To Split or Not to Split: Characterizing Chemical Pollution Impacts in Aquatic Ecosystems with Species Sensitivity Distributions for Specific Taxonomic Groups.

Bridging applied ecology and ecotoxicology is key to protect ecosystems. These disciplines show a mismatch, especially when evaluating pressures. Contrasting to applied ecology, ecotoxicological impacts are often characterized for whole species assemblages based on Species Sensitivity Distributions (SSDs). SSDs are statistical models describing per chemical across-species sensitivity variation based on laboratory toxicity tests. To assist in the aligning of the disciplines and improve decision-support uses of SSDs, we investigate taxonomic-group-specific SSDs for algae/cyanobacteria/aquatic plants, invertebrates, and vertebrates for 180 chemicals with sufficient test data. We show that splitting improves pollution impact assessments for chemicals with a specific mode of action and, surprisingly, for narcotic chemicals. We provide a framework for splitting SSDs that can be applied to serve in environmental protection, life cycle assessment, and management of freshwater ecosystems. We illustrate that using split SSDs has potentially large implications for the decision-support of SSD-based outputs around the globe.

Turner syndrome: skin, liver, eyes, dental and ENT evaluation should be improved.

Introduction: Turner syndrome association with multi-organ system comorbidities highlights the need for effective implementation of follow-up guidelines. We aimed to assess the adequacy of care with international guidelines published in 2007 and 2017 and to describe the phenotype of patients. Methods: In this multicenter retrospective descriptive cohort study, we collected growth and pubertal parameters, associated comorbidities, treatment, and karyotype in patients diagnosed at age <18 years between 1993 and 2022. We assessed age-appropriate recommendation follow-up (children, adolescents and adults) according to the 2007 guidelines if the last visit was before 2017 (18 recommendations) and the 2017 guidelines if the last visit was after 2017 (19 recommendations). Results: We included 68 patients followed at Lausanne University Hospital (n=64) and at Neuchatel Regional Hospital (RHNe) (n=4). 2.9% of patients underwent all recommended investigations.Overall, 68.9 ± 22.5% and 78.5 ± 20.6% of the recommendations were followed, before and after 2017 respectively. High implementation rates were found for height, weight and BMI (100%), cardiac (80 to 100%) and renal (90 to 100%) imaging. Low implementation rates were found for Ear, Nose and Throat (ENT) (56.5%), skin (38.5%), dental (23.1%), ophthalmological (10%) and cholestasis (0 to 29%) assessments, depending on age and time of visit. In adults (n=33), the mean proportion of followed recommendations was lower before than after 2017: 63.5 ± 25.8% vs. 78.7 ± 23.4%, p=0.039. Conclusion: Growth parameters, cardiac and renal imaging are well followed. However, efforts should be made for dental, ENT, ophthalmological, skin and cholestasis assessments. Adequacy of follow-up improved with the quality of transition to adult care.

Hybrid Prediction-Driven High-Throughput Sustainability Screening for Advancing Waste-to-Dimethyl Ether Valorization.

Assessing the prospective climate preservation potential of novel, innovative, but immature chemical production techniques is limited by the high number of process synthesis options and the lack of reliable, high-throughput quantitative sustainability pre-screening methods. This study presents the sequential use of data-driven hybrid prediction (ANN-RSM-DOM) to streamline waste-to-dimethyl ether (DME) upcycling using a set of sustainability criteria. Artificial neural networks (ANNs) are developed to generate in silico waste valorization experimental results and ex-ante model the operating space of biorefineries applying the organic fraction of municipal solid waste (OFMSW) and sewage sludge (SS). Aspen Plus process flowsheeting and ANN simulations are postprocessed using the response surface methodology (RSM) and desirability optimization method (DOM) to improve the in-depth mechanistic understanding of environmental systems and identify the most benign configurations. The hybrid prediction highlights the importance of targeted waste selection based on elemental composition and the need to design waste-specific DME synthesis to improve techno-economic and environmental performances. The developed framework reveals plant configurations with concurrent climate benefits (-1.241 and -2.128 kg CO2-eq (kg DME)-1) and low DME production costs (0.382 and 0.492 € (kg DME)-1) using OFMSW and SS feedstocks. Overall, the multi-scale explorative hybrid prediction facilitates early stage process synthesis, assists in the design of block units with nonlinear characteristics, resolves the simultaneous analysis of qualitative and quantitative variables, and enables the high-throughput sustainability screening of low technological readiness level processes.

