Connections between individuals and organizations can impact knowledge translation (KT). This finding has led to growing interest in the study of social networks as drivers of KT. Social networks are formed by the patterns of relationships or connections generated through interactions. These connections can be studied using social network analysis (SNA) methodologies. The relatively small yet diverse community in the field of child development and rehabilitation (CD&R) in Canada offers an ideal case study for applying SNA. The purposes of this work are to (1) quantify and map the structure of Canadian CD&R KT networks among four groups: families, health care providers, KT support personnel, and researchers; (2) explore participant perspectives of the network structure and of KT barriers and facilitators within it; and (3) generate recommendations to improve KT capacity within and between groups. Aligning with the principles of integrated KT, we have assembled a national team whose members contribute throughout the research and KT process, with representation from the four participant groups.A sequential, explanatory mixed-method study, within the bounds of a national case study in the field of CD&R. Objective 1: A national SNA survey of family members with advocacy/partnership experience, health care providers, KT support personnel, and researchers, paired with an anonymous survey for family member without partnership experience, will gather data to describe the KT networks within and between groups and identify barriers and facilitators of network connections. Objective 2: Purposive sampling from Phase 1 will identify semi-structured interview participants with whom to examine conventional and network-driven KT barriers, facilitators, and mitigating strategies. Objective 3: Intervention mapping and a Delphi process will generate recommendations for network and conventional interventions to strengthen the network and facilitate KT.This study will integrate network and KT theory in mapping the structure of the CD&R KT network, enhance our understanding of conventional and network-focused KT barriers and facilitators, and provide recommendations to strengthen KT networks. Recommendations can be applied and tested within the field of CD&R to improve KT, with the aim of ensuring children achieve the best health outcomes possible through timely access to effective healthcare.The online version contains supplementary material available at 10.1186/s43058-022-00372-5. Contributions to the literatureThis study leverages network theory and knowledge translation (KT) theory to advance our understanding of the structure and impact of social networks on KT in the field of child development and rehabilitationThe work addresses gaps in the social network analysis literature by using mixed methods and including multiple intersecting participant groupsIntervention mapping will link identified conventional and network-based KT barriers and facilitators to a range of potential solutions, including network interventionsRecommendations to strengthen KT and KT networks in the field of child development and rehabilitation will be generated by an expert panel using Delphi methodologySocial connections and relational processes have long been understood to influence knowledge exchange and the adoption of innovation . Despiteand informal  ties, which collectively support KT in Canada. These ties and the existing gaps between individuals, regions, and organizations that influence KT can be examined empirically using social network analysis (SNA), an emerging approach in KT science [The patterns of relationships or interactions (referred to here as “ties”) between individuals or organizations represent the relational data that can be used to describe social networks . These t science .The field of child development and rehabilitation (CD&R) in Canada presents an excellent case to apply SNA methods. This small but diverse field focuses on children with exceptionalities, which may be described in the health care setting as having developmental, behavioral, or neurological conditions, musculoskeletal diagnoses, and/or physical or primary sensory impairments . ResearcAcknowledging that many families experience systemic barriers to accessing CD&R services is also imperative. Racism, trauma, lack of service availability, persisting difficulties related to funding arrangements, and the privileging of western knowledge within the health system , 24 all SNA can lead to a better understanding of KT barriers and facilitators. The SNA research paradigm is rooted in ethnography and designed to describe and examine social relationships, group dynamics, and information flow , 26. SNANetworks can be measured at the individual (“ego-network”) or “whole network”  level . Relatiohow and why the KT network functions. Examining the interactions of multiple network member groups  allows for within- and between-group analyses to understand the determinants of strong, weak, or absent ties. Once a network’s structure is understood, tailored network-driven interventions can be used to address weak or missing ties  [While mixed methods SNA research has been limited , pairingactions) , 31, 32.actions) , these Kactions) , 34. Theactions) , 35. Thiactions) .The use of SNA in health research and KT has been increasing steadily , 37–39; and informal social network structures and practices and their intersections, as a baseline measure of connectedness for KT among groups involved in CD&R across Canada. Characterizing the nature of these formal and informal KT ties in CD&R allows for hypothesis generation and testing to improve national KT in this field and to inform KT science more broadly.SNA can be applied within the field of CD&R to identify strategies to improve knowledge exchange within and across groups, with the goal of improving health outcomes. Formal national research networks, such as the Networks of Centres of Excellence (NCE)-funded Kids Brain Health Network and the Strategy for Patient-Oriented Research-funded CHILD-BRIGHT Network have been created to improve research and KT in CD&R. These networks include KT within their organizational structures. In the clinical sector, CD&R organizations and formal clinical networks have also developed various mechanisms for evidence sharing and uptake , 41, 42.Strengths and gaps in the patterns of ties between people and organizations within and across participant groups ,Influential individuals and the characteristics that may explain their network positions ;Quantify and visually map the structure of Canadian CD&R KT networks of families, health care providers, KT support personnel, and researchers to identify:Identify family, health care provider, KT support personnel, and researcher perceptions of conventional and network-specific barriers and facilitators of KT within the network and understand the reasons for the CD&R KT network’s structure;.Generate recommendations to improve KT capacity within and between participant groups, by linking identified conventional and network-specific barriers and facilitators to KT strategiesThe objectives of this study are to:A sequential explanatory mixed-method design will be used within a descriptive SNA case study framework , 44. TheOnline national surveys will be used to quantify the structure of the CD&R KT networks. Data will be collected and managed using REDCap electronic data capture tools, hosted at the University of Manitoba. REDCap is a secure, web-based software platform designed to support data capture for research studies , 46. IntBoth survey options will collect information on participant attributes ability, ethnicity, CD&R area of interest, years of experience, profession) to understand network composition and to contribute to our understanding of diversity in CD&R related to KT roles. Open-ended questions will be used to collect data on KT network practices and participants’ perceptions of these.For the Standard SNA Survey, each respondent will be asked a name generator question . This quThe Family Survey mirrors the Standard SNA Survey in intent, but omits the name generator question . Instead, participants are asked about the roles of people with whom they connect  and the places where they look for information about CD&R . As access to health care services and knowledge sharing about health/health care are intertwined, in both the Standard SNA Survey and Family Survey, questions are posed to explore accessibility of health care, safety/trust in health care, and barriers and facilitators to knowledge sharing.Families through Facebook ads, local and national family support groups, health center Family Advisors, family/patient-engaged research networks, the CanChild/KBHN Family Engagement in Research Training Program through McMaster University, and online groups, such as the Parents Partnering in Research Facebook Group (CanChild/KBHN). We will pursue conversations with community organizations to further support recruitment of families who have not participated in research or health partnerships. Our collaborators  will support these processes;Health care providers through provincial regulatory colleges and associations, healthcare/rehabilitation centers, provincial pediatric special interest groups , professional councils; andKT support personnel and researchers through formal provincial and national research networks and collaboratives , research institutes, Strategy for Patient-Oriented Research Units, LinkedIn, and relevant university departments.Email, newsletters, blogs, webinars, and social media to leverage professional networks, as well as personal/informal connections, will be used to recruit:We have also developed a website (chrim.ca/connectingforcare) that includes information about the study and links to the survey. Social media will be leveraged to direct people to the website for more information. Participants will also be reached through our team’s professional contacts .For the Standard SNA Survey, relational data  will be entered into adjacency matrices, de-identified, and imported into UCINet SNA software  to derivFor both surveys, analysis of open-ended responses about KT activities will begin with directed content analysis . Data wiAdhering to the mixed methods paradigm, quantitative data from these Phase 1 surveys will be integrated with qualitative interview data (described below) at multiple points throughout the study to enrich overall data quality and interpretation , 43, 51.In Phase 2, consenting participants will take part in a semi-structured qualitative interview. “Intersectionality and KT” guidance for interview administration and analysis will be used to ensure that the safety of participants and that the complexity of lived experience is continuously considered and respected , 54. ForInterviews will further explore conventional and network-specific KT barriers and facilitators, KT practices, patterns of interaction, and how participants view themselves within the KT network. KT practices may be formal  or informal . As previously discussed, issues related to health care access will also be considered in discussions about KT barriers and facilitators. The interview guide will be informed by the TDF with intersectionality enhancements , Phase 1Stratified purposeful sampling with maximum variation (aiming for 1–2 cases per variation) , 56 willAudio-recorded interviews will be transcribed for line-by-line directed content analysis . QualitaPhase 3 will be accomplished through intervention mapping  and a DeThe roots of intervention mapping in community-engaged research underscore the need to align interventions to end-user and context-driven needs , 58. TheOnce interventions are mapped to their corresponding barriers and facilitators, we will verify the suitability of these pairings through structured engagement with end-users . We willPrior to the first Delphi round, participants will receive the study objectives and methods, and a summary of the survey and interview findings. They will be presented with the identified KT barriers and facilitators and a logic model that maps each identified barrier and facilitator to one or more intervention recommendation. These intervention pairings with their corresponding barrier/facilitator(s) will form the