The past few decades have witnessed a boom in nanotechnology in various areas, raising global concerns about the environmental health and safety of engineered nanomaterials (ENMs). It has always been a challenging task to grasp the full picture of nanotoxicology and nanoecotoxicology, as multiple parameters should be taken into consideration for assessments simultaneously, including the physicochemical properties of ENMs, the migration and transformation of ENMs in the environment and organisms, and the physiological and pathological conditions of the testing organisms. This topic intends to explore nano-bio interactions from the aspects of ecotoxicology and cytotoxicity of ENMs, so as to efficiently modulate their bioactivities and reduce the potential risks.Zhou et al.. The recent research progress of 2D TMDCs with particular focus on their biomedical applications and potential health risks are discussed. Authors also emphasize how 2D TMDCs interacting with biological systems can sometimes interfere with normal cellular functions, the metabolic processes, and cell death. More in detail, apart from 2D TMDCs' chemical composition, size, and surface modification, they underline how their thickness effectively contributes to the establishment of cytotoxic effects even without entering cells. In another review of this special issue, Sun et al. summarized the effects of surface chemistry on various cytotoxicity-related bioactivities induced by ENMs. Negatively charged nanoparticles have a high protein binding capacity, whereas positively charged and hydrophobic nanoparticles can be more easily internalized by cells, triggering oxidative stress induction and the related autophagy, necrosis, and/or apoptosis phenomena. However, PEG decoration can counteract these cytotoxicity-related bioactivities. In their review, Sun et al. recommend surface decoration by combinatorial chemistry methods as an effective strategy to reveal the impact of surface chemistry on nanotoxicology. Besides, specific molecular pathways regulated by surface chemistry of ENMs are also discussed.The Research Topic “Nano-Bio Interactions: Ecotoxicology and Cytotoxicity of Nanomaterials” includes three reviews, one systematic review, and one original research, with the purpose of maximizing the understanding of how ENMs' cellular internalization process affects cell damages and deaths, which are related to their ecotoxicology and cytotoxicity. The fascinating properties of two-dimensional transition metal dichalcogenides (2D TMDCs) make them highly attractive for applications ranging from electronics to nanomedicines. For a better understanding of 2D TMDCs, two kinds of synthesis and surface functionalization methods (top-down and bottom-up) have been reviewed by Yu et al. explored the effects of surface chemistry on the formation and dynamic behavior of the protein corona using a gold nanoparticle array with a wide range of surface hydrophobicities. Generally, nanoparticles coated by high hydrophobic surfaces adsorb smaller and negatively charged proteins, and exhibit a lower hard corona protein exchange rate than their hydrophilic counterparts. The types of adsorbed proteins are also affected by the hydrophobicity of ENMs. These findings enhance our understanding of protein corona formation and protein exchange dynamics, and will help researchers in the modulation of nanotoxic effects by controlling protein corona formation through surface NPs modifications.As one of the most important parameters in understanding possible health issues of ENMs, it is necessary to clarify the role of the “protein corona” in the interactions between NPs and physiological systems, such as biological media and blood. Gedda et al. ENMs may induce cytotoxicity through epigenetic changes at DNA, RNA, and protein levels. ENMs are considered as epimutagens, as they can promote neoplastic changes by disrupting the function of epigenetically preserved genes via global epigenetic processes. They may induce epigenetic toxicity by altering DNA methylation profiles, changing histone modifications, and regulating non-protein-coding RNAs at sub-cytotoxic and sub-genotoxic ENM concentrations. Although numerous “toxico-omics” studies have been conducted on ENMs, a specific “risk assessment paradigm” dealing with the epigenetic modulations in humans owing to the exposure of ENMs has not yet been defined. Thus, Gedda et al. propose that constructing a universally recognized and centralized database concerning reproducible ENMs' characterization and in vivo standardized evaluation on ENMs' epigenetic toxicity can be considered a benefit in understanding the nature and extent of NPs nanotoxicity.As discussed by Sanches et al. assessed whether 3D skin models can be considered as an appropriate evaluation method of the TiO2 nanoparticles toxicity. Through the evaluation of the reliability of data extracted from seven selected articles, they conclude that 3D skin models are suitable for testing the hazard effect of TiO2 nanoparticles, while emphasizing the need of standardized protocols for the related risk assessment procedures.As for biological systems used for nanotoxicity assessments, two-dimensional (2D) cell models can hardly reflect the complex tissue microenvironments and interactions between ENMs and different cells types, while animal models are not suitable for high-throughput toxicity screening. Three-dimensional (3D) cell models have been used as an improved cell-based assay with more biological relevance and as an alternative method to animal experimentation. In a systematic review, Taken together, although this topic included some very recent advances in the fields of nanotoxicity and nanoecotoxicology, challenges are still overwhelming, such as ever-increasing production, usage and disposal of ENMs and their based products, developing standardized high-throughput nanotoxicity testing protocols, establishing centralized database on nanotoxicity, and developing intelligent prediction models of all nano-bio interactions. To conclude, addressing these challenges is fundamental for a better understanding of nanotoxicity and for the design of the next generation of ENM with a better reliability and safety profile.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


By the end of this decade, the USA is projected to experience an increase of more than 50% in the number of people with poorer vision health as the population grows older. Using data from the NHANES III (1988–1994) for 7,186 White, Black, and Hispanic adults of ages 50 to 90 , this paper examines the racial/ethnic, and socioeconomic disparities in vision health in the older adult population. The focus of this paper is on Visual Impairment indicators: full/partial blindness and trouble seeing with glasses to demonstrate vision health disparities in these race/ethnic groups in terms of family income using logistic regression analysis. Controls include demographic characteristics like age, gender, marital status, region, education and behavioral features like alcohol consumption and smoking. We explore another component of vision health: days since last visit to healthcare provider to evaluate the inequalities in access to health care using OLS regression analysis. In Whites (OR=.85) and Blacks (OR=.63), people with less family income are more likely to experience blindness, however, there exists no significant variability in blindness in terms of family income among Hispanics. In Black (OR=.82) and Hispanics (OR=.85), people with less family income are more likely to have trouble seeing even with glasses, however, this relationship does not exist among Whites. Days since last visit can be explained by income for Whites (Beta=-92), not for Blacks and Hispanics. This compounded disparity puts a disproportionate economic burden on minority groups, but the current Medicare policy fails to address that.


