Academic literature on the topic 'Upper Canada Committee'

IntroductionTheRe-Evaluating theInhibition ofStressErosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE.Methods and analysisREVISE is an international, randomised, concealed, stratified, blinded parallel-group individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of ventilator-associated pneumonia,Clostridioides difficileinfection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial.Ethics and disseminationAll participating centres receive research ethics approval before initiation by hospital, region or country, including, but not limited to – Australia: Northern Sydney Local Health District Human Research Ethics Committee and Mater Misericordiae Ltd Human Research Ethics Committee; Brazil: Comissão Nacional de Ética em Pesquisa; Canada: Hamilton Integrated Research Ethics Board; Kuwait: Ministry of Health Standing Committee for Coordination of Health and Medical Research; Pakistan: Maroof Institutional Review Board; Saudi Arabia: Ministry of National Guard Health Affairs Institutional Review Board: United Kingdom: Hampshire B Research Ethics Committee; United States: Institutional Review Board of the Nebraska Medical Centre. The results of this trial will inform clinical practice and guidelines worldwide.Trial registration numberNCT03374800.

In 1787, a group of American refugee settlers in the western portion of Quebec, which would become the colony of Upper Canada in 1791, collectively petitioned the Governor General, Lord Dorchester, for schools. They insisted, in fact, on a relatively comprehensive network of schools funded directly through the government purse. Dorchester responded by appointing William Smith, the former Chief Justice of New York State with whom he had formed a political friendship during the American War of Independence, to head a special committee to report on the state of education throughout the entire province. Several hundred copies of the report were printed and released in 1789. The report recommended a government-supported tripartite elementary, secondary, and university school system. The recommendations were not acted upon, but the report's ideas lingered in public discourse for years to come. In the writing of the origins of schooling in Upper Canada, this report has not received considerable attention. Moreover, the intentions and goals of these early settlers advocating for government-aided schooling are characteristically overlooked. In the dominant view, the building of Upper Canada's school system was motivated by the bureaucratization and institutionalization concerns of major school advocates and politicians in the mid-nineteenth century.

In situ U–Pb sensitive high-resolution ion microprobe (SHRIMP) analyses of monazite from upper amphibolite-facies paragneiss of the Committee Bay supracrustal belt, central Rae domain, Canada, reveal three age populations: ca. 2350, 1850, and 1780 Ma. The ca. 1850 Ma age also corresponds to growth of low Th/U zircon as indicated by U–Pb SHRIMP analyses of zircon separates from melanosome and leucosome. The contextual advantage of the in situ monazite analysis allows evaluation of the geochronological data in terms of the regional structural and metamorphic evolution. The region is dominated by a northeast-striking S2 (±S1) fabric, axial planar to tight, northwest-vergent F2 folds. Early garnet is enveloped by this biotite–sillimanite ± cordierite S2 fabric. GarnetI hosts ca. 1850 Ma monazite inclusions (with ca. 2350 Ma cores), placing a maximum age on garnetI growth and S2 development. D2 metamorphic conditions progressed through ~3.5 kbar (1 kbar = 100 MPa) and 600 °C to near-peak conditions of ~5 kbar and 675 °C. A minimum age for S2 is provided by unstrained ca. 1820 Ma monzogranite that locally, and regionally, truncates S2. Dominantly ca. 1780 Ma matrix monazite is interpreted to date post-S2 garnetII and cordierite, which record ~5 kbar and 675 °C. These data indicate that the Committee Bay region experienced penetrative D2 tectonometamorphism at ca. 1850–1820 Ma, with a subsequent static overprint. The absence of a ca. 1.85 Ga plutonic suite in the region suggests that low-pressure metamorphism was a response to thick-skinned crustal thickening initiated at ca. 1870 Ma. The new data highlight the importance of Paleoproterozoic reworking of the central Rae domain in the hinterland of the Trans-Hudson orogen.

