Limnology in the North American Arctic and Subarctic

Distribution of arctic lakes is noted and the literature reviewed. General problems in arctic limnology include thermal and trophic classifications, water circulation, productivity as compared with arctic marine waters, and comparison of arctic and alpine lakes. Future research programs should comprise a reconnaissance of lakes in the Canadian Arctic, intensive investigation of selected lakes and a river, expansion of Ungava work and general studies on distribution of fresh-water fish. Cooperation between limnologists, plant ecologists, and geologists is urged

Limnology in the North American Arctic and Subarctic

Distribution of arctic lakes is noted and the literature reviewed. General problems in arctic limnology include thermal and trophic classifications, water circulation, productivity as compared with arctic marine waters, and comparison of arctic and alpine lakes. Future research programs should comprise a reconnaissance of lakes in the Canadian Arctic, intensive investigation of selected lakes and a river, expansion of Ungava work, and general studies on distribution of fresh-water fish. Cooperation between limnologists, plant ecologists, and geologists is urged

IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma

Neoadjuvant ipilimumab + nivolumab has demonstrated high pathologic response rates in stage III melanoma. Patients with low intra-tumoral interferon-γ (IFN-γ) signatures are less likely to benefit. We show that domatinostat (a class I histone deacetylase inhibitor) addition to anti-PD-1 + anti-CTLA-4 increased the IFN-γ response and reduced tumor growth in our murine melanoma model, rationalizing evaluation in patients. To stratify patients into IFN-γ high and low cohorts, we developed a baseline IFN-γ signature expression algorithm, which was prospectively tested in the DONIMI trial. Patients with stage III melanoma and high intra-tumoral IFN-γ scores were randomized to neoadjuvant nivolumab or nivolumab + domatinostat, while patients with low IFN-γ scores received nivolumab + domatinostat or ipilimumab + nivolumab + domatinostat. Domatinostat addition to neoadjuvant nivolumab ± ipilimumab did not delay surgery but induced unexpected severe skin toxicity, hampering domatinostat dose escalation. At studied dose levels, domatinostat addition did not increase treatment efficacy. The baseline IFN-γ score adequately differentiated patients who were likely to benefit from nivolumab alone versus patients who require other therapies. Analysis and support of clinical decision makin