Canada Ltd Research Articles

Improving grapevine virus diagnostics: Comparative analysis of three dsRNA enrichment methods for high-throughput sequencing

The extraction of double stranded (ds) RNA is a common enrichment method for the study, characterization, and detection of RNA viruses. In addition to RNA viruses, viroids, and some DNA viruses, can also be detected from dsRNA enriched extracts which makes it an attractive method for detecting a wide range of viruses when coupled with HTS. Several dsRNA enrichment strategies have been developed. The oldest utilizes the selective binding properties of dsRNA to cellulose. More recent methods are based on the application of anti-dsRNA antibodies and viral proteins with a specific affinity for dsRNA. All three methods have been used together with HTS for plant virus detection and study. To our knowledge, this is the first comparative study of three alternative dsRNA enrichment methods for virus and viroid detection through HTS using virus-infected, and healthy grapevine test plants. Extracts were performed in triplicate using methods based on, the anti-dsRNA antibody mAb rJ2 (Millipore Sigma Canada Ltd, Oakville, ON, Canada), the B2 dsRNA binding protein, and ReliaPrep™ Resin (Promega Corporation, Madison, WI, USA). The results show that the workflows for all three methods are effectively comparable, apart from purification steps related to antibody and binding protein construct. Both the cellulose resin and dsRNA binding protein construct methods provide highly enriched dsRNA extracts suitable for HTS with the B2 method providing a 36× and the ReliaPrep™ Resin a 163× increase in dsRNA enrichment compared to the mAb rJ2 antibody. The overall consistency and cost effectiveness of the ReliaPrep™ cellulose resin-based method and the potentially simpler adaptation to robotics made it the method of choice for future transfer to a semi-automated workflow.

Integrating risk assessment methods for carbon storage: A case study for the quest carbon capture and storage facility

This paper documents how tools developed by the National Risk Assessment Partnership (NRAP) complement the Bowtie risk assessment approach through the demonstration of a risk-based Area of Review (AoR) determination for the Quest Carbon Capture and Storage (CCS) facility near Edmonton, Alberta with the NRAP Open-Source Integrated Assessment Model (NRAP Open-IAM). The Bowtie risk assessment for the Quest CCS site was developed by Shell Canada Ltd., who operates the asset on behalf of the Athabasca Oil Sand Project — a joint venture, owned by Canadian Natural Resources Ltd, Chevron Canada and Shell Canada Ltd. The Quest Bowtie treats site risk comprehensively – considering a large set of technical and project risks (e.g., operational risks, above ground infrastructure, public perception, etc.). NRAP tools, methods, and analyses are focused on quantitative assessment of subsurface technical risks. NRAP-Open-IAM was used to evaluate potential groundwater impacts at the Quest site, i.e., a sufficient change above background groundwater quality levels to be measurable, should CO2 and/or brine leak from the reservoir via a faulty and/or compromised wellbore. Our results show there is a low potential for groundwater impact and support a further reduction (from ∼460 to 100 km2) to the established AoR for the Quest site. Integrating both approaches early in the site characterization period could significantly benefit commercial-scale projects by drastically reducing the region over which leakage risks (e.g., legacy wells) need to be evaluated, i.e., the AoR. This is especially true for brownfield sites, which could contain hundreds to thousands of legacy wells. Further, basing monitoring network design on those regions where impacts are most likely to occur has the potential to facilitate more efficient deployment of monitoring technologies and improve the likelihood of detecting a leak should one occur.

Symptom severity, impairment and health outcomes in patients with Functional Tic Like Behaviours (P11-11.011)

<h3>Objective:</h3> To quantitatively understand symptom severity, impairment, and health outcomes of patients with functional tic-like behaviours (FTLB) compared to Tourette Syndrome (TS) and healthy controls (HC). <h3>Background:</h3> Functional tic-like behaviors (FTLB) are a previously rare form of functional movement disorder that rose in incidence during the COVID-19 pandemic. Patients report significant disruptions in daily functioning. <h3>Design/Methods:</h3> As part of a larger data set, patients aged 11–25 years with FTLB (n= 34) were age and sex-matched to TS (n= 21), and healthy controls (HC) (n=21). Groups completed online self-report measures and a clinical neuropsychiatric interview that investigated quality of life, disability, loneliness, suicidality, depression, anxiety, social interaction anxiety, social phobia, current and peak tic-severity, and family functioning. Two-tailed group differences were Bonferroni corrected. <h3>Results:</h3> Compared to HC and TS, FTLB patients endure higher levels of total disability (p=.037), self-care disability (p=.019), disability related to participation in life activities such as school and work (p=.013), depression (p=.011), and suicidality (p&lt;.001). 61.8% of FTLB patients reported school absence that ranged up to 65% of the time (Mean=20.88%, SD=22.25). FTLB had higher current phonic tic severity (p=.048), and peak motor and phonic tic severity (p&lt;.001; p&lt;.001) than TS. FTLB experience lower quality of life in the physical, psychological, and environmental domains (p=.015; p=.031; p=.042) and significantly higher social interaction anxiety (p=.004), social phobia (p&lt;.001), and loneliness (p=.038) compared to HC. TS and FTLB reported similar levels of tic related impairment, anxiety, and social anxiety/phobia. Family functioning was not significantly different between groups. <h3>Conclusions:</h3> FTLB are a highly disabling disorder that severely impacts quality of life, social and adaptive functioning, and mental health. Comparable levels of social anxiety, loneliness, and tic related impairment in TS and FTLB may be due to social apprehension in response to common negative reactions to tics and tic-like behaviors. <b>Disclosure:</b> Ms. Berg has nothing to disclose. The institution of Dr. Pringsheim has received research support from Maternal Newborn Child and Youth Strategic Clinical Network. The institution of Dr. Pringsheim has received research support from Owerko Center of Alberta Children’s Hospital Research Institute. The institution of Dr. Pringsheim has received research support from Canadian Institutes of Health Research. The institution of Dr. Pringsheim has received research support from Public Health Agency of Canada. Dr. Martino has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Martino has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merz Pharma Canada Ltd..

