Artificial Intelligence (AI) has been developed and implemented in healthcare with the valuable potential to reduce health, social, and economic inequities, help actualize universal health coverage, and improve health outcomes on a global scale. The application of AI in emergency surgery settings could improve clinical practice and operating rooms management by promoting consistent, high-quality decision making while preserving the importance of bedside assessment and human intuition as well as respect for human rights and equitable surgical care, but ethical and legal issues are slowing down surgeons’ enthusiasm. Emergency surgeons are aware that prioritizing education, increasing the availability of high AI technologies for emergency and trauma surgery, and funding to support research projects that use AI to provide decision support in the operating room are crucial to create an emergency “intelligent” surgery. Artificial Intelligence (AI) has been developed and implemented worldwide in many fields.In healthcare, AI has the valuable potential to reduce health, social, and economic inequities, help actualize universal health coverage, and improve health outcomes on a global scale.The COVID-19 pandemic was characterized in its early period by a tremendous number of patients needing hospital admission, leading to collapsing healthcare systems globally. Healthcare system strain was exacerbated by limited hospital resources and the low availability of COVID tests and personal protective equipment (PPE). These limitations increased the interest of governments, private companies, and public healthcare systems in developing AI systems to improve the management of patients.In this time of need, AI tools and new digital technologies allowed institutions, medical staff, and stakeholders to clinically manage a large number of patients and large volume healthcare data, both in real-time and remotely .AI tools implemented on big data from electronic health records used heterogeneous, massive, and complex datasets that require integration of different types of information identifying clusters and correlations, and extracting value to transform large volumes data into information and knowledge in the form of predictive models to improve decision-making quality .This became technically possible by building big data platforms to store and integrate high-capacity and high-diversity biological, clinical, environmental, and lifestyle information related to health status collected from individuals and population at one or more time points for real-time demand .Advances in AI have helped big data technology to progress beyond the simple analysis of the traditional hypothesis and query paradigm.It is well accepted that traditional predictive analytics and clinical decision-support systems in surgery have a compromised clinical utility because of the time-consuming nature of manual data management and the suboptimal accuracy that is inherent in traditional clinical decision-support systems that conform to rules rather than learning from data. On the contrary, AI refers to computer systems that mimic human cognitive functions such as learning and problem-solving, which can be performed with or without human supervision .Machine learning (ML) is a subfield of AI that enables machines to learn and make predictions by recognizing patterns to support rational human decision-making and it is increasingly being applied to the medical fields. ML allows a computer to utilize human labelling of the data (supervised learning) or the structure detected in the data itself (unsupervised learning) to explain or make predictions about the data with fewer explicit human instructions to do so.Deep Learning (DL) is a type of ML in which computer systems learn and represent highly dimensional data by adjusting weighted associations among input variables via a layered hierarchy modelled on the anatomic structure of neurons and the neural cortex. DL networks are neural networks comprised of many layers and may learn more complex and subtle patterns than simple one or two-layer neural networks. An algorithm optimizes and updates weights as the model is trained to achieve the strongest possible association between input and output layers .AI has been progressively implemented in clinical practice in supporting physicians, and recently surgeons, in improving their clinical decision-making, diagnostics, and surgical procedures, in predicting and limiting human errors in critical highly stressful situations through preoperative risk stratification, intra-operative monitoring of surgical procedures, and postoperative phases of care.For example, in oncology, research has demonstrated that ML applications can be of great help for the diagnosis or detection of cancer . In the AI in surgery is developing more slowly than in medicine and radiology, which may be partially attributable to the high stakes and complexity of surgical decision-making, dominated by hypothetical-deductive reasoning, based on the unpredictable interaction with the patient, human intuition, and the environment.AI research in surgery involves algorithms and the development of semi-autonomously acting devices and robotics capable of doing interventional gestures/actions in different surgical procedures by a different interaction with the surgeon, but always under his/her supervision.This interaction and supervision had been classified into 6 levels, as summarized in Table Simple energy devices and power staplers used routinely in surgical practice may be considered as “intelligent” devices, in fact, they use algorithms to calculate hundreds of thousands of data points per second to determine the optimal coagulation velocity without movement or gesture of the surgeon, or they are provided of sensors that block the stapling action if the tissue is too thick or not thick enough, without interaction with the surgeon.Because of all these technological innovations, the enthusiasm towards AI developments is growing among surgeons.Diffusion of Innovations theory [Despite this high surgeons’ motivation, AI research in surgery is following a classic S-shaped curve, going through the “Peak of Inflated Expectations” to the “Trough of Disillusionment” according to Rogers’ s theory  Fig. 1)DiffusionAt present, the support of AI in surgical practice is mainly based on ML and computer vision (CV), which enables computers and systems to derive meaningful information from digital images, videos and other visual inputs and to take actions or make recommendations based on that information, augmented reality, and anatomical segmentation.CV softwares can improve surgeons' performance in critical situations such as difficult cholecystectomies , 12 usinFor example, surgical robots such as the da Vinci Surgical System allow surgeons to perform surgery from a remote booth with telemanipulation to control the arms of the robot and to use 3-D stereo endoscopes.AI segmentation and localization contribute to safe tool-tissue interaction and are essential to visually guided manipulation tasks, significantly improving surgical gesture flexibility, accuracy, and reliability over hand-crafted tool tracking methods , 14.Moreover, fusing multiple pre-operative and intra-operative imaging modalities in an augmented reality (AR) view of the surgical site enhances surgical navigation by vision-based AR systems that display the fused information to the surgeon .Panesar et al. discussed also the role of the internet or mobile platforms, controlled by AI, in providing surgical expertise remotely, allowing surgical robots to perform surgeries, alone but under the supervision of a connected surgeon, or guiding surgeons in difficult surgical procedures, where appropriate resources are unavailable or access is lacking, such as in war or during a disaster .Despite these extraordinary results reported in literature, significant problems persist in the implementation of these vision-based AR systems, such as adding contextual information to the visualization  and ensuring robust localization .Several pilot studies' results are promising, but AI algorithms and digital vision in the OR are not yet ready for large-scale implementation in clinical practice. Despite promising results from the pre-clinical development causal inference models, AI is not yet able to detect causal relationships in data at a necessary level for clinical practice.AI systems inside the operating room (OR) may have a promising future in monitoring OR access, occupation, and practice in evolving technology like the OR black box, a multiport synchronized data capture and analytic platform , 18.The OR Black Box technology, which leverages DL algorithms, continuously and simultaneously recorded intraoperative audiovisual data and physiological parameters from both patients and health care professionals, and multiple other sensors and devices . In-OR vAll data are stored on a secure server for further analysis based on procedural steps, disruptive environmental and organizational factors, OR team technical and nontechnical skills, surgeon physiological stress, intraoperative errors, events, and rectification processes .The main aim is to develop a “surgical control tower” that, using AI, can monitor, analyse and support workflows and outcomes in real-time, improving operating room management, surgical quality and safety, decreasing healthcare costs .Inside and outside of OR, decision-making is the most difficult and high responsibility surgeons’tasks. Surgeons have to evaluate the patient and all clinical informations correlated, in a short time and often in a stressful setting, to take complex decisions.This mental processus is dominated by hypothetical deductive reasoning and individual judgment and depends on personal behaviour, the patient and the environment, with high variability and risk of errors.Loftus et al.  showed tAI models, fed with live streaming intraoperative and electronic health record data (EHR), integrated with bedside assessment and human intuition could improve critical decision-making.For example, according to ML methods, the Predictive OpTimal Trees in Emergency Surgery Risk (POTTER)  smartphoThis calculator showed higher accuracy compared to American Society of Anesthesiologists (ASA) classification, Emergency Surgery Score (ESS), and ACS Surgical Risk Calculator . On the Main ethical issue with the implementation of these AI tools in clinical practice is concerning the validity and generalisability of ML prediction that depends on the accuracy, comprehensiveness and representativity of the data integrated.Before COVID pandemic broke out, emergency surgeons were already aware of the crucial role of implementing technology in clinical practice to improve the management of patients presenting acute abdominal pain when they proposed the Video-Consulting Emergency (VCE) protocol as a simple tool to improve the decision-making process between an on-site emergency physician and a remote acute care surgeon using a smartphone, the FaceTime application, and the Acute Abdominal Decision Making (AADM®) model , 23.The Artificial intelligence in Emergency and trauma Surgery (ARIES) project was conceived to increase research and availability of AI systems for emergency and trauma surgery .The first step of this project was to carry out an international web survey endorsed by the World Society of Emergency Surgery to assess the knowledge, attitude and practices of AI in emergency and acute care surgery. It was shown that there is a deep interest among emergency surgeons in investigating AI implementation in the emergency setting, in supporting decision-making, and in developing autonomous actions in surgery, to improve clinical and surgical outcomes.For only 37% (75/200) of responders, minimally invasive surgery (MIS) accounts for more than half of their surgical activity;MIS is performed for both elective and emergency procedures for 74% (149/200) of responders;90% (181/200) of emergency surgeons do not perform robotic surgery;75% (150/200) of emergency surgeons are not trained in robotic surgery;63% (127/200) of emergency surgeons do not have robotic surgery platforms in their institution;55% (110/200) of emergency surgeons have 3D vision experience;54% (109/200) of emergency surgeons use 3D vision tools only for elective surgical procedures.From this survey, significant data emerged