Search

Abstract Introduction Despite various efforts to improve human papillomavirus (HPV) vaccine coverage in France, it has always been lower than in most other high‐income countries. The health authorities launched in 2018 the national PrevHPV research programme to (1) co‐develop with stakeholders and (2) evaluate the impact of a multicomponent complex intervention aimed at improving HPV vaccine coverage amongst French adolescents. Objective To describe the development process of the PrevHPV intervention using the GUIDance for rEporting of intervention Development framework as a guide. Methods To develop the intervention, we used findings from (1) published evidence on effective strategies to improve vaccination uptake and on theoretical frameworks of health behaviour change; (2) primary data on target populations' knowledge, beliefs, attitudes, preferences, behaviours and practices as well as the facilitators and barriers to HPV vaccination collected as part of the PrevHPV Programme and (3) the advice of working groups involving stakeholders in a participatory approach. We paid attention to developing an intervention that would maximise reach, adoption, implementation and maintenance in real‐world contexts. Results We co‐developed three components: (1) adolescents' and parents' education and motivation using eHealth tools (web conferences, videos, and a serious video game) and participatory learning at school; (2) general practitioners' e‐learning training on HPV using motivational interviewing techniques and provision of a decision aid tool and (3) easier access to vaccination through vaccination days organised on participating middle schools' premises to propose free of charge initiation of the HPV vaccination. Conclusion We co‐developed a multicomponent intervention that addresses a range of barriers and enablers of HPV vaccination. The next step is to build on the results of its evaluation to refine it before scaling it up if proven efficient. If so, it will add to the small number of multicomponent interventions aimed at improving HPV vaccination worldwide. Patient or Public Contribution The public (adolescents, their parents, school staff and health professionals) participated in the needs assessment using a mixed methods approach. The public was also involved in the components' development process to generate ideas about potential activities/tools, critically revise the successive versions of the tools and provide advice about the intervention practicalities, feasibility and maintenance.

Abstract Background HPV vaccine coverage in France remained lower than in most other high-income countries. Within the diagnostic phase of the national PrevHPV program, we carried out a mixed methods study among school staff to assess their knowledge, beliefs and attitudes regarding HPV, HPV vaccine and vaccination in general, and regarding schools’ role in promoting HPV vaccination. Methods Middle school nurses, teachers and support staff from four French regions participated between January 2020 and May 2021. We combined: (i) quantitative data from self-administered online questionnaires (n = 301), analysed using descriptive statistics; and (ii) qualitative data from three focus groups (n = 14), thematically analysed. Results Less than half of respondents knew that HPV can cause genital warts or oral cancers and only 18% that no antiviral treatment exists. Almost 90% of the respondents knew the existence of the HPV vaccine but some misunderstood why it is recommended before the first sexual relationships and for boys; 56% doubted about its safety, especially because they think there is not enough information on this topic. Schools nurses had greater knowledge than other professionals and claimed that educating pupils about HPV was fully part of their job roles; however, they rarely address this topic due to a lack of knowledge/tools. Professionals (school nurses, teachers and support staff) who participated in the focus groups were unfavourable to offering vaccination at school because of parents’ negative reactions, lack of resources, and perceived uselessness. Conclusions These results highlight the need to improve school staff knowledge on HPV. Parents should be involved in intervention promoting HPV vaccination to prevent their potential negative reactions, as feared by school staff. Several barriers should also be addressed before organizing school vaccination programs in France.

From simple physical systems to full production lines, numerical models could be used to minimize downtime and to optimize performances. In this article, the system of interest is the SPIRAL2 heavy ion accelerator cryogenic system. This article illustrates three different applications based on a SPIRAL2 cryostat model: optimal controller synthesis, virtual sensor synthesis, and anomaly detection. The two first applications have been deployed on the system. Experimental results are used to illustrate the benefits of such applications. The third application is a case study based on data generated from a thermodynamic twin model.

