The challenges of moving from framework development to the real world: operationalising an oil vulnerability framework for oil spill response in the Canadian Pacific region

To support oil spill response planning, and to focus data collection within the Department of Fisheries and Oceans, Canada (DFO), an oil vulnerability framework was developed in 2016, and applied to the Pacific region. Using a criteria scoring (Exposure, Sensitivity and Recovery categories) and screening process, the framework identifies and ranks species sub-groups in terms of their vulnerability to oil. The framework outputs have been applied during oil spill exercises and during the recent Jake Shearer incident near Bella Bella in Nov 2017. Operationalising the framework at the spatial scale and within the time constraints of oil spill response requires a varied approach to deal with lack of spatial data for some groups. Here we present the current working model how we ensure the best available data is feed into the oil spill response

Oil spill preparedness planning: filling critical species data gaps using habitat suitability modelling

Under the World Class Tanker Safety System Initiative (WCTSS) a national framework was developed to identify marine biological organisms most vulnerable to ship-source oil spills. The Pacific regional application of this framework identified 27 highly vulnerable biological groups, with sea grasses, salt marsh grasses/succulents, sea otters, and baleen whales at the top of the list. A gap analysis during the Pacific regional application identified critical species data gaps that must now be filled to ensure effective response in marine oil spill emergencies. In the absence of robust species distribution and abundance data, habitat suitability models can be used to predict this information using environmental spatial data layers and limited species distribution data. The Oceans Protection Plan (OPP) Habitat Suitability Modelling team is developing a workbook of standardized habitat suitability modelling approaches to illustrate how critical species data gaps may be filled. This workbook will include recommendations for data requirements, models to use, and how to deal with modelling challenges. Models will be developed and tested using data from Canada’s North Central Coast study area and then applied in the Salish Sea to the Strait of Georgia study area in support of the south coast Area Response Plan. In addition to the modelling workbook and model predictions, another major output of this project is the extension of bottom type classification layers from 50-200 m depth, which will be useful for other marine spatial planning analyses. The habitat suitability modelling workbook, model predictions, and extended bottom type classification layers will serve as valuable pieces in the larger puzzle of international transboundary ecosystem protection and recovery

Comprehensive Parent-Metabolite PBPK/PD Modeling Insights into Nicotine Replacement Therapy Strategies

Background Nicotine, the pharmacologically active substance in both tobacco and many electronic cigarette (e-cigarette) liquids, is responsible for the addiction that sustains cigarette smoking. With 8 million deaths worldwide annually, smoking remains one of the major causes of disability and premature death. However, nicotine also plays an important role in smoking cessation strategies. Objectives The aim of this study was to develop a comprehensive, whole-body, physiologically based pharmacokinetic/ pharmacodynamic (PBPK/PD) model of nicotine and its major metabolite cotinine, covering various routes of nicotine administration, and to simulate nicotine brain tissue concentrations after the use of combustible cigarettes, e-cigarettes, nicotine gums, and nicotine patches. Methods A parent–metabolite, PBPK/PD model of nicotine for a non-smoking and a smoking population was developed using 91 plasma and brain tissue concentration–time profles and 11 heart rate profles. Among others, cytochrome P450 (CYP) 2A6 and 2B6 enzymes were implemented, including kinetics for CYP2A6 poor metabolizers. Results The model is able to precisely describe and predict both nicotine plasma and brain tissue concentrations, cotinine plasma concentrations, and heart rate profles. 100% of the predicted area under the concentration–time curve (AUC) and maximum concentration (Cmax) values meet the twofold acceptance criterion with overall geometric mean fold errors of 1.12 and 1.15, respectively. The administration of combustible cigarettes, e-cigarettes, nicotine patches, and nicotine gums was successfully implemented in the model and used to identify diferences in steady-state nicotine brain tissue concentration patterns. Conclusions Our PBPK/PD model may be helpful in further investigations of nicotine dependence and smoking cessation strategies. As the model represents the frst nicotine PBPK/PD model predicting nicotine concentration and heart rate profles after the use of e-cigarettes, it could also contribute to a better understanding of the recent increase in youth e-cigarette use

