Hypothalamic subunit volumes and relations to violence and psychopathy in male offenders with or without a psychotic disorder.

The hypothalamus is key to body homeostasis, including regulating cortisol, testosterone, vasopressin, and oxytocin hormones, modulating aggressive behavior. Animal studies have linked the morphology and function of the hypothalamus to aggression and affiliation, with a subregional pattern reflecting the functional division between the hypothalamic nuclei. We explored the relationship between hypothalamic subunit volumes in violent offenders with (PSY-V) and without (NPV) a psychotic disorder, and the association with psychopathy traits. 3T MRI scans (n = 628, all male 18-70 years) were obtained from PSY-V, n = 38, NPV, n = 20, non-violent psychosis patients (PSY-NV), n = 134, and healthy controls (HC), n = 436. The total hypothalamus volume and its eleven nuclei were delineated into five subunits using Freesurfer v7.3. Psychopathy traits were assessed with Psychopathy Checklist-revised (PCL-R). ANCOVAs and linear regressions were used to analyze associations with subunit volumes. Both groups with a history of violence exhibited smaller anterior-superior subunit volumes than HC (NPV Cohen's d = 0.56, p = 0.01 and PSY-V d = 0.38, p = 0.01). There were no significant differences between HC and PSY-NV. PCL-R scores were positively associated with the inferior tubular subunit on a trend level (uncorrected p = 0.045, Cohen's d = 0.04). We found distinct hypothalamic subunit volume reductions in persons with a history of violence independent of concomitant psychotic disorder but not in persons with psychosis alone. The results provide further information about the involvement of the hypothalamus in aggression, which ultimately may lead to the development of targeted treatment for the clinical and societal challenge of aggression and violent behavior.

A roadmap to strengthen standardisation efforts in risk governance of nanotechnology.

A roadmap was developed to strengthen standardisation activities for risk governance of nanotechnology. Its baseline is the available standardised and harmonised methods for nanotechnology developed by the International Organization for Standardization (ISO), the European Committee for Standardization (CEN), and the Organisation for Economic Co-operation and Development (OECD). In order to identify improvements and needs for new themes in standardisation work, an analysis of the state-of-the-art concepts and interpretations of risk governance of nanotechnology was performed. Eleven overall areas of action were identified, each including a subset of specific topics. Themes addressed include physical chemical characterisation, assessment of hazard, exposure, risk and socio-economic factors, as well as education & training and social dialogue. This has been visualised in a standardisation roadmap spanning a timeframe of ten years and including key outcomes and highlights of the analysis. Furthermore, the roadmap indicates potential areas of action for harmonisation and standardisation (H&S) for nanomaterials and nanotechnology. It also includes an evaluation of the current level (limited, moderate, intense) of ongoing H&S activities and indicates the time horizon for the different areas of action. As the identified areas differ in their state of development, the number and type of actions varied widely amongst the different actions towards achieving standardisation. Thus, priority areas were also identified. The overall objective of these actions is to strengthen risk governance towards a safe use of nanomaterials and nano-related products. Though not explicitly addressed, risk-based legislation and policies are supported via the proposed H&S actions.

Towards harmonisation of testing of nanomaterials for EU regulatory requirements on chemical safety - A proposal for further actions.

Over the recent years, EU chemicals legislation, guidance and test guidelines have been developed or adapted for nanomaterials to facilitate safe use of nanomaterials. This paper provides an overview of the information requirements across different EU regulatory areas. For each information requirement, a group of 22 experts identified potential needs for further action to accommodate guidance and test guidelines to nanomaterials. Eleven different needs for action were identified, capturing twenty-two information requirements that are specific to nanomaterials and relevant to multiple regulatory areas. These were further reduced to three overarching issues: 1) resolve issues around nanomaterial dispersion stability and dosing in toxicity testing, in particular for human health endpoints, 2) further develop tests or guidance on degradation and transformation of organic nanomaterials or nanomaterials with organic components, and 3) further develop tests and guidance to measure (a)cellular reactivity of nanomaterials. Efforts towards addressing these issues will result in better fit-for-purpose test methods for (EU) regulatory compliance. Moreover, it secures validity of hazard and risk assessments of nanomaterials. The results of the study accentuate the need for a structural process of identification of information needs and knowledge generation, preferably as part of risk governance and closely connected to technological innovation policy.

Psychopathy subdomains in violent offenders with and without a psychotic disorder.

