Driving Institutional Innovation for Agricultural Innovation Through R&D Projects: Learning From Two Experiences of Multi-Stakeholder Platforms Formation and Operation in Bolivia

The idea that agricultural innovation does not only result from the transfer of research outputs to farmers but involves heterogeneous individuals and organizations interacting with each other and organizational and institutional conditions that constitute incentives or impediments for innovation to take place, is increasingly recognized as a promising idea among researchers and development practitioners engaged in research and development projects in developing countries. However the challenge of how to make these ideas accessible to practitioners and researchers with action-oriented purposes, whether for the design and implementation of R&D projects or for the in-depth investigation of innovation processes, has not yet been sufficiently addressed. This is precisely the focus of this research. It seeks to begin filling this gap with theoretical, empirical and methodological contributions by studying in-depth two cases of R&D project-driven attempts to foster the establishment and operation of multi-stakeholder platforms within the Bolivian context of agricultural innovation. Combining conceptual developments offered by the innovation systems and collective action approaches, this research explores the formation and operation of two multi-stakeholder, R&D project-driven processes of collective institutional innovation. Using action-oriented research methods, it was found that how, and with what effects, R&D projects act as drivers of institutional innovations processes is influenced by the tradition of designing and managing R&D projects, as well as by the prescriptive nature of projects defining what should be done, by whom, how, with what results, and for the benefit of whom. There are implications for the design and management of R&D projects when they are used as institutional innovation drivers. The implications relate to the definition of objectives, outcomes and indicators of achievement; the definition of roles and positions of the players; and to the instruments for projects planning, monitoring and evaluation. These research findings can help to shape agricultural innovation in Bolivia

Attending sporting mega events during COVID-19: mitigation and messaging at UK EURO 2020 matches

The UEFA EURO 2020 football tournament was one of the largest Sporting Mega Events (SMEs) to take place during the COVID19 pandemic. Mitigating the risk of virus transmission requires a multi-layered approach for any large event, more so in this case due to staging the tournament across eleven host countries. Yet, little is known about COVID-19 risks and mitigation from attending an event of this scale and nature. We examined the implementation of mitigation and messaging at EURO 2020 matches hosted at venues in the UK. The tournament was postponed from the summer of 2020 and played in June and July of 2021. Structured observations were conducted by 11 trained fieldwork-supporters at 10 matches played at Wembley Stadium, London, or Hampden Park, Glasgow. Fieldwork-supporters observed one-way systems and signage, and hand sanitizing stations inside the stadia, but reported significant variation in the implementation of staggered timeslots, testing upon entry, and procedures for exit. Adherence to planned measures by ticket holders and implementation by stewards waned as the tournament progressed culminating in an absence of enforced measures at the final. The non-compliance with COVID-19 mitigation measures was likely to have led to a significantly increased risk of transmission. Future events should consider how COVID-19 mitigation measures could become ‘new norms’ of fan behaviour, learning from what is already known about football fandom. Tournament organizers of SMEs can use these findings to promote clearer messaging on pandemic-driven changes in fan behaviour and best practices in mitigating risk at future sporting and cultural events

Read Length and Repeat Resolution: Exploring Prokaryote Genomes Using Next-Generation Sequencing Technologies

Background: There are a growing number of next-generation sequencing technologies. At present, the most cost-effective options also produce the shortest reads. However, even for prokaryotes, there is uncertainty concerning the utility of these technologies for the de novo assembly of complete genomes. This reflects an expectation that short reads will be unable to resolve small, but presumably abundant, repeats. Methodology/Principal Findings: Using a simple model of repeat assembly, we develop and test a technique that, for any read length, can estimate the occurrence of unresolvable repeats in a genome, and thus predict the number of gaps that would need to be closed to produce a complete sequence. We apply this technique to 818 prokaryote genome sequences. This provides a quantitative assessment of the relative performance of various lengths. Notably, unpaired reads of only 150nt can reconstruct approximately 50 % of the analysed genomes with fewer than 96 repeat-induced gaps. Nonetheless, there is considerable variation amongst prokaryotes. Some genomes can be assembled to near contiguity using very short reads while others require much longer reads. Conclusions: Given the diversity of prokaryote genomes, a sequencing strategy should be tailored to the organism unde

