A B S T R A C T A radioimmunoassay lhas

Increasing human appropriation of freshwater resources presents a tangible limit to the sustainability of cities, agriculture, and ecosystems in the western United States. Marc Reisner tackles this theme in his 1986 classic Cadillac Desert: The American West and Its Disappearing Water . Reisner's analysis paints a portrait of region-wide hydrologic dysfunction in the western United States, suggesting that the storage capacity of reservoirs will be impaired by sediment infilling, croplands will be rendered infertile by salt, and water scarcity will pit growing desert cities against agribusiness in the face of dwindling water resources. Here we evaluate these claims using the best available data and scientific tools. Our analysis provides strong scientific support for many of Reisner's claims, except the notion that reservoir storage is imminently threatened by sediment. More broadly, we estimate that the equivalent of nearly 76% of streamflow in the Cadillac Desert region is currently appropriated by humans, and this figure could rise to nearly 86% under a doubling of the region's population. Thus, Reisner's incisive journalism led him to the same conclusions as those rendered by copious data, modern scientific tools, and the application of a more genuine scientific method. We close with a prospectus for reclaiming freshwater sustainability in the Cadillac Desert, including a suite of recommendations for reducing region-wide human appropriation of streamflow to a target level of 60%.

A B S T R A C T Mean plasma 1,,25-dihydroxyvitamin D [1,,25(OH)2D] was significantly increased and serum parathyroid hormone was suppressed in three patients with sarcoidosis and hypercalcemia. Prednisone lowered the mean plasma 1,,25(OH)2D to normal range and corrected the hypercalcemia. To elucidate the mechanism for the increased sensitivity to vitamin D in this disorder, the effects of orally-administered vitamin D2 were determined in seven normal subjects, four patients with sarcoidosis and normal calcium metabolism and three patients with sarcoidosis and a history of hypercalcemia who were normocalcemic when studied. Serum and urinary calcium, serum 25-hydroxyvitamin D (25-OHD), plasma 1a,,25(OH)2D and, in some studies, calcium balance were measured. Vitamin D2, 250 ,ug a day for 12 d, produced little, ifany, change in mean plasma 1a,25(OH)2D and in urinary calcium in the normals and in the patients with normal calcium metabolism. In contrast, vitamin D2 produced increases in plasma 10,,25(OH)2D from concentrations which were within the normal range (20-55 pg/ml) to abnormal values and increased urinary calcium in two patients with abnormal calcium metabolism. In an abbreviated study in the third patient, vitamin D2, 250 ,ug a day for 4 d, also increased plasma 1,,25(OH)2D abnormally from a normal value. There was a highly significant correlation between plasma 1,,25(OH)2D and urinary calcium. Serum 25-OHD and serum calcium remained within the normal range in all subjects and patients. These findings provide evidence that the defect in calcium metabolism in sarcoidosis probably results from impaired regulation of the production and(or) degrada-

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Reservoirs are sustainable only as long as they offer sufficient water storage space to achieve their design objectives. Life expectancy related to sedimentation is a measure of reservoir sustainability. We used data from the Army Corps of Engineers, U.S. Bureau of Reclamation, and U.S. Geological Survey (Reservoir Sedimentation Survey Information System II (RESIS II)) to explore the sustainability of American reservoirs. Sustainability varied by region, with the longest life expectancies in New England and the Tennessee Valley and the shortest in the interior west. In the Missouri and Colorado River basins, sedimentation and rates of loss of reservoir storage capacity were highly variable in time and space. In the Missouri River Basin, the larger reservoirs had the longest life expectancies, with some exceeding 1000 years, while smaller reservoirs in the basin had the shortest life expectancies. In the Colorado River Basin at the site of Glen Canyon Dam, sediment inflow varied with time, declining by half beginning in 1942 because of hydroclimate and upstream geomorphic changes. Because of these changes, the estimated life expectancy of Lake Powell increased from 300 to 700 years. Future surprise changes in sedimentation delivery and reservoir filling area are expected. Even though large western reservoirs were built within a limited period, their demise will not be synchronous because of varying sedimentation rates. Popular literature has incorrectly emphasized the possibility of rapid, synchronous loss of reservoir storage capacity and underestimated the sustainability of the water control infrastructure.

