No abstract

Snowmelt is a crucial source of water for many shallow subarctic lakes, but climate models predict that snowfall will decrease in some regions, with profound ecological consequences. Here we use lake water isotope data across gradients of terrestrial vegetation cover (open tundra to closed forest) and topographic relief to identify lakes that are vulnerable to desiccation under conditions of low snowmelt runoff in two subarctic landscapes—Old Crow Flats, Yukon, and Hudson Bay Lowlands, Manitoba (Canada). Lakes located in low‐relief, open tundra catchments in both landscapes displayed a systematic, positive offset between directly measured lake water δ18O over multiple sampling campaigns and lake water δ18O inferred from cellulose in recently deposited surface sediments. We attribute this offset to a strong evaporative 18O‐enrichment response to lower‐than‐average snowmelt runoff in recent years. Notably, some lakes underwent near‐complete desiccation during midsummer 2010 following a winter of very low snowfall. Based on the paleolimnological record of one such lake, the extremely dry conditions in 2010 may be unprecedented in the past ~200 years. Findings fuel concerns that a decrease in snowmelt runoff will lead to widespread desiccation of shallow lakes in these landscapes.

Background: The Glycine389 variant of the beta-1 adrenergic receptor (b1AR) generates markedly less cAMP when stimulated in vitro than the more prevalent Arginine389 variant. Aims: The aim of this MERIT-HF sub-study was to ascertain whether this Glycine389 variant favourably influences outcome in heart failure similar to that observed with beta-blockers. Methods: We identified the genotype at amino acid 389 of the b1AR in 600 patients enrolled in the MERIT-HF study (UK and Dutch participants). A risk-ratio (RR) for each genotype was calculated using the combined endpoint of all cause mortality or hospitalisation (time to first event). A pharmacogenetic effect of this polymorphism was also sought by evaluating the effect of Metoprolol CRyXL on heart rate amongst the three genotypes. Results: The prevalence of the three genotypes was ArgArg 51.3%, ArgGly 40.2%, GlyGly 8.5%. The presence of the Gly allele was not associated with a significant benefit on the combined endpoint, RRs0.94; confidence intervals (CI), 0.69-1.29 (Ps0.72). This is in contrast to the highly significant benefit of Metoprolol CRyXL observed in this sub-study population, RRs0.60; CI, 0.44-0.83 (Ps0.002). No effect of the polymorphism was observed on the magnitude of heart rate reduction attained by Metoprolol CRyXL. Conclusion: In contrast to the benefits of beta-1 selective blockade, we have demonstrated that the Gly389 allele does not confer a significant mortalityymorbidity benefit in heart failure patients. We have found no evidence of a pharmacogenetic effect of this biochemically functional polymorphism.

[1] An overview is presented of the meteorological and thermodynamic data obtained during the Radiative Atmospheric Divergence using Atmospheric Radiation Measurement (ARM) Mobile Facility, Geostationary Earth Radiation Budget (GERB) data, and African Monsoon Multidisciplinary Analysis (AMMA) stations (RADAGAST) experiment in Niamey, Niger, in 2006. RADAGAST combined data from the ARM Program Mobile Facility (AMF) at Niamey airport with broadband satellite data from the GERB instrument on Meteosat-8. The experiment was conducted in collaboration with the AMMA project. The focus in this paper is on the variations through the year of key surface and atmospheric variables. The seasonal advance and retreat of the Intertropical Front and the seasonal changes in near-surface variables and precipitation in 2006 are discussed and contrasted with the behavior in 2005 and with long-term averages. Observations from the AMF at Niamey airport are used to document the evolution of near-surface variables and of the atmosphere above the site. There are large seasonal changes in these variables, from the arid and dusty conditions typical of the dry season to the much moister and more cloudy wet season accompanying the arrival and intensification of the West African monsoon. Back trajectories show the origin of the air sampled at Niamey and profiles for selected case studies from rawinsondes and from a micropulse lidar at the AMF site reveal details of typical atmospheric structures. Radiative fluxes and divergences are discussed in the second part of this overview, and the subsequent papers in this special section explore other aspects of the measurements and of the associated modeling.

To explore the pharmacogenetic effects of the cytochrome P450 (CYP)2D6 genotype in patients with systolic heart failure treated using controlled/extended-release (CR/XL) metoprolol, this study assessed the CYP2D6 locus for the nonfunctional *4 allele (1846G>A; rs3892097) in the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF; n = 605). Participants were characterized as extensive, intermediate, or poor metabolizers (EMs, IMs, or PMs, respectively), based on the presence of the CYP2D6*4 allele (EM: *1*1, 60.4%; IM: *1*4, 35.8%; and PM: *4*4, 3.8%). Plasma metoprolol concentrations were 2.1-/4.6-fold greater in the IM/PM groups as compared with the EM group (P < 0.0001). Metoprolol induced significantly lower heart rates and diastolic blood pressures during early titration, indicating a CYP2D6*4 allele dose-response effect (P < 0.05). These effects were not observed at maximal dose, suggesting a saturable effect. Genotype did not adversely affect surrogate treatment efficacy. CYP2D6 genotype modulates metoprolol pharmacokinetics/pharmacodynamics during early titration; however, the MERIT-HF-defined titration schedule remains recommended for all patients, regardless of genotype.