A comparison of dermal toxicity models; assessing suitability for safe(r)-by-design decision-making and for screening nanomaterial hazards

The objective of Safe-by-Design (SbD) is to support the development of safer products and production processes, and enable safe use throughout a materials' life cycle; an intervention at an early stage of innovation can greatly benefit industry by reducing costs associated with the development of products later found to elicit harmful effects. Early hazard screening can support this process, and is needed for all of the expected nanomaterial exposure routes, including inhalation, ingestion and dermal. In this study, we compare in vitro and ex vivo cell models that represent dermal exposures (including HaCaT cells, primary keratinocytes, and reconstructed human epidermis (RhE)), and when possible consider these in the context of regulatory accepted OECD TG for in vitro dermal irritation. Various benchmark nanomaterials were used to assess markers of cell stress in each cell model. In addition, we evaluated different dosing strategies that have been used when applying the OECD TG for dermal irritation in assessment of nanomaterials, and how inconsistencies in the approach used can have considerable impact of the conclusions made. Although we could not demonstrate alignment of all models used, there was an indication that the simpler in vitro cell model aligned more closely with RhE tissue than ex vivo primary keratinocytes, supporting the use of HaCaT cells for screening of dermal toxicity of nanomaterials and in early-stage SbD decision-making

Safe(r)-by-design principles in the thermoplastics industry: guidance on release assessment during manufacture of nano-enabled products

Background: The application of nanomaterials (NMs) and nano-enabled products (NEPs) across many industries has been extensive and is still expanding decades after first being identified as an emerging technology. Additive manufacturing has been greatly impacted and has seen the benefits of integrating NMs within products. With the expansion of nanotechnology, there has been a need to develop more adaptive and responsive methods to ascertain risks and ensure technology is developed safely. The Safe(r)-by-Design (SbD) concept can be used to establish safe parameters and minimise risks during the materials’ lifecycle, including the early stages of the supply chain. Exposure monitoring has advanced in recent years with the creation of standardised protocols for occupational exposure assessment of nano-objects and their aggregates and agglomerates (NOAA).Methods: To aid in the development of an online SbD-supporting platform by the EU-funded project SAbyNA, we adopt a Europe Standard for monitoring release of NOAA to identify if a greater release of NOAA is associated with incorporation of NMs within NEPs compared to a polymer matrix alone. Case studies included filaments of polypropylene (PP) with nano-Ag or polycarbonate (PC) with single-walled carbon nanotubes (SWCNTs). NMs were received in masterbatch, and therefore previously modified to align with SbD interventions. Results were collected in line with European Standard recommendations: monitoring particle concentrations using direct reading instruments (DRI), sampling for offline chemical and morphological analysis, and collecting contextual information.Results and discussion: Based on the criteria described in the European standard (BS EN 17058), data from both case studies identified that inhalation exposure relating to NM was “unlikely”. Despite this, during the production of the SWCNT-PC filaments, some noteworthy observations were made, including several DRI activity measurements shown to be higher than background levels, and material morphologically similar to the reference SWCNT/polymeric masterbatch observed in offline analysis. The data collected during this campaign were used to discuss choices available for data interpretation and decision-making in the European Standard for monitoring release of NOAA and also to facilitate the development of SAbyNA’s user-friendly industry platform for the SbD of NMs and NEPs

Gender Differences in Acute and Chronic Pain in the Emergency Department: Results of the 2014 Academic Emergency Medicine Consensus Conference Pain Section

