Critical Analysis of the Value of Drought Information and Impacts on Land Management and Public Health

This paper reviews previous efforts to assign monetary value to climatic or meteorological information, such as public information on drought, climate, early warning systems, and weather forecast information. Methods and tools that have been explored to examine the benefits of climatic and meteorological information include the avoided cost, contingent valuation, choice experiments, benefit transfer, and descriptive approaches using surveys. The second part of this paper discusses specific considerations related to valuing drought information for public health and the Bureau of Land Management. We found a multitude of connections between drought and the land management and health sectors in the literature. The majority of the papers that we summarized only report biophysical change, because the economic losses of drought are not available. Only a few papers reported economic loss associated with drought. To determine the value of drought information, we need to know more about the role it plays in decision making and what sources of drought information are used in different sectors. This inventory of methods and impacts highlights opportunities for further research in valuing drought information in land management and public health

Valuation of Drought Information: Understanding the Value of the US Drought Monitor in Land Management

Droughts affect recreation and tourism, grazing, forests, and timber, and can have important indirect effects for the ecosystems and species that rely on water. Despite its importance, the effect of drought in the land management sector is less understood than in other water-intensive sectors, such as agriculture and public water supplies. This study presents the first-ever estimates of the economic valuation of the information provided by the U.S. Drought Monitor using the avoided cost method. These estimates are based on the time and labor saved by using the U.S. Drought Monitor rather than compiling drought-related information from other sources, or using other sources for tracking/monitoring droughts, communicating drought conditions, and dealing with drought-related issues. The results reflect rational behavior—the more time needed to compile or collect drought information provided by the U.S. Drought Monitor, the higher the dollar value in avoided cost. This dollar amount also varies by institution and organization, which indicates respondents from different organizations value the information from the U.S. Drought Monitor differently. For example, compared to the state offices, the field offices in the Bureau of Land Management value more of the information provided by the U.S. Drought Monitor. These estimates can be used to estimate the societal benefits and help policy makers evaluate the U.S. Drought Monitor in different sectors

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase. METHODS: We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety. RESULTS: Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P = 0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar-plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group. CONCLUSIONS: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. (Funded by Seattle Genetics; HER2CLIMB ClinicalTrials.gov number, NCT02614794.)

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. BET bromodomain inhibitors, which have shown efficacy in several models of cancer have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. BET bromodomain inhibitors, which have shown efficacy in several models of cancer, have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance

Critical Analysis of the Value of Drought Information and Impacts on Land Management and Public Health

This paper reviews previous efforts to assign monetary value to climatic or meteorological information, such as public information on drought, climate, early warning systems, and weather forecast information. Methods and tools that have been explored to examine the benefits of climatic and meteorological information include the avoided cost, contingent valuation, choice experiments, benefit transfer, and descriptive approaches using surveys. The second part of this paper discusses specific considerations related to valuing drought information for public health and the Bureau of Land Management. We found a multitude of connections between drought and the land management and health sectors in the literature. The majority of the papers that we summarized only report biophysical change, because the economic losses of drought are not available. Only a few papers reported economic loss associated with drought. To determine the value of drought information, we need to know more about the role it plays in decision making and what sources of drought information are used in different sectors. This inventory of methods and impacts highlights opportunities for further research in valuing drought information in land management and public health