basis of the Delphi survey. Surveys will be pilot tested by 3–4 individuals from different participant groups prior to finalization and distribution . Data wiDelphi surveys are conducted in an iterative manner: In Round 1, the anonymous online survey will list each recommended KT intervention and the barrier(s)/facilitator(s) to which it was mapped. Participants will indicate their level of agreement with the matches using a 9-point Likert Scale , with opIn rounds 2 and 3 (if necessary), participants will be provided with quantitative data from the previous round  , an anonTo enhance participation at each stage of the Delphi process, participants are recommended to have prior interaction with the study team, and be fully informed of the multi-stage process . ParticiUp to three survey rounds will be conducted using identical methods , with eqOur anticipated output from this objective is a set of recommendations for promising strategies that target conventional  and network-related  barriers and facilitators to improve capacity for KT within and among participant groups at the provincial or territorial and national levels. These interventions can be tested in future research using a multiple baseline design to monitor network dynamics prior to implementation .To our knowledge, this is the first study to systematically integrate network and KT theory in mapping barriers and facilitators to interventions to enhance KT networks. Results will advance KT science through an in-depth understanding of KT barriers and facilitators from diverse groups, purposefully selected based on network position and considering intersectional categories. The methods we use can be adapted by others to understand KT networks in their own fields. Data from CD&R can then be compared with that from other fields to determine unique and shared determinants of network-based KT. This project also addresses gaps in the SNA literature, through the use of mixed methods and its unique application within CD&R, where only one SNA study has been identified to date . FactorsPotential challenges include low recruitment within diversity categories, which would yield incomplete data related to barriers, facilitators, and KT strategies. To mitigate this challenge, we have assembled a pan-Canadian team to facilitate recruitment through its various affiliated institutes and networks. Strong support from national CD&R research networks, such as Kids Brain Health Network, and CHILD-BRIGHT Strategy for Patient Oriented Research Network, will support researcher recruitment. A detailed recruitment plan includes a contact list of all pediatric CD&R organizations and research institutes established for previous research  and fundOur team recognizes the limitations that we carry as a team of predominantly western-trained researchers and health care providers. We acknowledge that this study was initially conceptualized through a Eurocentric lens and that Indigenous knowledge and Indigenous relationality philosophy , 73 are Knowledge translation plans include sharing customized feedback on network structure and KT barriers/facilitators and strategies through discussion with formal research and family networks and represented organizations, as well as any new partners, to facilitate awareness and use of the study’s findings. Our partners have expressed interest in the results to inform the selection and prioritization of KT strategies to support network sustainability as part of their legacy planning. Results will be shared through written reports, academic publications, infographics explaining the network maps, and meetings with these entities’ KT support personnel, executive teams, and general membership as appropriate. We aim to create a venue for continued collaboration between individuals and organizations in Canada with an interest in KT within CD&R. We will document our decolonization journey throughout the study and will share our learnings and any further protocol changes in the spirit of transparency and as part of our KT efforts.While we have a primary focus on advancing science in the field of KT, this project will also have significant results for CD&R, by characterizing for the first time the national patterns of connections among its multiple participant groups. This insight is important for understanding the dynamics of KT at regional and national levels and offers a baseline assessment of its gaps and strengths. These findings, and the range of perspectives on factors hindering and supporting networks, will enable the development of a practical framework to design targeted interventions to enhance conventional and network-based KT processes and outcomes across Canada. We are excited to test the effectiveness of these network interventions to strengthen KT networks in future research. The integration of a network perspective offers an innovative approach to tailoring KT interventions, through a focus on the socially driven nature of KT, as a process facilitated by and carried out by and between people. These strategies will be employed proactively in partnership with our formal network collaborators to support long-term sustainability of the important gains they have generated within CD&R. Augmenting Canada’s capacity for KT at the local, provincial, and national levels is important to help children achieve the best health outcomes possible through timely access to the most effective healthcare.We close with words from one of our parent partners: “In my work as a parent in research, and in discussions with other parents, I am keenly aware of the frustration that comes from the time it takes to get good research into practice. I am passionate about this project as a preliminary step in understanding and addressing that gap.”Additional file 1 STROBE Statement—Checklist of items that should be included in reports of cross-sectional studies.


The number of cancer survivors are increasing and so are the oral toxicities from cancer therapy. Most patients receiving treatment for cancer develop some form of oral adverse events including, but not limited to, mucositis, opportunistic infections, dry mouth, and/or osteonecrosis of the jaw. One of the most common complications from head and neck cancer radiation therapy is salivary gland dysfunction (SGD). SGD is an umbrella term that includes the subjective sensation of dry mouth (xerostomia) and hyposalivation . Dry mouth in cancer patients may lead to functional defects , increase the risk of dental caries and oral candidiasis, and can have a negative effect on the nutritional and psychological status of the patients. The aim of this mini review was to summarize the current criteria for diagnosis and management of SGD associated with cancer treatment. Cancer survival rates continues to increase and by 2040, it is estimated that there will be 26 million cancer survivors in the United States –3. CanceSGD is one of the most frequent side effects from cancer therapy . Dry mouSGD has been defined as “any alteration in the qualitative or quantitative output of saliva caused by an increase (hyperfunction) or decrease (hypofunction) in salivary output” .Hyposalivation is assessed by measuring stimulated and unstimulated salivary flow and at times, by individual major gland secretion. Hyposalivation is defined as a resting (unstimulated) whole saliva flow rate of ≤ 0.1 mL/min and/or a stimulated whole saliva flow rate of ≤ 0.5 mL/min , 9. CommXerostomia in cancer patients is assessed by patient reported outcomes (PROs)  or by practitioner reported outcomes , where in addition to the patient symptoms, the unstimulated saliva is measured  12, 13], 1312, 1Excessive salivation is rare, and may occur in cancer patients due to dysphagia, odynophagia, malignancy, or local oral irritation. Non-pharmacologic treatment varies from functional dysphagia therapy to neurosensory approaches. Pharmacologic treatment aims to reduce salivary flow and includes several agents such as glycopyrrolate, scopolamine, atropine, benztropine, and botulinum toxin injection into the salivary glands . MucolytDry mouth is one of the most common and dismal effects of radiation therapy (RT) to the head and neck cancer patients. Salivary gland tissue, in particular acinar cells of the serous glands (parotid), is sensitive to RT with permanent salivary gland damage in patients receiving cumulative doses > 30 Gy . RT can Preventive strategies of salivary gland hypofunction and dry mouth secondary to RT have focused on the preservation of salivary gland function, primarily the parotid glands, by new advances in radiation techniques, including the appearance and optimizing of 3D treatment planning, conformal radiation techniques, and intensity-modified radiotherapy (IMRT) , 21. RecTreatment of salivary gland hypofunction secondary to RT includes systemic parasympathomimetic agents with muscarinic action (pilocarpine HCl and cevimeline) . PilocarChronic graft vs.-host-disease (cGVHD) is a complication that may occur in 30–70% of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) . Oral cGThe effects of salivary gland hypofunction in these patients include rampant decay and recurrent oral candidiasis, especially if there is ongoing topical corticosteroid therapy for management of mucosal cGVHD, which suppresses mucosal immunity. An additional feature of oral cGVHD is the development of recurrent superficial mucoceles, suggesting that the underlying inflammation may be secondary to generalized mucosal involvement or because of direct salivary gland tissue targeting , 40.Chemotherapy induced dry mouth is prevalent in 10–80% of patients undergoing treatment, regardless of the type of cancer . The onsChanges in salivary gland function can be caused by several chemotherapeutic agents including doxorubicin, cyclophosphamide, fluorouracil, methotrexate, and vinblastine . Some caClinical presentation of chemotherapy induced SGD is variable, with some patients presenting with dry mucous membranes of varying severity, while others complaining of excessive salivation with drooling because of dysphagia or odynophagia. As opposed to RT-induced dry mouth, chemotherapy-related dry mouth is typically reversible. Therefore, management is palliative in nature and aims to relieve the temporary symptoms that manifest during treatment. This includes lifestyle modifications, use of saliva substitutes and mucosal lubricants, and short-term use of non-pharmacologic stimuli  , 44. AcuImmune checkpoint inhibitors (ICIs) have proven to be an effective treatment option for patients with many forms of advanced cancers by preventing cancer cell evasion mechanisms through the suppression of major immune regulatory pathways, such as PD-1/PD-L1 and CTLA-4 . The intPatient who develops dry mouth secondary to cancer therapy are at risk of developing dental caries. A literature review conducted by the Oral Care Study Group of the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology (MASCC/ISOO) which included 37 head and neck cancer trials, showed that the prevalence of dental caries in head and neck cancer patients treated with radiation was 24% (4 studies) and 21% respectively (9 studies) for those receiving chemoradiation . PatientPatients with salivary gland hypofunction may develop a secondary Candida infection in 39–62% of cases while receiving cancer treatment , 55 AlthIn cancer patients an average loss of 8 to 10% of body weight is common, even with early nutritional support . SGD canIndividuals suffering from cancer are at high risk of experiencing major depressive episodes throughout treatment, although this risk appears to be especially prominent within the first year of diagnosis. The estimated prevalence of anxiety and depression among cancer survivors is 17.9% and 11.6%, respectively .et al. further looked at selective norepinephrine reuptake inhibitors (SNRIs) and found that they significantly increased the risk of developing dry mouth when compared to SSRIs [As part of the treatment regimen the most commonly prescribed medications include tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). While both classes of medications have been linked to hyposalivation, in a study done on parotid salivary flow rates, TCAs exhibited a 58% reduction in flow compared to 32% with SSRIs . A meta-to SSRIs . These dto SSRIs .SGD is a common and debilitating complication that affects almost two-thirds of patients undergoing cancer treatment. Early diagnosis and management may result in decreased morbidity associated with SGD and improve well-being. Dental specialists are integral part of the cancer treatment team, and provide comprehensive education, supportive care, and the therapy of SGD related to cancer treatment. The current management approach of SGD is mostly palliative and aims to increase the amount of saliva and minimize the risk of secondary effects such as dental caries, dysgeusia and fungal infections.Patients with SGD from cancer therapy should be followed by their dentist regularly for regular checkups and prescribed sodium fluoride 1.1% gel or toothpaste to reduce the risk of rampant decays.In summary, SGD therapy is an important component of care prior to and during cancer therapy and amongst survivors. A multi-disciplinary approach is fundamental in the successful management of this complication in oncology and bone marrow transplant patients.AVM is participated in conceptualization of the work, data collection and summary, and wrote the mini review. GP participated in data collection and preparation of the manuscript. VS provided feedback on the manuscript. CS participated as an advisor and in the manuscript preparation. AV supervised the work, participated in the analysis of the data, and manuscript preparation. All authors approved the final version of the manuscript.