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Supplementary Table S1 from Genetic Changes of Wnt Pathway Genes Are Common Events in Metaplastic Carcinomas of the Breast

Purpose: Metaplastic carcinomas are distinct invasive breast carcinomas with aberrant nonglandular differentiation, which may be spindle, squamous, or chondroid. The limited effective treatments result from the lack of knowledge of its molecular etiology. Given the role of the Wnt pathway in cell fate and in the development of breast cancer, we hypothesized that defects in this pathway may contribute to the development of metaplastic carcinomas.Design: In 36 primary metaplastic carcinomas, we comprehensively determined the prevalence of and mechanism underlying β-catenin and Wnt pathway deregulation using immunohistochemistry for β-catenin expression and localization and mutational analysis for CTNNB1 (encoding β-catenin), APC, WISP3, AXIN1, and AXIN2 genes. By immunohistochemistry, normal β-catenin was seen as membrane staining, and it was aberrant when >5% of tumor cells had nuclear or cytoplasmic accumulation or reduced membrane staining.Results: By immunohistochemistry, aberrant β-catenin was present in 33 of 36 (92%) cases, revealing deregulation of the Wnt pathway. CTNNB1 missense mutations were detected in 7 of 27 (25.9%) tumors available for mutation analyses. All mutations affected the NH2-terminal domain of β-catenin, presumably rendering the mutant protein resistant to degradation. Two of 27 (7.4%) tumors had mutations of APC, and 5 (18.5%) carried a frame shift mutation of WISP3. No AXIN1 or AXIN2 mutations were found.Conclusions: Activation of the Wnt signaling pathway is common in this specific subtype of breast carcinoma. The discovery of CTNNB1, APC, and WISP3 mutations may result in new treatments for patients with metaplastic carcinomas of the breast.

Drought-related decision-making and policy should go beyond numeric hydrometeorological data to incorporate information on how drought affects people, livelihoods, and ecosystems. The effects of drought are nested within environmental and human systems, and relevant data may not exist in readily accessible form. For example, drought may reduce forage growth, compounded by both late-season freezes and management decisions. An effort to gather crowdsourced drought observations in Missouri in 2018 yielded a much higher number of observations than did previous related efforts. Here we examine 1) the interests, circumstances, history, and recruitment messaging that coincided to produce a high number of reports in a short time; 2) whether and how information from volunteer observers was useful to state decision-makers and to U.S. Drought Monitor (USDM) authors; and 3) potential for complementary use of stakeholder and citizen science reports in assessing trustworthiness of volunteer-provided information. State officials and the Cattlemen’s Association made requests for reports, clearly linked to improving the accuracy of the USDM and the related financial benefit. Well-timed requests provided a focus for people’s energy and a reason to invest their time. State officials made use of the dense spatial coverage that observers provided. USDM authors were very cautious about a surge of reports coinciding closely with financial incentives linked to the Livestock Forage Disaster program. An after-the-fact comparison between stakeholder reports and parallel citizen science reports suggests that the two could be complementary, with potential for developing protocols to facilitate real-time use.

Land-use land-cover change (LULCC) has become an important topic of research for the central United States because of the extensive conversion of the natural prairie into agricultural land, especially in the northern Great Plains. As a result, shifts in the natural climate (minimum/maximum temperature, precipitation, etc.) across the north-central United States have been observed, as noted within the Fourth National Climate Assessment (NCA4) report. Thus, it is necessary to understand how further LULCC will affect the near-surface atmosphere, the lower troposphere, and the planetary boundary layer (PBL) atmosphere over this region. The goal of this work was to investigate the utility of a new future land-use land-cover (LULC) dataset within the Weather Research and Forecasting (WRF) modeling system. The present study utilizes a modeled future land-use dataset developed by the Forecasting Scenarios of Land-Use Change (FORE-SCE) model to investigate the influence of future (2050) land use on a simulated PBL development within the WRF Model. Three primary areas of LULCC were identified within the FORE-SCE future LULC dataset across Nebraska and South Dakota. Variations in LULC between the 2005 LULC control simulation and four FORE-SCE simulations affected near-surface temperature (0.5°–1°C) and specific humidity (0.3–0.5 g kg−1). The differences noted in the temperature and moisture fields affected the development of the simulated PBL, leading to variations in PBL height and convective available potential energy. Overall, utilizing the FORE-SCE dataset within WRF produced notable differences relative to the control simulation over areas of LULCC represented in the FORE-SCE dataset.

