3,356 research outputs found

    LIPIcs, Volume 251, ITCS 2023, Complete Volume

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    LIPIcs, Volume 251, ITCS 2023, Complete Volum

    La Forma del cáncer: Socialización y representación visual de la enfermedad en Instagram

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    Social media platforms like Instagram are a source of information and support for cancer patients. On this platform, millions of images shared by patients, organisations and the general public give shape to the social imagination of one of the most feared illnesses around the world. This thesis proposes a method to identify and obtain images of cancer from Instagram, a social media that in 2022 remains nearly inaccessible to research. Through a transdisciplinary lens, it combines the sociology of everyday life, visual sociology and methodologies from social media analysis to discover visual patterns in the images and find alternative discourses. The results show the variety of visual resources that patients use to communicate their illness and support the construction of their identity. They also show how Instagram’s economy of affection favours the publication of positive images, aligned with the discourse of survivorship, while they hamper the expression of other experiences. It concludes with the proposal for a new regime in the communication of cancer, based on the concept of socialisation.Las redes sociales visuales como Instagram son una fuente de información y apoyo para pacientes de cáncer. En esta red, millones de imágenes compartidas por pacientes, organizaciones y por el público general configuran la imaginación social de una de las enfermedades más temidas en todo el mundo. Esta tesis plantea una metodología para extraer y estudiar imágenes de esta red, prácticamente inaccesible para la investigación en 2022, y para su codificación. A través de un enfoque transdisciplinar, combina la sociología de la vida cotidiana, la sociología visual y las metodologías del análisis de redes sociales para descubrir patrones visuales en las imágenes de cáncer e identificar discursos alternativos. Los resultados muestran la variedad de recursos visuales que utilizan los pacientes de cáncer para comunicar su enfermedad y apoyar un proceso de construcción de la identidad. Muestran también cómo la economía afectiva de esta plataforma favorece la publicación de imágenes positivas y alineadas con el discurso de la supervivencia, mientras que supone un reto para visibilizar otras experiencias. Concluye con la propuesta de un nuevo modelo de comunicación sobre cáncer, basado en el concepto de la socialización.Departamento de Sociología y Trabajo SocialDoctorado en Investigación Transdisciplinar en Educació

    20th SC@RUG 2023 proceedings 2022-2023

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    Expert Ignorance:The Law and Politics of Rule of Law Reform

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    Second-Person Surveillance: Politics of User Implication in Digital Documentaries

