ALBERT

Description: Minor changes to seasonal air temperature and precipitation can have a substantial impact on the availability of water resources within large watersheds. Two such watersheds, the north-flowing Mackenzie and east-flowing Saskatchewan Basins have been identified as highly vulnerable to such changes, and, therefore, selected for study as part of the Climatic Redistribution of western Canadian Water Resources (CROCWR) project. CROCWR aims to evaluate spatial and temporal changes to water resource distribution through the analysis of a suite of hydroclimatic and streamflow variables. As part of this analysis, dominant summer (May-Oct) circulation patterns at 500-hPa for 1950-2011 are identified using the method of Self-Organizing Maps (SOM). Surface climate variables associated with these patterns are then identified, including both daily air temperature and precipitation, and seasonal Standardized Precipitation-Evapotranspiration Index (SPEI) values. Statistical methods are applied to assess the relationships between dominant circulation patterns and the Southern Oscillation Index (SOI) and Pacific Decadal Oscillation (PDO). Results indicate that mid-summer (Jul-Aug) is dominated by a split-flow blocking pattern, resulting in cool (warm), wet (dry) conditions in the southern (northern) portion of the study area. By contrast, the shoulder season (May and Oct) is dominated by a trough of low-pressure over the North Pacific Ocean. The frequency of weak split-flow blocking is higher during positive SOI and negative PDO, while ridging over the western continent is more frequent during negative SOI and positive PDO. Results from this analysis increase our knowledge of processes controlling the distribution of summer water resources in western Canada. This article is protected by copyright. All rights reserved.

Description: The Climatic Redistribution of western Canadian Water Resources (CROCWR) project was designed to identify regions of increased/decreased water availability by evaluating a suite of atmospheric, hydroclimatic, and streamflow variables. This research component focuses on the atmospheric drivers of air temperature and precipitation in the watersheds originating on the leeward slopes of the Rocky Mountains. Dominant winter (Nov-Apr) synoptic-scale mid-tropospheric circulation patterns from 1950-2011 are classified using Self-Organizing Maps (SOM), and frequency distributions for positive/negative phases of the Southern Oscillation Index (SOI), Pacific Decadal Oscillation (PDO), and Arctic Oscillation (AO) are statistically compared. Corresponding high-resolution gridded temperature and precipitation anomalies are calculated for each synoptic type and spatial patterns of above/below average temperature and precipitation and north/south gradients are identified. Gridded six-month values of the Standardized Precipitation-Evapotranspiration Index (SPEI) are also used to categorize winters into regions of high/low snowpack. Results indicate high-pressure ridges over the Pacific Ocean (western North America) and low-pressure troughs over western North America (Pacific Ocean) are associated with anomalously cool (warm), wet (dry) conditions in the study region. Several statistically different synoptic type frequencies were found for positive/negative phases of the SOI, PDO, and AO. Most notably, positive (negative) phases of the SOI and negative (positive) phases of the PDO are associated with a higher (lower) frequency of ridging over the Pacific Ocean (western North America). Through improved knowledge of the relationships between teleconnections, mid-tropospheric circulation, and surface climate, the spatial and temporal distribution of water resources in western Canada is better understood. This article is protected by copyright. All rights reserved.

Description: [1]  Rising CO 2 concentration in the atmosphere, global climate change, and the sustainability of the Earth's biosphere are great societal concerns for the 21st century. Global climate change has, in part, resulted in a higher frequency of flooding events, which allow for greater exchange between soil/plant litter and aquatic carbon pools. Here we demonstrate that the summer 2011 flood in the Mississippi River basin, caused by extreme precipitation events, resulted in a “flushing” of terrestrially derived dissolved organic carbon (TDOC) to the northern Gulf of Mexico. Data from the lower Atchafalaya and Mississippi rivers showed that the DOC flux to the northern Gulf of Mexico during this flood was significantly higher than in previous years. We also show that consumption of radiocarbon-modern TDOC by bacteria in floodwaters in the lower Atchafalaya River and along the adjacent shelf contributed to northern Gulf shelf waters changing from a net sink to a net source of CO 2 to the atmosphere in June and August 2011. This work shows that enhanced flooding, which may or may not be caused by climate change, can result in rapid losses of stored carbon in soils to the atmosphere via processes in aquatic ecosystems.

