Six dilemmas for stakeholders inherently affecting data sharing during a zoonotic (re-)emerging infectious disease outbreak response.

BACKGROUND: Timely access to outbreak related data, particularly in the early events of a spillover, is important to support evidence based control measures in response to outbreaks of zoonotic Emerging Infectious Diseases (EID). Yet, this is impeded by several barriers that need to be understood to promote timely sharing of data. Using the MERS epidemic as a model for a zoonotic EID outbreak, this study sought to provide an in-depth understanding of data sharing practices. METHODS: Semi-structured interviews with 25 experts were conducted, along with Focus Group Discussions with 15 additional experts. A root-cause analysis was performed to examine the causal relationships between barriers. Enablers were mapped to the root-cause analysis to understand their influence on the barriers. Finally, root causes were placed in context of core dilemmas identified from the qualitative analysis. FINDINGS: Eight barriers to data sharing were identified, related to collaboration, technical preparedness, regulations, and (conflict of) interests, and placed in the context of six dilemmas inherent to the multi-stakeholder collaboration required for a zoonotic outbreak response. Fourteen identified enablers showed the willingness of stakeholders to overcome or circumvent these barriers, but also indicated the inherent trial and error nature of implementing such enablers. INTERPRETATION: Addressing the barriers requires solutions that must consider the complexity and interconnectedness of the root causes underlying them, and should consider the distinct scopes and interests of the different stakeholders. Insights provided by this study can be used to encourage data sharing practices for future outbreaks FUNDING: Wellcome Trust and UK Aid; EU-H2020 Societal Challenges (grant agreement no. 643476), Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.Veni.201S.044).

A Case Study of European Collaboration between the Veterinary and Human Field for the Development of RSV Vaccines.

The One Health (OH) approach describes the interconnection between the health of animals, humans, and the environment. The need for collaboration between the veterinary and human fields is increasing due to the rise in several infectious diseases that cross human-animal barriers and need to be addressed jointly. However, such collaboration is not evident in practice, especially for non-zoonotic diseases. A qualitative research approach was used to explore the barriers and enablers influencing collaborative efforts on the development of vaccines for the non-zoonotic RSV virus. It was found that in the European context, most veterinary and human health professionals involved in RSV vaccine development see themselves as belonging to two distinct groups, indicating a lack of a common goal for collaboration. Next to this, the different conceptualizations of the OH approach, and the fact that RSV is not a zoonotic disease, strengthens the opinion that there is no shared need for collaboration. This paper adds insights on how, for a non-zoonotic situation, collaboration between human and veterinary professionals shaped the development of vaccines in both areas; thus, improving public health requires awareness, mutual appreciation, and shared goal setting.

Upscaling vaccine manufacturing capacity - key bottlenecks and lessons learned.

The COVID-19 pandemic put enormous pressure on the vaccine production chain as billions of vaccines had to be produced in the shortest timeframe possible. Vaccine production chains struggled to keep up with demand, resulting in disruptions and production delays. This study aimed to make an inventory of challenges and opportunities that occurred in the production chain of the COVID-19 vaccine. Insights derived through approximately 80 interviews and roundtable discussions were combined with findings from a scoping literature review. Data were analysed through an inductive process where barriers and opportunities were linked to specific facets of the production chain. Key bottlenecks identified include a lack of manufacturing facilities, a lack of tech-transfer personnel, inefficient arrangement of production stakeholders, critical shortages in raw materials, and restricting protectionist measures. A need for a central governing body to map out shortages and to coordinate allocation of available resource became evident. Other suggested solutions were to repurpose existing facilities and to build in more flexibility in the production process by making materials interchangeable. Also, simplification of the production chain could be achieved through geographical reengagement of processes. Three overarching themes were identified, impacting overall functioning of the vaccine production chain: regulatory and visibility, collaboration and communication, and funding and policy. The results in this study showed a multitude of interdependent processes underlying the vaccine production chain, executed by diverse stakeholders with differing objectives. It characterizes the global complexity of the pharmaceutical production chain and highlights its extreme vulnerability to disruptions. More resilience and robustness must be integrated into the vaccine production chain, and low-middle income countries should be empowered to manufacture vaccines themselves. In conclusion, there's a need to rethink the production system for vaccines and other essential medicines in order to become better prepared for future health crises.