Etiological factors associated with functional tic-like behaviours during the COVID-19 pandemic (P11-11.015)

<h3>Objective:</h3> To explore the hypothesized etiological factors affecting the functional tic like behaviour (FTLB) cohort that emerged since the onset of the pandemic. <h3>Background:</h3> FTLB are a form of functional movement disorder resembling Tourette Syndrome (TS) that surged in prevalence during the SARS-COV-2 pandemic. Exposure to tic-related social media content, pandemic stressors, and comorbid neuropsychiatric disorders are factors hypothesized to contribute to the sudden increase in FTLB. <h3>Design/Methods:</h3> FTLB patients (n= 34) age/sex matched with TS (n = 21), and healthy controls (HC) (n=21) completed self-report measures and a clinical neuropsychiatric interview that investigated social media use, suggestibility, distress tolerance, demographics, attachment style, SARS-COV-2 related experiences, family history, family functioning, loneliness, and neuropsychiatric comorbidities. Group differences were Bonferroni corrected. <h3>Results:</h3> FTLB had higher levels of depression (p &lt;.001), suicidality (p &lt;.001), panic disorder (p=.029), and were more likely to gender identify as trans/non-binary/genderfluid (p =.013) than TS and HC. Compared to HC, FTLB patients experienced higher levels of anxiety (p =.005), vulnerable attachment (p =.004), agoraphobia (p=.016), borderline personality traits (p =.004), psychotic symptoms (p =.049), ADHD (p =.035), neuropsychiatric family history (p &lt;.001), pandemic related sleep disturbance (p=.002) and loneliness (p =.038). FTLB reported poorer pandemic school performance compared to TS (p=.043). FTLB and HC were more likely to first learn about tics through social media than TS. Suggestibility, distress tolerance, family functioning, exposure to tic-related content on social media, time spent online, social media integration and comparison, and most pandemic experiences tested were not significantly different. Distress tolerance posed the only significant interaction between group and gender identity in HC. <h3>Conclusions:</h3> Neuropsychiatric comorbidities emerged as the strongest etiological factor related to FTLB. The insignificant direct relationship between FTLB to tic-related content on social media may be due to ubiquitous exposure to tic-content suggesting the influence of social media is mediated by unexplored factors. <b>Disclosure:</b> Ms. Berg has nothing to disclose. The institution of Dr. Pringsheim has received research support from Maternal Newborn Child and Youth Strategic Clinical Network. The institution of Dr. Pringsheim has received research support from Owerko Center of Alberta Children’s Hospital Research Institute. The institution of Dr. Pringsheim has received research support from Canadian Institutes of Health Research. The institution of Dr. Pringsheim has received research support from Public Health Agency of Canada. Dr. Martino has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Martino has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merz Pharma Canada Ltd..

Boundary Pass underwater listening station cabled hydrophone array system

An advanced cabled real-time underwater listening station was deployed in May 2020 in Boundary Pass, British Columbia, Canada, to measure underwater radiated noise of commercial vessels and to detect and track vocalizing marine mammals. This system was sponsored by Transport Canada and is operated jointly by Vancouver Fraser Port Authority and JASCO Applied Sciences (Canada) Ltd. The system consists of two synchronized tetrahedral hydrophone arrays, each with 1.65 m hydrophone spacings, deployed 300 m apart on the seabed in 190 m water depth. The hydrophone frames are connected to shore by two 2.8 km fiber-optic cables, and also support ADCP and CTD sensors, sound projectors for calibrations, and video cameras. The Boundary Pass location was chosen because of its relatively deep water and because the major inbound and outbound commercial shipping lanes leading to Vancouver become narrow and adjacent here, allowing acoustic measurements of ships passing in both directions. In this presentation we will discuss the system technical design and sensor specifications. We will also discuss its deployment and the data processing and presentation systems, with a brief overview of the substantial measurements obtained in the first full year of operation.

Validation of the Modified Self-Administered Pediatric Bleeding Assessment Questionnaire (Self-PBQ) in Children Aged 8-12 Years

IntroductionIn the pediatric population, pathologic bleeding is often more challenging to identify than in adult patients. Hemorrhagic symptoms are seen in healthy children as well as those with bleeding disorders and children have fewer exposures to events such as surgery that would cause symptoms to manifest. A pediatric bleeding assessment tool may facilitate the accurate evaluation of bleeding symptoms in children.The Pediatric Bleeding Questionnaire (PBQ) was developed as a screening tool for von Willebrand Disease (VWD), the most common hereditary bleeding disorder. The PBQ provides a quantitative score for bleeding symptoms based on the type and severity of episodes. When administered by experts, the PBQ had a sensitivity of 83% and a specificity of 79%. Recently, the expert-administered PBQ was modified to generate a self-administered PBQ which can be completed by children/parents themselves. A prospective multicentre study was undertaken to validate the Self-PBQ and found it to have a high level of agreement with the expert-administered PBQ, with an intraclass correlation (ICC) of 0.917. However, only children above age 12 yrs completed the Self-PBQ by themselves while those under 12 had a parent fill out the Self-PBQ on their behalf.The present study is sub-study of the recent multicentre study. Our objectives were to determine whether a modified school age Self-PBQ can be completed by younger children with minimal adult assistance, and to validate the school age Self-PBQ in the 8-12 year-old population.MethodologyThis sub-study was conducted in two phases. Phase 1 involved pre-testing and optimizing the Self-PBQ to be suitable for 8-12 year-olds. Seven subjects aged 8-11 yrs, 5 with a confirmed diagnosis of type 1 VWD and 2 healthy controls, underwent cognitive debriefing to identify any problems in the questionnaire. Based on respondent feedback, item reduction was performed to simplify the PBQ, and modifications were made to the question wording and response options.In Phase 2, the school age Self-PBQ was tested at 5 participating treatment centres across Canada. Patients aged 8-12 yrs with a known diagnosis of an inherited bleeding disorder were eligible for inclusion. Children completed the Self-PBQ independently or with assistance from their parent and the amount of help required was noted. Parents also filled out the Self-PBQ separately to serve as a comparison. Bleeding scores (BSs) derived from the child self-report were compared to those of the parent proxy. A single measure ICC based on absolute agreement was used to determine the degree of agreement between the child and parent reports. In addition, subgroup analyses were performed to examine whether the correlation differed in younger (8-9 yrs) versus older (10-12 yrs) age groups or based on the severity of the disease. An ICC ≥ 0.70 was considered the minimum standard for reliability based on existing quality criteria.ResultsThirty-one patients aged 8-12 yrs and their parents completed the Self-PBQ. Two pairs were excluded from the analysis because they did not answer portions of the PBQ and their BSs could not be calculated. Total BSs were used for reliability analysis, performed on a final sample size of 29 pairs. Child and parent scores demonstrated a high level of agreement with an ICC of 0.825. In the age subgroup analysis, the ICC was 0.834 and 0.824 for the 8-9 year-old and 10-12 year-old groups respectively. The ICC was also determined in children with type 1 VWD (ICC = 0.829) versus those with more severe bleeding disorders (ICC = 0.802). Thus, age and disease severity had no significant effect on degree of agreement (Figure).ConclusionOur study evaluated the effectiveness of a school age Self-PBQ when completed by children aged 8-12 yrs. The BSs derived from the child self-report were found to have sufficient concordance with those from the parent proxy report. Moreover, the agreement was maintained in younger children aged 8-9 yrs and in children on the more severe spectrum of bleeding disorders. These results indicate that the Self-PBQ is suitable to be incorporated into routine clinical care for the 8-12 year-old population.Figure: Agreement between child and parent (proxy) total reported bleeding scores (BSs). The difference between child and parent-derived BSs is plotted against the mean of the two measurements. The average of the differences is shown by the red line. The numbers plotted reflect ages of the children. [Display omitted] DisclosuresJames:Shire: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding. Klaassen:Baxalta: Honoraria; Agios Pharmaceuticals: Consultancy; Octapharma: Honoraria; Biogen Canada LTD: Consultancy; Amgen: Consultancy; Hoffman-La Roche LTD: Consultancy.