Drought contingency planning is an increasingly common tool in the ranchers’ climate adaptation toolboxes, but its effect on drought response has not yet been evaluated. We use cognitive models of protective action decision making and planning to explore the effects of having a drought plan on the use of drought early warning information and drought response (and timing). Results of a cross-sectional, probability-based survey of livestock producers affected by a 2016 flash-drought are used to describe the characteristics of operations with drought plans and provide evidence of whether having a plan predicts drought information use and response. While larger operations are more likely than others to have plans for drought, having a drought plan appears to play a unique role in ranchers’ use of information and decision making regardless of operation size. Findings suggest that encouraging the use of drought contingency planning may improve ranchers’ adaptive capacity. Increased use of planning may also increase the effectiveness of communicating risk and early warning information, by making such information more actionable by decision makers.

The Middle East and North Africa region experiences severe socioeconomic and political impacts during droughts and faces increasing drought risk in future climate projections. The UN Office for Disaster Risk Reduction’s Sendai Framework and the International Drought Management Programme provide a global standard (a norm) to manage droughts through natural hazard risk reduction approaches. We use participatory engagement to evaluate whether norm diffusion has taken place in four countries. Data were collected in interviews, focus groups, workshops, and policy documents. Analysis reveals incomplete norm diffusion; stakeholders subscribe to relevant values, but national policies and implementation do not fully reflect the norm. Process tracing reveals that the availability of drought early warning data is a key barrier to risk reduction. Further more, a drought early warning system would not be feasible or sufficient unless paired with policy measures and financial mechanisms to reduce the political and economic costs of a drought declaration.

State climatologists and other expert drought observers have speculated about the value of monitoring Twitter for #drought and related hashtags. This study statistically examines the relationships between the rate of tweeting using #drought and related hashtags, within states, accounting for drought status and news coverage of drought. We collected and geolocated tweets, 2017–18, and used regression analysis and a diversity statistic to explain expected and identify unexpected volumes of tweets. This provides a quantifiable means to detect state-weeks with a volume of tweets that exceeds the upper limit of the prediction interval. To filter out instances where a high volume of tweets is related to the activities of one person or very few people, a diversity statistic was used to eliminate anomalous state-weeks where the diversity statistic did not exceed the 75th percentile of the range for that state’s diversity statistic. Anomalous state-weeks in a few cases preceded the onset of drought but more often coincided with or lagged increases in drought. Tweets are both a means of sharing original experience and a means of discussing news and other recent events, and anomalous weeks occurred throughout the course of a drought, not just at the beginning. A sum-to-zero contrast coefficient for each state revealed a difference in the propensity of different states to tweet about drought, apparently reflecting recent and long-term experience in those states, and suggesting locales that would be most predisposed to drought policy innovation.

The U.S. Drought Monitor (USDM), a weekly map depicting severity and spatial extent of drought, is used to communicate about drought in state and federal decision-making, and as a trigger in response policies, including the distribution of hundreds of millions of dollars for agricultural financial relief in the United States annually. An accompanying classification table helps interpret the map and includes a column of possible impacts associated with each level of drought severity. However, the column describing potential drought impacts is generalized for the entire United States. To provide more geographically specific interpretation of drought, state and regionally specific drought impact classification tables were developed by linking impacts chronicled in the Drought Impact Reporter (DIR) to USDM severity levels across the United States and Puerto Rico and identifying recurrent themes at each level. After creating state-level tables of impacts observed for each level of drought, a nationwide survey was administered to drought experts and decision-makers (n = 89), including the USDM authors, to understand whether the tables provided accurate descriptions of drought impacts in their state. Seventy-six percent of respondents indicated the state table was an acceptable or good characterization of drought impacts for their respective state. This classification scheme was created with a reproducible qualitative methodology that used past observations to identify themes in drought impacts across multiple sectors to concisely describe expected impacts at different levels of drought in each state.

