Embedding Ethical Impact Assessment in Nanosafety Decision Support

Nanotechnology is a key enabling technology, which is developing fast and influences many aspects of life. Nanomaterials are already included in a broad range of products and industrial sectors. Nanosafety issues are still a matter of concern for policy makers and stakeholders, but currently, there is no platform where all stakeholders can meet and discuss these issues. A comprehensive overview of all the issues in one single dashboard presenting the output of a decision support system is also lacking. This article outlines a strategy for developing one innovative part of a modular decision support system, designed to support the work of a new Risk Governance Council (RGC) for nanomaterials which will be established through the combined efforts of the GOV4NANO, NANORIGO, and RiskGONE H2020 projects. This new module will consist of guidelines for Ethical Impact Assessment (EIA) for nanomaterials and nanoenabled products. This article offers recommendations for adapting the European Committee for Standardization (CEN) prestandard on Ethical Impact Assessment CWA (CEN Workshop Agreement) 17145-2:2017 (E), to fit into the more-encompassing decision support system for risk governance of nanomaterials within the RiskGONE project

Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Background: Lower muscle strength in midlife predicts disability and mortality in later life. Bloodborne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Methods: Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts (n=7,781, ages: 20-104 years, weighted mean=56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, male/female). Results: Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation and the stress response. Ten genes were only associated in younger individuals, four in males only and one in females only. For example PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (=60 years). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts Conclusions: This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age and sex specific gene expression signatures in blood for muscle strength.Wellcome TrustFHS gene expression profiling was funded through the Division of Intramural Research (Principal Investigator, Daniel Levy), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Dr. Murabito is supported by NIH grant R01AG029451. Dr. Kiel is supported by NIH R01 AR41398. The Framingham Heart Study is supported by National Heart, Lung, and Blood Institute contract N01-HC-25195.The InCHIANTI study was supported in part by the Intramural Research Program, National Institute on Aging, NIH, Baltimore MD USA. D.M. and L.W.H. were generously supported by a Wellcome Trust Institutional Strategic Support Award (WT097835MF). W.E.H. was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health in EnglandThe infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Scientific Institute for Quality of Healthcare (IQ healthcare), Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health and Addiction (Trimbos Institute).The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93- 28 015; RIDE2), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of RNA-expression array data for the Rotterdam Study was executed and funded by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. We thank Marjolein Peters, MSc, Ms. Mila Jhamai, Ms. Jeannette M. Vergeer-Drop, Ms. Bernadette van Ast-Copier, Mr. Marijn Verkerk and Jeroen van Rooij, BSc for their help in creating the RNA array expression databaseSHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG and the Caché Campus program of the InterSystems GmbH

Toezicht op strafvorderlijk overheidsoptreden

The central research question is: What kinds of supervision are currently present in the criminal justice system, and what caveats can be identified in both a legislative and a practical context?. Because of this, the concepts ‘supervision’ and ‘criminal justice system’ need to be delineated. This research confines itself to supervisory activities regarding the quality of actions within the criminal justice system, which means that purely organizational and procedural activities fall outside of its scope. Furthermore, a division is made between ‘internal’ and ‘external’ supervision. Internal supervision is the kind that happens within an organizational actor, while external supervision is handled by supervisory parties outside of the organization. Another form of external supervision is the judicial remedies (e.g.: appeals procedures) that can be used to review decisions made by an actor.In de nota die de contouren schetst van de voorgenomen modernisering van het Wetboek van Strafvordering in het kader van het programma Versterking Prestaties Strafrechtketen (VPS) (de Contourennota) is een paragraaf opgenomen over toezicht op strafvorderlijk optreden. In deze Contourennota heeft de minister van Veiligheid en Justitie de vraag gesteld of met het huidig samenstel van rechterlijk, intern en extern toezicht de naleving van de geldende wettelijke voorschriften binnen de strafrechtsketen adequaat en systematisch wordt gecontroleerd en gestimuleerd. De centrale onderzoeksvraag in dit onderzoek luidt: ‘Welke vormen van toezicht bestaan thans op het strafvorderlijk overheidsoptreden en welke mogelijke lacunes kunnen hierin worden geconstateerd in de wettelijke en praktische context?’. Hierdoor moeten de termen ‘toezicht’ en ‘strafvorderlijk overheidsoptreden’ initieel afgebakend worden. Dit onderzoek beperkt zich tot toezichtverhoudingen over de kwaliteit van strafvorderlijk overheidsoptreden, wat betekent dat de bevoegdheden ten aanzien van bedrijfsvoering en bedrijfsprocessen niet in dit onderzoek aan bod komen. Verder wordt een opsplitsing gemaakt tussen ‘intern’ en ‘extern’ toezicht. Met intern toezicht wordt bedoeld het toezicht dat binnen een actor zelf wordt georganiseerd, terwijl extern toezicht het toezicht is dat buiten de actor door andere toezichthoudende instanties wordt georganiseerd. INHOUD: 1. Algemene uitgangspunten 2. Theoretisch kader 3. Methodologische uitgangspunten 4. Inventarisatie toezichtmogelijkheden op strafvorderlijk overheidsoptreden in Nederland 5. Inventarisatie toezichtmogelijkheden op strafvorderlijk overheidsoptreden in België 6. Verslag van een rondetafelgesprek 7. Analyse 8. Conclusi

Risk Governance of Emerging Technologies Demonstrated in Terms of its Applicability to Nanomaterials

Nanotechnologies have reached maturity and market penetration that require nano-specific changes in legislation and harmonization among legislation domains, such as the amendments to REACH for nanomaterials (NMs) which came into force in 2020. Thus, an assessment of the components and regulatory boundaries of NMs risk governance is timely, alongside related methods and tools, as part of the global efforts to optimise nanosafety and integrate it into product design processes, via Safe(r)-by-Design (SbD) concepts. This paper provides an overview of the state-of-the-art regarding risk governance of NMs and lays out the theoretical basis for the development and implementation of an effective, trustworthy and transparent risk governance framework for NMs. The proposed framework enables continuous integration of the evolving state of the science, leverages best practice from contiguous disciplines and facilitates responsive re-thinking of nanosafety governance to meet future needs. To achieve and operationalise such framework, a science-based Risk Governance Council (RGC) for NMs is being developed. The framework will provide a toolkit for independent NMs' risk governance and integrates needs and views of stakeholders. An extension of this framework to relevant advanced materials and emerging technologies is also envisaged, in view of future foundations of risk research in Europe and globally

Risk Governance of Emerging Technologies Demonstrated in Terms of its Applicability to Nanomaterials

Nanotechnologies have reached maturity and market penetration that require nano-specific changes in legislation and harmonization among legislation domains, such as the amendments to REACH for nanomaterials (NMs) which came into force in 2020. Thus, an assessment of the components and regulatory boundaries of NMs risk governance is timely, alongside related methods and tools, as part of the global efforts to optimise nanosafety and integrate it into product design processes, via Safe(r)-by-Design (SbD) concepts. This paper provides an overview of the state-of-the-art regarding risk governance of NMs and lays out the theoretical basis for the development and implementation of an effective, trustworthy and transparent risk governance framework for NMs. The proposed framework enables continuous integration of the evolving state of the science, leverages best practice from contiguous disciplines and facilitates responsive re-thinking of nanosafety governance to meet future needs. To achieve and operationalise such framework, a science-based Risk Governance Council (RGC) for NMs is being developed. The framework will provide a toolkit for independent NMs' risk governance and integrates needs and views of stakeholders. An extension of this framework to relevant advanced materials and emerging technologies is also envisaged, in view of future foundations of risk research in Europe and globally

Identifying species likely threatened by international trade on the IUCN Red List can inform CITES trade measures

Overexploitation is a major threat to biodiversity and international trade in many species is regulated through the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). However, there is no established method to systematically determine which species are most at risk from international trade to inform potential trade measures under CITES. Here, we develop a mechanism using the International Union for Conservation of Nature’s Red List of Threatened Species to identify species that are likely to be threatened by international trade. Of 2,211 such species, CITES includes 59% (1,307 species), leaving two-fifths overlooked and in potential need of international trade regulation. Our results can inform deliberations on potential proposals to revise trade measures for species at CITES Conference of the Parties meetings. We also show that, for taxa with biological resource use documented as a threat, the number of species threatened by local and national use is four times greater than species likely threatened by international trade. To effectively address the overexploitation of species, interventions focused on achieving sustainability in international trade need to be complemented by commensurate measures to ensure that local and national use and trade of wildlife is well-regulated and sustainable

