Project description:Research of human vocal fold (VF) biology is hampered by several factors. The sensitive microstructure of the VF mucosa is one of them and limits the in vivo research, as biopsies carry the unbearable risk of scarring. A laryngeal organotypic model consisting of VF epithelial cells and VF fibroblasts (VFF) might overcome some of the limitations. Whereas human VFF are available in several forms, availability of VF epithelial cells is scarce. Buccal mucosa might be a good source, as it is easily accessible, and biopsies heal without scarring. For this project we generated organotypic constructs consisting of immortalized human VF fibroblasts and primary human buccal epithelial cells. The constructs (n = 3) were compared to native laryngeal mucosa on a histological and proteomic level. The engineered constructs reassembled into a mucosa-like structure, after a cultivation period of 35 days. Immunohistochemical staining confirmed a multi-layered stratified epithelium, a collagen type IV positive barrier-like structure resembling the basal membrane, and an underlying layer containing VFF. Proteomic analysis revealed a total number of 1961 proteins. Of these, 83.8% were detected in both native VF and constructs, with only 53 proteins having significantly different abundance. 15.3% of detected proteins were identified in native VF mucosa only, most likely due to endothelial, immune and muscle cells within the VF samples, while 0.9% were found only in the constructs. Based on easily available cell sources, we could demonstrate that our organotypic laryngeal mucosa model shares many characteristics with native VF mucosa. It represents a stable and reproducible in vitro model and offers a wide range of possibilities ranging from the exploration of VF biology to the testing of interventions (e.g. drug testing).
Project description:Continuous improvements in the resolution of three-dimensional imaging have led to an increased application of these techniques in conventional taxonomic research in recent years. Coupled with an ever increasing research effort in cybertaxonomy, three-dimensional imaging could give a boost to the development of virtual specimen collections, allowing rapid and simultaneous access to accurate virtual representations of type material. This paper explores the potential of micro-computed tomography (X-ray micro-tomography), a non-destructive three-dimensional imaging technique based on mapping X-ray attenuation in the scanned object, for supporting research in systematics and taxonomy. The subsequent use of these data as virtual type material, so-called "cybertypes", and the creation of virtual collections lie at the core of this potential. Sample preparation, image acquisition, data processing and presentation of results are demonstrated using polychaetes (bristle worms), a representative taxon of macro-invertebrates, as a study object. Effects of the technique on the morphological, anatomical and molecular identity of the specimens are investigated. The paper evaluates the results and discusses the potential and the limitations of the technique for creating cybertypes. It also discusses the challenges that the community might face to establish virtual collections. Potential future applications of three-dimensional information in taxonomic research are outlined, including an outlook to new ways of producing, disseminating and publishing taxonomic information.
Project description:IntroductionIn January 2013 a novel type of multicomponent protein-based vaccine against group B meningococcal disease was licensed by the European Medicines Agency. With the widespread use of the meningococcal serogroup C conjugate vaccines, serogroup B remains now the major cause of bacterial meningitis and septicaemia in young children in Europe. The aim of this study is to investigate the health and the economic outcomes of MenB vaccine introduction into the Italian routine mass vaccination programme.MethodsThe present work is structured in two main parts. Firstly, we assess the epidemiological burden of group B meningococcal disease using official hospitalisation and notification data from two of the most populated Italian regions (Lombardia and Piemonte) during a 6-year study period (2007-2012). Secondly, we evaluate the cost-effectiveness of the immunisation programme in Italy from the public health payer perspective under base case parameters assumptions and performing a comprehensive sensitivity analysis to assess the robustness and the uncertainty of our model results.ResultsMenB serotype is responsible for 59% of the 341 cases of Invasive Meningococcal Disease in Lombardia and Piemonte. Incidence rate for MenB infection is estimated to be 0.21/100,000/y resulting at the highest level in children ?4 years of age. Although the new MenB vaccine can potentially prevent about one third of the disease cases in the Italian population, model results show this strategy is unlikely to be cost-effective (ICER value over €350,000/QALY) with a vaccine that prevents disease only. These results are robust under most of the sensitivity scenarios except when allowing for lower discount rates.DiscussionThe introduction of the novel vaccine into the routine immunisation schedule needs to be carefully evaluated. The new MenB vaccine has the potential to reduce the disease burden at the population level. However, from the Italian Health Service perspective, the immunisation programme is unlikely to be cost-effective at the current incidence levels and vaccine price.