Description: Background ARRY-520 is a novel KSP inhibitor with encouraging activity in patients (pts) with RRMM. In preclinical models, the activity of ARRY-520 is synergistic with BTZ, providing a rationale to combine these drugs in the clinic. Methods ARRAY-520-111 is a Phase 1 study to identify the maximum tolerated dose of ARRY-520, BTZ and dex. Eligible pts have RRMM with ≥ 2 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent. ARRY-520 is administered intravenously (IV) on Days 1, 2, 15 and 16 (Schedule 1) or on Days 1 and 15 (Schedule 2); BTZ is administered IV or subcutaneously (SC) on Days 1, 8 and 15; and 40 mg oral dex, if applicable, is taken on Days 1, 8 and 15 in a 28-day cycle. Results A total of 41 pts have been treated to date at various dose levels of ARRY-520 and BTZ. Patients had a median of 5 prior regimens (range 2-10). All pts received a prior PI, 39 pts received prior BTZ, and 25 pts received at least 2 prior PI- including regimens (range 1-6). In Schedule 1, the initial dose level of ARRY-520 (1.0 mg/m2/day) with BTZ (1.3 mg/m2/day) and dex was not tolerated, with dose-limiting toxicities (DLT) in 2/3 pts (pneumonia and pseudomonal sepsis). After a protocol amendment, dose escalation resumed at reduced doses of ARRY-520 (0.5 mg/m2/day) and BTZ (1.0 mg/m2/day) without dex. The addition of prophylactic filgrastim (G-CSF) enabled escalation to full dose ARRY-520 and BTZ (1.5 and 1.3 mg/m2/day, respectively). Only 1 DLT of pneumonia was observed during the further dose escalation, at 1.0 mg/m2/day ARRY-520 and 1.0 mg/m2/day BTZ. Dex has been added to the combination at 1.25 mg/m2/day ARRY-520 and 1.3 mg/m2/day BTZ and this dose level has been well tolerated. Enrollment is ongoing in the final planned dose level. In Schedule 2, the initial dose level of ARRY-520 (2.25 mg/m2/day) with BTZ (1.3 mg/m2/day) and dex was well tolerated and enrollment is ongoing at 3.0 mg/m2/day ARRY-520 and 1.3 mg/m2/day BTZ + dex, the maximum planned dose of both drugs. The most commonly reported adverse events (AEs) (in ≥ 15% of pts) include anemia, diarrhea, pyrexia, upper respiratory tract infection, thrombocytopenia, cough, neutropenia, constipation, headache, fatigue, hyperuricemia, nausea, vomiting, and dizziness. All Grade 3 – 4 non-hematologic AEs have an incidence of 〈 10%. Based on the laboratory data, Grade 4 neutropenia was observed in 15% of patients, Grade 4 thrombocytopenia was observed in 10%. Apart from the one pt described above with the DLT of pseudomonal sepsis, no other febrile neutropenic events were reported. Neuropathy (Grade 2) was observed in 1 pt. Monopolar spindles have been observed in a post-dose biopsy for a pt treated at 1.0 mg/m2/day ARRY-520 + 1.3 mg/m2/day BTZ, indicating that pharmacodynamic activity of ARRY-520 is maintained in the presence of full dose BTZ. Preliminary signs of efficacy have been observed in this ongoing dose-escalation study. To date, among the subset of 13 evaluable pts who received doses at ≥ 1.25 mg/m2/day ARRY-520 + 1.3 mg/m2/day BTZ, 4 (31%) partial responses (PR) and 1 minimal response (MR) have been observed. By contrast, in the 27 patients receiving lower doses of ARRY-520 and BTZ, only 1 MR has been reported. An additional 29 pts experienced stable disease (SD) on ARRY-520 + weekly BTZ without the use of steroids (dex), including 17 pts with disease refractory to BTZ. Conclusions ARRY-520 + BTZ with prophylactic G-CSF appears well tolerated with manageable non-hematologic AEs in this heavily pretreated pt population and has demonstrated preliminary evidence of activity, including PRs and SD in pts with disease refractory to BTZ. These data support further exploration of this novel KSP inhibitor in combination with BTZ in expansion cohorts. The authors would like to acknowledge the dedicated research staff and physicians at the participating centers of the Multiple Myeloma Research Consortium for their contribution to this study. Disclosures: Chari: Onyx Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees; Millenium Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees. Off Label Use: ARRY-520 is an investigational drug being combined with bortezomib in multiple myeloma. Zonder:Celgene Corporation: Consultancy; Onyx: Consultancy; Skyline Diagnostics: Consultancy. Jakubowiak:Millenuim: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Janssen Cilag: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Onyx: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Hilder:Array BioPharma: Employment. Ptaszynski:Array BioPharma: Employment. Rush:Array BioPharma: Employment. Kaufman:Millenium: Consultancy; Merck: Research Funding; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Onyx: Consultancy; Janssen: Consultancy.