Figs. , 3, suchSo, despite the advancements in AI developing systems, there is still a problem of availability and accessibility of high technology tools that integrate with AI for emergency and trauma surgery in highly stressful settings where monitoring decision-making and surgeons’ performance has the potential to mitigate harm from preventable errors.Moreover, the adoption of innovative technology always involves early adopters  and late adopters . During the innovation process, when an individual is motivated to reduce uncertainty about the advantages and disadvantages of an innovation, it is important to emphasize the ethical and legal challenges.The quality and reliability of medical information;The lack of transparency in the decision-making process by the intellectual core of the system, according to the “black box” principle that refers to ML models that give an answer or make a decision without explaining or showing how they did it;The selection and development of personnel capable of effectively using and maintaining intelligent systems;The high cost of projects;The security of data storage.Litvin et al.  assessedO’Sullivan et al.  reviewedLegal issues concerning AI tools also include privacy, cybercrime and ethics to ensure that new technologies are used responsibly, including human representatives, to build trust between humans and AI techniques.https://gpai.ai/), OpenAI ([https://openai.com/about/), the Foundation for Responsible Robotics ([https://responsiblerobotics.org/), the Ethics and Governance of AI Initiative ([https://aiethicsinitiative.org/), the Montréal Declaration for Responsible Development of AI [https://www.fatml.org/resources/principles-for-accountable-algorithms).To address these concerns, many initiatives and principles documents were provided, including the Partnership on AI  and of disposing of large, international, secured databases (registers) to train algorithms with high reliability and accuracy.Emergency and trauma surgeons strongly believe that the implementation of AI in emergency and trauma settings is a major opportunity to improve outcomes, and are ready to be involved in future research projects about AI application in supporting decision-making and surgical procedures.The ARIES survey  showed tWe believe that advancements in AI for surgery require close collaborative working groups  and the development of non-surgical skills aiming to obtain an optimal clinical application of AI in surgery, with women and men from diverse training and sociodemographic backgrounds contributing equally to permit the deepest understanding of AI in surgery in a manner that represents the diversity and uniqueness of the patients we serve.According to this, emergency and trauma surgeons responded that prioritizing education, increasing the availability of high AI technologies for emergency and trauma surgery, and funding to support research projects that use AI to provide decision support in the OR in difficult and high stressful situations are crucial to develop an emergency “intelligent” surgery.Emergency and trauma surgeons have led the charge when it comes to creating and disseminating simulation-based education, most notably with the ATLS (Advanced Trauma Life Support) course. The creation of even more advanced AI-enabled simulations could enable even more significant reductions in preventable errors and delays in diagnosis and therapeutic administration, resulting in improved outcomes during trauma resuscitations.Education, accessibility to high technology devices and AI tools, and research funding are the keys to create an emergency “intelligent” surgery and improve the management of patients in difficult and stressful settings.The application of AI in emergency and trauma surgery settings could improve clinical practice by promoting consistent, high-quality decision making while preserving the importance of bedside assessment and human intuition as well as respect for human rights and equitable surgical care.Emergency surgeons are ready to contribute with international, high quality, clinical and surgical data (registers) to develop inclusive and effective algorithms and to work on an intelligence emergency and trauma surgery.


Regenerative medicine is the branch of medicine that effectively uses stem cell therapy and tissue engineering strategies to guide the healing or replacement of damaged tissues or organs. A crucial element is undoubtedly the biomaterial that guides biological events to restore tissue continuity. The polymers, natural or synthetic, find wide application thanks to their great adaptability. In fact, they can be used as principal components, coatings or vehicles to functionalize several biomaterials. There are many leading centers for the research and development of biomaterials in Italy. The aim of this review is to provide an overview of the current state of the art on polymer research for regenerative medicine purposes. The last five years of scientific production of the main Italian research centers has been screened to analyze the current advancement in tissue engineering in order to highlight inputs for the development of novel biomaterials and strategies. Regenerative medicine is the branch of medicine that effectively uses stem cell therapy and tissue engineering strategies to guide healing or replacement of damaged tissues or organs. In this scenario, biomaterials are crucial. In the last 20 years, the science of biomaterials has made advances in all fields from the development of full synthetic materials to green and nanostructured materials. Every novel biomaterial aims to have several advantages, including minimal antigenicity and fibrogenicity, the absence of local or systemic toxicity, infectious safety, hemocompatibility, a minimal infection-promoting effect, to serve as a substrate for cell adhesion and proliferation, to allow the deposition of the extracellular matrix (ECM), controlled degradability, mechanical resilience, ductility to processing, easy sterilization, and economically convenience.The Italian research centers have proposed a wide variety of biomaterials ranging from polymers through ceramics to metals. The aim of this review is to provide a snapshot of the main Italian research centers that deal with the design, development, production and testing of biomaterials for regenerative medicine purposes. The last five-year scientific production of the main Italian research centers has been screened to provide an overview of the current state of the art on polymer applications.A PubMed search was executed for research articles on polymers for tissue engineering applications performed by Italian research centers. The search was done by searching the main Italian universities as “affiliation” together with the terms “polymer”, “hydrogel”, “alginate, “chitosan”, “hyaluronic acid”, “pectin”, “fibroin”, “graphene”, “poly(lactic acid)”, “poly(glycolic acid)”, “poly(lactide-co-glycolic acid)”, “poly(caprolactone)”, “poly”, “poly(urethane)”, or “decellularized extracellular matrix”. Only English-language original articles published between 2017 and 2022 were considered. All in vitro, in vivo, preclinical studies regarding the development, production, analysis, and application of polymers for tissue engineering and regenerative medicine purposes were considered. Systematic reviews and meta-analyses were excluded.Polymers have significant importance in regenerative medicine due to their chemical and mechanical tunability. Polymers can be used for the production of cell culture systems, drug delivery systems, scaffolds, or biological substitutes . A largeAlginate is an anionic and hydrophilic polysaccharide that derives primarily from bacteria and brown seaweed. Genoa University  has developed microbeads made of alginate and chitosan with well-defined drug-loaded microvoids. These microbeads are a promising approach for the creation of biocompatible micro-structured scaffolds and for the development of a system with limited drug leakage .At the Institute of Nanotechnology , various polymers and composites such as thiol-ene alginate , chitosaThe Institute of Electronics, Computer and Telecommunications (IEIIT) of Genoa proposed a 3D alginate-based hydrogel as an extracellular microenvironment to evaluate the effects of three-dimensionality on biological and immunological properties of neuroblastoma cells. This cancer model allowed the analysis of neuroblastoma growth, immunophenotype, and susceptibility on therapies improving the efficacy of personalized therapeutic approaches . InsteadPVA is widely investigated by Padua University as a tailorable biomaterial for several tissue engineering applications. For instance, Conconi et al. indicated PVA as a promising biomaterial for the fabrication of artificial vessels . PVA oxiChitosan, mentioned above, is a biopolymer derived from the partial or total deacetylation of chitin, the second most abundant polysaccharide. At Trieste University, many studies have been conducted to characterize the properties of chitosan. This biopolymer possesses peculiar biological and rheological features, and in the presence of diol-binding and cross-linking molecules it is possible to generate mechano-responsive biomaterials for tissue engineering ,22,23. ITrento University  has conducted several studies on silk fibroins. The silk fibroin has been tailored modifying the secondary structure and molecular weight by linking specific active groups to the amino acid side chains . Silk fiHyaluronic acid is the chief component of the connective tissue that forms the gelatinous matrix around cells. The Institute of Polymers, Composites and Biomaterials of National Research Council (IPCB-CNR) of Naples is specialized in hyaluronic acid composites and derivates. For instance, in collaboration with Rome University, hyaluronics acid hydrogels have been proposed for the treatment of degenerative meniscus lesions or intervertebral disc degeneration ,36. In tHydrogels derived from the decellularized extracellular matrix (dECM) have been investigated at the Veneto Institute of Molecular Medicine . Different dECM hydrogels with tissue-specific signatures have been tested to support organoid culture and muscle regeneration ,38,39. TThe Department of Biotechnology and Biosciences (Milan University) and the Milan-Bicocca University have functionalized the gelatin polymer to improve mechanical stability at physiological temperatures. Cross-linked gelatin has been generated by homobifunctional triazolinediones , and homThe Basilicata University is focused on recombinant protein-based biomaterials for biomedical applications . Self-asIn biomedical neuroscience, biomaterials are used for regeneration, healing, the development of the central nervous system (CNS), and nerve grafting in peripheral nerve injuries. Polymers used for these purposes vary from synthetic biodegradable biomaterials, such as PLA and PCL, carbon-based materials such as carbon nanotubes (CNTs) and graphene oxides (GO), and natural biomaterials such as fibroin and chitosan .Synthetic materials exhibit a higher degree of purity compared to natural-based products; however, they are often less biocompatible . The NeuCNTs were investigated on nerve conduits and axon regeneration ,61,62. SPCL is a very resistant material that is primarily used for the replacement of hard tissues. However, its molecular weight can be adjusted for soft tissue engineering and nerve repair . At the Oxidized PVA has been studied by for injured peripheral nerve regeneration at Padua University. Hollow nerve conduits made of PVA partially oxidized with potassium permanganate or bromine were investigated as delivery systems of ciliary neurotrophic factor. In vitro and in vivo experiments demonstrated that the functionalized oxidized PVA conduits represent promising strategies to enhance peripheral nerve regeneration by guiding axon growth while delivering therapeutic neurotrophic factors ,68,69. ISeveral Italian groups have directed their research towards the production of biomaterials with natural polymers. The purification process of natural hydrogels and fibers might be more complex; however, raw materials are abundant and have better biocompatibility on average. The Department of Clinical and Biological Sciences of Turin University worked on mechanisms of nerve regeneration and Schwann cells differentiation using a