Project description:This paper introduces the 'Survey of Health, Ageing and Retirement in Europe' (SHARE) to researchers on ageing. SHARE provides an infrastructure to help researchers better understand the individual and population ageing process: where we are, where we are heading to, and how we can influence the quality of life as we age, both as individuals and as societies. The baseline wave in 2004 provides data on the life circumstances of some 27,000 persons aged 50 and over in 11 European countries, ranging from Scandinavia across Western and Central Europe to the Mediterranean. SHARE has made great efforts to deliver truly comparable data, so we can reliably study how differences in cultures, living conditions and policy approaches shape the life of Europeans just before and after retirement. The paper first describes the SHARE data. In order to demonstrate its value, it then presents highlights from the three main research areas covered by SHARE, namely economics, sociology, and health.
Project description:A new sequencing-based women's health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis
Project description:BackgroundOnline interventions to prevent mental health problems have proven to be effective. However, knowledge about their implementation in real-world practice as well as for dissemination to the target groups in different settings is scarce. The goal of the 'ICare' network is to establish a comprehensive model of eMental-health service delivery in and across different European countries. Since implementation and dissemination are influenced by many contextual factors, in the first phase of ICare a stakeholder survey was conducted. The survey aim was to explore stakeholders' experiences, needs and attitudes regarding Internet-based prevention of mental health problems and hindering and fostering factors for implementation and dissemination. This article is part of a supplement and describes the design of the stakeholder survey. Survey results are published in separate articles in the same supplement.MethodsBased on a literature review and the individual characteristics of the ICare interventions, stakeholder groups were identified in different settings across six European countries. The RE-AIM framework guided the development of the research questions and survey instruments. A concurrent mixed methods design was applied comprising focus groups with the intended target groups of ICare interventions, an online questionnaire with potential facilitators/delivery staff and semi-structured interviews with policy makers.ConclusionThe challenge was to develop a design that allowed flexibility but at the same did not jeopardize the validity of the study. Implications drawn from this survey are not restricted to specific preventive interventions but will provide general information on how online mental illness prevention can be best implemented in various settings.
Project description:Natural experimental studies are often recommended as a way of understanding the health impact of policies and other large scale interventions. Although they have certain advantages over planned experiments, and may be the only option when it is impossible to manipulate exposure to the intervention, natural experimental studies are more susceptible to bias. This paper introduces new guidance from the Medical Research Council to help researchers and users, funders and publishers of research evidence make the best use of natural experimental approaches to evaluating population health interventions. The guidance emphasises that natural experiments can provide convincing evidence of impact even when effects are small or take time to appear. However, a good understanding is needed of the process determining exposure to the intervention, and careful choice and combination of methods, testing of assumptions and transparent reporting is vital. More could be learnt from natural experiments in future as experience of promising but lesser used methods accumulates.