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    This dissertation analyzes digital documentaries that utilize second-person address and roleplay to make users feel implicated in contemporary refugee crises, mass incarceration in the U.S., and state and corporate surveillances. Digital documentaries are seemingly more interactive and participatory than linear film and video documentary as they are comprised of a variety of auditory, visual, and written media, utilize networked technologies, and turn the documentary audience into a documentary user. I draw on scholarship from documentary, game, new media, and surveillance studies to analyze how second-person address in digital documentaries is configured through user positioning and direct address within the works themselves, in how organizations and creators frame their productions, and in how users and players respond in reviews, discussion forums, and Let’s Plays. I build on Michael Rothberg’s theorization of the implicated subject to explore how these digital documentaries bring the user into complicated relationality with national and international crises. Visually and experientially implying that users bear responsibility to the subjects and subject matter, these works can, on the one hand, replicate modes of liberal empathy for suffering, distant “others” and, on the other, simulate one’s own surveillant modes of observation or behavior to mirror it back to users and open up one’s offline thoughts and actions as a site of critique. This dissertation charts how second-person address shapes and limits the political potentialities of documentary projects and connects them to a lineage of direct address from educational and propaganda films, museum exhibits, and serious games. By centralizing the user’s individual experience, the interventions that second-person digital documentaries can make into social discourse change from public, institution-based education to more privatized forms of sentimental education geared toward personal edification and self-realization. Unless tied to larger initiatives or movements, I argue that digital documentaries reaffirm a neoliberal politics of individual self-regulation and governance instead of public education or collective, social intervention. Chapter one focuses on 360-degree virtual reality (VR) documentaries that utilize the feeling of presence to position users as if among refugees and as witnesses to refugee experiences in camps outside of Europe and various dwellings in European cities. My analysis of Clouds Over Sidra (Gabo Arora and Chris Milk 2015) and The Displaced (Imraan Ismail and Ben C. Solomon 2015) shows how these VR documentaries utilize observational realism to make believable and immersive their representations of already empathetic refugees. The empathetic refugee is often young, vulnerable, depoliticized and dehistoricized and is a well-known trope in other forms of humanitarian media that continues into VR documentaries. Forced to Flee (Zahra Rasool 2017), I am Rohingya (Zahra Rasool 2017), So Leben Flüchtlinge in Berlin (Berliner Morgenpost 2017), and Limbo: A Virtual Experience of Waiting for Asylum (Shehani Fernando 2017) disrupt easy immersions into realistic-looking VR experiences of stereotyped representations and user identifications and, instead, can reflect back the user’s political inaction and surveillant modes of looking. Chapter two analyzes web- and social media messenger-based documentaries that position users as outsiders to U.S. mass incarceration. Users are noir-style co-investigators into the crime of the prison-industrial complex in Fremont County, Colorado in Prison Valley: The Prison Industry (David Dufresne and Philippe Brault 2009) and co-riders on a bus transporting prison inmates’ loved ones for visitations to correctional facilities in Upstate New York in A Temporary Contact (Nirit Peled and Sara Kolster 2017). Both projects construct an experience of carceral constraint for users to reinscribe seeming “outside” places, people, and experiences as within the continuation of the racialized and classed politics of state control through mass incarceration. These projects utilize interfaces that create a tension between replicating an exploitative hierarchy between non-incarcerated users and those subject to mass incarceration while also de-immersing users in these experiences to mirror back the user’s supposed distance from this mode of state regulation. Chapter three investigates a type of digital game I term dataveillance simulation games, which position users as surveillance agents in ambiguously dystopian nation-states and force users to use their own critical thinking and judgment to construct the criminality of state-sanctioned surveillance targets. Project Perfect Citizen (Bad Cop Studios 2016), Orwell: Keeping an Eye on You (Osmotic Studios 2016), and Papers, Please (Lucas Pope 2013) all create a dual empathy: players empathize with bureaucratic surveillance agents while empathizing with surveillance targets whose emails, text messages, documents, and social media profiles reveal them to be “normal” people. I argue that while these games show criminality to be a construct, they also utilize a racialized fear of the loss of one’s individual privacy to make players feel like they too could be surveillance targets. Chapter four examines personalized digital documentaries that turn users and their data into the subject matter. Do Not Track (Brett Gaylor 2015), A Week with Wanda (Joe Derry Hall 2019), Stealing Ur Feelings (Noah Levenson 2019), Alfred Premium (Joël Ronez, Pierre Corbinais, and Émilie F. Grenier 2019), How They Watch You (Nick Briz 2021), and Fairly Intelligent™ (A.M. Darke 2021) track, monitor, and confront users with their own online behavior to reflect back a corporate surveillance that collects, analyzes, and exploits user data for profit. These digital documentaries utilize emotional fear- and humor-based appeals to persuade users that these technologies are controlling them, shaping their desires and needs, and dehumanizing them through algorithmic surveillance

    Towards Sybil Resilience in Decentralized Learning

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    Federated learning is a privacy-enforcing machine learning technology but suffers from limited scalability. This limitation mostly originates from the internet connection and memory capacity of the central parameter server, and the complexity of the model aggregation function. Decentralized learning has recently been emerging as a promising alternative to federated learning. This novel technology eliminates the need for a central parameter server by decentralizing the model aggregation across all participating nodes. Numerous studies have been conducted on improving the resilience of federated learning against poisoning and Sybil attacks, whereas the resilience of decentralized learning remains largely unstudied. This research gap serves as the main motivator for this study, in which our objective is to improve the Sybil poisoning resilience of decentralized learning. We present SybilWall, an innovative algorithm focused on increasing the resilience of decentralized learning against targeted Sybil poisoning attacks. By combining a Sybil-resistant aggregation function based on similarity between Sybils with a novel probabilistic gossiping mechanism, we establish a new benchmark for scalable, Sybil-resilient decentralized learning. A comprehensive empirical evaluation demonstrated that SybilWall outperforms existing state-of-the-art solutions designed for federated learning scenarios and is the only algorithm to obtain consistent accuracy over a range of adversarial attack scenarios. We also found SybilWall to diminish the utility of creating many Sybils, as our evaluations demonstrate a higher success rate among adversaries employing fewer Sybils. Finally, we suggest a number of possible improvements to SybilWall and highlight promising future research directions

