370 research outputs found

    Return on investment of high-quality outplacement programs

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    Investments ; Unemployment ; Labor productivity

    Intrinsic noise and discrete-time processes

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    A general formalism is developed to construct a Markov chain model that converges to a one-dimensional map in the infinite population limit. Stochastic fluctuations are therefore internal to the system and not externally specified. For finite populations an approximate Gaussian scheme is devised to describe the stochastic fluctuations in the non-chaotic regime. More generally, the stochastic dynamics can be captured using a stochastic difference equation, derived through an approximation to the Markov chain. The scheme is demonstrated using the logistic map as a case study.Comment: Modified version accepted for publication in Phys. Rev. E Rapid Communications. New figures adde

    Modelling upper respiratory viral load dynamics of SARS-CoV-2

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    Relationships between viral load, severity of illness, and transmissibility of virus, are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response, and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with control of viral load. Neutralizing antibody correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralizing antibody. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions

    Comparative efficacy of two pyrethroid-piperonyl butoxide nets (Olyset Plus and PermaNet 3.0) against pyrethroid resistant malaria vectors: a non-inferiority assessment

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    Background Pyrethroid-PBO nets were conditionally recommended for control of malaria transmitted by mosquitoes with oxidase-based pyrethroid-resistance based on epidemiological evidence of additional protective effect with Olyset Plus compared to a pyrethroid-only net (Olyset Net). Entomological studies can be used to assess the comparative performance of other brands of pyrethroid-PBO ITNs to Olyset Plus. Methods An experimental hut trial was performed in Cové, Benin to compare PermaNet 3.0 (deltamethrin plus PBO on roof panel only) to Olyset Plus (permethrin plus PBO on all panels) against wild pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) following World Health Organization (WHO) guidelines. Both nets were tested unwashed and after 20 standardized washes compared to Olyset Net. Laboratory bioassays were also performed to help explain findings in the experimental huts. Results With unwashed nets, mosquito mortality was higher in huts with PermaNet 3.0 compared to Olyset Plus (41% vs. 28%, P < 0.001). After 20 washes, mortality declined significantly with PermaNet 3.0 (41% unwashed vs. 17% after washing P < 0.001), but not with Olyset Plus (28% unwashed vs. 24% after washing P = 0.433); Olyset Plus induced significantly higher mortality than PermaNet 3.0 and Olyset Net after 20 washes. PermaNet 3.0 showed a higher wash retention of PBO compared to Olyset Plus. A non-inferiority analysis performed with data from unwashed and washed nets together using a margin recommended by the WHO, showed that PermaNet 3.0 was non-inferior to Olyset Plus in terms of mosquito mortality (25% with Olyset Plus vs. 27% with PermaNet 3.0, OR = 1.528, 95%CI = 1.02–2.29) but not in reducing mosquito feeding (25% with Olyset Plus vs. 30% with PermaNet 3.0, OR = 1.192, 95%CI = 0.77–1.84). Both pyrethroid-PBO nets were superior to Olyset Net. Conclusion Olyset Plus outperformed PermaNet 3.0 in terms of its ability to cause greater margins of improved mosquito mortality compared to a standard pyrethroid net, after multiple standardized washes. However, using a margin of non-inferiority defined by the WHO, PermaNet 3.0 was non-inferior to Olyset Plus in inducing mosquito mortality. Considering the low levels of mortality observed and increasing pyrethroid-resistance in West Africa, it is unclear whether either of these nets would demonstrate the same epidemiological impact observed in community trials in East Africa

    Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract

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    Objectives: The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load. Methods: COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time. Results Eighty-two subjects (50% female, median age 54 years (range 3–73)) with COVID-19 were recruited. Paired URT viral load samples were available for 16 blood transcriptome samples, and 17 respiratory epithelial transcriptome samples. Natural Killer (NK) cells were the only blood cell type significantly correlated with URT viral load z-scores (r = −0.62, P = 0.010). Twenty-four blood gene expression modules were significantly correlated with URT viral load z-score, the most significant being a module of genes connected around IFNA14 (Interferon Alpha-14) expression (r = −0.60, P = 1e-10). In fixed repertoire analysis, prostanoid-related gene expression was significantly associated with higher viral load. In nasal epithelium, only GNLY (granulysin) gene expression showed significant negative correlation with viral load. Conclusions: Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral replication. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production and administration of interferon alpha-14 may be attractive transmission-blocking interventions

