We present spatially distributed seasonal and annual surface mass balances of Wolverine Glacier, Alaska, from 2016 to 2020. Our approach accounts for the effects of ice emergence and firn compaction on surface elevation changes to resolve the spatial patterns in mass balance at 10 m scale. We present and compare three methods for estimating emergence velocities. Firn compaction was constrained by optimizing a firn model to fit three firn cores. Distributed mass balances showed good agreement with mass-balance stakes (RMSE = 0.67 m w.e., r = 0.99, n = 41) and ground-penetrating radar surveys (RMSE = 0.36 m w.e., r = 0.85, n = 9024). Fundamental differences in the distributions of seasonal balances highlight the importance of disparate physical processes, with anomalously high ablation rates observed in icefalls. Winter balances were found to be positively skewed when controlling for elevation, while summer and annual balances were negatively skewed. We show that only a small percent of the glacier surface represents ideal locations for mass-balance stake placement. Importantly, no suitable areas are found near the terminus or in elevation bands dominated by icefalls. These findings offer explanations for the often-needed geodetic calibrations of glaciological time series.

We reanalyzed mass balance records at Taku and Lemon Creek Glaciers to better understand the relative roles of hypsometry, local climate and dynamics as mass balance drivers. Over the 1946–2018 period, the cumulative mass balances diverged. Tidewater Taku Glacier advanced and gained mass at an average rate of +0.25 ± 0.28 m w.e. a–1, contrasting with retreat and mass loss of −0.60 ± 0.15 m w.e. a−1 at land-terminating Lemon Creek Glacier. The uniform influence of regional climate is demonstrated by strong correlations among annual mass balance and climate data. Regional warming trends forced similar statistically significant decreases in surface mass balance after 1989: −0.83 m w.e. a–1 at Taku Glacier and −0.81 m w.e. a–1 at Lemon Creek Glacier. Divergence in cumulative mass balance arises from differences in glacier hypsometry and local climate. Since 2013 negative mass balance and glacier-wide thinning prevailed at Taku Glacier. These changes initiated terminus retreat, which could increase dramatically if calving begins. The future mass balance trajectory of Taku Glacier hinges on dynamics, likely ending the historic dichotomy between these glaciers.

Mountain glaciers integrate climate processes to provide an unmatched signal of regional climate forcing. However, extracting the climate signal via intercomparison of regional glacier mass-balance records can be problematic when methods for extrapolating and calibrating direct glaciological measurements are mixed or inconsistent. To address this problem, we reanalyzed and compared long-term mass-balance records from the US Geological Survey Benchmark Glaciers. These five glaciers span maritime and continental climate regimes of the western United States and Alaska. Each glacier exhibits cumulative mass loss since the mid-20th century, with average rates ranging from −0.58 to −0.30 m w.e. a−1. We produced a set of solutions using different extrapolation and calibration methods to inform uncertainty estimates, which range from 0.22 to 0.44 m w.e. a−1. Mass losses are primarily driven by increasing summer warming. Continentality exerts a stronger control on mass loss than latitude. Similar to elevation, topographic shading, snow redistribution and glacier surface features often exert important mass-balance controls. The reanalysis underscores the value of geodetic calibration to resolve mass-balance magnitude, as well as the irreplaceable value of direct measurements in contributing to the process-based understanding of glacier mass balance.

