Silent reflections remain unheard.

OBJECTIVE: To consider the contribution of non-clinical factors in the rising rate of mental health presentations and explore the associated silence within the psychiatric profession. CONCLUSION: Medicalisation, concept creep and group think, alongside societal demand and expectations, have collectively contributed toward a distorted view of mental health and illness. Equitable service provision has been hindered by the silence of important perspectives.

Long COVID - Can we deny a diagnosis without denying a person's reality?

OBJECTIVE: The aim is to consider Long COVID not as a new clinical entity but as another example of a disabling, historical phenomenon. CONCLUSIONS: A triad of polymorphic symptomatology, an elusive pathophysiological explanation and a hostile defensiveness has appeared throughout history. The reluctance to consider these contextually may delay early intervention and appropriate patient care.

Dual Ruthenium-Catalyzed Alkene Isomerization-Hydrogen Auto-Transfer Unlocks Skipped Dienes as Pronucleophiles for Enantioselective Alcohol C-H Allylation.

The first use of 1,4-pentadiene and 1,5-hexadiene as allylmetal pronucleophiles in regio-, anti-diastereo-, and enantioselective carbonyl addition from alcohol proelectrophiles is described. As corroborated by deuterium labeling experiments, primary alcohol dehydrogenation delivers a ruthenium hydride that affects alkene isomerization to furnish a conjugated diene, followed by transfer hydrogenative carbonyl addition. Hydrometalation appears to be assisted by the formation of a fluxional olefin-chelated homoallylic alkylruthenium complex II, which exists in equilibrium with its pentacoordinate η1 form to enable ß-hydride elimination. This effect confers remarkable chemoselectivity: while 1,4-pentadiene and 1,5-hexadiene are competent pronucleophiles, higher 1,n-dienes are not, and the olefinic functional groups of the products remain intact under conditions in which the 1,4- and 1,5-dienes isomerize. A survey of halide counterions reveals iodide-bound ruthenium-JOSIPHOS catalysts are uniquely effective in these processes. This method was used to prepare a previously reported C1-C7 substructure of (-)-pironetin in 4 vs 12 steps.

Earth Systems to Anthropocene Systems: An Evolutionary, System-of-Systems, Convergence Paradigm for Interdependent Societal Challenges.

Humans have made profound changes to the Earth. The resulting societal challenges of the Anthropocene (e.g., climate change and impacts, renewable energy, adaptive infrastructure, disasters, pandemics, food insecurity, and biodiversity loss) are complex and systemic, with causes, interactions, and consequences that cascade across a globally connected system of systems. In this Critical Review, we turn to our "origin story" for insight, briefly tracing the formation of the Universe and the Earth, the emergence of life, the evolution of multicellular organisms, mammals, primates, and humans, as well as the more recent societal transitions involving agriculture, urbanization, industrialization, and computerization. Focusing on the evolution of the Earth, genetic evolution, the evolution of the brain, and cultural evolution, which includes technological evolution, we identify a nested evolutionary sequence of geophysical, biophysical, sociocultural, and sociotechnical systems, emphasizing the causal mechanisms that first formed, and then transformed, Earth systems into Anthropocene systems. Describing how the Anthropocene systems coevolved, and briefly illustrating how the ensuing societal challenges became tightly integrated across multiple spatial, temporal, and organizational scales, we conclude by proposing an evolutionary, system-of-systems, convergence paradigm for the entire family of interdependent societal challenges of the Anthropocene.

A rapid micro chamber method to measure SVOC emission and transport model parameters.

Assessing exposure to semivolatile organic compounds (SVOCs) that are emitted from consumer products and building materials in indoor environments is critical for reducing the associated health risks. Many modeling approaches have been developed for SVOC exposure assessment indoors, including the DustEx webtool. However, the applicability of these tools depends on the availability of model parameters such as the gas-phase concentration at equilibrium with the source material surface, y0, and the surface-air partition coefficient, Ks, both of which are typically determined in chamber experiments. In this study, we compared two types of chamber design, a macro chamber, which downscaled the dimensions of a room to a smaller size with roughly the same surface-to-volume ratio, and a micro chamber, which minimized the sink-to-source surface area ratio to shorten the time required to reach steady state. The results show that the two chambers with different sink-to-source surface area ratios yield comparable steady-state gas- and surface-phase concentrations for a range of plasticizers, while the micro chamber required significantly shorter times to reach steady state. Using y0 and Ks measured with the micro chamber, we conducted indoor exposure assessments for di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP) and di(2-ethylhexyl) terephthalate (DEHT) with the updated DustEx webtool. The predicted concentration profiles correspond well with existing measurements and demonstrate the direct applicability of chamber data in exposure assessments.