An elephant in the glasshouse? Trade-offs between acceleration and transformation in COVID-19 vaccine innovation policies.

Against the backdrop of a failing vaccine innovation system, innovation policy aimed at creating a COVID-19 vaccine was surprisingly fast and effective. This paper analyzes the influence of the COVID-19 landscape shock and corresponding innovation policy responses on the existing vaccine innovation system. We use document analysis and expert interviews, performed during vaccine development. We find that the sharing of responsibility between public and private actors on various geographical levels, and the focus on accelerating changes in the innovation system were instrumental in achieving fast results. Simultaneously, the acceleration exacerbated existing societal innovation barriers, such as vaccine hesitancy, health inequity, and contested privatization of earnings. Going forward, these innovation barriers may limit the legitimacy of the vaccine innovation system and reduce pandemic preparedness. Next to a focus on acceleration, transformative innovation policies for achieving sustainable pandemic preparedness are still urgently needed. Implications for mission-oriented innovation policy are discussed.

Innovations in the veterinary intestinal health field: A patent landscape analysis.

In recent years it has become evident that a healthy intestinal microbiome is beneficial for the overall health of an individual. A healthy microbiome is diverse, increasing stability and resilience and strengthening the immune system. In addition, healthy intestinal metabolisms have a beneficial effect on many physiological processes such as the brain function. Looking from the One Health perspective, which recognizes that health of humans is closely connected to the health of animals and environment, it is inherently beneficial to stimulate the health of animals for the well-being of humans. However, the intensive administration of antibiotics to livestock for prevention and cure of disease, and even stimulation of growth, disrupts a healthy microbiome. With the rapid increase of emerging zoonotic diseases, alternatives to the use of antimicrobial compounds are urgently necessary. This research analyses the development of alternatives for antibiotic use contributing to veterinary intestinal health through an in-depth patent analysis of inventions for fodder additives. In the period 1999-2020, 1269 unique patent families describing the use of probiotics, enzymes and prebiotics for swine, poultry and ruminants were identified. Innovation trends, geography, key applicants, and classification of patents were analysed. Asian industrial applicants applied for the majority of patents comprising the largest share of patents for probiotics and enzymes in combination with fodder for swine. Followed by North American and European industrial applications, applying for patents for probiotics in combination with fodder for poultry, swine, and ruminants. Overall, our results do not show a clear increase in innovations, suggesting that innovations in the use of probiotics and enzymes in animal feed appear to be stalling. While in the near future a combination of the use of antibiotics and alternatives is most likely to be implemented, the use of probiotics stands a good chance of replacing antibiotics in animal husbandry and limiting the adverse effects of antibiotic abuse.

The Gut Microbiota: Master of Puppets Connecting the Epidemiology of Infectious, Autoimmune, and Metabolic Disease.

Infectious, autoimmune, and metabolic diseases put an enormous pressure on both quality of life and the economy. For all three disease types, it is known that the quality of the gut microbiota composition is correlated to both onset and progression of disease. Hence, maintaining eubiosis and preventing gradual irreversible loss of beneficial microbes within the gut microbial ecosystem is of utmost importance. As such, the epidemiological trends of these disease types may serve as proxies for the integrity of the human gut microbiota. Here, we present incidence data covering the last decades for prototypical infectious diseases (tuberculosis and measles), autoimmune disorders (type-1 diabetes and multiple sclerosis), and the prevalence of metabolic syndrome. Our findings reveal that vaccination efforts correlate with relatively low levels of archetypal infectious disease incidence. However, autoimmune and metabolic disorders are, together with the usage of antibiotics, steeply on the rise. These findings suggest that the status of the gut microbiota is persistently deteriorating, as reflected by the proxies. As such, the epidemiological trends shown here may serve as a starting point for a mechanistic understanding of the interplay between these different disease types that can be used for future prevention and mitigation strategies like targeted stimulation and suppletion of microorganisms by means of, e.g., fermented foods, prebiotics and probiotics.