Immune Tolerance Induction in Hemophilia A Patients Using Wilate® —a Canadian 10 Year Study (PREVAIL)

Introduction:Hemophilia A patients with inhibitors experience a higher morbidity, a worse orthopedic condition and a decreased quality of life. In children with severe hemophilia A, attempting to eliminate inhibitors with immune tolerance induction (ITI) is standard of care; however, in adults with longstanding inhibitors ITI has been less extensively studied. Although practical guidelines in adults are scarce there has been an increase in case reports highlighting the success of ITI in patients with long-standing inhibitors.The possibility that the type of factor VIII (FVIII) product used for ITI could influence the likelihood of successful tolerization is the subject of intense debate. It has been postulated that FVIII products containing von Willebrand factor (VWF) may improve the ITI success rate in some patients with inhibitors, especially those with poor prognostic characteristics, i.e., a historical peak inhibitor level >200 BU/mL, an inhibitor level >10 BU/mL at the start of ITI, age >5 years, or >24 months between inhibitor detection and start of ITI.Study RationaleWilate® is the most extensively used plasma-derived FVIII/VWF concentrate for hemophilia A in Canada. Wilate® has been successful in eliminating inhibitors and reducing bleeding in Canadian children and adults who had developed inhibitors during treatment with other FVIII concentrates, including poor-prognosis patients. Wilate® was well tolerated at the high doses required for ITI. Furthermore, anecdotal clinical experience with Wilate® ITI therapy suggest that patients may have less bleeding, which may limit the need for bypassing agents.This research study was designed to evaluate the efficacy of Wilate® in achieving complete or partial ITI success in severe and moderate hemophilia A patients with inhibitors. Secondary objectives are to determine: the time to achieve immune tolerance; bleeding frequency while on Wilate® ITI treatment; quality of life while on Wilate® ITI treatment; joint health while on Wilate® ITI treatment; relapse rate; and time to relapse following successful ITI using Wilate® .Additional optional sub-studies have been incorporated into this study to gain insight into the biology of ITI, including biomarkers that might predict ITI success or failure: genotyping, anti-FVIII antibody characterization including epitope mapping, and thrombin generation.Study ProceduresThis 10-year Canadian study is an open-label, uncontrolled, multi-centre observational trial with both prospective and retrospective cohorts. A total of at least 80 hemophilia A patients with inhibitors will be enrolled into this study.The dose and frequency of ITI treatment will be at the discretion of the treating physician. However, use of risk-determined treatment protocols is recommended. Patients with high-titre inhibitors (defined as one with historical peak titre ≥5 BU/m) who have inhibitor titre ≤10 BU/mL at the start of ITI are “good-risk” for ITI success, and those who have inhibitor titre >10 BU/mL at the start of ITI are “poor-risk”. Patients with high-titre inhibitors who are good-risk should receive 50 IU FVIII/kg BW every other day or 3 times per week; daily treatment may also be considered. Patients with high-titre inhibitors who are poor-risk should receive 100-200 IU FVIII/kg BW daily. Patients with low-titre inhibitors (defined as one with historical peak titre < 5 BU/mL) should receive 50 IU FVIII/kg BW every other day to 3 times per week.For complete success, an individual must achieve the following three criteria: inhibitor titre <0.6 BU (at least 2 separate blood samplings; incremental recovery of FVIII in the normal range (≥66% of normal); FVIII half-life ≥6 hours. For partial success an individual must meet two of the three criteria. In a partial response, one of the three criteria above is met. In a partial failure : none of the three criteria are met, but inhibitor titre has decreased to <5 BU. In a complete failure none of the three criteria are met, and inhibitor titre is still ≥5 BU.ConclusionThis research study aims to evaluate and document data on the success of Wilate ® ITI in hemophilia patients with FVIII-inhibitors. It is the first 10-year study of its kind in a Canadian setting. The results of this study will provide further insights into addressing one of the most serious complications of hemophilia A treatment. DisclosuresMoorehead:Bioverativ: Honoraria; Pfizer: Speakers Bureau; Octapharma: Honoraria; Bayer: Honoraria; Baxalta: Honoraria, Speakers Bureau. Klaassen:Baxalta: Honoraria; Agios Pharmaceuticals: Consultancy; Hoffman-La Roche LTD: Consultancy; Biogen Canada LTD: Consultancy; Amgen: Consultancy; Octapharma: Honoraria. Carcao:Octapharma: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding; Biogen: Honoraria, Research Funding; Baxter: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Biotest: Honoraria.

Re-Analysis of Next Generation Sequencing Gene Panel Data By Normalized Coverage Values Reveals Previously Undetected Copy Number Variations in Inherited Bone Marrow Failure Syndromes

Background: Inherited bone marrow failure syndromes (IBMFSs) comprise a group of genetic disorders affecting blood cell production in bone marrow, resulting in single or multilineage cytopenias. Patients with IBMFSs often have physical malformations and are at risk of developing leukemia and solid tumors. With advances in sequencing technologies, causal nucleotide-level mutations can readily be identified in many IBMFSs. In about half of IBMFS cases, however, a molecular mutation is not detected. Copy number variation (CNVs) have been reported to cause IBMFSs. Unfortunately, genome-wide methods to identify CNVs have major limitations as they may miss small lesions (e.g. by oligonucleotide or CGH arrays) or may have low sensitivity due to low read depths (e.g. by whole genome sequencing).Purpose: This study's purpose was to determine, after standard analysis of a next generation sequencing gene panel for causal mutations, whether re-analysis by normalized coverage value could identified CNVs and to characterize the genetic lesions.Methods & Materials: Patients with IBMFSs were enrolled in The Canadian Inherited Marrow Failure Registry (CIMFR). Genomic DNA was analyzed by next-generation panel gene panel of over 72 IBMFS-associated genes. After analysis for nucleotide level mutations, the NextGene software was used to detect copy number variation using nucleotide read depth in test samples versus normalized control coverage values. Monoalleic copy number deletions were indicated by ratio of <0.33;biallelic deletion was considered when the value was close to zero. PCR or Affymetrix SNP6.0 array were used to validate deletions.Results: Of the 258 patients who tested by the IBMFS next-generation gene panel, 93 (36%) were found to have causal nucleotide level mutations. 168 patients without identified mutations underwent analysis for copy number variation, of which 10 (6%) were found to have deletions. Genes most commonly exhibiting monoallelic deletions included RPS19, RPL11 and RPL5 (5 Diamond-Blackfan anemia patients). One patients with MDS was found to have monoalleic deletion of GATA2 . Moreover, a bialleic deletion of exon 1-5 in FANCA gene was detected in one Fanconi anemia patient. Lastly, we also identified monoalleic deletions of RBM8A in two thrombocytopenia with absent radii patients and of PARN in one unclassified pancytopenia patient. The last three patients were found to also have a nucleotide level mutation on the other allele by the NGS panel (compound heterozygousity). All the above deletions were validated by another method (PCR or Affymetrix SNP6.0 array).Conclusions: CNVs can be detected in some IBMFSs by next-generation sequencing (NGS) panels by careful analysis of normalized coverage values. Such analysis should become standard practice before usage of other mutation detection strategies such as CNV microarray or whole exome/genome sequencing, since the later techniques may not detect certain CNVs that can be detected by gene panels. DisclosuresKlaassen:Amgen: Consultancy; Baxalta: Honoraria; Biogen Canada LTD: Consultancy; Hoffman-La Roche LTD: Consultancy; Agios Pharmaceuticals: Consultancy; Octapharma: Honoraria. Dror:Alexion Canada: Research Funding.

