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Abstract Background Vulnerable social groups have greater difficulty in accessing care and a lower quality of care. Health systems focused on primary care appear to be more effective, efficient and equitable. However, difficulties in accessing primary care are persisting. We focused on primary care screening for cervical cancer through Cervico-Uterine Smear (CUS), which has been shown to be effective in reducing disease incidence and mortality. In this study, we aimed to investigate the characteristics of women who undergo CUS according to the category of health professionals (general practitioners or gynaecologists) performing CUS and to analyse potential differences in access to care in terms of socioeconomic and geographical characteristics. Methods This was a retrospective observational study based on data from the main health insurance schemes in France, allowing analysis of health care consumption according to socioeconomic levels and proximity to health care services. We included women aged 25 to 64 years in 2012 for whom CUS would be a relevant procedure (695,694). The sociodemographic and territorial indicators were age, geographical area deprivation, and the availability of gynaecological care. The analysis was performed using multinomial logistic regression. Results A total of 202,271 (29%) patients underwent CUS; of whom 68% underwent CUS administered by gynaecologists and 28% were administered by general practitioners (GPs). However, inequalities in CUS screening rates were observed, with a decrease in the number of CUSs performed with increased age, a rural location, deprivation, and sparse health care provisions. Deprived people seemed less penalised by GPs. Conclusions Involvement of General Practitioners may improve cervical screening equality in France. The organisation of health systems around primary care may allow a better access to care and to account for the specific needs of deprived populations.

Robotics and autonomous systems are reshaping the world, changing healthcare, food production and biodiversity management. While they will play a fundamental role in delivering the UN Sustainable Development Goals, associated opportunities and threats are yet to be considered systematically. We report on a horizon scan evaluating robotics and autonomous systems impact on all Sustainable Development Goals, involving 102 experts from around the world. Robotics and autonomous systems are likely to transform how the Sustainable Development Goals are achieved, through replacing and supporting human activities, fostering innovation, enhancing remote access and improving monitoring. Emerging threats relate to reinforcing inequalities, exacerbating environmental change, diverting resources from tried-and-tested solutions and reducing freedom and privacy through inadequate governance. Although predicting future impacts of robotics and autonomous systems on the Sustainable Development Goals is difficult, thoroughly examining technological developments early is essential to prevent unintended detrimental consequences. Additionally, robotics and autonomous systems should be considered explicitly when developing future iterations of the Sustainable Development Goals to avoid reversing progress or exacerbating inequalities.

Most of the allergenic proteins from fruits identified so far belong to different families of pathogenesis-related (PR) proteins. These PR proteins have been classified in different families of structurally and functionally unrelated proteins, but the majority of all fruit allergens belong to three groups, in particular PR-5 thaumatin-like proteins (TLP), PR-10 Bet v 1-like proteins, and PR-14 non-specific lipid transfer proteins (nsTLP). Some allergenic proteins from fruits can also be found among PR-protein families of PR-2 β1,3-glucanase proteins, PR-3 chitinases I, II, IV–VII, and PR-8 chitinases III. In addition, other important fruit allergens occur in protein families unrelated to the PR-protein families, such as the profilins and the newly emerging group of gibberellin-regulated proteins (GBRP). Finally, proteins that belong to seed storage proteins from higher plants, including 2S albumins, 7S globulins (vicilin), and 11S globulins (legumin), must be retained as possible potential fruit allergens resulting from the unintended consumption of the seeds. Here, we present an overview of the structural organization, functional properties, and phylogenetical relationships among these different groups of fruit allergens, supporting the occurrence of cross-reactivity and cross-allergenicity often described between fruit allergens, and the corresponding allergens from vegetables and pollens.