Probiotics for the Management of Infectious Diseases: Reviewing the State of the Art.

This review aims to provide insight into the potential of probiotics as a clinical modality targeted at infectious diseases by creating a comprehensive overview of the state of the art of research and development efforts as shown by patents and clinical trials of the past 20 years. Data were retrieved from patent and clinical trial databases to reflect the long- and short-term developments of probiotics research. The data were analyzed to extract information on the total number of patents and trials for each indication, application date and location, and applicant/sponsor type. A total of 80 infectious diseases were investigated, precipitating in 789 patents and 602 clinical trials for 67 indications studied as targets of probiotics. An increasing trend was seen for the number of patents and clinical trials that were applied for since 1999 with the highest number of patents and clinical trials targeted to digestive tract, respiratory, and urogenital indications. Overall, research demonstrated a substantial interest in probiotics targeting infectious diseases, which was in line with reported unmet needs and global probiotics sales estimates. However, the declining rate of translation from patents to clinical trials indicates that there are some barriers obstructing the research process.

A framework for measuring timeliness in the outbreak response path: lessons learned from the Middle East respiratory syndrome (MERS) epidemic, September 2012 to January 2019.

BackgroundEpidemics are a constant threat in the 21st century, particularly disease outbreaks following spillover of an animal virus to humans. Timeliness, a key metric in epidemic response, can be examined to identify critical steps and delays in public health action.AimTo examine timeliness, we analysed the response to the Middle East respiratory syndrome (MERS) epidemic, with a focus on the international and One Health response efforts.MethodsWe performed a historical review of the MERS epidemic between September 2012 and January 2019 in three steps: (i) the construction of a timeline identifying critical events in the global response, (ii) the performance of a critical path analysis to define outbreak milestones and (iii) a time gap analysis to measure timeliness in the execution of these milestones.ResultsWe proposed 14 MERS-specific milestones at different phases of the epidemic, assessing timeliness of the public health response as well as at the animal-human interface, where we identified the most significant delays.ConclusionsWhen comparing timeliness across three coronavirus epidemics, i.e. MERS (2012), SARS (2002) and COVID-19 (2019), we identified clear improvements over time for certain milestones including laboratory confirmation and diagnostics development, while this was not as apparent for others, as the identification of zoonotic hosts. To more efficiently respond to emerging threats, the global health community should widely assess and tackle specific delays in implementing response interventions by addressing challenges in the sharing of information, data and resources, as well as efficiency, quality, transparency and reliability of reporting events.

Identifying Cross-Utilization of RSV Vaccine Inventions across the Human and Veterinary Field.

The respiratory syncytial virus (RSV) has two main variants with similar impact, a human and a bovine variant. The human respiratory syncytial virus (HRSV) is the most frequent cause of acute respiratory disease (pneumonia) in children, leading to hospitalization and causing premature death. In Europe, lower respiratory tract infections caused by HRSV are responsible for 42-45 percent of hospital admissions in children under two. Likewise, the bovine respiratory syncytial virus (BRSV) is a significant cause of acute viral broncho-pneumonia in calves. To date no licensed HRSV vaccine has been developed, despite the high burden of the disease. In contrast, BRSV vaccines have been on the market since the 1970s, but there is still an articulated unmet need for improved BRSV vaccines with greater efficacy. HRSV/BRSV vaccine development was chosen as a case to assess whether collaboration and knowledge-sharing between human and veterinary fields is taking place, benefiting the development of new vaccines in both fields. The genetic relatedness, comparable pathogeneses, and similar severity of the diseases suggests much can be gained by sharing knowledge and experiences between the human and veterinary fields. We analyzed patent data, as most of pharmaceutical inventions, such as the development of vaccines, are protected by patents. Our results show only little cross-utilization of inventions and no collaborations, as in shared IP as an exchange of knowledge. This suggests that, despite the similarities in the genetics and antigenicity of HRSV and BRSV, each fields follows its own process in developing new vaccines.

On the Verge of a Catastrophic Collapse? The Need for a Multi-Ecosystem Approach to Microbiome Studies.