When drought hits water-scarce regions, there are significant repercussions for food and water security, as well as serious issues for the stability of broader social and environmental systems. To mitigate these effects, environmental monitoring and early warning systems aimed at detecting the onset of drought conditions can facilitate timely and effective responses from government and private sector stakeholders. This study uses multistage, participatory research methods across more than 135 interviews, focus groups, and workshops to assess extant climatic, agricultural, hydrological, and drought monitoring systems; key cross-sector drought impacts; and drought monitoring needs in four countries in the Middle East and North Africa (MENA) region: Morocco, Tunisia, Lebanon, and Jordan. This extensive study of user needs for drought monitoring across the MENA region is informing and shaping the ongoing development of drought early warning systems, a composite drought indicator (CDI), and wider drought management systems in each country. Overarching themes of drought monitoring needs include technical definitions of drought for policy purposes; information-sharing regimes and data-sharing platforms; ground-truthing of remotely sensed and modeled data; improved data quality in observation networks; and two-way engagement with farmers, organizations, and end-users of drought monitoring products. This research establishes a basis for informing enhanced drought monitoring and management in the countries, and the broad stakeholder engagement can help foster the emergence of effective environmental monitoring coalitions.

Heatwaves cause excess mortality and physiological impacts on humans throughout the world, and climate change will intensify and increase the frequency of heat events. Many adaptation and mitigation studies use spatial distribution of highly vulnerable local populations to inform heat reduction and response plans. However, most available heat vulnerability studies focus on urban areas with high heat intensification by Urban Heat Islands (UHIs). Rural areas encompass different environmental and socioeconomic issues that require alternate analyses of vulnerability. We categorized Nebraska census tracts into four urbanization levels, then conducted factor analyses on each group and captured different patterns of socioeconomic vulnerabilities among resultant Heat Vulnerability Indices (HVIs). While disability is the major component of HVI in two urbanized classes, lower education, and races other than white have higher contributions in HVI for the two rural classes. To account for environmental vulnerability of HVI, we considered different land type combinations for each urban class based on their percentage areas and their differences in heat intensifications. Our results demonstrate different combinations of initial variables in heat vulnerability among urban classes of Nebraska and clustering of high and low heat vulnerable areas within the highest urbanized sections. Less urbanized areas show no spatial clustering of HVI. More studies with separation on urbanization level of residence can give insights into different socioeconomic vulnerability patterns in rural and urban areas, while also identifying changes in environmental variables that better capture heat intensification in rural settings., Key Points Despite similar incidence rates, Heat Vulnerability Index (HVI) in rural areas is under studied in comparison to urban areasThe environmental vulnerability variables in rural areas are dissimilar to urban areas, so we applied different variables to calculate themWe found different organization of socioeconomic variables in calculated HVIs, suggesting separate heat strategies for urbanization levels

Drought is an inescapable reality in many regions, including much of the western United States. With climate change, droughts are predicted to intensify and occur more frequently, making the imperative for drought management even greater. Many diverse actors – including private landowners, business owners, scientists, non-governmental organizations (NGOs), and managers and policymakers within tribal, local, state, and federal government agencies – play multiple, often overlapping roles in preparing for and responding to drought. Managing water is, of course, one of the most important roles that humans play in both mitigating and responding to droughts; but, focusing only on “water managers” or “water management” fails to capture key elements related to the broader category of drought management. The respective roles played by those managing drought (as distinct from water managers), the interactions among them, and the consequences in particular contexts, are not well understood. Our team synthesized insights from 10 in-depth case studies to understand key facets of decision making about drought preparedness and response. We present a typology with four elements that collectively describe how decisions about drought preparedness and response are made (context and objective for a decision; actors responsible; choice being made or action taken; and how decisions interact with and influence other decisions). The typology provides a framework for system-level understanding of how and by whom complex decisions about drought management are made. Greater system-level understanding helps decision makers, program and research funders, and scientists to identify constraints to and opportunities for action, to learn from the past, and to integrate ecological impacts, thereby facilitating social learning among diverse participants in drought preparedness and response.

The combination of decreased water availability and increased temperatures can interfere with outdoor activities, particularly with surface water decline and the increased risk of wildfire. Drought is a longer-term climate trend, but there is a tendency toward short-term reactions only when a drought occurs. Policy mechanisms for drought, where present, are often left to managerial discretion because they are not needed every year, and lack specific indicators. Recreator choices contribute to adaptation and public lands managers also shape drought response by monitoring meteorological trends and managing resources wisely. Despite these trends, no singular recreational drought definition exists. To understand socio-environmental interactions from a management perspective, this study synthesizes interview findings to provide in-depth insight about drought monitoring, impacts, and management across a variety of ecological regions in Nebraska state parks. Collectively, the eight participating superintendents oversee more than 152 km2 of land, approximately 287 km2 of surface water, and more than 364 km of lakeshore. The emergent properties of drought in the recreation sector include a shortage of naturally available water needed for vegetation health and animal habitat, to support lake sports, to prevent permanent infrastructure damage, and maintain visitor volumes for economic stability. The study concludes with recommendations for increasing drought resilience within the sector.