variety of scaffolds. The team has optimized the hydrogel preparation process and composed blends of natural polymers for optimal drug incorporation. The obtained material has been tested for the controlled release of VEGF, crucial in tissue repair and angiogenesis. Beneficial effects were observed on motor neuron survival, Schwann cell proliferation and the sustained growth of regenerating peripheral nerve fibers . Some ofTM, a two-layered silk (Bombyx mori) nerve conduit obtained through the electrospinning technique. The novelty of SilkBringeTM lies in its architecture, as it is functional yet structurally solid; while silk itself is responsible for biocompatibility and strength . I. I141]. PLGA, thanks to its low toxicity and biocompatibility with tissue and cells, is used for devices that come in contact with the skin . The CenThe Institute of Applied Sciences and Intelligent Systems (CNR-ISASI) in Naples has recently developed hybrid flexible devices for sensing and transdermal drug delivery based on PEG diacrylate (PEGDA) hydrogels having different molecular weights  ,155. By The standard practices in bone defect repair involve autografts or allografts from a donor or cadaver. Both types of grafts promote the release of several bioactive molecules such as bone morphogenetic proteins and other growth factors that facilitate the differentiation of osteoprogenitor cells and MSCs . Both teThe Department of Industrial Engineering of Padua University has investigated the biofunctionalization for chitosan and wollastonite and diopside to improve bone integration ,166. A cIn Venice, the company Nadir—Plasma & Polymers produces biocompatible polymers filled with antibiotics to prevent infection during bone regeneration. The functionalized polymer can be 3D printed to produce antimicrobial scaffolds for MSCs differentiation into osteoblasts, allowing matrix mineralization and osteogenic marker expression . DiffereThe Institute of Science and Technology for Ceramics of the National Research Council  have enveloped strategies and calcium phosphate-based scaffolds for bone tissue reconstruction. A particular statistical tool has been used to design the biofabrication of hybrid hydroxyapatite/collagen scaffolds for bone regeneration and optimize their integration in a multilayer osteochondral device. The statistical tool allows for the selection of hydrogel concentration, hydroxyapatite/collagen ratio and cross-linker content. With these input parameters, multi-layer scaffolds have been synthesized with a graded mineralization rate that can be used to mimic the whole cartilage-bone interface . InsteadCalabrese et al. (Messina University) have tested innovative nanostructured scaffolds for BTE with MSC cultures. Mg/hydroxyapatite/collagen type I scaffolds have been nanofunctionalized with gold nanorods, palladium nanoparticles, or maghemite nanoparticles. Calabrese’s results are in agreement with previous studies that found cytotoxic effects for both gold nanorods and palladium nanoparticles. Instead, the high intrinsic magnetic field of superparamagnetic nanoparticles had improved both osteoconductivity and osteoinductivity in MSCs . LikewisAt Bologna University, synthetic polymer-based scaffolds doped with calcium silicates (CaSi) have been investigated. Highly porous scaffolds have been prepared combining PCL or PLA, dicalcium phosphate dihydrate (DCPD) and CaSi. The scaffolds had internal open porosity, which can be colonized by cells, release biologically active ions, and create nucleated apatite . In vitrStaphylococcus aureus and MSC proliferation and differentiation [Titanium and its alloys are commonly used for bone regeneration thanks to their biocompatibility and favorable mechanical properties. Nevertheless, porosity and coating are generally managed to improve the osteointegration of titanium-based implants. Randomized trabecular titanium structures obtained by the 3D printing technique have been investigated at Milan University . The hisntiation . Padua Untiation ,188. In ntiation . MoreoveCartilage has limited intrinsic self-repair capacity, therefore the effective treatment of its defects represents a challenging problem. The “Aldo Moro” Bari University has proposed composite scaffolds made of gellan gum, inorganic clay derived from mesoporous silica, and antibacterial Manuka honey. Polymeric scaffolds generally have poor mechanical properties, on contrary this mesoporous silica-composite hydrogels exhibited significant changes in peak elastic and dynamic moduli over time. Moreover, the scaffold showed in vitro cytocompatibility and antibacterial preventive capability . InsteadBlends of polymers have been studied to fabricate substitutes for tendon reconstruction. The ideal scaffold should have a structure mimicking the natural tendon while providing adequate mechanical strength and stiffness. Sensini et al. (Bologna University) developed electrospun nanofibers crosslinking PLLA and collagen. The nanofibers were then aligned and wrapped in bundles. Human fibroblasts seeded on the bundles had increased metabolic activity, meanwhile the stiffness, strength and toughness of the bundles were comparable to tendon fascicles . In TeraIn conclusion, this review summarizes the recent efforts of Italian research centers in studying and developing regenerative biomaterials . In part


Strategic and standardised approaches to analysis and reporting of surveillance data are essential to inform antimicrobial resistance (AMR) mitigation measures, including antibiotic policies. Targeted guidance on linking full-scale AMR and antimicrobial consumption (AMC)/antimicrobial residues (AR) surveillance data from the human, animal, and environmental sectors is currently needed. This paper describes the initiative whereby a multidisciplinary panel of experts , representing all three sectors, elaborated proposals for structuring and reporting full-scale AMR and AMC/AR surveillance data across the three sectors. An evidence-supported, modified Delphi approach was adopted to reach consensus among the experts for dissemination frequency, language, and overall structure of reporting; core elements and metrics for AMC/AR data; core elements and metrics for AMR data. The recommendations can support multisectoral national and regional plans on antimicrobials policy to reduce resistance rates applying a One Health approach. Numerous evidence supports that to minimise the emergence and transmission of AMR, it is crucial not only to improve infection prevention and control in the healthcare and veterinary setting, but also to ensure access to clean water, sanitation, and hygiene in healthcare facilities and in the community at large. A One Health approach to surveillance should include all components necessary to identify (new) emerging resistant microorganisms, inform about risk factors and cross-sectoral transmission dynamics, develop and implement relevant antibiotic stewardship interventions, orient patient treatment, and promote policy development in all three sectors to combat AMR.,Surveillance systems can collect different microbiological, clinical, and demographic data, which should be reported to relevant stakeholders in a structured and meaningful manner in order to efficiently and consistently drive actions to mitigate AMR. Recent surveillance protocols and guidance documents from major authorities and stakeholders extensively support the harmonized collection and analysis of AMR and antimicrobial consumption (AMC) surveillance data in the human and animal sectors at local, national, and international levels.The COMBACTE-MAGNET EPI-Net network, a European public-private partnership project, has been working towards harmonising AMR surveillance strategies and developing tools for improving surveillance since 2015.Using the lessons learnt from the previous efforts and to support the ongoing global initiatives, a consensus project was launched by EPI-Net in March 2021 to identify the most important actions for the human, animal, and environmental sectors toward implementing a One Health approach. Given the complex epidemiological interconnectedness and heterogeneous surveillance approaches at play, the task of combining multisectoral data from routine AMR and AMC/antimicrobial residue surveillance is a challenging endeavour that requires targeted guidance. The main objective of this initiative was to bring together a multidisciplinary panel of experts from all three sectors and discuss how to combine and report full-scale AMR and AMC/antimicrobial residues surveillance data from the One Health triad in order to drive judicious antibiotic usage in the human sector.For this objective we utilised a modified Delphi approach. An expert panel was selected and an evidence-based consensus building exercise was carried out between March 2021 and January 2022.To identify potential experts for the panel, we reviewed: 1) recent publications on One Health surveillance; 2) ongoing European One Health consortia or projects website; 3) experts from the COACH project.a priori by the research team and refined by the expert panel. Alongside this, a two-pronged literature search was carried out to review: a) recommendations available to support One Health reporting of AMR and AMC surveillance data; and b) current practices in reporting One Health surveillance data. Pertinent literature, i.e., guidance documents and One Health surveillance reports published between 2012 and 2021 in English Language were identified. A detailed description of the search and data extraction strategy is available on the EPI-Net websiteTo formulate the consensus statements which would form the backbone of the panel's recommendations, a multi-step approach was used: 1) development of key questions for the Delphi process; 2) literature review to summarise evidence; 3) presentation of the questions and evidence to the expert panel to obtain their preliminary statements via an online survey; 4) collation of statements; 5) first round of consensus via an online questionnaire; 6) second and final round of consensus during a virtual meeting on 3 December 2021; and 7) revisions, finalization, and approval of statements by the expert panel. Briefly, a preliminary set of questions was identified 1.Common definitions and strategies: What should be the frequency and language of reporting? Should a One Health surveillance report replace the individual sector-specific surveillance reports? Should data from both public and private (industry-funded) sectors be included? In addition, for the evolving concept of environmental surveillance, what should be the common definition for the term “environment” to ensure homogenous data reporting?2.Data reporting from AMC/antimicrobial residues surveillance: Should data on AMC and antimicrobial residues from all three sectors be reported in a One Health surveillance report? If so, data for which antimicrobials should be included and what should constitute data for the purpose of reporting? Should the results of a comparative or integrated analysis be additionally reported, and in this case how should the analysis be performed? Should information on cases of falsified and substandard antimicrobials be reported, and why?3.Data reporting from AMR surveillance: Should data on AMR from all three sectors be reported in a One Health surveillance report? If so, data for which bacteria–drug combinations should be included and what should constitute data for the purpose of reporting? Should the results of a comparative or integrated analysis be additionally reported, and in this case how should the analysis be performed?In all, 16 key questions were identified in order to support structuring and reporting of full-scale multisectoral. These questions concerned three major aspects in the thematic of AMR and AMC/antimicrobial residues reporting from the human, animal, environmental sectors:Escherichia coli using a “One Health” approach’ provides the most comprehensive guidance for surveillance and reporting of AMR from the One Health triad.Twelve guidance documents were identified in total see . Among tThe Delphi questions, together with summary documentsThe proposals from the expert panel serve as guidance to any stakeholder aiming to disseminate or communicate One Health surveillance data to have an impact at the local, national, or global level. This consensus is especially addressed