Abstract. The extent of global change in carbon system parameters can only be evaluated by comparing present with past measurements. In the northern North Pacific, where aragonite saturation horizons are among the shallowest in the world, historical measurements of carbonate parameters vary from rare to nonexistent. However, during the summer of 1956 and winter of 1957, an extensive survey of the oceanography of the Northeast Pacific, under the auspices of the Canadian Committee on Oceanography, was conducted by the Fisheries Research Board of Canada. Approximately 2500 measurements of pH at depths from surface to 2000 m were taken throughout the Gulf of Alaska, in addition to measurements of nutrient and hydrographic properties. After conversion to the contemporary total pH scale, these data revealed significant seasonal and latitudinal differences in pH in the upper 200 m. Estimates of aragonite saturation indicate that undersaturated water was a common feature of the surface mixed layer north of 51° N latitude in the winter of 1957. The North Pacific Survey data were compared with the results of a summer 2007 survey of the west coast of North America where pH levels were ~0.1 pH units lower (at a reference density of 26.2σθ than was found in the summer of 1956.

This speech was given by the Prime Minister at the closing banquet of the Conference on the Reform of Federal Institutions in Quebec on March 30, 1984. He suggested that Reform is desirable because Canadian Federalism is capable of evolution and renewal. Canada needs institutions in which a national consensus on its fundamental options can be developed frankly and openly. The federal government's representativeness and its authority to speak and act in the name of all regions and of all Canadians must be strengthened. The proposed reform of the Upper House conducted by the Special joint Committee on Senate Reform indicates that provinces and regions should be represented adequately, not the provincial governments. These governments, because regional interests were not perceived to be adequately represented within the federal institutions, have had a tendency to present themselves as the only legitimate representatives of the regions. The idea of a second chamber elected directly by the people would enhance the independence and authority of senators in their role as regional representative. Mr. Trudeau indicates that the institutionalization of federal-provincial conferences ought to be looked at with the aim of harmonizing the policies of the two orders of government. This should establish coordination and effective management in areas of shared jurisdiction.

BackgroundTherapeutic options are limited for patients with liver metastases and hepatocellular carcinoma (HCC). Intratumoral and subcutaneous injections of CMP-001, a CpG-A TLR9 agonist packaged within a virus-like particle, have shown evidence of antitumor activity in patients with melanoma refractory to PD-1 blockade. In mice, CMP-001 intravenous distributes primarily to the liver, while CMP-001 subcutaneous is found mostly in local tissues and draining lymph nodes. The antitumor activity of CMP-001 intravenous and subcutaneous were compared with PD-1 blockade or sorafenib in two Hepa1-6 orthotopic mouse models of HCC.MethodsGroups of 10–15 C57BL/6J mice were orthotopically implanted with syngeneic murine hepatoma cells using two different models. Model 1 used 1.5 x 106 Hepa1-6 cells injected into the spleen following a partial hepatectomy; Model 2 used 1 x 106 Hepa1-6-Luc cells injected into the upper left lobe of intact liver. Treatment was initiated 3–7 days later with either CMP-001 intravenous or subcutaneous Q4-5Dx3-4 doses, PD-1 blocking antibody intraperitoneal Q3-4Dx2 (Bio X Cell clone RPM1-14), or sorafenib QD oral. Antitumor activity was assessed by tumor imaging, liver weight, and/or survival.ResultsCMP-001 was compared with PD-1 blocking antibody therapy in Model 1, the more aggressive model. All animals were sacrificed at day 15 due to institutional welfare requirements. Tumor growth inhibition (TGI) was assessed by comparison of liver weight to body weight ratios, which relative to untreated control mice showed that CMP-001 intravenous achieved 85% mean TGI compared with 63% mean TGI for CMP-001 subcutaneous and 15% mean TGI for PD-1 blocking antibody intraperitoneal (table 1). CMP-001 intravenous was compared to sorafenib oral in Model 2, which utilized an engineered Hepa1-6 cell line that expresses luciferase to enable noninvasive monitoring of liver tumor growth. CMP-001 intravenous was active, with a 67% mean TGI, and survival that was comparable to sorafenib (table 2; figure 1).Abstract 604 Table 1Abstract 604 Table 2Abstract 604 Figure 1ConclusionsIn orthotopic mouse models of HCC, the antitumor activity of CMP-001 intravenous was greater than PD-1 blockade and comparable to sorafenib. CMP-001 intravenous was more active than CMP-001 subcutaneous in this model, which we hypothesize is due to increased liver exposure with intravenous infusion. Antitumor activity of CMP-001 monotherapy may be increased by combining it with standard of care or other therapies, as observed relative to historical benchmarks in ongoing CMP-001 clinical trials in patients with melanoma. CMP-001 intravenous may be a promising treatment option for patients with primary or metastatic liver cancers.AcknowledgementsThis work was supported by Checkmate Pharmaceuticals. Studies were performed at Oncodesign Biotechnology (Dijon, France) and Crown Bioscience UK Ltd (Osgathorpe, UK) and National Research Council Canada (Ottawa, Ontario, Canada) and funded by Checkmate Pharmaceuticals.Ethics ApprovalAt Oncodesign Biotechnology, animal housing and experimental procedures were conducted according to French and European Regulations and the National Research Council Guide for the Care and Use of Laboratory Animals. The animal facility is authorized by the French authorities (Dijon: Agreement B21231011EA). The study and all animal procedures were approved by the Institutional Animal Care and Use Committee of Oncodesign (Oncomet) approved by French authorities (CNREEA agreement number 91). At Crown Bioscience, animal care and experimental procedures were compliant with the UK Animals Scientific Procedures Act 1986 (ASPA) in line with Directive 2010/63/EU of the European Parliament and the Council of 22 September 2010 on the protection of animals used for scientific purposes. At National Research Council Canada, animals were maintained in accordance with the guidelines of the Canadian Council on Animal Care, and all experimental procedures were performed in accordance with regulations and guidelines reviewed and approved by the NRC Human Health Therapeutics Ottawa Animal Care Committee.

2024 SPE President Terry Palisch is the vice president of technology and engineering at CARBO Ceramics in Richardson, Texas. He began his career with ARCO, during which he served 4 years in Algeria and 10 years as a senior petroleum engineer in Alaska. Palisch joined CARBO in 2004 and in his current position leads a team of technologists developing and championing new products and services and advising clients on completion and fracture optimization. Palisch has been an active SPE member serving in various roles, including past chairman of the SPE Dallas Section, past chair of the SPE Annual Technical Conference and Exhibition (ATCE) technical program and former SPE Completions Technical Director. He is an SPE Distinguished Member and received the award for Distinguished Service, as well as the SPE Mid‑Continent Regional Completions Optimization and Technology Award and the Regional Service Award. In 2013, he was named one of the Top 15 Best Engineers by the Texas Independent Producers and Royalty Owners Association, and in 2015 he was named the SPE Dallas Section Engineer of the Year. He has authored more than 50 SPE technical papers and holds several patents. Palisch holds a bachelor’s degree in petroleum engineering from University of Missouri‑Rolla (now Missouri University of Science and Technology) and was recently recognized as a Distinguished Alumnus. North America Regional Director Robert C. Martinez is president and CEO of Titan Rock Exploration & Production and president of Alpine Gas. He has more than 23 years of experience developing and optimizing oil and gas assets throughout the US, including conventional assets, unconventional horizontal development programs, and enhanced oil recovery projects. Middle East and North Africa Regional Director Mohamed Al Marzouqi is senior vice president of development at ADNOC Upstream Directorate. He has been with ADNOC since 2005. He joined ZADCO (ADNOC Offshore) as a petroleum engineer in field development to head the maximum-reservoir- contact (MRC) well-design team during which first production began through MRC wells from an artificial island. As a senior manager for reservoir development at ZADCO, he developed reservoir management strategy to redevelop a multibillion-dollar project in the Upper Zakum field through artificial islands. He led the team in the development of integrated reservoir management for ADNOC Group. Drilling Technical Director Robin Macmillan is the chief sales officer at Data Gumbo. He was previously senior vice president for business development at NOV, manager of Schlumberger drilling and measurements in Canada, and president at drill-bit company ReedHycalog. In his early career he worked in offshore and onshore drilling operations in several countries across North and Latin America, Africa, the Middle East, and Europe. He is the current vice president of drilling services and a member of the Executive Committee at the International Association of Drilling Contractors, where he is also Chair Emeritus of the Advanced Rig Technology Committee and a member of the Drilling Engineering Committee. Health, Safety, Environment, and Sustainability Technical Director Susan (Sue) Staley is the sustainability director for vPSI Group LLC where she leads the company’s sustainability practice. Prior to joining vPSI, she was the general manager of soil and groundwater technology at Shell and held various positions there during her 18-year tenure. Prior to Shell, she worked as a consultant at ERM. Staley has been an environmental and safety engineer for 30 years.