Biosynthesis of 2-methylisoborneol is regulated by chromatic acclimation of Pseudanabaena.

Cyanobacteria can sense different light color by adjusting the components of photosynthetic pigments including chlorophyll a (Chl a), phycoerythrin (PE), and phycocyanin (PC), etc. Filamentous cyanobacteria are the main producer of 2-methylisoborneol (MIB) and many can increase their PE levels so that they are more competitive in subsurface layer where green light is more abundant, and have caused extensive odor problems in drinking water reservoirs. Here, we identified the potential correlation between MIB biosynthesis and ambient light color induced chromatic acclimation (CA) of a MIB-producing Pseudanabaena strain. The results suggest Pseudanabaena regulates the pigment proportion through Type III CA (CA3), by increasing PE abundance and decreasing PC in green light. The biosynthesis of MIB and Chl a share the common precursor, and are positively correlated with statistical significance regardless of light color (R2=0.68; p<0.001). Besides, the PE abundance is also positively correlated with Chl a in green light (R2=0.57; p=0.019) since PE is the antenna that can only transfer the energy to PC and Chl a. In addition, significantly higher MIB production was observed in green light since more Chl a was synthesized.

Comparing the RETeval® portable ERG device with more traditional tabletop ERG systems in normal subjects and selected retinopathies.

PURPOSE: Our study aimed to determine if ISCEV standard-like ERGs recorded with the LKC RETeval® portable ERG unit compared to those obtained using the more traditional tabletop unit. METHODS: ERGs recorded from normal subjects and patients affected with retinal ON and OFF pathway anomalies were compared. Analysis included peak time and amplitude measurements as well as time-frequency domain analysis with the discrete wavelet transform of waveforms obtained with the two systems. RESULTS: Although both systems were similarly able to record reliable and highly reproducible ERG responses, there were major discrepancies in ERG responses between the portable and tabletop units, pointing toward a weaker stimulation of the retinal OFF pathway with the portable RETeval® unit. CONCLUSION: The portable RETeval® unit appears to be able to record highly reproducible and diagnostically useful clinical ERGs, albeit with some significant differences in waveform composition compared to those obtained with more standard tabletop systems. Given the unknown origin of these waveform discrepancies, if left uncorrected, these differences could potentially lead to erroneous interpretation when used in the clinical context and/or compared to ERGs recorded using more traditional table top units. Clearly, more research is warranted before handheld devices, such as the RETeval®, can be homologated as a diagnostically sound ERG devices.

Differences in wild-type- and R338L-tenase complex formation are at the root of R338L-factor IX assay discrepancies.

Adeno-associated virus (AAV) gene therapy has the potential to functionally cure hemophilia B by restoring factor (F)IX concentrations into the normal range. Next-generation AAV therapies express a naturally occurring gain-of-function FIX variant, FIX-Padua (R338L-FIX), that increases FIX activity (FIX:C) by approximately eightfold compared with wild-type FIX (FIX-WT). Previous studies have shown that R338L-FIX activity varies dramatically across different clinical FIX:C assays, which complicates the monitoring and management of patients. To better understand mechanisms that contribute to R338L-FIX assay discrepancies, we characterized the performance of R338L-FIX in 13 1-stage clotting assays (OSAs) and 2 chromogenic substrate assays (CSAs) in a global field study. This study produced the largest R338L-FIX assay dataset to date and confirmed that clinical FIX:C assay results vary over threefold. Both phospholipid and activating reagents play a role in OSA discrepancies. CSA generated the most divergent FIX:C results. Manipulation of FIX:C CSA kits demonstrated that specific activity gains for R338L-FIX were most profound at lower FIX:C concentrations and that these effects were enhanced during the early phases of FXa generation. Supplementing FX into CSA had the effect of dampening FIX-WT activity relative to R338L-FIX activity, suggesting that FX impairs WT tenase formation to a greater extent than R338L-FIX tenase. Our data describe the scale of R338L-FIX assay discrepancies and provide insights into the causative mechanisms that will help establish best practices for the measurement of R338L-FIX activity in patients after gene therapy.

Ultraviolet dosage and decontamination efficacy were widely variable across 14 UV devices after testing a dried enveloped ribonucleic acid virus surrogate for SARS-CoV-2.