The most proactive approach to resolving current health and climate crises will require a long view, focused on establishing and fostering partnerships to identify and eliminate root causes of the disconnect between humans and nature. We describe the lessons learned through a unique scientific partnership that addresses a specific crisis, harmful algal blooms (HABs), along the northeast Pacific Ocean coast, that blends current-day technology with observational knowledge of Indigenous communities. This integrative scientific strategy resulted in creative solutions for forecasting and managing HAB risk in the Pacific Northwest as a part of the US Ocean and Human Health (OHH) program. Specific OHH projects focused on: (1) understanding genetic responses of tribal members to toxins in the marine environment, (2) knowledge sharing by elders during youth camps; (3) establishing an early warning program to alert resource managers of HABs are explicit examples of proactive strategies used to address environmental problems. The research and monitoring projects with tribal communities taught the collaborating non-Indigenous scientists the value of reciprocity, highlighting both the benefits from and protection of oceans that promote our well-being. Effective global oceans and human health initiatives require a collective action that gives equal respect to all voices to promote forward thinking solutions for ocean health. Our long history of dealing with environmental crises and degradation of aquatic ecosystems as well as studies of terrestrial ecosystems has convinced us that once an aquatic or terrestrial ecosystem is damaged, it is nearly impossible to return it to its original state [The confluence of a global pandemic and intensifying climate change has increased interest and yearning for contact with nature . The growing awareness about how important nature is to human well-being could be a game-changer in public attitudes toward the natural world ,2,3,4. Cd people ,8. Howeval state ,10,11,12In this paper, we focus on aquatic ecosystems, accepting humans as a part of this natural system, to explore the critical question: how can current-day technological advances be combined with historical knowledge, exemplified by traditional, Indigenous wisdom based on observations of natural systems, to result in a rich relationship of learning, discovery, and creative solutions for oceans and human health?As oceans comprise almost three fourths of the Earth’s surface, humans depend on the world’s seas in more ways than any other ecosystem. Rebalancing our relationship with oceans can be informed by learning from and supporting Indigenous peoples’ connection with the sea. Indigenous knowledge about conservation and resource management is being recognized with growing respect ,13,14,15https://www.oceandecade.org/; accessed on 4 March 2021) to design ocean solutions to combat climate change and environmental degradation. This initiative stems from the conviction that oceans will benefit from people who are inspired to implement conservation practices and advocate for positive change. Indeed, oceans and humans are inextricably linked: Our activities on land, sea, and in the air affect ocean health and, in turn, healthy oceans positively affect human health and well-being [Ocean scientists, lawmakers, industries committed to reducing and resolving the destruction faced by our world’s ocean(s), managers of natural resources, and the public are coming together during the 2021–2030 United Nations (UN) Decade of Ocean Science for Sustainable Development , aff’d, 520 F.2d 676 (9th Cir. 1975)), which reaffirmed the treaty-fishing rights of Washington State tribes while also recognizing individual tribes’ sacred histories of management and conservation. The Quinault and the Yakama Tribes were recognized as “self-regulatory” because of their demonstrated history of self-management and conservation of salmon stocks. A biocultural framework helps us “relearn Indigenous understandings of alternative ways for humans to relate with the natural world” . Thus, humans impacting nature), while shellfish toxicity due to HABs can cause human illness (nature impacting humans). Coast Salish tribes from the Pacific Northwest and other coastal, native communities have centuries of experience with HABs. One of the first written records of a poisoning event occurred in 1799 when over 100 Aleut tribal members died after eating toxic blue mussels while on a Russian fur trading expedition [To expound on this thesis, we describe a partnership with coastal tribes of Washington State, as a part of the US Ocean and Human Health (OHH) program in the Pacific Northwest (2004–2009), which included an emphasis on collaborative harmful algal bloom (HAB) research and monitoring. This HAB project built upon the initial National Oceanic and Atmospheric Administration (NOAA) National Centers for Coastal Ocean Science Monitoring and Event Response to HABs (NCCOS MERHAB) funding that was requested first by the Quileute Tribe as a need for establishing a system of solutions to cope with increasing HAB problems on the Washington coast. This alliance resulted in a joint proposal (2000–2005) among several science organizations  to develpedition . Our OHHThe West Coast Center for Oceans and Human Health (West Coast Center) was one of three national Centers of Excellence established by NOAA in 2004 . The WesThe partnership of NOAA scientists with coastal tribes generated several lessons for present and future scientific endeavors. Here we describe three such joint studies and the lessons learned, demonstrating proactive strategy toward addressing environmental problems. Specific OHH projects focused on understanding genetic responses tribal members to toxins in the marine environment, knowledge sharing by elders during youth camps, and establishing an early warning program to alert resource managers of HABs.Coastal tribes are the cornerstone collaborators of the OHH community in the Pacific Northwest (PNW). For centuries, native people in this region have lived interdependently with nature. Tribal participants in OHH invited us to learn more about the local ocean ecosystem through projects and partnerships that shared common goals with us. Members of the Makah Tribe spoke about a highly productive ocean region in their native seas, near the border of the U.S. and Canada, which they call The Prairie. The ORHAB and OHH partnerships confirmed that The Prairie is a highly productive site with abundant phytoplankton food available for higher levels of the marine food chain. However, among the phytoplankton species were some that can form HABs. Humans can be harmed when these HABs are transported by currents to the Washington coast where they are concentrated in shellfish, such as razor clams and Dungeness crabs, which are highly desirable food items, and necessary subsistence foods for coastal tribes who often live in remote regions. Although NOAA scientists believed that the origination of phytoplankton blooms at this site was a new discovery, the Makah Tribe explained what they had known for centuries: this is a site where the sea is bountiful; fishing for salmon and halibut is fruitful; marine birds are plentiful; and whales are commonly seen. That this site was an origination site or a “birthplace” of HABs was important information that eventually led to enhanced protection of seafood safety in coastal Washington State. This critical knowledge added to the overall strategy to promote seafood safety for coastal communities, including tribes, by providing an early warning system for blooms developing in The Prairie.Another collaborative discovery of the OHH partnership focused on how organisms, including humans, adapt to toxins in their environment. The Makah and other coastal tribes have a saying, “When the tide is out, the table is set”. In Neah Bay, Washington, where many Makah tribal members reside, shellfish, a major source of protein, are a subsistence food. Nearly 70% of households participate in shellfish harvest activities . MembersLesson 1, Share Knowledge). The overall goals of the camp were to improve ocean literacy, create enthusiasm and opportunity for hands on marine sciences, and encourage student empowerment. Part of the curriculum included listening to tribal elders tell traditional stories of the sea, including the observation of bioluminescent waters that warned of toxic algae. These listening events helped the tribal students see the wealth of traditional knowledge among the elders. It further demonstrated that the telling of the stories was a transfer of scientific and observational knowledge, proving its firm position and importance at the center of the non-Indigenous scientific canon.Our partnership with Indigenous scientists and communities has provided valuable lessons that can guide future collaborations among organizations across the globe . As partBox 11. Share knowledge2. Listen3. Foster collaborative and equitable relationships from the inception of an idea4. Conduct science as a collective action5. Cultivate mutual respectLesson 2, Listen). They continued to listen but offered their excitement only when we moved from telling them what we knew to talking about sharing knowledge. We suggested using new scientific tools and equipment together with all coastal tribes, including identification of phytoplankton using microscopy. This started the development of joint research proposals, first to MERHAB, then to OHH, which encompassed the viewpoints and scientific needs of all partners. Working collaboratively to learn new methods, such as testing for toxins in seafood and seawater using specific immunological assays, allowed the participant tribes to make decisions about the safety of their own harvest by conducting assays in their own, newly established labs. Currently, the Quinault Indian Nation, the Quileute Tribe, and Makah Tribe all have independent HAB toxin testing labs that were established by sharing ideas used to write successful grant proposals. Through this collaboration, we developed the Olympic Region Harmful Algal Bloom (ORHAB) Partnership . State resource managers joined with ocean scientists, including NOAA, the University of Washington Olympic Natural Resources Center, and members of the Quileute Tribe, the Quinault Indian Nation, and the Makah Tribe . This PNW HAB Bulletin , allowing the ORHAB partnership and its associated monitoring to continue well into the future. This is a clear example of inclusive science, not extractive, “helicopter” science, that ultimately was used to inform legislators to enact change that benefited these coastal communities, promoting environmental justice . ThroughBulletin , an earlPseudo-nitzschia, impacts the health of both humans and marine wildlife, including whales, sea lions, sea otters and marine birds, by permanently damaging the nerve receptors responsible for memory and learning. Humans, marine mammals and marine birds share the same symptoms during these poisoning events, including gastrointestinal distress, memory impairment and even death. Coastwide closures of shellfish harvest due to this toxin have historically lasted many months, resulting in an estimated $23–28 million total loss to local fishing communities [In October 1991, the first-ever domoic acid closure of razor clams and Dungeness crab harvest on the Washington coast  closed bmunities  and up tmunities , includiBy working together for the last 20 years to develop the HAB forecasting system initiated by the ORHAB partnership as its cornerstone, the PNW HAB Bulletin has allowed coastal managers to mitigate the economic effects of HABs on local economies. Tribal and non-tribal shellfish managers now use the PNW HAB Bulletin  to alertLesson 5, Cultivate Mutual Respect). A reverence for nature informs our current collaborative studies on the resilience of coastal communities to climate change, using integrative social-ecological systems approaches  to addrs (e.g., , in Washs (e.g.,  and in os (e.g., ,46, Guats (e.g.,  and Indis (e.g., . In the Taking to heart these lessons that non-Indigenous scientists have learned through their collaboration with Indigenous, place-based, communities, we are convinced that for global oceans and human health initiatives to be successful, we must think of ourselves as an integral part of the natural world to promote reciprocal healing ,3,4,7,8.In summary, taking the long view is required for our survival and necessary to reverse the impacts of climate change and other insults on oceans, including the increasing expansion and intensity of marine debris, pathogens and HABs. Our relationship with tribal communities taught us reciprocity, highlighting both the benefits from and protection of the environment that promote our well-being. Similarly, our partnerships with one another provided opportunities for joint learning and accomplishment. Proactive action by governments, organizations and communities with close attention to social and cultural factors  is vital


The availability of data generated from different sources is increasing with the possibility to link these data sources with each other. However, linked administrative data can be complex to use and may require advanced expertise and skills in statistical analysis. The main objectives of this study were to describe the current use of data linkage at the individual level and artificial intelligence (AI) in routine public health activities, to identify the related estimated health indicators  and health determinants of non-communicable diseases and the obstacles to linking different data sources.We performed a survey across European countries to explore the current practices applied by national institutes of public health, health information and statistics for innovative use of data sources .The use of data linkage and AI at national institutes of public health, health information and statistics in Europe varies. The majority of European countries use data linkage in routine by applying a deterministic method or a combination of two types of linkages  for public health surveillance and research purposes. The use of AI to estimate health indicators is not frequent at national institutes of public health, health information and statistics. Using linked data, 46 health outcome indicators, 34 health determinants and 23 health intervention indicators were estimated in routine. The complex data regulation laws, lack of human resources, skills and problems with data governance, were reported by European countries as obstacles to routine data linkage for public health surveillance and research.Our results highlight that the majority of European countries have integrated data linkage in their routine public health activities but only a few use AI. A sustainable national health information system and a robust data governance framework allowing to link different data sources are essential to support evidence-informed health policy development. Building analytical capacity and raising awareness of the added value of data linkage in national institutes is necessary for improving the use of linked data in order to improve the quality of public health surveillance and monitoring activities. The availability of administrative data generated from different sources is increasing. The possibility to link these data sources with other databases offers unique opportunities to answer those research questions, which require a large sample size or detailed data on hard-to-reach populations. This methodology link available information