Description: Background The availability of multiple immunomodulators (IMiDs) and proteasome inhibitors (PIs) has resulted in improved outcomes for patients (pts) with multiple myeloma (MM). Pts refractory to these 2 classes of drugs have a poor prognosis and new drugs with novel mechanisms of action are needed. ARRY-520, a potent, selective inhibitor of the novel drug target KSP, has shown single-agent activity in MM. The acute-phase protein AAG can bind ARRY-520, reducing free drug, possibly resulting in reduced treatment effect in pts with high AAG. Methods ARRAY-520-212 is a Phase 1/2 study. The Phase 2 portion was designed to evaluate the efficacy and safety of 1.5 mg/m2/day ARRY-520 administered intravenously on Days 1 and 2 every 2 weeks with filgrastim support. 2 Cohorts have been enrolled: Cohort 1 investigated single-agent ARRY-520 in pts with relapsed or refractory MM with ≥ 2 prior lines of therapy, including both bortezomib (BTZ) and an IMiD. Cohort 2 (cohort2) investigated ARRY-520 with Low-dose dexamethasone (LoDex -40mg weekly) in pts with RRMM with ≥ 2 prior lines of therapy, refractory (progression on or within 60 days of last treatment) to last line of therapy, and refractory to BTZ, lenalidomide (Len) and dexamethasone (triple-refractory). Pts intolerant to Len or BTZ were not included in cohort2. Baseline plasma AAG levels were measured in both cohorts. Results Results are summarized in the attached table. In cohort 1, 32 pts have been treated, with a median age of 65 years and a median of 6 prior regimens. 41% of cohort 1 pts were refractory to BTZ and Len. 6/27 pts (22%) had high baseline AAG. In cohort 2, 50 pts have been treated to date, with a median age of 63 years and a median of 9 prior regimens. As described in the table, cohort 2 pts had more prior treatment regimens, were primarily triple refractory and had a short time to progression (TTP) on prior therapy. 13/44 (30%) of cohort 2 pts had high baseline AAG. ARRY-520 showed a similar safety profile in both Cohorts. The most commonly reported (≥ 10% of pts) treatment-emergent Grade 3/4 adverse events, regardless of attribution, were thrombocytopenia (44% cohort 1, 42% cohort 2), anemia (38% and 50%), neutropenia (38% and 38%), fatigue (16% and 8%), leukopenia (13 and 4%) and pneumonia (3% and 12%). The incidence of febrile neutropenia was low in both cohorts (3% and 6%). ARRY-520 has shown activity both alone and with LoDex (See table). To date, in both cohorts, pts with High AAG have had no objective responses as compared to pts with Low AAG. In the completed cohort 1, ARRY-520 showed a durable 16% overall response rate (ORR) with an 8.6 month (mo) duration of response. In pts with Low AAG a prolonged OS (median = 23 mo) was observed compared to pts with High AAG (OS = 4.5 mo). Follow-up in cohort 2 is ongoing and ARRY-520+LoDex has shown a 16% ORR to date in this very heavily pretreated population. Notably in cohort 2, 4 PR were observed in the 16 patients (25%) who were previously treated with either a novel PI (carfilzomib or MLN9708) and/or IMiD (pomalidomide). Conclusions ARRY-520 is a novel first-in class agent in MM. In this Phase 2 analysis, ARRY-520 showed a similar activity and safety profile both alone and in combination with LoDex. While transient non-cumulative neutropenia is observed, the incidence of febrile neutropenia was low. ARRY-520 showed clear activity both alone and in combination with LoDex. Activity in pts refractory to novel PI and IMiDs suggests a lack of cross-resistance with drugs with existing mechanisms of action. High levels of AAG are associated with a lack of tumor responses and shorter OS following treatment with ARRY-520, suggesting AAG may be a potential patient selection marker identifying pts unlikely to benefit from ARRY-520. Disclosures: Lonial: Millennium: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy; Celgene Corporation: Consultancy. Off Label Use: ARRY-520 (Investigational Drug). Shah:Array BioPharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Onyx Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Zonder:Celgene Corporation: Consultancy; Onyx: Consultancy; Skyline Diagnostics: Consultancy. Kaufman:Onyx: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Millenium: Consultancy; Merck: Research Funding. Hilder:Array BioPharma: Employment. Rush:Array BioPharma: Employment. Ptaszynski:Array BioPharma: Employment. Walker:Array BioPharma: Employment. Orlowski:Array Biopharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Resverlogix: Research Funding; Onyx Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Millenium Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity’s Board of Directors or advisory committees.