Objective: To systematically review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of ustekinumab to inform pharmacists and other healthcare professionals of this new biologic therapy for psoriasis. Data Sources: A search of PubMed/MEDLINE, EMBASE, and International Pharmaceutical Abstracts was performed through July 2009, limited to publications in English, using the search terms CNTO-1275, ustekinumab, interleukin-12, interleukin-23, and/or psoriasis to identify literature sources. References from the retrieved articles were also evaluated to identify relevant literature. An abstract from a Congress of the European Academy of Dermatology and Venereology and unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov ) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidances, and advisory committee briefing packets. Study Selection and Data Extraction: All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of ustekinumab for the treatment of psoriasis were included, with preference for human data. Data Synthesis: Ustekinumab, an anti-interleukin-12/23 monoclonal antibody, achieved the primary endpoint of 75% reduction in the Psoriasis Area and Severity Index score in a large proportion of patients in the Phase 3 PHOENIX trials. Commensurate improvements were also seen in the Physician's Global Assessment and Dermatology Life Quality Index scores. These efficacy results were reproduced in the ACCEPT trial, demonstrating superiority of ustekinumab to etanercept. The frequency of adverse events was similar between ustekinumab and placebo; common adverse events reported included nasopharyngitis, upper respiratory tract infection, headache, arthralgia, cough, and injection site reactions. Phase 3 studies indicate that the optimal dosing appears to be 45 mg for patients weighing less than 100 kg or 90 mg for patients weighing more than 100 kg, with both doses administered subcutaneously. In these studies, the second dose was given 4 weeks after the first and then every 8–12 weeks thereafter, based upon response. Conclusions: Ustekinumab, a promising new therapy, reduces the extent and severity of psoriasis and was well tolerated in clinical trials. Ongoing clinical trials will allow clinicians to further assess the efficacy/safety profile of this novel biologic.

