addition, if the community is not able to recover from the impact of a disease on their health and livelihoods, the consequences of an outbreak can persist even after the disease is no longer present. Stability, therefore, depends on a variety of factors, including the ability of a community to overcome the effects of a disease outbreak or other destabilising event. The FAO approach to helping families and communities to cope with the destabilizing effects of animal diseases is to build resilience, particularly amongst the most vulnerable households. This requires individuals and governments to gain a better understanding of what drives disease at the interface between human and animal health. In addition, it requires governments to invest in social protection programmes, establish a long-term risk reduction strategy that decreases vulnerability, and improve the sustainability of safe agricultural and marketing practices.

L'instabilité sociale est généralement une conséquence des conflits armés, des guerres civiles ou des catastrophes naturelles telles que tremblements de terre, inondations ou sécheresse. Les maladies animales, zoonoses incluses, sont des signes précurseurs de l'instabilité sociale, mais aussi son résultat. En période d'instabilité sociale, les mécanismes d'adaptation aux crises liés notamment à des politiques judicieuses, à la confiance dans l'action du gouvernement et à des infrastructures solides s'effondrent. Ces défaillances entraînent souvent un déclin à la fois de la santé publique et des ressources essentielles de l'agriculture et de l'élevage, créant ainsi un cercle vicieux caractérisé par une nutrition inadéquate, des moyens d'existence menacés et des possibilités raréfiées d'accéder à des marchés sûrs. L'essentiel de cet article est consacré à l'analyse théorique de la dynamique des liens entre les maladies animales et l'instabilité sociale. À partir de l'expérience acquise en travaillant pour l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO), les auteurs donnent de nombreux exemples de ces liens, qui concernent pour la plupart des pays dont l'environnement est fragilisé ou qui sont exposés à des crises prolongées. Toute maladie a un effet direct et immédiat sur la communauté atteinte ; or, dans les situations où une communauté n'est pas en capacité de se relever après avoir subi cet impact ni d'assurer un retour à la situation antérieure en matière de santé et de moyens de subsistance, les conséquences d'un foyer persistent bien au-delà de la durée de la maladie. Par conséquent, la stabilité dépend de facteurs variés, dont l'aptitude d'une communauté à surmonter les effets d'un foyer ou d'autres événements déstabilisants. La méthode suivie par la FAO pour aider les familles et les communautés à faire face aux effets déstabilisants des maladies animales consiste à renforcer leur capacité de résilience, en particulier dans les foyers les plus vulnérables. Cela suppose que les individus et les gouvernements améliorent leur connaissance des facteurs propices à l'apparition des maladies à l'interface entre la santé humaine et animale. En outre, cela suppose que les gouvernements investissent dans des programmes de protection sociale, qu'ils mettent en place une stratégie de réduction des risques sur le long terme qui limite les vulnérabilités et qu'ils œuvrent pour une meilleure durabilité des pratiques agricoles et commerciales exemptes de risques.

La inestabilidad social es producto de guerras, disturbios civiles o catástrofes naturales como terremotos, inundaciones o sequías. Las enfermedades animales, comprendidas las zoonosis, pueden ser un precursor o un resultado de la inestabilidad social. En condiciones de inestabilidad civil se agrietan los mecanismos de un país para hacer frente a esas enfermedades (tales como políticas sólidas, confianza en los poderes públicos e infraestructuras robustas), lo que suele traducirse en un deterioro de la salud pública y de la cabaña ganadera en que reposan la alimentación y la agricultura, generándose así un círculo vicioso que trae consigo una nutrición deficiente, pone en peligro los medios de sustento y dificulta un comercio seguro. Los autores examinan básicamente los aspectos teóricos de la dinámica que conecta entre sí las enfermedades animales y la inestabilidad social. Recurriendo a su experiencia de trabajo para la Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO), ofrecen numerosos ejemplos de la relación existente entre ambos fenómenos, sobre todo en países que presentan un medio ambiente fragilizado y sufren crisis prolongadas. La enfermedad repercute directa e inmediatamente en la población, pero además, si esta no puede recuperarse de los efectos de una enfermedad sobre su estado sanitario y sus medios de vida, las consecuencias de un brote pueden dejarse sentir hasta mucho después de que la enfermedad haya desaparecido. La estabilidad depende por lo tanto de diversos factores, en particular la capacidad de las comunidades para superar los efectos de un brote infeccioso u otros episodios que las hayan desestabilizado. Desde la FAO se trata de ayudar a las familias y comunidades a lidiar con los efectos desestabilizadores de las enfermedades animales generando resiliencia, especialmente en las familias más vulnerables. Para ello es menester que tanto individuos como poderes públicos conozcan mejor los factores que hacen que una enfermedad se manifieste en la interfaz de la salud humana con la sanidad animal. Es preciso, además, que las administraciones inviertan en programas de protección social, instituyan una estrategia a largo plazo de reducción del riesgo, que redunde en una menor vulnerabilidad, e instauren procedimientos agrícolas y de comercialización más sostenibles.

