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Numerous developmental findings suggest that infants and toddlers engage predictive processing during language comprehension. However, a significant limitation of this research is that associative (bottom-up) and predictive (top-down) explanations are not readily differentiated. Following adult studies that varied predictiveness relative to semantic-relatedness to differentiate associative vs. predictive processes, the present study used eye-tracking to begin to disentangle the contributions of bottom-up and top-down mechanisms to infants’ real-time language processing. Replicating prior results, infants (14-19 months old) use successive semantically-related words across sentences (e.g., eat, yum, mouth) to predict upcoming nouns (e.g., cookie). However, we also provide evidence that using successive semantically-related words to predict is distinct from the bottom-up activation of the word itself. In a second experiment, we investigate the potential effects of repetition on the findings. This work is the first to reveal that infant language comprehension is affected by both associative and predictive processes.
It is not often that international collaborations are sustained for any significant period, let alone for three decades. However, despite relying on largely voluntary contributions of individuals within its member institutions, the International Network of Agencies for Health Technology Assessment (INAHTA) has not only been an example of sustained collaboration over 30 years but also an example of how an initially modest collaboration can grow and thrive. Current and former serving Chairs and secretariat of the Network have come together to review network documents and outputs and reflect on the history of INAHTA, since its inception in Paris in 1993. Building on the paper from Hailey et al 2009 that documented the growth of the network after 15 years, we have considered and documented the factors that we believe have helped sustain the network and enable it to flourish in the subsequent 15 years. We have also considered the various challenges experienced along the way, as these too can aid in making a collaboration stronger. Future directions for the network have also been contemplated, given the evolving nature of HTA and the regional collaborations that have recently emerged. We hope that by sharing the lessons learned from this living example of international global collaboration relationships between like-minded organizations can be similarly fostered and enhanced into sustainable collaborations, for the benefit of all.
Seeds are crucial for plant reproduction, dispersal and agriculture. Seed quality and vigour greatly impact crop production by enabling rapid and uniform germination under various environmental conditions. This leads to healthy seedlings that can withstand both biotic and abiotic stresses, which are particularly important in the context of the accentuation of global climate change. Upon imbibition during germination sensu stricto, seeds release exudates, complex mixtures of organic and inorganic molecules, into the microenvironment surrounding them, known as the spermosphere. These exudates play a pivotal role in seedling development and overall plant fitness by influencing microbial selection, growth and interactions in the spermosphere, ultimately shaping the plant's microbiome. Proteins such as enzymes with protection properties have previously been demonstrated to be released by the seeds in their exudates. However, limited information is available pertaining to peptides in seed exudates. Here, we developed an experimental protocol to extract and identify peptides in the spermosphere of germinating common bean seeds. We showed that our methodology was successful in identifying a broad spectrum of peptides and that extraction solvent choice impacts peptide identification both qualitatively and quantitatively. We also show the possibility of using online prediction tools to predict the properties of identified peptides based on their amino acid sequence. We propose that this approach may be used to identify potential molecules that could be used as candidates for developing strategies to enhance seed quality and improve crop productivity.
There are significant delays in the funded access to medicines. Studies indicate that in many countries it takes more than a year for patients to have funded access to medicines after market authorization. This study aimed to understand the disparities in timelines for funded access to medicines across different countries and to identify underlying reasons for this access gap.
Methods
We conducted a scoping review to examine the nature of health technology assessment (HTA) processes, current methods, and policies for medicines in ten jurisdictions. The jurisdictions included in this study are Australia, Canada, France, Germany, South Korea, the Netherlands, United Kingdom (divided into England, Scotland and Wales), and United States of America. The information was extracted from the websites of International Network of Agencies for Health Technology Assessment (INAHTA) member agencies in the selected jurisdictions, grey literature from governments’ websites, and peer-reviewed literature.
Results
Overall median time from submission of the evidence dossier to HTA recommendations for most jurisdictions is 22 weeks. Although there are similarities in the time taken to reach a funding decision, there are considerable variations in the time taken for patients to have funded access to medicines after HTA recommendations. Only a few countries mentioned a specific timeline within which medicines approved for funding should be listed. Time taken for price negotiations and other arrangements (i.e., risk-sharing agreements) may contribute to varying timelines for listing medicines for funding. Mostly, such negotiations are confidential and may not be time limited.
Conclusions
There was surprising consistency, globally, in the time it takes for funding decisions after medicines registration. The causes of delays in the medicines’ listing decisions are multifactorial and mostly occur after HTA recommendations. The parallel regulatory-assessment process and prioritization tend to reduce the time to a funding decision. However, transparency is needed in the listing process to improve overall timeliness.
Defining the population, intervention, comparator, outcomes (PICO) criteria is an essential step prior to performing a health technology assessment (HTA), but variations exist in how this step is performed.
Methods
A scoping review was performed to compare the processes and guidance provided for developing the PICO criteria for the assessment of new medicines across Australia, the UK, Canada, the US, European Union (as a single jurisdiction), Germany, France, the Netherlands, South Korea, and Taiwan. The websites of HTA agencies in these jurisdictions were searched for methodological guidance, and PubMed, Embase, and the HTA database were also searched for published literature on the topic of the process or methods for developing the PICO criteria.
Results
Two main approaches are used for developing the PICO criteria. In the UK, US, and European Union, a separate scoping process is used; in the remaining countries, the pharmaceutical manufacturer defines the PICO criteria as part of developing their dossier for submission. Guidance on PICO elements were similar in content but highly varied in the degree of guidance provided. The largest differences were in whether outcomes for people beyond the treated individual were recommended to be assessed.