to individual or organizational leaders in human, animal, and environmental health with an impact on the practices and policies in all three sectors. It also serves to optimise surveillance efforts and reporting. This is a first attempt at combining full-scale One Health triad data with the purpose of a better holistic understanding of global health. The provided consensus is mostly designed based on settings with high income where abundant resources allow the implication of all the contributors to human, animal, and environmental health. Although applying this guidance at global level would be desirable, implementation in low- and middle-income countries (LMICs) could be challenging and should be further explored in dedicated guidance documents.,Box 1▪Emission pointsoWastewater, including wastewater from the community and hospital settings, pharmaceutical companies and wastewater treatment plants, maritime shipping oFarm effluentsoAquaculture residual wateroSoil (e.g. contaminated by effluents or wastewater)oAir (e.g. contaminated by effluents or wastewater)▪Exposure pointsoDrinking wateroSurface water oFood of plant origin (e.g. raw vegetables)oWildlifeOn a larger perspective, human and animal behaviours, as well as social and cultural factors, can also be considered “environment”; however, for the time being such definitions would probably not lead to actionable surveillance measures and ultimately would not serve the purpose of One Health surveillance.Environment is “the combination of physical, chemical, and biotic factors  that act upon an organism or an ecological community and have a role in its form and survival, and which are not yet covered by human and animal surveillance efforts.” Within this context, the term "environmental sector" should comprise:Although there have been advances in the monitoring of AMR and AMC/antimicrobial residues at the human-animal-environment interface 20,21, a As an integrated approach to AMR, AMC, and antimicrobial residues surveillance becomes common, the relevance of sector-specific reports was discussed with the expert panel. There was agreement that the significance of sector-specific reports cannot be overlooked. Since the three sectors are diverse, the panel recommended that a One Health surveillance report encompassing the most common and relevant aspects of the three sectors should be produced in addition to unilateral, sector-specific reports. The frequency of reporting was however extensively debated. Providing timely access to surveillance data is key; however, when both sector-specific and One Health surveillance reports are to be produced, feasibility plays a crucial role. Although agreement was achieved that the production of a yearly report would be ideal, the panel recognised that yearly reporting could result in excessive workload. Therefore, it was suggested that reporting of surveillance data every 2 years could be considered in case of limited infrastructure and resources. In case of the emergence of a serious resistance pattern that could have a clinical impact for human health, shorter reporting times could be considered to facilitate immediate response. The panel also agreed that for a One Health report a common language (English) should be used and prioritised to enable comparability, while local languages could be used to summarise only key information.The need to share surveillance data between the public and private sectors at both the local and global levels is recognised as a clear need.To date, there are no well-established guidelines for surveying antimicrobial residues in the environmental sector, and a common strategy for the collection and reporting of AMC surveillance data and antimicrobial residue data encompassing the human, animal, and environmental sectors has not yet been fully developed. Within a One Health report, provision of reliable and comparable AMC surveillance data is essential to understand the epidemiology of AMR and to identify areas for potential intervention. Consequently, the panel agreed that AMC data are necessary and should thus be regularly provided. Although knowledge of environmental concentrations is critical to understand the risk of environmental selection, data on antibiotic residues are usually not reported . The panIn 2005, the WHO proposed categorisation of antibiotics classified as Critically Important Antimicrobials (WHO CIA) for human health, which is periodically revised.Since substandard and falsified (SF) antimicrobials drive the emergence and development of AMR, and antimicrobials are among the most commonly reported SF medical products worldwide,Clear definition and standardisation of metrics allows comparative approaches. Many of the routinely used surveillance indicators for AMC are highly sector-specific and the panel recognised the need for a trans-sectorial overarching reach to ensure comparability and compatibility of data. A list of core elements and metrics identified by the expert panel for AMC data reporting is shown in ,For the animal sectors, mg of active substance per kg of estimated biomass and defined daily doses for animals (DDDvet) per kg of biomass should be used.Through the longstanding collaboration between the ECDC, EFSA, and EMA, inter-agency reports on integrated analyses of AMC and occurrence of AMR in bacteria from humans and food-producing animals (JIACRA) were published.The extension of such an approach to the environmental sector requires acknowledging the differences in the metrics currently used within and across the three sectors. Although the experts recognised that ongoing discussion is still needed to better understand how to utilise and analyse data across sectors, it was suggested that raw data from each sector should be presented independently within a report and that trends should be reported at a minimum. Integrated analyses across sectors could also be performed whenever possible. When common metrics cannot be identified, thus making it difficult to perform an integrated analysis, trends using the same metric for a given sector over time could be described to allow comparisons.When appropriate sampling and bacteria–drug combinations are targeted, data generated through AMR surveillance activities from the human, animal, and environmental sectors can provide the most comparable evidence necessary to understand the complex epidemiology of AMR and establish policy and research actions.,E. coli as an indicator organism.In 2017, the WHO prioritised for the first time a list of antibiotic-resistant bacteria to guide global research and discovery of new antibioticsTo support the interpretation of the AMR estimates, values must be accompanied by background information collected as part of a surveillance system. The concept of surveillance of AMR is well established, but the quality of data generated highly depends on standardised reporting and collection and often varies across sectors. The expert panel, therefore, defined core elements and associated metrics to provide a definition for data reporting from the different sectors . Both co,Furthermore, the ability to test AMR in various sectors is very different. For example, molecular diagnostics of AMR using solely culture-independent techniques (CITs) is not a norm for surveillance in the human and animal sectors. Due to the necessity of culture-based phenotypic antibiotic susceptibility testing methods in detecting clinically-relevant levels of antibiotic resistance, low cost/complexity molecular techniques typically complement phenotypic methods of AMR detection.Evidence on the role of ‘spill-over’ has been well established for AMR; although spill-over points have been mainly evaluated in the community and hospital settings (wastewater/sewage), progress in other settings is currently being made. The expert panel therefore agreed that even though spill-over points are largely under research and integrated analyses are aspirational, they can still be performed whenever feasible to give an overview of how the different sectors influence each other, where potential interventions can be deployed, and help identify research hypotheses. Thus, it was recommended that the inclusion of results from additional comparative or integrated analysis, always accounting for (likely) biases, should be considered for added value. References to current One Health surveillance reports that include a combined analysis are provided in Box 2The recommendations have some limitations. Firstly, the panel mainly assessed antibiotics although role of other substances such as biocides should be included. Secondly, some recommendations may lack specificity due to lack of internationally-recognised gold standard. Finally, transferability could be limited to economic resources of countries. These limitations and suggestions for future research are detailed in The recommendations from the EPI-Net One Health consensus working group represent the first practical outline to support multisectoral data reporting of antimicrobials resistance rates and usage. We believe the document can support discussion among major international and national stakeholders for coordinated One Health surveillance reporting from the human, animal, and environmental sectors within national and regional plans for antibiotic policy to reduce the burden of AMR.Contributors’ initials listed alphabetically when multiple authors were involved in the same task. ET conceived the consensus initiative. NBR oversaw the conduct of the project. CMB, FA, LG, MC, MT, and NBR drafted the protocol. CMB, FA, LG, MT, and NBR carried out the finalization of the protocol; literature search; data extraction; multiple survey organization and results analysis; organization of the virtual consensus meeting and collation of the resulting discussions; finalization of statements. EM, ET, GDA, JRB, MDP, NM, and OS chaired the virtual consensus meeting. CMB wrote the preliminary draft of the manuscript; FA and NBR revised it to develop the first draft of the manuscript; all co-authors contributed to review and feedback of this first draft. NBR finalized the manuscript together with CMB, ET, FA, GDA, LC, MDP, NM, OS, RD, and SK. All co-authors approved the final version. ET was responsible for the final decision to submit the manuscript.JA received grants/contracts from the Spanish Ministry of Agriculture, Food and Fisheries and EU Horizon 2020. Work of BPG was funded by the German Center for Infection research Clinical Research Unit (DZIF-CRU) at Tübingen. RD participated on Data Safety Monitoring Board of the ASTARTÉ study (for which no payments were received). WG received grants/contracts from the Horizon Europe grant (supported by UKRI) on AMR and pathogen evolution in costal environments and the UK Natural Environment Research Council grants on AMR Knowledge Exchange NE/V019279/1 and AMR evolution NE/W006251/1; WG received consultation fee for EU DG Sante AMR policy evaluation and recommendations. Work of AK was funded in the context of the project One Health EJP, which has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 773830. EP received grants/contracts from the Austrian Ministry of Health for the National Surveillance Network of healthcare-associated infections (ANISS); EP received honorarium for participation as a chair of the Advisory board on AMR and MDRO Pfizer Austria (27.09.22). MB received grants/contracts from Janssen Vaccines, Novartis, CureVac, and Merck; MB received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Takeda (November 2019); MB participated on Data Safety Monitoring Board or Advisory Board of Sanofi, Spherecydes, Pfizer, Merck, Novartis, and Astra-Zeneca. MM received support for attending meetings and/or travel from the Global Antibiotic Research and Development Partnership (12.10.22–13.10.2022). LS received grants or contracts from the JPIAMR network grant 2020; LS received support for attending meetings and/or travel from ESCMID for the attendance of ECCMID 2022. DT is an employee of GlaxoSmithKline and holds shares in GlaxoSmithKline. TVB received consultation fees from Stonehaven Consulting; TVB received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Swedish Veterinary Council. Work of AV was supported by the COMBACTE-MAGNET consortium; AV serves as the ISAC president  and board member of NVMM (Dutch Microbiology Society). All other authors declare no competing interests.


