Research Efforts Research Articles

Introduction of novel complex integrated care models supported by digital health interventions in European primary settings: a scoping review

IntroductionThere remains the need to develop comprehensive organisational care models supported by digital health interventions (DHIs) to manage chronic conditions in primary healthcare. Objectivethis review aimed to identify and map methods, interventions and outcomes investigated regarding the introduction of novel complex integrated care models supported by DHIs in the European primary care setting, as well as the level of integration achieved. Methodsa scoping review to identify literature from 2013 to 2023 in the European context was conducted across PubMed, Scopus and Web of Science. DHIs description, care models and outcomes were reported using the PRISMA- ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. ResultsA total of 53 studies was included. The models introduced, along with a DHI, at least one innovation in their structure or in the modality of care delivery: either a new figure (44%), interprofessional collaboration (37%), new functions like person-centred care (59%) or population stratification (11%). As regarding the DHIs, 56% implemented monitoring/management platforms and apps for chronic conditions. The most frequent combination of care model-DHI was the introduction of an app/platform, supported by phone calls/texts and electronic health records, paired with the introduction of a new healthcare professional/person centred care/ multidisciplinary team. All the studies reaching statistically significant outcomes introduced, along with one or more DHIs, either a new figure or a multidisciplinary team as part of the organizational change to support the technology. Conclusionsnovel complex integrated care models are focusing on introducing multidisciplinary perspectives and personalization of care, in line with the complex needs of chronic patients. The predominant development of monitoring/management platforms for patients is a further confirmation of this trend. Future research efforts should focus on the investigation of the effectiveness of current complex integrated care models integrating DHIs.

Dyeing waters: Does indiscriminate dye use threaten aquatic ecosystems?

Aquatic ecosystem conservation is imperative to reaching global biodiversity and sustainability targets. However, the ecological status of waters has been continuously eroded through mismanagement in the face of existing and emerging anthropogenic stressors, such as pollutants. There has been an emerging trend towards the use of dyes to manage algae and plants as well as to alter aesthetics within various aquatic environments. This artificial colouring has potential ecological implications through reductions in light levels and disruptions to thermoclines (i.e., temperature regime changes with depth). Abiotic regime shifts could in turn drive ecological cascades by depowering primary production, hampering top-down trophic interactions, and affecting evolved animal behaviours. Despite commercial dyes being marketed as acutely non-toxic, very little is known about the chronic effects of these dyes across ecological scales and contexts. We thus call for greater research efforts to understand the ecological consequences of dye usage in aquatic environments, as well as the socio-cultural drivers for its application. This emerging research area could harness approaches such as biological assays, community module experiments, remote sensing, culturomics, and social surveys to elucidate dye effects, trends, and perspectives under a pollution framework. A greater understanding of the potential effects of dye in aquatic ecosystems under relevant contexts would help to inform management decisions and regulation options, while helping to mediate ecocentric and anthropocentric perspectives.

Tracking sustainability compliance of buildings in rapidly urbanizing Southeastern Nigeria

This study examines sustainability compliance in Southeast Nigeria, a region experiencing rapid economic, social, and environmental changes. The research uses a mixed-methods approach to collect both quantitative and qualitative data from various stakeholders, including enterprises, governments agencies, civil society organizations, and local communities. The findings reveal a complex landscape of sustainability compliance, highlighting gaps and barriers such as inadequate regulatory frameworks, limited resource access, and a lack of awareness and capacity-building initiatives. Additionally, cultural and societal factors significantly influence attitudes and behaviours towards sustainability. The study emphasizes the importance of context-specific approaches to sustainability compliance in a region characterized by unique socio-cultural and economic dynamics. It provides recommendations for policymakers, businesses, and civil society organizations to foster greater sustainability awareness, promote responsible practices, and create an enabling environment for sustainable development. Further research and collaborative efforts are needed to address these challenges and advance sustainability objectives in the Southeast region.

Economic viability requires higher recycling rates for imported plastic waste than expected

The environmental impact of traded plastic waste hinges on how it is treated. Existing studies often use domestic or scenario-based recycling rates for imported plastic waste, which is problematic due to differences in recyclability and the fact that importers pay for it. We estimate the minimum required recycling rate (RRR) needed to break even financially by analysing import prices, recycling costs, and the value of recycled plastics across 22 leading importing countries and four plastic waste types during 2013–2022. Here we show that at least 63% of imported plastic waste must be recycled, surpassing the average domestic recycling rate of 23% by 40 percentage points. This discrepancy suggests that recycled plastics volumes from the global North-to-South trade may be underestimated. The country-specific RRR provided could enhance research and policy efforts to better quantify and mitigate the environmental impact of plastic waste trade.