While the COVID-19 pandemic has led to increased focus on pathogenic microbes that cross the animal-human species barrier, calls to include non-pathogenic interactions in our perspective on public health are gaining traction in the academic community. Over generations, the diversity of the human gut microbiota is being challenged by external perturbations and reduced acquisition of symbiotic species throughout life. When such reduced diversity concerns not only the microbial species, but also the higher taxonomic levels and even the guild level, adequate compensation for possible losses may be lacking. Shifts from a high-abundance to a low-abundance state, known as a tipping point, may result in simultaneous shifts in covarying taxa and ultimately to a catastrophic collapse in which the ecosystem abruptly and possibly irreversibly shifts to an alternative state. Here, we propose that co-occurrence patterns within and between microbial communities across human, animal, soil, water, and other environmental domains should be studied in light of such critical transitions. Improved mechanistic understanding of factors that shape structure and function is needed to understand whether interventions can sustainably remodel disease-prone microbiota compositions to robust and resilient healthy microbiota. Prerequisites for a rational approach are a better understanding of the microbial interaction network, both within and inter-domain, as well as the identification of early warning signs for a catastrophic collapse, warranting a timely response for intervention. We should not forget that mutualism and pathogenicity are two sides of the same coin. Building upon the planetary health concept, we argue that microbiome research should include system level approaches to conserve ecosystem resilience. HIGHLIGHTS 1. Non-pathogenic interactions between ecosystems play a key role in maintaining health. 2. The human gut microbiome may be on the verge of a catastrophic collapse. 3. Research should identify keystone taxa and guilds that interconnect different domains. 4. We should not forget that mutualism and pathogenicity are two sides of the same coin.

Barriers Influencing Vaccine Development Timelines, Identification, Causal Analysis, and Prioritization of Key Barriers by KOLs in General and Covid-19 Vaccine R&D.

A frequently mentioned factor holding back the introduction of new vaccines on the market are their prohibitively long development timelines. These hamper their potential societal benefit and impairs the ability to quickly respond to emerging new pathogens. This is especially worrisome since new pathogens are emerging at all-time high rates of over one per year, and many age-old pathogens are still not vaccine preventable.Through interviews with 20 key-opinion-leaders (KOLs), this study identified innovation barriers that increase vaccine development timelines. These innovation barriers were visualized, and their underlying causes revealed by means of qualitative root cause analysis. Based on a survey the innovation barriers were quantitatively ranked based on their relative impact on both regular, and Covid-19 vaccine development timelines. KOLs identified 20 key innovation barriers, and mapping these barriers onto the Vaccine Innovation Cycle model revealed that all phases of vaccine development were affected. Affected by most barriers is the area between the preclinical studies and the market entry. Difficult hand-off between academia and industry, lack of funding, and lack of knowledge of pathogen targets were often mentioned as causes. Quantitative survey responses from 93 KOLs showed that general vaccine development and Covid-19 vaccine development are impacted by distinct sets of innovation barriers. For the general vaccine development three barriers were perceived of the highest impact; limited ROI for vaccines addressing disease with limited market size, limited ROI for vaccines compared to non-vaccine projects, and academia not being able to progress beyond proof of principle. Of highest impact on Covid-19 vaccine development, are lack of knowledge concerning pathogen target, high risk of upscaling unlicensed vaccines, and proof of principle not meeting late-stage requirements. In conclusion, the current study demonstrates that barriers hampering timelines in vaccine development are present across the Vaccine Innovation Cycle. Prioritizing the impact of barriers in general, and in Covid-19 vaccine development, shows clear differences that can be used to inform policies to speed up development in both war and peace time.

Lower Respiratory Tract Infection Trends in East and South-East Asia: In the Light of Economic and Health Care Development.