Wavelet-based grid resolution adaptation driven by the ‘multiresolution analysis’ (MRA) of the Haar wavelet (HW) allows to devise an adaptive first-order finite volume (FV1) model (HWFV1) that can readily preserve the modelling fidelity of its reference uniform-grid FV1 counterpart. However, the MRA entails an enormous computational effort as it involves ‘encoding’ (coarsening), ‘decoding’ (refining), analysing and traversing modelled data across a deep hierarchy of nested, uniform grids. GPU-parallelisation of the MRA is needed to handle its computational effort, but its algorithmic structure (1) hinders coalesced memory access on the GPU and (2) involves an inherently sequential tree traversal problem. This work redesigns the algorithmic structure of the MRA in order to parallelise it on the GPU, addressing (1) by applying Z-order space-filling curves and (2) by adopting a parallel tree traversal algorithm. This results in a GPU-parallelised HWFV1 model (GPU-HWFV1). GPU-HWFV1 is verified against its CPU predecessor (CPU-HWFV1) and its GPU-parallelised reference uniform-grid counterpart (GPU-FV1) over five shallow water flow test cases. GPU-HWFV1 preserves the modelling fidelity of GPU-FV1 while being up to 30 times faster. Compared to CPU-HWFV1, it is up to 200 times faster, suggesting that the GPU-parallelised MRA could be used to speed up other FV1 models. HIGHLIGHTS Wavelet-based grid adaptation is parallelised on the GPU via a Z-order space-filling curve and a parallel tree traversal algorithm.; An adaptive Haar wavelet first-order finite volume shallow water model running on the GPU is developed (GPU-HWFV1).; GPU-HWFV1 is 20–300 times faster than its single-core serial CPU version 4.; GPU-HWFV1 is 1.3–30 times faster than its GPU-parallelised reference uniform-grid counterpart.;

Assessing the robustness of a water resource system's performance under climate change involves exploring a wide range of streamflow conditions. This is often achieved through rainfall–runoff models, but these are commonly validated under historical conditions with no guarantee that calibrated parameters would still be valid in a different climate. In this note, we introduce a new method for the statistical generation of plausible streamflow futures. It flexibly combines changes in average flows with changes in the frequency and magnitude of high and low flows. It relies on a three-parameter analytical representation of the flow duration curve (FDC) that has been proved to perform well across a range of basins in different climates. We rigorously prove that, for common sets of streamflow statistics mirroring average behaviour, variability, and low flows, the parameterisation of the FDC under this representation is unique. We also show that conditions applied to these statistics for a solution to exist are commonly met in practice. These analytical results imply that streamflow futures can be explored by sampling wide ranges of three key flow statistics and by deriving the corresponding FDC in relation to model basin response across the full spectrum of flow conditions. We illustrate this method by exploring in which hydro-climatic futures a proposed run-of-river hydropower plant in eastern Turkey is financially viable. Results show that, contrary to approaches that modify streamflow statistics using multipliers applied uniformly throughout a time series, our approach seamlessly represents a large range of futures with increased frequencies of both high and low flows. This matches expected impacts of climate change in the region and supports analyses of the financial robustness of the proposed infrastructure to climate change. We conclude by highlighting how refinements to the approach could further support rigorous explorations of hydro-climatic futures without the help of rainfall–runoff models.

The TRPA1 ion channel is activated by electrophilic compounds through the covalent modification of intracellular cysteine residues. How non-covalent agonists activate the channel and whether covalent and non-covalent agonists elicit the same physiological responses are not understood. Here, we report the discovery of a non-covalent agonist, GNE551, and determine a cryo-EM structure of the TRPA1-GNE551 complex, revealing a distinct binding pocket and ligand-interaction mechanism. Unlike the covalent agonist allyl isothiocyanate, which elicits channel desensitization, tachyphylaxis, and transient pain, GNE551 activates TRPA1 into a distinct conducting state without desensitization and induces persistent pain. Furthermore, GNE551-evoked pain is relatively insensitive to antagonist treatment. Thus, we demonstrate the biased agonism of TRPA1, a finding that has important implications for the discovery of effective drugs tailored to different disease etiologies.