Description: Background: Re-admission to the hospital within 30 days is a measure for quality care and a point of emphasis for reducing health care costs in individuals with chronic disease. Potentially modifiable risk factors for 30 day re-admission in children with sickle cell disease (SCD) includes not being seen in the SCD clinic within 30-days of discharge (OR 7.7, 95% CI 2.4–24.4), 3 or more admissions in the previous 12 months (OR 7.3, 95% CI 2.8–18.9) and co-morbid asthma (OR 2.9, 95% CI 1.2–7.3) (Pediatr Blood Cancer. 2009 Apr;52(4):481-5). Limited data exists regarding potentially modifiable risk factors for 30-day re-admission in adults with SCD. The primary objective of this study was to define modifiable risk factors for 30-day re-admission in adults with SCD, leading to a prospective intervention study to decrease re-admission rates. Procedure: At a tertiary care center, we performed a retrospective analysis of the medical records, from 2010 to 2013, to determine risk factors for 30-day re-admission in adults with SCD. Initial admission was defined as the first admission associated with uncomplicated vaso-occlusive pain episode in each focus year (2011- 2013). To decrease bias associated with multiple admissions from the same individual, the first admission for vaso-occlusive pain in each year was evaluated as the index admission for each record. Cases and controls were defined as adults with SCD initially admitted for pain and subsequently re-admitted to the hospital within 30 days of the initial admission. A multi-variable logistic regression analysis was performed on seven postulated risk factors. All data was collected and double checked by a single reviewer, and at least 10% of the chart was checked by a medical student for further assurance of accuracy. Results : A total of 158 first admissions and 49 re-admissions (31%) were evaluated. The mean age of the cohort was 30.38 (IQR 13.55 years). The median time to re-admission was 10 days (IQR 19 days). Approximately 50% of the cohort was not evaluated in the outpatient setting by the hematology team within 30 days post-discharge. Upon discharge patients either were not given a follow up appointment (35%) or were given an appointment beyond 30 days of discharge (13%). Only two predictors were significantly associated with re-admission within 30 days: not having a primary care provider listed in the electronic medical record (odds ratio 0.35, 95% CI 0.146-0.858; p = 0.022) and the number of hospital admissions due to vaso-occlusive pain in the prior year (odds ratio 1.28, 95% confidence interval 1.15-1.42; p 〈 0.001), table and figure below. Five covariates were not significantly associated with re-admission within 30 days: age (odds ratio 0.982, 95% CI 0.94-1.02; p = 0.369), sex (odds ratio 0.715, 95% CI 0.28-1.81, p =0.481), hemoglobin phenotype (odds ratio 0.50, 95% CI 0.19-1.287; p = 0.15), median lifetime oxygen saturation (odds ratio 0.892, 95% CI 0.75-1.05; p = .186), and presence of government insurance (odds ratio 1.90, 95% CI 0.67-5.37; p =0.222). Conclusions: Not having a primary care provider listed in the electronic medical record and multiple admissions in the prior year are potentially modifiable risk factors for re-admission within 30 days in adults with SCD. In addition, discharge planning with a hematology visit scheduled within a week of discharge may also impact the 30-day re-admission rate. We recently introduced a strategy focused on improved discharge planning, ensuring a primary care provider for every adult patient with SCD and targeted therapeutic intervention for those with high admissions. Table: Multivariable analysis of risk factors for 30-day re-admission in adults with sickle cell disease over a course of 3 years. A total of 158 admissions were evaluated with 31% being re-admissions within 30 days. Sig. Odds ratio 95% C.I.for EXP(B) Lower Upper Age Upon Admission to the Hospital 0.369 0.982 0.944 1.021 Sex 0.481 0.715 0.281 1.817 Hemoglobin Phenotype 0.152 0.504 0.197 1.287 Median Lifetime Oxygen Saturation Level 0.186 0.892 0.753 1.057 Primary Care Provider 0.022 0.354 0.146 0.858 Government Insurance 0.222 1.907 0.676 5.378 Number of Hospitalizations Due to Vaso-Occlusive Pain in the Prior Year 0.000 1.278 1.148 1.422 Figure. A graph depicting the predicted probablity of a re-admission within 30 days in indivdiuals with and without hospitalization versus the number of hospitalizations in the prior years. Figure. A graph depicting the predicted probablity of a re-admission within 30 days in indivdiuals with and without hospitalization versus the number of hospitalizations in the prior years. Disclosures No relevant conflicts of interest to declare.