from different sources and can generate evidence at population level with a high level of external validity and relevance for policy making . Over anThe value of any surveillance system ultimately depends on timely and reliable information . There aLinking various data sources improves the completeness and comprehensiveness of information to guide health policy process, effective patient care and health services management . Data liWe explored the differential use of data linkage in routine health monitoring based on the latest developments in new methods and analysis across European countries. This study was carried out under the InfAct (Information for Action) project  which isWe performed the following steps to achieve the objectives of this study:We reviewed the existing literature published on the use of data linkage and AI  for health status monitoring using PubMed on Dec. 1, 2018. We included in our search peer-reviewed articles, systematic reviews and published reports in English language. The search strategies are reported in additional file The linkage of different data sources , 2. In Progress , and 3. Not yet .We developed a questionnaire and requested information from European countries on the data sources used for linkage, general characteristics of the data linkage, use of AI to estimate health indicators, related health outcomes and intervention indicators estimated and health determinants of non-communicable diseases. We reported these results according to three levels of using data linkage or AI in routine public health activities across European countries: Survey participants were also asked to report at least three health indicators, which are related to priority medical conditions in their country. We adopted the Euro-REACH Framework   to classThe survey participants were the partners of the InfAct project and/or national representatives, experts, health information advisors in their countries, employed by their government, national institutes of public health, health information and statistics institutes or research departments of the universities.. For the United Kingdom, data were provided separately by three countries England, Scotland and Wales but counted as one member state. The first reminder was sent via-email one month after the survey launch, on May 3, 2019, and the second reminder another two weeks later, on May 23, 2019. The abbreviations of the member countries and the names of the survey respondents are reported in the additional file The invitation email with an electronic link to the questionnaire was sent on April 1, 2019, to the identified representatives in 31 European countries [28 EU-MSs + 2 EEA (Iceland and Norway) + Others (Serbia)] and they were asked to complete the survey in four weeks The main outcomes of this study were the current data linkage and AI practices and related health indicators estimated in routine public health activities across European countries. A descriptive analysis of the web-based questionnaire results was performed using Microsoft Excel.We reviewed 137 citations from PubMed and four reports from the following organizations: OECD (Organization for Economic Co-operation and Development) , Euro-REi.Countries responseThe survey results include the countries response, use of data linkage in routine public health activities, use of AI in routine public health activities, health indicators estimated using linked data and main obstacles to linking different data sources. All survey respondents have validated these results.ii.Use of data linkage in routine public health activitiesTwenty-nine countries  participated in the survey with a response rate of 94% (29/31). Hungary, Iceland and Northern Ireland did not participate.Our survey results highlight that 24 European countries perform data linkage in their routine public health activities. These countries link administrative data such as EHRs , mortality data, and disease specific registries whereas six of them  are also developing this technique further to link with other types of data sources . Ireland and Latvia have ongoing initiatives of data linkage Table .Table 1Three countries  have not yet planned to integrate data linkage in their routine public health activities. The following reasons were mentioned by some countries for not having institutionalized data linkage: lack of a public health institution, which should collect and govern the health related data, data linkage is not part of the health agenda, lack of commitment from the ministry of health, lack of resources to establish a national health information system, the institutional complexity of the Ministry of Health and strict laws and regulations, which hinder data linkage with different data sources.Data linkage can be performed in routine for different objectives such as for health status monitoring, health system performance, health policy development or for scientific research  purposes. Our results showed that data linkage was performed for health status monitoring in 20 countries , for health policy development in 13  and for scientific research  purposes in 13 . Finland, Spain, Sweden and Scotland also perform data linkages to identify population risk factors. In Sweden, data linkage is also used to monitor compliance with national treatment guidelines to improve health care quality.Our results showed that 24 European countries, who perform data linkage in routine, use most frequently the five following types of data sources: health-related administrative data sources, non-health related administrative data sources, disease-specific registries, national health surveys, population-based epidemiological cohort and clinical trials  in routine public health activitiesThere are ongoing projects to integrate data linkage  as part of this technology in their routine public health activities in following European countries: Austria, Cyprus, Czech Republic, Ireland, Italy, Latvia, Norway, Poland, Portugal, and Spain.The use of AI is not frequent across European countries Table . Only fiThere are ongoing projects to integrate the use of AI in routine public health activities in the next five years in following countries: Croatia, Czech Republic, France, Germany, Norway, Portugal, and Spain. The objectives of these initiatives are for epidemiological research and surveillance of non-communicable and communicable disease estimating the prevalence and prediction of incidences of certain health conditions at various geographical levels.Two countries mentioned that due to lack of human resources (Lithuania) and capacities/skills (Republic of Serbia) within their public health institutes, AI techniques are not applied in routine public health activities.iv.Health indicators estimated using linked dataSome European countries also mentioned the use of classical statistical techniques without the use of AI Table .iv.HealUsing linked data, the majority of European countries estimate the following health indicators:ardiovascular (14), neurodegenerative disease (6), maternal and perinatal health (6), diabetes (6), suicide/trauma/injury (7), cancer (6) and hepatic failure (1) . These determinants are related to the physical environment (12), socioeconomic status and the environment (10), health behavior and lifestyle (6) and biological and metabolic parameters (3)  corresponding to the given health conditions which are most important for public health in their country. Using linked data, 23 health intervention indicators related to the following six health conditions were reported from 17 member states: maternal and perinatal health (7), cancer (6), diabetes (4), cardiovascular (2), neurodegenerative disease (2), suicide/trauma/injury (1) and lower/upper respiratory infections (1), , 2. Lack of human resources and capacities/skills within national institutes of public health and health information statistics , 3. Lack of governance of health information (data governance) and 4. Limited resources to support the health information infrastructure .The majority of European countries we surveyed identified the following main obstacles associated with the implementation and the use of data linkage and advanced statistics: 1. The complex laws and data protection regulations, which block linkage between different data sources with a deterministic approach The results of this study showed the variability in the use of data linkage and AI at national institutes of public health, health information and statistics across European countries. The majority of countries use data linkage in routine by applying either deterministic or a combination of two types of linkages  for public health surveillance and research purposes. The use of a universal unique identifier, social security number or unique pseudonymous identifier is common to applying deterministic linkage technique among European countries. The use of AI is less common to estimate health indictors at national public health institutes. Across European countries, using data linkage, 46 health outcome indicators related to seven health conditions, 34 related to determinants and 23 health intervention indicators were reported. Some initiatives are ongoing as pilot projects to test these techniques to improve health surveillance and to guide health policy development. Four main obstacles to linking different data sources have been identified by the European experts.A systematic review has shown that data linkage is used in the field of perinatal health for both health surveillance and research purposes in European countries . SeveralAs for AI, there are some studies available which have discussed the advantages of using this technology for early detection and diagnosis of certain medical conditions, for treatment, as well as for outcome prediction and prognosis evaluation with a high level of precision , 37 but Our results highlighted that a few member countries have achieved the most advanced levels of data linkage by linking health information  with non-health population data sources and registers of education, occupation, housing quality, air pollution, criminal statistics and transport/road accidents, etc. These innovative linkages offer the exceptional opportunities to enrich information, investigate non-health determinants and to perform high quality epidemiological research, health surveillance, to guide health policies to improve population health. These innovative linkages are especially relevant and of high value when considering health-in-all policies approaches. However, the majority of European countries have not reached that level of use in data linkage and AI and underlined main obstacles associated with the implementation and the use of data linkage and AI. These are related to legal, technical and data governance issues as well as organizational and structural aspects.: A. Legal aspects: 1. More flexible data governance frameworks to support data linkage of different data sources should be encouraged [B. Technical aspects: 4. More collaborations and partnerships should be encouraged to build up capacities for using new health information related technologies, to share new methods, skills, experiences and data for comparative research studies among EU national institutes of public health, health information and statistics; C. Data  governance, 5. Initiatives to strengthen national health information infrastructure should be encouraged; D. Organizational and structural aspects, 6. Ministries of health and research from European countries should provide their support  for the development of integrated national health data hubs/data platforms to strengthen the national health information infrastructure.To address these issues and to increase the uptake of innovative and high-performance technologies in public health activities, we propose the following recommendationscouraged , 2. Speccouraged ; B. TechFirst, our study may not have a complete coverage of data linkage practices within countries. The current linkages reported by national institutes of public health, health information and statistics we surveyed may differ from those conducted by other research institutes in that country which we did not cover in the survey. This might influence the results of this study. Second, we acknowledge that there are other innovative methods exist such as use of data clouds or blockchain. However, these methods are not frequently used for routine public health surveillance and research purposes. Third, we limited the response burden of health indicators to three priority health conditions. Therefore, our results do not constitute an exhaustive list of health indicators that are used in the country to inform policy and practice. It may limit the number of health indicators being estimated using linked data and advanced statistics. Nevertheless, this survey provides the latest overview of current practices in data linkage and AI in European countries and highlights the related obstacles in using these technologies for routine public health activities.There are a few limitations in this study. To our knowledge, this is the first study, which provides the information on current practices of data linkage and AI use at national institutes of public health, health information and statistics across European countries. Our results highlight that the majority of countries have integrated data linkage in their routine public health activities but few use AI. The European countries who are advanced in using both techniques i.e., data linkage and AI, could guide others by an exchange of their experiences and examples of good practices. A sustainable national health information system and flexible data governance frameworks to link different data sources are essential to support evidence-based practices for health policy development. Building analytical capacity and raising awareness of the added value of data linkage in national institutes of public health, health information and statistics is necessary for increasing the use of linked data in order to improve the quality of public health surveillance and monitoring activities. The recommendations we have put forth could ultimately contribute to strengthening national health information systems in Europe and would facilitate moving towards the establishment of an integrated EU- Health Information System.Additional file 1. It is a doc. Word file. It describes the search strategies used to identify citations related to data linkage and machine learning technique used for health status monitoring.Additional file 2. It is a doc. Word file. It describes the definitions of different data sources used for data linkage for health surveillance and research purposes.Additional file 3. It is a doc. Word file and include a table describing the names of survey respondents, their institutes and email addresses.Additional file 4. It is a doc. Word file and describes different data sources used for linkage across European countries in 2019.Additional file 5. It is a doc word file and describes examples of different combinations of data linkage across European countries in 2019.Additional file 6. It is a doc. Word file and describes examples of health outcome indicators estimated using linked data across European countries in 2019.Additional file 7. It is a doc. Word file and describes examples of health determinants identified using linked data across European countries in 2019.Additional file 8. It is a doc. Word file and describes examples of health intervention indicators estimated using linked data across European countries in 2019.


