Self-reported estimation of usual walking speed improves the performance of questionnaires estimating walking capacity in patients with vascular-type claudication

OBJECTIVE: Most questionnaires do not estimate the usual walking speed of the patient, although it is well known that patients may experience apparently different walking capacities if walking slow or fast. We hypothesized that correcting the self-reported estimated walking capacity by a coefficient issued from the self-reported estimation of usual walking speed would significantly improve the correlation between questionnaire-estimated and treadmill-measured walking capacity. METHODS: Three hundred ten consecutive patients complaining of vascular-type claudication were asked to estimate their usual walking speed in comparison to people of their age (or friends or relatives) with ratings ranging from much slower (1 pt) to much faster (5 pts), in addition to the filling out of the walking impairment questionnaire (WIQ) and the estimated ambulatory capacity by history questionnaire (EACH-Q). Corrected WIQ (WIQc) and corrected EACH-Q (EACH-Qc) scores were obtained by multiplying the scores of each questionnaire by the "usual-speed" coefficient and dividing by 5. Results for questionnaire scores were compared to maximal walking time (MWT) on a treadmill. RESULTS: All but four patients self-completed the usual-speed question. Median scores (25-75 centiles) were 41% (26-59) for the WIQ and 24% (11-41) for the EACH-Q. Coefficients of correlation of the three WIQ subscales and of the EACH-Q with treadmill results were significantly improved after correction by the "usual-speed" question. Overall, WIQ (mean of the three WIQ subscales) tended to improve but did not reach significance. CONCLUSION: Correcting the self-reported estimation of walking capacity by a self-reported estimation of usual walking pace significantly improves the correlation of all WIQ subscale scores and of the EACH-Q score with treadmill measurements of capacity. This confirms the interest of speed estimation in patients with peripheral arterial occlusive disease and claudication

CHR11, a chromatin-remodeling factor essential for nuclear proliferation during female gametogenesis in Arabidopsis thaliana

Chromatin-remodeling factors regulate the establishment of transcriptional programs during plant development. Although 42 genes encoding members of the SWI2/SNF2 family have been identified in Arabidopsis thaliana, < 10 have been assigned a precise function on the basis of a mutant phenotype, and none have been shown to play a specific role during the gametophytic phase of the plant life cycle. A. thaliana chromatin-remodeling protein 11 (CHR11) encodes an imitation of switch (ISWI)-like chromatin-remodeling protein abundantly expressed during female gametogenesis and embryogenesis in Arabidopsis. To determine the function of CHR11 in wild-type plants, we introduced a hairpin construct leading to the production of double-stranded RNA, which specifically degraded the endogenous CHR11 mRNA by RNA interference (RNAi). Transcription of the RNAi-inducing hairpin RNA was driven by either a constitutive cauliflower mosaic virus 35S promoter (CaMV35S) acting at most stages of the sporophytic phase or a newly identified specific promoter acting at the onset of the female gametophytic phase (pFM1). All adult trans-formants that constitutively lacked sporophytic CHR11 activity showed reduced plant height and small cotyledonary embryos with limited cell expansion. In contrast, RNAi lines in which CHR11 was specifically silenced at the onset of female gametogenesis (megagametogenesis) had normal height and embryo size but had defective female gametophytes arrested before the completion of the mitotic haploid nuclear divisions. These results show that CHR11 is essential for haploid nuclear proliferation during megagametogenesis and cell expansion during the sporophytic phase, demonstrating the functional versatility of SW12/SNF2 chromatin-remodeling factors during both generations of the plant life cycle

