Plant macrofossil data for 48-0 ka in the USGS North American Packrat Midden Database, version 5.0.

Plant macrofossils from packrat (Neotoma spp.) middens provide direct evidence of past vegetation changes in arid regions of North America. Here we describe the newest version (version 5.0) of the U.S. Geological Survey (USGS) North American Packrat Midden Database. The database contains published and contributed data from 3,331 midden samples collected in southwest Canada, the western United States, and northern Mexico, with samples ranging in age from 48 ka to the present. The database includes original midden-sample macrofossil counts and relative-abundance data along with a standardized relative-abundance scheme that makes it easier to compare macrofossil data across midden-sample sites. In addition to the midden-sample data, this version of the midden database includes calibrated radiocarbon (14C) ages for the midden samples and plant functional type (PFT) assignments for the midden taxa. We also provide World Wildlife Fund ecoregion assignments and climate and bioclimate data for each midden-sample site location. The data are provided in tabular (.xlsx), comma-separated values (.csv), and relational database (.mdb) files.

A Model Oncologic Emergency Medicine Curriculum for Residency Training.

Background Emergency medicine (EM) resident training in oncologic emergencies is limited, and significant gaps have been identified. Although 90% of emergency medicine residency program directors recognize the importance of residency training in oncologic emergencies, there is no standardized oncologic emergency curriculum. Objective We propose a focused oncologic EM curriculum that serves as a complement to existing EM didactics curriculums to prepare EM residents to recognize and manage the most common oncologic emergencies. It will also allow for familiarization with constantly evolving therapies, such as chimeric antigen receptor cellular therapy and immune checkpoint inhibitors.Discussion This curriculum consists of 10 hours of didactic instruction, which can be incorporated into an already existing didactic curriculum. The curriculum encompasses education on the recognition, rapid diagnosis, and management of oncologic emergencies, with the goal of improving the EM resident's understanding of cancer complications. The suggested topics can be delivered in a variety of methods, allowing for flexible integration in an already existing emergency education curriculum. The proposed curriculum should be introduced during the first postgraduate year and then in the second or third year of the residency to reinforce the learning points.Conclusions Our proposal of a focused, standardized 10 hour program curriculum aims to help to fill the gaps in knowledge of oncologic emergencies. To assist in wide dissemination and standardization of these curriculum topics, outlines for each module are given in the article and we also propose creation of open access online lectures and content to be shared for education purposes.

CAR-T and checkpoint inhibitors: toxicities and antidotes in the emergency department.

INTRODUCTION: New cancer treatments with immunotherapy have led to unique toxicities affecting cancer patients. As cancer-related visits to the emergency department increase, the emergency physician and the medical toxicologist should be aware of immunotherapy-related toxicities. In this review we discuss immune related adverse events (irAEs) from chimeric antigen receptor T (CAR-T) cell therapy and immune checkpoint inhibitors (ICI). DISCUSSION: While presentation of the irAEs may mimic common conditions, it is important to recognize them as they may be life-threatening. A thorough history and examination of the patient, including their cancer treatment history in the past year is crucial. Conditions such as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), which can occur after CAR-T treatment, can progress rapidly to a fatal outcome if not recognized and managed in a timely manner. ICI can affect any organ system and irAEs may present like a typical autoimmune disease of the affected organ. While most of the irAEs we discuss in this review will benefit from treatment with glucocorticoids, it is important to know the grade of the condition, as it will determine the treatment dose, route and further management considerations. CONCLUSION: Patients experiencing irAEs from ICI and CAR-T can present with subtle symptoms that can rapidly progress if not recognized early. The emergency physician and the medical toxicologist should keep in mind these toxicities and the patient's oncologic history to adequately recognize and manage these conditions.

Optimal timing of chemoradiotherapy after surgical resection of glioblastoma: Stratification by validated prognostic classification.

BACKGROUND: Previous studies examining the time to initiate chemoradiation (CRT) after surgical resection of glioblastoma have been conflicting. To better define the effect that the timing of adjuvant treatment may have on outcomes, the authors examined patients within the National Cancer Database (NCDB) stratified by a validated prognostic classification system. METHODS: Patients with glioblastoma in the NCDB who underwent surgery and CRT from 2004 through 2013 were analyzed. Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (III, IV, V) was extrapolated for the cohort. Time intervals were grouped weekly, with weeks 4 to 5 serving as the reference category for analyses. Kaplan-Meier analysis, log-rank testing, and multivariate (MVA) Cox proportional hazards regression were performed. RESULTS: In total, 30,414 patients were included. RPA classes III, IV, and V contained 5250, 20,855, and 4309 patients, respectively. On MVA, no time point after week 5 was associated with a change in overall survival for the entire cohort or for any RPA class subgroup. The periods of weeks 0 to 1 (hazard ratio [HR], 1.18; 95% CI, 1.02-1.36), >1 to 2 (HR, 1.23; 95% CI, 1.16-1.31), and >2 to 3 (HR, 1.11; 95% CI, 1.07-1.15) demonstrated slightly worse overall survival (all P < .03). The detriment to early initiation was consistent across each RPA class subgroup. CONCLUSIONS: The current data provide insight into the optimal timing of CRT in patients with glioblastoma and describe RPA class-specific outcomes. In general, short delays beyond 5 weeks did not negatively affect outcomes, whereas early initiation before 3 weeks may be detrimental.