The identification of reproducible subtypes within autistic populations is a priority research area in the context of neurodevelopment, to pave the way for identification of biomarkers and targeted treatment recommendations. Few previous studies have considered medical comorbidity alongside behavioural, cognitive, and psychiatric data in subgrouping analyses. This study sought to determine whether differing behavioural, cognitive, medical, and psychiatric profiles could be used to distinguish subgroups of children on the autism spectrum in the Australian Autism Biobank (AAB).Latent profile analysis was used to identify subgroups of children on the autism spectrum within the AAB (n = 1151), utilising data on social communication profiles and restricted, repetitive, and stereotyped behaviours (RRBs), in addition to their cognitive, medical, and psychiatric profiles.Our study identified four subgroups of children on the autism spectrum with differing profiles of autism traits and associated comorbidities. Two subgroups had more severe clinical and cognitive phenotype, suggesting higher support needs. For the ‘Higher Support Needs with Prominent Language and Cognitive Challenges’ subgroup, social communication, language and cognitive challenges were prominent, with prominent sensory seeking behaviours. The ‘Higher Support Needs with Prominent Medical and Psychiatric and Comorbidity’ subgroup had the highest mean scores of challenges relating to social communication and RRBs, with the highest probability of medical and psychiatric comorbidity, and cognitive scores similar to the overall group mean. Individuals within the ‘Moderate Support Needs with Emotional Challenges’ subgroup, had moderate mean scores of core traits of autism, and the highest probability of depression and/or suicidality. A fourth subgroup contained individuals with fewer challenges across domains (the ‘Fewer Support Needs Group’).Data utilised to identify subgroups within this study was cross-sectional as longitudinal data was not available.Our findings support the holistic appraisal of support needs for children on the autism spectrum, with assessment of the impact of co-occurring medical and psychiatric conditions in addition to core autism traits, adaptive functioning, and cognitive functioning. Replication of our analysis in other cohorts of children on the autism spectrum is warranted, to assess whether the subgroup structure we identified is applicable in a broader context beyond our specific dataset.The online version contains supplementary material available at 10.1186/s13034-023-00565-3. Autism spectrum disorder is a common neurodevelopmental condition characterized by social and communication difficulties in the presence of restricted, repetitive, and stereotyped behaviours , with a The identification of reproducible, valid subtypes within autistic populations is a priority research area in the context of neurodevelopment, to pave the way for identification of genetic and other biomarkers, and targeted treatment and support recommendations for this population . It is eThe most replicated findings from empirical studies of subgroup classification in autistic populations to date have yielded between two and four subgroups, defined in terms of a severity gradient  –13, and/Co-occurring medical conditions are common in children with ASD and can significantly affect child and family functioning , 19, butIn this study, we sought to empirically identify subgroups of children on the autism spectrum in the large, well-characterised, and nationally representative Australian Autism Biobank (AAB). We sought to do so on the basis of differing presentations of core traits of autism and co-occurring cognitive, medical, and psychiatric profiles. The AAB is a national data repository overseen by the Cooperative Research Centre for Living with Autism (Autism CRC) .Ethics to perform this study was granted by the University of New South Wales Human Research Ethics & Clinical Trials Governance Committee (HC190924). Access to phenotypic data for all children on the autism spectrum within the AAB (n = 1151), was obtained via the Autism CRC Utilisation Grant 1.073RU.The AAB has previously been described in detail by Alvares et al. 2018) , and con8 , and cn = 754 children on the AS within the AAB for whom the deepest phenotypic data  was available. All standardized assessments were administered by raters without knowledge of cytokine measurements.Phenotypic data within the AAB was obtained from clinical assessments that utilised a range of administered measures and standardised questionnaires completed by parents or caregivers, including the Autism Diagnostic Observation Schedule-2 (ADOS-2)  or AutisIn this study, indicator variables pertaining to the core autism traits and psychiatric comorbidity were based on data obtained using the 3di, a standardised parental interview . To reflLatent class analysis (LCA) and latent profile analysis (LPA) are empirical methods of identifying underlying subgroups (often termed classes) within a dataset based on patterns of data across categorical variables, or continuous variables (or a mixture of both), respectively . In thisn = 754 participants, who were selected for use in the latent profile analysis. These children had similar demographic profiles to those in the overall AAB cohort [Table The overall AAB cohort had a mean age of 7.5 ± 3.9 years, and was predominantly male 78.2%). Deep phenotypic data  was avart Table . Cohort %. Deep pLatent profile analysis of 37 indicator variables describing 14 core traits of autism and 23 other aspects of phenotype yielded a best-fitting model with four-classes. Table Based on goodness of fit statistics, both the three- and four-class models were further considered with the focus on understanding whether addition of the fourth profile provided clinically meaningful information over the three-profile solution. The three-class model described subgroups that are best characterized by the severity gradient across measures of core autism traits, medical comorbidities, and psychiatric comorbidities rather than showing distinct clinical profiles. The four-class model was deemed to be more substantively meaningful and showed unique patterns across specific clinical subdomains rather than being only distinguished by overall severity. Identified profiles were characterized as a ‘Fewer Support Needs Group,’ ‘Higher Support Needs with Prominent Language and Cognitive Challenges Group,’ ‘Moderate Support Needs with Emotional Challenges Group’ and a ‘Higher Support Needs with Prominent Medical and Psychiatric and Comorbidity Group’ Table . NotableIn this study, Class 1 (29.2%) described a ‘Fewer Support Needs Subgroup,’ with fewer social communication difficulties and fewer restricted, repetitive and stereotyped behaviours than the overall group, with higher levels of adaptive functioning. This subgroup was somewhat more likely to have had delayed acquisition of early gross motor milestones than the overall group, but were less likely to have experienced developmental regression, and had lower likelihood of cognitive, psychiatric, and medical comorbidity, compared to the overall group Table 5Class 2 (11.0%) described a ‘Higher Support Needs with Prominent Language and Cognitive Challenges Subgroup,’ with the greatest social communication and cognitive difficulties overall. This subgroup had the highest probability of regression, language delay, and self-injurious behaviour. Compared to the overall group, this subgroup had higher mean scores for sensory seeking behaviours, and lower mean scores for all other RRBs . This subgroup had a similar probability of seizures, gastrointestinal dysfunction, and allergy, compared to the overall group, but had a higher probability of sleep maintenance difficulties.Class 3 (34.4%) described a ‘Moderate Support Needs with Emotional Challenges Subgroup,’ that had similar mean scores of core autism traits, cognitive ability, and adaptive functioning, to the overall group. This group had the highest probability of experiencing depression and/or suicidality, and had a higher probability of exhibiting sleep onset difficulties and defiant behaviours than the overall group.Finally, Class 4 (25.5%) described a ‘Higher Support Needs with Prominent Medical and Psychiatric Comorbidity Subgroup.’ This subgroup had the highest amount of social communication difficulties and the highest scores of restricted, repetitive and stereotyped behaviours overall. Their mean scores of cognitive ability were similar to the overall group, but with lower levels of adaptive functioning. This subgroup had the highest probabilities of medical comorbidity, sleep dysfunction, and psychiatric comorbidity.This latent profile analysis identified four subgroups within the AAB that were distinguished not solely on the basis of an overall severity gradient, but on differing profiles in relation to core autism traits and associated comorbidities. Class 2 and Class 4 both described subgroups of children with higher mean scores of social communication difficulty than the overall group, but Class 2 had the highest probability of language delay and lowest mean cognitive scores, highest scores of sensory seeking behaviour, with lower scores of all other RRBs compared to the overall group. For children within Class 2, social communication challenges, language delay, and cognitive impairment appear to be prominent features of the neurodevelopmental profile, with sensory seeking behaviours but otherwise less prominent RRBs. Class 2 had the lowest probability of depression and a lower probability of anxiety than children in Class 4, who also had high support needs , with cognitive scores similar to the overall group mean. Finally, children in Class 3 had mean scores that were similar to the overall group mean for measure of core autism traits, cognitive ability, and adaptive functioning, but had the highest probability of experiencing depression and/or suicidality.Comparison of findings reported between empirical subtyping studies in autistic populations is complicated by significant diversity in the range of variables utilised to construct subgroups. The strengths of this study include deep phenotyping encompassing the comprehensive range of behavioural, cognitive, medical, and psychiatric variables that were utilised in our subtyping analysis and sample size that afforded good power to detect distinct subgroups. In a recent systematic review of published subtyping studies in autistic populations, of the 156 identified studies, only 16% had a sample size greater than N = 1000 . StudiesWiggins et al. performed latent class analysis in a similarly sized sample of 707 children on the autism spectrum, and incorporated variables reflecting a similar range of behavioural, cognitive, psychiatric, and medical aspects of phenotype, to those used in this study, although standardised measures used to reflect these differed [More limited comparison is possible between our findings and those reported in other empirical subgrouping studies in autistic populations, even among other studies that examined medical comorbidity, due to differences in the overall range of variables utilised. Veatch et al. performed hierarchical clustering using variables representing core autism traits, adaptive