Aims: The dosages and efficacy of 14 ultraviolet (UV) decontamination technologies were measured against a SARS-CoV-2 surrogate virus that was dried onto different materials for laboratory and field testing. Methods and results: A live enveloped, ribonucleic acid (RNA) virus surrogate for SARS-CoV-2 was dried on stainless steel 304 (SS304), Navy Top Coat-painted SS304 (NTC), cardboard, polyurethane, polymethyl methacrylate (PMMA), and acrylonitrile butadiene styrene (ABS) materials at > 8.0 log10 plaque-forming units (PFU) per test coupon. The coupons were then exposed to UV radiation during both laboratory and field testing. Commercial and prototype UV-emitting devices were measured for efficacy: four handheld devices, three room/surface-disinfecting machines, five air disinfection devices, and two larger custom-made machines. UV device dosages ranged from 0.01 to 729 mJ cm-2. The antiviral efficacy among the different UV devices ranged from no decontamination up to nearly achieving sterilization. Importantly, cardboard required far greater dosage than SS304. Conclusion: Enormous variability in dosage and efficacy was measured among the different UV devices. Porous materials limit the utility of UV decontamination. Significance and impact of the study: UV devices have wide variability in dosages, efficacy, hazards, and UV output over time, indicating that each UV device needs independent technical measurement and assessment for product development prior to and during use.

Independent Predictors for Hospitalization-Associated Radiation therapy Interruptions.

Purpose: Radiation treatment interruption associated with unplanned hospitalization remains understudied. The intent of this study was to benchmark the frequency of hospitalization-associated radiation therapy interruptions (HARTI), characterize disease processes causing hospitalization during radiation, identify factors predictive for HARTI, and localize neighborhood environments associated with HARTI at our academic referral center. Methods and Materials: This retrospective review of electronic health records provided descriptive statistics of HARTI event rates at our institutional practice. Uni- and multivariable logistic regression models were developed to identify significant factors predictive for HARTI. Causes of hospitalization were established from primary discharge diagnoses. HARTI rates were mapped according to patient residence addresses. Results: Between January 1, 2015, and December 31, 2017, 197 HARTI events (5.3%) were captured across 3729 patients with 727 total missed treatments. The 3 most common causes of hospitalization were malnutrition/dehydration (n = 28; 17.7%), respiratory distress/infection (n = 24; 13.7%), and fever/sepsis (n = 17; 9.7%). Factors predictive for HARTI included African-American race (odds ratio [OR]: 1.48; 95% confidence interval [CI], 1.07-2.06; P = .018), Medicaid/uninsured status (OR: 2.05; 95% CI, 1.32-3.15; P = .0013), Medicare coverage (OR: 1.7; 95% CI, 1.21-2.39; P = .0022), lung (OR: 5.97; 95% CI, 3.22-11.44; P < .0001), and head and neck (OR: 5.6; 95% CI, 2.96-10.93; P < .0001) malignancies, and prescriptions >20 fractions (OR: 2.23; 95% CI, 1.51-3.34; P < .0001). HARTI events clustered among Medicaid/uninsured patients living in urban, low-income, majority African-American neighborhoods, and patients from middle-income suburban communities, independent of race and insurance status. Only the wealthiest residential areas demonstrated low HARTI rates. Conclusions: HARTI disproportionately affected socioeconomically disadvantaged urban patients facing a high treatment burden in our catchment population. A complementary geospatial analysis also captured the risk experienced by middle-income suburban patients independent of race or insurance status. Confirmatory studies are warranted to provide scale and context to guide intervention strategies to equitably reduce HARTI events.

Modeling Primary Emissions of Chemicals from Liquid Products Applied on Indoor Surfaces.

Liquid products applied on material surfaces and human skin, including many household cleaning products and personal care products, can lead to intermittent emissions of chemicals and peak concentrations in indoor air. The existing case-based models do not allow inter-comparison of different use scenarios and emission mechanisms. In this context, the present work developed a mechanistic model based on mass transfer theories, which allowed emissions into the air from the liquid product to be characterized. It also allowed for diffusion into the applied surface during product use and re-emission from the applied surface after the depletion of the liquid product. The model was validated using literature data on chemical emissions following floor cleaning and personal care product use. A sensitivity analysis of the model was then conducted. The percentage of the chemical mass emitted from the liquid to the air varied from 45% (applied on porous material) to 99% (applied on human skin), and the rest was absorbed into the applied material/skin. The peak gas-phase concentration, the time to reach the peak concentration, and the percentage of the liquid-to-air emission depended significantly on the chemical's octanol/gas and material/gas partition coefficients and the diffusion coefficient of the chemical in the applied material/skin.