A framework to assess vulnerability of biological components to ship-source oil spills in the marine environment

A structured approach to identify biological components most affected by a ship-source oil spill has been developed utilising a suite of criteria to assess vulnerability. Our approach divides criteria into three categories: exposure, sensitivity, and recovery, each encompassing a number of criteria which are envisaged to be consistent and broad enough to be usable in any region in Canada. In support of this, we are working with biologists from other Canadian regions who are currently developing ship-source oil spill response plans (i.e. Pacific, Quebec and Maritimes) to test the usability of this approach in multiple marine environments. For the Pacific region, a full application of this process is underway for the Salish Sea. If successful, we anticipate this approach will be useful for identification of biological components most affected by ship-source oil spills in any marine environment

Keeping connected : identity, social connection and education for young people living with chronic illness

The ‘Keeping Connected’ project was a three year project \ud (2006-2009) co-funded by the Australian Research Council\ud and The Royal Children’s Hospital Education Institute.\ud Its focus was on young people who experience chronic illness-related \ud interruptions to their schooling. Its aims were to make visible the young\ud people, their experiences, voices, and concerns, and to explore the ways\ud in which they were being supported or hampered in various aspects\ud of their education trajectories. \ud The project brought together a large multi-disciplinary research team working\ud in collaboration with the RCH Education Institute with the aim of achieving\ud a better understanding of issues related to the support and engagement\ud of young people living and learning with ongoing health conditions.\ud Who and what do young people feel is important in creating, strengthening,\ud and maintaining educational and social connections in their lives? What do \ud parents feel are significant supports or challenges for young people (and their \ud families) experiencing interrupted schooling due to ongoing health issues?\ud What do education and health care professionals see as key areas of focus\ud in supporting young people to maintain social and educational connections?\ud This report highlights the clear and pressing need for a system of advocacy\ud on the part of young people and families within both health and education\ud systems—and between schools and hospitals. The Royal Children’s Hospital \ud Education Institute is well positioned to influence policy and practice\ud across these sectors

Extracellular Vesicle-Mediated Macrophage Activation: An Insight Into the Mechanism of Thioredoxin-Mediated Immune Activation

Extracellular vesicles (EVs) generated from redox active anticancer drugs are released into the extracellular environment. These EVs contain oxidized molecules and trigger inflammatory responses by macrophages. Using a mouse model of doxorubicin (DOX)-induced tissue injury, we previously found that the major sources of circulating EVs are from heart and liver, organs that are differentially affected by DOX. Here, we investigated the effects of EVs from cardiomyocytes and those from hepatocytes on macrophage activation. EVs from H9c2 rat cardiomyocytes (H9c2 EVs) and EVs from FL83b mouse hepatocytes (FL83 b EVs) have different levels of protein-bound 4-hydroxynonenal and thus different immunostimulatory effects on mouse RAW264.7 macrophages. H9c2 EVs but not FL83 b EVs induced both pro-inflammatory and anti-inflammatory macrophage activation, mediated by NFκB and Nrf-2 pathways, respectively. DOX enhanced the effects of H9c2 EVs but not FL83 b EVs. While EVs from DOX-treated H9c2 cells (H9c2 DOXEVs) suppressed mitochondrial respiration and increased glycolysis of macrophages, EVs from DOX-treated FL83b cells (FL83b DOXEVs) enhanced mitochondrial reserve capacity. Mechanistically, the different immunostimulatory functions of H9c2 EVs and FL83 b EVs are regulated, in part, by the redox status of the cytoplasmic thioredoxin 1 (Trx1) of macrophages. H9c2 DOXEVs lowered the level of reduced Trx1 in cytoplasm while FL83b DOXEVs did the opposite. Trx1 overexpression alleviated the effect of H9c2 DOXEVs on NFκB and Nrf-2 activation and prevented the upregulation of their target genes. Our findings identify EVs as a novel Trx1-mediated redox mediator of immune response, which greatly enhances our understanding of innate immune responses during cancer therapy

"My Children and I Will no Longer Suffer from Malaria": A Qualitative Study of the Acceptance and Rejection of Indoor Residual Spraying to Prevent Malaria in Tanzania.