Comparative analysis of phosphorylated proteomes between plerocercoid and adult Spirometra mansoni reveals phosphoproteomic profiles of the medical tapeworm

BackgroundPlerocercoid larvae of the tapeworm Spirometra mansoni can infect both humans and animals, leading to severe parasitic zoonosis worldwide. Despite ongoing research efforts, our understanding of the developmental process of S. mansoni remains inadequate. To better characterize posttranslational regulation associated with parasite growth, development, and reproduction, a comparative phosphoproteomic study was conducted on the plerocercoid and adult stages of S. mansoni.MethodsIn this study, site-specific phosphoproteomic analysis was conducted via 4D label-free quantitative analysis technology to obtain primary information about the overall phosphorylation status of plerocercoids and adults.ResultsA total of 778 differentially abundant proteins (DAPs) were detected between adults and plerocercoids, of which 704 DAPs were upregulated and only 74 were downregulated. DAPs involved in metabolic activity were upregulated in plerocercoid larvae compared with adults, whereas DAPs associated with binding were upregulated in adults. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses indicated that most DAPs involved in signal transduction and environmental information processing pathways were highly active in adults. DAPs upregulated in the plerocercoid group were enriched mainly in metabolic activities. The kinases PKACA, GSK3B, and smMLCK closely interact, suggesting potential active roles in the growth and development of S. mansoni.ConclusionsThe dataset presented in this study offers a valuable resource for forthcoming research on signaling pathways as well as new insights into functional studies on the molecular mechanisms of S. mansoni.Graphical abstract

Recent Advances in Prodrug Approach over Conventional Drug Therapy

Background: Prodrugs represent a strategically designed category of medicinal compounds aimed at optimizing drug pharmacokinetics. By modifying the pharmacological action of the drug within a prodrug, subsequent enzymatic bioconversion in the human body facilitates the release of the active drug. This strategy has been highly effective, as demonstrated by the substantial number of prodrugs found in commercial pharmaceutical products. Prodrugs have emerged as a recognized strategy for augmenting the physical, chemical, biological, or pharmacokinetic attributes of pharmacologically active molecules in the realm of drug research and development. Objective: This systematic review intended to offer insights into the recent developments in the prodrug approach used in drug research and development, with a focus on highlighting its effectiveness. The objective was to illustrate the diverse applications of prodrugs and their impact on enhancing drug properties and therapeutic outcomes. Area covered: This review is centered on the most recent developments in the prodrug approach used for drug development and research. The prodrug concept has a wide range of practical uses, some of which are illustrated in this review article. These illustrations are categorized based on the intention behind their creation. Results: Prodrugs have been designed to address challenges, such as poor water solubility and low bioavailability. Strategies, like using neutral or charged promoieties, have been reported to be successful in enhancing solubility. For permeability and bioavailability, prodrugs have been employed to mask polar groups, enabling better absorption. Prolonged half-life prodrugs have been developed to extend drug action, while tissue-targeted delivery prodrugs have shown promise in enhancing drug delivery to specific sites. Conclusion: Prodrug design offers promising strategies to optimize drug delivery and efficacy. Despite challenges, ongoing clinical trials and research efforts indicate the potential of prodrugs in improving therapeutic outcomes. Addressing formulation challenges and understanding pharmacokinetic variability are essential for successful prodrug development.

Moonlighting on the Fasciola hepatica tegument: Enolase, a glycolytic enzyme, interacts with the extracellular matrix and fibrinolytic system of the host.