1629-P: Association of Patient-Reported Outcomes (PROs) Scores with Glycemic Target Achievement in Type 1 Diabetes (T1D) in the SAGE Study

T1D is a chronic disease affecting both physical and psychosocial health. SAGE was a multinational, cross-sectional observational study using data from medical records and interviews of people (N=3858) aged ≥26 years with T1D for ≥1 year. The association between the achievement of general (HbA1c &amp;lt;7 %) or individualized HbA1c targets and PRO scores was analyzed by multivariate logistic regression, adjusted for region and age group. The following PROs are reported: Hypoglycemia Fear Survey (HFS-II) worry subscore, Problem Areas in Diabetes (PAID), Insulin Treatment Satisfaction Questionnaire (ITSQ), Audit of Diabetes-Dependent Quality of Life (ADDQoL). Overall, 24.3% of people achieved the general HbA1c target; 20.9% achieved individualized targets (most common target, HbA1c 7 % to &amp;lt;7.5 %). Lower emotional distress (PAID score) and higher treatment satisfaction (all ITSQ scores except Lifestyle domain) were associated with achievement of general and individualized HbA1c targets (Table). Lower HFS-II worry score and higher ADDQoL total scores were associated with achievement of HbA1c general target, but neither was associated with achieving individualized HbA1c targets. In people with T1D, lower diabetes-related emotional distress and higher treatment satisfaction appear to be associated with achievement of both general and individualized HbA1c targets. Disclosure E.G. Wilmot: Advisory Panel; Self; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic. Speaker’s Bureau; Self; Abbott, Eli Lilly and Company, Insulet Corporation, Novo Nordisk Inc., Sanofi. F. Ampudia Blasco: None. L. Berard: Consultant; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Becton, Dickinson and Company, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Montméd, Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim (Canada) Ltd. S. Brette: Other Relationship; Self; Sanofi. L.P. Calliari: Board Member; Self; Abbott, Medtronic, Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Lilly Diabetes. E. Fitts: Other Relationship; Self; N/A. K.L. Close: Other Relationship; Self; Abbott, Air Liquide, American Diabetes Association, AstraZeneca, Dexcom, Inc., Janssen Pharmaceuticals, Inc., JDRF, Leona M. and Harry B. Helmsley Charitable Trust, Lilly Diabetes, Merck &amp; Co., Inc. J.J. Gagliardino: None. F. Lauand: Employee; Self; Sanofi. A.L. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medscape, Novo Nordisk Inc., Sanofi US. Consultant; Self; Livongo Health. Research Support; Self; Dexcom, Inc., vTv Therapeutics. Other Relationship; Self; Livongo Health, Mellitus Health, Omada Health, Stability Healthcare, Whole Biome Inc. E. Renard: Board Member; Self; Abbott, Insulet Corporation, Novo Nordisk A/S, Roche Diabetes Care. Consultant; Self; Air Liquide, Eli Lilly and Company, Sanofi. Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. A. Roborel de Climens: Employee; Self; Sanofi. J. Seufert: Research Support; Self; Sanofi. Speaker’s Bureau; Self; Sanofi.

1626-P: Differences in Patient-Reported Outcomes (PROs) by Age and Region in Adults with Type 1 Diabetes (T1D) in the SAGE Study

T1D is a chronic disease impacting patients’ lives and psychosocial health; we explored how this may vary by age and region. SAGE was a multinational, cross-sectional observational study using data from medical records and interviews of participants (N=3858) aged ≥26 years with T1D for ≥1 year. Results from PROs questionnaires (Hypoglycemia Fear Survey [HFS-II], Problem Areas in Diabetes [PAID], Insulin Treatment Satisfaction Questionnaire [ITSQ], Audit of Diabetes-Dependent Quality of Life [ADDQoL]) were analyzed by region (Asia [A], Eastern Europe [EE], Western Europe [WE], Latin America [LA], Middle East [ME]) and age group (26-&amp;lt;45; 45-&amp;lt;65; ≥65 years). HFS-II scores showed fear of hypoglycemia was lowest in A for all age groups (Table). HFS-II scores increased with age in EE and decreased with age in LA. PAID scores showed highest levels of emotional distress in ME for all age groups. ITSQ scores showed treatment satisfaction increased with age in WE, LA and ME, and was more stable in EE and A. ADDQoL total scores showed a small negative impact of T1D on quality of life, with the highest and lowest impact in EE and ME, respectively, across all ages. PROs scores indicated relatively low levels of diabetes-related impact and high treatment satisfaction. Age and regional differences may reflect variations in T1D control and management, as well as cultural and healthcare-system-related factors. Disclosure L. Berard: Consultant; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Becton, Dickinson and Company, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Montméd, Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim (Canada) Ltd. F. Ampudia Blasco: None. S. Brette: Other Relationship; Self; Sanofi. D. Bruttomesso: Consultant; Self; Abbott, Eli Lilly and Company, Movi, Novo Nordisk, Roche Diagnostics, Sanofi. K.L. Close: Other Relationship; Self; Abbott, Air Liquide, American Diabetes Association, AstraZeneca, Dexcom, Inc., Janssen Pharmaceuticals, Inc., JDRF, Leona M. and Harry B. Helmsley Charitable Trust, Lilly Diabetes, Merck &amp; Co., Inc. H. Ikegami: None. D. Jurišic-Eržen: None. F. Lauand: Employee; Self; Sanofi. A.L. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MannKind Corporation, Medscape, Novo Nordisk Inc., Sanofi US. Consultant; Self; Livongo Health. Research Support; Self; Dexcom, Inc., vTv Therapeutics. Other Relationship; Self; Livongo Health, Mellitus Health, Omada Health, Stability Healthcare, Whole Biome Inc. V. Pilorget: Employee; Self; Sanofi. R. Balamurugan: None. E. Renard: Board Member; Self; Abbott, Insulet Corporation, Novo Nordisk A/S, Roche Diabetes Care. Consultant; Self; Air Liquide, Eli Lilly and Company, Sanofi. Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. E.G. Wilmot: Advisory Panel; Self; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic. Speaker’s Bureau; Self; Abbott, Eli Lilly and Company, Insulet Corporation, Novo Nordisk Inc., Sanofi. A. Roborel de Climens: Employee; Self; Sanofi. Funding Sanofi

