Insights from quantitative and mathematical modelling on the proposed 2030 goal for gambiense human African trypanosomiasis (gHAT)

Gambiense human African trypanosomiasis (gHAT) is a parasitic, vector-borne neglected tropical disease that has historically affected populations across West and Central Africa and can result in death if untreated. Following from the success of recent intervention programmes against gHAT, the World Health Organization (WHO) has defined a 2030 goal of global elimination of transmission (EOT). The key proposed indicator to measure achievement of the goal is to have zero reported cases. Results of previous mathematical modelling and quantitative analyses are brought together to explore both the implications of the proposed indicator and the feasibility of achieving the WHO goal. Whilst the indicator of zero case reporting is clear and measurable, it is an imperfect proxy for EOT and could arise either before or after EOT is achieved. Lagging reporting of infection and imperfect diagnostic specificity could result in case reporting after EOT, whereas the converse could be true due to underreporting, lack of coverage, and cryptic human and animal reservoirs. At the village-scale, the WHO recommendation of continuing active screening until there are three years of zero cases yields a high probability of local EOT, but extrapolating this result to larger spatial scales is complex. Predictive modelling of gHAT has consistently found that EOT by 2030 is unlikely across key endemic regions if current medical-only strategies are not bolstered by improved coverage, reduced time to detection and/or complementary vector control. Unfortunately, projected costs for strategies expected to meet EOT are high in the short term and strategies that are cost-effective in reducing burden are unlikely to result in EOT by 2030. Future modelling work should aim to provide predictions while taking into account uncertainties in stochastic dynamics and infection reservoirs, as well as assessment of multiple spatial scales, reactive strategies, and measurable proxies of EOT

Open Education as a threshold concept in Teacher Education: a theoretical framework for further research

Threshold concept framework: A threshold concept can be considered as akin to a portal, opening up a new and previously inaccessible way of thinking about something. It represents a transformed way of understanding, or interpreting, or viewing something without which the learner cannot progress. As a consequence of comprehending a threshold concept there may thus be a transformed internal view of subject matter, subject landscape, or even worldview (Meyer and Land, 2003). Threshold concepts have been explored in many disciplines (Bradbeer, 2006) and may have a key role for the transformation of the students? learning experience (Cousin, 2006). Since open education has implications for innovation and change (Peter and Deimann, 2013), we suggest exploring it as a threshold concept. There are five main attributes defined originally by Meyer and Land (2003) and three more have also been listed stemming from comments made by the authors (UCL, 2013): transformative, troublesome, irreversible, integrative, bounded, discursive, reconstitutive and liminal. Openness as a threshold concept: 1. Transformative - Is openness transformative for students involved in open educational practices? 2. Troublesome - What difficulties do students face when being involved in open educational practices? 3. Irreversible - How do students? perceptions change when being involved in open educational practices? How do these changes impact visions of their own future professional careers? 4. Liminality - How can the progressive change towards the open movement be scaffolded? How can feedback help in the construction of authentic open educational practices? 5. Discursive - What kind of narrative do students involved in open educational practices develop? Does it reflect authentic construction of the open movement understanding? This is the theoretical framework for future research about openness as a threshold concept. More research is needed to obtain data that would throw light on how to address each particular attribute. This is an open call to those interested in going further in this line of research

Global burden of human brucellosis : a systematic review of disease frequency

BACKGROUND: This report presents a systematic review of scientific literature published between 1990-2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY) estimate for brucellosis.METHODS/PRINCIPAL FINDINGS: Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden.CONCLUSIONS: High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understand of disease dynamics at the animal-human interface, as well as a more cost-effective utilisation of resources

Coherent combining of two high-brightness laser diodes phase-locked by a Michelson-type external cavity (Orale)

International audienceWe describe a new coherent beam combin- ing architecture based on the passive phase- locking of two laser diodes in a Michelson external cavity on their rear side, and their coherent combination on their front side