Project description:Bovine pancreatic ribonuclease (RNase A) is the founding member of the RNase A superfamily. Members of this superfamily of ribonucleases have high sequence diversity, but possess a similar structural fold, together with a conserved His-Lys-His catalytic triad and structural disulfide bonds. Until recently, RNase A proteins had exclusively been identified in eukaryotes within vertebrae. Here, we discuss the discovery by Batot et al. of a bacterial RNase A superfamily member, CdiA-CTYkris: a toxin that belongs to an inter-bacterial competition system from Yersinia kristensenii. CdiA-CTYkris exhibits the same structural fold as conventional RNase A family members and displays in vitro and in vivo ribonuclease activity. However, CdiA-CTYkris shares little to no sequence similarity with RNase A, and lacks the conserved disulfide bonds and catalytic triad of RNase A. Interestingly, the CdiA-CTYkris active site more closely resembles the active site composition of various eukaryotic endonucleases. Despite lacking sequence similarity to eukaryotic RNase A family members, CdiA-CTYkris does share high sequence similarity with numerous Gram-negative and Gram-positive bacterial proteins/domains. Nearly all of these bacterial homologs are toxins associated with virulence and bacterial competition, suggesting that the RNase A superfamily has a distinct bacterial subfamily branch, which likely arose by way of convergent evolution. Finally, RNase A interacts directly with the immunity protein of CdiA-CTYkris, thus the cognate immunity protein for the bacterial RNase A member could be engineered as a new eukaryotic RNase A inhibitor.
Project description:Indirect forms of speech, such as sarcasm, jocularity (joking), and 'white lies' told to spare another's feelings, occur frequently in daily life and are a problem for many clinical populations. During social interactions, information about the literal or nonliteral meaning of a speaker unfolds simultaneously in several communication channels (e.g., linguistic, facial, vocal, and body cues); however, to date many studies have employed uni-modal stimuli, for example focusing only on the visual modality, limiting the generalizability of these results to everyday communication. Much of this research also neglects key factors for interpreting speaker intentions, such as verbal context and the relationship of social partners. Relational Inference in Social Communication (RISC) is a newly developed (English-language) database composed of short video vignettes depicting sincere, jocular, sarcastic, and white lie social exchanges between two people. Stimuli carefully manipulated the social relationship between communication partners (e.g., boss/employee, couple) and the availability of contextual cues (e.g. preceding conversations, physical objects) while controlling for major differences in the linguistic content of matched items. Here, we present initial perceptual validation data (N = 31) on a corpus of 920 items. Overall accuracy for identifying speaker intentions was above 80% correct and our results show that both relationship type and verbal context influence the categorization of literal and nonliteral interactions, underscoring the importance of these factors in research on speaker intentions. We believe that RISC will prove highly constructive as a tool in future research on social cognition, inter-personal communication, and the interpretation of speaker intentions in both healthy adults and clinical populations.
Project description:BackgroundThe planning, resourcing, implementation and monitoring of new programmes by district health managers is integral for success and sustainability. Ethiopia introduced the Community-Based Newborn Care programme in 2014 to improve newborn survival: an innovative component allowed community health workers to provide antibiotics for young infants with possible serious bacterial infection when referral was not possible. Informed by the World Health Organization health system building block framework, we aimed to study the capacity and operational challenges of introducing this new health service from the perspective of programme implementers and managers at the district level 20 months after programme initiation.MethodsThis qualitative study was part of a programme evaluation. From November to December of 2015, we conducted 28 semi-structured interviews with staff at district health offices, health centres and implementing Non-Governmental Organisations in 15 districts of four regions of Ethiopia. Verbatim transcripts were analysed using a priori and emerging themes.ResultsIn line with the government's commitment to treat sick newborns close to their homes, participants reported that community health workers had been successfully trained to provide injectable antibiotics. However, the Community-Based Newborn Care programme was scaled up without allowing the health system to adapt to programme needs. There were inadequate processes and standards to ensure consistent availability of (1) trained staff for technical supervision, (2) antibiotics and (3) monitoring data specific to the programme. Furthermore, Non-Governmental Organizations played a central implementing role, which had implications for the long-term district level ownership and thus for the sustainability of the programme.ConclusionIn settings where sustainable local implementation depends on district-level health teams, new programmes should assess health system preparedness to absorb the service, and plan accordingly. Our findings can inform policy makers and implementers about the pre-conditions for a health system to introduce similar services and maximize long-term success.