The PLAC1-homology region of the ZP domain is sufficient for protein polymerisation

BACKGROUND: Hundreds of extracellular proteins polymerise into filaments and matrices by using zona pellucida (ZP) domains. ZP domain proteins perform highly diverse functions, ranging from structural to receptorial, and mutations in their genes are responsible for a number of severe human diseases. Recently, PLAC1, Oosp1-3, Papillote and CG16798 proteins were identified that share sequence homology with the N-terminal half of the ZP domain (ZP-N), but not with its C-terminal half (ZP-C). The functional significance of this partial conservation is unknown. RESULTS: By exploiting a highly engineered bacterial strain, we expressed in soluble form the PLAC1-homology region of mammalian sperm receptor ZP3 as a fusion to maltose binding protein. Mass spectrometry showed that the 4 conserved Cys residues within the ZP-N moiety of the fusion protein adopt the same disulfide bond connectivity as in full-length native ZP3, indicating that it is correctly folded, and electron microscopy and biochemical analyses revealed that it assembles into filaments. CONCLUSION: These findings provide a function for PLAC1-like proteins and, by showing that ZP-N is a biologically active folding unit, prompt a re-evaluation of the architecture of the ZP domain and its polymers. Furthermore, they suggest that ZP-C might play a regulatory role in the assembly of ZP domain protein complexes

The Role of Solid Friction in the Sedimentation of Strongly Attractive Colloidal Gels

We study experimentally and theoretically the sedimentation of gels made of strongly aggregated colloidal particles, focussing on the long time behavior, when mechanical equilibrium is asymptotically reached. The asymptotic gel height is found to vary linearly with the initial height, a finding in stark contrast with a recent study on similar gels [Manley \textit{et al.} 2005 \textit{Phys. Rev. Lett.} \textbf{94} 218302]. We show that the asymptotic compaction results from the balance between gravity pull, network elasticity, and solid friction between the gel and the container walls. Based on these ingredients, we propose a simple model to account for the dependence of the height loss on the initial height and volume fraction. As a result of our analysis, we show that the static friction coefficient between the gel and the container walls strongly depends on volume fraction: the higher the volume fraction, the weaker the solid friction. This nonintuitive behavior is explained using simple scaling arguments.Comment: 13 pages, 5 figures. Submitted to JSTA

Aspects and Challenges of Resource Use Measurement in Health Economics:Towards a Comprehensive Measurement Framework

BACKGROUND: While the methods for conducting health economics research in general are improving, current guidelines provide limited guidance regarding resource use measurement (RUM). Consequently, a variety of methods exists, yet there is no overview of aspects to consider when deciding on the most appropriate RUM methodology. Therefore, this study aims to (1) identify and categorize existing knowledge regarding aspects of RUM, and (2) develop a framework that provides a comprehensive overview of methodological aspects regarding RUM. METHODS: Relevant articles were identified by enrolling a search string in six databases and handsearching the DIRUM database. Included articles were descriptively reviewed and served as input for a comprehensive framework. Health economics experts were involved during the process to establish the framework’s face validity. RESULTS: Forty articles were included in the scoping review. The RUM framework consists of four methodological RUM domains: ‘Whom to measure’, addressing whom to ask and whom to measure; ‘How to measure’, addressing the different approaches of measurement; ‘How often to measure’, addressing recall period and measurement patterns; and ‘Additional considerations’, which covers additional aspects that are essential for further refining the methodologies for measurement. Evidence retrieved from the scoping review was categorized according to these domains. CONCLUSION: This study clustered the aspects of RUM methodology in health economics into a comprehensive framework. The results may guide health economists in their decision making regarding the selection of appropriate RUM methods and developing instruments for RUM. Furthermore, policy makers may use these findings to review study results from an evidence-based perspective. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40273-021-01048-z

Clarifying terminology and definitions in education services for mental health users:A disambiguation study

In the wake of the mental health crisis in children and adolescents, the coordination of education and mental health services has become a global priority. However, differing terminologies and classifications across sectors, hinder effective comparison. The classification in education focuses mainly on outputs like qualifications or throughputs like teaching programs. This proof-of-concept study tested the applicability of a standard classification of health services, the Description and Evaluation of Services and DirectoriEs (DESDE), to evaluate education services for mental health users in the context of Spain and The Netherlands. It was conducted alongside the PECUNIA project, that sought to develop methods for the assessment of mental health costs and outcomes in different sectors. The study followed an ontoterminology approach involving: 1) identification of services from a predefined list of 46 resource-use items, 2) disambiguation of identified services with the DESDE, and classifying them as accurate, ambiguous, vague or confuse; and 3) external validation by an expert panel. The analysis was conducted at the level of type of resource, target population and care provision. From the initial list, only ten of the resources could be categorized as services using DESDE, and not activities, interventions or professionals. Only four of them (8,65%) were accurate across all disambiguation categories. Experts were unaware of terminology problems in classification of service provision in the education sector. Classifications and glossaries can clarify service naming, description and costing allowing comparative effectiveness analysis and facilitating cross-sectoral planning. This should be grounded in common methodologies, tools, and units of analysis

Clarifying terminology and definitions in education services for mental health users:A disambiguation study