Previously we have examined the effects of diets deficient in folic acid ( − F) or folate deficient with low methionine and choline ( − F LM LC) on the relative abundance of soluble proteins in the liver of the pregnant rat. In the present study we report the corresponding changes in the fetal liver at day 21 of gestation. The abundance of eighteen proteins increased when dams were fed the − F diet. When dams were fed the − F LM LC diet, thirty-three proteins increased and eight decreased. Many of the differentially abundant proteins in the fetal liver could be classified into the same functional groups as those previously identified in the maternal liver, namely protein synthesis, metabolism, lipid metabolism and proteins associated with the cytoskeleton and endoplasmic reticulum. The pattern was consistent with reduced cell proliferation in the − F LM LC group but not in the − F group. Metabolic enzymes associated with lipid metabolism changed in both the − F and − F LM LC groups. The mRNA for carnitine palmitoyl transferase were up-regulated and CD36 (fatty acid translocase) down-regulated in the − F group, suggesting increased mitochondrial oxidation of fatty acids as an indirect response to altered maternal lipid metabolism. In the − F LM LC group the mRNA for acetyl CoA carboxylase was down-regulated, suggesting reduced fatty acid synthesis. The mRNA for transcriptional regulators including PPARα and sterol response element-binding protein-1c were unchanged. These results suggest that an adequate supply of folic acid and the related methyl donors may benefit fetal development directly by improving lipid metabolism in fetal as well as maternal tissues.

The importance of folic acid and the methionine cycle in fetal development is well recognised even though the mechanism has not been established. Since the cycle is active in the maternal liver, poor folate status may modify hepatic metabolism. Pregnant rats were fed diets deficient in folic acid (–F) or in three key methyl donors, folic acid, choline and methionine (–FLMLC) and the maternal liver was analysed on day 21 of gestation. Two-dimensional gel electrophoresis of soluble proteins identified differentially abundant proteins, which could be allocated into nine functional groups. Five involved in metabolic processes, namely, folate/methionine cycle, tyrosine metabolism, protein metabolism, energy metabolism and lipid metabolism, and three in cellular processes, namely, endoplasmic reticulum function, bile production and antioxidant defence. The mRNA for sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase-1 (fatty acid synthesis) were decreased by both –F and –FLMLC diets. The mRNA for PPARα and PPARγ and carnitine palmitoyl transferase (fatty acid oxidation) were increased in the animals fed the –FLMLC diets. Changes in the abundance of proteins associated with intracellular lipid transport suggest that folate deficiency interferes with lipid export. Reduced fatty acid synthesis appeared to prevent steatosis in animals fed the –F diet. Even with increased oxidation, TAG concentrations were approximately three-fold higher in animals fed the –FLMLC diet and were associated with an increase in the relative abundance of proteins associated with oxidative stress. Fetal development may be indirectly affected by these changes in hepatic lipid metabolism.

Aims: Bosentan is efficacious in idiopathic pulmonary arterial hypertension, and the variants associated with connective tissue disease, but not currently approved for treatment of pulmonary arterial hypertension due to Eisenmenger's syndrome. We sought to evaluate its effect in adults with Eisenmenger's syndrome. Methods: We administered bosentan on the basis of compassionate use in 23 patients with Eisenmenger's syndrome, aged 37 plus or minus 14 years. Of the patients, 17 had never received specific treatment for pulmonary arterial hypertension, five were transitioned from treprostinil, and one from beraprost to bosentan. We measured functional class, saturation of oxygen, haemoglobin levels and six-minute walk distance at baseline, one, six months and at most recent follow-up. Results: Baseline functional class was IV in three, III in fifteen, and II in five patients. At follow-up, with a mean of 15 plus or minus 10 months, 13 of the 23 patients (57%) had improved by at least one functional class, from a median baseline of III to II (p equal to 0.016), mean saturation of oxygen at rest had increased from 81% to 84% (p equal to 0.001), and levels of haemoglobin had decreased from 178 plus or minus 26 grams per litre to 167 plus or minus 19 grams per litre (p equal to 0.001). Overall, the six-minute walk distance did not change from baseline of 335 metres. The distance walked by those not previously receiving specific therapy, however, improved from 318 plus or minus 129 to 345 plus or minus 123 metres (p equal to 0.03). Conclusion: Treatment of adults with Eisenmenger's syndrome using bosentan significantly improved functional class, saturation of oxygen at rest, and decreased levels of haemoglobin. Treatment with bosentan was associated with improvement in six-minute walk distance in those not previously receiving specific therapy. In patients already in receipt of specific therapy, transition to bosentan resulted in no clinical deterioration.