Celiac peptide-generating α- and γ-gliadins consist of a disordered N-terminal domain extended by an α-helical-folded C-terminal domain. Celiac peptides, primarily located along the disordered part of α- and γ-gliadin molecules, are nicely exposed and directly accessible to proteolytic enzymes occurring in the gastric (pepsin) and intestinal (trypsin, chymotrypsin) fluids. More than half of the potential celiac peptides identified so far in gliadins exhibit cleavage sites for pepsin. However, celiac peptides proteolytically truncated by one or two amino acid residues could apparently retain some activity toward HLA-DQ2 and HLA-DQ8 receptors in docking experiments. Together with the uncleaved peptides, these still active partially degraded CD peptides account for the incapacity of the digestion process to inactivate CD peptides from gluten proteins. In contrast, sourdough fermentation processes involve other proteolytic enzymes susceptible to the deep degradation of celiac peptides. In particular, sourdough supplemented by fungal prolyl endoproteases enhances the degrading capacities of the sourdough fermentation process toward celiac peptides. Nevertheless, since tiny amounts of celiac peptides sufficient to trigger deleterious effects on CD people can persist in sourdough-treated bread and food products, it is advisable to avoid consumption of sourdough-treated food products for people suffering from celiac disease. As an alternative, applying the supplemented sourdough process to genetically modified low gluten or celiac-safe wheat lines should result in food products that are safer for susceptible and CD people.

The present work was aimed at identifying the IgE-binding epitopic regions on the surface of the Cup s 3 allergen from the common cypress Cupressus sempervirens, that are possibly involved in the IgE-binding cross-reactivity reported between Cupressaceae species. Three main IgE-binding epitopic regions were mapped on the molecular surface of Cup s 3, the PR-5 thaumatin-like allergen of common cypress Cupressus sempervirens. They correspond to exposed areas containing either electropositive (R, K) or electronegative (D, E) residues. A coalescence occurs between epitopes #1 and #2, that creates an extended IgE-binding regions on the surface of the allergen. Epitope #3 contains a putative N-glycosylation site which is actually glycosylated and could therefore comprise a glycotope. However, most of the allergenic potency of Cup s 3 depends on non-glycosylated epitopic peptides. The corresponding regions of thaumatin-like allergens from other closely related Cupressaceae (Cryptomeria, Juniperus, Thuja) exhibit a very similar conformation that should account for the IgE-binding cross-reactivity observed among the Cupressaceae allergens.

Background The general practitioner (GP) is central to managing patients with cancer, whose numbers are increasing worldwide. The GP’s involvement requires better coordination between involved partners, in particular oncologists and GPs. Objectives To conduct a feasibility study of remote participation of GPs in multi-disciplinary consultation meetings (MCMs). We analysed participation, participants’ satisfaction, and their impact on therapeutic decisions. Methods We conducted a feasibility study in the regional cancer centre of Toulouse, France. All patient cases discussed in the MCMs for myelodysplasia from 1 January to 31 March 2016 were included. Cases of patients aged over 18 years, with a diagnosis of myelodysplasia and registered with a GP were included if patients gave informed consent. One investigator collected the data provided by GPs during three telephone or video calls: before, during, and after the MCM, respectively. Results Of 86 patient cases discussed during three months of MCMs, 44 were eligible for GP participation; 27 GPs participated in discussions of 27 patient cases. The GP’s participation in the MCM led to a change in management in five cases, with four times treatment intensifications and once de-intensification. Medical, social, family-related, and psychological domains were discussed with input from the GPs. Overall, all participants were satisfied with the MCMs. Conclusion Remote participation of GPs in MCMs is feasible and may result in adapting oncological and haematological management for patients. This patient-centred approach requires a specific organisation that, when implemented, satisfies the needs of all participants.

Pectate-lyase allergens, the group 1 of allergens from Cupressaceae pollen, consist of glycoproteins exhibiting an extremely well-conserved three-dimensional structure and sequential IgE-binding epitopes. Up to 10 IgE-binding epitopic regions were identified on the molecular surface, which essentially cluster at both extremities of the long, curved β-prism-shaped allergens. Most of these IgE-binding epitopes possess very similar conformations that provide insight into the IgE-binding cross-reactivity and cross-allergenicity commonly observed among Cupressaceae pollen allergens. Some of these epitopic regions coincide with putative N-glycosylation sites that most probably consist of glycotopes or cross-reactive carbohydrate determinants, recognized by the corresponding IgE antibodies from allergic patients. Pectate-lyase allergens of Cupressaceae pollen offer a nice example of structurally conserved allergens that are widely distributed in closely-related plants (Chamæcyparis, Cryptomeria, Cupressus, Hesperocyparis, Juniperus, Thuja) and responsible for frequent cross-allergenicity.