Intercomparison of retrospective radon detectors.

We performed both a laboratory and a field intercomparison of two novel glass-based retrospective radon detectors previously used in major radon case-control studies performed in Missouri and Iowa. The new detectors estimate retrospective residential radon exposure from the accumulation of a long-lived radon decay product, (210)Pb, in glass. The detectors use track registration material in direct contact with glass surfaces to measure the alpha-emission of a (210)Pb-decay product, (210)Po. The detector's track density generation rate (tracks per square centimeter per hour) is proportional to the surface alpha-activity. In the absence of other strong sources of alpha-emission in the glass, the implanted surface alpha-activity should be proportional to the accumulated (210)Po, and hence to the cumulative radon gas exposure. The goals of the intercomparison were to a) perform collocated measurements using two different glass-based retrospective radon detectors in a controlled laboratory environment to compare their relative response to implanted polonium in the absence of environmental variation, b) perform collocated measurements using two different retrospective radon progeny detectors in a variety of residential settings to compare their detection of glass-implanted polonium activities, and c) examine the correlation between track density rates and contemporary radon gas concentrations. The laboratory results suggested that the materials and methods used by the studies produced similar track densities in detectors exposed to the same implanted (210)Po activity. The field phase of the intercomparison found excellent agreement between the track density rates for the two types of retrospective detectors. The correlation between the track density rates and direct contemporary radon concentration measurements was relatively high, considering that no adjustments were performed to account for either the residential depositional environment or glass surface type. Preliminary comparisons of the models used to translate track rate densities to average long-term radon concentrations differ between the two studies. Further calibration of the retrospective detectors' models for interpretation of track rate density may allow the pooling of studies that use glass-based retrospective radon detectors to determine historic residential radon exposures

Movements and spatial use of odontocetes in the western main Hawaiian Islands: results from satellite-tagging and photo-identification off Kaua‘i and Ni‘ihau in July/August 2011

Although considerable information is available on residency patterns and spatial use of odontocetes in the eastern half of the Hawai‘i Range Complex (HRC), much less is known about odontocetes in the western half of the HRC. In the second year of a three-year effort in the western main Hawaiian Islands we undertook surveys off Kaua‘i and Ni‘ihau in July/August 2011, to examine spatial use and residency patterns using satellite tags, to provide visual verification of acoustically-detected odontocetes on the Pacific Missile Range Facility (PMRF), and to obtain individual identification photographs and biopsy samples for assessment of population identity and structure. During 18 days of field effort we covered 1,972 km of trackline and had 65 encounters with five species of odontocetes. Twenty-four of the encounters, of three species, were cued by acoustic detections from the Marine Mammal Monitoring on Navy Ranges (M3R) system, thus providing species verifications for future use of the M3R system on the PMRF range. During the 65 encounters we obtained 22,645 photos for individual and species identification, and collected 48 biopsy samples for genetic analyses. One encounter with a group of four killer whales was only the second encounter with this species in 12 years of directed field surveys in Hawaiian waters. Photos from that encounter were compared to our photo-identification catalog but no matches were found, further suggesting that there is no population of this species resident to the Hawaiian Islands. There were three encounters with a lone pantropical spotted dolphin, each time in association with a group of spinner dolphins. Photos of this individual matched to a spotted dolphin identified off Kaua‘i in 2004 and in 2005, both times with spinner dolphins, suggesting this individual may be part of a long-term association with spinner dolphins. Four satellite tags were deployed; three on rough-toothed dolphins and one on a bottlenose dolphin. These are the first tag deployments on either species in Hawaiian waters and the first deployments of satellite tags on free-ranging rough-toothed dolphins anywhere in the world. Rough-toothed dolphin tag data were obtained over periods from 7.6 to 18.5 days. Over these periods the three rough-toothed dolphins moved cumulative horizontal distances ranging from 573 to 1,295 km, yet remained an average distance from the tagging locations of from 10.4 to 13.9 km. Median depths used by the three rough-toothed dolphins ranged from 816 to 1,107 m, with median distance from shore ranging from 11.6 to 12.2 km. Two of the three individuals had been previously photo-identified off Kaua‘i (in 2007 or 2008), and all link by association with the resident population from Kaua‘i and Ni‘ihau. Movement and habitat use data were obtained over a 34-day period for the satellite-tagged bottlenose dolphin. During this time the individual remained associated with the island of Kaua‘i using waters with a median depth of 82 m. Although this individual had not been previously photo-identified, others from the group it was in had been previously documented off Kaua‘i and/or Ni‘ihau in 2003-2005, suggesting it is part of the island-resident population. Overall these efforts provide the first unbiased movement and habitat use data for both species in Hawaiian waters.Grant No. N00244-10-1-004

Glider observations of enhanced deep water upwelling at a shelf break canyon: a mechanism for cross-slope carbon and nutrient exchange