Enolase is a 47 kDa enzyme that functions within the glycolysis and gluconeogenesis pathways involved in the reversible conversion of D-2-phosphoglycerate (2PGA) to phosphoenolpyruvate (PEP). However, in the context of host-pathogen interactions, enolase from different species of parasites, fungi and bacteria have been shown to contribute to adhesion processes by binding to proteins of the host extracellular matrix (ECM), such as fibronectin (FN) or laminin (LM). In addition, enolase is a plasminogen (PLG)-binding protein and induces its activation to plasmin, the main protease of the host fibrinolytic system. These secondary 'moonlighting' functions of enolase are suggested to facilitate pathogen migration through host tissues. This study aims to uncover the moonlighting role of enolase from the parasite Fasciola hepatica, shedding light on its relevance to host-parasite interactions in fasciolosis, a global zoonotic disease of increasing concern. A purified recombinant form of F. hepatica enolase (rFhENO), functioning as an active homodimeric glycolytic enzyme of ~94 kDa, was successfully obtained, fulfilling its canonical role. Immunoblotting studies on adult worm extracts showed that the enzyme is present in the tegument and the excretory/secretory products of the parasite, which supports its key role at the host-parasite interface. Confocal immunolocalisation studies of the protein in newly excysted juveniles and adult worms also localised its expression within the parasite tegument. Finally, we showed by ELISA that rFhENO can act as a parasitic adhesin by binding host LM, but not FN. rFhENO also binds PLG and enhances its conversion to plasmin in the presence of the tissue-type and urokinase-type PLG activators (t-PA and u-PA). This moonlighting adhesion-like function of the glycolytic protein enolase could contribute to the mechanisms by which F. hepatica efficiently invades and migrates within its host and encourages further research efforts that are designed to impediment this function by vaccination or drug design.

HIV-1 and IgA Antibodies: Interactions and implications

Antibodies, particularly Immunoglobulin A (IgA), play a crucial role in mucosal tissues as immune effectors against pathogens and as immunomodulators of the microbiota. During infection with human immunodeficiency virus type 1 (HIV-1), a systemic and mucosal IgA antibody response is triggered. Although naturally produced serum IgA specific to HIV-1 envelope protein are quantitatively and qualitatively lower than their IgG counterparts, they also possess antiviral properties such as neutralization and Fc-dependent effector functions. Neutralizing IgA antibodies can block mucosal transmission of HIV-1 in animal models, suggesting that their induction through vaccination could be pivotal for infection prevention. Recently, broadly neutralizing IgA antibodies have been identified in some individuals living with HIV-1. Given the potential for vaccination to induce these mucosally protective antibodies, research efforts are needed to better understand their development and functions. This review discusses the general roles of IgA antibodies in homeostasis and antimicrobial immunity, and explores their implications in antibody responses during HIV-1 infection.

Discovering Consumer Behavior Towards Back-of-Pack Nutrition Labels: A Systematic Literature Review

This systematic literature review aims to examine the impact of back-of-pack (BOP) labels on food manufacturers' practices in the field of consumer behaviour research. The review comprehensively analyses a wide range of articles spanning over two decades to provide an up-to-date and comprehensive analysis of the subject matter. It focuses specifically on how BOP labels affect consumers, food manufacturers' behaviors and practices. The findings highlight that BOP labels conveying intuitive information effectively prompt product reformulation, particularly in reducing unhealthy nutrients such as sodium, sugar, and calories. Voluntary BOP labeling has limited uptake and is often applied to already healthier products. Consumers and food producers' response varies based on label design and enforcement type, suggesting strategic labeling of healthier choices. The review provides valuable insights for future public health research and policymaking efforts, emphasizing the importance of mandatory policies and specific guidance in BOP labels. This research brings novelty by comprehensively examining the impact of back-of-pack (BOP) labeling on consumers and food manufacturers' practices. The findings contribute to the literature by highlighting the differential effects of mandatory and voluntary BOP labeling approaches and offering insights into label design and enforcement types. As per the researcher knowledge there is no available systematic literature review (SLR) specifically focusing on BOP labeling in recent years. Future research should explore the long-term impacts of mandatory versus voluntary BOP labeling on consumer dietary habits and food manufacturers' product reformulation strategies.

Mesenchymal stem cell therapy in veterinary ophthalmology: clinical evidence and prospects.

Mesenchymal stem cell (MSC) therapy presents a promising strategy for treating various ocular conditions in veterinary medicine. This review explores the therapeutic potential of MSCs in managing corneal ulcers, immune-mediated keratitis, chronic superficial keratitis, keratoconjunctivitis sicca, retinal degeneration, and ocular burns in feline, equine, and canine patients. Studies have demonstrated the immunomodulatory and regenerative properties of MSCs, highlighting their ability to mitigate inflammation and promote tissue regeneration. Experimental studies have shown the potential of MSC therapy in reducing corneal opacity and vascularization, indicating significant therapeutic advantages. Delivery methods play a crucial role in optimizing the therapeutic efficacy of MSCs in ocular diseases. Various delivery methods, such as intravitreal injection, subconjunctival injection, topical administration, and scaffold-mediated delivery, are being explored to optimize MSC delivery to the target ocular tissues. Clinical trials have shown significant improvements in clinical signs following MSC therapy, underscoring its efficacy in treating ocular diseases. Additionally, tissue engineering approaches incorporating MSCs, growth factors, and scaffolds offer innovative strategies for corneal regeneration and tissue repair. Despite challenges such as standardization of protocols and long-term safety assessment, ongoing research endeavours seek to unlock the full therapeutic potential of MSC therapy in ocular diseases. Future prospects in MSC therapy involve exploring scaffold and hydrogel-based approaches and cell-free therapies leveraging the bioactive molecules released by MSCs. Continued research and development efforts are essential to unlock the full therapeutic potential of MSCs and realize their transformative impact on ocular diseases in veterinary patients.