2216-PUB: Patient Preferences for Newer Oral Therapies in Type 2 Diabetes

ADA/EASD guidelines emphasize the importance of patient engagement in therapy decisions. Beyond glycemic effects of type 2 diabetes (T2D) therapies, only SGLT2i and GLP-1RA have cardiovascular (CV) benefits. Key attributes of such therapies may influence their use/adoption. We evaluated patient preferences towards three oral T2D therapies using conjoint analysis. This analysis used an online survey, completed by 553 respondents with T2D in the U.S. (mean age ±SD was 64±9; 55% had CV risk; 27% had CV disease), to present 7 hypothetical, blinded pair-wise drug profile comparison choices composed of different benefit-risk attributes and effect ranges (levels). Attributes/levels were derived from combinations of phase 3 trial data for empagliflozin 25mg (SGLT2i), oral semaglutide 14mg (GLP-1RA) and sitagliptin 100mg (DPP-4i). The predicted therapy preference outcomes and the relative importance of one attribute relative to another were calculated (in %). The preference outcome was highest for the profile matching empagliflozin, ranked first by 56% (z-test, p&amp;lt;0.05), versus 38% for sitagliptin and 6% for oral semaglutide. Results were overall consistent in subgroup analyses. Genital infection risk was the most important perceived attribute with a relative score of 19% (z-test, p&amp;lt;0.05). Second and similarly important were fasting requirements (15%), weight reduction (15%), risk of vomiting (14%) and CV benefit (12%). Next was risk of nausea (11%). Last were HbA1c reduction (8%) and ability to take medication with other drugs (6%). While blinded to drug name/dose, respondents were also asked to choose explicitly between drug profiles similar to empagliflozin (chosen by 41%), sitagliptin (31%), oral semaglutide (11%), and ’none of the options’ (17%). The drug profile comparable to empagliflozin was the preferred agent; however, CV benefit was not the top patient priority. A shared physician-patient decision model and increased patient education are needed to ensure optimal use of guideline directed therapies in T2D. Disclosure G. Savarese: Advisory Panel; Self; AstraZeneca. Consultant; Self; Genesis, Societ Prodotti Antibiotici. Research Support; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Vifor Pharma Group. Speaker’s Bureau; Self; Roche Pharma, Servier, Vifor Pharma Group. A. Sharma: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Roche Pharma. Research Support; Self; Bristol-Myers Squibb, Merck &amp; Co., Inc. Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation. C. Pang: None. R. Wood: Consultant; Self; Abbott, ADOCIA, American Diabetes Association, Ascensia Diabetes Care, Boehringer Ingelheim Pharmaceuticals, Inc., CeQur Corporation, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation. Employee; Self; dQ&amp;A Market Research Inc. J.T. George: Employee; Self; Boehringer Ingelheim International GmbH. N. Soleymanlou: Employee; Self; Boehringer Ingelheim (Canada) Ltd. Funding Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance

1198-P: The M-EASE Studies: A Modeling and Simulation Approach to Further Characterize the Efficacy of Low-Dose Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes (T1DM)

Among the two phase 3 trials of empagliflozin (EMPA) in T1DM, one (EASE-3), demonstrated diabetic ketoacidosis risk minimization by including a lower dose (2.5 mg) than approved for use in T2DM while maintaining HbA1c benefit of -0.28%. We aimed to determine the effect of HbA1c lowering of EMPA 2.5 mg by modelling and simulation in the phase 3 trial (EASE-2) that did not investigate this dose. The effect of insulin adjustment on HbA1c was also characterized. Independent of empiric data from EASE-3 (that evaluated EMPA 2.5 mg), M-EASE-2, an empirical model, evaluated the direct effect of EMPA exposure on changes in HbA1c after simulated 26- and 52-week treatment durations in the EASE-2 study. M-EASE-2 model development was informed by EASE-2 and EASE-1 (phase 2 study, included EMPA 2.5 mg) data. M-EASE-1, a semi-mechanistic model (informed by EASE-1 and EASE-2 data), simulated changes in HbA1c after a 26-week treatment period (with/without insulin dose adjustment) driven by changes in EMPA exposure, insulin dose and mean daily glucose. Trial simulations were conducted in 239 and 500 patients per dose group in M-EASE-2/-1, respectively. The models were validated using EASE-3 trial data. In M-EASE-2, the simulated mean (median; 95% CI) HbA1c change for EMPA 2.5 mg was -0.29% (-0.29; -0.39, -0.19) at Week 26 and -0.29% (-0.29; -0.40, -0.19) at Week 52. The simulations performed were consistent with EASE-3 results. In M-EASE-1, the 26-week HbA1c change for EMPA 2.5 mg was -0.28% (-0.28; -0.40, -0.09) and -0.41% (-0.40; -0.53, -0.20) with adjusted and stable insulin therapy, respectively. The HbA1c benefit from low-dose EMPA 2.5 mg that was directly observed in a phase 3 clinical trial was confirmed using two modelling approaches from independent studies. Efficacy was sustained over 52 weeks, and the approach predicted that greater efficacy of EMPA as adjunct to insulin in T1DM can be achieved on a stable vs. variable insulin dose. Disclosure B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. N. Soleymanlou: Employee; Self; Boehringer Ingelheim Canada Ltd. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Melior Pharmaceuticals, Inc., Bukwang Pharm. Co., Ltd., Merck &amp; Co., Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. J.S. Skyler: Advisory Panel; Self; ADOCIA, Applied Therapeutics, Dance Biopharm Holdings Inc., Orgenesis Ltd., Tolerion, Inc., Viacyte, Inc. Board Member; Self; Dexcom, Inc., Intarcia Therapeutics, Inc., Moerae Matrix, Inc. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dalcor, Dialogics, Elcelyx Therapeutics, Inc., Esperion, GeNeuro Innovation, Ideal Life, Immunomolecular Therapeutics, Intrexon, Kamada, Nestlé, Sanofi, Valeritas, Inc., Zafgen, Inc. Stock/Shareholder; Self; Dexcom, Inc., Ideal Life, Intarcia Therapeutics, Inc., Intrexon, Moerae Matrix, Inc. L.M. Laffel: Advisory Panel; Self; Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Janssen Pharmaceuticals, Inc., UpToDate. K. Liesenfeld: Employee; Self; Boehringer Ingelheim International GmbH. D. Neubacher: Employee; Self; Boehringer Ingelheim Pharma GmbH &amp; Co. KG. M. Riggs: Consultant; Self; Boehringer Ingelheim International GmbH. C.K. Johnston: Consultant; Self; Boehringer Ingelheim International GmbH. R.J. Eudy-Byrne: Consultant; Self; Boehringer Ingelheim International GmbH. Other Relationship; Spouse/Partner; Eli Lilly and Company, Medtronic, Tandem Diabetes Care. A. Elmokadem: None. J. George: Employee; Self; Boehringer Ingelheim International GmbH. J. Marquard: Employee; Self; Boehringer Ingelheim International GmbH. V.C. Nock: Employee; Self; Boehringer Ingelheim Pharma GmbH &amp; Co. KG. Funding Boehringer Ingelheim; Eli Lilly and Company