Remnant populations of Betula papyrifera Marshall have persisted in the Great Plains after the Wisconsin Glaciation along the Niobrara River Valley, Nebraska. Population health has declined in recent years, which has been hypothesized to be due to climate change. We used dendrochronological techniques to assess the response of B. papyrifera to microclimate (1950–2014) and the normalized difference vegetation index (NDVI) derived from satellite imagery (Landsat 5 TM (1985–2011) and MODIS (2000–2014)) as a proxy for population health. Growing-season streamflow and precipitation were positively correlated with raw and standardized tree-ring widths and basal area increment increase. Increasing winter and spring temperatures were unfavorable for tree growth, while increasing summer temperatures were favorable in the absence of drought. The strongest predictor for standardized tree rings was the Palmer Drought Severity Index, suggesting that B. papyrifera is highly responsive to a combination of temperature and water availability. The NDVI from the vegetation community was positively correlated with standardized tree-ring growth, indicating the potential of these techniques to be used as a proxy for ex situ monitoring of B. papyrifera. These results aid in forecasting the dynamics of the species in the face of climate variability and change in both remnant populations and across its current distribution in northern latitudes of North America.

In Great Plains rangelands, drought is a recurring disturbance. Ranchers in this region expect to encounter drought but may not be adequately prepared for it. Efforts to encourage drought preparedness would benefit from a better understanding of the conditions under which managers make decisions to minimize the impacts of drought. We tested the direct and moderating roles of the drought hazard and the social-ecological context on drought impacts and response. This study was conducted with ranchers in western and central South Dakota and Nebraska following the drought that began in 2012. We surveyed ranchers regarding the effects of the drought and their responses and used multimodel analysis to explore the relationships among measures of drought preparedness, drought response, and drought impacts. Drought severity was the primary predictor of all impacts, but specific types of impacts were varied depending on the operation’s enterprise mix, resources, and management. The socioecological characteristics of the ranch system predicted drought response actions taken, by either providing the necessary resources and capacity to take action or creating sensitivity in the system that required action to be taken. We conclude with recommendations for learning from current drought experiences in order to better adapt to future drought events.

Drought is an abstract and complex phenomenon that can be difficult for many people to comprehend. Proactive planning to improve response during drought events is necessary but complicated because it involves stakeholders and decision-makers with competing interests. A category of games, called serious games, have proven to be helpful when learning about abstract concepts, and for improving communication and conflict resolution with respect to water-related issues. In this study, we present a new in-person role-playing game that serves as a drought educational tool in both classroom and professional settings. The message of the game emphasizes the importance of communication and cooperation between various communities and sectors that can be affected by drought. Furthermore, it also encourages discussions and collaborations between stakeholders involved in drought planning and can serve as an icebreaker activity. The game has been played in a variety of settings including university classes, university extension workshops, and drought workshops. This study describes the game itself, its development, and the results of surveys from game participants that were used to evaluate the usability of the game as an educational and icebreaker activity.

We used monthly precipitation and temperature data to give early warning of years with higher West Nile Virus (WNV) risk in Nebraska. We used generalized additive models with a negative binomial distribution and smoothing curves to identify combinations of extremes and timing that had the most influence, experimenting with all combinations of temperature and drought data, lagged by 12, 18, 24, 30, and 36 months. We fit models on data from 2002 through 2011, used Akaike's Information Criterion (AIC) to select the best‐fitting model, and used 2012 as out‐of‐sample data for prediction, and repeated this process for each successive year, ending with fitting models on 2002–2017 data and using 2018 for out‐of‐sample prediction. We found that warm temperatures and a dry year preceded by a wet year were the strongest predictors of cases of WNV. Our models did significantly better than random chance and better than an annual persistence naïve model at predicting which counties would have cases. Exploring different scenarios, the model predicted that without drought, there would have been 26% fewer cases of WNV in Nebraska through 2018; without warm temperatures, 29% fewer; and with neither drought nor warmth, 45% fewer. This method for assessing the influence of different combinations of extremes at different time intervals is likely applicable to diseases other than West Nile, and to other annual outcome variables such as crop yield., Key Points A dry year preceded by a wet year in combination with warm temperatures increases the number of human cases of West Nile Virus in NebraskaWe found that drought accounted for 26% of WNV cases 2002–2018, and drought and temperature together accounted for 45% of cases