functioning, age, and head circumference, but did not include other aspects of psychiatric or medical comorbidity in their analysis . Their ak-means clustering in a cohort of 3,278 children on the AS [Another previous study that used a range of behavioural, cognitive, psychiatric, and medical aspects of phenotype performed n the AS . Three sn the AS . As was n the AS .k-means [Medical aspects of comorbidity have previously been important in distinguishing between subgroups of children on the AS using hierarchical clustering and k-means . Four suk-means . The subk-means . Our finFuture opportunities for research will explore additional validation methods of the four subgroups identified in our LPA, as outlined in the recently proposed framework for subgroup validation, named the SUbtyping Validation Checklist (SUVAC) . Cross-mBeyond replication, identification of subgroups among children with AS will facilitate targeted, individualized treatment recommendations and identification of biological associations that may not be apparent when treating the heterogenous overall population as one cohort. In turn, we will seek to identify which subgroups of children with ASD are most likely to benefit from specific intervention options, and to better understand the varying aetiological pathways relevant to autism.Our study identified four subgroups within the AAB that were distinguished not solely on the basis of a ‘support needs gradient’, but on differing profiles in relation to core autism traits and associated comorbidities. Individuals within subgroups share greater homogeneity in relation to their phenotype presentations than the group overall, and may have greater similarity in terms of shared aetiology and response to treatments. Our findings highlight the importance of including co-occurring medical, psychiatric, and cognitive aspects of phenotype among the indicator variables utilised in subgrouping analyses in autistic populations. Further replication studies are warranted for validation of the subgroups identified in our analysis, including longitudinal follow-up studies to explore stability over time and prognosis.Additional file 1: Table S1: Indicator Variables Describing Core Autism Traits based on 3di Data. Table S2: Indicator Variables Describing Comorbid Conditions.


Conservation biogeography, which applies principles, theories, and analyses of biodiversity distribution patterns to address conservation challenges, can provide valuable insight and guidance to policy making for protection of biodiversity at multiple scales. The temperate and tropical ecosystems of the Nearctic-Neotropical transition in the small western state of Colima, Mexico, support a mosaic of remarkably diverse fauna and flora and provide a rare opportunity to determine spatial distribution patterns of terrestrial vertebrate species, assess human-induced threats, and identify potential conservation strategies. We analyzed the spatial distribution patterns and correlated them with the current land cover and extent of the protected areas. Despite its limited geographic extension, 29% (866) of all vertebrates, and almost a quarter of both endemic and threatened species in Mexico, live in Colima. Our analysis identified clear high-richness concentration sites  coincident for all groups and that elevation and both temperate and tropical ecosystems composition exert significant influence on richness patterns. Furthermore, current species´ distribution also showed significant correlation with natural and disturbed landcover. Significant hotspots for all species groups coincided poorly with the limited protected areas in the state (only 3.8%). The current state of natural land cover (less than 16%) in the state, coupled with its remarkable biological importance, highlights the need for further complementary conservation efforts including expansion and creation of new protected areas, significant restoration efforts and other conservation measures to maintain this uniquely biogeographic and biological diverse region of the country. Conservation biogeography is an ecological approach that recognizes small-scale conservation may not be adequate to protect regional biodiversity. Information on the spatial and temporal characteristics of biodiversity, such as species distribution  is critiCtenosaura pectinata), Orange-breasted bunting (Passerina leclancherii), and Colima Long‐nosed bat (Musonycteris harrisoni), the temperate forests of the Trans-Mexican Volcanic Belt , Mexican Short-nosed skink (Plestiodon indubitus), Bell’s false brook salamander (Isthmura bellii), and Allen’s cotton rat (Sigmodon mascotensis), and the mixed forest of the Sierra Madre del Sur  .https://avibase.bsc-eoc.org/checklist.jsp?region=MXcl and the ASM Mammalian Diversity Database  to gather information of their distribution, conservation status and updated taxonomy. The maps used are relatively recent as they come from the continuous review carried out by the IUCN and BirdLife through the consultation of experts; a period of 10 years or less can be considered depending on the species. Although these data are relatively recent, they hardly reflect the current conditions of land use and vegetation type. It is precisely for these reasons that we analyzed the distribution patterns of species richness with respect to land use to assess the potential of threats to biodiversity and define priority areas to be protected. We used these distribution layers because they come from systematic and standardized processes under IUCN standards, thus allow proper comparison given the nature of the construction processes for all groups [We compiled a comprehensive list of vertebrate species from our field work, specialized literature, and databases maintained by the National Commission for the Understanding and Use of Biodiversity (CONABIO). The IUCN Red List of Threatened Species  and the l groups , 55–61. l groups , 61. Furl groups –64. In t2 (or 100 ha) quadrants within the Colima boundaries and then established their centroids, this resolution was selected as our minimum mapping unit to include some amphibian and rodent species with an extreme restricted geographical distribution [https://www.python.org) to create a histogram of the mean Jaccard index [We used digitalized (shapefiles) geographic distribution maps for Mexican vertebrate species from the BirdLife International and Handbook of the Birds of the World  and the ribution , 38; addribution , 66. We rd index  by cell.We used vector data sets which contain information at the 1:250,000 scale obtained by photointerpretation from 2014 Landsat 8 satellite images used by the most recent national forest inventory  to reclaOur first treatment in the analysis involved a description of the distribution patterns and given the non-normality of the data, species richness for all groups on each grid-cell were compared using the Spearman correlation test and then plotted. We then estimated the distribution of hotspots across Colima by applying the Getis-Ord Gi* statistic  which idWe then plotted the values of the four vertebrate groups in each cell to identify their relationship and to determine if one of those groups could be use as surrogate for the others. To determine the influence of environmental variables on species richness for all vertebrates, each group independently and endemic and threatened species , 70, we Finally, we made an overlay species richness and significant hot spot data with the most recent map version of protected areas  to deterColima, home to 867 species including 42 amphibians, 122 reptiles, 545 birds and 158 mammals, has almost one-third of all vertebrate and mammal species, nearly half of the bird and Mexican bat species, and about one-tenth of the reptile and amphibian species in Mexico ; there aEleutherodactylus colimotl, E. grunwaldi and E. manantlanensis, are endemic to Colima only.Human activities have severely impacted the natural ecosystems throughout Mexico and imperiled a large proportion of vertebrate species , 86, 87,While a large portion of Colima is species rich , there iSpatial distribution of species richness differs by taxonomic group  as exempA total of 744 grid cells were identified as hotspots for all taxon groups, total vertebrates, endemic species, and threatened species , and the2 = 0.45), while threatened species showed the lowest variation explained , therefore we retained all variables for building potential candidate models. The relationship between the different groups of species and each variable varied in terms of intercept, specific influence of each variable (measured by the corresponding coefficient), and especially, the direction of such influence. For instance, Elevation has a negative influence on reptiles, while Potential Evapotranspiration has a negative effect on mammals and birds but not relation with endemic species. Other cases of a lack of relation were found with the Normalized Difference Vegetation Index in amphibians or for the Topographic index with threatened species . Total vThe topography of Colima is characterized by a steady and generally gradual increase in elevation from the coast to the north and northwest and a significantly more dramatic rise in in the eastern part of the state culminating in the 3,827-meter Volcán de Colima which sits on the border with the neighboring state of Jalisco. Most of the elevation of the state is below 573 masl  while a significant proportion of the state has a slope greater than 60% . Such toOur analysis revealed most (83%) of the landscape in Colima has been modified  . NaturalThe direct and indirect relationship between land use and species richness , once accounting with the effect of elevation, indicated a significant correlation between natural vegetation and all taxa (p<0.001) and between disturbed land and taxon groups and conservation status . However, there was no significant correlation between transformed areas and any taxon groups  and conservation status . These results suggest there is a direct correlation between species richness and land use and that elevation has an indirect effect. The strongest correlation occurred between natural vegetation and endemic species (0.236), while the weakest correlation was with reptiles, which interestingly had the strongest positive correlation with natural vegetation but a strong negative relationship with elevation . In contFinally, our analyses showed that only 281 grid cells  were included in any protected area, but their location is highly significant in terms of species richness. When all vertebrates , and eacIn this work, as we expected, the small state of Colima contains a high degree of species richness and endemism. This rich biodiversity could be related to the geographical position, environmental heterogeneity, and geological history of this territory. There are several studies that detail the importance of this region due to its geological past, location, considerable environmental heterogeneity, and biodiversity , 88–90. Our results indicate that vertebrate species richness in Colima increases gradually from the coast to higher elevations in northern and northwestern Colima. While bird, mammal and amphibian species richness followed similar patterns, it was the opposite for reptiles. Taking into consideration ecological characteristics, this similarity