Glucose variability in 6-12-month-old healthy infants.

Background: Metabolic programming of glucose homeostasis in the first 1,000 days of life may impact lifelong metabolic and cardiovascular health. Continuous glucose monitoring (CGM) devices may help measure the impact of dietary intake on glucose rhythms and metabolism in infants during the complementary feeding period. Objectives: Demonstrate the feasibility of CGM to measure and quantify glucose variability in response to infant feeding and to evaluate associations between macronutrient meal composition and glucose variability. Methods: The "FreeStyle Libre Pro®" device interstitial glucose meter was applied to the anterior thigh of 10 healthy 6-12-month-old infants. Parents recorded food intake, time of feeding, and used daily dairies to record sleep time and duration. Descriptive statistics were employed for food intake, sleep and key glycemic parameters over three full days. Mixed linear models were used to assess glycemic changes. Results: Mid-day, afternoon, and evening feeds contained >30 g carbohydrate and induced higher 2-h iAUC (3.42, 3.41, and 3.50 mmol/L*h respectively) compared to early and mid-morning feedings with ≤25 g carbohydrates (iAUC 2.72 and 2.81 mmol/L*h, p < 0.05). Early morning and evening milk feedings contained approximately 9 g of fat and induced a longer time to reach maximal glucose value (Tmax; 75 and 68 min, respectively) compared to lower fat feedings (2.9-5.9 g; Tmax range: 34-60 min; p < 0.05). Incremental glucose value at time of food intake (C0) increased significantly from 0.24 ± 0.39 mM in early morning to 1.07 ± 0.57 mM in the evening (p < 0.05). Over the day, 70% of glucose values remained within the normal range (3.5-5.5 mmol/L), 10% were between 5.5-10 mmol/L, and 20% were < 3.5 mmol/L. Conclusion: Our data support the feasibility of using CGM to measure glucose in 6-12-month-old infants. The observation of possible diurnal glucose variability and typical glucose values may have implications for future studies investigating metabolic adaptation to nutritional intake in early life.

Resource efficiency analysis through planetary boundary-based life cycle assessment: a case study of sugarcane in Pakistan.

Purpose: Extensive agriculture activities for crop production have led to increasing environmental impacts that threaten to exceed environmentally safe limits. The purpose of this study is to analyze resource efficiency of the agri-food industry, considering the case of sugarcane production in Pakistan. Methods: A holistic approach has been applied by determining the relevant impact categories and Sustainable Development Goals (SDGs), and linking them with Planetary Boundary-based Life Cycle Assessment (PB-LCA). Both the spatially generic and spatially resolved approaches were considered with application of different sharing principles. Results and discussion: Application of different sharing principles showed high variations in the assigned share of the safe operating space values. When taking a spatially generic approach, most of the impacts (except marine eutrophication and water consumption) were within the safe operating space for equal per capita, economic, caloric, and grandfathering sharing principles. However, all the impacts exceeded their limits considering the agri-land sharing and land use impact surpassed its budget considering the grandfathering sharing. In the spatially resolved approach, most of the impact values surpassed the available budgets. Furthermore, the failure to attain the pertinent SDG targets from a PB-LCA perspective is indicated by the exceeding of safe operating space for relevant impact categories. Conclusions: Overall, the production of sugarcane was found to be unsustainable, requiring urgent action to promote resource improvement and contain the impacts within safe limits. The developed framework enabled the evaluation of the SDGs using PB-LCA at the product level. The target-driven impact reduction values would help in achieving the targets and prioritizing the efforts by making informed decisions for reducing impacts within safe limits. Supplementary Information: The online version contains supplementary material available at 10.1007/s11367-023-02185-7.