Insights into herpesvirus assembly from the structure of the pUL7:pUL51 complex

Funder: Nvidia; FundRef: http://dx.doi.org/10.13039/100007065Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440Funder: John Lucas Walker StudentshipFunder: Commonwealth Scholarship Commission; FundRef: http://dx.doi.org/10.13039/501100000867Herpesviruses acquire their membrane envelopes in the cytoplasm of infected cells via a molecular mechanism that remains unclear. Herpes simplex virus (HSV)−1 proteins pUL7 and pUL51 form a complex required for efficient virus envelopment. We show that interaction between homologues of pUL7 and pUL51 is conserved across human herpesviruses, as is their association with trans-Golgi membranes. We characterized the HSV-1 pUL7:pUL51 complex by solution scattering and chemical crosslinking, revealing a 1:2 complex that can form higher-order oligomers in solution, and we solved the crystal structure of the core pUL7:pUL51 heterodimer. While pUL7 adopts a previously-unseen compact fold, the helix-turn-helix conformation of pUL51 resembles the cellular endosomal complex required for transport (ESCRT)-III component CHMP4B and pUL51 forms ESCRT-III–like filaments, suggesting a direct role for pUL51 in promoting membrane scission during virus assembly. Our results provide a structural framework for understanding the role of the conserved pUL7:pUL51 complex in herpesvirus assembly

Amino acid sequence of the ligand-binding domain of the aryl hydrocarbon receptor 1 predicts sensitivity of wild birds to effects of dioxin-like compounds

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Toxicological Sciences 131 (2013): 139-152, doi:10.1093/toxsci/kfs259.The sensitivity of avian species to the toxic effects of dioxin-like compounds (DLCs) varies up to 1000-fold among species and this variability has been associated with inter-species differences in aryl hydrocarbon receptor 1 ligand binding domain (AHR1 LBD) sequence. We previously showed that LD50 values, based on in ovo exposures to DLCs, were significantly correlated with in vitro EC50 values obtained with a luciferase reporter gene (LRG) assay that measures AHR1-mediated induction of cytochrome P4501A in COS-7 cells transfected with avian AHR1 constructs. Those findings suggest that the AHR1 LBD sequence and the LRG assay can be used to predict avian species sensitivity to DLCs. In the present study, the AHR1 LBD sequences of 86 avian species were studied and differences at amino acid sites 256, 257, 297, 324, 337 and 380 were identified. Site-directed mutagenesis, the LRG assay and homology modeling highlighted the importance of each amino acid site in AHR1 sensitivity to 2,3,8,8-tetrachlorodibenzo-p-dioxin and other DLCs. The results of the study revealed that: (1) only amino acids at sites 324 and 380 affect the sensitivity of AHR1 expression constructs of 86 avian species to DLCs and (2) in vitro luciferase activity in AHR1 constructs containing only the LBD of the species of interest is significantly correlated (r2 = 0.93, p<0.0001) with in ovo toxicity data for those species. These results indicate promise for the use of AHR1 LBD amino acid sequences independently, or combined with the LRG assay, to predict avian species sensitivity to DLCs.This research was supported by unrestricted grants from the Dow Chemical Company and Georgia-Pacific LLC to the University of Ottawa, Environment Canada’s STAGE program and, in part, by a Discovery Grant from the National Science and Engineering Research Council of Canada (Project # 326415-07). The authors wish to acknowledge the support of an instrumentation grant from the Canada Foundation for Infrastructure. Professor Giesy was supported by the Canada Research Chair program and an at large Chair Professorship at the Department of Biology and Chemistry and State Key Laboratory in Marine Pollution, City University of Hong Kong, the Einstein Professor Program of the Chinese Academy of Sciences and the Visiting Professor Program of King Saud University. M. Hahn and S. Karchner were supported by NOAA Sea Grant (grant number NA06OAR4170021 (R/B-179)), and by the Walter A. and Hope Noyes Smith endowed chair.2013-08-2

High-power operation of coherently coupled tapered laser diodes in an external cavity