This study explored to what degree economic development and improvement of healthcare are associated with lower respiratory tract infection (LRTI) mortality. A correlation analysis between LRTI mortality and Gross Domestic Product (GDP) per capita, and the Health Access and Quality Index (HAQI), respectively was conducted for 15 countries in East and South-East Asia. The results revealed a dramatic decrease in LRTI mortality in total populations for lower-middle income (LMI) countries but at the same time an increase in upper-middle income (UMI) and high-income (HI) countries. A highly significant (P < .001) growth-dependent relationship between LRTI mortality and economic growth was observed. Improvements in HAQI were significantly associated with a decrease in LRTI mortality in LMI countries, but an increase in UMI and HI countries. The decline of LRTI mortality amongst children in LMI countries is an encouraging trend and efforts against LRTI must be continued, though not at the expense of preparing health systems for the growing burden.

Quantity vs. quality: an assessment of the current pipeline for rabies.

OBJECTIVES: To gain insight in the potential of the current pipeline for rabies to decrease the burden of disease by evaluating its relevance to high-risk countries. METHODS: Rabies-related patent documents and clinical trials were retrieved from Espacenet and the WHO ICTRP, respectively. Data were cleaned, modulated and categorised into a pre-defined set of indicators those were used for (statistical) analyses on the number of patent applications, patent quality and type of stakeholders involved for different geographical areas. RESULTS: Analysis of 583 unique patent families applied for in the period 1954-2017 showed a steep growth in the yearly number of patent applications. A significant portion of new patent applications concern Chinese patents with relatively low quality that are filed by a dispersed group of applicants. Excluding these patents, the number of patent applications has been virtually stable over the years. A shift is seen in public stakeholders becoming more prolific as patent applicants. This shift is also reflected in clinical trials; key sponsors of clinical trials include public and private stakeholders originating from high-risk rabies countries. The majority of clinical trials investigate adjustments to existing vaccines that may improve accessibility. CONCLUSION: The results show a discrepancy between the quantity and quality of rabies patent applications that reflects national patent regulations rather than real progress in decreasing the burden of disease. This is in contrast to clinical trials, which focus on incremental innovations that are tested in clinical trials but may nevertheless have a potentially strong impact in high-risk countries.

OBJECTIFS: Comprendre le potentiel du pipeline actuel pour la rage pour réduire la charge de morbidité en évaluant sa pertinence pour les pays à haut risque. MÉTHODES: Les documents de brevet liés à la rage et les essais cliniques ont été récupérés auprès de réseau Espacenet et de l'OMS ICTRP, respectivement. Les données ont été triées, modulées et classées en un ensemble prédéfini d'indicateurs qui a été utilisé pour des analyses (statistiques) sur le nombre de demandes de brevet, la qualité des brevets et le type de parties prenantes impliquées pour différentes zones géographiques. RÉSULTATS: L'analyse de 583 familles de brevets uniques déposées au cours de la période 1954-2017 a montré une forte croissance du nombre annuel de demandes de brevet. Une part importante des nouvelles demandes de brevet concerne des brevets chinois de qualité relativement faible soumises par un groupe dispersé de déposants. A l'exclusion de ces brevets, le nombre de demandes de brevet est resté pratiquement stable au fil des ans. Un changement est observé dans les acteurs publics devenant plus prolifiques en tant que demandeurs de brevet. Ce changement se reflète également dans les essais cliniques; les principaux sponsors des essais cliniques comprennent des parties prenantes publiques et privées originaires de pays à haut risque pour la rage. La majorité des essais cliniques étudient les ajustements aux vaccins existants qui pourraient améliorer l'accessibilité. CONCLUSION: Les résultats montrent un écart entre la quantité et la qualité des demandes de brevet liées à la rage qui reflète les réglementations nationales en matière de brevets plutôt que de réels progrès dans la réduction de la charge de morbidité. Cela contraste avec les essais cliniques, qui se concentrent sur des innovations incrémentales qui sont testées dans des essais cliniques mais qui peuvent néanmoins avoir un impact potentiellement fort dans les pays à haut risque.

Overcoming challenges for designing and implementing the One Health approach: A systematic review of the literature.