in spatial patterns (except for reptiles) indicate that members of one group may be used as an indicator of the distribution of the other groups. This “substitution” may facilitate systematic conservation planning and establishment of protected areas , 93. FurUnderstanding the strong relationship between geography and species characteristics  at multiple scales is a critical component of biodiversity conservation. For instance, the distribution pattern for the herpetofauna species richness along the Pacific lowlands and adjacent interior valleys of Mexico is similar to those for the endemic and endangered species probably because the high endemism and endangerment (30% across the region) is driving the species richness pattern . This spIsthmura bellii [Crotalus campbelli, a new described species from the C. triseriatus species group [Cryptotis alticola [Crotalus and Sistrurus genera [The extreme biogeographical heterogeneity and biodiversity of Colima, especially in the northern reaches of the state, is probably attributed to its geographical location. Colima is situated within both the Neotropical Realm and Mexican Transition Zone which include the contact zone of the Pacific Lowlands, Trans-Mexican Volcanic Belt and Sierra Madre del Sur Provinces where the Neotropical and Neartic biotas overlap , 15, 23.a bellii ; Crotalues group ; and Cryalticola . Centralalticola , 104 ands genera .The hotspots of all vertebrate groups, endemic and threatened species showed a similar spatial distribution across Colima; however, this pattern was not replicated among some groups for the coldspots. Only 28% of the hotspot grid cells are located within any of Colima’s four NPAs, and they do not represent enough area to protect all the hot spots and other conservation priority areas. These NPAs and the Cuyutlán Ramsar Site  which protect many different groups of vertebrates, endemics, and threatened species, currently enjoy formal protection because of their exceptional ecological and biodiversity value. For example, the 7,200-ha Laguna Cuyutlán (35 km long and 6 km in its widest point) which encompasses the 4,051 ha Ramsar site, is the largest wetland in a span of 1,150 km along the Pacific Coast , 107. ThThe use of multiple environmental variables to understand their influence on diversity patterns has been at the core of biogeographic research , 110, anWe contend that the strong spatial relationships we identified provides a valuable tool for immediate and longer-term systematic conservation planning by facilitating identification of critical areas throughout the state. Protection of Colima hotspots must be an urgent priority because of the rapid loss of natural vegetation and overall habitat loss in recent years. Currently, more than 80% of the landscape in Colima has been transformed or disturbed to varying degrees and only 16% has been conserved or has natural vegetation. Even though the Colima NPAs protect an important number of species, some of these areas have suffered severe deforestation and their role as refugia has been compromised. A comparison of the historical primary vegetation cover  with theS1 Fig(JPG)Click here for additional data file.S2 Fig(JPG)Click here for additional data file.S1 File(DOCX)Click here for additional data file.S2 File(XLSX)Click here for additional data file.S3 File(DOCX)Click here for additional data file.


Inequity, racism, and health care disparities negatively impact the well-being of children with kidney disease. This review defines social determinants of health and describes how they impact pediatric nephrology care; outlines the specific impact of systemic biases and racism on chronic kidney disease care and transplant outcomes; characterizes and critiques the diversity of the current pediatric nephrology workforce; and aims to provide strategies to acknowledge and dismantle bias, address barriers to care, improve diversity in recruitment, and strengthen the pediatric nephrology community. By recognizing historical and current realities and limitations, we can move forward with strategies to address racism and bias in our field and clinical practices, thereby cultivating inclusive training and practice environments. Sociologist Edwin Lindo defines race as “a socio-politically constructed taxonomy…invented on factors such as perceived skin color and culture, not science or biology”. Yet, inaccurate assumptions about the biological significance of race have permeated medical science at all levels—in the classroom, in the laboratory, in the operating suite, and at the bedside. In 2004, as science became capable of articulating new knowledge about human genetic variation, geneticist Francis Collins asserted that “‘race’ and ‘ethnicity’ are poorly defined terms that serve as flawed surrogates for multiple environmental and genetic factors in disease causation, including ancestral geographic origins, socioeconomic status, education and access to health care. Research must move beyond these weak and imperfect proxy relationships to define the more proximate factors that influence health” .Twenty years later, race and racism continue to impact health inequities. In 2020, the deaths of Ahmaud Arbery, Breonna Taylor, George Floyd, and multiple other victims forced broader acknowledgement of the enduring life-and-death reality of racism. The concomitant COVID-19 pandemic cast a brighter light on how social determinants of health (SDoH) influenced exposure to illness, access to care, and mortality rates  convened a series of lectures designed to educate the pediatric nephrology community on the most recent and impactful data describing barriers to equitable care, the impact of SDoH and racism on pediatric CKD and transplant outcomes, and the state of the current pediatric nephrology workforce through the lens of diversity, equity and inclusion. A roadmap of curricular resources and next directions was also presented. This review summarizes salient points communicated during those lectures.“When it comes to health, your zip code is more important than your genetic code.”—Dr. Garth Graham .In 400 BC, Hippocrates observed that poor environmental settings are bad for health , a truthThe World Health Organization (WHO) convened a Commission on SDoH in 2008 and called for a three-tiered approach: (1) Improve daily conditions, (2) Tackle the inequitable distribution of power, money and resources, and (3) Measure and understand the problem and assess the impact of action. The American Academy of Pediatrics (AAP) issued a policy statement in 2016 entitled “Poverty and child health in the US,” which urged pediatricians to routinely screen for SDoH. In 2019, an AAP survey found that 62% of pediatricians felt that SDoH screening was important, however, only 39% felt it was feasible, and just 20% felt prepared to address patient needs . Data frIn 2019, Crews and Novick characterized chronic kidney disease (CKD) hotspots: “countries, regions, communities or ethnicities with higher-than-average incidence of CKD when compared with the worldwide, country or regional rates” . They anThe role that diet and access to food plays in the causation and prevention of obesity and heart disease has been studied for decades, and food deserts are often seen in lower income areas and where greater numbers of people of color live. Morland et al. examined populations in four states , and discovered an association between the physical availability of food stores and food service businesses and people's adherence to health authorities’ recommendations for a healthy diet . Authors•“Within the past 12 months [we] worried whether [our] food would run out before [we] got money to buy more”•“Within the past 12 months the food [we] bought just didn't last and [we] didn't have money to get more.”In this group, there was an association between food insecurity and number of emergency department visits, unplanned admissions, and a statistically significant link between positive screening for food insecurity and number of infections  as lack of consistent access to a sufficient quantity of affordable and nutritious food, is linked to increased health care use and expenditure, even when accounting for other socioeconomic factors. Berkowitz et al. determined that food insecurity was associated with higher rates of emergency department visits, hospitalizations, and duration of days hospitalized . Living fections . In respfections .Income and education. A pediatric subspecialty study in British Columbia determined that in children with CKD, lower level of family income  was associated with more rapid decline in glomerular filtration rate (GFR). Moreover, lower caregiver education was associated with poorer health outcomes . MontiniIntensive early education of children poses the potential to improve health and social outcomes. The Carolina Abecedarian Project (ABC) was a randomized controlled trial of early education which enrolled infants from 1972 to 1977 at the Frank Porter Graham Child Development Institute in Chapel Hill, North Carolina . One-hunIn summary, SDoHs play a profound role in health outcomes. They intersect with racism and discrimination, and such inequities confer significantly increased morbidity and mortality particularly in Black and Hispanic children. As such, pediatricians and subspecialists should advocate for regular SDoH screening and for creating systems to connect patients to resources, especially when needs could close existing gaps in health inequities. Health care systems, and local and national governments can address SDoH for children by advocating for and supporting greater distribution of funding and access to resources for all children, especially in communities that have historically experienced systematic denial of capital. Studying CKD “hotspots” more closely may prove an additional strategy to implement interventions in the kidney patient population .In addition to providing a direct barrier to equitable health services, racism also exerts a biological impact on the sufferer, further contributing to poor health outcomes. The biological effects of racism and discrimination include increased allostatic load which represents the cumulative burden of chronic stress. This manifests as increased sympathetic nervous system activity, altered gene expression and alterations in the metabolism of hormones like cortisol and insulin. This combination contributes to the genesis of disparate disease outcomes. For kidney disease, these mechanisms are directly associated with factors which worsen kidney disease progression including hyperfiltration, inflammation, and renin angiotensin aldosterone system activation .CKD and ESKD disproportionately affect patients of color, with a four-fold increased incidence in Black patients and two-fold increase in Hispanic individuals . Compareaccentuated with higher maternal education.In pediatrics, racial bias has been linked to numerous disparate outcomes in care, even before infants are born, and these impacts can be observed in the pediatric nephrology clinic. Disparities in gestational age and birth weight are of interest to the nephrologist due to the link between nephron endowment and later CKD and hypertension (HTN) risk . Burris Orchard et al. underscored the connection between health outcomes and the experience of racism in their 2017 study examining