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In this study, nine types of carbon reduction measures were adopted to achieve carbon neutrality in the region, among which the highest carbon reduction was achieved by biomass energy measures, accounting for 29% of the total carbon reduction of 33,745.27 T. The objective of this study is to accurately and quantitatively assess the carbon targets of urban spaces at different scales and adopt effective measures to achieve carbon neutrality.Much of the research on climate change has focused on carbon reduction in cities or countries. However, more attention needs to be paid to how to achieve carbon neutrality in the urban design and planning stage, and the lack of quantitative analysis of carbon related to urban space makes it difficult to locate urban space and provide direct guidance for urban planning and design. This study proposed three optimization paths to achieve carbon neutrality in multi-scale urban building clusters. Firstly, we reconstructed the quantitative calculation system of urban building communities with the goal of carbon neutrality; secondly, we screened the carbon source reduction and carbon sink interventions that are suitable for multi-scale urban building communities; finally, we constructed a carbon emission and carbon sink calculation system of planning and design schemes based on the layout of relevant elements of planning and design schemes with a grid cell of 100 × 100 m. In practice, there was a gap of about 115,000 tons of CO Carbon neutrality is achieved by applying carbon reduction related technologies to offset greenhouse gases generated by human activities within a specific period, and the built environment of cities is a major source of greenhouse gases. Therefore, urban planning and design with a carbon-neutral perspective, as well as the layout of effective carbon reduction schemes in the urban design phase, are crucial to sustainable urban development . In addi2 estimation, some scholars use empirical CO2 equations and carbon assessment software to measure the values and impacts of urban CO2. Others precisely assess the current CO2 impact factors with neighborhoods or streets as the study unit. Moreover, some studies include carbon sink or source reduction in the study of carbon reduction measures.During the urban planning process, urban planners and governments set policy and strategic goals, and these decisions and plans significantly affect the energy efficiency and carbon emissions of cities. However, there need to be more quantitative indicators and intervention strategies for locatable spaces to assist urban planners and policymakers in achieving urban low-carbon development goals at the planning and design stages. In the existing studies on urban CO2 emissions from urban residents in China as urban carbon emissions. Chao Liu (2017) constructs a model to calculate carbon emissions  and carbon sinks to explore the relevance of integrated urban carbon dioxide (CO2) emission models and CO2 mitigation plans at the new urban scale [The empirical formula of carbon emission is constructed by studying the influence of urban elements on carbon emission. Urban features mainly include buildings, transportation and citizens. Empirical formulas are usually divided into two types: carbon emission calculations and carbon reduction calculations . For exaan scale . Congronan scale . S. Zubean scale . Both ofan scale . Street-o Liu 201 construcan scale . Baghi  pointed out that urban carbon source carbon reduction mainly refers to the curbing effect of renewable energy on carbon emission intensity. This study also verified that for every 1% of renewable energy development, carbon emission intensity decreases by 0.028–0.043% . However20 pointe2 assessment methods for urban design scenarios compared to traditional formula calculations, such as the City Energy Analyst (CEA) architecture evaluation system developed by ETH Zurich. CEA integrated urban planning, thinking and energy systems technology in a comprehensive evaluation system and realized the adjustment of urban design scenarios and the calculation of urban carbon emissions to design plans and calculate energy infrastructure layouts as well as urban carbon emissions. However, most platforms are based on sensor-based monitoring of carbon emission and sink and present the data as a platform, which only applies to some cities. Trimble’s Tekla 2022, Sefaira, RIB’s iTWO 4.0 and GBSWARE’s CEEB 2023 allow for the real-time modification of building design materials and structures, carbon emission calculations and comparative calculations of multiple building design options. Systems (including control strategies), the integration of local energy resources and the intervention of regional energy systems. It also allows for urban form modifications such as new zoning, and changes in occupancy and building type, allowing for real-time carbon evaluation calculations. The Tupau carbon monitoring platform developed by Xiamen Tupau Software aims to detect carbon emissions in real time. In addition, some carbon assessment software also incorporates models of carbon interventions, such as the carbon emission measurement system of the China Institute of Planning with regional boundary selection and carbon reduction measures selection, thus performing carbon evaluation. However, most of the existing carbon assessment platforms are limited to the visualization of urban carbon emission, without considering the realization path to reach the total demand of urban carbon sink and carbon reduction and without considering the comprehensiveness of interventions and the combination scenarios of multiple approaches To reconstruct a carbon-neutral assessment system at the scale of urban building clusters;(2)To realize a portfolio of interventions for urban planning with the goal of carbon neutrality;(3)2 assessment and interventions by concretely locating the assessment results and intervention design results in urban spaces.To provide practical theoretical support for urban small-scale COGiven the above, the objectives of this study are: Fine assessment of carbon emission and carbon sink in 100m*100m urban building complex space, which is convenient for planners and decision-makers to compare carbon indicators in different scales of space visually.Take more comprehensive carbon reduction measures to achieve the goal of carbon neutrality in urban building cluster area and locate the specific space, and put forward refined suggestions for the planning and implementation of locating.With the perspective of carbon neutrality, we make suggestions on industrial transformation, energy use types, ecological space layout and green building integration.The innovation points of this paper are:Lihu Future City is located in the middle of Wuxi City, Jiangsu Province, China. The core area of Lihu Future City is about 3.7 square kilometres, located at 120°14′8″–120°15′32″ E and 31°31′6″–31°32′32″ N. Lihu Future City will carry the science and innovation exchange hub functions of the city’s science and innovation space, landscape tourism and leisure around Taihu Lake. Therefore, it is vital to achieving the goal of carbon neutrality in the future city of Lihu to construct the new town .This paper collected the traffic network, land use, building-related and functional zoning data of the first round of preliminary plan of Lihu Future City. All data came from the “Wuxi Lihu Future City Master Plan”. The road network includes main roads, secondary roads, branch roads, internal access roads, etc. The land use includes residential-led composite land, public service facility-led combined land, commercial business and residential-led composite land, commercial business-led composite land, technology R&D-led composite land, parks, green areas and functional zoning. The land use includes residential-led complex land, public service facility-led complex land, commercial and residential-led complex land, commercial and commercial-led complex land, technology R&D-led complex land, park green space, square land, development reserve land and water area. Building-related data include building height data, building area data and building profile data. There are seven types of functional zoning data: central green axis, TOD complex, commercial and residential complex, waterfront commercial, science and technology-led public, science and technology-led home and public services .The classification of assessment factors in the calculation system needs to be generalized to spatial units at any scale. In addition, the calculation modules and modalities can be applied to spatial elements in spatial units as well as interventions. The design of intervention measures does not only stop at strategy formulation but also needs to estimate the carbon reduction or sink potential of carbon intervention measures in a quantitative way and to consider the carbon intervention methods that can be carried out for the whole category and the whole element carrier on the basis of quantitative assessment, such as to consider different combination scenarios of both carbon reduction and carbon sink measures in a comprehensive way. The assessment results and quantitative intervention design are located in the smallest standard spatial unit so that the assessment results and intervention results can be seen visually in order to provide intuitive and effective design strategies for different urban scale planning and design.To achieve carbon neutrality at different scales of urban clusters in the design process, the calculation system of carbon assessment and interventions is reconstructed: The units and calculation methods of the traditional index evaluation system are not uniform and cannot be evaluated for all cities . BuildinThe building community scale aggregates the carbon information of spatial carriers, such as buildings, building operations and traffic flows between clusters. Accordingly, this study summarized urban carbon sources and organized the methods of urban carbon emissions calculation, and divided urban carbon sources into three major categories of urban carbon emissions. The first type of urban carbon emissions is carbon emissions generated from human use, mainly from building maintenance and operation, such as carbon emissions generated from maintenance and energy consumption of the building itself, e.g., air conditioning, ventilation, heating, lighting and elevator operation. The second type of urban carbon emissions is carbon emissions generated from industrial energy consumption, mainly from the building due to commercial use. The third category is carbon emission from travel, mainly from building clusters and carbon emission from transportation service facilities