We demonstrate a rear-side phase-locking architecture with two high-brightness diode lasers. This technique is based on the passive phase-locking of emitters in an external cavity on their rear facet, and their coherent combination on the front facet. Two high-brightness high-power tapered laser diodes are coherently combined using a Michelson-based cavity. The combining efficiency is above 80% and results in an output power of 6.7 W in a nearly diffraction-limited beam. The rear-side architecture is then used with a laser bar of 5 tapered emitters using an interferometric extended cavity, based on a diffractive optical element. We describe the experimental evaluation of the diffractive optical element, and the phase-locked operation of the laser bar

Functional Traits Explain Amphibian Distribution in the Brazilian Atlantic Forest

Aim: Species distributions are one of the most important ways to understand how communities interact through macroecological relationships. The functional abilities of a species, such as its plasticity in various environments, can determine its distribution and beta diversity patterns. In this study, we evaluate how functional traits influence the distribution of amphibians, and hypothesize which functional traits explain the current pattern of amphibian species composition in the Atlantic Forest. Location: Atlantic Forest, Brazil. Methods: Using potential distributions of Brazilian Atlantic Forest of amphibian species, we analysed the relative importance of abiotic factors and species functional traits in explaining species richness, endemism (with permutation multivariate analysis), and beta diversity components (i.e. total, turnover and nestedness dissimilarities). Results: Environmental variables explained 59.5% of species richness, whereas functional traits explained 15.8% of species distribution for Anuran and 88.8% for 58 Gymnophiona. Body size had the strongest correlation with the species distribution. Results of nestedness dissimilarities showed that species with medium to large body size, and species that are adapted to living in open areas tended to disperse from west to east direction. Current forest changes directly affected beta diversity patterns (i.e. most species adapted to novel environments increased their ranges). Beta diversity partitioning between humid and dry forests showed decreased nestedness and increased turnover by increasing altitude in the southeastern region of the Atlantic Forest. Main conclusions: Our study shows that functional traits directly influence the ability of the species to disperse. With the alterations of the natural environment, species more apt to these alterations have dispersed or increased their distribution, which consequently changes community structure. As result, there is nested species distribution patterns and homogenization of amphibian species composition throughout the Brazilian Atlantic Forest

Separate phase-locking and coherent combining of two laser diodes in a Michelson cavity

We describe a new coherent beam combining architecture based on passive phase-locking of two laser diodes in a Michelson external cavity on their rear facet, and their coherent combination on the front facet. As a proof-of-principle, two ridge lasers have been coherently combined with >90 % efficiency. The phase-locking range, and the resistance of the external cavity to perturbations have been thoroughly investigated. The combined power has been stabilized over more than 15 min with an optical feedback as well as with an automatic adjustment of the driving currents. Furthermore, two high-brightness high-power tapered laser diodes have been coherently combined in a similar arrangement; the combining efficiency is 70% and results in an output power of 4 W. We believe that this new configuration combines the simplicity of passive self-organizing architectures with the optical efficiency of master-oscillator power-amplifier ones

From reverse innovation to global innovation in animal health: a review

Reverse innovation refers to learning from or diffusion of innovations developed in low income settings and further translated to industrialized countries. There is lack of consensus regarding terminology, but the idea that innovations in low-income countries are promising for adoption in high-income contexts is not new. However, in healthcare literature globally, the vast majority of publications referring to 'disruptive innovation' were published in the last ten years. To assess the potential of innovative developments and technologies for improving animal health, we initiated a literature review in 2020. We used a combined approach, incorporating targeted searching in PubMed using a key word algorithm with a snowball technique, to identify 120 relevant publications and extract data for qualitative coding. Heterogeneity of articles precluded meta-analysis, quality scoring and risk of bias analysis. We can distinguish technical innovations like new digital devices, diagnostic tests and procedures, and social innovations of intersectoral cooperation. We profile two case studies to describe potential global innovations: an integrated surveillance and response system in Somali Regional State, Ethiopia and a blockchain secured One Health intervention to optimally provide post-exposure prophylaxis for rabies exposed people in West Africa. Innovation follows no borders and can also occur in low-income settings, under constraints of cost, lack of services and infrastructure. Lower administrative and legal barriers may contribute to produce innovations that would not be possible under conditions of high density of regulation. We recommend using the term global innovation, which highlights those emanating from international partnership to solve problems of global implications