In the wake of the mental health crisis in children and adolescents, the coordination of education and mental health services has become a global priority. However, differing terminologies and classifications across sectors, hinder effective comparison. The classification in education focuses mainly on outputs like qualifications or throughputs like teaching programs. This proof-of-concept study tested the applicability of a standard classification of health services, the Description and Evaluation of Services and DirectoriEs (DESDE), to evaluate education services for mental health users in the context of Spain and The Netherlands. It was conducted alongside the PECUNIA project, that sought to develop methods for the assessment of mental health costs and outcomes in different sectors. The study followed an ontoterminology approach involving: 1) identification of services from a predefined list of 46 resource-use items, 2) disambiguation of identified services with the DESDE, and classifying them as accurate, ambiguous, vague or confuse; and 3) external validation by an expert panel. The analysis was conducted at the level of type of resource, target population and care provision. From the initial list, only ten of the resources could be categorized as services using DESDE, and not activities, interventions or professionals. Only four of them (8,65%) were accurate across all disambiguation categories. Experts were unaware of terminology problems in classification of service provision in the education sector. Classifications and glossaries can clarify service naming, description and costing allowing comparative effectiveness analysis and facilitating cross-sectoral planning. This should be grounded in common methodologies, tools, and units of analysis

Exploring the identification, validation, and categorization of the cost and benefits of criminal justice in mental health: the PECUNIA project

Background Mental health disorders and their treatments produce significant costs and benefits in both healthcare and non-healthcare sectors. The latter are often referred to as intersectoral costs and benefits (ICBs). Little is known about healthcare-related ICBs in the criminal justice sector and how to include these in health economics research. Objectives The triple aim of this study is (i) to identify healthcare-related ICBs in the criminal justice sector, (ii) to validate the list of healthcare-related ICBs in the criminal justice sector on a European level by sector-specific experts, and (iii) to classify the identified ICBs. Methods A scientific literature search in PubMed and an additional grey literature search, carried out in six European countries, were used to retrieve ICBs. In order to validate the international applicability of the ICBs, a survey was conducted with an international group of experts from the criminal justice sector. The list of criminal justice ICBs was categorized according to the PECUNIA conceptual framework. Results The full-text analysis of forty-five peer-reviewed journal articles and eleven grey literature sources resulted in a draft list of items. Input from the expert survey resulted in a final list of fourteen unique criminal justice ICBs, categorized according to the care atom. Conclusion This study laid further foundations for the inclusion of important societal costs of mental health-related interventions within the criminal justice sector. More research is needed to facilitate the further and increased inclusion of ICBs in health economics research

1st EFORT European Consensus: Medical & Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices

Innovations in Orthopaedics and Traumatology have contributed to the achievement of a high-quality level of care in musculoskeletal disorders and injuries over the past decades. The applications of new implants as well as diagnostic and therapeutic techniques in addition to implementation of clinical research, have significantly improved patient outcomes, reduced complication rates and length of hospital stay in many areas. However, the regulatory framework is extensive, and there is a lack of understanding and clarity in daily practice what the meaning of clinical & pre‐clinical evidence as required by the MDR is. Thus, understanding and clarity are of utmost importance for introduction of new implants and implant-related instrumentation in combination with surgical technique to ensure a safe use of implants and treatment of patients. Therefore EFORT launched IPSI, The Implant and Patient Safety Initiative, which starting from an inaugural workshop in 2021 issued a set of recommendations, notably through a subsequent Delphi Process involving the National Member Societies of EFORT, European Specialty Societies as well as International Experts. These recommendations provide surgeons, researchers, implant manufacturers as well as patients and health authorities with a consensus of the development, implementation, and dissemination of innovation in the field of arthroplasty. The intended key outcomes of this 1st EFORT European Consensus on “Medical & Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices”are consented, practical pathways to maintain innovation and optimisation of orthopaedic products and workflows within the boundaries of MDR 2017/745. Open Access practical guidelines based on adequate, state of the art pre-clinical and clinical evaluation methodologies for the introduction of joint replacements and implant-related instrumentation shall provide hands-on orientation for orthopaedic surgeons, research institutes and laboratories, orthopaedic device manufacturers, Notified Bodies but also for National Institutes and authorities, patient representatives and further stakeholders. We would like to acknowledge and thank the Scientific Committee members, all International Expert Delegates, the Delegates from European National & Specialty Societies and the Editorial Team for their outstanding contributions and support during this EFORT European Consensus

The Relative Importance of Education and Criminal Justice Costs and Benefits in Economic Evaluations

Objectives Mental and behavioural disorders (MBDs) and interventions targeting MBDs lead to costs and cost savings in the healthcare sector, but also in other sectors. The latter are referred to as intersectoral costs and benefits (ICBs). Interventions targeting MBDs often lead to ICBs in the education and criminal justice sectors, yet these are rarely included in economic evaluations. This study aimed to investigate the attitudes held by health economists and health technology assessment experts towards education and criminal justice ICBs in economic evaluations and to quantify the relative importance of these ICBs in the context of MBDs. Methods An online survey containing open-ended questions and two best–worst scaling object case studies was conducted in order to prioritise a list of 20 education ICBs and 20 criminal justice ICBs. Mean relative importance scores for each ICB were generated using hierarchical Bayes analysis. Results Thirty-nine experts completed the survey. The majority of the respondents (68%) reported that ICBs were relevant, but only a few (32%) included them in economic evaluations. The most important education ICBs were “special education school attendance”, “absenteeism from school”, and “reduced school attainment”. The most important criminal justice ICBs were “decreased chance of committing a crime as a consequence/effect of mental health programmes/interventions”, “jail and prison expenditures”, and “long-term pain and suffering of victims/victimisation”. Conclusions This study identified the most important education and criminal justice ICBs for economic evaluations of interventions targeting MBDs and suggests that it could be relevant to include these ICBs in economic evaluations

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin