Towards a whole-system framework for wildfire monitoring using Earth observations.

Fire seasons have become increasingly variable and extreme due to changing climatological, ecological, and social conditions. Earth observation data are critical for monitoring fires and their impacts. Herein, we present a whole-system framework for identifying and synthesizing fire monitoring objectives and data needs throughout the life cycle of a fire event. The four stages of fire monitoring using Earth observation data include the following: (1) pre-fire vegetation inventories, (2) active-fire monitoring, (3) post-fire assessment, and (4) multi-scale synthesis. We identify the challenges and opportunities associated with current approaches to fire monitoring, highlighting four case studies from North American boreal, montane, and grassland ecosystems. While the case studies are localized to these ecosystems and regional contexts, they provide insights for others experiencing similar monitoring challenges worldwide. The field of remote sensing is experiencing a rapid proliferation of new data sources, providing observations that can inform all aspects of our fire monitoring framework; however, significant challenges for meeting fire monitoring objectives remain. We identify future opportunities for data sharing and rapid co-development of information products using cloud computing that benefits from open-access Earth observation and other geospatial data layers.

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies.

Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity.

A global review of beaver dam impacts: Stream conservation implications across biomes.

Beaver are recolonizing previously occupied regions, expanding into new territories, and increasingly being introduced and protected for stream conservation and restoration across numerous biomes. However, beaver dam effects on the physical, chemical, and biological characteristics of streams may vary within and among biomes. A comprehensive review of these impacts is lacking. The goals of this review were to: 1) summarize the distribution of studies by biome on beaver dam effects related to channel morphology, hydrology, water quality, and aquatic biota, as well as on beaver habitat selection, 2) summarize the extent to which beaver dam impacts have been consistent within and among biomes, and 3) share testable hypotheses regarding beaver impacts within understudied biomes. We quantify the directionality of beaver dam impacts from 267 peer-reviewed studies. Results show that the majority of studies have been completed within temperate forest environments and that many biomes are understudied. Across biomes, beaver preferred sites for dam development characterized by relatively low gradients and unconfined reaches with small drainage areas. Overall, parameters related to stream morphology and hydrology showed relatively consistent responses to beaver dams within and among biomes, yet water quality and biotic responses were variable among biomes. Responses also varied by parameter within water quality and biotic impact categories. The findings of this study can be useful for stream conservation and restoration efforts that introduce or protect beaver. Additional studies are needed within arid and cold biomes historically occupied by beaver and in novel biomes where beaver populations are currently expanding.

Monitoring uranium mine pollution on Native American lands: Insights from tree bark particulate matter on the Spokane Reservation, Washington, USA.

The uranium boom in the United States from the 1940's to the 1980's was a period of extensive uranium mining on Native American lands. However, detailed environmental investigations of the resulting uranium pollution are sparse and typically ignore contributions from airborne particulate matter. The Midnite Mine is a 350-acre inactive open pit uranium mine located on the Spokane Indian Reservation in eastern Washington that operated from 1954 to 1981. Approximately 2.4 million tons of ore and 33 million tons of waste rock were left behind in stockpiles and have also been utilized as gravel on access and haul roads. Although the Midnite Mine is now a Superfund Site, and governmental investigations of water and soil contamination have been done, no investigations of airborne particulate matter pollution have been conducted. This study applies tree bark from 31 Pinus ponderosa trees as a biomonitor of this airborne particulate matter. Bulk trace elemental analyses via inductively coupled plasma - mass spectrometry (ICP-MS) of tree bark show that U is the most abundant trace element of interest present up to 232 ppb. Other metals that are of potential human health concern include Th, Pb, and As which are present at 20 ppb, 104 ppb, and 20 ppb respectively. Calculated geoaccumulation indices determine these metals to be at high (U), moderate (Th), and low (Pb and As) levels of contamination. Detailed scanning electron microscopy (SEM) investigations of particulate matter from the surface of tree bark confirm that U and Th-bearing particulate matter exist in the

Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma.

Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m2 on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 106 , 1 × 107 , 5 × 107 and 1 × 108 CB-NK cells/kg. Ten patients had either high-risk chromosomal changes or a history of relapsed/progressed disease. There were no infusional toxicities and no graft-versus-host disease. One patient failed to engraft due to poor autologous graft quality and was rescued with a back-up autologous graft. Overall, 10 patients achieved at least a very good partial response as their best response, including eight with near complete response or better. With a median follow-up of 21 months, four patients have progressed or relapsed, two of whom have died. CB-NK cells were detected in vivo in six patients, with an activated phenotype (NKG2D+ /NKp30+ ). These data warrant further development of this novel cellular therapy.

Development of the crop residue and rangeland burning in the 2014 National Emissions Inventory using information from multiple sources.