Background: The development and testing of a deep learning (DL)-based approach for detection and measurement of regions of Ellipsoid Zone (EZ) At-Risk to study progression in nonexudative age-related macular degeneration (AMD). Methods: Used in DL model training and testing were 341 subjects with nonexudative AMD with or without geographic atrophy (GA). An independent dataset of 120 subjects were used for testing model performance for prediction of GA progression. Accuracy, specificity, sensitivity, and intraclass correlation coefficient (ICC) for DL-based EZ At-Risk percentage area measurement was calculated. Random forest-based feature ranking of EZ At-Risk was compared to previously validated quantitative OCT-based biomarkers. Results: The model achieved a detection accuracy of 99% (sensitivity = 99%; specificity = 100%) for EZ At-Risk. Automatic EZ At-Risk measurement achieved an accuracy of 90% (sensitivity = 90%; specificity = 84%) and the ICC compared to ground truth was high (0.83). In the independent dataset, higher baseline mean EZ At-Risk correlated with higher progression to GA at year 5 (p < 0.001). EZ At-Risk was a top ranked feature in the random forest assessment for GA prediction. Conclusions: This report describes a novel high performance DL-based model for the detection and measurement of EZ At-Risk. This biomarker showed promising results in predicting progression in nonexudative AMD patients.

Background: We previously conducted a single-profile discrete choice experiment to elicit preferences of adolescents around HPV vaccine communication, finding that only half of participants made variable choices (non-uniform respondents) from which preferences were elicited. In this paper we provide a framework to evaluate post-choice certainty information to elicit preferences even among respondents who uniformly accepted (serial demanders) or refused (serial non-demanders) hypothetical vaccination scenarios. Methods: During an in-class online questionnaire among 1458 French adolescents aged 13–15 years old, we collected certainty levels (0–10) after decisions on nine hypothetical scenarios, including four vaccination attributes: information on vaccine-preventable disease type, on vaccine safety, on potential for indirect protection and on vaccine coverage. We developed a vaccine eagerness scale (ranging from −10 to 10), by combining information on the binary decision (accept vs. refuse the hypothetical vaccine) and the decision certainty level. We used random effects linear regressions to evaluate attributes’ impact on vaccine eagerness. Sensitivity analyses were performed taking into account low response quality, assessed as invariant certainty and low response time. Results: Attributes’ impact on decision certainty were similar between serial demanders (N = 659) and non-uniform respondents (N = 711): mentioning a positive benefit-risk balance significantly decreased certainty to accept (coefficient −0.93), while information on 80% coverage in other countries (+0.33) and potential for disease elimination (+0.09) increased it. Among serial non-demanders, significant attribute impacts were observed only after exclusion of low-quality responses (N = 31): a potential for disease elimination (coefficient: +0.24) and 80% coverage in other countries (+0.42) significantly increased certainty of refusing vaccination. Combining decision and certainty into a vaccine eagerness indicator allowed analysing preferences in the full sample, including “hesitant” respondents, who were sensitive to the content of the vaccination profile. Conclusion: Choice certainty informs on respondents’ preferences in single-profile discrete-choice experiments, in particular among those with uniform responses.

Introduction Vaccination is an effective and safe strategy to prevent Human papillomavirus (HPV) infection and related harms. Despite various efforts by French authorities to improve HPV vaccine coverage (VC) these past few years, VC has remained far lower than in most other high-income countries. To improve it, we have coconstructed with stakeholders a school-based and primary care-based multicomponent intervention, and plan to evaluate its effectiveness, efficiency and implementation through a cluster randomised controlled trial (cRCT).Methods and analysis This pragmatic cRCT uses an incomplete factorial design to evaluate three components applied alone or in combination: (1) adolescents and parents’ education and motivation at school, using eHealth tools and participatory learning; (2) general practitioners’ training on HPV using motivational interviewing techniques and provision of a decision aid tool; (3) free-of-charge access to vaccination at school. Eligible municipalities (clusters) are located in one of 14 preselected French school districts and must have only one secondary school which enrols at least 2/3 of inhabitants aged 11–14 years. A randomisation stratified by school district and deprivation index allocated 90 municipalities into 6 groups of 15. The expected overall sample size estimate is 41 940 adolescents aged 11–14 years. The primary endpoint is the HPV VC (≥1 dose) among adolescents aged 11–14 years, at 2 months, at the municipality level (data from routine databases). Secondary endpoints include: HPV VC (≥1 dose at 6 and 12 months; and 2 doses at 2, 6 and 12 months); differences in knowledge, attitudes, behaviours, and intention among adolescents, parents and general practitioners between baseline and 2 months after intervention (self-administered questionnaires); incremental cost-effectiveness ratio. Implementation measures include dose, fidelity, adaptations, reached population and satisfaction (activity reports and self-administered questionnaires).Ethics and dissemination This protocol was approved by the French Ethics Committee ‘CPP Sud-Est VI’ on 22 December 2020 (ID-RCB: 2020-A02031-38). No individual consent was required for this type of research; all participants were informed of their rights, in particular not to participate or to oppose the collection of data concerning them. Findings will be widely disseminated (conference presentations, reports, factsheets and academic publications).Trial registration number NCT04945655.