LAF1, a MYB transcription activator for phytochrome A signaling

The photoreceptor phytochrome (phy) A has a well-defined role in regulating gene expression in response to specific light signals. Here, we describe a new Arabidopsis mutant, laf1 (long after far-red light 1) that has an elongated hypocotyl specifically under far-red light. Gene expression studies showed that laf1 has reduced responsiveness to continuous far-red light but retains wild-type responses to other light wavelengths. As far-red light is only perceived by phyA, our results suggest that LAF1 is specifically involved in phyA signal transduction. Further analyses revealed that laf1 is affected in a subset of phyA-dependent responses and the phenotype is more severe at low far-red fluence rates. LAF1 encodes a nuclear protein with strong homology with the R2R3-MYB family of DNA-binding proteins. Experiments using yeast cells identified a transactivation domain in the C-terminal portion of the protein. LAF1 is constitutively targeted to the nucleus by signals in its N-terminal portion, and the full-length protein accumulates in distinct nuclear speckles. This accumulation in speckles is abolished by a point mutation in a lysine residue (K258R), which might serve as a modification site by a small ubiquitin-like protein (SUMO)

The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses

Flaviviruses replicate in a wide variety of species and have a broad cellular tropism. They are isolated from various body fluids, and Zika virus (ZIKV), Japanese encephalitis virus (JEV), and West Nile virus (WNV) RNAs have been detected in nasopharyngeal swabs. Consequently, we evaluated the cellular tropism and host responses upon ZIKV, JEV, WNV, and Usutu virus (USUV) infection using a relevant model of the human upper respiratory tract epithelium based on primary human nasal epithelial cells (NECs) cultured at the air-liquid interface. NECs were susceptible to all the viruses tested, and confocal analysis showed evidence of infection of ciliated and non-ciliated cells. Each flavivirus productively infected NECs, leading to apical and basolateral live virus shedding with particularly high basal release for JEV and WNV. As demonstrated by a paracellular permeability assay, the integrity of the epithelium was not affected by flavivirus infection, suggesting an active release of live virus through the basolateral surface. Also, we detected a significant secretion of interferon type III and the pro-inflammatory cytokine IP-10/CXCL10 upon infection with JEV. Taken together, our data suggest that the human upper respiratory tract epithelium is a target for flaviviruses and could potentially play a role in the spread of infection to other body compartments through basolateral virus release. Undoubtedly, further work is required to evaluate the risks and define the adapted measures to protect individuals exposed to flavivirus-contaminated body fluids

A dynamic Game Model of Strategic RD&D Cooperation and GHG Emission Mitigation

This report describes the game structures implemented in the TOCSIN project to find self-enforcing and stable international environmental agreements. It presents the first results obtained with the use of these models. The document starts with a review of the different approaches that have been proposed in the literature to represent in a game theoretic framework the concept of self-enforcing or stable international environmental agreement

Producing policy-relevant science by enhancing robustness and model integration for the assessment of global environmental change

We use the flexible model coupling technology known as the bespoke framework generator to link established existing modules representing dynamics in the global economy (GEMINI_E3), the energy system (TIAM-WORLD), the global and regional climate system (MAGICC6, PLASIM-ENTS and ClimGEN), the agricultural system, the hydrological system and ecosystems (LPJmL), together in a single integrated assessment modelling (IAM) framework, building on the pre-existing framework of the Community Integrated Assessment System. Next, we demonstrate the application of the framework to produce policy-relevant scientific information. We use it to show that when using carbon price mechanisms to induce a transition from a high-carbon to a low-carbon economy, prices can be minimised if policy action is taken early, if burden sharing regimes are used, and if agriculture is intensified. Some of the coupled models have been made available for use at a secure and user-friendly web portal

Pension systems compared : a polarised perspective, a diverse reality

Production of INCASI Project H2020-MSCA-RISE-2015 GA 691004Globalisation and international competition have a spillover effect on the reforms of pension systems that imposes a similar pattern of dismantling, hardening access to pensions, reducing expenditure and retrenchment in said reforms. The comparative analysis of four countries with different pension systems: two liberal (United Kingdom and Chile) and another two with contributory-proportional systems (Spain and Argentina) serves to determine the details of the reform processes, which discursively seem to have a shared pattern recommended by the international financial and economic institutions. But the reality of the four case studies shows considerable differences in the implementation of the pension reform policies. The reforms depend on the societal context, institutions, history, the role of unions, the government in power, demographic factors and economic perspectives, among other matters. Many countries need to sustain pension systems because they are associated with many pensioners' political vote. Therefore, the spillover effect of globalisation and the convergence in certain uniform patterns of reforms is far from reality in the four countries, and as such, the measures adopted are specific for each country