Introduction: Renal impairment (RI) is a common feature in multiple myeloma (MM) and an adverse predictor of survival. Anti-myeloma treatments that can also improve renal function in patients (pts) with MM are required. Isatuximab (Isa), a monoclonal CD38 antibody, is approved in combination with pomalidomide and dexamethasone (d), in the United States, the European Union, Canada, Australia, Switzerland, and Japan for the treatment of adult pts with relapsed/refractory MM who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. IKEMA (NCT03275285) was a randomized, open-label, multicenter, Phase 3 study that demonstrated the benefit of adding Isa to carfilzomib (K) plus d vs Kd in pts with relapsed MM. This subgroup analysis of IKEMA examined efficacy, renal response, and safety in pts with RI. Methods: Pts with 1-3 prior lines of therapy were randomized 3:2 and stratified by number of prior lines and revised international staging system (R-ISS) stage to receive Isa-Kd or Kd. The Isa-Kd arm received Isa 10 mg/kg intravenously weekly for 4 weeks, then every 2 weeks thereafter. Both arms received recommended doses of Kd. Treatment continued until disease progression or unacceptable adverse events. Interim efficacy analysis was planned when 65% of the total expected progression-free survival (PFS) events determined by an Independent Response Committee were observed. RI was defined as estimated glomerular filtration rate ([eGFR]; using the Modification of Diet in Renal Disease equation) <60 mL/min/1.73m² at baseline. Complete renal response (CrR) was defined as improvement in eGFR from <50 mL/min/1.73m² at baseline to ≥60 mL/min/1.73m² (no RI) in at least one post-baseline assessment (International Myeloma Working Group recommendations), and was classified as durable if lasting ≥60 days. Results: A total of 302 pts (179 Isa-Kd; 123 Kd) were randomized. Pts with baseline eGFR as low as 15 mL/min/1.73m² (severe RI) were allowed to enroll. more pts with RI in the Isa-Kd arm (26.1%) vs Kd (16.2%). As expected, elderly pts had more RI. The median age in years (range) was 67 (39-86) for Isa-Kd vs 69 (49-90) for Kd among RI pts, and 64 (37-81) for Isa-Kd vs 62 (33-78) for Kd among pts with no RI. In RI pts, 60.5% vs 72.2% pts had ≥2 prior lines of therapy, 11.6% vs 16.7% had R-ISS stage III, and 20.9% vs 27.8% had high risk cytogenetics, in Isa-Kd vs Kd, respectively. More RI pts were still on treatment at the cut-off date in Isa-Kd (55.8%) vs Kd (16.7%). Median PFS for RI pts was not reached for Isa-Kd vs 13.4 months for Kd (HR 0.27; 95% CI 0.11-0.66), and not reached for both study arms among pts with no RI (HR 0.63; 95% CI 0.39-1.00). The overall response rate, ≥very good partial response rate, and minimal residual disease negativity for RI pts was higher with Isa-Kd than Kd: 93.0% vs 61.1%, 79.1% vs 44.4%, and 30.2% vs 11.1%, respectively. CrR accessed in pts with eGFR <50 mL/min/1.73m² (15.2% Isa-Kd vs 11.7% Kd) occurred more frequently in Isa-Kd (52%) vs Kd (30.8%), and these were durable in 32.0% vs 7.7% pts. The treatment exposure was higher in RI pts treated with Isa-Kd, with median number of cycles started and median duration of exposure being 20 vs 9 cycles and 81.0 vs 35.7 weeks in Isa-Kd vs Kd. In pts with RI, Grade ≥3 and serious treatment emergent adverse events (TEAEs) were reported in 79.1% (Isa-Kd) vs 77.8% (Kd) and 62.8% (Isa-Kd) vs 77.8% (Kd) pts, respectively. Grade 5 TEAEs (Isa-Kd, 0%; Kd, 11.1%) and TEAEs leading to treatment discontinuation were lower with Isa-Kd (Isa-Kd, 7.0%; Kd, 27.8%). End-stage renal disease on treatment occurred in 1.8% Isa-Kd vs 2.7% Kd pts. The most common TEAEs in RI pts in Isa-Kd vs Kd were diarrhea (41.9% vs 22.2%), upper respiratory tract infection (39.5% vs 27.8%), infusion reaction (37.2% vs 5.6%), hypertension (34.9% vs 27.8%), fatigue (34.9% vs 22.2%), and dyspnea (32.6% vs 11.1%). The most common Grade ≥3 TEAEs in RI pts in Isa-Kd vs Kd were hypertension (20.9% vs 22.2%) and pneumonia (11.6% vs 22.2%). Conclusions: The addition of Isa to Kd improved PFS and disease response in pts with RI, with a manageable safety profile, consistent with the benefit observed in the overall IKEMA study population. Also, more pts treated with Isa-Kd showed reversal of RI and durable renal responses compared with Kd. Finally, RI pts treated with Isa-Kd received twice the number of cycles and had a lower treatment discontinuation rate compared with Kd pts. Disclosures Martin: AMGEN: Research Funding; Sanofi: Research Funding; GSK: Consultancy; Seattle Genetics: Research Funding; Janssen: Research Funding. Moreau:Novartis: Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Honoraria. Baker:Sanofi: Research Funding. Leleu:Karyopharm: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; AbbVie: Honoraria; Amgen: Honoraria; Oncopeptide: Honoraria; Incyte: Honoraria; Merck: Honoraria; Carsgen: Honoraria; Janssen: Honoraria; BMS-celgene: Honoraria; GSK: Honoraria. Mohty:Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau. Leblanc:Celgene: Research Funding; Celgene Canada; Janssen Inc.; Amgen Canada; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Risse:Sanofi: Current Employment. Malinge:AIXIAL: Consultancy. Schwab:Sanofi: Current Employment. Dimopoulos:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau.