Heart rate and heart rate variability in emergency medicine.

BACKGROUND: Tachycardia may be indicative of mental stress, which in turn can decrease performance, reduce information processing capacity, and hinder memory recall. The objective of this study is to examine heart rate trends present among emergency medicine trainees over a standard emergency room shift to measure the frequency and severity of stress experienced while on shift. METHODS: We assessed heart rate in emergency medicine residents using the Empatica E4 device, a mobile wrist-worn physiological monitor. The 31 consenting residents received training in wearing the monitor and uploading the data during a typical critical care shift. Data was deindividualized, compiled, and analyzed with descriptive statistics using Microsoft Excel. RESULTS: Data collected from 31 critical care shifts illustrated that the mean range in HR was 53.9-162.7 bpm per shift and the overall range in HR across all shifts was 49-202.7 bpm. There was a mean of 10.2 peaks in the 120-129.9 bpm range, 11.3 peaks within 130-159.9 bpm, and 1.06 peaks above 160 bpm per shift. The mean length of time that HR rose above 130 bpm was 660.6 s per shift. Only 2 of the 31 shifts examined did not have any accelerations above 130 bpm. CONCLUSIONS: Continuous monitoring of HR in emergency medicine residents during standard critical care shifts using a wrist-worn device found marked elevations suggestive of episodic tachycardia.

Reconciling divergent trends and millennial variations in Holocene temperatures.

Cooling during most of the past two millennia has been widely recognized and has been inferred to be the dominant global temperature trend of the past 11,700 years (the Holocene epoch). However, long-term cooling has been difficult to reconcile with global forcing, and climate models consistently simulate long-term warming. The divergence between simulations and reconstructions emerges primarily for northern mid-latitudes, for which pronounced cooling has been inferred from marine and coastal records using multiple approaches. Here we show that temperatures reconstructed from sub-fossil pollen from 642 sites across North America and Europe closely match simulations, and that long-term warming, not cooling, defined the Holocene until around 2,000 years ago. The reconstructions indicate that evidence of long-term cooling was limited to North Atlantic records. Early Holocene temperatures on the continents were more than two degrees Celsius below those of the past two millennia, consistent with the simulated effects of remnant ice sheets in the climate model Community Climate System Model 3 (CCSM3). CCSM3 simulates increases in 'growing degree days'-a measure of the accumulated warmth above five degrees Celsius per year-of more than 300 kelvin days over the Holocene, consistent with inferences from the pollen data. It also simulates a decrease in mean summer temperatures of more than two degrees Celsius, which correlates with reconstructed marine trends and highlights the potential importance of the different subseasonal sensitivities of the records. Despite the differing trends, pollen- and marine-based reconstructions are correlated at millennial-to-centennial scales, probably in response to ice-sheet and meltwater dynamics, and to stochastic dynamics similar to the temperature variations produced by CCSM3. Although our results depend on a single source of palaeoclimatic data (pollen) and a single climate-model simulation, they reinforce the notion that climate models can adequately simulate climates for periods other than the present-day. They also demonstrate that amplified warming in recent decades increased temperatures above the mean of any century during the past 11,000 years.

Increase in Adverse Reactions Associated with Use of Synthetic Cannabinoids - Anchorage, Alaska, 2015-2016.

In July 2015, personnel in the Alaska Division of Public Health's Section of Epidemiology became aware of an increase in the number of patients being treated in Anchorage hospital emergency departments for adverse reactions associated with use of synthetic cannabinoids (SCs). SCs are a chemically diverse class of designer drugs that bind to the same cannabinoid receptors as tetrahydrocannabinol, the main psychoactive component of cannabis. A public health investigation was initiated to describe clinical outcomes, characterize the outbreak, and identify SC chemicals circulating in Anchorage. During July 15, 2015-March 15, 2016, a total of 1,351 ambulance transports to Anchorage emergency departments for adverse SC reactions were identified. A review of charts obtained from two Anchorage hospitals determined that among 167 emergency department visits for adverse SC reactions during July 15-September 30, 2015, 11 (6.6%) involved a patient who required endotracheal intubation, 17 (10.2%) involved a patient who was admitted to the intensive care unit, and 66 (39.5%) involved a patient classified as being homeless. Testing of 25 product and paraphernalia samples collected from patients at one hospital identified 11 different SC chemicals. Educational outreach campaigns focused on the considerable health risks of using SCs need to complement judicial and law enforcement actions to reduce SC use.