Conclusions
A separate scoping phase allows stakeholder input into the criteria, which is important with the shift to incorporating more patient input into each phase of HTA. It can come at the cost of timeliness, so requires manufacturers to engage with the HTA systems earlier in the process.
Health technology assessment (HTA) guidelines are intended to support the successful implementation of HTA by enhancing consistency and transparency in concepts, methods, processes, and use, thereby enhancing the legitimacy of the decision-making process. This report lays out good practices and practical recommendations for developing or updating HTA guidelines to ensure successful implementation.
Methods
The task force was established in 2022 and comprised experts and academics from various geographical regions, each with substantial experience in developing HTA guidelines for national health policy making. Literature reviews and key informant interviews were conducted to inform these good practices. Stakeholder consultations, open peer reviews, and expert opinions validated the recommendations. A series of teleconferences among task force members was held to iteratively refine the report.
Results
The recommendations cover six key aspects throughout the guideline development cycle: (1) setting objectives, scope, and principles of the guideline, (2) building a team for a quality guideline, (3) defining a stakeholder engagement plan, (4) developing content and utilizing available resources, (5) putting in place appropriate institutional arrangements, and (6) monitoring and evaluating guideline success.
Conclusion
This report presents a set of resources and context-appropriate practices for developing or updating HTA guidelines. Across all contexts, the recommendations emphasize transparency, building trust among stakeholders, and fostering a culture of ongoing learning and improvement. The report recommends timing development and revision of guidelines according to the HTA landscape and pace of HTA institutionalization. Because HTA is increasingly used to inform different kinds of decision making in a variety of country contexts, it will be important to continue to monitor lessons learned to ensure the recommendations remain relevant and effective.
Social network data represent interactions and relationships among groups of individuals. One aspect of social interaction is social influence, the idea that beliefs or behaviors change as a result of one’s social network. The purpose of this article is to introduce a new model for social influence, the latent space model for influence, which employs latent space positions so that individuals are affected most by those who are “closest” to them in the latent space. We describe this model along with some of the contexts in which it can be used and explore the operating characteristics using a series of simulation studies. We conclude with an example of teacher advice-seeking networks to show that changes in beliefs about teaching mathematics may be attributed to network influence.
This chapter details the tenacious efforts to bring dignity and justice to domestic workers in Massachusetts, culminating in the passage of the Domestic Workers’ Bill of Rights of 2014. Natalicia R. Tracy, who led the Brazilian Workers’ Center’s efforts to pass the law, provides us with a front-line view of this particular national workers’ rights movement, how it manifested in Massachusetts, and how her organization partnered with artists and designers to place workers’ dignity at the center of the successful organizing strategy.
Early adversity increases risk for child mental health difficulties. Stressors in the home environment (e.g., parental mental illness, household socioeconomic challenges) may be particularly impactful. Attending out-of-home childcare may buffer or magnify negative effects of such exposures. Using a longitudinal observational design, we leveraged data from the NIH Environmental influences on Child Health Outcomes Program to test whether number of hours in childcare, defined as 1) any type of nonparental care and 2) center-based care specifically, was associated with child mental health, including via buffering or magnifying associations between early exposure to psychosocial and socioeconomic risks (age 0–3 years) and later internalizing and externalizing symptoms (age 3–5.5 years), in a diverse sample of N = 2,024 parent–child dyads. In linear regression models, childcare participation was not associated with mental health outcomes, nor did we observe an impact of childcare attendance on associations between risk exposures and symptoms. Psychosocial and socioeconomic risks had interactive effects on internalizing and externalizing symptoms. Overall, the findings did not indicate that childcare attendance positively or negatively influenced child mental health and suggested that psychosocial and socioeconomic adversity may need to be considered as separate exposures to understand child mental health risk in early life.
The March 2, 2022, United Nations Environment Assembly Resolution 5/14: “End plastic pollution: Toward an international legally binding instrument by 2024” provides an important path for addressing global plastic pollution, from monomer design and production through the value chain to the final fate of plastic products, including resource recovery. Of the goals set for this effort, simplifying the polymer and additive universe is among the most significant. One primary obstacle to resource recovery from plastic waste is polymer variability, which renders post-use plastic inherently waste-like. While simplification will not address microplastics and leaching of chemicals during use, these measures simplify the plastic universe and mitigate leakage which is critical to ensuring circular plastic use. This study provides a pathway for simplification of formulations through the elimination of problematic additives and revealing paths toward simplifying and reducing the variability in polymers, waste streams and pollution, while preserving critical uses. This study focuses on phenolic antioxidants to support this concept; however, these principles can be applied to other additive classes. The results show extensive duplication of chemical species with different trade names and the appearance of only minor changes to species with the intention of evergreening patents for improved marketability.
Individuals less closely professionally connected to the deceased may simply be a witness of fact at court instead of being an interested person. Some people worry that being an interested person means that they are in ‘trouble’ with the coroner or more likely to face censure. This is not usually the case. This chapter gives an understanding of what an interested person is, in the context of an inquest, and the advantages and disadvantages of that position.
Risks or vulnerabilities can arise from any death and part of any professional’s role is to be alert to remediating them as part of patient safety. This chapter will look at how to identify these risks. It will also consider what to do when criticism occurs, and how to remediate to allow for a satisfactory or moderated outcome.