The substantial impact of foodborne disease outbreaks on public health and the economy has led to multidisciplinary research aimed to understand the biology underlying the different contamination processes and how to mitigate food hazards. Here we review the knowledge, opportunities, and challenges of plant breeding as a tool to enhance the food safety of plant-based food products. First, we discuss the significant effect of plant genotypic and phenotypic variation in the contamination of plants by heavy metals, mycotoxin-producing fungi, and human pathogenic bacteria. In addition, we discuss the various factors  that can influence the interaction between plant genetic diversity and contaminant. This exposes the necessity of a multidisciplinary approach to understand plant genotype × environment × microbe × management interactions. Moreover, we show that the numerous possibilities of crop/hazard combinations make the definition and identification of high-risk pairs, such as Salmonella-tomato and Escherichia coli-lettuce, imperative for breeding programs geared toward improving microbial safety of produce. Finally, we discuss research on developing effective assays and approaches for selecting desirable breeding germplasm. Overall, it is recognized that although breeding programs for some human pathogen/toxin systems are ongoing , it would be premature to start breeding when targets and testing systems are not well defined. Nevertheless, current research is paving the way toward this goal and this review highlights advances in the field and critical points for the success of this initiative that were discussed during the Breeding Crops for Enhanced Food Safety workshop held 5–6 June 2019 at University of California, Davis.An increasing global population demands a continuous supply of nutritious and safe food. Edible products can be contaminated with biological ( At the 1, the American Phytopathological Society-Public Policy Board (APS-PPB) convened the first formal activity in 2007 in a symposium titled “Cross Domain Bacteria: Emerging Threats to Plants, Humans, and Our Food Supply”2. A working group on “Human Pathogens on Plants” was assembled to create solutions for this problem and has since convened as a satellite meeting during annual APS meetings. Similar activities have been conducted in Europe through the COST Action on “Control of Human Pathogenic Micro-organisms in Plant Production Systems”3.Following a number of large multistate foodborne disease outbreaks linked to contaminated fresh produce4. During this period, lettuce and spinach were reported as the main vehicles of food safety incidents  subsequently implemented the Food Safety Modernization Act (FSMA) to address the significant public health burden of preventable foodborne diseases. Under FSMA, the Produce Safety Rule established, for the first time, science-based minimum standards that include on-farm regulation of fresh fruits and vegetables grown for human consumption6.Leafy greens are annually involved in food safety incidents in the United States. From 1996 to 2016, 134 confirmed incidents, including 46 outbreaks, were identified to be linked to products from California  that pro7 to identify knowledge gaps and research priorities in this emerging field to inform the USDA-NIFA and other agencies for funding and research priorities. This workshop connected plant scientists, plant breeders, extension specialists, microbiologists, and food safety experts from industry and academia to discuss collaborative efforts and multidisciplinary approaches geared toward preventing the occurrence of hazardous microbes, mycotoxins, elements, and allergens in crop and food production systems. Together, these pivotal steps by academia, industry, and government groups have laid out the opportunities to enhance food safety with plant breeding and created avenues for unique collaborative efforts and new research directions, which formed the basis for this review.Food safety is a complex issue that requires a concerted effort among scientists, regulators, seed/nursery industry, processors, retailers, and other stakeholders from diverse disciplines and research fields who do not often have the opportunity to meet and discuss global, comprehensive, and objective solutions. On 5–6 June 2019, the University of California, Davis hosted the first workshop on Breeding Crops for Enhanced Food Safetyi.e., aflatoxin resistant maize; e.g., Fusarium resistant wheat; e.g., removal of peanut allergens via transformation; The presence of mycotoxins, elements, and allergens in affected food crops has a high potential for mitigation via plant breeding . These se.g., non-typhoidal Salmonella enterica and Escherichia coli O157:H7) may have adapted to both animal and plant hosts, enabling them to survive in the food production chain  for decreased microbial hazards in several systems.Mounting evidence suggests that zoonotic bacterial pathogens of humans  is exploring cultivar variability in fatty acid content in tomato fruit as a means to reduce the favorability of tomato fruit for lmonella . Maeli Mgetables . Additioe.g., human pathogen–fresh produce) that create the largest burden on public health and the economy. Typically, the severity of an outbreak is estimated by the number of illnesses, hospitalizations, and deaths. With a hazard × occurrence (probability of infection or accumulation of toxin) risk model, one can begin classifying crop/hazard pairs. Although these are relevant metrics, it is very difficult to calculate the relative risk of each crop–hazard pair due to the low re-occurrence of particular pairs associated with outbreak events and the need to accumulate a substantial amount of data over extended periods of time (sometimes decades). Nonetheless, potential targets for plant breeding that are being identified may be the basis of future research to reduce human pathogens, mycotoxins, heavy metals, toxic elements, and allergens in foods.Given the complexity of produce safety issues and the need to prioritize efforts for the highest impact, a logical step would be to identify the crop–hazard pairs (8) of the Centers for Disease Control and Prevention reports disease outbreaks in the United States and maintains a comprehensive searchable database with information spanning from 1998 to 2017. Using this resource, we have generated a heatmap illustrating the relative importance of the major fresh produce in combination with reported etiological agents of outbreaks  for breeding programs geared toward improving microbial safety of produce    may overFully elucidating the interaction between food safety-relevant microbes and crops necessitates the consideration of the entire plant microbiome below and above ground. Plant microbiota are complex and strongly driven by plant genetics, plant age, plant anatomical structure, and environmental factors . Identifi.e., traits that affect the entry of the pathogen cells into the plant  is relatively easy with standard tissue analysis. Allergens can often be detected by routine (but still somewhat costly) assays  assays . However) assays 9. These An additional hurdle comes from the fact that microbial colonization is a complex behavior influenced by the plant host–pathogen combination and crop management practice such as irrigation type and crop fertilization . Human pe.g., Fusarium in wheat), it would be premature to engage in plant breeding for other aspects of food safety for which targets and testing systems are not yet well defined. Nevertheless, current research is paving the way toward this goal. To ensure advances in the field, the following points are critical to the success of this initiative:It is generally recognized that although breeding programs for certain human pathogen/toxin systems are ongoing ((1)Continue foundational research to generate crucial knowledge of plant interactions with human pathogens and contamination of food with microbes, mycotoxins, elements, and allergens.(2)Initiate pre-breeding screening strategies to characterize genetic variability, heritability, and efficacy of target traits.(3)e.g., breeding lines that accumulate less aflatoxins or heavy metals).Support breeding programs where genetic variation and efficacy is established (Ultimately, in combination with agricultural practices and interventions, the recognition that plant breeding for enhanced food safety can be another layer in our fight to reduce foodborne illness associated with crops necessitates research goals and funding prioritization to enable advances in this area.All authors have contributed to the writing of the review.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Shortages of personal protective equipment during the coronavirus disease 2019 (COVID-19) pandemic have led to the extended use or reuse of single-use respirators and surgical masks by frontline healthcare workers. The evidence base underpinning such practices warrants examination.To synthesize current guidance and systematic review evidence on extended use, reuse, or reprocessing of single-use surgical masks or filtering face-piece respirators.We used the World Health Organization, the European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and Public Health England websites to identify guidance. We used Medline, PubMed, Epistemonikos, Cochrane Database, and preprint servers for systematic reviews.Two reviewers conducted screening and data extraction. The quality of included systematic reviews was appraised using AMSTAR-2. Findings were narratively synthesized.In total, 6 guidance documents were identified. Levels of detail and consistency across documents varied. They included 4 high-quality systematic reviews: 3 focused on reprocessing (decontamination) of N95 respirators and 1 focused on reprocessing of surgical masks. Vaporized hydrogen peroxide and ultraviolet germicidal irradiation were highlighted as the most promising reprocessing methods, but evidence on the relative efficacy and safety of different methods was limited. We found no well-established methods for reprocessing respirators at scale.Evidence on the impact of extended use and reuse of surgical masks and respirators is limited, and gaps and inconsistencies exist in current guidance. Where extended use or reuse is being practiced, healthcare organizations should ensure that policies and systems are in place to ensure these practices are carried out safely and in line with available guidance. The identified documents were screened for inclusion and verified.2 online for search strategy). A systematic review search filter was not applied in Medline but was applied in Epistemonikos, the