Hypoxia Abrogates Tumor-Suppressive Activities of C/EBPδ in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a low 5-year survival rate of only 13%. Despite intense research efforts, PDAC remains insufficiently understood. In part, this is attributed to opposing effects of key players being unraveled, including the stroma but also molecules that act in a context-dependent manner. One such molecule is the transcription factor C/EBPδ, where we recently showed that C/EBPδ exerts tumor-suppressive effects in PDAC cells in vitro. To better understand the role of C/EBPδ in different contexts and the development of PDAC, we here build on these findings and assess the effect of C/EBPδ in a PDAC model in mice. We establish that the lack of oxygen in vivo-hypoxia-counteracts the tumor-suppressive effects of C/EBPδ, and identify a reciprocal feedback loop between C/EBPδ and HIF-1α. RNA sequencing of C/EBPδ-induced cells under hypoxia also suggests that the growth-limiting effects of C/EBPδ decrease with oxygen tension. Consequently, in vitro proliferation assays reveal that the tumor-suppressive activities of C/EBPδ are abrogated due to hypoxia. This study demonstrates the importance of considering major physiological parameters in preclinical approaches.

ECD-CDGI: An efficient energy-constrained diffusion model for cancer driver gene identification.

The identification of cancer driver genes (CDGs) poses challenges due to the intricate interdependencies among genes and the influence of measurement errors and noise. We propose a novel energy-constrained diffusion (ECD)-based model for identifying CDGs, termed ECD-CDGI. This model is the first to design an ECD-Attention encoder by combining the ECD technique with an attention mechanism. ECD-Attention encoder excels at generating robust gene representations that reveal the complex interdependencies among genes while reducing the impact of data noise. We concatenate topological embedding extracted from gene-gene networks through graph transformers to these gene representations. We conduct extensive experiments across three testing scenarios. Extensive experiments show that the ECD-CDGI model possesses the ability to not only be proficient in identifying known CDGs but also efficiently uncover unknown potential CDGs. Furthermore, compared to the GNN-based approach, the ECD-CDGI model exhibits fewer constraints by existing gene-gene networks, thereby enhancing its capability to identify CDGs. Additionally, ECD-CDGI is open-source and freely available. We have also launched the model as a complimentary online tool specifically crafted to expedite research efforts focused on CDGs identification.

Benchmarking in pancreatic surgery: a systematic review of metric development and validation.

Benchmarking in healthcare, particularly in the context of complex surgical procedures like pancreatic surgery, plays a pivotal role in comparing and evaluating the quality of care provided to patients. There is a growing body of evidence validating existent metrics and introducing new ones in the pursuit of safety and excellence in pancreatic surgery. A systematic review adhering to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was conducted on metric development and validation across multiple databases, including PUBMED Medline, Scopus, and Web of Science, until February 2024. The extracted data were categorized into three domains according to the Donabedian model: structure, process, and outcomes. Thirty-four studies were deemed eligible for inclusion in this review. Among these articles, 20 contributed to metric development, while 14 studies validated them. A total of 234 metrics were identified across the 34 studies, of which 185 were included in the analysis. Thirty-three of these metrics were relative to structure, 79 to processes, and 73 to outcomes. The distribution of metric domains across the included studies revealed that structure, process, and outcome domains were reported in 12, 26, and 26 studies, respectively. In conclusion, this systematic review underscores the heterogeneity in metric development methodologies and the varying degrees of consensus among different quality indicators, despite the growing interest in benchmarking in pancreatic surgery. This review aims to inform future research efforts and contribute to the ongoing pursuit of excellence in pancreatic surgical care.