Multicompartment Depletion Factors for Water Consumption on a Global Scale.

Balancing human communities' and ecosystems' need for freshwater is one of the major challenges of the 21st century as population growth and improved living conditions put increasing pressure on freshwater resources. While frameworks to assess the environmental impacts of freshwater consumption have been proposed at the regional scale, an operational method to evaluate the consequences of consumption on different compartments of the water system and account for their interdependence is missing at the global scale. Here, we develop depletion factors that simultaneously quantify the effects of water consumption on streamflow, groundwater storage, soil moisture, and evapotranspiration globally. We estimate freshwater availability and water consumption using the output of a global-scale surface water-groundwater model for the period 1960-2000. The resulting depletion factors are provided for 8,664 river basins, representing 93% of the landmass with significant water consumption, i.e., excluding Greenland, Antarctica, deserts, and permanently frozen areas. Our findings show that water consumption leads to the largest water loss in rivers, followed by aquifers and soil, while simultaneously increasing evapotranspiration. Depletion factors vary regionally with ranges of up to four orders of magnitude depending on the annual consumption level, the type of water used, aridity, and water transfers between compartments. Our depletion factors provide valuable insights into the intertwined effects of surface and groundwater consumption on several hydrological variables over a specified period. The developed depletion factors can be integrated into sustainability assessment tools to quantify the ecological impacts of water consumption and help guide sustainable water management strategies, while accounting for the performance limitations of the underlying model.

Advancing water footprint assessments: Combining the impacts of water pollution and scarcity.

Several water footprint indicators have been developed to curb freshwater stress. Volumetric footprints support water allocation decisions and strive to increase water productivity in all sectors. In contrast, impact-oriented footprints are used to minimize the impacts of water use on human health, ecosystems, and freshwater resources. Efforts to combine both perspectives in a harmonized framework have been undertaken, but common challenges remain, such as pollution and ecosystems impacts modelling. To address these knowledge gaps, we build upon a water footprint assessment framework proposed at conceptual level to expand and operationalize relevant features. We propose two regionalized indicators, namely the water biodiversity footprint and the water resource footprint, that aggregate all impacts from toxic chemicals, nutrients, and water scarcity. The first impact indicator represents the impacts on freshwater ecosystems. The second one models the competition for freshwater resources and its consequences on freshwater availability. As part of the framework, we complement the two indicators with a sustainability assessment representing the levels above which ecological and human freshwater needs are no longer sustained. We test our approach assessing the sustainability of water use in the European Union in 2010. Water stress hampers 15 % of domestic, agricultural and industrial water demand, mainly due to irrigation and pesticide emissions in southern Europe. Moreover, damage to the freshwater ecosystems is widespread and mostly resulting from chemical emissions from industry. Approximately 5 % of the area is exceeding the regional sustainability limits for ecosystems and human water requirements altogether. Concerted efforts from all sectors are needed to reduce the impacts of emissions and water consumption under the sustainability limits. These advances are considered an important step toward the harmonization of volumetric and impact-oriented approaches to achieve consistent and holistic water footprinting as well as contributing to strengthen the policy relevance of water footprint assessments.

[Monogenic diabetes : a pioneer in precision medicine management]. / Diabète monogénique : pionnier dans la prise en charge par la médecine de précision.

Diabetes mellitus in children is subdivided into several categories depending on the underlying pathological mechanism. Type 1 diabetes is due to the autoimmune destruction of pancreatic beta-cells, type 2 diabetes to progressive impairment in insulin secretion or insulin sensitivity, and monogenic diabetes due to genetic abnormalities, impairing insulin secretion. In monogenic diabetes, genetic defects result in pancreatic or beta-cell defects (abnormal function or destruction), resulting in neonatal or MODY (Maturity-Onset Diabetes of the Young) diabetes, depending on the age of onset. The identification of monogenic diabetes is crucial as it allows the initiation of targeted and personalized treatment.