Collaborative approaches in health, such as One Health (OH), are promising; nevertheless, several authors point at persistent challenges for designing and implementing OH initiatives. Among other challenges, OH practitioners struggle in their efforts to collaborate across disciplines and domains. This paper aims to provide insights into the existing challenges for designing and implementing OH initiatives, their causes and solutions, and points out strategic solutions with the potential to solve practical challenges. A systematic literature search was performed for emerging challenges and proposed solutions in the process of conducting OH initiatives. Next, a thematic and a causal analysis were performed to unravel challenges and their causes. Finally, solutions were discriminated on whether they were only recommended, or implemented as a proof-of-principle. The 56 included papers describe 21 challenges endured by OH initiatives that relate to different themes (policy and funding; education and training; surveillance; multi-actor, multi-domain, and multi-level collaborations; and evidence). These challenges occur in three different phases: the acquisition of sufficient conditions to start an initiative, its execution, and its monitoring and evaluation. The findings indicate that individual challenges share overlapping causes and crosscutting causal relations. Accordingly, solutions for the successful performance of OH initiatives should be implemented to tackle simultaneously different types of challenges occurring in different phases. Still, promoting collaboration between the wide diversity of stakeholders, as a fundamental aspect in the OH approach, is still by far the most challenging factor in performing OH initiatives. Causes for that are the difficulties in promoting meaningful and equal participation from diverse actors. Solutions proposed for this challenge focused on guiding stakeholders to think and collaborate beyond their professional and cultural silos to generate knowledge co-creation and innovative methodologies and frameworks. Finally, the biggest knowledge gap identified, in terms of proposed solutions, was for monitoring and evaluating OH initiatives. This highlights the need for future research on evaluation methods and tools specific for the OH approach, to provide credible evidence on its added value. When considering challenges endured by former OH initiatives and the proposed solutions for these challenges, practitioners should be able to plan and structure such initiatives in a more successful way, through the strategic pre-consideration of solutions or simply by avoiding known barriers.

A research agenda to reinforce rabies control: A qualitative and quantitative prioritization.

BACKGROUND: Despite the existence of safe and effective vaccines, rabies disease still causes an estimated 59,000 human deaths a year in the endemic areas in Asia and Africa. These numbers reflect severe drawbacks regarding the implementation of PrEP and PEP in endemic settings, such as lack of political will and low priority given to rabies. Since these contextual factors have proven to be persistent, there is an urgency to improve current strategies or develop novel approaches in order to control rabies disease in the future. METHODS/FINDINGS: This study aimed to identify and systematically prioritize the research needs, through interviews and questionnaires with key-opinion-leaders (KOLs). A total of 46 research needs were identified and prioritized. The top research needs are considered very high priority based on both importance for rabies control and need for improvement. KOLs agree that animal rabies control remains most important for rabies control, while research on human host, agent (rabies virus) and the environment should be prioritized in terms of need for improvement. A wide variety in perceptions is observed between and within the disciplines of virology, public health and veterinary health and between KOLs with more versus those with less experience in the field. CONCLUSION/SIGNIFICANCE: The results of this study give well-defined, prioritized issues that stress the drawbacks that are experienced by KOLs in daily practice. The most important research domains are: 1) cheap and scalable production system for RIG 2) efficacy of dog mass vaccination programs and 3) cheap human vaccines. Addressing these research needs should exist next to and may reinforce current awareness and mass vaccination campaigns. The differences in perspectives between actors revealed in this study are informative for effective execution of the One Health research agenda.

How ownership rights over microorganisms affect infectious disease control and innovation: A root-cause analysis of barriers to data sharing as experienced by key stakeholders.