Pain is a leading public health problem in the United States, with an annual economic burden of more than $630 billion, and is one of the most common reasons that individuals seek emergency department (ED) care. There is a paucity of data regarding sex differences in the assessment and treatment of acute and chronic pain conditions in the ED. The Academic Emergency Medicine consensus conference convened in Dallas, Texas in May of 2014 to develop a research agenda to address this issue among others related to sex differences in the ED. Prior to the conference, experts and stakeholders from emergency medicine and the pain research field reviewed the current literature and identified eight candidate priority areas. At the conference, these eight areas were reviewed and all eight were ratified using a nominal group technique to build consensus. These priority areas were: 1) gender differences in the pharmacologic and non-pharmacologic interventions for pain, including differences in opioid tolerance, side effects, or misuse; 2) gender differences in pain severity perceptions, clinically meaningful differences in acute pain, and pain treatment preferences; 3) gender differences in pain outcomes of ED patients across the lifespan; 4) gender differences in the relationship between acute pain and acute psychological responses; 5) the influence of physician-patient gender differences and characteristics on the assessment and treatment of pain; 6) gender differences in the influence of acute stress and chronic stress on acute pain responses; 7) gender differences in biologic mechanisms and molecular pathways mediating acute pain in ED populations; and 8) gender differences in biologic mechanisms and molecular pathways mediating chronic pain development after trauma, stress, or acute illness exposure. These areas represent priority areas for future scientific inquiry, and gaining understanding in these will be essential to improving our understanding of sex and gender differences in the assessment and treatment of pain conditions in emergency care settings

Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

Peer reviewe

Remembering Lucile: a Virginia family's rise from slavery and a legacy forged a mile high

Includes bibliographical references and index.The University of Colorado erroneously recognized Dr. Ruth Cave Flowers as its first Black graduate. In 1918--six years before Flowers's graduation--Lucile Berkeley Buchanan Jones received her bachelor's degree. McLean introduces this woman who lived through an extraordinary time and rectifies the omission from institutional history.--Provided by publisher.Prologue: her voice can be heard -- Inquiry and epiphany -- Born in slavery: the master, the mistress, and their chattel -- The Berkeleyes: a slave named Harriet Bishop, and her daughter, Sarah -- Slavery's chain done broke at last -- Colorado and the promise of freedom -- From Denver's bottoms to P.T. Barnum's town -- Education, politics and leisure -- The frontier in our souls -- School, community, and love lost -- A fly in the buttermilk: Colorado and the world of higher education -- "Goin' to Kansas City": education and baseball -- It's Mister Jones, if you please! -- Chicago, take two -- "Lincoln was a Republican, that's all I need to know!" -- Coming home and going home -- Epilogue: the end of the living line

Simulated biological fluids - a systematic review of their biological relevance and use in relation to inhalation toxicology of particles and fibres

The use of simulated biological fluids (SBFs) is a promising in vitro technique to better understand the release mechanisms and possible in vivo behaviour of materials, including fibres, metal-containing particles and nanomaterials. Applications of SBFs in dissolution tests allow a measure of material biopersistence or, conversely, bioaccessibility that in turn can provide a useful inference of a materials biodistribution, its acute and long-term toxicity, as well as its pathogenicity. Given the wide range of SBFs reported in the literature, a review was conducted, with a focus on fluids used to replicate environments that may be encountered upon material inhalation, including extracellular and intracellular compartments. The review aims to identify when a fluid design can replicate realistic biological conditions, demonstrate operation validation, and/or provide robustness and reproducibility. The studies examined highlight simulated lung fluids (SLFs) that have been shown to suitably replicate physiological conditions, and identify specific components that play a pivotal role in dissolution mechanisms and biological activity; including organic molecules, redox-active species and chelating agents. Material dissolution was not always driven by pH, and likewise not only driven by SLF composition; specific materials and formulations correspond to specific dissolution mechanisms. It is recommended that SLF developments focus on biological predictivity and if not practical, on better biological mimicry, as such an approach ensures results are more likely to reflect in vivo behaviour regardless of the material under investigation

Contextualising journalism education and training in Southern Africa

In this article it is argued that journalism education in Southern Africa must contend with defining a new academic identity for itself, extricating itself from dependency on Western oriented models of journalism education and training, as this has been a perennial challenge in most of Africa

Establishing relationships between particle-induced in vitro and in vivo inflammation endpoints to better extrapolate between in vitro markers and in vivo fibrosis.

We extracted in vivo and in vitro dose-response information for particles known to induce this pulmonary fibrosis (crystalline silica, specifically α-quartz). To test the in vivo-in vitro extrapolation (IVIVE) determined for crystalline silica, cerium dioxide nanoparticles (nano-CeO2) were used as a case study allowing us to evaluate our findings with a less studied substance. The IVIVE methodology outlined in this paper is formed of five steps, which can be more generally summarised into two categories (i) aligning the in vivo and in vitro dosimetry, (ii) comparing the dose-response curves and derivation of conversion factors