such as the subway and buses between buildings and external locations. Based on the above carbon emission classification method, we established an integrated framework of carbon emission and carbon sink calculation methods to evaluate carbon emission and carbon sink of the urban design scheme and built a carbon neutral evaluation system for urban design schemes . At the According to the three types of urban carbon sources mentioned above, three types of carbon emission studies were included in this study, which was building carbon emissions from human use  and biodigesters (biomass fuel) . Solar pian Plan . Thus, o2 emissions of a country (region) more scientifically than carbon emissions [In terms of carbon technology in the construction industry structure, carbon emission intensity (CI) refers to carbon emissions per unit GDP, which can reflect the actual economic development and COmissions . Industrmissions . From thmissions ,43,44. Tmissions . Therefomissions .In terms of greenland carbon sink system, the key to carbon reduction was to increase the area of green space scale and consider the carbon sink efficiency of plant types. For example, one hectare (2.5 acres) of forest can absorb 1.5 to 30 metric tons (1.6 to 33 tons) of carbon dioxide per year, but the carbon sink of the same area of space grass is one per cent or even one thousand of that of trees. Therefore, the construction of terrestrial green space ecosystems should give priority to the planting technology of trees or unique plants that can efficiently carry out carbon sink or the optimization technology of the original vegetation. In addition, the choice of carbon reduction technology for building clusters can consider three-dimensional greening and rooftop greening technology. The increase in three-dimensional greening and rooftop greening in densely built areas is relatively limited in terms of the increase in total carbon sink. However, a rough estimate of the potential area range of greenery on the facade (excluding windows) is twice the ground footprint of buildings within the city. In comparison with green roofs, an even more tremendous potential to realize the environmental benefits of vegetated building surfaces with facade greening. VGS offer multiple benefits as innovative components of urban design and increased greenery in built environments lacking green areas . The carThe assessment model should divide the urban design scheme into a standardized calculation grid to accurately assess the city carbon emission and carbon sink values at the scale of urban building clusters. The Inverse distance weighted method (IDW) can predict the overall spatial distribution and has higher prediction accuracy with limited sample points than other difference methods . Based o2, the total carbon reduction was about a mere 0.1 million tons of CO2, and there was a gap of about 115,000 tons of CO2 from the carbon-neutral target. It was mainly distributed in the Xiajiabian Station TOD Complex, which accounted for 26% of the total carbon emission, and the Fisherman’s Island TOD Complex, which accounted for 25% of the total carbon emission, followed by industrial and Charming Creative Neighborhood, each accounting for 6% and 4% of total carbon emissions. The central carbon sink areas were concentrated on the waterfront shoreline accounting for 48% of the whole carbon sink, and the central garden axis accounted for 27% of the whole carbon sink (Based on the existing ecological foundation layout scheme, the total carbon sink of Lihu Future City was about 116,000 tons of CObon sink .The top 5 most urgent carbon reduction 100 × 100 m spaces of Lihu Future City were distributed in the Xiajiabian Station TOD Complex area and the Fisherman’s Island TOD Complex. Within the area of the Xiajiabian Station TOD Complex, the space most urgently in need of carbon reduction is space 1, which has a carbon emission of approximately 5000 tons, accounting for about 16% a. WithinIn the layout of interventions in Lihu Future City, based on the base site attributes, current conditions of building density, and a large carbon neutral gap, nine types of carbon reduction measures were considered in this study, namely dense forest planting, three-dimensional greening technology, green roof system, solar panel system, LED street lights, biodigester, conversion of intensive commercial areas into research-led industries and upgrading industrial enterprises into research pilot industries .The carbon sink measures were mainly distributed in the Xiajiabian Station TOD complex, the charming creative block, the lakeside green corridor, the Fisherman’s Island TOD complex, the three-dimensional composite landscape green axis and other open space areas to increase partnership dense forest planting. The carbon sink potential reached about 16,000 tons, accounting for about 14% of total carbon reduction. The increase in three-dimensional greening measures in the façade space of buildings across the region and the growth of green roof technology, comprehensive carbon sink and carbon reduction potential in the roof space of buildings across the region reached 15,500 tons, accounting for about 14% of the whole carbon reduction. The solar panel power supply technology, ground-source heat pump heating technology and bio-digester heating technology for nearly the whole area of the building, and the arrangement of LED street light sets on Wang Shan Road, Yinxiu Road, Shuanghong Road, Wang Hu Road, Huanhu Road and Hongqiao Road, reduced carbon by a total of 54,000 tons, accounting for 47% of the whole carbon reduction, and were the most effective types of carbon reduction measures. By upgrading industrial to scientific experimental industries and converting waterfront commercial dense areas to scientific experimental industries, a total of 3000 tons of carbon was reduced, accounting for 25% of the whole carbon reduction. Thus, based on the layout of the nine types of carbon reduction measures, the design scheme of Lihu Future City could reach the carbon-neutral target .Studies have been conducted to investigate the relationship between the national level, city level and individual elements of the city, such as separate buildings and transportation, and carbon emissions. However, more research needs to be carried out to calculate and comprehensively lay out carbon reduction and sink measures in advance at the urban planning stage with carbon neutrality targets and to locate specific spaces. However, it is crucial to lay out carbon source reduction and carbon sink measures in advance in the planning and design stage. For example, as we can see in the above project application, if we need to achieve the city’s carbon neutrality target, more than 50% of the building facades need to install the three-dimensional greening system, and more than 70% of the building roofs need to lay out green roofs .In the planning and design stage, carbon indicators are quantitatively calculated for each element of the city. The division of fixed calculation units allows designers to consider carbon metrics at different scales in the design process and thus obtain a specific carbon-carbon neutral gap. After receiving the carbon-neutral opening, it is easier for designers to check the interaction between carbon targets and building design, industrial layout, transportation planning, etc., through iterative design solutions. This iterative process allows urban planners to deploy carbon reduction and sink measures in detail at the design stage. By differing from existing carbon prospective studies, our study locates specific design elements and flexible small-scale units of carbon emissions in urban design to support urban planners in the design process to achieve carbon neutrality goals. For example, in the intervention mentioned above layout of carbon reduction measures in Lihu Future City, the layout of clean energy carbon reduction can lead to a sharp decrease in urban carbon emissions . Still, 2/year and 195.57 €/m2/year, respectively [2/year [This paper only considered one scenario in which the new city achieves the carbon neutrality goal. It is worth exploring whether the new town has a more significant potential for carbon reduction. In our future research, we will investigate whether there is potential for larger-scale carbon reduction targets based on the city’s characteristics and current situations. In addition, the choice of carbon reduction interventions should also consider their cost. For example, the average total costs of installation, operation and maintenance for green roof and 3D green system installations were 103.28 €/mectively , while t [2/year . TherefoThe dimensions of carbon assessment in existing studies are primarily urban scale and urban macro-level elements, without careful consideration of carbon emission values generated by human use, industrial types, transportation, etc., in building complexes. Interventions are mostly building or energy-specific studies, lacking comprehensiveness and the assessment of the benefits of interventions needs to consider the effects of urban building clusters. The carbon assessment results and interventions cannot be localized in urban spaces on a small scale and cannot achieve multi-scale spatial carbon neutrality assessment. Based on the above gaps and challenges, we aimed to carbon assess multi-scale urban spaces and to lay out carbon reduction interventions in advance at the urban design stage to achieve the goal of carbon neutrality in urban building clusters.To achieve our research objectives, in this paper, we proposed three optimization methods and used Lihu Future City as our practice case. Firstly, the assessment and intervention system was reconstructed to be able to be used to assess multi-scale spatial carbon indicators; secondly, on this basis, carbon reduction measures suitable for multi-scale space were summarized and divided into four categories: building energy saving and emission reduction technologies, building industrial structure carbon reduction methods, infrastructure carbon reduction technologies and green space carbon sink systems for building clusters, and their specific categories and calculation methods were detailed, respectively, and finally, the specific intervention measures were matched with urban design elements match, and established the “technology-spatial” intervention design model; thirdly, established the unit calculation method, and placed the assessment results and intervention results specifically in the 100 × 100 m urban space unit. Finally, we took the Lihu Future City as a practical example for explaining how to apply the three optimal paths to achieve the carbon neutrality goals of different scales of urban design. For urban planning and design, it is of great significance to dynamically assess the carbon emission and carbon sink of urban schemes during the design process. It is also crucial to make comprehensive carbon reduction and carbon sink interventions for urban design elements based on the assessment data results and to obtain the evolution trend of carbon emission and carbon sink data in real-time for the carbon neutral target.We reconstructed the computational model and the quantitative intervention system in order to apply to the quantification of carbon indicators in multi-scale urban design.We more comprehensively considered carbon reduction measures that can be applied to urban design elements.We specifically located the interventions in the 100 × 100 m urban space and design elements, thus proposing the most direct and effective recommendations for carbon neutrality in urban design schemes.This paper has three contributions: 2 detection data and potential quantitative data for the intervention, it is not possible to assess the accuracy of the relevant data and coefficients presented. In future studies, we will calibrate the parameters involved in the method with measured data to obtain more accurate results.Due to the lack of field validation of the CO