1199-P: Analysis of Patient Preferences for Adjunct Therapy to Insulin in T1D

Recent ADA/EASD recommendations emphasize the importance of the patient role in therapy decisions. Adjunct to insulin SGLT inhibitor (SGLTi) therapy for T1D has been evaluated in RCTs but patient reaction to the benefit-risk profile of these agents is unknown. We aimed to objectively evaluate patient preferences for different therapy options, using a Discrete Choice Experiment (DCE) form of conjoint analysis, a validated methodology. The DCE used an online survey, completed by 701 respondents with T1D (231 U.S., 242 Canada, 228 Germany), to present 6 hypothetical, masked pair-wise drug profile comparison choices composed of different benefit-risk attributes and clinical effect ranges (levels). Attributes and levels were derived from different combinations of phase 3 trial data for a low dose SGLTi (comparable to empagliflozin 2.5mg); a high dose SGLTi (comparable to sotagliflozin 400mg); and an available adjunct to insulin therapy (pramlintide 60µg TID). Based upon respondents’ choices, DCE calculated, in %, the relative importance of one attribute to another and the overall predicted therapy preferences. DKA risk was the most important attribute with a relative importance of 23% (z-test, p&amp;lt;0.05). Second and similarly important were HbA1c reduction (14%), risk of hypoglycemia (13%), oral vs. injection treatment (13%), and risk of genital infection (12%). Next was risk of nausea (11%); weight reduction (8%) and risk of diarrhea (7%) were least important. The predicted therapy preference share was highest for low dose SGLTi, ranked first by 83% (z-test, p&amp;lt;0.05), compared with 8% for high dose SGLTi and 9% for pramlintide. In a separate question, respondents were asked to explicitly choose (masked to drug profile name and dose) among the clinical trial profiles of low dose SGLTi (chosen by 69%), high dose SGLTi (17%), pramlintide (6%), and ‘none of the above’ (9%). In conclusion, the DCE and head-to-head explicit choice identified low dose SGLTi as the favored patient preference for adjunct therapy to insulin in T1D. Disclosure B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Melior Pharmaceuticals, Inc., Bukwang Pharm. Co., Ltd., Merck &amp; Co., Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. J.S. Skyler: Advisory Panel; Self; ADOCIA, Applied Therapeutics, Dance Biopharm Holdings Inc., Orgenesis Ltd., Tolerion, Inc., Viacyte, Inc. Board Member; Self; Dexcom, Inc., Intarcia Therapeutics, Inc., Moerae Matrix, Inc. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dalcor, Dialogics, Elcelyx Therapeutics, Inc., Esperion, GeNeuro Innovation, Ideal Life, Immunomolecular Therapeutics, Intrexon, Kamada, Nestlé, Sanofi, Valeritas, Inc., Zafgen, Inc. Stock/Shareholder; Self; Dexcom, Inc., Ideal Life, Intarcia Therapeutics, Inc., Intrexon, Moerae Matrix, Inc. L.M. Laffel: Advisory Panel; Self; Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Janssen Pharmaceuticals, Inc., UpToDate. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi. C. Mathieu: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Speaker's Bureau; Self; AstraZeneca, Novartis AG, Novo Nordisk A/S, Sanofi. C. Pang: Consultant; Self; dQ&amp;A Market Research, Inc. R. Wood: Other Relationship; Self; Multiple companies in the diabetes field (&amp;gt;10 companies). O. Kinduryte: Employee; Self; Boehringer Ingelheim International GmbH. Stock/Shareholder; Self; Novo Nordisk A/S, Zealand Pharma A/S. J. George: Employee; Self; Boehringer Ingelheim International GmbH. J. Marquard: Employee; Self; Boehringer Ingelheim International GmbH. N. Soleymanlou: Employee; Self; Boehringer Ingelheim Canada Ltd. Funding Boehringer Ingelheim; Eli Lilly and Company

Health Related Quality of Life and Fatigue Improve on Second Line Treatments in Pediatric Immune Thrombocytopenia (ITP)

Background: The impact of second line therapies on health related quality of life (HRQoL) and fatigue in pediatric patients with ITP is not well studied.Objective: To describe the impact of second line therapies on HRQoL and fatigue in North American pediatric patients with ITP.Methods: A longitudinal observational cohort of 120 children with ITP starting second line treatments was enrolled from 2013-2015 at 21 ICON centers. Enrollment requirements included age 1-17y and starting a second line treatment (not IVIG, corticosteroids or anti-D immunoglobulin) as monotherapy. HRQoL (Kids ITP Tool - KIT) and fatigue (Hockenberry Fatigue Scale - FS) surveys were completed prior to starting treatment (baseline) and 1 and 12 months after starting treatment by patient/caregiver. KIT is scored from 0 (worst) to 100 (best), and the FS scores were re-scaled so that 0 is no fatigue and 100 is highest fatigue. At the same time points as the patient/caregiver surveys, physicians assessed the perceived effect of treatment on patient HRQoL using a 7-point scale. ANOVA was used to compare the baseline means of the treatment groups. This study specifically compared change from baseline to 1 month in the KIT and FS using paired t-tests within each treatment group. The 12 month timepoint was not used in the paired analysis of individual treatments due to attrition between 1 and 12 months.Results: The median age at enrollment was 11.3 y (1.2-17.8), and 16% (19/120) had newly diagnosed ITP, 31% (37/120) had persistent ITP, and 53% (64/120) had chronic ITP. The median number of prior treatments was 3 (range: 1-9). Fifty-eight (48%) patients had received at least one prior second line treatment. Treatments selected for second line treatment included: rituximab (n=43), romiplostim (n=31), eltrombopag (n=20), oral immunosuppressants (n=19), splenectomy (n=4), and dapsone (n=3).The child and parent proxy KIT scores significantly improved on rituximab (p<0.001 for both), oral immunosuppressants (p=0.02, p=0.001), and eltrombopag (p=0.01 for both). Child KIT scores also significantly improved on romiplostim (p=0.003); however, there was no significant change in the parent proxy score (p=0.29). The parent impact KIT scores significantly improved from baseline to 1 month on all treatments (p<0.001), although the scores were not significantly different between treatment types (p=0.67). Child, parent proxy, and parent impact KIT scores significantly increased between 1 month and 12 months in paired analysis combining treatments (p<0.001).As previously described, at enrollment, physicians reported that ITP had impacted the patients' HRQoL severely in 15%, significantly in 45%, moderately in 38%, and almost not at all in 3%. Physicians reported that HRQoL improved in 68% (range: 64-75%) of patients while on treatment from baseline to 1 month with no significant difference by treatment group (p=0.46). The physician's assessment of the patient's baseline HRQoL significantly correlated with the child and parent proxy KIT report (p<0.0001); however, after 1 month of treatment, the physician's assessment no longer correlated with the child (p=0.26) or parent proxy KIT report (p=0.11).At enrollment, the median FS-Child score (n=54) was 18.5 (range 0-85), the median FS-Adolescent score (n=42) was 20.2 (0-73), and the median FS-Parent (n= 100) score was 35 (7-81). One month FS-Child improved for those who were treated with rituximab (p=0.03); there was no significant change in fatigue on the other treatments. One month FS-Parent significantly improved for those treated with rituximab (p=0.015) and eltrombopag (p=0.009).Conclusions: In this pediatric cohort, all second line treatments appear to significantly improve HRQoL in ITP. Rituximab had the greatest impact in decreasing fatigue at one month. Physician assessment of patient HRQoL did not correlate well with patient assessment after treatment was started, suggesting there may be challenges in ascertaining the effect of treatment on HRQoL. Future analysis of ICON1 will consider the impact of treatment on HRQoL and fatigue while also accounting for the treatment effect on bleeding and platelet count. [Display omitted] DisclosuresGrace:Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Klaassen:Amgen: Consultancy; Hoffman-La Roche LTD: Consultancy; Octapharma: Honoraria; Baxalta: Honoraria; Biogen Canada LTD: Consultancy; Agios Pharmaceuticals: Consultancy. Despotovic:Sanofi: Consultancy; Schell Cooley LLP: Other: Expert witness. Bussel:Protalex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Momenta: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Rothman:Pfizer: Consultancy; Agios Pharmaceuticals: Honoraria. Haley:Genentech: Honoraria; Baxalta: Honoraria; CSL Behring: Honoraria. Neufeld:Octapharma: Consultancy, Honoraria; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Lambert:Educational Concepts in Medicine: Honoraria; Novartis: Honoraria; AstraZeneca: Research Funding.

