The influence of weathering and soil organic matter on Zn isotopes in soils

Zinc is an essential micronutrient that is ultimately released during mineral weathering. In soils, organic matter plays a key role in influencing Zn partitioning and therefore on Zn biogeochemical cycling. Soil organic matter is partitioned between carbon that is more readily available for decomposition by microorganisms, and more stable carbon transiently preserved from decomposition. The role of the stable pool of soil organic matter on Zn biogeochemical cycling remains poorly understood. The pool of stable carbon is controlled by combination with mineral constituents or is material that is intrinsically resistant to decomposition. The Zn stable isotopes are fractionated by interactions between Zn and soil mineral and organic constituents. This study reports the Zn isotope composition of five Icelandic soil profiles derived from the same parent basalt and characterized by contrasting degrees of weathering and organic matter content (δ66Zn = + 0.10 ± 0.05 to + 0.35 ± 0.02‰), the distribution of reactive mineral constituents available to form associations with soil organic matter, and the amount of stable organic carbon. Throughout these soils, the δ66Zn isotope variations are little influenced by mineral constituents, but rather by soil organic matter content. These data suggest that a combination of organic matter accumulation and Zn loss by leaching is required to explain the observed decrease in Zn concentration in soils and lighter soil δ66Zn with increasing organic carbon content. These results suggest that the presence of stable organic carbon in soils provides a pool of light Zn, attributed to the Zn isotope signature of organic matter partially preserved from decomposition. Crucially, this stable organic carbon pool may also contribute to the formation of the light Zn isotope sink reported in organic-rich marine sediments, a key output required to explain the oceanic mass balance of Zn isotopes

The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma

Background The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study. Objective This report provides long-term follow-up data collected up to 12 months after the last patient was randomized. Methods In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review. Results Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively). Limitations No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved. Conclusion With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC. © 2016 American Academy of Dermatology, Inc