Is It Adverse, Nonadverse, Adaptive, or Artifact?

One of the principal challenges facing a toxicologic pathologist is to determine and differentiate a true adverse effect from a nonadverse or an adaptive response. Recent publications from the Society of Toxicologic Pathology (STP) and the European STP provide guidance for determining and communicating adversity in nonclinical toxicology studies. In order to provide a forum to inform and engage in a discussion on this important topic, a continuing education (CE) course was held during the 2016 STP Annual meeting in San Diego, CA. The lectures at this course provided guidance on determining and communicating adversity using case studies involving both clinical pathology and anatomic pathology. In addition, one talk also focused on data quality, study design, and interpretation of artifacts that could hinder the determination of adversity. The CE course ended with a talk on understanding adversity in preclinical studies and engaging the regulatory agencies in the decision-making process. This manuscript is designed to provide brief summaries of all the talks in this well-received CE course.

Analysis of the Candida albicans Phosphoproteome.

Candida albicans is an important human fungal pathogen in both immunocompetent and immunocompromised individuals. C. albicans regulation has been studied in many contexts, including morphological transitions, mating competence, biofilm formation, stress resistance, and cell wall synthesis. Analysis of kinase- and phosphatase-deficient mutants has made it clear that protein phosphorylation plays an important role in the regulation of these pathways. In this study, to further our understanding of phosphorylation in C. albicans regulation, we performed a deep analysis of the phosphoproteome in C. albicans. We identified 19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2,896 proteins. The ratios of serine, threonine, and tyrosine phosphosites were 80.01%, 18.11%, and 1.81%, respectively. The majority of proteins (2,111) contained at least two detected phosphorylation sites. Consistent with findings in other fungi, cytoskeletal proteins were among the most highly phosphorylated proteins, and there were differences in Gene Ontology (GO) terms for proteins with serine and threonine versus tyrosine phosphorylation sites. This large-scale analysis identified phosphosites in protein components of Mediator, an important transcriptional coregulatory protein complex. A targeted analysis of the phosphosites in Mediator complex proteins confirmed the large-scale studies, and further in vitro assays identified a subset of these phosphorylations that were catalyzed by Cdk8 (Ssn3), a kinase within the Mediator complex. These data represent the deepest single analysis of a fungal phosphoproteome and lay the groundwork for future analyses of the C. albicans phosphoproteome and specific phosphoproteins.

Serum and bal beta-D-glucan for the diagnosis of Pneumocystis pneumonia in HIV positive patients.

BACKGROUND/PURPOSE: The diagnosis of patients with pulmonary infiltrates and human immunodeficiency virus (HIV) infection remains a challenge. In current clinical practice the gold standard for Pneumocystis jirovecii pneumonia (PCP) diagnosis remains the identification of the organism in bronco alveolar lavage (BAL) using microscopy (e.g., silver stain). (1->3)-ß -d-glucan (BG) is a polysaccharide that is present within the cell wall of Pneumocystis and other fungi. METHODS: We analyzed serum and BAL lavage fluid from a cohort of 119 patients that did have HIV, a diagnosis of pneumonia and underwent bronchoscopy (FOB) for diagnosis of PCP. RESULTS: The discriminative power of serum BG for the diagnosis of PCP in this group of patients was very high. Using a cutoff of 300 pg/mL, the sensitivity, specificity, positive predictive value(PPV) and negative predictive value (NPV) were 91%, 92%, 89% and 93% respectively. A model for ROC with just serum BG (N = 108) had an AUC of 0.95. Serum procalcitonin (PCT) and BAL BG were not as accurate for the diagnosis of PCP. For BAL BG using a cutoff of 783 pg/mL, the sensitivity,specificity, positive predictive value (PPV) and negative predictive value (NPV) were 72%, 79%,72% and 79% respectively. The differences between the medians for serum PCT between the group with a without PCP did not reach statistical significance (p = 0.6137). CONCLUSION: The measurement of serum BG should be incorporated in the diagnostic work up of HIV positive patients with dyspnea and infiltrates on chest X X-ray. Our study confirms the diagnostic value of serum BG previously reported by others but we add a cutoff value that we believe is more accurate for patients with AIDS and suspicion of PCP.

GAL-021, a new intravenous BKCa-channel blocker, is well tolerated and stimulates ventilation in healthy volunteers.