Using underwater gliders we have identified canyon driven upwelling across the Celtic Sea shelf-break, in the vicinity of Whittard Canyon. The presence of this upwelling appears to be tied to the direction and strength of the local slope current, which is in itself highly variable. During typical summer time equatorward flow, an unbalanced pressure gradient force and the resulting disruption of geostrophic flow can lead to upwelling along the main axis of two small shelf break canyons. As the slope current reverts to poleward flow, the upwelling stops and the remnants of the upwelled features are mixed into the local shelf water or advected away from the region. The upwelled features are identified by the presence of sub-pycnocline high salinity water on the shelf, and are upwelled from a depth of 300 m on the slope, thus providing a mechanism for the transport of nutrients across the shelf break onto the shelf

Reasons for hospitalizations in patients with type 2 diabetes in the CANVAS programme: A secondary analysis

Aim: To determine the reasons for hospitalizations in the CANagliflozin cardioVascular Assessment Study (CANVAS) programme and the effects of the sodium-glucose co-transporter-2 inhibitor canagliflozin on hospitalization. Materials and Methods: A secondary analysis was performed on the CANVAS programme that included 10 142 participants with type 2 diabetes randomized to canagliflozin or placebo. The primary outcome was the rate of total (first plus all recurrent) all-cause hospitalizations (ACH). Secondary outcomes were total hospitalizations categorized by the Medical Dictionary for Regulatory Activities hierarchy at the system organ class level, reported by investigators at each centre. Outcomes were assessed using negative binomial models. Results: Of the 7115 hospitalizations reported, the most common reasons were cardiac disorders (23.7%), infections and infestations (15.0%), and nervous system disorders (9.0%). The rate of total ACH was lower in the canagliflozin group (n = 5795) compared with the placebo group (n = 4347): 197.9 versus 215.8 participants per 1000 patient-years, respectively (rate ratio [RR] 0.92; 95% confidence interval [CI] 0.86, 0.98). Canagliflozin reduced the rate of total hospitalizations because of cardiac disorders (RR 0.81; 95% CI 0.75, 0.88). There was no significant difference between the canagliflozin and placebo groups in the rates of total hospitalizations because of infections and infestations (RR 0.96; 95% CI 0.86, 1.02) or nervous system disorders (RR 0.96; 95% CI 0.88, 1.05). Conclusions: In the CANVAS programme, the most common reasons for hospitalization were cardiac disorders, infections and infestations, and nervous system disorders. Canagliflozin, compared with placebo, reduced the rate of total ACH

Canagliflozin and heart failure in Type 2 diabetes mellitus: results from the CANVAS Program (Canagliflozin Cardiovascular Assessment Study)

BACKGROUND : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure and cardiovascular death overall, in those with and without a baseline history of heart failure, and in other participant subgroups. METHODS : The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks. The primary end point for these analyses was adjudicated cardiovascular death or hospitalized heart failure. RESULTS : Participants with a history of heart failure at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all P0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of heart failure (P=0.03). CONCLUSIONS : In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin reduced the risk of cardiovascular death or hospitalized heart failure across a broad range of different patient subgroups. Benefits may be greater in those with a history of heart failure at baseline. CLINICAL TRIAL REGISTRATION : URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01032629 and NCT01989754

Different eGFR decline thresholds and renal effects of cnagliflozin: data from the CANVAS program

BACKGROUND: Traditionally, clinical trials evaluating effects of a new therapy with creatinine-based renal end points use doubling of serum creatinine (equivalent to a 57% eGFR reduction), requiring large sample sizes. METHODS: To assess whether eGFR declines <57% could detect canagliflozin's effects on renal outcomes, we conducted a post hoc study comparing effects of canagliflozin versus placebo on composite renal outcomes using sustained 57%, 50%, 40%, or 30% eGFR reductions in conjunction with ESKD and renal death. Because canagliflozin causes an acute reversible hemodynamic decline in eGFR, we made estimates using all eGFR values as well as estimates that excluded early measures of eGFR influenced by the acute hemodynamic effect. RESULTS: Among the 10,142 participants, 93 (0.9%), 161 (1.6%), 352 (3.5%), and 800 (7.9%) participants recorded renal outcomes on the basis of 57%, 50%, 40%, or 30% eGFR reduction, respectively, during a mean follow-up of 188 weeks. Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions. In analyses that controlled for the acute hemodynamic fall in eGFR, effect sizes were comparable, regardless of whether a 57%, 50%, 40%, or 30% eGFR reduction was used. Estimated sample sizes for studies on the basis of lesser eGFR reductions were much reduced by controlling for this early hemodynamic effect. CONCLUSIONS: Declines in eGFR <57% may provide robust estimates of canagliflozin's effects on renal outcomes if the analysis controls for the drug's acute hemodynamic effect. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629 and CANVAS-R, NCT01989754