Le diabète sucré de l'enfant est subdivisé en plusieurs catégories en fonction du mécanisme pathologique sous-jacent : de type 1 par destruction autoimmune des cellules bêta du pancréas, de type 2 par perte progressive d'une sécrétion adéquate ou de sensibilité à l'insuline et monogénique par anomalie génétique perturbant la sécrétion d'insuline. Dans ce dernier, les anomalies génétiques entraînent des défauts du développement du pancréas ou de la cellule bêta (anomalie de fonction ou destruction), menant à un diabète néonatal ou un diabète MODY (Maturity-Onset Diabetes of the Young) en fonction de l'âge d'apparition. L'identification du diabète monogénique est primordiale puisqu'elle permet l'instauration d'un traitement ciblé et personnalisé.

[Obesity in infancy: new precision treatment]. / Obésité infantile : nouveautés thérapeutiques ciblées.

Obesity is a chronical disease, which leads to multiple short- and long-term complications. 4% of Swiss children and adolescents are obese. A prompt diagnosis and multicomponent lifestyle intervention is mandatory to avoid persistence of the disease into adulthood. Growth and BMI charts are still the essential tools to diagnose and define the etiology of obesity. A precocious and severe obesity, accompanied by hyperphagia, will raise the suspicion of monogenic obesity. The precise molecular diagnosis enables in some patients the use of a specific treatment. Leptine in case of LEP gene defects, or setmelanotide when the affected gene is part of the MC4R signaling pathway (LEPR, POMC, PCSK1).

L'obésité est une maladie chronique, associée à de multiples complications à court et à long termes, présente chez 4 % des enfants et adolescents en Suisse. Un dépistage et une intervention multidisciplinaire précoces sont essentiels pour éviter la persistance de la maladie à l'âge adulte. Les courbes de croissance et de l'IMC sont les outils indispensables pour repérer la maladie et orienter l'étiologie. Ainsi, une obésité d'apparition précoce, de caractère sévère et accompagnée d'une hyperphagie oriente le clinicien vers le diagnostic d'obésité monogénique. Un diagnostic moléculaire précis permet de connaître le gène défectueux et offre, dans certains cas, un traitement ciblé très efficace pour le patient : la leptine en cas de mutation du gène LEP, ou le setmélanotide dans les défauts de la voie de signalisation du MC4R (LEPR, POMC, PCSK1).

Linking freshwater ecotoxicity to damage on ecosystem services in life cycle assessment.

Freshwater ecosystems provide major benefits to human wellbeing-so-called ecosystem services (ES)-but are currently threatened among others by ecotoxicological pressure from chemicals reaching the environment. There is an increased motivation to incorporate ES in quantification tools that support decision-making, such as life cycle assessment (LCA). However, mechanistic models and frameworks that can systematically translate ecotoxicity effect data from chemical tests into eventual damage on species diversity, functional diversity, and ES in the field are still missing. While current approaches focus on translating predicted ecotoxicity impacts to damage in terms of species loss, no approaches are available in LCA and other comparative assessment frameworks for linking ecotoxicity to damage on ecosystem functioning or ES. To overcome this challenge, we propose a way forward based on evaluating available approaches to characterize damage of chemical pollution on freshwater ES. We first outline an overall framework for linking freshwater ecotoxicity effects to damage on related ES in compliance with the boundary conditions of quantitative, comparative assessments. Second, within the proposed framework, we present possible approaches for stepwise linking ecotoxicity effects to species loss, functional diversity loss, and damage on ES. Finally, we discuss strengths, limitations, and data availability of possible approaches for each step. Although most approaches for directly deriving damage on ES from either species loss or damage to functional diversity have not been operationalized, there are some promising ways forward. The Threshold Indicator Taxa ANalysis (TITAN) seems suitable to translate predicted ecotoxicity effects to a metric of quantitative damage on species diversity. A Trait Probability Density Framework (TPD) approach that incorporates various functional diversity components and functional groups could be adapted to link species loss to functional diversity loss. An Ecological Production Function (EPF) approach seems most promising for further linking functional diversity loss to damage on ES flows for human wellbeing. However, in order to integrate the entire pathway from predicted freshwater ecotoxicity to damage on ES into LCA and other comparative frameworks, the approaches adopted for each step need to be harmonized in terms of assumptions, boundary conditions and consistent interfaces with each other.