Description: Background ARRY-520, a kinesin spindle protein (KSP) inhibitor, has demonstrated promising clinical activity, both as a single agent and combined with dexamethasone in patients (pts) with bortezomib- and lenalidomide-refractory MM with a single agent response rate (≥ MR) of 19-33%. The maximum tolerated dose (MTD) of ARRY-520 as a single agent was 1.5 mg/m2 administered on days 1 and 2 every 2 weeks with minimal non-hematologic toxicity. Carfilzomib, an irreversible proteasome inhibitor (PI), also has demonstrated single agent activity in RRMM and received accelerated approval by the Food & Drug Administration (FDA). Preclinical data demonstrate synergy between the combination of a PI and ARRY-520 and the minimal overlapping side effect profile support the hypothesis that the combination of carfilzomib and ARRY-520 could be an attractive regimen. Methods The primary objective was to determine the MTD and the safety/tolerability of carfilzomib and ARRY-520 in RRMM. Secondary objectives were to determine efficacy as measured by the overall response rate (ORR), time to progression, progression free survival and time to next therapy. Pts had to be ineligible for autologous stem cell transplant (ASCT), have disease refractory/intolerant to bortezomib, and have had prior lenalidomide exposure. ARRY-520 was administered intravenously (iv) on days 1, 2, 15 and 16; carfilzomib was administered intravenously on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle. All pts received growth factor support in cycle 1. Dose-escalation used a standard 3+3 schema with dose-limiting toxicities (DLTs) assessed during cycle 1. Four dose levels were studied with ARRY-520 escalated from 0.75 to 1.5 mg/m2 with the approved fixed dose of carfilzomib 20/27 mg/m2. Adverse events (AEs) were graded by NCI-CTCAE v4, while responses were assessed by the modified International Uniform Response Criteria. Results 20 pts were enrolled in the completed phase 1 dose escalation portion of the study. The median age was 61 (range 43-80), and pts had received a median of 4 lines of prior therapy (range 2-10). 16/20 pts were lenalidomide refractory/intolerant; 20/20 pts were bortezomib refractory/intolerant; and 18/20 pts had prior ASCT. Two pts in cohort 2 were not DLT evaluable due to non-compliance with study-related therapy in cycle 1 and replaced for assessment of DLT. No DLTs were observed in 3 patients dosed in cohort 1, with ARRY-520 at 0.75 mg/m2. In cohort 2, 1/6 patients encountered a DLT with influenza pneumonia and non-neutropenic fever. In cohort 3, 5 patients were enrolled, ARRY-520 was dose escalated to 1.25 mg/m2, 2 patients were unevaluable for assessment of DLT, and no DLTs were encountered in the remaining 3 patients. The final planned cohort 4 was full dose ARRY-520 at 1.5 mg/m2 and carfilzomib 20/27 mg/m2, where 1/6 patients encountered a DLT of non-neutropenic fever and pneumonia. Therefore, the MTD of ARRY-520 with carfilzomib 20/27 mg/m2 was established at 1.5 mg/m2. Among 19/20 patients evaluable for efficacy, for an ORR (≥ MR) was 58%: including nCR (n=1), uPR/PR (n=6), MR (n=4), uSD/SD (n=4) and PD (n=4). Among 20 pts enrolled to date, 10 patients remain on study, 6 discontinued due to progressive disease, 1 pt was lost to follow-up, 1 patient died with febrile neutropenia in cycle 4 related to treatment, and 2 pts withdrew consent after 1 cycle of therapy. Treatment emergent SAEs included 5 pts with 6 incidences of pneumonia (influenza; n=1), 1 patient each with G3 bacteremia, G2 lethargy, G3 febrile neutropenia(FN) and G5 FN. Conclusions MTD has been established at the maximum planned dose level 4, with carfilzomib 20/27mg/m2 and ARRY-520 at 1.5 mg/m2. ARRY-520 can be safely combined carfilzomib in patients with RRMM and the combination is well tolerated with limited hematologic toxicity with growth factor support. The combination is very active in a heavily pretreated patient population with an ORR (≥MR) of 58%. Enrollment in a dose expansion at dose level 4 is underway. In addition a second dose escalation of ARRY-520 and increasing doses of carfilzomib in a 30 minute infusion is also enrolling. Disclosures: Shah: Array biopharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Research Funding; Onyx: Honoraria, Research Funding; Millennium: Research Funding; Novartis: Honoraria, Research Funding. Off Label Use: ARRY-520 in relapsed/refractory myeloma. Thomas:Celgene: Research Funding; Novartis: Research Funding; Millenium: Research Funding; Immunomedics: Research Funding; Pharmacyclics: Membership on an entity’s Board of Directors or advisory committees; Onyx: Membership on an entity’s Board of Directors or advisory committees. Hilder:Array BioPharma: Employment. Orlowski:Bristol-Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Millennium: The Takeda Oncology Company: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Resverlogix: Research Funding; Array Biopharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Merck: Membership on an entity’s Board of Directors or advisory committees.