    Rational development of stabilized cyclic disulfide redox probes and bioreductive prodrugs to target dithiol oxidoreductases

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    Countless biological processes allow cells to develop, survive, and proliferate. Among these, tightly balanced regulatory enzymatic pathways that can respond rapidly to external impacts maintain dynamic physiological homeostasis. More specifically, redox homeostasis broadly affects cellular metabolism and proliferation, with major contributions by thiol/disulfide oxidoreductase systems, in particular, the Thioredoxin Reductase Thioredoxin (TrxR/Trx) and the Glutathione Reductase-Glutathione-Glutaredoxin (GR/GSH/Grx) systems. These cascades drive vital cellular functions in many ways through signaling, regulating other proteins' activity by redox switches, and by stoichiometric reductant transfers in metabolism and antioxidant systems. Increasing evidence argues that there is a persistent alteration of the redox environment in certain pathological states, such as cancer, that heavily involve the Trx system: upregulation and/or overactivity of the Trx system may support or drive cancer progression, making both TrxR and Trx promising targets for anti-cancer drug development. Understanding the biochemical mechanisms and connections between certain redox cascades requires research tools that interact with them. The state-of-the-art genetic tools are mostly ratiometric reporters that measure reduced:oxidized ratios of selected redox pairs or the general thiol pool. However, the precise cellular roles of the central oxidoreductase systems, including TrxR and Trx, remain inaccessible due to the lack of probes to selectively measure turnover by either of these proteins. However, such probes would allow measuring their effective reductive activity apart from expression levels in native systems, including in cells, animals, or patient samples. They are also of high interest to identify chemical inhibitors for TrxR/Trx in cells and to validate their potential use as anti-cancer agents (to date, there is no selective cellular Trx inhibitor, and most known TrxR inhibitors were not comprehensively evaluated considering selectivity and potential off-targets). However, small molecule redox imaging tools are underdeveloped: their protein specificity, spectral properties, and applicability remain poorly precedented. This work aimed to address this opportunity gap and develop novel, small molecule diagnostic and therapeutic tools to selectively target the Trx system based on a modular trigger cargo design: artificial cyclic disulfide substrates (trigger) for oxidoreductases are tethered to molecular agents (cargo) such that the cargo’s activity is masked and is re-established only through reduction by a target protein. The rational design of these novel reduction sensors to target the cell's strongest disulfide-reducing enzymes was driven by the following principles: (i) cyclic disulfide triggers with stabilized ring systems were used to gain low reduction potentials that should resist reduction except by the strongest cellular reductases, such as Trx; and (ii) the cyclic topology also offers the potential for kinetic reversibility that should select for dithiol-type redox proteins over the cellular monothiol background. Creating imaging agents based on such two-component designs to selectively measure redox protein activity in native cells required to combine the correct trigger reducibility, probe activation kinetics, and imaging modalities and to consider the overall molecular architecture. The major prior art in this field has applied cyclic 5-membered disulfides (1,2 dithiolanes) as substrates for TrxR in a similar way to create such tools. However, this motif was described elsewhere as thermodynamically instable and was due to widely used for dynamic covalent cascade reactions. By comparing a novel 1,2 dithiolane-based probe to the state-of-the-art probes, including commercial TrxR sensors, by screening a conclusive assay panel of cellular TrxR modulations, I clarified that 1,2 dithiolanes are not selective substrates for TrxR in biological settings (Nat Commun 2022). Instead, aiming for more stable ring systems and thus more robust redox probes, during this work, I developed bicyclic 6 membered disulfides (piperidine fused 1,2 dithianes) with remarkably low reduction potentials. I showed that molecular probes using them as reduction sensors can be mostly processed by thioredoxins while being stable against reduction by GSH. The thermodynamically stabilized decalin like topology of the cis-annelated 1,2 dithianes requires particularly strong reductants to be cleaved. They also select for dithiol type redox proteins, like Trx, based on kinetic reversibility and offer fast cyclization due to the preorganization by annelation (JACS 2021). This