Radiation Adverse Outcome pathways (AOPs): examining priority questions from an international horizon-style exercise.

Purpose: The Organisation for Economic Co-operation and Development (OECD) Adverse Outcome Pathway (AOP) Development Programme is being explored in the radiation field, as an overarching framework to identify and prioritize research needs that best support strengthening of radiation risk assessment and risk management strategies. To advance the use of AOPs, an international horizon-style exercise (HSE) was initiated through the Radiation/Chemical AOP Joint Topical Group (JTG) formed by the OECD Nuclear Energy Agency (NEA) High-Level Group on Low Dose Research (HLG-LDR) under the auspices of the Committee on Radiological Protection and Public Health (CRPPH). The intent of the HSE was to identify key research questions for consideration in AOP development that would help to reduce uncertainties in estimating the health risks following exposures to low dose and low dose-rate ionizing radiation.

Leadership education as democracy-in-action: In pursuit of the United Nations Sustainable Development Goals.

With the world growing in complexity and interconnectedness, the demand for leaders equipped to solve compound problems will only increase. Higher education is called upon to develop leadership in students and needs to engage relevant tools and techniques to prepare students for the tasks ahead. Democratic engagement-from voter education and engagement to critical service learning-and leadership development are powerful vehicles for student development.

Considerations for application of benchmark dose modeling in radiation research: workshop highlights.

Background: Exposure to different forms of ionizing radiation occurs in diverse occupational, medical, and environmental settings. Improving the accuracy of the estimated health risks associated with exposure is therefore, essential for protecting the public, particularly as it relates to chronic low dose exposures. A key aspect to understanding health risks is precise and accurate modeling of the dose-response relationship.

Radiation adverse outcome pathways (AOPs) are on the horizon: advancing radiation protection through an international Horizon-Style exercise.

Purpose: The Adverse Outcome Pathway (AOP) framework, a systematic tool that can link available mechanistic data with phenotypic outcomes of relevance to regulatory decision-making, is being explored in areas related to radiation risk assessment. To examine the challenges including the use of AOPs to support the radiation protection community, an international horizon-style exercise was initiated through the Organisation for Economic Co-operation and Development Nuclear Energy Agency High-Level Group on Low Dose Research Radiation/Chemical AOP Joint Topical Group. The objective of the HSE was to facilitate the collection of ideas from a range of experts, to short-list a set of priority research questions that could, if answered, improve the description of the radiation dose-response relationship for low dose/dose-rate exposures, as well as reduce uncertainties in estimating the risk of developing adverse health outcomes following such exposures.

A localized calcium transient and polar body abscission.

Polar body emission is a special form of cytokinesis in oocyte meiosis that ensures the correct number of chromosomes in reproduction-competent eggs. The molecular mechanism of the last step, polar body abscission, is poorly understood. While it has been proposed that Ca signaling plays important roles in embryonic cytokinesis, to date transient increases in intracellular free Ca have been difficult to document in oocyte meiosis except for the global Ca wave induced by sperm at fertilization.

Celiac Disease After Administration of Immune Checkpoint Inhibitors: A Case Report.

Immune checkpoint inhibitors (ICI) reinvigorate the immune system to recognize and destroy tumor cells. Because of this biological mechanism, patients might develop autoimmune toxicities, notably in the digestive tract (most frequently, hepatitis or colitis). A 70-year-old man with relapsed mesothelioma was treated with nivolumab in 3rd line.

Adverse outcome pathway: a path toward better data consolidation and global co-ordination of radiation research.

Background: The purpose of toxicology is to protect human health and the environment. To support this, the Organisation for Economic Co-operation and Development (OECD), operating via its Extended Advisory Group for Molecular Screening and Toxicogenomics (EAGMST), has been developing the Adverse Outcome Pathway (AOP) approach to consolidate evidence for chemical toxicity spanning multiple levels of biological organization. The knowledge transcribed into AOPs provides a structured framework to transparently organize data, examine the weight of evidence of the AOP, and identify causal relationships between exposure to stressors and adverse effects of regulatory relevance.

Delirium and Inflammation in Older Adults Hospitalized for COVID-19: A Cohort Study.