Biomass burning has been identified as an important contributor to the degradation of air quality because of its impact on ozone and particulate matter. One component of the biomass burning inventory, crop residue burning, has been poorly characterized in the National Emissions Inventory (NEI). In the 2011 NEI, wildland fires, prescribed fires, and crop residue burning collectively were the largest source of PM2.5. This paper summarizes our 2014 NEI method to estimate crop residue burning emissions and grass/pasture burning emissions using remote sensing data and field information and literature-based, crop-specific emission factors. We focus on both the postharvest and pre-harvest burning that takes place with bluegrass, corn, cotton, rice, soybeans, sugarcane and wheat. Estimates for 2014 indicate that over the continental United States (CONUS), crop residue burning excluding all areas identified as Pasture/Grass, Grassland Herbaceous, and Pasture/Hay occurred over approximately 1.5 million acres of land and produced 19,600 short tons of PM2.5. For areas identified as Pasture/Grass, Grassland Herbaceous, and Pasture/Hay, biomass burning emissions occurred over approximately 1.6 million acres of land and produced 30,000 short tons of PM2.5. This estimate compares with the 2011 NEI and 2008 NEI as follows: 2008: 49,650 short tons and 2011: 141,180 short tons. Note that in the previous two NEIs rangeland burning was not well defined and so the comparison is not exact. The remote sensing data also provided verification of our existing diurnal profile for crop residue burning emissions used in chemical transport modeling. In addition, the entire database used to estimate this sector of emissions is available on EPA's Clearinghouse for Inventories and Emission Factors (CHIEF, http://www3.epa.gov/ttn/chief/index.html ). IMPLICATIONS: Estimates of crop residue burning and rangeland burning emissions can be improved by using satellite detections. Local information is helpful in distinguishing crop residue and rangeland burning from all other types of fires.

Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells.

BACKGROUND: T cells expressing antigen-specific chimeric antigen receptors (CARs) improve outcomes for CD19-expressing B cell malignancies. We evaluated a human application of T cells that were genetically modified using the Sleeping Beauty (SB) transposon/transposase system to express a CD19-specific CAR. METHODS: T cells were genetically modified using DNA plasmids from the SB platform to stably express a second-generation CD19-specific CAR and selectively propagated ex vivo with activating and propagating cells (AaPCs) and cytokines. Twenty-six patients with advanced non-Hodgkin lymphoma and acute lymphoblastic leukemia safely underwent hematopoietic stem cell transplantation (HSCT) and infusion of CAR T cells as adjuvant therapy in the autologous (n = 7) or allogeneic settings (n = 19). RESULTS: SB-mediated genetic transposition and stimulation resulted in 2,200- to 2,500-fold ex vivo expansion of genetically modified T cells, with 84% CAR expression, and without integration hotspots. Following autologous HSCT, the 30-month progression-free and overall survivals were 83% and 100%, respectively. After allogeneic HSCT, the respective 12-month rates were 53% and 63%. No acute or late toxicities and no exacerbation of graft-versus-host disease were observed. Despite a low antigen burden and unsupportive recipient cytokine environment, CAR T cells persisted for an average of 201 days for autologous recipients and 51 days for allogeneic recipients. CONCLUSIONS: CD19-specific CAR T cells generated with SB and AaPC platforms were safe, and may provide additional cancer control as planned infusions after HSCT. These results support further clinical development of this nonviral gene therapy approach. TRIAL REGISTRATION: Autologous, NCT00968760; allogeneic, NCT01497184; long-term follow-up, NCT01492036. FUNDING: National Cancer Institute, private foundations, and institutional funds. Please see Acknowledgments for details.

Management and climate contributions to satellite-derived active fire trends in the contiguous United States.

Fires in croplands, plantations, and rangelands contribute significantly to fire emissions in the United States, yet are often overshadowed by wildland fires in efforts to develop inventories or estimate responses to climate change. Here we quantified decadal trends, interannual variability, and seasonality of Terra Moderate Resolution Imaging Spectroradiometer (MODIS) observations of active fires (thermal anomalies) as a function of management type in the contiguous U.S. during 2001-2010. We used the Monitoring Trends in Burn Severity database to identify active fires within the perimeter of large wildland fires and land cover maps to identify active fires in croplands. A third class of fires defined as prescribed/other included all residual satellite active fire detections. Large wildland fires were the most variable of all three fire types and had no significant annual trend in the contiguous U.S. during 2001-2010. Active fires in croplands, in contrast, increased at a rate of 3.4% per year. Cropland and prescribed/other fire types combined were responsible for 77% of the total active fire detections within the U.S and were most abundant in the south and southeast. In the west, cropland active fires decreased at a rate of 5.9% per year, likely in response to intensive air quality policies. Potential evaporation was a dominant regulator of the interannual variability of large wildland fires, but had a weaker influence on the other two fire types. Our analysis suggests it may be possible to modify landscape fire emissions within the U.S. by influencing the way fires are used in managed ecosystems. KEY POINTS: Wildland, cropland, and prescribed fires had different trends and patternsSensitivity to climate varied with fire typeIntensity of air quality regulation influenced cropland burning trends.