prejudice and the association with preterm birth . Using rA 2011 study by Gutierrez et al. illustrated the impact of SDoH on CKD-relevant outcomes. Fourteen thousand adult participants enrolled in the National Health and Nutrition Examination Survey (NHANES) were evaluated, and in both the unadjusted and fully adjusted models, worsening poverty was associated with increased odds of hyperphosphatemia. The most severely impoverished patients had a 2.2-fold higher odds of hyperphosphatemia as compared to the highest income group. This association was observed despite lower reported phosphate intake within the most impoverished group. This discrepancy may reflect hidden phosphorus sources such as the consumption of phosphorus-rich additives frequently found in highly processed foods .Recent literature details the impact of systemic bias and racism on pediatric nephrology care and outcomes. The Chronic Kidney Disease in Children (CKiD) study demonstrated racial differences in CKD progression. In 110 Black or African-American and 493 non-African American children with non-glomerular CKD, Ng et al. reported a higher rate of decline in GFR per year with children identified as Black or African-American, with a decline of 6.2% per year decline as compared to a decline of 4.3% per year in non-African-American children . Of notep < 0.001). Furthermore, in multivariate analysis, Black patients without the high risk APOL1 genotype also had greater risk of GFR decline as compared to White patients. This latter finding suggests that despite promising targets like APOL1 impacting genetic predisposition to ESKD progression, this is only part of the story and does not fully account for observed disparities.Another area of interest is in understanding the role of genetic markers, such as Apolipoprotein L1 (APOL1), on mediating disparities in CKD progression. Parsa et al. recognized that patients of black ancestry were at increased risk for ESKD compared to White patients, and examined the effects of gene variants encoding APOL1 on progression to ESKD . PatientUnfortunately, once patients progress to end stage kidney disease and require dialysis, racial-ethnic differences in survival are further highlighted. Laster et al. analyzed approximately 2,600 children from a large dialysis organization and found a 64% higher risk of mortality in Black children as compared to White children . There wPre-emptive transplantation requires early recognition of kidney disease progression and rapid access to pre-ESKD nephrology care. There are known racial-ethnic differences in the receipt of pre-emptive transplant. Patzer et al. collected 9 years of data on living donor transplant in children between 2000 and 2009  and deteNot only are minority children less likely to receive a pre-emptive transplant, they are also less likely to receive a living donor transplant in general. Amaral et al. studied 19,722 incident ESKD pediatric patients who received living donor transplants and demonstrated that the overall number of living donor transplants decreased between 2005 and 2015 with rates varying according to racial group. Black children were 62% less likely to receive a living donor kidney transplant (LDKT), Hispanic children were 46% less likely, and children of Asian background were 63% less likely than White children . There wEven after receiving a transplant, survival in Black patients is lower when compared to White patients. Becerra et al. provided a comprehensive view of survival and transplant outcomes by analyzing data from approximately 28,000 participants included in the United States Renal Data System (USRDS) wherein kidney replacement therapy was initiated prior to 18 years of age. Thirty years after the onset of kidney replacement therapy , 39% of Black patients survived as compared to 57% of White patients, indicating a 45% higher risk of mortality for Black patients, even after adjusting for clinical factors, income, and insurance status . Black cAn additional factor crucial to this discussion is that the effects of racism may directly impair patients’ abilities to process and implement medical recommendations. A 2021 study on executive functioning in a multiethnic cohort of 319 college students evaluated the association between recent experiences of discrimination and the components of executive function including working memory, cognitive flexibility and inhibitory control . Having One potentially modifiable factor protecting minoritized patient populations is physician-patient racial concordance. Physician-patient racial concordance improves patient satisfaction, patient-provider communication and medication adherence . In a stUnfortunately, certain racial and ethnic populations remain under-represented in medicine (URiM). In 2003, the AAMC defined URiM as “those racial and ethnic populations that are underrepresented in the medical profession relative to their numbers in the general population” with the objective to evolve with the changing demographics of society and the medical profession, and focus on regional and local perspectives . URiM poThe most recent AMA Physician Masterfile Survey indicated that of 936,254 physicians surveyed in 2019, 63.7% of physicians were male and 36.3% were female . The datvia 14 distinct ethnic groups which are not sub-analyzed  and that Asians represent 21%, though analyzed . The peranalyzed . Similarvia email survey to any candidates listed by the American Board of Pediatrics as “board eligible” or “board certified” in pediatric nephrology, members of the ASPN, and members of the AAP Section on Nephrology at the time of the survey. 504 of 766 eligible physicians responded (response rate: 65.8%). Trainees were not included. Although 51% of pediatric nephrologists identified as male, 64% of recent fellowship graduates (<15 years from training) were women  of 1st year medical students were from the top quintile of US household income, defined as >$225,251, reflecting the top 5% earners . Data su“Our ability to reach unity in diversity will be the beauty and the test of our civilization.”—Mahatma Gandhi.There is no denying the overwhelming evidence on the importance of diversifying the pediatric nephrology workforce to better serve our patients. Additionally, diversity has been shown to enhance scientific advancement. Teams that include a broad array of backgrounds  benefit from a broader network of ideas . MembersLow applicant diversity stems from lack of role models which then leads to less engagement by URiM candidates into the pipeline. Recognizing the critical role of mentorship, various stakeholders in nephrology including the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), ASN, and ASPN have developed targeted nephrology trainee pipeline programs that provide undergraduate, medical and PhD students, and pediatric residents with early exposure to the field . While tAnother unique aspect in pediatric nephrology is the large proportion of International Medical Graduates (IMGs) which constitute approximately 30%–55% of the US pediatric nephrology trainee workforce based on the trends tracked by the American Board of Pediatrics (ABP) since 2004 . The abiAppointment bias refers to a perpetual culture of hiring practices that fail to recruit diverse candidates due to a combination of explicit and/or implicit bias, and lack of institutional commitment to equity, diversity and inclusion. The notion of “colorblind” hiring practices that aim to treat individuals as equally as possible, have unfortunately perpetuated pre-existing negative racial experiences of people of color, rejecting their heritage, and invalidating their unique perspectives. While most, if not all institutions have clear policies and escalation procedures to address explicit bias in the workplace, implicit bias is much more difficult to discern. Implicit bias refers to the unconscious attitude and beliefs that affect the feelings, behavior and judgment of a person towards another. On many occasions, the person exhibiting the implicit bias is unaware of the implications of their actions at that moment. However, those actions (or inactions) can negatively affect the quality of the interaction with the other party and potentially contribute to adverse recruitment outcomes. The medical field, and pediatrics specifically, is not immune to implicit bias in its many forms, be it gender bias, racial-ethnic bias, or others. Reference letters within medicine and medical education exhibit language discrepancies between men and women applicants with women applicants more likely to be described using communal adjectives, such as “delightful” or “compassionate”, while men applicants more likely to be described using agentic adjectives, such as “leader” or “exceptional” , though a collective institutional led effort to engage in meaningful discussions surrounding IAT test results is likely necessary for those individual efforts to reduce appointment bias. On an institutional level, adopting diverse recruitment strategies that include restructuring interview and search panels to include more diverse perspectives, using inclusive language in job advertisements, implicit bias staff training, and extending recruitment outreach beyond a typical “safe” pool of candidates used in the past, is key to mitigating appointment bias.Departure bias describes the comparison of the diversity of the employees leaving an institution with the overall diversity of that institution  members of the trainee pipeline and academic workforce; many of whom may hide or do not disclose their sexual or gender identity due to fear of discrimination . These aIt is evident that given the historical underpinnings of structural racism, dismantling inequities will require collective advocacy on a legislative level. Issues such as pediatric subspecialty loan repayment, NIH funding priorities, and payment parity with our adult nephrology counterparts are all critical to improving applicant diversity, and mitigating appointment and departure bias in pediatric nephrology. The ASPN has long supported those efforts by establishing the John E. Lewy Foundation (JELF) Advocacy Scholars program that serves as a mechanism to train and develop the next generation of effective pediatric nephrology advocates . The JELFinally, pediatric nephrology divisions require intentional strategic planning in regards to health equity. Dawson et al. describe the Nationwide Children's Hospital Kidney Health Advocacy and Community Engagement (KHACE) initiative, wherein multidisciplinary teams promote layered changes in the domains of research, education, engagement and policy within a socioecologic model of health . Action via two main mechanisms: first, by enforcing a pervasive system of inequality through social determinants of health; and secondly, by generating a biologic impact on sympathetic nervous system activity, altered gene expression and altered hormonal metabolism (The pediatric nephrology care team must understand that race is a social construct with lasting and profound impacts on the minoritized, and that physicians should acknowledge social determinants of health along with understanding of pathophysiology, diagnosis, and treatment planning. Pediatric specialists must acknowledge the role racism contributes to disparate health outcomes tabolism . The imptabolism , and it