Consequently, present screening tools and interventions for EDs lack adaptation and translation to neurodivergent populations  is a lifelong neurodevelopmental condition characterized by anomalies in two domains: social interactions and communication, and restricted/repetitive patterns of behaviors  among autistic individuals, including: (i) body self-schema, (ii) cognitive biases, (iii) compensatory behaviors, and (iv) psychological risk factors for developing and/or maintaining disordered body and eating pathology  consists of behaviors denoting an underlying neurobiological endophenotype identified within the diagnostic profile for autism : the cognitive ability to compensate for, and overcome, maladaptive AP features through learning and carrying out adaptive responses  AP acts as a “first-hit” for precipitating ED-like behavior , as an individual reports differences in cognitive and body-sensory processes, such as altered interoceptive awareness . For instance, autistic individuals report differing social interaction and communication abilities (the AP) and, when met with the lower ability to adaptively learn from social interactions (lower CC), present secondary disordered body and eating pathology as a maladaptive resource  within this population. We hypothesize that autistic individuals will understand and/or experience theoretical constructs, such as body dissatisfaction and internalization, differently to neurotypical groups. Taken together, this suggests testing the applicability and acceptability of existing models using a mixed methods design. We therefore propose a current, actionable, and accessible framework which enhances inclusive ED theory and practice and follows guidelines for conducting research with the autism community (see Gowen et al., development should be carried out prior to systematically developing an intervention. Thus, the third stage involves identifying or developing theory through examining modeling processes and outcomes using structural equation modeling (e.g., Oh et al., As a contextual factor, researchers may test the Acceptance Model of Intuitive Eating (Augustus-Horvath and Tylka, The autistic experience of EDs receives little theoretical or empirical investigation, despite autistic individuals presenting poorer and long-enduring outcomes (Westwood and Tchanturia, PL and LC contributed to writing and editing the manuscript. Both authors contributed to the article and approved the submitted version.PL was employed by the British Association for Counselling and Psychotherapists. The remaining author 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Epilepsy and related psychiatric comorbidities are major public health problems affecting many millions of people across the globe. Complementary and alternative medicine (CAM) has increasingly become a viable option for treating epilepsy and related psychiatric conditions. Due to this, the advanced understanding of CAMs for epilepsy is particularly expected and valuable.Complementary/Alternative Therapies for Epilepsy and Related Psychiatric Comorbidities,” was initiated on June 4th 2020, with a dedicated team of handling editors to facilitate the timely peer-review and publication of relevant manuscripts. Within about 1 year and 9 months (from June 4th 2020 to February 28th 2022), 15 manuscripts were submitted, of which six were published, including two reviews and four original research contributions from 44 prominent scientists in the field. The content of each of these articles is summarized below.The special topic, entitled “Girgis et al. explored the use of CAM among patients with epilepsy and diabetes mellitus using a self-developed questionnaire. They found the ratio of CAM use was 9.7% in the overall study population (127 patients with epilepsy and 100 patients with diabetes mellitus). Among patients with epilepsy, the ratio of CAM use was less than that among diabetic patients; 7.9 and 12%, respectively. Of note, the most commonly used CAM here are capable of modulating cytochrome P450 enzymes and hence may result in drug interactions and adverse drug reactions. Thus, Girgis et al. further suggest that educating patients and including a clinical pharmacist specialized in the CAM field in their treatment advisory team is essential.A Hungarian study by Synedrella nodiflora is a weed that grows abundantly in Ghana mainly in water-logged and shady areas. Extracts of Synedrella nodiflora (SNE) are used traditionally for the management of epilepsy in the West African sub-region, including Ghana. Amoateng et al. from Ghana focused on the neuronal basis of anticonvulsant effects of SNE. They found SNE not only concentration-dependently depressed excitatory synaptic transmission but also suppressed in vitro seizure activities induced by zero Mg2+ and high K+ -containing artificial cerebrospinal fluid in the CA1 region of the hippocampus. This preliminary study provides cellular evidence in support of the use of Synedrella nodiflora in traditional practice to manage convulsions.Lin and Hsieh summarized the clinical use and mechanisms, which indicate different herbs can be combined to increase antiepileptic effects through various mechanisms, including anti-inflammation, antioxidation, enhancement of GABAergic inhibition, modulation of NMDA channels and sodium channel, and neuroprotection. Besides, they also provide evidence for the efficacy of medical diet therapy. Of note, adequate experimental evidence and randomized controlled clinical trials are still required to confirm the antiepileptic effects of most Chinese herbal medicine.Chinese herbal medicine has a long history of use for treating epilepsy. A review from Ligusticum chuanxiong Hort. A study by Jiang et al. showed that the early application of TMP, but not in the late period, alleviates neuropsychiatric comorbidities (anxiety and depression) and increases the hippocampal BDNF/ERK expression in two different neurological diseases mouse model, including 6 Hz corneal rapid kindling model of epilepsy and Complete Freund's adjuvant (CFA) model of chronic pain. This preclinical experimental study emphasizes the importance of early treatment of psychiatric comorbidities in both epilepsy and chronic pain.Tetramethylpyrazine (TMP) is the main activity compound of Chinese herbal medicine Xiao et al. analyzed routinely acquired functional magnetic resonance imaging (fMRI) data of adults with refractory focal epilepsy who had clinical language fMRI scans as part of their pre-surgical evaluation at the National Hospital for Neurology and Neurosurgery (NHNN), London, United Kingdom, between January 2010 and January 2017. By comparing the effects of different drug loads of anti-seizure medications (ASM) on the verbal fluency fMRI in patients, they mainly found: (1) ASMs are associated with altered cognitive fMRI activation patterns during verbal fluency, especially for drugs with severe cognitive side effects (n = 119 for both moderate and severe ASMs group); (2) ASMs with moderate cognitive side effects act greater effect on fMRI activations when given in polytherapy. Thus, this study highlights the cognitive effects of adding ASMs and a high drug load of ASM. Similar to western ASMs, these phenomena may also exist in other CAMs for epilepsy, which needs to be further studied.The retrospective study by Sadanandan et al. explores the safety, efficacy, and potential mechanisms of stem cell therapy as a novel treatment for neurological and neuropsychiatric symptoms of epilepsy. Based on current preclinical findings and some clinical trials, stem cell therapy seems to benefit epilepsy and related psychiatric comorbidities. The potential mechanisms mainly include ameliorating aberrant neuronal circuitry, restoring deplete GABAergic inhibitory neurons, releasing neurotrophic factors, maintaining adenosine homeostasis, and exerting neuroprotective effects. Further preclinical investigations are still warranted to test the safety and efficacy of stem cell therapy in clinically relevant models of epilepsy; and the optimal stem cell dosage, delivery method, and timing of transplantation remain unclear.Except for these above drug related studies, a review of Overall, this special topic provides an insight into the role of CAMs on epilepsy and related psychiatric comorbidities. These studies may be beneficial both in understanding how different pathophysiological processes contribute to epilepsy (and related psychiatric comorbidities) and in offering new treatment options. Of note, caution needs to be emphasized as some of the published manuscripts may have different methods of analysis, different procedures for presenting their data, or differences in interpretation of certain observations among the many different perspectives. We hope that our special topic provides useful information that will inspire other researchers to further this exciting research area.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Most studies demonstrate that exercise is not only safe for cancer patients undergoing treatment, but also highly beneficial for physical and mental health during and after cancer treatment.,+ breast cancer,,JACC: CardioOncology, Peck et al+ breast cancer. MVPA and outcomes were measured at 6 time points over the course of approximately 1 year: near the time of diagnosis before treatment initiation; following anthracyclines, but before initiating trastuzumab; every 3 months during trastuzumab treatment; and at the completion of trastuzumab treatment. They found that higher MVPA was associated with better quality of life, measures of cardiac function, and post-treatment CRF. The findings around cardiac function are of particular importance, given the documented negative effects of anthracyclines and trastuzumab on cardiac function for women with HER2+ breast cancer.,+ breast cancer patients receiving sequential anthracyclines and trastuzumab.The benefits of exercise during breast cancer treatment are among the most extensively studied of any cancer type. Studies in breast and other cancer patients have demonstrated the benefits of exercise in improving cardiorespiratory fitness (CRF) in cancer patients during treatment.These findings are consistent with other prior studies of breast cancer patients and support the continued need to promote exercise as part of oncology care, but there are some limitations of this study that should be acknowledged. Many of these limitations were acknowledged by the investigators including the small sample size and use of self-reported MVPA data. The investigators stated that pre-existing cardiovascular disease risk factors contribute to poor cardiac outcomes, but they had a limited measure of important potential confounders such as prediagnosis levels of alcohol, diet quality, and excess body fatness. The investigators were also unable to explore the role of prediagnosis MVPA, which may be a limitation given the documented association between MVPA before diagnosis and improved cardiovascular disease outcomes among breast cancer survivors.,Future studies addressing these limitations will be important and should, in particular, include: 1) measures of quality of life and CRF before treatment initiation to examine treatment-related changes; and 2) more detailed measures of physical activity measured before and during treatment. Although the Godin physical activity survey instrument used in the present study has shown moderate comparability with other self-reported measures of MVPA, the lack of detail on MVPA type, strength training, and sedentary time prevent analyses on of the roles of these distinct domains. As cancer survivor-specific recommendations for physical activity include aerobic exercise, resistance training, or a combination of both for expected patient benefits, future studies relying on self-report should consider newer, more detailed, validated survey instruments that capture all of these activity domains.+ breast cancer patients receiving anthracyclines followed by trastuzumab. Given the well-established benefits of exercise on physical and mental health, various patient-reported outcomes, improved survival, and other endpoints among cancer survivors, and the mounting evidence for improving CRF during treatment, guidelines are increasingly calling for the incorporation of exercise into oncology care.,,This study reinforces the benefits of MVPA during treatment for breast cancer, here particularly for HER2The authors have reported that they have no relationships relevant to the contents of this paper to disclose.