Changes in temperature and precipitation can affect tourist experiences. This study examines how summer park visitation has changed in response to temperature and precipitation extremes. The study goals were two-fold. The first is to introduce a framework and the second is to test it in a pilot region with four mountainous National Parks. The framework is designed to compare the vulnerability of seasonal park visitation to shifts in a combined indicator of temperature and precipitation. It uniquely considers needed measurements, and the data required to conduct an analysis. The second goal is to test it in four destinations in the U.S. Northern Rockies, including Glacier, Yellowstone, Grand Teton, and Rocky Mountain National Parks. The preliminary test reveals outlier cases of visitation under wet and dry extremes. The analysis connects time series climate and visitation data for the peak summer season from 1991–2012. Outlier analysis illustrates more change in extremely dry conditions, with four ...

The ability to identify medical reversals and other low-value medical practices is an essential prerequisite for efforts to reduce spending on such practices. Through an analysis of more than 3000 randomized controlled trials (RCTs) published in three leading medical journals (the Journal of the American Medical Association, the Lancet, and the New England Journal of Medicine), we have identified 396 medical reversals. Most of the studies (92%) were conducted on populations in high-income countries, cardiovascular disease was the most common medical category (20%), and medication was the most common type of intervention (33%).

Vigorous discussions and disagreements about the future changes in drought intensity in the U.S. Great Plains have been taking place recently within the literature. These discussions have involved widely varying estimates based on drought indices and model-based projections of the future. To investigate and understand the causes for such a disparity between these previous estimates, the authors analyzed the soil moisture at the near-surface soil layer and the entire soil column, as well as the Palmer drought severity index, the Palmer Z index, and the standardized precipitation and evaporation index using the output from the Community Climate System Model, version 4 (CCSM4), and 25 state-of-the-art climate models. These drought indices were computed using potential evapotranspiration estimated by the physically based Penman–Monteith method (PE_pm) and the empirically based Thornthwaite method (PE_th). The results showed that the short-term drought indices are similar to modeled surface soil moisture and show a small but consistent drying trend in the future. The long-term drought indices and the total column soil moisture, however, are consistent in projecting more intense future drought. When normalized, the drought indices with PE_th all show unprecedented future drying, while the drought indices with PE_pm show comparable dryness with the modeled soil moisture. Additionally, the drought indices with PE_pm are closely related to soil moisture during both the twentieth and twenty-first centuries. Overall, the drought indices with PE_pm, as well as the modeled total column soil moisture, suggest a widespread and very significant drying in the Great Plains toward the end of the century. The results suggest that the sharp contrasts about future drought risk in the Great Plains discussed in previous studies are caused by 1) comparing the projected changes in short-term droughts with that of the long-term droughts and/or 2) computing the atmospheric evaporative demand using an empirically based method (e.g., PE_th). The analysis here may be applied for drought projections in other regions across the globe.

Monitoring crop phenology provides essential information for crop management, as well as for understanding regional to global scale vegetation dynamics. In this study, a hybrid phenology detection method is presented that incorporates the “shape-model fitting” concept of the two-step filtering method and a simulation concept of the crop models to detect the critical vegetative stages and reproductive stages of corn (Zea mays L.) and soybeans (Glycine max L.) from MODIS 250-m Wide Dynamic Range Vegetation Index (WDRVI) time-series data and 1000-m Land Surface Temperature (LST) data. The method was first developed and tested at the field scale over a ten-year period (2003–2012) for three experimental study sites in eastern Nebraska of USA, where the estimated phenology dates were compared to the ground-based phenology observations for both corn and soybeans. The average root mean square error (RMSE) of phenology stage estimation of the individual development stages across all sites ranged from 1.9 to 4.3 days for corn and from 1.9 to 4.9 days for soybeans. The approach was then tested at a regional scale over eastern Nebraska and the state of Iowa to evaluate its ability to characterize the spatio-temporal variation of targeted corn and soybean phenology stage dates over a larger area. Quantitative regional assessments were conducted by comparing the estimated crop stage dates with crop developmental stage statistics reported by the USDA NASS Crop Progress Reports (NASS-CPR) for both eastern Nebraska and Iowa. The accuracy of the regional-scale phenology estimation in Iowa (RMSE ranged from 2.6 to 3.9 days for corn and from 3.2 to 3.9 days for soybeans) was slightly lower than in eastern Nebraska (RMSE ranged from 1.8 to 2.9 days for corn and from 1.7 to 2.9 days for soybeans), However, the estimation accuracy in Iowa was still reasonable with the estimated phenology dates being within 4 days or less of the observed dates for both corn and soybeans.