Literature Survey on Revolutionizing Fake Currency Detection: CNN-Based Approach for Indian Rupee Notes

The proliferation of counterfeit currency poses a significant challenge in various economies, including India. To address this issue, several studies have proposed innovative image processing and machine learning techniques for detecting counterfeit coins and banknotes. Leveraging digital image processing, these studies aim to enhance the security measures against counterfeit currency through accurate and efficient recognition systems. Techniques such as preprocessing, segmentation, feature extraction, and clustering are employed to identify fraudulent currency. The use of Support Vector Machines (SVM), k-means clustering, and Convolutional Neural Networks (CNN) facilitates the recognition and classification of genuine and counterfeit currency. Moreover, these studies explore the application of spatial coding, component-based recognition, and deep learning algorithms to improve the accuracy and robustness of counterfeit detection systems. By developing real-time recognition systems capable of identifying counterfeit currency, these research efforts contribute to combating financial fraud and safeguarding economic integrity.

A Critical Review on the Advancements in Exploration and Production of Shale Gas

The exploration and production of shale gas have seen significant advancements in recent years, driven by the increasing global demand for clean energy sources. These advancements encompass the understanding of a wide range of areas, including the formation theory of shale gas reservoirs, evaluation methods, well drilling, completion, and simulation techniques. Innovative design, modelling, and field practices have been developed for shale gas well drilling and completion, as well as its production techniques. Furthermore, new simulation techniques, software, algorithms, and other tools have been introduced to improve the modelling and simulation of shale gas production. Experimental and simulation research in shale gas exploration, development, and production using hydraulic fracturing has also seen considerable progress. These advancements are contributing significantly to the global demand for clean energy sources with a promise to achieve sustainable development goals. This review work explores the exploration and exploitation of shale gas with a detailed description of multidisciplinary research efforts, providing valuable insights into shale reservoir/rock characterization and geo-mechanics, fluid-surface interactions, gas adsorption behaviours and single- and multi-phase flow mechanics. These advancements are not only increasing the efficiency and productivity of shale gas extraction but also paving the way to meet the future global energy demand while also contributing to the goal of achieving net-zero carbon emissions. The novelty of the review work is that it exhibits a combined qualitative and quantitative study of recent advancements in the sphere of exploration and production of shale gas reserves and its discoveries around the globe.

Assessing the potential impacts of exotic reptile species advertised for sale in the South African pet trade

Assessing the impacts of non-native species is essential for preventing, monitoring and eradicating introduced species. In South Africa, impact assessment has been adopted for species introduced through various pathways, including the legal and illegal wildlife trade. We conducted a comprehensive literature search to collate information on the impacts associated with 76 non-native reptiles sold as pets in South Africa, using the Generic Impact Scoring System (GISS), Environmental Impact Classification for Alien Taxa (EICAT), and Socio-Economic Impact Classification for Alien Taxa (SEICAT). Using GISS, we found that 12 species were associated with environmental impacts (E_GISS), and 10 had socio-economic impacts (SE_GISS). For EICAT and SEICAT, 12 species had environmental and seven had socio-economic impacts, respectively. Despite extensive research efforts, most (82 %) of the evaluated species had no documented impacts, implying that these species are unlikely to have significant impacts. Environmental impact scores differed between GISS and EICAT, indicating that both schemes should be used when assessing environmental impacts. In contrast, while the socio-economic impact scores of GISS and SEICAT were comparable, both schemes provide a comprehensive assessment by capturing different aspects. Popular pet species such as the Iguana iguana, Python bivittatus, and Trachemys scripta elegans, already introduced in the country, scored the highest impacts in all schemes, prompting strict monitoring and policy development regarding their trade. Using multiple impact schemes, we show that despite extensive research efforts, 82 % of reptile species sold as pets in South Africa have no documented impacts. Concerningly, species with documented impacts showed high environmental but minor socio-economic impacts.

COVID-19 school closures in Latin America: untangling approaches impacting student health and wellbeing

PurposeThis study compared approaches to school closures in four Latin American countries (Bolivia, Colombia, Ecuador, Peru), describing the impact on the health and educational wellbeing of school-age children and youth, and evaluating their approaches in regard to continuing education through the pandemic.Design/methodology/approachWe collected 75 publicly available documents including scientific and gray literature (government documents and news releases), that referred to school closures and their impact on children’s health and wellbeing. We did thematic analyses using open, axial, and selective coding and applied the latest Health Promoting Schools standards and indicators to the findings.FindingsResults showed that countries followed epidemiological reasons for prioritizing school closures while adopting some policies that abide by Health Promoting School principles. While they emphasized the need to reopen schools so that instruction could continue, school closures were among the longest in the world. The most significant impacts on wellbeing identified in the four countries were related to food security and mental health.Research limitations/implicationsThis study focused on a particular set of documents, and it may not capture the full spectrum of relevant information in different contexts or regions.Practical implicationsBy comparing school closures approaches among four Latin American countries, this study highlights the importance of context-specific interventions. In a post-pandemic era, lessons learned from these experiences should help foster more resilient and inclusive educational systems and explore the paths forward for following the new Health Promoting Schools framework in the region.Originality/valueCross-country qualitative analyses on this topic are rare. This study adds to the knowledge base by eliciting lessons for future health education research and policy efforts.