The cost‐effectiveness of HIV pre‐exposure prophylaxis in men who have sex with men and transgender women at high risk of HIV infection in Brazil

Abstract Introduction: Men who have sex with men (MSM) and transgender women (TGW) in Brazil experience high rates of HIV infection. We examined the clinical and economic outcomes of implementing a pre‐exposure prophylaxis (PrEP) programme in these populations. Methods: We used the Cost‐Effectiveness of Preventing AIDS Complications (CEPAC)‐International model of HIV prevention and treatment to evaluate two strategies: the current standard of care (SOC) in Brazil, including universal ART access (No PrEP strategy); and the current SOC plus daily tenofovir/emtracitabine PrEP (PrEP strategy) until age 50. Mean age (31 years, SD 8.4 years), age‐stratified annual HIV incidence (age ≤ 40 years: 4.3/100 PY; age > 40 years: 1.0/100 PY), PrEP effectiveness (43% HIV incidence reduction) and PrEP drug costs ($23/month) were from Brazil‐based sources. The analysis focused on direct medical costs of HIV care. We measured the comparative value of PrEP in 2015 United States dollars (USD) per year of life saved (YLS). Willingness‐to‐pay threshold was based on Brazil's annual per capita gross domestic product (GDP; 2015:$8540 USD). Results: Lifetime HIV infection risk among high‐risk MSM and TGW was 50.5% with No PrEP and decreased to 40.1% with PrEP. PrEP increased per‐person undiscounted (discounted) life expectancy from 36.8 (20.7) years to 41.0 (22.4) years and lifetime discounted HIV‐related medical costs from $4100 to$8420, which led to an incremental cost‐effectiveness ratio (ICER) of $2530/YLS. PrEP remained cost‐effective (<1x GDP) under plausible variation in key parameters, including PrEP effectiveness and cost, initial cohort age and HIV testing frequency on/off PrEP. Conclusion: Daily tenofovir/emtracitabine PrEP among MSM and TGW at high risk of HIV infection in Brazil would increase life expectancy and be highly cost‐effective

The effect of an autologous cellular gel-matrix integrated implant system on wound healing

<p>Abstract</p> <p>Background</p> <p>This manuscript reports the production and preclinical studies to examine the tolerance and efficacy of an autologous cellular gel-matrix integrated implant system (IIS) aimed to treat full-thickness skin lesions.</p> <p>Methods</p> <p>The best concentration of fibrinogen and thrombin was experimentally determined by employing 28 formula ratios of thrombin and fibrinogen and checking clot formation and apparent stability. IIS was formed by integrating skin cells by means of the <it>in situ </it>gelification of fibrin into a porous crosslinked scaffold composed of chitosan, gelatin and hyaluronic acid. The <it>in vitro </it>cell proliferation within the IIS was examined by the MTT assay and PCNA expression. An experimental rabbit model consisting of six circular lesions was utilized to test each of the components of the IIS. Then, the IIS was utilized in an animal model to cover a 35% body surface full thickness lesion.</p> <p>Results</p> <p>The preclinical assays in rabbits demonstrated that the IIS was well tolerated and also that IIS-treated rabbit with lesions of 35% of their body surface, exhibited a better survival rate (p = 0,06).</p> <p>Conclusion</p> <p>IIS should be further studied as a new wound dressing which shows promising properties, being the most remarkable its good biological tolerance and cell growth promotion properties.</p

Detection of transcriptional triggers in the dynamics of microbial growth: application to the respiratorily versatile bacterium Shewanella oneidensis

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nucleic Acids Research 40 (2012): 7132-7149, doi:10.1093/nar/gks467.The capacity of microorganisms to respond to variable external conditions requires a coordination of environment-sensing mechanisms and decision-making regulatory circuits. Here, we seek to understand the interplay between these two processes by combining high-throughput measurement of time-dependent mRNA profiles with a novel computational approach that searches for key genetic triggers of transcriptional changes. Our approach helped us understand the regulatory strategies of a respiratorily versatile bacterium with promising bioenergy and bioremediation applications, Shewanella oneidensis, in minimal and rich media. By comparing expression profiles across these two conditions, we unveiled components of the transcriptional program that depend mainly on the growth phase. Conversely, by integrating our time-dependent data with a previously available large compendium of static perturbation responses, we identified transcriptional changes that cannot be explained solely by internal network dynamics, but are rather triggered by specific genes acting as key mediators of an environment-dependent response. These transcriptional triggers include known and novel regulators that respond to carbon, nitrogen and oxygen limitation. Our analysis suggests a sequence of physiological responses, including a coupling between nitrogen depletion and glycogen storage, partially recapitulated through dynamic flux balance analysis, and experimentally confirmed by metabolite measurements. Our approach is broadly applicable to other systems.Office of Science (BER), U.S. Department of Energy [DE-FG02-07ER64388 to D.S. and DE-FG02- 08ER64511 to M.H.S.]; National Aeronautics and Space Administration, NASA Astrobiology Institute [NNA08CN84A to D.S.]