Ecotoxicity characterization of chemicals: Global recommendations and implementation in USEtox.

Chemicals emitted to the environment affect ecosystem health from local to global scale, and reducing chemical impacts has become an important element of European and global sustainability efforts. The present work advances ecotoxicity characterization of chemicals in life cycle impact assessment by proposing recommendations resulting from international expert workshops and work conducted under the umbrella of the UNEP-SETAC Life Cycle Initiative in the GLAM project (Global guidance on environmental life cycle impact assessment indicators). We include specific recommendations for broadening the assessment scope through proposing to introduce additional environmental compartments beyond freshwater and related ecotoxicity indicators, as well as for adapting the ecotoxicity effect modelling approach to better reflect environmentally relevant exposure levels and including to a larger extent chronic test data. As result, we (1) propose a consistent mathematical framework for calculating freshwater ecotoxicity characterization factors and their underlying fate, exposure and effect parameters; (2) implement the framework into the USEtox scientific consensus model; (3) calculate characterization factors for chemicals reported in an inventory of a life cycle assessment case study on rice production and consumption; and (4) investigate the influence of effect data selection criteria on resulting indicator scores. Our results highlight the need for careful interpretation of life cycle assessment impact scores in light of robustness of underlying species sensitivity distributions. Next steps are to apply the recommended characterization framework in additional case studies, and to adapt it to soil, sediment and the marine environment. Our framework is applicable for evaluating chemicals in life cycle assessment, chemical and environmental footprinting, chemical substitution, risk screening, chemical prioritization, and comparison with environmental sustainability targets.

High Prevalence of Hypovitaminosis D in Adolescents Attending a Reference Centre for the Treatment of Obesity in Switzerland.

Background: Hypovitaminosis D is common in populations with obesity. This study aimed at assessing (1) the prevalence of hypovitaminosis D and (2) the associations between vitamin D levels and cardiovascular risk factors in adolescents attending a reference centre for the treatment of obesity. Design: Cross-sectional pilot study conducted in the paediatric obesity unit of the Lausanne university hospital, Switzerland. Methods: Participants were considered eligible if they (1) were aged between 10 to 16.9 years and (2) consulted between 2017 and 2021. Participants were excluded if (1) they lacked vitamin D measurements or (2) the vitamin D measurement was performed one month after the base anthropometric assessment. Hypovitaminosis D was considered if the vitamin D level was <30 ng/mL (<75 nmol/L). Severe obesity was defined as a BMI z-score > 3 SD. Results: We included 52 adolescents (31% girls, mean age 13 ± 2 years, 33% with severe obesity). The prevalence of hypovitaminosis D was 87.5% in girls and 88.9% in boys. The vitamin D levels were inversely associated with BMI, Spearman r and 95% CI: −0.286 (−0.555; −0.017), p = 0.037; they were not associated with the BMI z-score: −0.052 (−0.327; 0.224), p = 0.713. The vitamin D levels were negatively associated with the parathormone levels (−0.353 (−0.667; −0.039), p = 0.028) and positively associated with the calcium levels (0.385 (0.061; 0.708), p = 0.020), while no association was found between vitamin D levels and blood pressure and lipid or glucose levels. Conclusion: almost 9 out of 10 adolescents with obesity in our cohort presented with hypovitaminosis D. Hypovitaminosis D does not seem to be associated with a higher cardiovascular risk profile in this group.