A Comprehensive Review on the Isolation, Bioactivities, and Structure-Activity Relationship of Hawthorn Pectin and Its Derived Oligosaccharides.

Hawthorn (Crataegus pinnatifida Bunge) has been highlighted as an excellent source of a variety of bioactive polymers, which has attracted increasing research interest. Pectin, as a kind of soluble dietary fiber in hawthorn, is mainly extracted by hot water extraction and ultrasonic or enzymatic hydrolysis and is then extensively used in food, pharmaceutical, and nutraceutical industries. Numerous studies have shown that hawthorn pectin and its derived oligosaccharides exhibit a wide range of biological activities, such as antioxidant activity, hypolipidemic and cholesterol-reducing effects, antimicrobial activity, and intestinal function modulatory activity. As discovered, the bioactivities of hawthorn pectin and its derived oligosaccharides were mainly contributed by structural features and chemical compositions and were highly associated with the extraction methods. Additionally, hawthorn pectin is a potential resource for the development of emulsifiers and gelling agents, food packaging films, novel foods, and traditional medicines. This review provides a comprehensive summary of current research for readers on the extraction techniques, functional characteristics, structure-activity relationship, and applications in order to provide ideas and references for the investigation and utilization of hawthorn pectin and its derived oligosaccharides. Further research and development efforts are imperative to fully explore and harness the potential of hawthorn pectin-derived oligosaccharides in the food and medicine fields.

Genetic diversity of apple heirloom germplasm in Bosnia and Herzegovina, as revealed by SNP markers

The cultivated apple (Malus domestica Borkh.) is an economically important fruit crop in countries worldwide, including Bosnia and Herzegovina (BIH).The gene bank activities in BIH were initiated in the 1930s and continued until the war in the 1990s, when much of the documentation was lost. Since then, uncoordinated efforts were made to establish apple collections in different regions, but a comprehensive analysis of genetic resources was lacking. This prompted the current study where we present the first thorough overview of the national genetic resources of BIH apples. Thus, we analyzed 165 accessions in the apple gene bank at the Institute for Genetic Resources (IGR) established at Banja Luka using the 20 K apple Infinium® single nucleotide polymorphism (SNP) array. We combined the results with previously published data on the germplasm collections at Srebrenik and Goražde, genotyped using the Axiom® Apple 480 K SNP array. In total, 234 accessions were included in the study of which 220 were presumed to be local cultivars and 14 were known international reference cultivars. We identified numerous genotypic duplicates within and between collections and suggested preferred names to be used in the future. We found the BIH germplasm to have relatively few parent-offspring relationships, particularly among local cultivars, which might reflect the country’s history and patterns of apple cultivar introduction. A number of cultivars unique to BIH and a weakly defined genetic group were identified via STRUCTURE analysis, representing interesting targets for future research and preservation efforts.

MPES-R: Multi-Parameter Evidence Synthesis in R for Survival Extrapolation-A Tutorial.

Survival extrapolation often plays an important role in health technology assessment (HTA), and there are a range of different approaches available. Approaches that can leverage external evidence (i.e. data or information collected outside the main data source of interest) may be helpful, given the extent of uncertainty often present when determining a suitable survival extrapolation. One of these methods is the multi-parameter evidence synthesis (MPES) approach, first proposed for use in HTA by Guyot et al., and more recently by Jackson. While MPES has potential benefits over conventional extrapolation approaches (such as simple or flexible parametric models), it is more computationally complex and requires use of specialist software. This tutorial presents an introduction to MPES for HTA, alongside a user-friendly, publicly available operationalisation of Guyot's original MPES that can be executed using the statistical software package R. Through two case studies, both Guyot's and Jackson's MPES approaches are explored, along with sensitivity analyses relevant to HTA. Finally, the discussion section of the tutorial details important considerations for analysts considering use of an MPES approach, along with potential further developments. MPES has not been used often in HTA, and so there are limited examples of how it has been used and perceived. However, this tutorial may aid future research efforts exploring the use of MPES further.