Unstable Maternal Environment, Separation Anxiety, and Heightened CO2 Sensitivity Induced by Gene-by-Environment Interplay

Background: In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO2 hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO2 through genetic control of sensitivity to the environment. Methodology: Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were crossfostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O2), CO2-enriched air (6% CO2), hypoxic air (10%O2), and avoidance of CO2-enriched environments. Results: Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO2-enriched air and heightened aversion towards CO2- enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO2 was present at 16–20, and 75–90 postnatal days, implying the trait’s stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO2 breathing was significantly higher (Bartlett x = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO2 increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals. Conclusions: A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO2 sensitivity and anxiety. Some no

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Supplementary information files for Attending sporting mega events during COVID-19: mitigation and messaging at UK EURO 2020 matches

Supplementary files for article Attending sporting mega events during COVID-19: mitigation and messaging at UK EURO 2020 matches The UEFA EURO 2020 football tournament was one of the largest Sporting Mega Events (SMEs) to take place during the COVID-19 pandemic. Mitigating the risk of virus transmission requires a multi-layered approach for any large event, more so in this case due to staging the tournament across eleven host countries. Yet, little is known about COVID-19 risks and mitigation from attending an event of this scale and nature. We examined the implementation of mitigation and messaging at EURO 2020 matches hosted at venues in the UK. The tournament was postponed from the summer of 2020 and played in June and July of 2021. Structured observations were conducted by 11 trained fieldwork-supporters at 10 matches played at Wembley Stadium, London, or Hampden Park, Glasgow. Fieldwork-supporters observed one-way systems and signage, and hand sanitizing stations inside the stadia, but reported significant variation in the implementation of staggered timeslots, testing upon entry, and procedures for exit. Adherence to planned measures by ticket holders and implementation by stewards waned as the tournament progressed culminating in an absence of enforced measures at the final. The non-compliance with COVID-19 mitigation measures was likely to have led to a significantly increased risk of transmission. Future events should consider how COVID-19 mitigation measures could become 'new norms' of fan behaviour, learning from what is already known about football fandom. Tournament organizers of SMEs can use these findings to promote clearer messaging on pandemic-driven changes in fan behaviour and best practices in mitigating risk at future sporting and cultural events.  </p

Attending sporting mega events during COVID-19: mitigation and messaging at UK EURO 2020 matches

The UEFA EURO 2020 football tournament was one of the largest Sporting Mega Events (SMEs) to take place during the COVID-19 pandemic. Mitigating the risk of virus transmission requires a multi-layered approach for any large event, more so in this case due to staging the tournament across eleven host countries. Yet, little is known about COVID-19 risks and mitigation from attending an event of this scale and nature. We examined the implementation of mitigation and messaging at EURO 2020 matches hosted at venues in the UK. The tournament was postponed from the summer of 2020 and played in June and July of 2021. Structured observations were conducted by 11 trained fieldwork-supporters at 10 matches played at Wembley Stadium, London, or Hampden Park, Glasgow. Fieldwork-supporters observed one-way systems and signage, and hand sanitizing stations inside the stadia, but reported significant variation in the implementation of staggered timeslots, testing upon entry, and procedures for exit. Adherence to planned measures by ticket holders and implementation by stewards waned as the tournament progressed culminating in an absence of enforced measures at the final. The non-compliance with COVID-19 mitigation measures was likely to have led to a significantly increased risk of transmission. Future events should consider how COVID-19 mitigation measures could become 'new norms' of fan behaviour, learning from what is already known about football fandom. Tournament organizers of SMEs can use these findings to promote clearer messaging on pandemic-driven changes in fan behaviour and best practices in mitigating risk at future sporting and cultural events