428 Background: Avelumab is a human anti‒PD-L1 IgG1 antibody approved in the US, Canada, and Israel for the treatment of locally advanced or metastatic urothelial carcinoma (mUC) progressed after platinum chemotherapy. In the JAVELIN Solid Tumor study, patients (pts) in various subgroups had a favorable objective response rate (ORR) with avelumab. Here, we report further post hoc analyses of safety and efficacy outcomes with avelumab in high-risk mUC subgroups. Methods: Pts with mUC that had progressed after platinum-based therapy in the JAVELIN Solid Tumor study were analyzed. Best overall response (per RECIST 1.1) was adjudicated by an independent review committee. ORR, disease control rate (DCR), progression-free survival (PFS), and adverse event (AE) profiles for pre-specified subgroups of high-risk pts were compared. Results: 242 pts with mUC received avelumab and were followed up for ≥2 years (data cutoff, Apr 2018). No difference was found in ORR between pts with renal insufficiency (creatine clearance [CrCl], <60 mL/min; n=107) and pts with CrCl ≥60 mL/min (n=131; 17.8% [95% CI: 11.0-26.3] vs 15.3% [95% CI: 9.6-22.6]) or between pts with upper (n=56) vs lower tract tumors (n=186; 14.3% [95% CI: 6.4-26.2] vs 17.2% [95% CI: 12.1-23.4]). ORR in pts with baseline liver metastases (n=83) was 6.0% (95% CI: 2.0-13.5) vs 22.0% (95% CI: 15.8-29.3) in pts without (n=159). ORR in elderly pts (≥75 years; n=68) was 25.0% (95% CI: 15.3-37.0) vs 13.2% (95% CI: 8.6-19.2) in younger pts (n=174). ORR in pts with albumin ≥35 g/L (n=197) was 19.8% (95% CI: 14.5-26.1) vs 2.2% (95% CI: 0.1-11.8) in pts with <35 g/L (n=45). Except for the albumin levels and age subgroups (where the trend in ORR was not confirmed), subgroups showed DCR and PFS that were consistent with ORR trends. AE profiles did not exhibit any higher risk of adverse effects in these subgroups. Conclusions: Responses to avelumab occurred in select assessed subgroups previously defined as poor prognostic or high risk, suggesting that immunotherapy may achieve comparable efficacy irrespective of factors such as site of disease and renal status; no difference in safety profiles was identified. Clinical trial information: NCT01772004.