Cochrane Database, and PubMed to minimize duplication and increase specificity. Records were imported into Covidence and were double-screened by 2 reviewers independently at the title and abstract stage and at the full-text stage.We sought to identify systematic reviews of primary studies exploring any aspect of the extended use, reuse, or reprocessing of any type of surgical mask or filtering face-piece respirator on outcomes including technical performance standards, decontamination outcomes, or impact on healthcare workers . Systematic electronic database searches of Medline, the Cochrane Database of Systematic Reviews, Epistemonikos, and PubMed were conducted by an experienced information specialist on April 28, 2020. This procedure was supplemented with searches of preprint repositories Litcovid, medRxiv, and Open Science Framework. We scanned reference lists of included documents and contacted authors of included reviews to identify additional records. No date limit or language restrictions were applied. Search terms included (masks OR respiratory devices) AND (infection control OR decontamination) AND (reuse OR extended use)  and NVIVO . Data extraction fields included categories  and free text . Data extracted from guidelines were tabulated according to recommendations regarding extended use, reuse, and reprocessing. No quality appraisal was undertaken on guidelines because the purpose of this part of the review was to document recommendations. Included systematic reviews were assessed independently for quality by experienced systematic reviewers using AMSTAR 2. Data extracted from systematic reviews were tabulated to allow comparisons across reviews and with guidance documents.Extracted data were analyzed using a narrative synthesis approach with a critical to ensure that the narrative synthesis reflected original findings of source documents. Critical input was also provided by experts in infection control, occupational medicine, and PPE to ensure relevance and applicability.3 online). The search for reviews retrieved 458 records, and 60 full-text articles were screened; 4 relevant systematic reviews were included . The US CDC, the WHO, and PHE recommend additional procedures at the organizational level: appropriate documentation and recording of reuse or reprocessing, quality assurance of reprocessing measures, suitable reprocessing and storage facilities and systems, and staff training regarding safe use and donning or doffing of masks or respirators if reusing or extending use.We reviewed 3 guidance documents from the US CDCAll guidance documents favored extended use over reuse because of reduced risk of contact transmission. All recommended ensuring good fit, performing a seal check, and inspecting for function and potential damage prior to use or reuse of any mask or respirator. The US CDC and the WHO acknowledged that face masks and respirators that have passed their expiry date may sometimes be used in situations of limited capacity. Table 19 and 1 study covered reprocessing of surgical masks and ‘precontamination’ interventions applied before use to enable extended use or reuse. No reviews in our sample examined the impact of extended use or reuse of filtering face-piece respirators or surgical masks on the ability to meet technical standards or on healthcare worker acceptability outcomes such as comfort. The AMSTAR 2 ratings for each study are provided in Supplementary File 4 (online). The included reviews were judged to be predominantly of high quality. However, none provided a list of excluded studies or justified the reasons for exclusion, and no study reported on the sources of funding for included primary studies.The 3 systematic reviews were conducted between March and April 2020 and at the time of submission were preprints or were under peer review. All were conducted in Canada; 3 were conducted by the same research team. These 3 focused on reprocessing of filtering face-piece respirators using different decontamination interventions ,5 (online). The 3 reviews on filtering face-piece respirators included between 11 and 13 studies . The included studies evaluated the effects of reprocessing on various outcomes including effective decontamination, appearance, performance (including filtration efficiency and airflow resistance), user comfort, fit, and safety . In relation to decontamination, most of the evidence in the reviews supported vaporized hydrogen peroxide, moist/dry heat , and ultraviolet germicidal irradiation interventions. The studies included in the reviews were generally at low risk of bias. However, few primary studies investigated the impact of these methods on fit or user comfort, and there was substantial variability in the models of filtering face-piece respirator used across studies. Only 2 studies21 included in 1 review19 explored the effect of reprocessing on SARS-CoV-2. In addition, 7 studies were included in the review of surgical mask decontamination, but only 1 of these had specifically evaluated decontamination interventions after use to enable reuse. The review concluded that there was insufficient evidence regarding the safety or efficacy of any decontamination intervention for reprocessing surgical masks.Detailed descriptions of the reviews and their findings are provided in Supplementary File Table Our review of guidance documents and systematic reviews highlights several inconsistencies that warrant exploration, even though the COVID-19 pandemic presents unique challenges for different contexts. This is particularly true of the emerging science of reprocessing respirators, for which authorities appear to have proceeded with different degrees of caution in making recommendations.23Although the ECDC recommends the addition of either a surgical mask or a cleanable face shield over a respirator, the US CDC strongly recommends a face shield rather than a surgical mask due to supply issues and concerns that a surgical mask could affect the function of the N95 respirator. Moreover, evidence suggests that the addition of a surgical mask does not improve respiratory protection and may increase user discomfort and impair communication.The US CDC and ECDC make specific recommendations regarding respirators and aerosol-generating procedures. Both recommend discarding and not reprocessing respirators after use in aerosol-generating procedures, and the US CDC also recommends not using a reprocessed respirator while carrying out an aerosol-generating procedure (subject to manufacturer guidance). However, the WHO and PHE do not explicitly recommend that respirators be discarded after aerosol-generating procedures, nor do they mention the use of reprocessed respirators in aerosol-generating procedures. No guidance mentions the use or discarding of respirators in areas where aerosols may be present.24 suggesting that SARS-CoV-2 viral particles may remain infective for up to 72 hours, the US CDC suggests a system in which each healthcare worker is allocated 5 respirators for daily use in strict rotation, using careful storage to essentially ‘quarantine’ the devices. The US CDC suggest that if 5 respirators are not available for each worker, then decontamination may be necessary, potentially suggesting that this should be an initial strategy prior to attempting reprocessing. We found no systematic review evidence testing this approach, and neither PHE or ECDC explicitly discuss reuse with or without reprocessing. Moreover, data from the study cited showed that the 72-hour period was just the length of the measurement period and that survival followed a decay curve, not a fixed “all dead” time, implying that the length of time an amount greater than or equal to the infective dose survives depends on the starting quantity of virions.24Guidance regarding the reuse of respirators without reprocessing is inconsistent and lacks clarity. The WHO guidance strongly discourages the reuse of respirators without appropriate decontamination. However, citing a recent study by Van Doremalen et alThe systematic reviews included laboratory studies to test whether reprocessing changed the properties of a respirator. None of the reviews or research reported in guidance documents described practical or operational studies of facilitating reuse or reprocessing of respirators at scale. This is a key gap in the research, given the existing strain on healthcare resources and the requirement to ensure that a respirator remains matched to a healthcare worker throughout its use.Our systematic review yielded 5 key findings. First, while extended use or reuse of single-use surgical masks or respirators (with or without reprocessing) is generally not recommended, guidance from various organizations supports such measures (preferably extended use rather than reuse) as a last-resort measure during critical shortage. Second, comparisons across guidance documents and systematic reviews highlight limited evidence, varying levels of detail, and areas of inconsistency, especially in relation to the reuse of respirators (with or without reprocessing) during and after aerosol-generating procedures. Third, the reprocessing of surgical masks is not recommended. Fourth, the reprocessing of respirators under controlled and standardized conditions is recommended, but there is inconsistency regarding how or when this should take place. Fifth, where extended use or reuse is being practiced, healthcare facilities and institutions should ensure that policies and systems are in place to enable these practices to be carried out in the safest way possible in line with available guidance.Our findings highlight the numerous risks related to the extended use, reuse, or reprocessing of single-use surgical masks and respirators. The guidance is unanimous that these practices should be considered only in situations of extreme critical shortage, after all other strategies have been employed to minimize strain on supply. Where extended use or reuse is unavoidable, risks should be carefully assessed and policies and decision making should be made on the best available evidence. Where evidence is lacking or unclear, difficult judgments need to be made to balance current safety of staff regarding the conservation of supply and the future protection of staff. Given the rapidly growing body of related research, guidance should be regularly reviewed and updated.Surgical masks and respirators have different properties and functions. They should be distinguished clearly in policies and guidance, which should also take into consideration the variability of respirator models and manufacturer guidance. Policies should also be developed