A scientific framework on exposure science will boost the multiuse of exposure knowledge across EU chemicals-related policies and improve risk assessment, risk management and communication across EU safety, security and sustainability domains.To stimulate public and private actors to align and strengthen the cross-policy adoption of exposure assessment data, methods and tools across EU legislation.By mapping and analysing the EU regulatory landscape making use of exposure information, policy and research challenges and key areas of action are identified and translated into opportunities enhancing policy and scientific efficiency.Identified key areas of actions are to develop a common scientific exposure assessment framework, supported by baseline acceptance criteria and a shared knowledge base enhancing exchangeability and acceptability of exposure knowledge within and across EU chemicals-related policies. Furthermore, such framework will improve communication and management across EU chemical safety, security and sustainability policies comprising sourcing, manufacturing and global trade of goods and waste management. In support of building such a common framework and its effective use in policy and industry, exposure science innovation needs to be better embedded along the whole policymaking cycle, and be integrated into companies’ safety and sustainability management systems. This will help to systemically improve regulatory risk management practices.This paper constitutes an important step towards the implementation of the EU Green Deal and its underlying policy strategies, such as the Chemicals Strategy for Sustainability. Since the inception of the European Union (EU) chemical legislation in the 1960s, the contribution of exposure science to EU legislation has evolved from providing ex-post evidence to enabling prospective identification and control of chemical exposure and risks at workplaces, private homes, in food, human bodies and in environmental compartments. In addition to EU legislation, the role of exposure science is at present also recognised by international law  and global policy initiatives focusing on evaluating the safety, security and sustainability of chemicals , UN Sustainable Development Goals (SDGs) , World BAcross international legislation, exposure science is applied to protect against adverse health effects in humans and the environment from intended and unintended exposures covering the domains of health and safety, security and sustainability , 2, 5–10The current EU chemical’s legislative landscape targeting protection of human and environmental health comprises numerous legislations, each focussing on a specific domain or protection target comprising health, safety, security and sustainability. Thereby, chemical safety refers to measures and conditions to prevent adverse effects via releases of chemicals from products and processes. Chemical security, in contrast, refers to measures to prevent deliberate releases of chemicals with the goal to cause harm to humans, the environment and/or assets, and to mitigate related impacts . SustainWith respect to hazard identification and communication, common global horizontal frameworks have emerged, such as the UN Globally Harmonised System of Classification and Labelling of Chemical substances and mixtures –16, implAchieving the objectives of the EU Green Deal and related policy strategies requiring the EU to become climate neutral, waste-free and non-toxic by 2050, relies on the excellence of exposure science applied within current and future regulatory domains , 18, 19.At the EU level, initial efforts have focused on harmonising exposure assessment methods and tools within individual policy domains falling under the remit of specific European Agencies. This includes, for example, the European Food Safety Authority (EFSA), which developed harmonised models and tools related to food safety, animal, plant and ecological health , 27, conThe European Commission has recently completed a series of policy evaluations, including the REACH review , the fitOver the last 4 years, the ‘Europe Regional Chapter of the International Society of Exposure Science’ (ISES Europe) mobilised experts from different disciplines, policy domains and stakeholder groups to jointly prepare the foundation for a European Strategy on Exposure Science 2020–2030 , 48. As https://eur-lex.europa.eu/homepage.html) using combinations of ‘exposure’ with a topical term covering the domain of chemicals  resulting in 566 records with full-text regulations and directives of in-force legislation. Records were clustered into 16 policy domains relevant for chemicals management that make use of exposure information domains with varying numbers of records. To account for sub-regulations within a certain domain, the number of records within each domain was divided by the total number of records for all domains, thus creating a weighted domain size as illustrated in Fig. To create a snapshot of the current EU regulatory landscape with provisions making use of exposure information, search queries were made in EURLEX (n = 133) where exposure is relevant. The numbers are determined by the legal architecture of the decision-making processes in a certain policy area and reflect the regulatory density in the different domains.Figure Another way to analyse how exposure science feeds into scientific assessments across policy domains is to map EU legislation regulating chemicals against pathways of human and environmental exposure Fig. . LegislaThe sectorial nature of the current framework, and especially of product-level legislation, is partly motivated by the choice of the legislator to tailor risk management to policy-specific objectives and constraints. Accordingly, guidance and tools for exposure assessment have evolved sector-specifically, designed to meet the needs of specific policy domains. With that, the current policy framework appears fragmented rather than integrated. It also reflects a linear economy model, falling short of capturing multiple circularity processes .https://knowledge4policy.ec.europa.eu)) comprises policy design with impact assessment of policy options, adoption, implementation, application (enforcement and monitoring), evaluation and revision. At each phase, the Commission is guided by its policy design principles  authorisation under REACH . HoweverFrom the perspective of risk managers, one important limitation of HBM is the difficulty in tracing the internal exposure back to the sources, which in principle might hamper effective risk management measures. Reconstructing the sources and exposure pathways driving human exposure represents a huge challenge given the multitude of combinations of chemicals, products, and exposure pathways, which can be achieved through iterative processes of integrating HBM data with mechanistic models. However, a systematic solution requires an integrated model framework, which is currently missing.Examples have shown that chemicals, individually present at levels that do not adversely affect human health or the environment, may cause harm when they occur in combination with each other , 27. SevDespite recent scientific progress, regulatory adoption is still slow. Partly, this is due to technical issues, such as the lack of standardised methodologies, particularly regarding the selection of substance combinations to prioritise from a virtually infinite combination of exposures . PerhapsIn the longer term, the assessment of (unintended) environmental mixtures should be fully explored in the broader policy cycle. Recent related evaluations of EU policy could not take advantage of state-of-the-art methodologies to evaluate the overall effectiveness of chemical legislation. Evidence was limited to exposure and risk of a few single substances  . The nexProtection of human and environmental health against threats is a common objective across all chemical-related policies. Administrations with limited knowledge and capacity to manage chemicals present a risk to health and the environment but also a security threat. Intended chemical poisoning incidences using consumer products, food items and chemical weapons are examples of security threats , 96, 97.Existing chemical assessments are often focused on managing the risks posed by chemicals to human health, including occupational health and safety and environmental health. However, considered risks posed are often related to intended chemical use, accidental or negligent misuse of chemicals, while the scope of the assessments do currently not consider that risks may also be related to the intentional misuse of chemicals . Professhttp://www.pic.int/TheConvention/Chemicals/AnnexIIIChemicals). This allows exporters to claim an ‘incorrect’ use category to bypass rules, deliberately causing a potential risk.Globally, knowledge about the identification of chemicals on the market, their properties and their uses remains scattered , 23. TheSecurity-driven risk assessment needs to estimate the likelihood that hazardous substances are intentionally used to cause harm and the potential of eventual consequences of related incidents. Owing to the difficulty to establish the criteria against which risk should be assessed, there is hardly any guidance defining the scope of assessments or methodologies to systematically address this problem. Consequence-assessment models estimate health and environmental impacts based on toxic release and dispersion algorithms in potential combination with thermal radiation of chemical fires and explosions of vapour flammable clouds , and on International actors need to step up efforts to build a shared knowledge base and technical capacity to better identify and assess security threats and to improve coordination of risk management (prevention and preparedness). Interconnecting exposure science across health, safety and security regulatory domains comprise (i) chemical inventories and tools facilitating tracking of hazardous substances, materials and waste, (ii) exposure and risk assessment models for intended or unintended release  and (iii) chemical monitoring including timely environmental and human (bio)monitoring following emergencies.Box 3 An example of malicious trade and misuse of chemicalsCouncil Regulation (EC) No 428/2009 deals with the export of dual-use items, including substances used for both civilian and military purposes. Its infringement impacts both safety and security risks especially when it concerns a chemical substance with a dual-use (both civilian and military purposes) such as listed in Annex I of the Regulation. For example, sodium fluoride used in the fluoridation of drinking water and the production of toothpaste and phosphorus trichloride used in the production of organophosphate insecticides and glyphosate herbicides are two cases where misuse occurred. Sodium fluoride and phosphorus trichloride were employed to synthesise the deadly chemical weapon, sarin. In 2013, a UN investigation found clear and convincing evidence that sarin was used against civilians in the Ghouta area of Damascus, Syria on 21 August 2013 and promptly after the incident, blame was directed in part at the exporters of chemical compounds from the UK, and Germany .Creating a common scientific framework for exposure assessment interfacing EU chemical policies for environment, health, safety/risk and sustainability assessments, with particular emphasis on different exposure aspects, including common