On the Ground Drought is a persistent problem on rangelands and adjusting management to respond appropriately is critical to both preserving natural resources and to maintaining financial viability. We explore the value of using a structured assessment approach to determining both social and ecological vulnerability. This approach allows for the identification of vulnerable ecosystems and business operations at regional and local scales as a basis for developing effective policies and programs.

This study investigated the climatic influence on the corn sowing date in the Midwestern United States by comparing the survey data of corn cultivation with meteorological records in nine states for the last 36 years (1979–2014). The results show that the year-to-year changes in the sowing date were significantly affected by springtime air temperature and precipitation in the nine states, although large state-to-state differences were found in the degree of sowing date–meteorology relationship. We determined that the 36-year climatological warm period (CWP) with daily mean temperatures ≥10 °C plays an important role in the state-to-state differences. For the states with longer CWPs, the influence of air temperature (precipitation) was generally weaker (stronger). This observed counteractive relationship should be considered for crop modelling for more effective assessment of the impact of climate change on agriculture.

Long-term monitoring of crop phenology is a critical process to understand changes in cropland vegetation dynamics related to climate and human management. During the last four decades, seasonal changes in vegetation have been measured by satellite instruments, the Advanced Very High Resolution Radiometers (AVHRRs). However, an acceptable detection of crop phenology has been prevented due to its coarse spatial resolution (~8 km) pixels in which croplands are frequently mixed with non-cropland. This study introduces a novel method for detecting the start of the growing season in cropland (SOSC) from the AVHRR Normalized Difference Vegetation Index (NDVI) to examine the long-term changes in SOSC at the 8-km pixel level across the core cropping regions of the Midwestern United States (the so-called ‘the Corn Belt’) for 1982–2015. The AVHRR-based SOSC was compared with the SOSC retrieved from the pixels covering mostly croplands of the 250-m Moderate Resolution Imaging Spectroradiometer (MODIS) NDVI. These two satellite-based SOSC shows reasonable correspondence in spatial patterns so that the annual values of the root mean square difference ranges from 3.6 to 7.4 days during the overlapping period of 2008–2015. Also, an acceptable correspondence was found between the interannual variations in the AVHRR SOSCs and in the state-level survey of crop stages. For sowing stages, correlation coefficients ranged from 0.43 to 0.68; for flowering stages those ranged from 0.51 to 0.83. By analyzing long-term SOSC changes with climate factors, we found a strong tendency that warmer pre-season condition is accompanied with earlier SOSC. In addition, larger pre-season precipitation tends to postpone SOSC as strongly as the pre-season temperature affects SOSC in a considerable portion of the core cropland. This study suggests that the postponing of sowing due to larger precipitation, which has rarely been highlighted in previous studies, requires more attentions in order for better understanding of vegetation dynamics in agriculture-climate studies.

The connection between drought early warning information and the timing of rangeland managers’ response actions is not well understood. This study investigates U.S. Northern Plains range and livestock managers’ decision-making in response to the 2016 flash drought, by means of a postdrought survey of agricultural landowners and using the Protective Action Decision Model theoretical framework. The study found that managers acted in response to environmental cues, but that their responses were significantly delayed compared to when drought conditions emerged. External warnings did not influence the timing of their decisions, though on-farm monitoring and assessment of conditions did. Though this case focused only on a one-year flash drought characterized by rapid drought intensification, waiting to destock pastures was associated with greater losses to range productivity and health and diversity. This study finds evidence of unrealized potential for drought early warning information to support proactive response and improved outcomes for rangeland management.

The U.S. Food and Drug Administration's drug advisory committees provide expert assessments of the safety and efficacy of new therapies considered for approval. A committee hears from a variety of speakers, from six groups, including voting members of the committee, FDA staff members, employees of the pharmaceutical company seeking approval of a therapy, patient and consumer representatives, expert speakers invited by the company, and public participants. The committees convene at the request of the FDA when the risks and harms of novel products are not immediately clear, and their final decisions carry significant weight, as most therapies that receive advisory committee approval are subsequently approved by the FDA. In recent years, across a series of diverse publications, the financial conflicts of interest of each category of participants in the meetings have been investigated. Here, we summarize these findings and their ethical implications, focusing on the FDA Oncologic Drugs Advisory Committee, and we suggest ways to move toward more transparent and impartial advisory committee meetings.