that address reuse clearly in relation to different reprocessing methods, and also address use and reuse of respirators in different situations, for example, during and after aerosol-generating procedures. Policies on reuse and extended use need to address both individual factors , and organizational factors .Certain steps can be taken to mitigate risk, such as the extending use of single-use masks or respirators before resorting to reuse and regularly inspecting masks and respirators for integrity, visible damage, and fit. Knowing when equipment must be discarded is crucial, as is appropriate storage and clear labelling of respirators between use to avoid cross use between workers. Organizations should ensure that adequate training in this is provided.7 Surgical masks and filtering face-piece respirators are only 1 component of PPE, which typically includes gloves, long-sleeved fluid repellent gown, and eye protection.3 Safe donning and doffing are critical.3 PPE is considered a last line of defense within the hierarchy of infection control measures which also includes administrative and environmental and engineering controls.Policy guidance emphasizes the need to assess the contagion risk of an encounter and the need to use recommended protective ensemble for that situation.Several areas warrant further investigation in relation to reprocessing. In the current context, research is needed to explore the impact of respirator decontamination methods for SARS-CoV-2, taking the heterogeneity of models into account. Research that explores the impact of decontamination on important outcomes  and the feasibility of reprocessing methods at scale is scarce.25 Houghton et al26 recently identified user comfort as an important factor influencing adherence with infection prevention and control guidelines26; comfort becomes particularly important when PPE is worn for extended periods.Despite consideration in some guidance documents for the extended use and reuse of surgical masks in crisis capacity situations, evidence is limited. Further research is needed regarding the effects of extended use of masks and respirators on outcomes such as fit and user comfort to determine the number of uses possible and the optimum length of extended use. Our recent review of respirator performance and standards found that all respirator types carry a burden to the user of discomfort and interference with communication.9 and guidance on respiratory protective equipment more broadly.27 However, the former did not address surgical masks, and neither study compared recommendations with current evidence. Our study integrates recommendations and evidence for single-use surgical masks and respirators to enable a clearer understanding of current evidence and research gaps to facilitate evidence-informed decision making in this area.This review was conducted to a high standard in adherence with current Cochrane rapid review guidance. Our interdisciplinary research team is a particular strength; we included frontline healthcare workers, expertise in occupational medicine, infection control, respiratory protective equipment design and performance, emergency nursing, evidence synthesis, and an information specialist. To facilitate timeliness, we limited our guidance search to 4 major health organizations, and we did not search exhaustively for primary studies. Recent research has compared international regulations regarding the reuse and extended use of filtering face-piece respiratorsIn conclusion, extended use and reuse of single-use surgical masks and respirators (with or without reprocessing) should only be considered in situations of extremely critical shortage. Where extended use or reuse is being practiced, healthcare organizations should ensure that policies and systems are in place to ensure that these practices are carried out as safely as possible and in line with available guidance. Areas of guidance lacking clarity and consistency warrant further attention and investigation.


The “Wet Tropics” of Australia host a unique variety of plant lineages that trace their origins to the super-continent of Gondwanaland. While these “ancient” evolutionary records are rightly emphasized in current management of the region, multidisciplinary research and lobbying by Rainforest Aboriginal Peoples have also demonstrated the significance of the cultural heritage of the “Wet Tropics.” Here, we evaluate the existing archeological, paleoenvironmental, and historical evidence to demonstrate the diverse ways in which these forests are globally significant, not only for their ecological heritage but also for their preservation of traces of millennia of anthropogenic activities, including active burning and food tree manipulation. We argue that detailed paleoecological, ethnobotanical, and archeological studies, working within the framework of growing national and world heritage initiatives and active application of traditional knowledge, offer the best opportunities for sustainable management of these unique environments in the face of increasingly catastrophic climate change and bushfires.  Environmental Science; Environmental Monitoring; Nature Conservation; Environmental Resource; Biological Sciences; Plant Biology; Botany; Plant Ecology; Ethnobotany; Agricultural Science Howeverblelands . There i Tropics , and Pleears ago   are particularly prominent after 2,000 years ago. Yellow walnuts are toxic and, as noted ethnographically, require leaching and processing, often using specialized basketry, to become edible , black walnut , black pine (Sundacarpus amara), cycads (Cycas media), and round yams (Dioscorea bulbifera) have also been recorded as part of the Aboriginal rainforest diet , musky rat-kangaroo (Hypsiprymnodon moschatus), wallaby (Macropod family), and white-tailed rat (Uromys caudimaculatus), as well as snakes, birds, lizards, and fish (Dendrolagus spp.) were historically recorded as a highly sought-after flesh, hunted using tamed rainforest dingoes and elaborate rainforest lawyer cane  traps. Perhaps most intriguing are historical references to the Aboriginal capture and taming of young cassowaries (Casuarius casuarius) before the raising and fattening of these birds for later slaughter during large inter-tribal gatherings   , for exaexcelsa) .Elaeocarpus bancroftii) grew much closer together than would be expected as a product of natural seed dispersal  and palms (Livistona mariae) have been shown to be anthropogenically dispersed species  based on its narrow genetic diversity and wide distribution across dissected territory in northern New South Wales  have been successfully used to reconstruct precipitation and forest dynamics  heritage with UNESCO . This wo


Despite an advanced ability to forecast ecosystem functions and climate at regional and global scales, little is known about relationships between local variations in water and carbon fluxes and large-scale phenomena. To enable data collection of local-scale ecosystem functions to support such investigations, we developed the EcoSpec system, a highly equipped remote sensing system that houses a hyperspectral radiometer (350–2500 nm) and five optical and infrared sensors in a compact tower. Its custom software controls the sequence and timing of movement of the sensors and system components and collects measurements at 12 locations around the tower. The data collected using the system was processed to remove sun-angle effects, and spectral vegetation indices computed from the data , Normalized Difference Water Index (NDWI), Photochemical Reflectance Index (PRI), and Moisture Stress Index (MSI)) were compared with the fraction of photochemically active radiation (fPAR) and canopy temperature. The results showed that the NDVI, NDWI, and PRI were strongly correlated with fPAR; the MSI was correlated with canopy temperature at the diurnal scale. These correlations suggest that this type of near-surface remote sensing system would complement existing observatories to validate satellite remote sensing observations and link local and large-scale phenomena to improve our ability to forecast ecosystem functions and climate. The system is also relevant for precision agriculture to study crop growth, detect disease and pests, and compare traits of cultivars. Atmosphere, plants, and soils control terrestrial carbon and water cycles ,2,3,4,5.Gaining insights for local-scale ecosystem functions using near-surface remote sensing is not a new concept. Spectroscopy, fluorescence sensing, and thermal imaging are three examples of the most promising near-surface remote sensing techniques for studying plant responses to environmental conditions at a fine scale . Plant sR2 = 0.82 and 0.73, respectively) as well as with fPAR  [Sun-induced chlorophyll fluorescence (SIF) is known to capture rapid change in photosynthesis, and its study is a fast-growing research area in remote sensing of vegetation . To tracctively) . Yang etctively)  further ctively)  integratctively) .Increased canopy temperature caused by plant water stress is widely studied using thermal infrared (TIR) remote sensing ,20. For These near-surface remote sensing systems have demonstrated that continuous optical and infrared measurements at atmosphere–biosphere interfaces would fill the data and knowledge gaps toward understanding the linkage between local- and regional/global-scale phenomena by providing new datasets at fine spatial and temporal scales. If we could integrate these sensing technologies and complementary sensors into a single synchronized system, that would enable a range of simultaneous environmental and ecological measurements and allow for various experiments and modeling of local atmosphere–biosphere interactions. This paper presents a highly equipped hyperspectral remote sensing system, the EcoSpec system, that integrates complementary environmental sensors to simultaneously collect measurements with hyperspectral reflectance of land surfaces. The ultimate goal of this system is to enable investigation of temporal patterns and associations between continuous measurements of hyperspectral reflectance of land surface and continuous meteorological and biological measurements under natural and managed environments .The EcoSpec system is equipped with five types of optical and infrared sensors powered by solar energy  installeThe upper package consists of a spectrometer and true-color ) camera, two TIR sensors, a white reference panel with a custom panel housing, and an actuator. All of these components are mounted on a pan-tilt unit (PTU) . The speThe spectrometer  measures electromagnetic radiation (EMR) that is reflected