Purpose: The occurrence and predictors of delirium in older adults hospitalized for coronavirus disease 2019 (COVID-19) have not been well described. Highlighting the association with inflammatory markers may be useful for identifying delirium. This study aimed to determine the prevalence and incidence of delirium and explore its association with the C-reactive protein (CRP).

COHERE - strengthening cooperation within the Canadian government on radiation research.

Purpose: Canadian Organization on Health Effects from Radiation Exposure (COHERE) is a government initiative to better understand biological and human health risks from ionizing radiation exposures relevant to occupational and environmental settings (<100 mGy, <6 mGy/h). It is currently a partnership between two federal agencies, Health Canada (HC) and the Canadian Nuclear Safety Commission (CNSC). COHERE's vision is to contribute knowledge to reduce scientific uncertainties from low dose and dose-rate exposures.

Bringing together scientific disciplines for collaborative undertakings: a vision for advancing the adverse outcome pathway framework.

Background: Decades of research to understand the impacts of various types of environmental occupational and medical stressors on human health have produced a vast amount of data across many scientific disciplines. Organizing these data in a meaningful way to support risk assessment has been a significant challenge. To address this and other challenges in modernizing chemical health risk assessment, the Organisation for Economic Cooperation and Development (OECD) formalized the adverse outcome pathway (AOP) framework, an approach to consolidate knowledge into measurable key events (KEs) at various levels of biological organisation causally linked to disease based on the weight of scientific evidence (http://oe.

Diffusive gradients in thin films (DGT): A suitable tool for metals/metalloids monitoring in continental waterbodies at the large network scale.

The contribution of Diffusive Gradients in Thin films (DGT) passive sampling to continental water quality monitoring was assessed in a real measurement network (6 sampling campaigns, 17 stations). Ten metals/metalloids (Al, Zn, Ni, Cd, Cu, Pb, Cr, As, Se and Sb) were studied using the control laboratory's working conditions with grab and DGT passive sampling. The DGT field deployments were robust, with a 3% sampler loss rate and a <65% average relative deviation between duplicates.

Agranulocytosis Induced by Tamoxifen in a Breast Cancer Patient.

Background: The main side effects of tamoxifen are menopausal symptoms. We report a case of agranulocytosis induced by tamoxifen in a 33-year-old woman treated in the adjuvant setting.

Case Presentation: Ten days after the beginning of tamoxifen treatment, the patient complained of asthenia and mucositis.

Fulvestrant and palbociclib combination in heavily pretreated hormone receptor-positive, HER2-negative metastatic breast cancer patients.

Purpose: We report the results of a retrospective analysis of the fulvestrant and palbociclib combination within a temporary authorization of use (TAU) program in 77 heavily pretreated patients with hormone receptor-positive (HR+), HER2-negative metastatic breast cancer.

Methods: All patients who received the fulvestrant and palbociclib combination within this TAU program were included. Toxicities were graded using the CTCAE v5 scale.

Measles Hospitalizations at a United States Children's Hospital 2011-2017.

Background: There are no recent descriptions of measles hospitalizations and complications in US children despite outbreaks within the past decade-including 2 in Minnesota (2011 and 2017). The objective of our study was to describe complications, hospital management and resource utilization for children hospitalized for measles at a US children's hospital.

Methods: Retrospective case series of children (0-18 years of age) hospitalized for measles (observation/inpatient diagnosis code for measles) at Children's Minnesota, January 1, 2011, to September 1, 2017.

Radiation Biology and Its Role in the Canadian Radiation Protection Framework.

The linear no-threshold (linear-non-threshold) model is a dose-response model that has long served as the foundation of the international radiation protection framework, which includes the Canadian regulatory framework. Its purpose is to inform the choice of appropriate dose limits and subsequent as low as reasonably achievable requirements, social and economic factors taken into account. The linear no-threshold model assumes that the risk of developing cancer increases proportionately with increasing radiation dose.

Is there a role for the adverse outcome pathway framework to support radiation protection?

Purpose: In 2012, the Organization for Economic Cooperation and Development (OECD) formally launched the Adverse Outcome Pathway (AOP) Programme. The AOP framework has the potential for predictive utility in identifying early biological endpoints linked to adverse effects. It uses the weight of correlative evidence to identify a minimal set of measurable key events that link molecular initiating events to an adverse outcome.