work further expanded the system’s modularity with structural cores based on piperazine-fused 1,2 dithianes with the two amines allowing independent derivatization. Diagnostic tools using them as reduction sensors proved equally robust but with highly improved activation kinetics and were thus cellularly activated. Cellular studies evolved that they are substrates for both Trxs and their protein cousins Grxs, so measuring the cellular dithiol protein pool rather than solely Trx activity (preprint 2023). Finally, a trigger based on a slightly adapted reduction sensor, a desymmetrized 1,2 thiaselenane, was designed for selective reduction by TrxR’s selenol/thiol active site, then combined with a precipitating large Stokes’ shift fluorophore and a solubilizing group, to evolve the first selective probe RX1 to measure cellular TrxR activity, which even allowed high throughput inhibitor screening (Chem 2022). The central principle of this work was further advanced to therapeutic prodrugs based on the duocarmycin cargo (CBI) with tunable potency (JACS Au 2022) that can be used to create off-to-on therapeutic prodrugs. Such CBI prodrugs employing stabilized 1,2 dichalcogenide triggers proved to be cytotoxins that depend on Trx system activity in cells. They could further be exploited for cell-line dependent reductase activity profiling by screening their redox activation indices, the reduction-dependent part of total prodrug activation, in 177 cell lines. Beyond that, these prodrugs were well-tolerated in animals and showed anti-cancer efficacy in vivo in two distinct mouse tumor models (preprint 2022). Taken together, I introduced unique monothiol-resistant reducible motifs to target the cellular Trx system with chemocompatible units for each for TrxR and Trx/Grx, where the cyclic nature of the dichalcogenides avoids activation by GSH. By using them with distinct molecular cargos, I developed novel selective fluorescent reporter probes; and introduced a new class of bioreductive therapeutic constructs based on a common modular design. These were either applied to selectively measure cellular reductase activity or to deliver cytotoxic anti cancer agents in vivo. Ongoing work aims to differentiate between the two major redox effector proteins Trx and Grx, requiring additional layers of selectivity that may be addressed by tuned molecular recognition. The flexible use of various molecular cargos allows harnessing the same cellular redox machinery by either probes or prodrugs. This allows predictive conclusions from diagnostics to be directly translated into therapy and offers great potential for future adaptation to other enzyme classes and therapeutic venues.Die zelluläre Redox-Homöostase hängt von Thiol/Disulfid-Oxidoreduktasen ab, die den Stoffwechsel, die Proliferation und die antioxidative Antwort von Zellen beeinflussen. Die wichtigsten Netzwerke sind die Thioredoxin Reduktase-Thioredoxin (TrxR/Trx) und Glutathion Reduktase-Glutathion-Glutaredoxin (GR/GSH/Grx) Systeme, die über Redox-Schalter in Substratproteinen lebenswichtige zelluläre Funktionen steuern und so an der Redox-Regulation und -Signalübertragung beteiligt sind. Persistente Veränderungen des Redoxmilieus in pathologischen Zuständen, wie z. B. bei Krebs, sind in hohem Maße mit dem Trx-System verbunden. Eine Hochregulierung und/oder Überaktivität des Trx-Systems, die bei vielen Krebsarten auftreten, unterstützt zudem das Fortschreiten des Krebswachstums, was TrxR/Trx zu vielversprechenden Zielproteinen für die Entwicklung neuer Krebsmedikamente macht. Um die biochemischen Prozesse dahinter zu erforschen, sind spezielle Techniken zur Visualisierung und Messung enzymatischer Aktivität nötig. Die hierzu geeigneten, meist genetischen Sensoren messen ratiometrisch das Verhältnis reduzierter/oxidierter Spezies in zellulärem Umfeld oder spezifisch ausgewählte Redoxpaare. Die weitere Erforschung der exakten Funktion von TrxR/Trx und deren Substrate ist jedoch durch mangelnde Nachweismethoden limitiert. Diese sind außerdem zur Validierung chemischer Hemmstoffe für TrxR/Trx in Zellen und deren potenziellen Verwendung als Krebsmittel von großem Interesse. Bislang gibt es keinen selektiven zellulären Trx-Inhibitor und potenzielle Off-Target-Effekte der bekannten TrxR-Inhibitoren wurden nicht abschließend bewertet. Ziel dieser Arbeit ist die Entwicklung niedermolekularer, diagnostischer und therapeutischer Werkzeuge, die selektiv auf das Trx-System abzielen und auf einem modularen Trigger-Cargo Design basieren. Hierzu werden zyklische Disulfid-Substrate (Trigger) für Oxidoreduktasen so mit molekularen Wirkstoffen (Cargo) verknüpft, dass dabei die Wirkstoffaktivität maskiert, und erst nach Reduktion durch ein Zielprotein wiederhergestellt wird. Diese neuartigen, synthetischen Reduktionssensoren basieren auf den folgenden Grundprinzipien: (i) Zyklische Disulfide