We report on recent progress in deploying a continuous solid hydrogen ribbon as a debris-free and renewable laser-driven source of pure proton beams generated by a 30-fs laser with ∼1-J laser energy focused on target at relativistic intensities of ∼1019 W/cm2 and repetition rate of 0.1 Hz. The stability of the ribbon position versus the laser interaction point and maximum repetition rate was tested up to 3.3 Hz. The acceleration of protons with cut-off energies up to 1.5 MeV is demonstrated using a 100-μm thick hydrogen ribbon as proof-of-principle capability of the relatively thick target delivery system. The laser-target geometry presented demonstrates an experimental technique that can potentially enables the operation of a laser–plasma source at Hz-level repetition rate.

Computer vision is one of AI’s most successful fields. In the last twenty years, machines have become increasingly good at extracting information from images and at identifying objects. But does this mean that machines really can see, or is computer vision just a fancy metaphor for object detection? This paper aims to provide a reasoned answer to the question. First, three criteria for vision attribution are reviewed and it is argued that a functionalist criterion, in terms of exploitable internal representations based on visual stimuli, fares better than behaviourist or phenomenological ones. The functionalist criterion is then applied to vision algorithms based on neural networks and it is argued that such machines can indeed see, insofar as neural networks are precisely trained to generate representations of the visual data they are fed with. Those representations present the specific traits associated with successful training: They are hierarchical, robust, and versatile. We argue that these properties may be used as further constraints on representational devices in general, helping to solve some of the classical issues faced by teleosemantic theories of representation such as that expounded by Dretske.

Cell-type specific transcriptional programs underlie the development and maintenance of organs. Not only distinct cell types within a tissue, even cells with supposedly identical cell fates show a high degree of transcriptional heterogeneity. Inevitable, low cell numbers are a major hurdle to study transcriptomes of pure cell populations. Here we describe DigiTAG, a high-throughput method that combines transposase fragmentation and molecular barcoding to retrieve high quality transcriptome data of rare cell types in Drosophila melanogaster. The protocol showcases how DigiTAG can be used to analyse the transcriptome of rare neural stem cells (type II neuroblasts) of Drosophila larval brains, but can also be utilized for other cell types or model systems.

The Immune Deficiency (IMD) pathway in Drosophila melanogaster is activated upon microbial challenge with Gram-negative bacteria to trigger the innate immune response. In order to decipher this nuclear factor κB (NF-κB) signaling pathway, we undertook an in vitro RNAi screen targeting E3 ubiquitin ligases specifically and identified the HECT-type E3 ubiquitin ligase Hyperplastic discs (Hyd) as a new actor in the IMD pathway. Hyd mediated Lys63 (K63)-linked polyubiquitination of the NF-κB cofactor Akirin was required for efficient binding of Akirin to the NF-κB transcription factor Relish. We showed that this Hyd-dependent interaction was required for the transcription of immunity-related genes that are activated by both Relish and Akirin but was dispensable for the transcription of genes that depend solely on Relish. Therefore Hyd is key in NF-κB transcriptional selectivity downstream of the IMD pathway. Drosophila depleted of Akirin or Hyd failed to express the full set of genes encoding immune-induced anti-microbial peptides and succumbed to immune challenges. We showed further that UBR5, the mammalian homolog of Hyd, was also required downstream of the NF-κB pathway for the activation of Interleukin 6 (IL6) transcription by LPS or IL-1β in cultured human cells. Our findings link the action of an E3 ubiquitin ligase to the activation of immune effector genes, deepening our understanding of the involvement of ubiquitination in inflammation and identifying a potential target for the control of inflammatory diseases.

