Skill of managers and the wisdom of herds: examining an alternative approach to grazing management in larkspur habitat, The

2019 Spring.Includes bibliographical references.The many species of larkspur (Delphinium spp. L.) are among the most dangerous poisonous plants on rangelands in the western United States, causing death losses estimated at 2-5% (up to 15%) per year for cattle grazing in larkspur habitat. Research has estimated the value of these losses at $234 million per year. Other effects, such as altered grazing management practices and consequent lost forage quantity and quality, are significant but poorly understood. Current best management practice recommendations stress seasonal avoidance of pastures with larkspur present, with little evidence that this is practical or ultimately effective. Alternative approaches to addressing this complex challenge are difficult to design, test, and apply due to the threat of dead livestock. In this dissertation I explore an alternative approach based on the idea that it may be possible to manage cattle grazing such that no individual consumes a lethal dose, regardless of timing of grazing or larkspur density. This idea was inspired by producers past and present who have reported such success. I examine this hypothesis using agent-based models and a field experiment with Geyer's larkspur (D. geyeri Greene), the focal species throughout this research. Chapter 2 presents a conceptual model that situates this work within the broader context of livestock grazing management and rangeland science. This synthesis also highlights the potential for conceptual models to aid in the design, application, communication, and consilience of research in rangelands. Drawing on a wide range of work, this model challenges the discipline of rangeland science to integrate a broader array of methods and epistemologies to create knowledge sufficient to the complexity of the systems under study. Agent-based models (ABMs) provide an effective method of testing alternate management strategies without risk to livestock. ABMs are especially useful for modeling complex systems such as livestock grazing management and allow for realistic bottom-up encoding of cattle behavior. In Chapter 3, I introduce a spatially-explicit, behavior-based ABM of cattle grazing in a pasture with a dangerous amount of D. geyeri. This model tests the role of herd cohesion and stocking density in larkspur intake, finds that both are key drivers of larkspur-induced toxicosis, and indicates that alteration of these factors within realistic bounds can mitigate risk. Crucially, the model points to herd cohesion, which has received little attention in the discipline, as playing an important role in reducing lethal acute toxicosis. As the first agent-based model to simulate grazing behavior at realistic scales, this study also demonstrates the tremendous potential of ABMs to illuminate grazing management dynamics, including fundamental aspects of livestock behavior amidst ecological heterogeneity. Chapter 3 raises the question of the potential response of larkspur to being grazed. In Chapter 4, I examine the response of D. geyeri to two seasons of 25% or 75% aboveground plant mass removal. The 75% treatment led to significantly lower alkaloid concentrations (mg•g-1) and pools (mg per plant), while the 25% treatment had a lesser effect. Combined with lessons from previous studies, this indicates that Geyer's larkspur plants subject to aboveground mass removal such as may occur via grazing can be expected to become significantly less dangerous to cattle. We suggest that the mechanisms for this reduction are both alkaloid removal and reduced belowground root mass, as significant evidence indicates that alkaloids are synthesized and stored in the roots. The most common explanations for the evolution and persistence of herd behavior in large herbivores relate to decreased risk of predation. However, poisonous plants such as larkspur can present a threat comparable to predation. Chapters 3 and 4 point to the cattle herd itself as the potential solution to this seemingly intractable challenge and suggest that larkspur and forage patchiness may drive deaths. In Chapter 5, I present an agent-based model that incorporates neutral landscape models to assess the interaction between plant patchiness and herd behavior within the context of poisonous plants as predator and cattle as prey. The simulation results indicate that larkspur patchiness is indeed a driver of toxicosis and that highly cohesive herds can greatly reduce the risk of death in even the most dangerous circumstances. By placing the results in context with existing theories about the utility of herds, I demonstrate that grouping in large herbivores can be an adaptive response to patchily distributed poisonous plants. Lastly, the results hold significant management-relevant insight, both for cattle producers managing grazing in larkspur habitat and in general as a call to reconsider the manifold benefits of herd behavior among domestic herbivores. The findings in this dissertation build a strong case for an alternative approach to grazing management in larkspur habitat but fall short of actionable recommendations. For one, this is because a one-size-fits-all solution that would work across the great diversity of habitats and management systems in which larkspur is found is unlikely. Instead, these findings must be placed in context with existing knowledge and the complex multiscale decision-making processes of producers. Future work will thus focus on improving our understanding of the diverse set of management circumstances under which the many species of problematic larkspur are found

One place doesn't fit all: improving the effectiveness of sustainability standards by accounting for place