sind thermodynamisch stabilisiert und können nur durch die stärksten Reduktasen gespalten werden; und (ii) die zyklische Topologie ermöglicht die kinetische Reversibilität der zwei Thiol-Disulfid-Austauschreaktionen, die eine erste Reaktion mit Monothiolen, wie z. B. GSH, sofort umkehrt und so eine vollständige Reduktion verhindert. Die meisten früheren Arbeiten auf diesem Gebiet verwendeten ein zyklisches, fünfgliedriges Disulfid (1,2 Dithiolan) als Substrat für TrxR. Das gleiche Strukturmotiv wurde jedoch an anderer Stelle als thermodynamisch instabil beschrieben und aufgrund dieser Eigenschaft explizit für dynamische Kaskadenreaktionen verwendet. Deshalb vergleicht diese Arbeit zu Beginn einen neuen 1,2 Dithiolan basierten fluorogenen Indikator mit bestehenden, z. T. kommerziellen, Redox Sonden für TrxR in einer Reihe von Zellkultur-Experimenten unter Modulation der zellulären TrxR Aktivität und stellt so einen Widerspruch in der Literatur klar: 1,2 Dithiolane eignen sich nicht als selektive Substrate für TrxR, da sie labil sowohl gegen die Reduktion durch andere Redoxproteine, als auch gegen den Monothiol Hintergrund in Zellen sind (Nat. Commun. 2022). Als alternatives Strukturmotiv wird in dieser Arbeit ein bizyklisches sechsgliedriges Disulfid (anneliertes 1,2 Dithian) etabliert. Durch sein niedriges Reduktionspotenzial, also seine hohe Resistenz gegen Reduktion, werden molekulare Sonden basierend auf diesem 1,2 Dithian als Reduktionssensor fast ausschließlich von Trx aktiviert, nicht aber von TrxR oder GSH (JACS 2021). Dieses Kernmotiv bestimmt dabei die Reduzierbarkeit, und damit die Enzymspezifität, durch seine zyklische Natur und die Annelierung, auch unter Verwendung unterschiedlicher Farb-/Wirkstoffe. Auf dieser Grundlage konnte die molekulare Struktur durch einen weiteren Modifikationspunkt für die flexible Verwendung weiterer funktioneller Einheiten ergänzt werden. Obwohl zelluläre Studien ergaben, dass diese neuartigen 1,2 Dithian Einheiten in Zellen sowohl Trx als auch das strukturell verwandte Grx adressieren, sind die daraus resultierenden diagnostischen Moleküle wertvoll, um den katalytischen Umsatz zellulärer Dithiol-Reduktasen, der sogenannten Trx Superfamilie, selektiv anzuzeigen (Preprint 2023). Begünstigt durch das modulare Moleküldesign stellt diese Arbeit zudem das erste Reportersystem RX1 zum selektiven Nachweis der TrxR-Aktivität in Zellen vor. Es basiert auf der Verwendung eines zyklischen, unsymmetrischen Selenenylsulfid-Sensors (1,2 Thiaselenan), der selektiv von dem einzigartigen Selenolat der TrxR angegriffen wird, und dadurch letztlich nur von TrxR reduziert werden kann. RX1 eignete sich zudem für eine Hochdurchsatz-Validierung bestehender TrxR Inhibitoren und unterstreicht dadurch den kommerziellen Nutzen derartiger Diagnostika (Chem 2022). Das zentrale Trigger-Cargo Konzept dieser Arbeit wurde für therapeutische Zwecke weiterentwickelt und nutzt dabei den einzigartigen Wirkmechanismus der Duocarmycin-Naturstoffklasse (CBI) (JACS Au 2022) zur Entwicklung reduktiv aktivierbarer Therapeutika. CBI Prodrugs basierend auf stabilisierten Redox-Schaltern (1,2 Dithiane für Trx; 1,2 Thiaselenan für TrxR) reagierten signifikant auf TrxR-Modulation in Zellen. Sie wurden darüber hinaus durch das Referenzieren ihrer Aktivität gegenüber nicht-reduzierbaren Kontrollmoleküle für die Erstellung zelllinienabhängiger Profile der Reduktaseaktivität in 177 Zelllinien genutzt. Schließlich waren diese neuen Krebsmittel im Tiermodell gut verträglich und zeigten in zwei verschiedenen Mausmodellen eine krebshemmende Wirkung (Preprint 2022b). Zusammenfassend präsentiert diese Dissertation monothiol-resistente reduzierbare Trigger-Einheiten für das zelluläre Trx-System zur Entwicklung neuartiger, selektiver Reporter-Sonden, sowie eine neue Klasse reduktiv aktivierbarer Krebsmittel auf Basis eines adaptierbaren Trigger-Cargo Designs. Diese fanden entweder zur selektiven Messung zellulärer Proteinaktivität oder zum Einsatz als Antikrebsmittel Verwendung. Es wurden chemokompatible Motive sowohl für TrxR als auch für Trx/Grx identifiziert, wobei deren zyklische Natur eine Aktivierung durch GSH verhindert. Eine weitere Differenzierung zwischen den beiden Redox-Proteinen Trx und Grx und anderen Proteinen der Trx-Superfamilie erfordert eine zusätzliche Ebene der Selektierung, z. B. durch molekulare Erkennung, und ist Gegenstand laufender Arbeiten. Die flexible Verwendung verschiedener molekularer Wirkstoffe ermöglicht dabei die „Pipeline-Entwicklung“ von Diagnostika und Therapeutika, die von der zellulären Redox-Maschinerie analog umgesetzt werden, und dadurch Schlussfolgerungen aus der Diagnostik direkt auf eine Therapie übertragbar machen. Dies birgt großes Potenzial für künftige Entwicklungen bei einer potenziellen Übertragung des modularen Konzepts auf andere Enzymklassen und therapeutische Einsatzgebiete