Metformin for treatment of cytopenias in children and young adults with Fanconi anemia

Fanconi anemia (FA), a genetic DNA repair disorder characterized by marrow failure and cancer susceptibility. In FA mice, metformin improves blood counts and delays tumor development. We conducted a single institution study of metformin in nondiabetic patients with FA to determine feasibility and tolerability of metformin treatment and to assess for improvement in blood counts. Fourteen of 15 patients with at least 1 cytopenia (hemoglobin < 10 g/dL; platelet count < 100 000 cells/µL; or an absolute neutrophil count < 1000 cells/µL) were eligible to receive metformin for 6 months. Median patient age was 9.4 years (range 6.0-26.5). Thirteen of 14 subjects (93%) tolerated maximal dosing for age; 1 subject had dose reduction for grade 2 gastrointestinal symptoms. No subjects developed hypoglycemia or metabolic acidosis. No subjects had dose interruptions caused by toxicity, and no grade 3 or higher adverse events attributed to metformin were observed. Hematologic response based on modified Myelodysplastic Syndrome International Working Group criteria was observed in 4 of 13 evaluable patients (30.8%; 90% confidence interval, 11.3-57.3). Median time to response was 84.5 days (range 71-128 days). Responses were noted in neutrophils (n = 3), platelets (n = 1), and red blood cells (n = 1). No subjects met criteria for disease progression or relapse during treatment. Correlative studies explored potential mechanisms of metformin activity in FA. Plasma proteomics showed reduction in inflammatory pathways with metformin. Metformin is safe and tolerable in nondiabetic patients with FA and may provide therapeutic benefit. This trial was registered at as #NCT03398824

Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review

<p>Abstract</p> <p>Background</p> <p>Over the past several decades, complementary and alternative medications have increasingly become a part of everyday treatment. With the rising cost of prescription medications and their production of unwanted side effects, patients are exploring herbal and other natural remedies for the management and treatment of psychological conditions. Psychological disorders are one of the most frequent conditions seen by clinicians, and often require a long-term regimen of prescription medications. Approximately 6.8 million Americans suffer from generalized anxiety disorder. Many also suffer from the spectrum of behavioural and physical side effects that often accompany its treatment. It is not surprising that there is universal interest in finding effective natural anxiolytic (anti-anxiety) treatments with a lower risk of adverse effects or withdrawal.</p> <p>Methods</p> <p>An electronic and manual search was performed through MEDLINE/PubMed and EBSCO. Articles were not discriminated by date of publication. Available clinical studies published in English that used human participants and examined the anxiolytic potential of dietary and herbal supplements were included. Data were extracted and compiled into tables that included the study design, sample population, intervention, control, length of treatment, outcomes, direction of evidence, and reported adverse events.</p> <p>Results</p> <p>A total of 24 studies that investigated five different CAM monotherapies and eight different combination treatments and involved 2619 participants met the inclusion criteria and were analyzed. There were 21 randomized controlled trials and three open-label, uncontrolled observational studies. Most studies involved patients who had been diagnosed with either an anxiety disorder or depression (n = 1786). However, eight studies used healthy volunteers (n = 877) who had normal levels of anxiety, were undergoing surgery, tested at the upper limit of the normal range of a trait anxiety scale, had adverse premenstrual symptoms or were peri-menopausal, reported anxiety and insomnia, or had one month or more of elevated generalized anxiety. Heterogeneity and the small number of studies for each supplement or combination therapy prevented a formal meta-analysis. Of the randomized controlled trials reviewed, 71% (15 out of 21) showed a positive direction of evidence. Any reported side effects were mild to moderate.</p> <p>Conclusions</p> <p>Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects. There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders. However, based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava and combinations of L-lysine and L-arginine as treatments for anxiety symptoms and disorders. Magnesium-containing supplements and other herbal combinations may hold promise, but more research is needed before these products can be recommended to patients. St. John's wort monotherapy has insufficient evidence for use as an effective anxiolytic treatment.</p