Producing Policy-relevant Science by Enhancing Robustness and Model Integration for the Assessment of Global Environmental Change

We use the flexible model coupling technology known as the bespoke framework generator to link established existing modules representing dynamics in the global economy (GEMINI_E3), the energy system (TIAM-WORLD), the global and regional climate system (MAGICC6, PLASIM-ENTS and ClimGEN), the agricultural system, the hydrological system and ecosystems (LPJmL), together in a single integrated assessment modelling (IAM) framework, building on the pre-existing framework of the Community Integrated Assessment System. Next, we demonstrate the application of the framework to produce policy-relevant scientific information. We use it to show that when using carbon price mechanisms to induce a transition from a high-carbon to a low-carbon economy, prices can be minimised if policy action is taken early, if burden sharing regimes are used, and if agriculture is intensified. Some of the coupled models have been made available for use at a secure and user-friendly web portal. © 2018 The Author

Where is the EU headed given its current climate policy? A stakeholder-driven model inter-comparison.

Recent calls to do climate policy research with, rather than for, stakeholders have been answered in non-modelling science. Notwithstanding progress in modelling literature, however, very little of the scenario space traces back to what stakeholders are ultimately concerned about. With a suite of eleven integrated assessment, energy system and sectoral models, we carry out a model inter-comparison for the EU, the scenario logic and research questions of which have been formulated based on stakeholders' concerns. The output of this process is a scenario framework exploring where the region is headed rather than how to achieve its goals, extrapolating its current policy efforts into the future. We find that Europe is currently on track to overperforming its pre-2020 40% target yet far from its newest ambition of 55% emissions cuts by 2030, as well as looking at a 1.0-2.35 GtCO2 emissions range in 2050. Aside from the importance of transport electrification, deployment levels of carbon capture and storage are found intertwined with deeper emissions cuts and with hydrogen diffusion, with most hydrogen produced post-2040 being blue. Finally, the multi-model exercise has highlighted benefits from deeper decarbonisation in terms of energy security and jobs, and moderate to high renewables-dominated investment needs

A Statistical Model for Estimating Maternal-Zygotic Interactions and Parent-of-Origin Effects of QTLs for Seed Development

Proper development of a seed requires coordinated exchanges of signals among the three components that develop side by side in the seed. One of these is the maternal integument that encloses the other two zygotic components, i.e., the diploid embryo and its nurturing annex, the triploid endosperm. Although the formation of the embryo and endosperm contains the contributions of both maternal and paternal parents, maternally and paternally derived alleles may be expressed differently, leading to a so-called parent-of-origin or imprinting effect. Currently, the nature of how genes from the maternal and zygotic genomes interact to affect seed development remains largely unknown. Here, we present a novel statistical model for estimating the main and interaction effects of quantitative trait loci (QTLs) that are derived from different genomes and further testing the imprinting effects of these QTLs on seed development. The experimental design used is based on reciprocal backcrosses toward both parents, so that the inheritance of parent-specific alleles could be traced. The computing model and algorithm were implemented with the maximum likelihood approach. The new strategy presented was applied to study the mode of inheritance for QTLs that control endoreduplication traits in maize endosperm. Monte Carlo simulation studies were performed to investigate the statistical properties of the new model with the data simulated under different imprinting degrees. The false positive rate of imprinting QTL discovery by the model was examined by analyzing the simulated data that contain no imprinting QTL. The reciprocal design and a series of analytical and testing strategies proposed provide a standard procedure for genomic mapping of QTLs involved in the genetic control of complex seed development traits in flowering plants