Reading to learn? The co-development of mathematics and reading during primary school.

Understanding how early reading and mathematics co-develop is important from both theoretical and pedagogical standpoints. Previous research has provided mixed results. This paper investigates the development of reading and mathematics in a longitudinal sample of N = 355,883 students from the United Kingdom (2005-2019) aged 5 to 12 (49% girls). Results indicate a positive relation between the development of the two domains. In addition, a substantial statistically significant positive association between prior reading scores and subsequent changes in achievement in mathematics was found, whereas changes in reading were smaller for students with a higher prior performance in mathematics. The findings suggest that acquiring good reading skills is highly relevant for developing mathematics skills. Implications for theory and practice are discussed.

A modular mechanistic framework for estimating exposure to SVOCs: Next steps for modeling emission and partitioning of plasticizers and PFAS.

Estimates of human exposure to semi-volatile organic compounds (SVOCs) such as phthalates, phthalate alternatives, and some per- and polyfluoroalkyl substances (PFAS) are required for the risk-based evaluation of chemicals. Recently, a modular mechanistic modeling framework to rapidly predict SVOC emission and partitioning in indoor environments has been presented, in which several mechanistically consistent source emission categories (SECs) were identified. However, not all SECs have well-developed emission models. In addition, data on model parameters are missing even for frequently studied SVOCs. These knowledge gaps impede the comprehensive prediction of the fate of SVOCs indoors. In this paper, sets of high-priority phthalates, phthalate alternatives, and PFAS were identified based on chemical occurrence indoors and additional selection criteria. These high-priority chemicals served as the basis for exploring model parameter availability for existing indoor SVOC emission and partitioning models. The results reveal that additional experimental and modeling work is needed to fully understand the behavior of SVOCs indoors and to predict exposures with greater confidence and lower uncertainty. Modeling approaches to fill some of the identified gaps are proposed. The prioritized sets of chemicals and proposed new modeling approaches will help guide future research. The inclusion of polar phases in the framework will further expand its applicability and scope. IMPACT STATEMENT: This paper compiles data on high-priority chemicals commonly found indoors and information on the availability of applicable models and model parameters to predict emission, partitioning, and subsequent exposure to these chemicals. Modeling approaches for a selection of the missing SECs (source emission categories) are proposed, to illustrate the path forward. The comprehensive data set helps inform researchers, exposure assessors, and policy makers to better understand the state of the science regarding modeling of indoor exposure to semi-volatile organic compounds (SVOCs) and per- and polyfluoroalkyl substances (PFAS).

Demonstrating a systems approach for integrating disparate data streams to inform decisions on children's environmental health.

BACKGROUND: The use of systems science methodologies to understand complex environmental and human health relationships is increasing. Requirements for advanced datasets, models, and expertise limit current application of these approaches by many environmental and public health practitioners. METHODS: A conceptual system-of-systems model was applied for children in North Carolina counties that includes example indicators of children's physical environment (home age, Brownfield sites, Superfund sites), social environment (caregiver's income, education, insurance), and health (low birthweight, asthma, blood lead levels). The web-based Toxicological Prioritization Index (ToxPi) tool was used to normalize the data, rank the resulting vulnerability index, and visualize impacts from each indicator in a county. Hierarchical clustering was used to sort the 100 North Carolina counties into groups based on similar ToxPi model results. The ToxPi charts for each county were also superimposed over a map of percentage county population under age 5 to visualize spatial distribution of vulnerability clusters across the state. RESULTS: Data driven clustering for this systems model suggests 5 groups of counties. One group includes 6 counties with the highest vulnerability scores showing strong influences from all three categories of indicators (social environment, physical environment, and health). A second group contains 15 counties with high vulnerability scores driven by strong influences from home age in the physical environment and poverty in the social environment. A third group is driven by data on Superfund sites in the physical environment. CONCLUSIONS: This analysis demonstrated how systems science principles can be used to synthesize holistic insights for decision making using publicly available data and computational tools, focusing on a children's environmental health example. Where more traditional reductionist approaches can elucidate individual relationships between environmental variables and health, the study of collective, system-wide interactions can enable insights into the factors that contribute to regional vulnerabilities and interventions that better address complex real-world conditions.