terminology, common principles and a suite of accepted data, methods and tools. EU Agencies are well placed to coordinate the development of an overarching scientific guidance describing how exposure data, models and knowledge fit together, considering terminologies, principles, methods and tools inside and outside EU. The main principles and core method described in REACH Annex I for CSA may provide a suitable starting point. Scientists and policy makers could jointly explore how existing scientific concepts and tools for integrated human and environmental exposure assessment could contribute to a comprehensive, modular scientific framework. Member States’ Competent Authorities, industry and the scientific community should contribute to identify opportunities for linking and consolidating approaches with the ambition to establish internationally recognised standards and tools , supporting and facilitating data sharing, harmonisation and coordinated research and development globally , 104. ImImproving the coordination of regulatory processes. A common scientific framework can facilitate risk assessors to coordinate their assessments. In addition, also requires strong commitment by policy actors to implement the mechanisms for policy integration and coordination. This includes improved coordination of assessments and management processes in horizontal chemicals legislation , product-level legislation and downstream legislation  and environmental quality control (water/air legislation). This has been recognised by the Commission in its commitment to implement the principle of ‘One Substance – One Assessment’ . Its sucIntegration of exposure knowledge into companies’ management systems is a prerequisite to ensure safety and sustainability of products and processes, and hence to securing  business. Responsibility put on industry is a paradigm commonly encountered in several pieces of chemical legislation; however, practical implementation is still lacking. Firstly, chemicals health and safety risk evaluation and management expertise and knowledge should be integrated across business functions  rather than being addressed as only a compliance task that can eventually even be outsourced . DesigniImproving the uptake of exposure science innovation into the policy cycle. Scientists and policy makers should take advantage of existing mechanisms , to ensure that policy developments benefit from innovations in exposure science. EU-funded research should better respond to the gaps in knowledge identified through policy evaluations . Following the adoption of the Chemicals Strategy for Sustainability , new mecHarmonising and utilising exposure science across health, safety and security policies. At the international level, improved access to global chemical inventories, exposure data, tools, guidance and knowledge enables stronger connections across scientific frameworks underpinning chemical health, safety and security policies . NationaThe present paper focuses on the specific requirements and actions relevant to increase the use exposure science and its regulatory uptake in Europe. To address the challenges outlined above, also with a view to their global dimension, we have identified five key areas for actions:At the EU level, chemical hazards and risks identified under policies dealing with direct and indirect security matters  No 428/2009 setting up a Community regime for the control of exports, transfer, brokering and transit of dual-use items) should be assessed and managed based on the same scientific principles used under chemical safety legislation. For example, risk assessments triggered for dual-use substances and major-accident risks involving dangerous substances usually focus on the short-term consequences of potential exposures following accidents  or incidences . Their scope should include the potential effects on human health of long-term exposures, in line with scientific guidance established for unintentional chemical accidents. Assessments should take advantage of data and tools available under chemical legislation . For certain identified hazards  and security risks , coordinated solutions to risk communication and management should be considered , 112–114The present ‘European Exposure Science Strategy 2020–2030’ is the starting point aimed at engaging all relevant European and global stakeholders to ensuring that its implementation will lead to an ultimately more efficient development, implementation and acceptance of exposure science and its underlying data, information and knowledge and related application across EU and global policy domains. All relevant stakeholders concerned are encouraged to align their strategic institutional and organisational objectives and targets embedding exposure science into current and future operating modes within a synergistic context and perspective. In the light of the absence of a thorough global analysis, both the process and outcome of the European exposure science strategy would be helpful for other geographical areas around the world boosting global policy uptake of exposure science embedded into global policy strategies and frameworks .


Infection Prevention and Control (IPC) measures are critical to the reduction in healthcare-associated infections, especially during pandemics, such as that of COVID-19. We conducted a hospital-based cross-sectional study in August 2021 at Connaught Hospital, Princess Christian Maternity Hospital and Ola During Children’s Hospital located in Freetown, Sierra Leone. We used the World Health Organization’s Infection Prevention and Control Assessment Framework Tool to assess the level of IPC compliance at these healthcare facilities. The overall IPC compliance score at Connaught Hospital was 323.5 of 800 points, 313.5 of 800 at Ola During Children’s Hospital, 281 of 800 at Princess Christian Maternity Hospital, implying a ‘Basic’ IPC compliance grade. These facilities had an IPC program, IPC committees and dedicated IPC focal persons. However, there were several challenges, including access to safe and clean water and insufficient quantities of face masks, examination gloves and aprons. Furthermore, there was no dedicated budget or no healthcare-associated infection (HAI) surveillance, and monitoring/audit of IPC practices were weak. These findings are of concern during the COVID-19 era, and there is an urgent need for both financial and technical support to address the gaps and challenges identified. Antimicrobial Resistance (AMR) is a silent pandemic and a global public health threat that the world is ill-prepared to respond to . In Low-The World Health Organization’s (WHO) global action plan to combat AMR has five strategic objectives, one of which is to reduce the incidence of infections through sanitation, hygiene and by instituting Infection Prevention and Control (IPC) measures ,4. EveryThe ongoing COVID-19 pandemic has had devastating global socioeconomic and health consequences. In response to the COVID-19 pandemic, healthcare facilities worldwide have stepped up their IPC efforts. IPC helps to reduce the spread of infections, including those caused by resistant microbes, and promotes health worker and patient safety. Importantly, good IPC standards also help to protect vulnerable frontline healthcare workers given the limited and effective treatment options against COVID-19 ,8,9. In Sierra Leone, the National Infection Prevention and Control Unit (NIPCU) was established in 2015 during the 2014–2016 Ebola outbreak to strengthen the country’s response to infectious disease outbreaks and provide a safe environment for patients, visitors and healthcare workers. NIPCU has been crucial in reducing the risk of COVID-19 transmission in healthcare facilities ,11. The Despite the establishment of NIPCU, data regarding the implementation of IPC programs in healthcare facilities in Sierra Leone are scarce. In 2019, with the support of WHO, the Ministry of Health of Sierra Leone (MOHS) conducted a baseline assessment of IPC standards in tertiary care hospitals using the Infection Prevention and Control Assessment Framework (IPCAF) tool. The average IPCAF assessment scores ranged from ‘Inadequate’ to ‘Basic’ grades of compliance, as detailed in A recent study conducted in three secondary hospitals in Sierra Leone reported a high rate (28.9%) of secondary infection among healthcare workers. The poor healthcare worker-to-patient ratio that is seen in all healthcare facilities in the country will increase the incidence of healthcare-associated infections such as COVID-19 among healthcare workers. Additionally, poor IPC programs at healthcare facilities will increase the risk of transmission of COVID-19 among healthcare workers . IdentifThis was a hospital-based cross-sectional study involving primary data collection.Sierra Leone is bordered by Guinea, Liberia and the Atlantic Ocean, and is divided into 16 districts with an estimated population of 8 million people with most (59%) of the population living in rural areas . In 2018Sierra Leone has 34 government hospitals and 1320 peripheral health units . The stuThe hospital was established in 1912 to provide healthcare services to freed slaves and named in memory of the Duke of Connaught. Today, the hospital is a tertiary government referral center and is supported by the Government of Sierra Leone through the Ministry of Health and Sanitation. The hospital offers a range of medical and surgical services through 25 departments/units and has 16 wards with more than 300 beds [Princess Christian Maternity Hospital (PCMH) is a tertiary referral government hospital that provides obstetric and gynecological healthcare services. It receives support mainly from the Government of Sierra Leone through the Ministry of Health and Sanitation with the Free Health Care Initiative (FHCI) introduced in 2010 to provide free healthcare services to pregnant women, lactating mothers and under-five children . The Ola During Children’s Hospital (ODCH) is the national referral pediatric hospital. It started as a community self-help project which the government took over and renovated in 1961. The hospital has an inpatient capacity of 139 beds and comprises an emergency room, intensive care units, step down (transition ward), therapeutic feeding center, Special Care Baby Unit (SCBU) or neonatal unit, observation ward, resuscitation ward and two general wards . The hosThe study was conducted in PCMH, ODCH and Connaught hospitals, which account for approximately 60% of COVID-19 infections among the healthcare workers (HCWs) in the country. They were in the epicenter  of the COVID-19 outbreak. These facilities account for 12% of all the healthcare workers in the country . Based oThese facilities were part of the nationwide assessment carried out in 2019 using the IPCAF tool as a pilot project. Additionally, these facilities established isolation units where suspected COVID-19 patients were admitted until COVID-19 laboratory results were released. All the staff working at the isolation units and a small number of staff who provide routine healthcare services to patients had received training on IPC for COVID-19. Core component (CC) 1: IPC program;CC2: IPC guidelines;CC3: IPC education and training;CC4: healthcare-associated infection surveillance (HAI);CC5: multimodal strategies for implementation of IPC interventions;CC6: monitoring/audit of IPC practices and feedback;CC7: workload, staffing and bed occupancy;CC8: environments, materials and equipment