<em>Abstract</em>.-Consensus-based research uses scientific inquiry as an unbiased tool to contrast opposing positions in resource conflicts. However, when applied inappropriately, science is more likely to polarize opposing parties. Opposing parties also may use a consensus-based research process to delay actions not in their interest. The recreational smallmouth bass (SMB) <em>Micropterus dolomieu </em>fishery in the St. Croix River, New Brunswick-Maine is an example of how consensus-based research failed to bring opposing sides in a natural resource conflict to a mutually agreeable resolution. Recreational fishing guides blamed high alewife <em>Alosa pseudoharengus </em>returns for the crash of a naturalized SMB fishery in the upper watershed and proposed an exclusion law in response. In 1995, Maine legislated that all fishways in the St. Croix River be closed to alewives, with a resulting decline from 2.6 million alewives in 1987 to 900 by 2002. Claims of insufficient data to describe alewife ecological impacts on SMB led to formation of a local, state, provincial, U.S., and Canadian stakeholders science committee charged with developing a study that would describe SMB and alewife interactions. The committee identified the question "has alewife presence contributed to poor SMB population performance" as of primary importance to moving forward to a resolution. To test this hypothesis, SMB condition and growth, and the diet habits and diet overlap of alewives and SMB, were used as indicators of competition. Results, presented here, indicate that growth did not decline in the presence of alewives, age-0 SMB condition did not decline when alewives were present, and diet overlap between the two species was low in three of four lakes examined. Thus, the available data did not indicate that alewives caused poor SMB population performance. The project results helped break down institutional barriers between Maine natural resource agencies. However, local recreational fishermen were not satisfied with the project process or results, claiming that their interests, as represented by the state freshwater fish and game agency, were not seriously considered. They opposed and nearly defeated a bill to reintroduce alewives to the St. Croix River in 2008, again citing insufficient data to justify the action.

According to UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiations), no less than 10% of lung cancer diseases registered annually are caused by radon radiation. Born in the belly of the earth, the same gas, a class I cancirogen, increases the risk of non-cancerous diseases of the upper respiratory tract and cardiovascular diseases. The radon problem occupies an important place in the radioecological programs of the USA, Japan, Western Europe and Russia. However, the natural radiation varies in the background from location to location. In many countries, survey work is being carried out, including an assessment of the intensity of the radon hazards of sites allocated for construction. In Russia, the Radiation Safety Standards are stipulating that the concentration of radon in the air of residential premises should not exceed 200 Bq/m3; in Sweden, the maximum radon concentration is taken as 100 Bq/m3, in Finland and Canada - 400 Bq/m3, and in Germany and Great Britain - 200 Bq/m3. It is necessary to carefully choose the constructive site, with the minimum concentration of radon in the soil. Our purpose is to carry out a cartographic analysis of radon intake from soil in the territory of Kazan. An important component is the creation of unique maps based on the measurement of radon escalation. The practical significance of the work lies in the application of the results for making management decisions, in engineering and environmental surveys, for conducting hygienic assessments, or simply being used by citizens for informational purposes.

Between 2.62 and 2.58 Ga, Rae Province was intruded from Lake Athabasca to Melville Peninsula (more than 1700 km) by mafic to felsic plutons (Snow Island Suite), and overlain by volcanic rocks that are now mostly preserved beneath Paleoproterozoic basins. The Snow Island Suite was preceded by offshore arc volcanism and possible back-arc basin activity, with a U-Pb age peak at 2.635 Ga (Marjorie peak). About 50% of the Snow Island Suite is an infracrustal granitoid with K-enriched and tonalitic subtypes; the remainder lies on a sanukitoid spectrum. The sanukitoidal rocks are dominantly orthopyroxene-bearing magnesian diorite and monzodiorite with Mesoarchean Nd model ages. Some isotopically juvenile Snow Island Suite and Marjorie peak mafic rocks also have strong sanukitoid or adakite trace-element signatures. Four important features in the data are: 1) Marjorie peak mafic assemblages are prominent on the southeastern edge of Rae Province. Related nickel showings are present in south Rae Province Marjorie peak and early Snow Island Suite rocks; 2) U-Pb ages in the Snow Island Suite young toward the west edge of the province; 3) the Committee Bay Block (north-central Rae Province) is distinctively rich in infracrustal Snow Island Suite migmatite and poor in Snow Island Suite sanukitoid rocks and in tonalite of any age; and 4) there is a marked shift from tonalite-rich infracrustal sources in south Rae Province to more tonalite-poor sources in central Rae Province. The data are consistent with the Snow Island Suite, representing a continental magmatic arc segment, verging westward, with ponding of mafic magmas, inducing melting in the lower lithosphere to generate intermediate melts that ascended and induced additional melting in the middle to upper crust to generate granite.