by land surfaces, such as plants and soils . EMR refThe RGB camera  housed in the enclosure is installed perpendicular to the land surface , Table 1Two TIR sensors , downward-looking and upward-looking, are installed on the side of the metal casing of the fiber cable , Table 1® panel extends only when reference data collection is needed. Movement of the reference subsystem is synchronized with movement of the PTU and the spectrometer’s preparatory activities, such as parameter optimization , actuator , and custom housing , Table 1mization . The refThe lower package consists of an albedometer and diffuse radiometer , Table 1The diffuse radiometer (Irradiance Rotating Shadowband Radiometer (RSR2); Cambridge, MA, USA) measures direct and diffused light separately and allows for quantifying the incoming radiation components. At least every 30 s, a narrow arm passes over the sensor to cast a shadow. This movement briefly blocks direct sunlight, and the sensor only measures diffused light during that time. The radiometer measures diffused light more frequently under partly cloudy conditions than sunny conditions in order to track rapidly changing irradiance.The lower package also includes the control box. The control box houses a single-board computer, data logger, small battery, and cellular modem , Table 1We developed custom software to operate the EcoSpec system in a Linux environment, including collection of hyperspectral EMR measurements. The software package allows a range of autonomous functions for the system, which include (1) initiating the system 20 min before sunrise each day, (2) triggering activities of the components in a synchronized manner, (3) monitoring system functions and sending an email alert when malfunction is detected, (4) rebooting the system when malfunction is detected, (5) transmitting the data approximately every 30 min throughout the day, and (6) shutting down the system at sunset each day.® panel and records the average value. The actuator retracts and stores the white panel in the custom housing  to test the functionality of the platform and return to position 1. The first spectrometer data collection begins at sunrise at position 1. The actuator extends and places the white reference panel under the fiber optic cable . The spe housing . This pr housing . While rAt each position, a set of hyperspectral EMR measurements is comprised of gain, offset, integration time, white reference (2150 features), dark current (2150 features), and land surface measurements (2150 features), and all measurements are temporally recorded in the Raspberry Pi along with measurement identification, PTU position, and sample date and time . A set oThe system allows us to collect an array of land surface measurements, including hyperspectral reflectance of plants and soils, true-color photos capturing contextual information of land surface, radiant temperature of sky and land, incoming and reflected shortwave radiation, and incoming radiation components (direct and diffuse), as frequently as every minute. Several of the sensors are mounted on a pan-tilt unit on top of the tower to collect hyperspectral reflectance, land surface photos, and radiant temperature of sky and land from 12 discrete positions around the tower. This allows for capturing inherent heterogeneity of the terrestrial ecosystem at a local scale and to obtain representative spectral signatures of the plant and soil surfaces via averaging those measurements.Hyperspectral reflectance measurements that are collected using the EcoSpec system must be preprocessed prior to analysis. For this paper, we prepared the data using parsimonious processing methods to remove outliers and mitigate sun-angle effects to demonstrate the usefulness of measurements collected using the system.We first identified outliers in hyperspectral reflectance measurements by applying two criteria that define the allowable range for instantaneous data values  and the allowable change in reflectance values within a limited time period . We removed data points that were identified as outliers from the dataset for subsequent processing and analyses. We developed a prototype methodology for minimizing the sun-angle effects on hyperspectral reflectance collected from land surface, known as a bidirectional reflectance distribution function (BRDF). We modeled an overall temporal trend and pattern in reflectance values on each date. Sunny dates had stronger, more symmetric pattern than cloudy dates. We removed the modeled trend and pattern from the reflectance values prior to analyses. To preserve the integrity of the measurements, an independent model was developed for each of the 2150 spectral channels.After the measurements were preprocessed as described above, we calculated the average hyperspectral reflectance values over 30 min to match the temporal frequency to that of the meteorological data collected using an eddy covariance method. Using the half-hourly hyperspectral data, we computed the Normalized Difference Vegetation Index (NDVI) ,22, NormThe following results are examples from the 2015 study conducted at the soybean field in AmeriFlux US-B1 site located within Fermi National Accelerator Laboratory, Batavia, Illinois. Examples of spectral reflectance values of land surfaces that were collected using the EcoSpec system are shown in Diurnal trajectories of selected spectral vegetation indices and TIR on 21 August 2015 DoY 234) are shown in 4 are shoRGB photos on the selected dates during the 2015 growing season that were captured using the EcoSpec system are shown in Seasonal trajectories of the NDVI, NDWI, and PRI along with the trajectory of the fPAR that was measured using the eddy covariance system are shown in Seasonal trajectories of TIR temperature, soil moisture, and NDVI of the 2015 growing season are shown in Collection of measurements from 12 locations spanning a 300 degree rotation of the platform to account for heterogeneity of the land surface.Integration of five optical and infrared sensors to collect a suite of measurements that complements hyperspectral reflectance measurements, enabling various modeling approaches, such as surface and sky temperature, direct and diffused sunlight, incoming and outgoing albedo, and RGB photos of the land surface.Custom software to control synchronized movements and functions of the system components so that every sensor collects measurements properly without interference of other sensors. This software manages a specific order or timing of actuator movement, reference reflectance measurement, target reflectance measurement, and platform movement in a compact package.Portability of the system as being powered by a relatively compact power generating system, such as the solar power system evaluated during the entire testing period, which allows for deployment at a range of sites, including existing research stations/observatories, short-term/temporary locations, remote locations, and agricultural fields.Understanding interactions of ecosystem functions and climate across varying spatial and temporal scales could improve climate forecasting capability. However, determining the linkage between very different scales  is particularly difficult because key processes at each scale operate at different rates and create complex heterogeneity and dynamics. Recognizing that existing instrumentation would not fully support the type of data collection needed to investigate the interaction of two extreme scales, we developed a tower-based remote sensing system to automatically collect a range of optical and infrared measurements of land surface across the visible to TIR spectral region throughout the day over the growing season. While many existing near-surface remote sensing systems continuously collect measurements in an automated manner over an extended period of time, the uniqueness of the EcoSpec system includes the following:When examining the measurements collected using the system, temporal trajectories between narrow-band spectral vegetation indices—NDVI, NDWI, and PRI—and a biophysical variable directly correlated with the primary production—fPAR—were strongly correlated. TIR temperature that correlates with the MSI at the diurnal scale appeared to correspond to soil moisture across the season. These patterns suggest that hyperspectral reflectance and simultaneously collected complementary optical and infrared measurements could provide valuable observations for investigating ecosystem functions, such as photosynthesis or gross primary production and possibly ecosystem respiration in response to environmental changes, which would provide critical information to understand interactions between biosphere and atmosphere at its interfaces.Optical and infrared measurements of land surface—plants and surface soils—properties would provide critical data for understanding ecosystem functions and their responses and contributions to environmental changes and variability. Instrumentation that allows measurements from multiple locations at high temporal frequency would enable experiments and modeling with great flexibility by providing replicates of samples and options for temporal aggregation. This type of near-surface remote sensing system can be used to complement existing science observatories to validate satellite remote sensing observations, link local- and regional/global-scale phenomena, and ultimately improve our ability to forecast ecosystem functions and climate. When applying this system for precision agriculture, measurements would be useful for studying crop growth, detecting disease and pests, and comparing traits of breeds or cultivars to improve our future food security.The EcoSpec system developed in this study is best suited for research that aims to explore various modeling and analysis approaches to understand fine-scale plant properties and/or ecosystem functions for heterogeneous land. When studying a relatively uniform and homogenous area, an instrument that continuously collects measurements from a single patch of land may be sufficient. When the types of measurements required for research are already known, the system having only those sensors necessary may be more efficient than using a highly equipped system like the EcoSpec system.The examples presented in this paper utilized a preliminary method to account for BRDF and did not consider the effects of varying sky conditions on hyperspectral measurements. When more sophisticated models are applied for data cleansing, the quantity and quality of the hyperspectral reflectance measurements useful for the analysis are expected to improve significantly.