    Malnutrition and disability: unexplored opportunities for collaboration

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    There is increasing international interest in the links between malnutrition and disability: both are major global public health problems, both are key human rights concerns, and both are currently prominent within the global health agenda. In this review, interactions between the two fields are explored and it is argued that strengthening links would lead to important mutual benefits and synergies. At numerous points throughout the life-cycle, malnutrition can cause or contribute to an individual&apos;s physical, sensory, intellectual or mental health disability. By working more closely together, these problems can be transformed into opportunities: nutrition services and programmes for children and adults can act as entry points to address and, in some cases, avoid or mitigate disability; disability programmes can improve nutrition for the children and adults they serve. For this to happen, however, political commitment and resources are needed, as are better data

    Malnutrition and disability: unexplored opportunities for collaboration.

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    There is increasing international interest in the links between malnutrition and disability: both are major global public health problems, both are key human rights concerns, and both are currently prominent within the global health agenda. In this review, interactions between the two fields are explored and it is argued that strengthening links would lead to important mutual benefits and synergies. At numerous points throughout the life-cycle, malnutrition can cause or contribute to an individual's physical, sensory, intellectual or mental health disability. By working more closely together, these problems can be transformed into opportunities: nutrition services and programmes for children and adults can act as entry points to address and, in some cases, avoid or mitigate disability; disability programmes can improve nutrition for the children and adults they serve. For this to happen, however, political commitment and resources are needed, as are better data

    Microbial transformations of selenite by methane-oxidizing bacteria

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    Abstract Methane oxidizing bacteria are well known for their role in the global methane cycle and their potential for microbial transformation of wide range of hydrocarbon and chlorinated hydrocarbon pollution. Recently, it has also emerged that methane-oxidizing bacteria interact with inorganic pollutants in the environment. Here we report what we believe to be the first study of the interaction of pure strains of methane-oxidizing bacteria with selenite. Results indicate that the commonly used laboratory model strains of methane oxidizing bacteria, Methylococcus capsulatus (Bath) and Methylosinus trichosporium OB3b are both able to reduce the toxic selenite (SeO32-) but not selenate (SeO42-) to red spherical nanoparticulate elemental selenium (Se0), which was characterised via EDX and EXAFS. The cultures also produced volatile selenium-containing species, which suggests that both strains may have an additional activity that can either transform Se0 or selenite into volatile methylated forms of selenium. Transmission electron microscopy (TEM) measurements and experiments with the cell fractions: cytoplasm, cell wall and cell membrane show that the nanoparticles are formed mainly on the cell wall. Collectively these results are promising for the use of methane-oxidizing bacteria for bioremediation or suggest possible uses in the production of selenium nanoparticles for biotechnology

    Engineering Multi-Agent Systems: State of Affairs and the Road Ahead

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    The continuous integration of software-intensive systems together with the ever-increasing computing power offer a breeding ground for intelligent agents and multi-agent systems (MAS) more than ever before. Over the past two decades, a wide variety of languages, models, techniques and methodologies have been proposed to engineer agents and MAS. Despite this substantial body of knowledge and expertise, the systematic engineering of large-scale and open MAS still poses many challenges. Researchers and engineers still face fundamental questions regarding theories, architectures, languages, processes, and platforms for designing, implementing, running, maintaining, and evolving MAS. This paper reports on the results of the 6th International Workshop on Engineering Multi-Agent Systems (EMAS 2018, 14th-15th of July, 2018, Stockholm, Sweden), where participants discussed the issues above focusing on the state of affairs and the road ahead for researchers and engineers in this area
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