Remote sensing-based estimates of annual and seasonal emissions from crop residue burning in the contiguous United States.

Crop residue burning is an extensive agricultural practice in the contiguous United States (CONUS). This analysis presents the results of a remote sensing-based study of crop residue burning emissions in the CONUS for the time period 2003-2007 for the atmospheric species of carbon dioxide (CO2), methane (CH4), carbon monoxide (CO), nitrogen dioxide (NO2, sulfur dioxide (SO2), PM2.5 (particulate matter [PM] < or = 2.5 microm in aerodynamic diameter), and PM10 (PM < or = 10 microm in aerodynamic diameter). Cropland burned area and associated crop types were derived from Moderate Resolution Imaging Spectroradiometer (MODIS) products. Emission factors, fuel load, and combustion completeness estimates were derived from the scientific literature, governmental reports, and expert knowledge. Emissions were calculated using the bottom-up approach in which emissions are the product of burned area, fuel load, and combustion completeness for each specific crop type. On average, annual crop residue burning in the CONUS emitted 6.1 Tg of CO2, 8.9 Gg of CH4, 232.4 Gg of CO, 10.6 Gg of NO2, 4.4 Gg of SO2, 20.9 Gg of PM2.5, and 28.5 Gg of PM10. These emissions remained fairly consistent, with an average interannual variability of crop residue burning emissions of +/- 10%. The states with the highest emissions were Arkansas, California, Florida, Idaho, Texas, and Washington. Most emissions were clustered in the southeastern United States, the Great Plains, and the Pacific Northwest. Air quality and carbon emissions were concentrated in the spring, summer, and fall, with an exception because of winter harvesting of sugarcane in Florida, Louisiana, and Texas. Sugarcane, wheat, and rice residues accounted for approximately 70% of all crop residue burning and associated emissions. Estimates of CO and CH4 from agricultural waste burning by the U.S. Environmental Protection Agency were 73 and 78% higher than the CO and CH4 emission estimates from this analysis, respectively. This analysis also showed that crop residue burning emissions are a minor source of CH4 emissions (< 1%) compared with the CH4 emissions from other agricultural sources, specifically enteric fermentation, manure management, and rice cultivation.

The spatial and temporal distribution of crop residue burning in the contiguous United States.

Burning crop residue before and/or after harvest is a common farming practice however; there is no baseline estimate for cropland burned area in the contiguous U.S. (CONUS). We present the results of a study, using five years of remotely sensed satellite data to map the location and areal extent of crop residue burning in the CONUS. Our burned area approach combines 500 m Moderate Resolution Imaging Spectroradiometer (MODIS) Normalized Burn Ratio (dNBR) data, with 1 km MODIS active fire counts calibrated using coincident high resolution satellite data to generate area estimates. Our results show that cropland burning is an extensive and recurring annual event in several states in the CONUS. On average, 1,239,000 ha of croplands burn annually, which is equivalent to 43% of the annual average area of wildland fires in the U.S., as reported by the United States Forest Service for the same period. Several states experience high levels (>30,000 ha yr(-1)) of crop residue burning, including Arkansas, California, Colorado, Florida, Idaho, Kansas, Louisiana, North Dakota, Oklahoma, Oregon, South Dakota, Texas, and Washington. Validation with high resolution burn scar imagery and GPS data collected during targeted field campaigns showed a moderate to high-level accuracy for our burned area estimates, ranging from 78 to 90%. Our approach provides a more consistent methodology for quantifying cropland burned area at regional scales than the previously available U.S. national and state-level statistics on crop residue burning.

Monitoring agricultural burning in the Mississippi River Valley region from the moderate resolution imaging spectroradiometer (MODIS).

The 2003 active fire observations from the Moderate Resolution Imaging Spectroradiometer (MODIS), on board NASA's Terra and Aqua satellites, were analyzed to assess burning activity in the cropland areas of the Mississippi River Valley region. Agricultural burning was found to be an important contributor to fire activity in this region, accounting for approximately one-third of all burning. Agricultural fire activity showed two seasonal peaks: the first, smaller peak, occurring in June during the spring harvesting of wheat; and the second, bigger peak, in October during the fall harvesting of rice and soy. The seasonal signal in agricultural burning was predominantly evident in the early afternoon MODIS Aqua fire detections. A strong diurnal agricultural fire signal was prevalent during the fall harvesting months, as suggested by the substantially higher number (approximately 3.5 times) of fires detected by MODIS Aqua in the early afternoon, compared with those detected by MODIS Terra in the morning. No diurnal variations in agricultural fire activity were apparent during the springtime wheat-harvesting season. The seasonal and diurnal patterns in agricultural fire activity detected by MODIS are supported by known crop management practices in this region. MODIS data provide an important means to characterize and monitor agricultural fire dynamics and management practices.