Evaluating the Theoretical Background of STOFFENMANAGER® and the Advanced REACH Tool.

STOFFENMANAGER® and the Advanced REACH Tool (ART) are recommended tools by the European Chemical Agency for regulatory chemical safety assessment. The models are widely used and accepted within the scientific community. STOFFENMANAGER® alone has more than 37 000 users globally and more than 310 000 risk assessment have been carried out by 2020. Regardless of their widespread use, this is the first study evaluating the theoretical backgrounds of each model. STOFFENMANAGER® and ART are based on a modified multiplicative model where an exposure base level (mg m-3) is replaced with a dimensionless intrinsic emission score and the exposure modifying factors are replaced with multipliers that are mainly based on subjective categories that are selected by using exposure taxonomy. The intrinsic emission is a unit of concentration to the substance emission potential that represents the concentration generated in a standardized task without local ventilation. Further information or scientific justification for this selection is not provided. The multipliers have mainly discrete values given in natural logarithm steps (…, 0.3, 1, 3, …) that are allocated by expert judgements. The multipliers scientific reasoning or link to physical quantities is not reported. The models calculate a subjective exposure score, which is then translated to an exposure level (mg m-3) by using a calibration factor. The calibration factor is assigned by comparing the measured personal exposure levels with the exposure score that is calculated for the respective exposure scenarios. A mixed effect regression model was used to calculate correlation factors for four exposure group [e.g. dusts, vapors, mists (low-volatiles), and solid object/abrasion] by using ~1000 measurements for STOFFENMANAGER® and 3000 measurements for ART. The measurement data for calibration are collected from different exposure groups. For example, for dusts the calibration data were pooled from exposure measurements sampled from pharmacies, bakeries, construction industry, and so on, which violates the empirical model basic principles. The calibration databases are not publicly available and thus their quality or subjective selections cannot be evaluated. STOFFENMANAGER® and ART can be classified as subjective categorization tools providing qualitative values as their outputs. By definition, STOFFENMANAGER® and ART cannot be classified as mechanistic models or empirical models. This modeling algorithm does not reflect the physical concept originally presented for the STOFFENMANAGER® and ART. A literature review showed that the models have been validated only at the 'operational analysis' level that describes the model usability. This review revealed that the accuracy of STOFFENMANAGER® is in the range of 100 000 and for ART 100. Calibration and validation studies have shown that typical log-transformed predicted exposure concentration and measured exposure levels often exhibit weak Pearson's correlations (r is <0.6) for both STOFFENMANAGER® and ART. Based on these limitations and performance departure from regulatory criteria for risk assessment models, it is recommended that STOFFENMANAGER® and ART regulatory acceptance for chemical safety decision making should be explicitly qualified as to their current deficiencies.

An integrated exposure and pharmacokinetic modeling framework for assessing population-scale risks of phthalates and their substitutes.

To effectively incorporate in vitro-in silico-based methods into the regulation of consumer product safety, a quantitative connection between product phthalate concentrations and in vitro bioactivity data must be established for the general population. We developed, evaluated, and demonstrated a modeling framework that integrates exposure and pharmacokinetic models to convert product phthalate concentrations into population-scale risks for phthalates and their substitutes. A probabilistic exposure model was developed to generate the distribution of multi-route exposures based on product phthalate concentrations, chemical properties, and human activities. Pharmacokinetic models were developed to simulate population toxicokinetics using Bayesian analysis via the Markov chain Monte Carlo method. Both exposure and pharmacokinetic models demonstrated good predictive capability when compared with worldwide studies. The distributions of exposures and pharmacokinetics were integrated to predict the population distributions of internal dosimetry. The predicted distributions showed reasonable agreement with the U.S. biomonitoring surveys of urinary metabolites. The "source-to-outcome" local sensitivity analysis revealed that food contact materials had the greatest impact on body burden for di(2-ethylhexyl) adipate (DEHA), di-2-ethylhexyl phthalate (DEHP), di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), and di(2-propylheptyl) phthalate (DPHP), whereas the body burden of diethyl phthalate (DEP) was most sensitive to the concentration in personal care products. The upper bounds of predicted plasma concentrations showed no overlap with ToxCast in vitro bioactivity values. Compared with the in vitro-to-in vivo extrapolation (IVIVE) approach, the integrated modeling framework has significant advantages in mapping product phthalate concentrations to multi-route risks, and thus is of great significance for regulatory use with a relatively low input requirement. Further integration with new approach methodologies will facilitate these in vitro-in silico-based risk assessments for a broad range of products containing an equally broad range of chemicals.