Description: Minor changes to seasonal air temperature and precipitation can have a substantial impact on the availability of water resources within large watersheds. Two such watersheds, the north-flowing Mackenzie and east-flowing Saskatchewan Basins, have been identified as highly vulnerable to such changes and, therefore, selected for study as part of the Climatic Redistribution of western Canadian Water Resources project. This project aims to evaluate spatial and temporal changes to water resource distribution through the analysis of a suite of hydroclimatic and streamflow variables. As part of this analysis, dominant summer (May-October) circulation patterns at 500hPa for 1950-2011 are identified using the method of self-organizing maps. Surface climate variables associated with these patterns are then identified, including both daily air temperature and precipitation and seasonal Standardized Precipitation Evapotranspiration Index values. Statistical methods are applied to assess the relationships between dominant circulation patterns and the Southern Oscillation Index (SOI) and Pacific Decadal Oscillation (PDO). Results indicate that mid-summer (July-August) is dominated by a split-flow blocking pattern, resulting in cool (warm), wet (dry) conditions in the southern (northern) portion of the study area. By contrast, the shoulder season (May and October) is dominated by a trough of low pressure over the North Pacific Ocean. The frequency of weak split-flow blocking is higher during positive SOI and negative PDO, whereas ridging over the western continent is more frequent during negative SOI and positive PDO. Results from this analysis increase our knowledge of processes, controlling the distribution of summer water resources in western Canada. © 2014 John Wiley & Sons, Ltd.

Description: The Climatic Redistribution of western Canadian Water Resources project was designed to identify regions of increased/decreased water availability by evaluating a suite of atmospheric, hydroclimatic and streamflow variables. This research component focuses on the atmospheric drivers of air temperature and precipitation in the watersheds originating on the leeward slopes of the Rocky Mountains. Dominant winter (November-April) synoptic-scale mid-tropospheric circulation patterns from 1950 to 2011 are classified using self-organizing maps, and frequency distributions for positive/negative phases of the Southern Oscillation Index (SOI), Pacific Decadal Oscillation (PDO) and Arctic Oscillation are statistically compared. Corresponding high-resolution gridded temperature and precipitation anomalies are calculated for each synoptic type, and spatial patterns of above/below-average temperature and precipitation and north/south gradients are identified. Gridded 6-month values of the Standardized Precipitation-Evapotranspiration Index are also used to categorize winters into regions of high/low snowpack. Results indicate high-pressure ridges over the Pacific Ocean (western North America), and low-pressure troughs over western North America (Pacific Ocean) are associated with anomalously cool (warm) and wet (dry) conditions in the study region. Several statistically different synoptic type frequencies were found for positive/negative phases of the SOI, PDO and Arctic Oscillation. Most notably, positive (negative) phases of the SOI and negative (positive) phases of the PDO are associated with a higher (lower) frequency of ridging over the Pacific Ocean (western North America). Through improved knowledge of the relationships between teleconnections, mid-tropospheric circulation and surface climate, the spatial and temporal distribution of water resources in western Canada is better understood. © 2014 John Wiley & Sons, Ltd.