BACKGROUND: Violence in psychosis has been linked to antisocial behavior and psychopathy traits. Psychopathy comprises aspects of interpersonal, affective, lifestyle, and antisocial traits which may be differently involved in violent offending by persons with psychotic disorders. We explored psychopathy subdomains among violent offenders with and without a psychotic disorder. METHODS: 46 males, with a history of severe violence, with (n = 26; age 35.85 ± 10.34 years) or without (n = 20; age 39.10 ± 11.63 years) a diagnosis of a psychotic disorder, were assessed with the Psychopathy Checklist-Revised (PCL-R). PCL-R was split into subdomains following the four-facet model. Group differences in total and subdomain scores were analyzed with a general linear model with covariates. RESULTS: Total PCL-R scores did not differ between the groups (p = 0.61, Cohen's d = 0.17). The violent offenders without psychotic disorders had higher facet 2 scores than the patient group with psychotic disorders (p = 0.029, Cohen's d = 0.77). Facet 1, 3, or 4 scores did not differ between the groups. Controlling for age did not alter the results. CONCLUSION: Patients with a psychotic disorder and a history of severe violence have lower affective psychopathy scores than violent offenders without psychotic disorders. This observation may point toward distinct underlying mechanisms for violence and may provide a target for focused treatment and prevention.

How to formulate hypotheses and IATAs to support grouping and read-across of nanoforms.

Manufacturing and functionalizing materials at the nanoscale has led to the generation of a whole array of nanoforms (NFs) of substances varying in size, morphology, and surface characteristics. Due to financial, time, and ethical considerations, testing every unique NF for adverse effects is virtually impossible. Use of hypothesis-driven grouping and read-across approaches, as supported by the GRACIOUS Framework, represents a promising alternative to case-by-case testing that will make the risk assessment process more efficient. Through application of appropriate grouping hypotheses, the Framework facilitates the assessment of similarity between NFs, thereby supporting grouping and read-across of information, minimizing the need for new testing, and aligning with the 3R principles of replacement, reduction, and refinement of animals in toxicology studies. For each grouping hypothesis an integrated approach to testing and assessment (IATA) guides the user in data gathering and acquisition to test the hypothesis, following a structured format to facilitate efficient decision-making. Here we present the template used to generate the GRACIOUS grouping hypotheses encompassing information relevant to "Lifecycle, environmental release, and human exposure", "What they are: physicochemical characteristics", "Where they go: environmental fate, uptake, and toxicokinetics", and "What they do: human and environmental toxicity". A summary of the template-derived hypotheses focusing on human health is provided, along with an overview of the IATAs generated by the GRACIOUS project. We discuss the application and flexibility of the template, providing the opportunity to expand the application of grouping and read-across in a logical, evidence-based manner to a wider range of NFs and substances.

Analytical and toxicological aspects of nanomaterials in different product groups: Challenges and opportunities.

The widespread integration of engineered nanomaterials into consumer and industrial products creates new challenges and requires innovative approaches in terms of design, testing, reliability, and safety of nanotechnology. The aim of this review article is to give an overview of different product groups in which nanomaterials are present and outline their safety aspects for consumers. Here, release of nanomaterials and related analytical challenges and solutions as well as toxicological considerations, such as dose-metrics, are discussed. Additionally, the utilization of engineered nanomaterials as pharmaceuticals or nutraceuticals to deliver and release cargo molecules is covered. Furthermore, critical pathways for human exposure to nanomaterials, namely inhalation and ingestion, are discussed in the context of risk assessment. Analysis of NMs in food, innovative medicine or food contact materials is discussed. Specific focus is on the presence and release of nanomaterials, including whether nanomaterials can migrate from polymer nanocomposites used in food contact materials. With regard to the toxicology and toxicokinetics of nanomaterials, aspects of dose metrics of inhalation toxicity as well as ingestion toxicology and comparison between in vitro and in vivo conclusions are considered. The definition of dose descriptors to be applied in toxicological testing is emphasized. In relation to potential exposure from different products, opportunities arising from the use of advanced analytical techniques in more unique scenarios such as release of nanomaterials from medical devices such as orthopedic implants are addressed. Alongside higher product performance and complexity, further challenges regarding material characterization and safety, as well as acceptance by the general public are expected.

Counting Small Particles in Electron Microscopy Images-Proposal for Rules and Their Application in Practice.

Electron microscopy (EM) is the gold standard for the characterisation of the morphology (size and shape) of nanoparticles. Visual observation of objects under examination is always a necessary first step in the characterisation process. Several questions arise when undertaking to identify and count particles to measure their size and shape distribution. In addition to challenges with the dispersion and identification of the particles, more than one protocol for counting particles is in use. This paper focuses on precise rules for the counting of particles in EM micrographs, as this influences the measurement accuracy of the number of particles, thus implicitly affecting the size values of the counted particles. We review and compare four different, commonly used methods for counting, which we then apply in case studies. The impact of the selected counting rule on the obtained final particle size distribution is highlighted. One main aim of this analysis is to support the application of a specific, well-defined counting approach in accordance with regulatory requirements to contribute to achieving more reliable and reproducible results. It is also useful for the new harmonised measurement procedures for determining the particle size and particle size distribution of nanomaterials.

[Neurosyphilis].

This review focuses on typical and atypical manifestations of neurosyphilis. The manifestations of neurosyphilis are manyfold and may involve many specialties. Today, clinicians have limited experience with the well-described manifestations of neurosyphilis. Many screening opportunities for men who have sex with men might catch the majority of cases of syphilis in this group. However, a concern could be if disclosure about heterosexuality or, in general, monosymptomatic neurosyphilis constitute a risk for delayed diagnosis.

Refinement of the selection of physicochemical properties for grouping and read-across of nanoforms.

Before placing a new nanoform (NF) on the market, its potential adverse effects must be evaluated. This may e.g. be done via hazard and risk assessment. Grouping and read-across of NFs is a possible strategy to reduce resource consumption, maximising the use of existing data for assessment of NFs. The GRACIOUS project provides a framework in which possible grouping and read-across for NFs is mainly based on an evaluation of their similarity. The impact of NFs on human health and the environment depends strongly on the concentration of the NF and its physicochemical properties, such as chemical composition, size distribution, shape, etc. Hence, knowledge of the most relevant physicochemical properties is essential information for comparing similarity. The presented work aims to refine existing proposals for sets of descriptors (descriptor array) that are needed to describe distinct NFs of a material to identify the most relevant ones for grouping and read-across. The selection criteria for refining this descriptor array are explained and demonstrated. Relevant protocols and methods are proposed for each physicochemical property. The required and achievable measurement accuracies of the refined descriptor array are reviewed, as this information is necessary for similarity assessment of NFs based on individual physicochemical properties.

Clinical Importance of Superior Sensitivity of the Aptima TMA-Based Assays for Mycoplasma genitalium Detection.

Mycoplasma genitalium (MG) is a common cause of nongonococcal cervicitis and urethritis. We investigated the demographic and clinical characteristics of patients tested in Denmark with the Conformité Européenne (CE)/in vitro diagnostics (IVD) Aptima Mycoplasma genitalium assay (CE/IVD AMG; Hologic) and examined the clinical significance of the higher sensitivity of the TMA-based MG assays. From March to June 2016, urogenital and extragenital specimens from consecutive attendees at a sexually transmitted infection clinic in Copenhagen, Denmark were tested with the CE/IVD AMG assay (TMA-based), the research-use-only MG Alt TMA-1 assay (Hologic), a laboratory-developed TaqMan mgpB quantitative real-time PCR (qPCR), and the Aptima Combo 2 (CT/NG; Hologic). Demographic characteristics and clinical symptoms were collected from the patient records. There were 1,245 patients included in the study. The MG prevalence among female subjects was 9.4%, and the MG prevalence among male subjects was 8.7%. Compared to the TMA-based assays, the sensitivity of the PCR-based MG assay was 64.52%, and 55 specimens from 48 individuals were missed in the mgpB qPCR. Of these, 26 individuals (54.2%) were symptomatic, whereas, among 64 individuals with concordant results, 30 individuals (46.9%) were symptomatic; no statistically significant difference was found between the groups (P = 0.567). The improved sensitivity of the TMA-based assays resulted in diagnoses of more patients with clinically relevant symptoms for which antibiotic treatment is indicated. However, approximately half of the MG-infected patients reported no symptoms, and future research is needed to investigate the pros and cons of diagnosing and treating MG in asymptomatic subjects.

Safe- and sustainable-by-design: The case of Smart Nanomaterials. A perspective based on a European workshop.

The European Commission's Green Deal is a major policy initiative aiming to achieve a climate-neutral, zero-pollution, sustainable, circular and inclusive economy, driving both the New Industrial Strategy for Europe and the Chemicals Strategy for Sustainability. Innovative materials can help to reach these policy goals, but they need to be safe and sustainable themselves. Thus, one aim is to shift the development of chemicals to Safe- and Sustainable-by-Design, and define a new systems approach and criteria for sustainability to achieve this. An online workshop was organised in September 2020 by the Joint Research Centre and the Directorate-General Research and Innovation of the European Commission, with participants from academia, non-governmental organisations, industry and regulatory bodies. The aims were to introduce the concept of Safe- and Sustainable-by-Design, to identify industrial and regulatory challenges in achieving safer and more sustainable Smart Nanomaterials as an example of innovative materials, and to deliver recommendations for directions and actions necessary to meet these challenges. The following needs were identified: (i) an agreed terminology, (ii) a common understanding of the principles of Safe- and Sustainable-by-Design, iii) criteria, assessment tools and incentives to achieve a transition from Safe-by-Design to Safe- and Sustainable-by-Design, and (iv) preparedness of regulators and legislation for innovative chemicals/nanomaterials. This paper presents the authors' view on the state of the art as well as the needs for future activities, based on discussions at the workshop and further considerations. The case of Smart Nanomaterials is used to illustrate the Safe- and Sustainable-by-Design concept and challenges for its implementation. Most of the considerations can be extended to other advanced materials and to chemicals and products in general.

Associations between amygdala nuclei volumes, psychosis, psychopathy, and violent offending.

The amygdala is involved in fear perception and aggression regulation, and smaller volumes have been associated with psychotic and non-psychotic violence. We explored the relationship between amygdala nuclei volumes in violent offenders with and without psychosis, and the association to psychopathy traits. 3T MRI scans (n = 204, males, 18-66 years) were obtained from psychotic violent offenders (PSY-V, n = 29), non-psychotic violent offenders (NPV, n = 19), non-violent psychosis patients (PSY-NV, n = 67), and healthy controls (HC, n = 89). Total amygdala and 9 amygdala nuclei volumes were obtained with FreeSurfer. Psychopathy traits were measured with the Psychopathy Checklist-revised (PCL-R). Multivariate analyses explored diagnostic differences in amygdala nuclei volumes and associations to psychosis, violence, and psychopathy traits. PSY-V had a smaller basal nucleus, anterior amygdaloid area, and cortical amygdalar transition area (CATA), whereas PSY-NV had a smaller CATA than HC. Volumes in NPV did not differ from HC, and there were no associations between PCL-R total or factor scores and any of the nuclei or whole amygdala volumes. The lower volumes of amygdala nuclei involved in fear modulation, stress responses, and social interpretation may point towards some mechanisms of relevance to violence in psychosis, but the results warrant replication in larger subject samples.

Advanced materials foresight: research and innovation indicators related to advanced and smart nanomaterials.

Background: Advanced materials are most likely to bring future economic, environmental and social benefits. At the same time, they may pose challenges regarding their safety and sustainability along the entire lifecycle. This needs to be timely addressed by the stakeholders (industry, research, policy, funding and regulatory bodies). As part of a larger foresight project, this study aimed to identify areas of scientific research and technological development related to advanced materials, in particular advanced nanomaterials and the sub-group of smart nanomaterials. The study identified and collected data to build relevant research and innovation indicators and analyse trends, impact and other implications. Methods: This study consisted of an iterative process including a documentation phase followed by the identification, description and development of a set of core research and innovation indicators regarding scientific publications, EU projects and patents. The data was extracted mainly from SCOPUS, CORDIS and PATSTAT databases using a predefined search string that included representative keywords. The trends, distributions and other aspects reflected in the final version of the indicators were analysed, e.g. the number of items in a period of time, geographical distribution, organisations involved, categories of journals, funding programmes, costs and technology areas. Results: Generally, for smart nanomaterials the data used represent around 3.5% of the advanced nanomaterials data, while for each field analysed, they represent 4.4% for publications, 13% for projects and 1.1% for patents. The study shows current trends for advanced nanomaterials at a top-level information that can be further extended with sub-indicators. Generally, the results indicated a significant growth in research into advanced nanomaterials, including smart nanomaterials, in the last decade, leading to an increased availability of information. Conclusion: These indicators identify trends regarding scientific and technological achievements and represent an important element when examining possible impacts on society and policy implications associated to these areas.

Gender Marginalization in Sports Participation through Advertising: The Case of Nike.