The stable isotopes of site wide waters at an oil sands mine in northern Alberta, Canada

Oil sands mines have large disturbance footprints and contain a range of new landforms constructed from mine waste such as shale overburden and the byproducts of bitumen extraction such as sand and fluid fine tailings. Each of these landforms are a potential source of water and chemical release to adjacent surface and groundwater, and consequently, the development of methods to track water migration through these landforms is of importance.The stable isotopes of water (i.e. 2H and 18O) have been widely used in hydrology and hydrogeology to characterize surface water/groundwater interactions but have not been extensively applied in mining applications, or specifically to oil sands mining in northern Alberta. A prerequisite for applying these techniques is the establishment of a Local Meteoric Water Line (LMWL) to characterize precipitation at the mine sites as well as the development of a ‘catalogue’ of the stable water isotope signatures of various mine site waters.This study was undertaken at the Mildred Lake Mine Site, owned and operated by Syncrude Canada Ltd. The LMWL developed from 2 years (2009/2012) of sample collection is shown to be consistent with other LMWLs in western Canada. The results of the study highlight the unique stable water isotope signatures associated with hydraulically placed tailings (sand or fluid fine tailings) and overburden shale dumps relative to natural surface water and groundwater. The signature associated with the snow melt water on reclaimed landscapes was found to be similar to ground water recharge in the region. The isotopic composition of the shale overburden deposits are also distinct and consistent with observations made by other researchers in western Canada on undisturbed shales. The process water associated with the fine and coarse tailings streams has highly enriched 2H and 18O signatures. These signatures are developed through the non-equilibrium fractionation of imported fresh river water during evaporation from cooling towers used within the raw water process circuit. This highly fractionated surface water eventually becomes part of the recycled tailings water circuit, and as a consequence it undergoes further non-equilibrium fractionation as a result of surface evaporation, leading to additional enrichment along local evaporation lines.

Characterization of physical mass transport through oil sands fluid fine tailings in an end pit lake: a multi-tracer study

Soft tailings pose substantial challenges for mine reclamation due to their high void ratios and low shear strengths, particularly for conventional terrestrial reclamation practices. Oil sands mine operators have proposed the development of end pit lakes to contain the soft tailings, called fluid fine tailings (FFT), generated when bitumen is removed from oil sands ore. End pit lakes would be constructed within mined-out pits with FFT placed below the lake water. However, the feasibility of isolating the underlying FFT has yet to be fully evaluated. Chemical constituents of interest may move from the FFT into the lake water via two key processes: (1) advective-diffusive mass transport with upward pore water flow caused by settling of the FFT; and (2) mixing created by wind events or unstable density profiles through the lake water and upper portion of the FFT. In 2013 and 2014, temperature and stable isotopes of water profiles were measured through the FFT and lake water in the first end pit lake developed by Syncrude Canada Ltd. Numerical modelling was undertaken to simulate these profiles to identify the key mechanisms controlling conservative mass transport in the FFT. Shallow mixing of the upper 1.1 m of FFT with lake water was required to explain the observed temperature and isotopic profiles. Following mixing, the re-establishment of both the temperature and isotope profiles required an upward advective flux of approximately 1.5 m/year, consistent with average FFT settling rates measured at the study site. These findings provide important insight on the ability to sequester soft tailings in an end pit lake, and offer a foundation for future research on the development of end pit lakes as an oil sands reclamation strategy.

FLIP-TOP not distinctive of Philip Morris, rules Federal Court of Canada

In Philip Morris Products SA v Imperial Tobacco Canada Ltd, 2014 FC 1237 the Federal Court of Canada held that the term ‘FLIP-TOP’ was not distinctive of Philip Morris as it described a type of packaging and was not necessarily indicative of source.