The objective of this study was to identify attitudes and misconceptions related to acceptance or refusal of indoor residual spraying (IRS) in Tanzania for both the general population and among certain groups (e.g., farmers, fishermen, community leaders, and women). This study was a series of qualitative, semi-structured, in-depth interviews and focus group discussions conducted from October 2010 to March 2011 on Mainland Tanzania and Zanzibar. Three groups of participants were targeted: acceptors of IRS (those who have already had their homes sprayed), refusers (those whose communities have been sprayed, but refused to have their individual home sprayed), and those whose houses were about to be sprayed as part of IRS scale-up. Interviews were also conducted with farmers, fishermen, women, community leaders and members of non-government organizations responsible for community mobilization around IRS. Results showed refusers are a very small percentage of the population. They tend to be more knowledgeable people such as teachers, drivers, extension workers, and other civil servants who do not simply follow the orders of the local government or the sprayers, but are skeptical about the process until they see true results. Refusal took three forms: 1) refusing partially until thorough explanation is provided; 2) accepting spray to be done in a few rooms only; and 3) refusing outright. In most of the refusal interviews, refusers justified why their houses were not sprayed, often without admitting that they had refused. Reasons for refusal included initial ignorance about the reasons for IRS, uncertainty about its effectiveness, increased prevalence of other insects, potential physical side effects, odour, rumours about the chemical affecting fertility, embarrassment about moving poor quality possessions out of the house, and belief that the spray was politically motivated. To increase IRS acceptance, participants recommended more emphasis on providing thorough public education, ensuring the sprayers themselves are more knowledgeable about IRS, and asking that community leaders encourage participation by their constituents rather than threatening punishment for noncompliance. While there are several rumours and misconceptions concerning IRS in Tanzania, acceptance is very high and continues to increase as positive results become apparent

Childhood Physical Neglect Is Associated With Exaggerated Systemic and Intracellular Inflammatory Responses to Repeated Psychosocial Stress in Adulthood

Experiences of child maltreatment are associated with a host of adverse mental and physical health outcomes in adulthood. Altered reactivity to psychosocial stress exposure may partially explain known associations between early experiences of maltreatment and later life health. The present study focuses on examining whether experiences of child maltreatment are associated with physiological reactions to initial and repeated psychosocial stress in adulthood. To this end, 44 healthy adults (52% male, aged 18–65) completed the Childhood Trauma Questionnaire to provide information about exposure to child maltreatment and completed the Trier Social Stress Test (TSST) on 2 consecutive days. Peripheral blood was collected prior to as well as 30 and 120 min following the TSST on each day. Plasma Interleukin-6 (IL-6) and gene expression of IL-6, IL-1β, nuclear factor-kB (NF-kB), and inhibitor of kB (IkB) were measured from each blood sample. Total CTQ scores were unrelated to plasma IL-6 and gene expression (ps > .10) but a history of childhood physical neglect was associated with increased interleukin-1β (β =.35; p =.02; R2 =.19) and nuclear factor-kB (β =.30; p =.046; R2 =.13) expression following initial stress. Following repeated exposure to the TSST, childhood physical neglect was associated with increased plasma IL-6 reactivity (β =.34; p =.02; R2 =.16) and increased expression of nuclear factor-kB (β =.31; p =.04; R2 =.08). Finally, childhood physical neglect was associated with decreased habituation following repeated exposure to the TSST. Other CTQ subscales were not related to plasma IL-6 and gene expression when considered individually. Results from this study are suggestive of a unique effect of childhood physical neglect on the physiological stress response following initial and repeated exposure to a common psychosocial stressor. This provides important directions for future research because the effect of childhood physical neglect on long-term neglect are not well understood and in need of further investigation