Projected Future Vegetation Changes for the Northwest United States and Southwest Canada at a Fine Spatial Resolution Using a Dynamic Global Vegetation Model.

Future climate change may significantly alter the distributions of many plant taxa. The effects of climate change may be particularly large in mountainous regions where climate can vary significantly with elevation. Understanding potential future vegetation changes in these regions requires methods that can resolve vegetation responses to climate change at fine spatial resolutions. We used LPJ, a dynamic global vegetation model, to assess potential future vegetation changes for a large topographically complex area of the northwest United States and southwest Canada (38.0-58.0°N latitude by 136.6-103.0°W longitude). LPJ is a process-based vegetation model that mechanistically simulates the effect of changing climate and atmospheric CO2 concentrations on vegetation. It was developed and has been mostly applied at spatial resolutions of 10-minutes or coarser. In this study, we used LPJ at a 30-second (~1-km) spatial resolution to simulate potential vegetation changes for 2070-2099. LPJ was run using downscaled future climate simulations from five coupled atmosphere-ocean general circulation models (CCSM3, CGCM3.1(T47), GISS-ER, MIROC3.2(medres), UKMO-HadCM3) produced using the A2 greenhouse gases emissions scenario. Under projected future climate and atmospheric CO2 concentrations, the simulated vegetation changes result in the contraction of alpine, shrub-steppe, and xeric shrub vegetation across the study area and the expansion of woodland and forest vegetation. Large areas of maritime cool forest and cold forest are simulated to persist under projected future conditions. The fine spatial-scale vegetation simulations resolve patterns of vegetation change that are not visible at coarser resolutions and these fine-scale patterns are particularly important for understanding potential future vegetation changes in topographically complex areas.

The Adaptation for Conservation Targets (ACT) framework: a tool for incorporating climate change into natural resource management.

As natural resource management agencies and conservation organizations seek guidance on responding to climate change, myriad potential actions and strategies have been proposed for increasing the long-term viability of some attributes of natural systems. Managers need practical tools for selecting among these actions and strategies to develop a tailored management approach for specific targets at a given location. We developed and present one such tool, the participatory Adaptation for Conservation Targets (ACT) framework, which considers the effects of climate change in the development of management actions for particular species, ecosystems and ecological functions. Our framework is based on the premise that effective adaptation of management to climate change can rely on local knowledge of an ecosystem and does not necessarily require detailed projections of climate change or its effects. We illustrate the ACT framework by applying it to an ecological function in the Greater Yellowstone Ecosystem (Montana, Wyoming, and Idaho, USA)--water flows in the upper Yellowstone River. We suggest that the ACT framework is a practical tool for initiating adaptation planning, and for generating and communicating specific management interventions given an increasingly altered, yet uncertain, climate.

Projected climate impacts for the amphibians of the Western hemisphere.

Given their physiological requirements, limited dispersal abilities, and hydrologically sensitive habitats, amphibians are likely to be highly sensitive to future climatic changes. We used three approaches to map areas in the western hemisphere where amphibians are particularly likely to be affected by climate change. First, we used bioclimatic models to project potential climate-driven shifts in the distribution of 413 amphibian species based on 20 climate simulations for 2071-2100. We summarized these projections to produce estimates of species turnover. Second, we mapped the distribution of 1099 species with restricted geographic ranges. Finally, using the 20 future climate-change simulations, we mapped areas that were consistently projected to receive less seasonal precipitation in the coming century and thus were likely to have altered microclimates and local hydrologies. Species turnover was projected to be highest in the Andes Mountains and parts of Central America and Mexico, where, on average, turnover rates exceeded 60% under the lower of two emissions scenarios. Many of the restricted-range species not included in our range-shift analyses were concentrated in parts of the Andes and Central America and in Brazil's Atlantic Forest. Much of Central America, southwestern North America, and parts of South America were consistently projected to experience decreased precipitation by the end of the century. Combining the results of the three analyses highlighted several areas in which amphibians are likely to be significantly affected by climate change for multiple reasons. Portions of southern Central America were simultaneously projected to experience high species turnover, have many additional restricted-range species, and were consistently projected to receive less precipitation. Together, our three analyses form one potential assessment of the geographic vulnerability of amphibians to climate change and as such provide broad-scale guidance for directing conservation efforts.

Projected climate-induced faunal change in the Western Hemisphere.