    Reducing Library Anxiety in the Information Seeking Behavior Of First Year College Students

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    This study explored the use of interactive technology to reduce library anxiety in the information seeking behavior of first year students enrolled in a historically Black college or university. Based on the research focus, the following questions were formulated: What are the determinants for reducing library anxiety in first year college students’ information seeking behavior? Related questions were formatted to test the hypotheses and for data collection: (1) Can interactive applications included as part of the information retrieval process decrease library anxiety? (2) Can familiarity, as measured by a pre and post survey, decrease library anxiety? Interactive applications may include virtual and augmented reality, online chat, games and artificial intelligence technology. These are relatively new forms of technology used in education, and research indicates that these technologies promote immersive experiences that can contribute to learning. The research hypothesized that these technologies may also increase familiarity of the library and the related resources, which may reduce library anxiety. This research may provide vital information to higher education administrators and librarians to ensure that all students receive adequate resources to find information needed for their classes and that barriers that prevent progress in student’s education are removed. Keywords: information seeking behavior, library anxiety, virtual reality, augmented realit

    Development of core competencies for field veterinary epidemiology training programs

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    A workforce with the adequate field epidemiology knowledge, skills and abilities is the foundation of a strong and effective animal health system. Field epidemiology training is conducted in several countries to meet the increased global demand for such a workforce. However, core competencies for field veterinary epidemiology have not been identified and agreed upon globally, leading to the development of different training curricula. Having a set of agreed core competencies can harmonize field veterinary epidemiology training. The Food and Agriculture Organization of the United Nations (FAO) initiated a collective, iterative, and participative process to achieve this and organized two expert consultative workshops in 2018 to develop core competencies for field veterinary epidemiology at the frontline and intermediate levels. Based on these expert discussions, 13 competencies were identified for the frontline and intermediate levels. These competencies were organized into three domains: epidemiological surveillance and studies; field investigation, preparedness and response; and One Health, communication, ethics and professionalism. These competencies can be used to facilitate the development of field epidemiology training curricula for veterinarians, adapted to country training needs, or customized for training other close disciplines. The competencies can also be useful for mentors and employers to monitor and evaluate the progress of their mentees, or to guide the selection process during the recruitment of new staff
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