The Ni–Cr–Cu content of biotite as pathfinder elements for magmatic sulfide exploration associated with mafic units of the Sudbury Igneous Complex, Ontario, Canada

Laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) was used to evaluate the dissolved Ni–Cr–Cu content of biotite as an exploration pathfinder for magmatic Ni–Cu–platinum-group element (PGE) sulfide deposits associated with mafic igneous units of the Worthington quartz diorite offset dyke and their host rocks at the Totten Mine (Vale Canada Ltd), Sudbury Igneous Complex (SIC), Ontario, Canada. Enrichment in Cu in biotite (up to two orders of magnitude higher than background) occurs within barren to weakly mineralized, sublayer quartz diorite and adjacent Huronian metasediments within ~200m of massive sulfide. With respect to Ni and Cr, three distinct populations of biotite were distinguished based on textural and chemical criteria: (i) type I — isolated, euhedral laths within only inclusion-rich sublayer quartz diorite (IQD; the main mineralized host lithology), and high Ni (~1400ppm<[Ni]Bt<~2700ppm), low to moderate Cr (~50ppm<[Cr]Bt<~2450ppm) and variable Ni/Cr ratios (always >2). (ii) Type II — coarse-grained poikiloblasts (enclosing amphibole, chlorite, and type III biotite) within country rocks, and having moderate to high Ni (~500ppm<[Ni]Bt<~1400ppm), moderate to very high Cr (~1750ppm<[Cr]Bt<~6000ppm) but consistently low Ni/Cr ratios (always <0.5); and (iii) type III — subhedral to euhedral laths, intergrown with amphibole in dense, foliated aggregates and having low Ni ([Ni]Bt<~300ppm), very low to moderate Cr (~4ppm<[Cr]Bt<~1200ppm), and variable Ni/Cr ratios (<20), found within Huronian country rocks, sublayer quartz diorite (QD), and cross-cutting diabase dykes (Sudbury dyke swarm). Type I biotite within IQD is compositionally distinct from those observed in all other lithologies associated with the Sudbury Igneous Complex and its footwall rocks, and can be most readily discriminated in a Ni/Cr vs. Ni binary diagram or in a Ni–Cr–Cu ternary diagram by anomalously high Ni content and Ni/Cr ratio >2.Application of biotite chemistry to routine exploration requires establishing local “background” metal-in-biotite concentrations for each potential host lithology, and scrutiny of anomalous or heterogeneous metal contents in biotite resulting from discrete sulfide microinclusions that contaminate the analytical volume, and chloritization or coeval sulfide minerals in direct contact with biotite causing localized modifications to primary biotite metal abundance.In the Sudbury environment, the Ni–Cr–Cu chemistry of biotite can be used (i) in drill core to identify proximity to mineralization, and to differentiate QD (hosting minimal sulfides) from IQD (primary host to sulfide ore bodies), rock types for which bulk textural and compositional discrimination is problematic; and (ii) in soils and tills through the analysis of biotite and its weathering products to locate buried or surface-exposed IQD. The results may be extended to other mafic–ultramafic systems where sulfide-saturated or metal-enriched intrusive phases grew metal-enriched biotite during primary crystallization, or through secondary processes of metasomatic enrichment involving remobilization of base metals by magmatic-hydrothermal fluids.

Growing season water balance of wetland reclamation test cells, Fort McMurray, Alberta

AbstractIn the oil sands mining region near Fort McMurray, Alberta, strategies to construct wetlands and peatlands and methods to evaluate their success are just beginning. Reclamation of wetlands is particularly challenging in this region as growing seasons are short, precipitation is variable and often limiting, and the presence of elevated salinity associated with the mining process can be harmful to vegetation. As part of their reclamation programme, Syncrude Canada Ltd constructed a series of test plots (termed cells) to examine specific procedures and management strategies associated with wetland reclamation. In this study, water balance of 12 cells (each ~400 m2 in area) with different soil and vegetation treatments were studied over two growing seasons to understand the influence of soil salvage, vegetation, and placement strategy on water balance components. Cells were constructed in (i) the summer or winter, (ii) with either stockpiled material planted with vegetation or with soils directly transplanted from a nearby wetland and (iii) with soil depths of 15, 50 and 100 cm. Cells were built on a liner to eliminate leakage and were watered using an irrigation system along with receiving precipitation inputs. In 2010, cells were irrigated between ~100 and 400 mm, and water tables were maintained at or near the surface for the duration of the growing season at most cells. In 2011, watering was reduced considerably, and water tables were on average much lower. Evapotranspiration (ET) losses measured using lysimetres varied throughout the season and among cells. ET rates were greater in 2010 than in 2011 because of wet conditions at the surface, and cells placed in the winter and with shallower organic soils (15 cm) also had enhanced ET. Cumulative water balance suggests that some cells had considerable leakage despite being constructed atop a geotextile. Copyright © 2014 John Wiley &amp; Sons, Ltd.

Quantitative characteristics of clustered DNA damage in irradiated cells by heavy ion beams

Heavy ion beam as typical high linear energy transfer (LET) radiation produces more expanding ionization domain around their tracks than low LET radiation such as X-rays and gamma rays. Thus, heavy ion beam can cause more densely accumulated damage cluster in the target DNA, termed clustered DNA damage. This damage exhibits difficulty for repair and inhibition of DNA replication with its complex structure [ 1]. So, clustered DNA damage is thought to be strongly involved in the biological effectiveness of heavy ion beam. However, a lot of studies have presented no certain correlation between yields of clustered DNA damage and severity of radiation effect. We previously indicated that the yields of clustered DNA damage decreased with increasing LET in the DNA molecules irradiated in test tubes with gamma rays, and carbon and iron ion beams whose showed different LET, respectively [ 2]. In this study, we aimed to reveal correlation between clustered DNA damage and the LET of heavy ion beam in the irradiated cells.In the experiments, Chinese hamster ovary AA8 cells growing exponentially were irradiated by carbon, silicon, argon and iron ion beams from Heavy Ion Medical Accelerator in Chiba (HIMAC) of the National Institute of Radiological Sciences, Japan. These LETs were 13, 55, 90 and 200 keV/µm, respectively. For comparison, we used gamma rays from 137Cs-gamma source, Gammacell 40 (Atomic Energy of Canada Ltd), at Saga University. The irradiated cells were subjected by static-field gel electrophoresis to quantify clustered DNA damage of the genomic DNA. For this analysis, we used Fpg and endonuclease III for clustered DNA damage including oxidative purine and pyrimidine lesions, respectively. We also analysed the corresponding isolated DNA damages by aldehyde reactive probe method [ 3], and the surviving fractions of the irradiated cells in this study.The electrophoretic results indicated that total yields of clustered DNA damage in the irradiated cells decreased with increasing LET, including the double-strand break (DSB) and the respective clustered base damages (Fig. 1). This result conforms to our previous study with the irradiated DNA molecules [ 2]. The damage kinetics is thought to be mainly derived from two reasons: decreasing fluxes and increasing reaction with reactive oxygen species each other in increase in LET. In the clustered DNA damage induced by each radiation, the most decremental fraction was clustered base damage, but not DSB. The isolated DNA damages decreased with increasing LET like clustered DNA damage in this study (data not shown). These results make us realize the degree of contribution of direct and indirect effects of ionizing radiation. The certain amount of DSB were derived from the direct effect and showed less reactivity to LET. In contrast, oxidative base lesions were mainly generated by indirect effect with reactive oxygen species, which sensitively responded to LET change. We also found seemingly conflicted result of the relationship between LET and RBE (data not shown). We need further study to elucidate act of clustered DNA damage in radiobiological effect with heavy ion beams. Fig. 1.The yields of clustered DNA damages in the cells irradiated with respective ionizing radiations. Each clustered DNA damage consists of DSB (open bar) and clustered base damage (closed bar), and calculated from the strength of released band on electrophoretic gel.Clinical trial registration number if required: None.