Tumor cells display features that are not found in healthy cells. How they become immortal and how their specific features can be exploited to combat tumorigenesis are key questions in tumor biology. Here we describe the long non-coding RNA cherub that is critically required for the development of brain tumors in Drosophila but is dispensable for normal development. In mitotic Drosophila neural stem cells, cherub localizes to the cell periphery and segregates into the differentiating daughter cell. During tumorigenesis, de-differentiation of cherub-high cells leads to the formation of tumorigenic stem cells that accumulate abnormally high cherub levels. We show that cherub establishes a molecular link between the RNA-binding proteins Staufen and Syncrip. As Syncrip is part of the molecular machinery specifying temporal identity in neural stem cells, we propose that tumor cells proliferate indefinitely, because cherub accumulation no longer allows them to complete their temporal neurogenesis program.

Hintikka and Sandu have developed IF logic as a genuine alternative to classical first-order logic : liberalizing dependence schemas between quantifiers, IF would carry out all the ideas already underlying classical logic. But they are alternatives to Hintikka’s game-theoretic approach; one could use instead Henkin quantifiers. We will present here some arguments of both technical and philosophical nature in favor of IF. We will show that its notion of independence, once extended to connectives, can indeed claim to be fully general, and that IF logic provides an analysis of independence patterns. This last point will be argued for thanks to an explanation of the epistemic content of IF, through a partial translation into modal logic.

Hintikka makes a distinction between two kinds of games: truthconstituting games and truth-seeking games. His well-known game-theoretical semantics for first-order classical logic and its independence-friendly extension belongs to the first class of games. In order to ground Hintikka’s claim that truth-constituting games are genuine verification and falsification games that make explicit the language games underlying the use of logical constants, it would be desirable to establish a substantial link between these two kinds of games. Adapting a result from Thierry Coquand, we propose such a link, based on a slight modification of Hintikka’s games, in which we allow backward playing for ∃loïse. In this new setting, it can be proven that sequent rules for first-order logic, including the cut rule, are admissible, in the sense that for each rule, there exists an algorithm which turns winning strategies for the premisses into a winning strategy for the conclusion. Thus, proofs, as results of truth-seeking games, can be seen

A high-power pulsed laser is focused onto a solid-hydrogen target to accelerate forward a collimated stream of protons in the range 0.1–1 MeV, carrying a very high energy of about 30 J (∼5% laser-ion conversion efficiency) and extremely large charge of about ∼0.1 mC per laser pulse. This result is achieved for the first time through the combination of a sophisticated target system (H_{2} thin ribbon) operating at cryogenic temperature (∼10 K) and a very hot H plasma (∼300 keV “hot electron” temperature) generated by a subnanosecond laser with an intensity of ∼3×10^{16} W/cm^{2}. Both the H plasma and the accelerated proton beam are fully characterized by in situ and ex situ diagnostics. Results obtained using the ELISE (experiments on laser interaction with solid hydrogen) H_{2} target delivery system at PALS (Prague) kJ-class laser facility are presented and discussed along with potential multidisciplinary applications.

This paper presents an extension of a recently proposed hierarchical control framework applied to linearization-based unconstrained control of a cryogenic refrigerator. The extension concerns the validation of the framework in the presence of both nonlinear models and constraints. It is also shown that real-time handling of these features requires a specific complexity reduction technique. This technique performs the distribution of the optimization process over cyclically changed decision variables aiming at limiting the number of iterations per updating period. Numerical simulations are proposed in order to show the impact of the parameters choices and to assess the real-time implementability of the proposed framework. [ABSTRACT FROM AUTHOR]