[New technology of diabetes management: learning together and in situation]. / Nouvelle technologie de gestion du diabète: apprendre ensemble et en situation.

The introduction of a new technology for the management of diabetes raises questions about their actual use. This is the case with the Freestyle Libre sensor, a tool that measures the interstitial glucose levels. Some studies have provided recommendations about its use, but little is known about how users learn to use it in the daily management of the disease. This ethnographic research explores this issue in the context of a summer camp for young people living with diabetes. The results describe three different levels (material, epistemic and moral) at which learning occurs. They show that its use requires an active appropriation process, the importance of a setting that promotes interactions between the participants and that the features of the tend to reconfigure the expert-lay person relationship.

L'introduction d'une nouvelle technologie de gestion du diabète soulève des questions sur son usage effectif. C'est le cas du capteur FreeStyle Libre, un outil mesurant la glycémie interstitielle. Des études ont fourni des recommandations sur son usage, mais on en sait peu sur la manière dont les usager-ère-s apprennent à l'utiliser dans la gestion quotidienne du diabète. Cette recherche ethnographique étudie cette question dans le cadre d'un camp d'été pour jeunes vivant avec un diabète. Les résultats décrivent trois niveaux différents (matériel, épistémique et moral) auxquels cet apprentissage se réalise. Ils montrent que son usage requiert un travail d'appropriation actif, l'intérêt d'un dispositif qui favorise les interactions entre participant-e-s et que les caractéristiques de l'outil tendent à reconfigurer la relation expert-profane.

Navigating Disrupted Puberty: Development and Evaluation of a Mobile-Health Transition Passport for Klinefelter Syndrome.

Klinefelter syndrome (KS) is the most common aneuploidy in men and has long-term sequelae on health and wellbeing. KS is a chronic, lifelong condition and adolescents/young adults (AYAs) with KS face challenges in transitioning from pediatric to adult-oriented services. Discontinuity of care contributes to poor outcomes for health and wellbeing and transition programs for KS are lacking. We aimed to develop and test a mobile health tool (KS Transition Passport) to educate patients about KS, encourage self-management and support successful transition to adult-oriented care. First, we conducted a retrospective chart review and patient survey to examine KS transition at a university hospital. Second, we conducted a systematic scoping review of the literature on AYAs with KS. Last, we developed a mobile health transition passport and evaluated it with patient support groups. Participants evaluated the tool using the System Usability Scale and Patient Education Materials Assessment Tool (PEMAT). Chart review identified 21 AYAs diagnosed between 3.9-16.8 years-old (median 10.2 years). The survey revealed only 4/10 (40%) were on testosterone therapy and fewer (3/10, 30%) had regular medical care. The scoping review identified 21 relevant articles highlighting key aspects of care for AYAs with KS. An interprofessional team developed the mobile-health KS transition passport using an iterative process. Support group members (n=35) rated passport usability as 'ok' to 'good' (70 ± 20, median 73.5/100). Of PEMAT dimensions, 5/6 were deemed 'high quality' (86-90/100) and participants knew what to do with the information (actionability = 83/100). In conclusion, many patients with KS appear to have gaps in transition to adult-oriented care. Iterative development of a KS transition passport produced a mobile health tool that was usable, understandable and had high ratings for actionability.

Spatially differentiated marine eutrophication method for absolute environmental sustainability assessments.

Marine eutrophication and hypoxia caused by excess nutrient availability is a growing environmental problem. In this study, we explore marine nitrogen enrichment in the context of Absolute Environmental Sustainability Assessment (AESA), a method combining life cycle assessment (LCA) with environmental boundaries aiming to compare environmental impacts from an activity (product or system) with the safe operating space (SOS) for the activity. Specifically, we aim to increase the spatial resolution and improve life cycle impact assessment (LCIA) models for marine eutrophication for use in AESAs. By estimating a proxy of the areal extent of eutrophication and hypoxia in coastal large marine ecosystems (LME), we increased model resolution from 66 LMEs in the original LCIA method to 289 coastal LME subsegments and updated relevant LME parameters to the new scale (residence time, bottom water volume, reference O2 concentration, primary production rates and depths). The new method was tested and validated by comparing the global and spatially differentiated occupation of SOS by global nitrogen emissions with observations and it showed an improved ability to identify critical areas where the SOS is exceeded, in accordance with observations of hypoxic events. Despite limitations such as the estimation of benthic zone volume and low spatial differentiation of environmental boundaries, the method can be used by AESA and LCA practitioners wishing to assess the impact of nitrogen release on marine eutrophication with a higher and more relevant spatial resolution.