The sport sector functions as a site of health-promotion by encouraging and enabling individuals to invest in their health and giving them tools to do so. This investment is often initiated by, or altered by, role modeling, or seeing other individuals engaging in sport. This could include family or peers but could also include depictions of sport in popular media. Inclusive role-modeling could subsequently encourage more sport participation, thus expanding access to health benefits that arise from sport. However, stereotypical depictions of sports role models could make sports seem like a more exclusive space and discourage participation. We examine a case study of a prominent athletic brand and their advertising to examine the ways they expand or reify stereotypes of gender in sport. Through a qualitative content analysis of 131 commercials released by Nike in the past decade, we explore whether their stated goals of being a socially progressive company extend to genuinely diverse and inclusive portrayals of gender in their commercials. Our results indicate that Nike commercials continue to treat sports as a predominantly and stereotypically masculine realm, therefore marginalizing athletes who are female, who do not fit traditional gender binaries, or who do not display traditionally masculine qualities. We also find that the bulk of athletes portrayed by Nike are those who adhere to gender stereotypes. Despite their purported goal of encouraging individuals to participate in sports, Nike's promotion of gendered sport behaviors may be having an opposite effect for some consumers by discouraging sports participation for those who do not align with the gendered behavior Nike promotes. The stereotyped role modeling of the sport sector portrayed in a majority of Nike commercials could dissuade already marginalized individuals from participating in the health-promoting behaviors available through sport.

Towards FAIR nanosafety data.

Nanotechnology is a key enabling technology with billions of euros in global investment from public funding, which include large collaborative projects that have investigated environmental and health safety aspects of nanomaterials, but the reuse of accumulated data is clearly lagging behind. Here we summarize challenges and provide recommendations for the efficient reuse of nanosafety data, in line with the recently established FAIR (findable, accessible, interoperable and reusable) guiding principles. We describe the FAIR-aligned Nanosafety Data Interface, with an aggregated findability, accessibility and interoperability across physicochemical, bio-nano interaction, human toxicity, omics, ecotoxicological and exposure data. Overall, we illustrate a much-needed path towards standards for the optimized use of existing data, which avoids duplication of efforts, and provides a multitude of options to promote safe and sustainable nanotechnology.

Commentary on "Safe(r) by design implementation in the nanotechnology industry" [NanoImpact 20 (2020) 100267] and "Integrative approach in a safe by design context combining risk, life cycle and socio-economic assessment for safer and sustainable nanomaterials" [NanoImpact 23 (2021) 100335].

Commentary on two recent papers published in NanoImpact "Safe(r) by design implementation in the nanotechnology industry" and "Integrative approach in a safe by design context combining risk, life cycle and socio-economic assessment for safer and sustainable nanomaterials".

A Weight of Evidence approach to classify nanomaterials according to the EU Classification, Labelling and Packaging Regulation criteria.

In the context of the European Union (EU) Horizon 2020 GRACIOUS project (Grouping, Read-Across, Characterisation and classification framework for regulatory risk assessment of manufactured nanomaterials and Safer design of nano-enabled products), we proposed a quantitative Weight of Evidence (WoE) approach for hazard classification of nanomaterials (NMs). This approach is based on the requirements of the European Regulation on Classification, Labelling and Packaging of Substances and Mixtures (the CLP regulation), which implements the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS) in the European Union. The goal of this WoE methodology is to facilitate classification of NMs according to CLP criteria, following the decision trees defined in ECHA's CLP regulatory guidance. In the WoE, results from heterogeneous studies are weighted according to data quality and completeness criteria, integrated, and then evaluated by expert judgment to obtain a hazard classification, resulting in a coherent and justifiable methodology. Moreover, the probabilistic nature of the proposed approach enables highlighting the uncertainty in the analysis. The proposed methodology involves the following stages: (1) collection of data for different NMs related to the endpoint of interest: each study related to each NM is referred as a Line of Evidence (LoE); (2) computation of weighted scores for each LoE: each LoE is weighted by a score calculated based on data quality and completeness criteria defined in the GRACIOUS project; (3) comparison and integration of the weighed LoEs for each NM: A Monte Carlo resampling approach is adopted to quantitatively and probabilistically integrate the weighted evidence; and (4) assignment of each NM to a hazard class: according to the results, each NM is assigned to one of the classes defined by the CLP regulation. Furthermore, to facilitate the integration and the classification of the weighted LoEs, an online R tool was developed. Finally, the approach was tested against an endpoint relevant to CLP (Aquatic Toxicity) using data retrieved from the eNanoMapper database, results obtained were consistent to results in REACH registration dossiers and in recent literature.