BACKGROUND: Genetic information of pathogens is an essential input for infectious disease control, public health and for research. Efficiency in preventing and responding to global outbreaks relies on timely access to such information. Still, ownership barriers stand in the way of timely sharing of genetic data from pathogens, frustrating efficient public health responses and ultimately the potential use of such resources in innovations. Under a One Health approach, stakeholders, their interests and ownership issues are manifold and need to be investigated. We interviewed key actors from governmental and non-governmental bodies to identify overlapping and conflicting interests, and the overall challenges for sharing pathogen data, to provide essential inputs to the further development of political and practical strategies for improved data sharing practices. METHODS & FINDINGS: To identify and prioritize barriers, 52 Key Opinion Leaders were interviewed. A root-cause analysis was performed to identify causal relations between barriers. Finally, barriers were mapped to the innovation cycle reflecting how they affect the range of surveillance, innovation, and sharing activities. Four main barrier categories were found: compliance to regulations, negative consequences, self-interest, and insufficient incentives for compliance. When grouped in sectors (research institutes, public health organizations, supra-national organizations and industry) stakeholders appear to have similar interests, more than when grouped in domains (human, veterinary and food). Considering the innovation process, most of barriers could be mapped to the initial stages of the innovation cycle as sampling and sequencing phases. These are stages of primary importance to outbreak control and public health response. A minority of barriers applied to later stages in the innovation cycle, which are of more importance to product development. CONCLUSION: Overall, barriers are complex and entangled, due to the diversity of causal factors and their crosscutting features. Therefore, barriers must be addressed in a comprehensive and integrated manner. Stakeholders have different interests highlighting the diversity in motivations for sharing pathogen data: prioritization of public health, basic research, economic welfare and/or innovative capacity. Broad inter-sectorial discussions should start with the alignment of these interests within sectors. The improved sharing of pathogen data, especially in upstream phases of the innovation process, will generate substantial public health benefits through increased availability of data to inform surveillance systems, as well as to allow the (re-)use of data for the development of medical countermeasures to control infectious diseases.

Self-Centric and Altruistic Unmet Needs for Ebola: Barriers to International Preparedness.

OBJECTIVE: Barriers to international Ebola preparedness may be elucidated by identifying heterogeneities in arguments to invest in countermeasures during "peace time." METHODS: For each patent family (related patent documents that differed only by limited alterations to the same invention) concerning Ebola and published until the end of 2014 the oldest patent document was analyzed. Grounded theory coding identified 5 unmet needs for (1) vaccines and therapies, (2) control of outbreaks in endemic areas, (3) detection and control of outbreaks in nonendemic areas, (4) better understanding of filoviruses, and (5) protection against bioterrorism. Odds ratios for unmet needs by geographic regions and institution types were compared by using Pearson's chi-square test. RESULTS: Statistically significant heterogeneities in unmet need profiles were found. US applicants combined self-centric and altruistic arguments, focusing on medical unmet needs and bioterrorism protection. Russian and Asian applicants emphasized self-centric motives, specifically, detection and control of nonendemic outbreaks. A clear, statistically significant mismatch between industry and academia was found: whereas industrial applicants focused on bioterrorism and neglected detection and control of nonendemic outbreaks, academic applicants did the opposite. CONCLUSIONS: This research identified heterogeneities in articulated needs between geographic regions and stakeholder types. Structural articulation of unmet needs may form the basis for attuning stakeholder engagement strategies while progression across the demand-driven value chain might necessitate international concordance. (Disaster Med Public Health Preparedness. 2016;10:644-648).

Long-lasting cognitive deficits resulting from adolescent nicotine exposure in rats.

Adolescence is a developmental period, during which the brain and particularly medial prefrontal cortical (mPFC) regions thereof have not fully matured. Because epidemiological data have suggested that adolescent nicotine use may result in disturbances in cognitive function in adulthood, we investigated the long-term effects of adolescent nicotine exposure in rats. Male Wistar rats were exposed to either nicotine (three times daily, 0.4 mg/kg s.c.) or saline for 10 days during (postnatal day (PND) 34-43) or following (PND 60-69) adolescence. After 5 weeks during adulthood, separate groups of animals were tested in operant paradigms taxing attention and distinct measures of impulsivity. Visuospatial attention and impulsive action were tested in the five-choice serial reaction time task, whereas impulsive choice was assessed in the delayed reward task. Our data show that adolescent, but not postadolescent, nicotine exposure affects cognitive performance in adulthood and results in diminished attentional performance and increments in impulsive action, while leaving impulsive choice intact. This altered cognitive performance appeared to be associated with enhanced releasability of dopamine in the mPFC. Together, these data suggest that adolescence is a time window during which the brain is vulnerable to long-lasting cognitive disturbances resulting from nicotine exposure.