Purpose: To assess the short-term efficacy and safety profile of intravitreal brolucizumab injection in Indian eyes with neovascular age-related macular degeneration (nAMD) under real-world conditions. Patients and Methods: This was a multicenter, retrospective chart review of 94 eyes of 94 patients with nAMD (treatment-naïve and switch-therapy) undergoing brolucizumab therapy. Re-treatment as per pro-re-nata protocol was performed based on fixed visual and tomographic criteria. The main outcome measures were changes in the best-corrected visual acuity (BCVA), intraretinal fluid (IRF), subretinal fluid (SRF), central subfield thickness (CST), and pigment epithelial detachment (PED) along with safety analysis. Results: Of the 94 eyes, 20 eyes (21.3%) were treatment-naïve, whereas the rest 74 eyes (78.7%) underwent switch therapy. One hundred and twenty-six injections were given over a mean followup of 7.3 ± 2.2 (range 5-30) weeks. The BCVA improved significantly from 0.82 ± 0.5 LogMAR at baseline to 0.66 ± 0.5 LogMAR at the final visit (p < 0.0001). Significant reduction in CST was simultaneously noted (Baseline: 408.45 ± 65.63 µm; Final: 281.14 ± 37.74 µm; p < 0.0001). On qualitative analysis, resolution of subretinal fluid (SRF), intraretinal fluid (IRF), and pigment epithelial detachment (PED) was observed in 15.5%, 39.29%, and 23.81% of the eyes, respectively. The mean interval of repeat injection was 10.2 ± 2.1 weeks. Three episodes of ocular adverse drug reaction were reported, including two patients developing subretinal hemorrhage while one having a retinal pigment epithelial (RPE) tear. Notably, no intraocular inflammation (IOI) was seen in any of the eyes, and no systemic side effects were identified. Conclusion:In a real-world scenario, brolucizumab therapy is efficacious and safe in the management of nAMD over the short term. Further long-term studies are warranted to validate these findings. Additionally, lack of ocular inflammation after 126 brolucizumab injections in our Indian data is peculiar and underlines the necessity to explore the role of race and genetics in predisposing to/safeguarding against brolucizumab-related IOIs.

Abstract. Skillful seasonal streamflow forecasts obtained from climate and land surface conditions could significantly improve water and energy management. Since climate forecasts are updated on a monthly basis, we evaluate the potential in developing operational monthly streamflow forecasts on a continuous basis throughout the year. Further, basins in the rainfall-runoff regime critically depend on the forecasted precipitation in the upcoming months as opposed to snowmelt regimes where initial hydrological conditions (IHC) play a critical role. The goal of this study is to quantify the role of updated monthly precipitation forecasts and IHC in forecasting 6-month lead monthly streamflow and soil moisture for a rainfall-runoff mechanism dominated basin -Apalachicola River at Chattahoochee, FL. The Variable Infiltration Capacity (VIC) land surface model is implemented with two forcings: (a) updated monthly precipitation forecasts from ECHAM4.5 Atmospheric General Circulation Model (AGCM) forced with sea surface temperature forecasts and (b) daily climatological ensembles. The difference in skill between the above two quantifies the improvements that could be attainable using the AGCM forecasts. Monthly retrospective streamflow forecasts are developed from 1981 to 2010 and streamflow forecasts estimated from the VIC model are also compared with those predicted by using the principal component regression (PCR) model. The mean square error (MSE) in predicting monthly streamflows, using the VIC model, are compared with the MSE of streamflow climatology under ENSO (El Niño Southern Oscilation) conditions as well as under normal years. Results indicate that VIC forecasts obtained using ECHAM4.5 are significantly better than VIC forecasts obtained using climatological ensembles and PCR models over 2-6 month lead time during winter and spring seasons in capturing streamflow variability and reduced mean square errors. However, at 1-month lead time, streamflow utilizing the climatological forcing scheme outperformed ECHAM4.5 based streamflow forecasts during winter and spring, indicating a dominant role of IHCs up to a 1-month lead time. During ENSO years, streamflow forecasts exhibit better skill even up to a six-month lead time.Comparisons of the seasonal soil moisture forecasts, developed using ECHAM4.5 forcings, with seasonal streamflows also show significant skill, up to a 6-month lead time, in the four seasons.

Seasonal cycles of freezing and thawing influence surface energy and water cycle fluxes. Specifically, soil frost can lead to the reduction in infiltration and an increase in runoff response, resulting in a greater potential for soil erosion. An increase in the number of soil freeze-thaw cycles may reduce soil compaction, which could affect various hydrologic processes. In this study, the authors test for the presence of significant trends in soil freeze-thaw cycles and soil temperatures at several depths and compare these with other climatic variables including air temperature, snowfall, snow cover, and precipitation. Data for the study were obtained for three research stations located in northern, central, and southern Indiana that have collected soil temperature observations since 1966. After screening for significant autocorrelations, testing for trends is conducted at a significance level of 5% using Mann-Kendall's test. Observations from 1967 to 2006 indicate that air temperatures during the cold season are increasing at all three locations, but there is no significant change in seasonal and annual average precipitation. At the central and southern Indiana sites, soil temperatures are generally warming under a bare soil surface, with significant reductions in the number of days with soil frost and freeze-thaw cycles for some depths. Meanwhile, 5-cm soils at the northernmost site are experiencing significant decreases in cold season temperatures, as an observed decrease in annual snowfall at the site is counteracting the increase in air temperature. Seasonal mean maximum soil temperatures under grass cover are increasing at the southernmost site; however, at the central site, it appears that seasonal minimum soil temperatures are decreasing and the number of freezethaw cycles is increasing.