Kinetic multi-layer model of film formation, growth, and chemistry (KM-FILM): Boundary layer processes, multi-layer adsorption, bulk diffusion, and heterogeneous reactions.

Large surface area-to-volume ratios indoors cause heterogeneous interactions to be especially important. Semi-volatile organic compounds can deposit on impermeable indoor surfaces forming thin organic films. We developed a new model to simulate the initial film formation by treating gas-phase diffusion and turbulence through a surface boundary layer and multi-layer reversible adsorption on rough surfaces, as well as subsequent film growth by resolving bulk diffusion and chemical reactions in a film. The model was applied with consistent parameters to reproduce twenty-one sets of film formation measurements due to multi-layer adsorption of multiple phthalates onto different indoor-relevant surfaces, showing that the films should initially be patchy with the formation of pyramid-like structures on the surface. Sensitivity tests showed that highly turbulent conditions can lead to the film growing by more than a factor of two compared to low turbulence conditions. If surface films adopt an ultra-viscous state with bulk diffusion coefficients of less than 10-18  cm2 s-1 , a significant decrease in film growth is expected. The presence of chemical reactions in the film has the potential to increase the rate of film growth by nearly a factor of two.

Three Cases of Recovery from Sensorineural Hearing Loss in the First Year of Life: Implications for Monitoring and Management.

BACKGROUND: Three infants with different risk factors, behavioral and physiologic audiometric histories, and diagnoses were fit with amplification between 3 and 8 months of age. Two of the three met criteria for cochlear implantation. PURPOSE: This article aims to heighten awareness of the rare possibility of recovery from sensorineural hearing loss in infants with varying histories and emphasize the importance of a full diagnostic test battery in all infants diagnosed with sensorineural hearing loss every 3 months until objective and subjective thresholds are stable to ensure appropriate intervention. RESEARCH DESIGN: Case reports. RESULTS: All three infants demonstrated improvement or full recovery of hearing and cochlear function by approximately 12 months old. Their change in hearing was discovered due to frequent follow-up and/or caregiver report. One of these infants was tentatively scheduled to have cochlear implant surgery 2 months later. CONCLUSION: Appropriate early intervention for infants with hearing loss is critical to ensure maximum accessibility to speech and language cues. The Federal Drug Administration approves cochlear implantation in infants as young as 12 months. When providing audiometric management of infants with sensorineural hearing loss, it is imperative to conduct a full diagnostic test battery every 3 months (including tympanometric, acoustic reflex, and otoacoustic emission measurement) until objective and subjective thresholds are stable. There was no apparent pattern of factors to predict that the infants highlighted in these cases would recover. Discussion among pediatric audiologists and otologists and comparison of data from clinics across the U.S. is needed to identify predictive patterns and determine appropriate, consistent monitoring of infants with sensorineural hearing loss.

Socio-technical scales in socio-environmental modeling: Managing a system-of-systems modeling approach.

System-of-systems approaches for integrated assessments have become prevalent in recent years. Such approaches integrate a variety of models from different disciplines and modeling paradigms to represent a socio-environmental (or social-ecological) system aiming to holistically inform policy and decision-making processes. Central to the system-of-systems approaches is the representation of systems in a multi-tier framework with nested scales. Current modeling paradigms, however, have disciplinary-specific lineage, leading to inconsistencies in the conceptualization and integration of socio-environmental systems. In this paper, a multidisciplinary team of researchers, from engineering, natural and social sciences, have come together to detail socio-technical practices and challenges that arise in the consideration of scale throughout the socio-environmental modeling process. We identify key paths forward, focused on explicit consideration of scale and uncertainty, strengthening interdisciplinary communication, and improvement of the documentation process. We call for a grand vision (and commensurate funding) for holistic system-of-systems research that engages researchers, stakeholders, and policy makers in a multi-tiered process for the co-creation of knowledge and solutions to major socio-environmental problems.

Anosognosia and schizophrenia - a reminder.

OBJECTIVE: To remind the clinical and legal practitioner that anosognosia is a recognised facet of schizophrenia with implications for capacity assessment and for relating effectively with people who experience it. CONCLUSIONS: The term anosognosia emphasises that, in schizophrenia, lack of capacity is the result of a neurological deficit. Under-appreciation of this may place that person at risk of a preventable harm.