BACKGROUND: Potassium-channels in the carotid body and the brainstem are important regulators of ventilation. The BKCa-channel contains response elements for CO, O2, and CO2. Its block increases carotid body signalling, phrenic nerve activity, and respiratory drive. GAL-021, a new BKCa-channel blocker, increases minute ventilation in rats and non-human primates. This study assessed the single-dose safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of GAL-021 in healthy volunteers. METHODS: Thirty subjects participated in a nine-period, randomized, double-blinded, placebo-controlled, crossover, ascending dose, first-in-human study with i.v. infusions of 0.1-0.96 mg kg(-1) h(-1) for 1 h and intermediate doses up to 4 h. RESULTS: Adverse event rates were generally similar among dose levels and between placebo- and GAL-021-treated subjects. At higher GAL-021 doses, a mild/moderate burning sensation at the infusion site occurred during the infusion. No clinically significant changes in vital signs or clinical chemistries were noted. Minute ventilation increased (AUE0-1 h ≈ 16%, P<0.05) and end-tidal carbon dioxide ([Formula: see text]) decreased (AUE0-1 h ≈ 6%, P<0.05) during the first hour at 0.96 mg kg(-1) h(-1) with 1/2-maximal [Formula: see text] and [Formula: see text]-change occurring by 7.5 min. Drug concentration rose rapidly during the infusion and decreased rapidly initially (distribution t1/2 of 30 min) and then more slowly (terminal t1/2 of 5.6 h). CONCLUSIONS: GAL-021 was safe and generally well tolerated with adverse events comparable with placebo except for an infusion site burning sensation. GAL-021 stimulated ventilation at the highest doses suggesting that greater infusion rates may be required for maximum PD effects. GAL-021 had PK characteristics consistent with an acute care medication.

Reprint of "Methylmercury production in and export from agricultural wetlands in California, USA: the need to account for physical transport processes into and out of the root zone".

Concentration and mass balance analyses were used to quantify methylmercury (MeHg) loads from conventional (white) rice, wild rice, and fallowed fields in northern California's Yolo Bypass. These analyses were standardized against chloride to distinguish transport pathways and net ecosystem production (NEP). During summer, chloride loads were both exported with surface water and moved into the root zone at a 2:1 ratio. MeHg and dissolved organic carbon (DOC) behaved similarly with surface water and root zone exports at ~3:1 ratio. These trends reversed in winter with DOC, MeHg, and chloride moving from the root zone to surface waters at rates opposite and exceeding summertime root zone fluxes. These trends suggest that summer transpiration advectively moves constituents from surface water into the root zone, and winter diffusion, driven by concentration gradients, subsequently releases those constituents into surface waters. The results challenge a number of paradigms regarding MeHg. Specifically, biogeochemical conditions favoring microbial MeHg production do not necessarily translate to synchronous surface water exports; MeHg may be preserved in the soils allowing for release at a later time; and plants play a role in both biogeochemistry and transport. Our calculations show that NEP of MeHg occurred during both summer irrigation and winter flooding. Wild rice wet harvesting and winter flooding of white rice fields were specific practices that increased MeHg export, both presumably related to increased labile organic carbon and disturbance. Outflow management during these times could reduce MeHg exports. Standardizing MeHg outflow:inflow concentration ratios against natural tracers (e.g. chloride, EC) provides a simple tool to identify NEP periods. Summer MeHg exports averaged 0.2 to 1µgm(-2) for the different agricultural wetland fields, depending upon flood duration. Average winter MeHg exports were estimated at 0.3µgm(-2). These exports are within the range reported for other shallow aquatic systems.

Measurement of Compton scattering from the deuteron and an improved extraction of the neutron electromagnetic polarizabilities.

The electromagnetic polarizabilities of the nucleon are fundamental properties that describe its response to external electric and magnetic fields. They can be extracted from Compton-scattering data-and have been, with good accuracy, in the case of the proton. In contradistinction, information for the neutron requires the use of Compton scattering from nuclear targets. Here, we report a new measurement of elastic photon scattering from deuterium using quasimonoenergetic tagged photons at the MAX IV Laboratory in Lund, Sweden. These first new data in more than a decade effectively double the world data set. Their energy range overlaps with previous experiments and extends it by 20 MeV to higher energies. An analysis using chiral effective field theory with dynamical Δ(1232) degrees of freedom shows the data are consistent with and within the world data set. After demonstrating that the fit is consistent with the Baldin sum rule, extracting values for the isoscalar nucleon polarizabilities, and combining them with a recent result for the proton, we obtain the neutron polarizabilities as αn=[11.55±1.25(stat)±0.2(BSR)±0.8(th)]×10(-4) fm(3) and ßn=[3.65∓1.25(stat)±0.2(BSR)∓0.8(th)]×10(-4) fm(3), with χ(2)=45.2 for 44 degrees of freedom.