Weakness is the primary impairment in paediatric neuromuscular diseases, impacting gait and gait-related functional activities in ambulant children affected by these rare and often degenerative diseases. Gait speed is an indicator of health and disability, yet gait is a complex, multi-faceted activity. Using the International Classification of Function, Health and Disability (ICF) model, assessment of gait and functional ambulation should consider the impairments, activity limitations and participation restrictions due to disease, and factors related to the environment and the individual person.This narrative review involved a literature search of databases including Medline, Embase and Pubmed from 1946 to October 2019. Inclusion criteria included assessments of gait, endurance and ambulatory function in paediatric (0–18 years) neuromuscular diseases.Fifty-two papers were identified reporting assessments of gait speed, timed function, endurance and ambulatory capacity, gait-related balance and qualitative descriptive assessments of gait function and effect of disease on gait and gait-related activities. Gait speed is an indicator of disability and children with neuromuscular disease walk slower than typically developing peers. Increasing disease severity and age were associated with slower walking in children with Duchenne muscular dystrophy and Charcot-Marie-Tooth disease. The six-minute walk test is used widely as a test of endurance and ambulatory capacity; six-minute walk distance was substantially reduced across all paediatric neuromuscular diseases. Endurance and ambulatory capacity was more limited in children with spinal muscular atrophy type 3, congenital muscular dystrophy and older boys with Duchenne muscular dystrophy. Only a few papers considered normalisation of gait parameters accounting for the effect on gait of height in heterogeneous groups of children and linear growth in longitudinal studies. Balance related to gait was considered in five papers, mainly in children with Charcot-Marie-Tooth disease. There was limited investigation of factors including distance requirements and terrain in children’s typical environments and personal factors related to self-perception of disease effect on gait and gait-related function.Assessments of gait and functional ambulation are important considerations in documenting disease progression and treatment efficacy in the clinical setting; and in clinical trials of disease-modifying agents and physiotherapeutic interventions in paediatric neuromuscular diseases. There is a need for expert consensus on core gait and functional ambulation assessments for use in clinical and research settings. Neuromuscular diseases (NMD) include disorders affecting the anterior horn cells, peripheral nerves, neuromuscular junction and muscles, are often progressive and exhibit a wide range of impairment and disability in affected individuals. Relatively rare, in children these diseases include spinal muscular atrophy   and DuchWeakness is the primary impairment in NMD, often presenting in childhood and adversely affecting gait and functional ambulation. Additionally, muscle tightness, contracture, musculoskeletal deformities, poor standing balance and reduced endurance, all arising from weakness, affect functional ambulatory tasks such as standing and walking. Patterns of weakness differ depending on the NMD, some affecting more proximal muscles (e.g. DMD) and others more distal muscles (e.g. CMT). For the majority of NMD of childhood, disease is progressive leading to increasing weakness and disability across the lifespan. The degree of disability in childhood NMD is variable ranging from children who are extremely weak and unable to sit (e.g. SMA type 1) to those with milder weakness who remain ambulant, albeit with gait difficulties including foot drop, poor balance and reduced gait speed .Gait dysfunction has important implications for function in everyday life. Ambulant children with NMD, commonly report problems with walking, poor balance, frequent trips and falls, increased fatigue and difficulty keeping up with peers –11. In tThis narrative review considered the literature relating to gait and functional ambulation in children and adolescents with neuromuscular disease. Literature was searched in Ovid Medline, Embase and PubMed from 1946 up to and including October 2019. Keywords and search terms included gait, walk*, ambul*, locomotion, functional ambul*, paed*, pediatr*, child*, adoles*, neuromuscular disease, Duchenne and Becker muscular dystrophy, Charcot-Marie-Tooth disease, peripheral neuropathy not diabetes, spinal muscular atrophy, myopathy, Pompe, myotonic dystrophy, collagen VI disorders, fascioscapulohumeral dystrophy or FSHD. Only full-text human studies in English were considered , Becker and Duchenne muscular dystrophies (B/DMD) 21 papers), SMA (7 papers), congenital myotonic dystrophy (CMD) (2 papers), fascioscapulohumeral dystrophy (FSHD) (1 paper), Pompe disease (1 paper), collagen VI disorders (1 paper) and other mixed cohorts (4 papers)  with DMD did not walk significantly slower than their typically developing peers , 45. HowGait speed was reported in two other studies in children with CMD  and a miThe 6MWT is a valid and reliable standardised test of physical endurance in boys with DMD . A test Six-minute walk distance (6MWD) is reduced in children and adolescents with NMD when compared to typically developing controls or normative reference data. In boys with DMD and children with SMA type 3 and CMT, 6MWD declines with increasing age, reflecting disease progression and increasing disability , 39, 40.The timed 10 m walk/run is widely used to assess function in NMD and is a sensitive measure of disease progression in ambulant boys with DMD , 74, 75.Assessments of balance, endurance and alternative distance and timed tests  were reported less frequently. The balance subset of the Bruininks-Oseretsky Test of Motor Proficiency, 2nd Ed  is a ten-item standardised test of balance in standing and walking . It is wThe TUG was reported in two studies and is a valid, reliable and responsive measure of gait-related balance in children with physical disabilities , 77, 78.Alternatives to the 6MWT were reported in two studies. Alfano and colleagues (2017) reported the development and validation of a 100 m timed test in boys with DMD as an assessment of functional ambulatory performance. Their study included the establishment of typically developing normative reference data . Findingthe inability to perform prolonged repetitive tasks during activities of daily life”, and have developed a group of endurance tests to assess fatigability [The 6MWT and more recently the 100 m timed test and 2MWT, are all described as tests of physical endurance in paediatric NMD and as surrogate measures of physical fatigue in DMD, SMA and CMT , 25, 44.gability . The EndThe advent of wireless wearable activity monitors allows remote measurement of gait-related physical activity in children with NMD. Several studies have included wearable devices to measure steps and physical activity in DMD, CMD and mixed NMD , 53, 61.Together with quantitative measures of gait and function, descriptive scales and questionnaires are used to characterise gait and functional ambulation in paediatric NMD. Two such measures reported in this review are the Functional Mobility Scale (FMS)  and the The Functional Mobility Scale (FMS) is a clinical tool used to classify typical mobility over three distance categories – 5, 50 and 500 m in children with gait dysfunction . These dThe Walk-12 is a self-reported questionnaire of perceived impact of disease on gait and gait related activities, such as running, using stairs and balance, modified and validated in adults with peripheral neuropathies , 79. TheGait performance and functional ambulation are biomarkers of disease severity in paediatric NMD, providing a measure of disability. Assessment of gait and functional ambulation are important outcome measures in the toolbox of assessments for clinical research trials and in the clinical setting. With the advent of disease-modifying pharmacological treatments and uptake of physiotherapeutic exercise, younger people, including children with NMD are likely to benefit most from treatments. Therefore, it is important to utilise functional measures specific to children and adolescents to monitor disease progression and treatment efficacy.There remains a need for further research and development of functional gait outcome measures for paediatric NMD. Limitations including the heterogeneity of the study populations and differences in assessment protocols precluded meta-analysis of these studies. As evidence accumulates, a more analytical systematic review may provide additional insights. The disparity of gait assessments in paediatric neuromuscular diseases also suggests that a Delphi survey would be useful in establishing expert consensus on which measures to use. Factors such as the normalization of gait parameters is important when comparing gait across age ranges and longitudinally to account for growth in children and should be standardly applied both clinically and in research. Further development and publication of paediatric normative reference datasets and MCIDs will be a valuable resource for clinicians working in neuromuscular clinics. Qualitative characterisation of gait and functional ambulation with scales or questionnaires enables clinicians to gain an understanding of the effect of disease on the day-to-day lives of children with NMD, beyond the neuromuscular outpatient clinic. The self-reported scales of functional mobility and gait-related activities require validation in paediatric NMD populations to ensure that they provide meaningful information and enable greater uptake by clinicians. Further exploration and utilization of technology for remote and wireless monitoring and measurement of walking in the typical environments of children, including home, school and the community provide greater understanding of the effect of disease on function.This narrative review has highlighted clinical measures of gait ranging from gait speed to tests of ambulatory capacity, physical endurance and gait-related balance that can be conducted in clinical and research settings with relative ease. Consideration of environmental factors affecting function including distance requirements necessitated by school and community settings is important when understanding the effect of disease. An individual’s perception of the effect of disease on walking and everyday function are important considerations in the clinical setting. Person-centred characterization and assessment of gait dysfunction discussed in this narrative review provides a rich and holistic illustration of disability, and offers genuine outcome measures of potential therapeutic benefits on gait and functional ambulation in paediatric NMD. However, consensus is required amongst experts in paediatric neuromuscular disorders to establish a core set of gait and functional ambulatory assessments that can be used clinically and in research settings.Additional file 1. Search strategy for narrative review “Walking and weakness in children: a narrative review of gait and functional ambulation in paediatric neuromuscular disease”.