Toward Assessing Absolute Environmental Sustainability of Chemical Pollution.

Chemicals are widely used in modern society, which can lead to negative impacts on ecosystems. Despite the urgent relevance for global policy setting, there are no established methods to assess the absolute sustainability of chemical pressure at relevant spatiotemporal scales. We propose an absolute environmental sustainability framework (AESA) for chemical pollution where (1) the chemical pressure on ecosystems is quantified, (2) the ability for ecosystems to withstand chemical pressure (i.e., their carrying capacity) is determined, and (3) the "safe space" is derived, wherein chemical pressure is within the carrying capacity and hence does not lead to irreversible adverse ecological effects. This space is then allocated to entities contributing to the chemical pressure. We discuss examples involving pesticide use in Europe to explore the associated challenges in implementing this framework (e.g., identifying relevant chemicals, conducting analyses at appropriate spatiotemporal scales) and ways forward (e.g., chemical prioritization approaches, data integration). The proposed framework is the first step toward understanding where and how much chemical pressure exceeds related ecological limits and which sources and actors are contributing to the chemical pressure. This can inform sustainable levels of chemical use and help policy makers establish relevant and science-based protection goals from regional to global scale.

Outside the Safe Operating Space of the Planetary Boundary for Novel Entities.

We submit that the safe operating space of the planetary boundary of novel entities is exceeded since annual production and releases are increasing at a pace that outstrips the global capacity for assessment and monitoring. The novel entities boundary in the planetary boundaries framework refers to entities that are novel in a geological sense and that could have large-scale impacts that threaten the integrity of Earth system processes. We review the scientific literature relevant to quantifying the boundary for novel entities and highlight plastic pollution as a particular aspect of high concern. An impact pathway from production of novel entities to impacts on Earth system processes is presented. We define and apply three criteria for assessment of the suitability of control variables for the boundary: feasibility, relevance, and comprehensiveness. We propose several complementary control variables to capture the complexity of this boundary, while acknowledging major data limitations. We conclude that humanity is currently operating outside the planetary boundary based on the weight-of-evidence for several of these control variables. The increasing rate of production and releases of larger volumes and higher numbers of novel entities with diverse risk potentials exceed societies' ability to conduct safety related assessments and monitoring. We recommend taking urgent action to reduce the harm associated with exceeding the boundary by reducing the production and releases of novel entities, noting that even so, the persistence of many novel entities and/or their associated effects will continue to pose a threat.

Elevated lactate in Mauriac syndrome: still a mystery.

BACKGROUND: The Mauriac syndrome was described in 1930 as a peculiar combination of poorly controlled diabetes mellitus type 1, stunted growth and glycogenic hepatopathy. More recently, lactic acidosis was recognized as an additional feature, often induced by insulin treatment. CASE PRESENTATION: A 17-year old girl known for diabetes type 1A and Mauriac syndrome was admitted to the emergency room with hyperglycemia of > 41 mmol/l without ketoacidosis. Under a standard insulin regimen, hyperglycemia was rapidly corrected but marked hyperlactatemia occurred. CONCLUSIONS: The mechanism of impaired glucose utilization and lactate elevation independent of ketoacidosis in Mauriac syndrome is intriguing. The rarity of Mauriac syndrome and its resemblance to glycogen storage diseases suggest the presence of a specific metabolic or genetic predisposition that remains to be identified.