for IPC.The WHO IPCAF was used to assess IPC programs and activities in these three tertiary hospitals. The tool is a self-assessment tool that should be administered by the facility IPC focal person; however, it can also be used for joint assessment by external assessors. The IPCAF is divided into eight sections, which reflect the eight WHO ‘Core Components of Infection Prevention and Control Programmes’. These are:For each CC, a maximum score of 100 points can be achieved. Hence, the highest possible overall IPCAF score is 800 points. Depending on the overall score, an IPC grade is allocated to a healthcare facility. Scores from 0 to 200 points correspond to ‘Inadequate’, 201–400 points indicate ‘Basic’, 401–600 points indicate ‘Intermediate’, and 601–800 points indicate ‘Advanced’ IPC compliance . IPC perThe IPCAF tool was filled in by the IPC focal person of each hospital , and the information was cross-validated by the principal investigator. Additionally, direct observations were carried out by the principal investigator where necessary. A Microsoft Excel spreadsheet was created for this study, and the 2021 prospective data were added to the workbook. The principal investigator screened the datasets to check for incompleteness and inconsistencies and ensure data quality. A descriptive analysis of each core component of IPC was carried out at the different healthcare facilities followed by a comparative analysis. Average scores for each of the core components and subcomponents were computed for each healthcare facility. The overall IPC compliance scores were 333.5 of 800 for Connaught Hospital, 323.5 of 800 for Ola During Children’s Hospital and 296 of 800 for Princess Christian Maternity Hospital. These equate to a ‘Basic’ level of compliance grade at these three tertiary healthcare facilities .For the individual core components, the majority of the scores for the three tertiary healthcare facilities ranged from ‘Inadequate’ to ‘Basic’. The components with the least scores were ‘healthcare-associated infection surveillance’. The component with the best level of compliance was the ‘IPC programme’. Additionally, Connaught Hospital scored higher in ‘built environment, materials and equipment’ as compared to the other two healthcare facilities . FurtherThe major strengths and gaps at the three tertiary healthcare facilities related to the different components of the IPC framework are shown in The three tertiary healthcare facilities had an IPC program with a dedicated IPC focal person. However, there was no dedicated IPC budget to support the implementation of activities. The IPC focal persons at Connaught and Ola During Children’s hospitals had received the national advanced IPC training, while the IPC focal person at Princess Christian Maternity Hospital had yet to receive any formal training in IPC. Both Connaught and Ola During Children’s hospitals had access to a microbiology laboratory onsite, whereas Princess Christian Maternity hospital accessed the ODCH microbiology laboratory. However, they were not reporting results of ‘culture and sensitivity’ testing.The three healthcare facilities used the national IPC guidelines (2015), which did not include guidance on outbreak management and preparedness, prevention of HAI or prevention of transmission of multidrug-resistant pathogens. There was no well-defined HAI surveillance protocol, including surveillance of infections that affect healthcare workers in the clinical, laboratory and other settings. Even though a multimodal strategy was employed for IPC intervention, a multidisciplinary approach was not being used. There were no clearly defined objectives and targets to monitor IPC activities. The healthcare facilities monitored hand hygiene compliance quarterly and conducted the WHO Hand Hygiene Self-Assessment Framework Survey annually. Among the healthcare facilities, there was no agreed healthcare worker-to-patient ratio, and staffing levels were not assessed according to patient load. Single patient rooms for grouping patients with similar pathogens were not available. Each facility had a burning pit/waste dump, incinerators were non-functional, and the areas for cleaning, disinfecting and sterilizing medical devices/equipment were not functioning reliably. Personal protective equipment such as examination gloves, facemasks and aprons were not continuously available and had been largely donated to these healthcare facilities.Despite these similarities, there were some marked differences. At Connaught Hospital, water services were available and of sufficient quantity while at Ola During Children’s Hospital and Princess Christian Maternity Hospital, water supply was available on average less than five days per week. The water supply in all facilities was not considered safe for drinking by staff, patients or family members. At the Ola During Children’s Hospital, there was sufficient power supply present at all times and in all departments while at Connaught and Princess Christian Maternity Hospitals there was insufficient power supply in all areas, day and night. Connaught and Ola During Children’s hospitals had the required number of functional toilets in their facilities, while this was not the case at Princess Christian Maternity Hospital.This is the first study conducted in tertiary hospitals in Sierra Leone using a globally accepted and standardized tool such as the WHO IPCAF tool to evaluate the effectiveness of implementation of IPC programs at healthcare facilities. All of the three study hospitals scored a ‘Basic’ grade for IPC implementation. This implies suboptimal implementation, indicating a great scope for improvement. These findings are similar to those found in a study carried out at the Lira university hospital in Uganda . In contA positive finding was that all three study hospitals had an IPC program, an IPC committee and a dedicated IPC focal person. However, the IPC committees were not multidisciplinary and did not provide oversight of the IPC focal person in the implementation of IPC interventions at their facilities. These findings are consistent with studies from Georgia and Tanzania ,26. A keAn uninterrupted supply of clean and safe water has been a challenge in most healthcare facilities in Sierra Leone. Of the three facilities in our study, only one facility had a water supply seven days a week. None of the facilities had constant safe drinking water for patients, visitors or healthcare workers. These findings are similar to those of a study in Pakistan . The chaIPC supplies such as hand gloves, face masks, and aprons were not readily available in any of the three healthcare facilities. This is in line with findings from Ghana, wherein only 19 out of the 56 healthcare facilities had a sufficient quantity of examination gloves, face masks, aprons and other personal protective equipment . To promOur study revealed that the hospital IPC focal persons have the ability and capacity to monitor IPC practices and feedback. However, there was no defined monitoring plan with clear goals, targets and activities at these three healthcare facilities. The national IPC officers are implementing the WHO hand hygiene self-assessment framework at these healthcare facilities annually as recommended by WHO. Implementing the hand hygiene survey is a good practice as it is a key indicator for evaluating the implementation of an IPC program at healthcare facilities . Our finA WHO panel of experts recommends that facility-based HAI surveillance should be performed to guide IPC interventions and detect outbreaks, including AMR surveillance with timely feedback of results to healthcare workers and stakeholders . None ofOur study had several strengths. First, we addressed identified national and global operational research priorities. Second, data collection was carried out by IPC focal persons and validated by the principal investigator, all of whom were well-versed in IPC terminologies. Third, we used a structured and validated data collection pro forma, the WHO IPCAF tool. This facilitated implementation of uniform procedures in data collection. Fourth, we adhered to ‘STROBE’  guidelines for data collection and reporting of study findings.There were some limitations to our study. First, this was a one-time study and hence provides only a baseline assessment. Follow-up assessments should be conducted to track progress. Second, our findings are not generalizable as only three healthcare facilities located in the capital city were included in the study. A wider study using a representative sample of health facilities across the country is needed.Finally, this was a self-assessment by the hospital IPC focal persons, which might have led to overestimation of scores in certain components. However, the level of bias was reduced as the principal investigator cross-validated the responses, and the tool was developed by WHO as a self-assessment instrument.The hospital IPC teams, with both technical and financial support from the national IPC unit, WHO, Centres for Disease Control (CDC) and other agencies, should conduct new employee orientation and training for all healthcare workers and administrative staff. Additionally, continuous professional development programs should be made available to all IPC focal persons to improve their knowledge and understanding of IPC.The national IPC unit and its implementing partners should develop a national HAI surveillance strategy and support the hospital IPC team in conducting regular HAI surveillance. The national IPC unit and hospital IPC teams should conduct quarterly implementation of the WHO IPCAF tool at healthcare facilities to monitor the implementation of IPC programs at national and facility levels. IPC materials, such as examination gloves, face masks, aprons and other IPC materials, should be supplied in an uninterrupted manner to protect healthcare workers and patients from HAI and AMR.The government of Sierra Leone, through the Ministry of Health and Sanitation and its implementing partners, should provide technical and financial support  to the national and hospital IPC team for the implementation of the IPC program at healthcare facilities to reduce the burden of HAI and AMR.Our study found that all of the three tertiary healthcare facilities in Freetown scored a ‘Basic’ level of IPC compliance, and several gaps were identified in all eight WHO core components, specifically in built environments, materials and equipment, monitoring/audit of IPC practices and HAI surveillance. Availability of a clean, safe and uninterrupted water supply is essential for the implementation of the IPC program at the facility level, and the purchase of IPC supplies, such as personal protective equipment, hand hygiene stations and cleaning agents, should be a priority. Furthermore, a dedicated IPC budget is necessary for the implementation of IPC activities. As the country has updated its national IPC guidelines to reflect the WHO core component approach, we recommend that healthcare workers be trained on the updated national guidelines, emphasizing HAI surveillance and monitoring/audit of IPC practices. All these activities have the potential to reduce the burden of HAI and AMR on our healthcare facilities and support quality healthcare service delivery and the achievement of universal health coverage by the year 2030. Our study findings have added to the national and global body of evidence on the implementation of IPC programs at healthcare facilities.