Drought has had large impacts on economies, societies and the environment, and could become even more disruptive given the context of climate change characterized by increasing temperature and more variable and extreme precipitation. Changes in the frequency, duration, and severity of droughts will have enormous impacts on the hydrological cycle, water management and agricultural production. Therefore, one major concern arising from climate change is its potential effects on water resources. Although South Korea has been experiencing serious drought and water scarcity issues in recent years, preparedness for potential changes in the frequency, severity and duration of drought disasters due to climate change effects has received only limited attention. It is important to detect changes in temporal trends of drought at the regional scale. This information will aid understanding the impacts of climate change and its subsequent effects on hydrology and agriculture. In this paper, we have addressed the question of how climate change might influence the impact of drought hazard by estimating the potential changes in temporal trends of drought in South Korea. We have assessed the temporal trends of future drought with drought indices (Standardized Precipitation Index [SPI], Standardized Precipitation Evapotranspiration Index [SPEI], and Self-Calibrating Palmer Drought Severity Index [SC-PDSI]) using past observed data (1981–2010) from 54 meteorological stations maintained by the Korea Meteorological Administration (KMA) and projected climate change scenarios (2011–2100) as depicted by the Representative Concentration Pathways models (RCPs). The drought hazard assessment was quantitatively evaluated by analyzing drought frequency, duration, severity and magnitude using the run theory method based on different timescales of the drought indices. The results demonstrated a significant increase of potential drought impacts in the future. Additionally, significant increases in the drought magnitude and severity were found at different time scales for each drought indicator. The results indicated that the temporal pattern of potential drought progression and recession across South Korea can be used for the development of proactive drought risk management and mitigation strategies.

Wetter et al. (2014; hereinafter W14) conclude that western Europe experienced significantly higher temperatures in AD 1540 compared to all other years in the instrumental record, including the summer heat waves of 2003 and 2010 (Schär et al. 2004; Barriopedro et al. 2011). Based on 300+ first-hand documentary weather reports, the authors argue that large parts of Europe were hit by an unprecedented, 11-month-long, ‘Megadrought' in 1540 exceeding all recorded and reconstructed levels, and falling outside the probability range of state-of-the-art palaeoclimate model simulations. Despite compiling, transforming and interpreting an exceptional pool of documentary evidence, W14 neglected to systematically analyse the existing collection of European tree ring-based climate reconstructions. An independent comparison of their findings from societal entries against natural proxy archives, however, would have been beneficial. For example, Pauling et al. (2006), already identified low precipitation amounts in 1540 derived mainly from tree-ring analyses, a study not cited in W14. In this reply we look into some of the tree-ring data available back to 1540 and before, and demonstrate that W14's conclusion regarding the inability of natural proxy archives to record climate extremes is not defensible.

Central Europe is generally not considered a drought-prone region compared with, for example, the Mediterranean. However, Central Europe, including the Czech Republic, recently experienced a series of drought events with substantial impacts, especially on crop production. Because agriculture systems, and vegetation in general, have adapted to evenly distributed precipitation, the region is susceptible to even short-term droughts. The recent drought events may be the result of multi-decadal climate variability or a more general trend, with some studies showing a link to a more frequent occurrence of atmospheric circulation patterns that are conducive to drought. This study introduces an innovation to the standard methodological approaches in evaluating drought climatology by analysing soil moisture conditions over more than 50 years. This approach relies on state-of-the-art observed weather data and state-of-the-art soil moisture model data, and focuses on the dynamic simulation of soil moisture content with high temporal (daily) and spatial (500 m) resolution in a diverse landscape. Statistically significant trends of decreasing soil moisture content were found, notably during May and June between 1961 and 2012. In contrast, trends towards higher soil moisture content were noted during the October-March time period. When the periods of 2001-2012 and 1961-1980 were compared, the probability of drought between April and June was found to increase by 50%. This indicates a loading of the climate dice' towards drier conditions. The probability of extreme drought events has also been found to increase. These results support concerns about the potentially increased severity of drought events in Central Europe under projected climate change.