In vivo animal studies help achieve international consensus on standards and guidelines for health risk estimates for chronic exposure to low levels of tritium in drinking water.

Existing and future nuclear fusion technologies involve the production and use of large quantities of tritium, a highly volatile, but low toxicity beta-emitting isotope of hydrogen. Tritium has received international attention because of public and scientific concerns over its release to the environment and the potential health impact of its internalization. This article provides a brief summary of the current state of knowledge of both the biological and regulatory aspects of tritium exposure; it also explores the gaps in this knowledge and provides recommendations on the best ways forward for improving our understanding of the health effects of low-level exposure to it.

Practice Patterns in the Treatment and Monitoring of Acute T Cell-Mediated Kidney Graft Rejection in Canada.

Background: One of the goals of the Canadian National Transplant Research Program (CNTRP) is to develop novel therapies for acute rejection that could positively affect graft outcomes with greater efficacy or less toxicity. To develop innovative management strategies for kidney graft rejection, new modalities need to be compared with current clinical practices. However, there are no standardized practices concerning the management of acute T cell-mediated rejection (TCMR).

Any place left for induction chemotherapy for locally advanced head and neck squamous cell carcinoma?

The issue of induction chemotherapy (ICT) interest in locoregionally advanced squamous cell cancer of the head and neck is a real epic that has been carried out over four phase III studies: PARADIGM, DECIDE, NCT01086826 and lastly the conclusive GORTEC 2007-02. With no significant benefit in overall survival of ICT, followed by concurrent chemoradiation over the standard chemoradiotherapy alone, in three of these studies, and a significant number of treatment-related deaths with the standard regimen docetaxel, cisplatin, and fluorouracil, ICT is no longer a hot topic. However, this strategy might still be useful in the aim of limiting the metastatic extension affecting up to 30% of patients: ICT is systematically associated with a reduced metastatic relapse even though the survival effect is never statistically significant when compared directly with concomitant radiochemotherapy.

Two sampling strategies for an overview of pesticide contamination in an agriculture-extensive headwater stream.

Two headwaters located in southwest France were monitored for 3 and 2 years (Auvézère and Aixette watershed, respectively) with two sampling strategies: grab and passive sampling with polar organic chemical integrative sampler (POCIS). These watersheds are rural and characterized by agricultural areas with similar breeding practices, except that the Auvézère watershed contains apple production for agricultural diversification and the downstream portion of the Aixette watershed is in a peri-urban area. The agricultural activities of both are extensive, i.

Spindle function in Xenopus oocytes involves possible nanodomain calcium signaling.

Intracellular calcium transients are a universal phenomenon at fertilization and are required for egg activation, but the exact role of Ca in second-polar-body emission remains unknown. On the other hand, similar calcium transients have not been demonstrated during oocyte maturation, and yet, manipulating intracellular calcium levels interferes with first-polar-body emission in mice and frogs. To determine the precise role of calcium signaling in polar body formation, we used live-cell imaging coupled with temporally precise intracellular calcium buffering.

[Pertuzumab and solid tumors: perspectives].

Over the past decade, trastuzumab was the only available monoclonal anti-HER2 antibody for the treatment of HER2 positive breast and gastric cancer. Recently, pertuzumab added to docetaxel and trastuzumab showed dramatic overall survival improvement in first line treatment of HER2 positive metastatic breast cancer. Pertuzumab is the first approved monoclonal antibody in a new class of drugs called dimerization inhibitors.

An outbreak of measles in an undervaccinated community.

Measles is readily spread to susceptible individuals, but is no longer endemic in the United States. In March 2011, measles was confirmed in a Minnesota child without travel abroad. This was the first identified case-patient of an outbreak.

Pertuzumab: development beyond breast cancer.

Pertuzumab (Perjeta®) represents the first monoclonal antibody in a new class of agents known as dimerization inhibitors. Pertuzumab was recently approved for the treatment of Human Epidermal Receptor 2 (HER2)-positive breast cancer in the metastatic and neo-adjuvant setting. This approval for first-line therapy for metastatic breast cancer was based on the results of a large randomized multicenter phase III trial showing a significant improvement in overall survival when pertuzumab was combined with trastuzumab and docetaxel in HER2-positive metastatic breast cancer.