Climate change is predicted to be one of the greatest drivers of ecological change in the coming century. Increases in temperature over the last century have clearly been linked to shifts in species distributions. Given the magnitude of projected future climatic changes, we can expect even larger range shifts in the coming century. These changes will, in turn, alter ecological communities and the functioning of ecosystems. Despite the seriousness of predicted climate change, the uncertainty in climate-change projections makes it difficult for conservation managers and planners to proactively respond to climate stresses. To address one aspect of this uncertainty, we identified predictions of faunal change for which a high level of consensus was exhibited by different climate models. Specifically, we assessed the potential effects of 30 coupled atmosphere-ocean general circulation model (AOGCM) future-climate simulations on the geographic ranges of 2954 species of birds, mammals, and amphibians in the Western Hemisphere. Eighty percent of the climate projections based on a relatively low greenhouse-gas emissions scenario result in the local loss of at least 10% of the vertebrate fauna over much of North and South America. The largest changes in fauna are predicted for the tundra, Central America, and the Andes Mountains where, assuming no dispersal constraints, specific areas are likely to experience over 90% turnover, so that faunal distributions in the future will bear little resemblance to those of today.

The related retinoblastoma (pRb) and p130 proteins cooperate to regulate homeostasis in the intestinal epithelium.

pRb, p107, and p130 are related proteins that play a central role in the regulation of cell cycle progression and terminal differentiation in mammalian cells. Nevertheless, it is still largely unclear how these proteins achieve this regulation in vivo. The intestinal epithelium is an ideal in vivo system in which to study the molecular pathways that regulate proliferation and differentiation because it exists in a constant state of development throughout an animal's lifetime. We studied the phenotypic effects on the intestinal epithelium of mutating Rb and p107 or p130. Although mutating these genes singly had little or no effect, loss of pRb and p107 or p130 together produced chronic hyperplasia and dysplasia of the small intestinal and colonic epithelium. In Rb/p130 double mutants this hyperplasia was associated with defects in terminal differentiation of specific cell types and was dependent on the increased proliferation seen in the epithelium of mutant animals. At the molecular level, dysregulation of the Rb pathway led to an increase in the expression of Math1, Cdx1, Cdx2, transcription factors that regulate proliferation and differentiation in the intestinal epithelium. The absence of Cdx1 function in Rb/p130 double mutant mice partially reverted the histologic phenotype by suppressing ectopic mitosis in the epithelium. These studies implicate the Rb pathway as a regulator of epithelial homeostasis in the intestine.

Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer.

Epithelial ovarian tumors present a complex clinical, diagnostic and therapeutic challenge because of the difficulty of early detection, lack of known precursor lesions and high mortality rates. Endometrioid ovarian carcinomas are frequently associated with endometriosis, but the mechanism for this association remains unknown. Here we present the first genetic models of peritoneal endometriosis and endometrioid ovarian adenocarcinoma in mice, both based on the activation of an oncogenic K-ras allele. In addition, we find that expression of oncogenic K-ras or conditional Pten deletion within the ovarian surface epithelium gives rise to preneoplastic ovarian lesions with an endometrioid glandular morphology. Furthermore, the combination of the two mutations in the ovary leads to the induction of invasive and widely metastatic endometrioid ovarian adenocarcinomas with complete penetrance and a disease latency of only 7 weeks. The ovarian cancer model described in this study recapitulates the specific tumor histomorphology and metastatic potential of the human disease.

Topographic, bioclimatic, and vegetation characteristics of three ecoregion classification systems in North America: comparisons along continent-wide transects.

Ecoregion classification systems are increasingly used for policy and management decisions, particularly among conservation and natural resource managers. A number of ecoregion classification systems are currently available, with each system defining ecoregions using different classification methods and different types of data. As a result, each classification system describes a unique set of ecoregions. To help potential users choose the most appropriate ecoregion system for their particular application, we used three latitudinal transects across North America to compare the boundaries and environmental characteristics of three ecoregion classification systems [Küchler, World Wildlife Fund (WWF), and Bailey]. A variety of variables were used to evaluate the three systems, including woody plant species richness, normalized difference in vegetation index (NDVI), and bioclimatic variables (e.g., mean temperature of the coldest month) along each transect. Our results are dominated by geographic patterns in temperature, which are generally aligned north-south, and in moisture, which are generally aligned east-west. In the west, the dramatic changes in physiography, climate, and vegetation impose stronger controls on ecoregion boundaries than in the east. The Küchler system has the greatest number of ecoregions on all three transects, but does not necessarily have the highest degree of internal consistency within its ecoregions with regard to the bioclimatic and species richness data. In general, the WWF system appears to track climatic and floristic variables the best of the three systems, but not in all regions on all transects.