Includes bibliographical references (pages 8-10).The growing interest in incentivizing sustainable agricultural practices is supported by a large network of voluntary production standards, which aim to offer farmers and ranchers increased value for their product in support of reduced environmental impact. To be effective with producers and consumers alike, these standards must be both credible and broadly recognizable, and thus are typically highly generalizable. However, the environmental impact of agriculture is strongly place-based and varies considerably due to complex biophysical, socio-cultural, and management-based factors, even within a given sector in a particular region. We suggest that this contradiction between the placeless generality of standards and the placed-ness of agriculture renders many sustainability standards ineffective. In this policy and practice review, we examine this contradiction through the lens of beef production, with a focus on an ongoing regional food purchasing effort in Denver, Colorado, USA. We review the idea of place in the context of agricultural sustainability, drawing on life cycle analysis and diverse literature to find that recognition of place-specific circumstances is essential to understanding environmental impact and improving outcomes. We then examine the case of the Good Food Purchasing Program (GFPP), a broad set of food-purchasing standards currently being implemented for institutional purchasing in Denver. The GFPP was created through a lengthy stakeholder-inclusive process for use in Los Angeles, California, USA, and has since been applied to many cities across the country. The difference between Los Angeles' process and that of applying the result of Los Angeles' process to Denver is instructive, and emblematic of the flaws of generalizable sustainability standards themselves. We then describe the essential elements of a place-based approach to agricultural sustainability standards, pointing toward a democratic, process-based, and outcome-oriented strategy that results in standards that enable rather than hinder the creativity of both producers and consumers. Though prescription is anathema to our approach, we close by offering a starting point for the development of standards for beef production in Colorado that respect the work of people in place

Connecting urban food plans to the countryside: leveraging Denver's food vision to explore meaningful rural-urban linkages

Includes bibliographical references (pages 14-18).Cities are increasingly turning to food policy plans to support goals related to food access, food security, the environment, and economic development. This paper investigates ways that rural farmers, communities, and economies can both support and be supported by metropolitan food-focused initiatives. Specifically, our research question asked what opportunities and barriers exist to developing food policies that support urban food goals, particularly related to local procurement, as well as rural economic development. To address this question, we described and analyzed a meeting of urban stakeholders and larger-scale rural producers related to Colorado’s Denver Food Vision and Plan. We documented and explored “findings” gleaned from a supply chain diagraming and data compilation process that were then used to inform an event that brought together diverse supply chain partners. Three findings stand out. First, facilitating dialog between urban food policymakers and rural producers to understand potential tensions, mitigate such tensions, and capitalize on opportunities is essential. Second, perceptions and expectations surrounding “good food” are nuanced—a timely finding given the number of preferred procurement programs emerging across the county. Third, critical evaluation is needed across a diverse set of value chain strategies (e.g., conventional and alternative distribution) if food policy intends to support heterogeneous producers, their communities, and urban food policy goals

Evaluation of Pulmonary Fibrosis Outcomes by Race and Ethnicity in US Adults

Importance: Pulmonary fibrosis (PF) is characterized by progressive scarring of lung tissue and poor survival. Racial and ethnic minority populations face the greatest risk of morbidity and mortality from disparities impacting respiratory health, but the pattern of age at clinically relevant outcomes across diverse racial and ethnic populations with PF is unknown. Objective: To compare the age at PF-related outcomes and the heterogeneity in survival patterns among Hispanic, non-Hispanic Black, and non-Hispanic White participants. Design, setting, and participants: This cohort study included adult patients with a PF diagnosis and used data from prospective clinical registries: the Pulmonary Fibrosis Foundation Registry (PFFR) for the primary cohort and registries from 4 geographically distinct tertiary hospitals in the US for the external multicenter validation (EMV) cohort. Patients were followed between January 2003 and April 2021. Exposures: Race and ethnicity comparisons between Black, Hispanic, and White participants with PF. Main outcomes and measures: Age and sex distribution of participants were measured at the time of study enrollment. All-cause mortality and age at PF diagnosis, hospitalization, lung transplant, and death were assessed in participants over 14 389 person-years. Differences between racial and ethnic groups were compared using Wilcoxon rank sum tests, Bartlett 1-way analysis of variance, and χ2 tests, and crude mortality rates and rate ratios were assessed across racial and ethnic categories using Cox proportional hazards regression models. Results: In total, 4792 participants with PF were assessed (mean [SD] age, 66.1 [11.2] years; 2779 [58.0%] male; 488 [10.2%] Black, 319 [6.7%] Hispanic, and 3985 [83.2%] White); 1904 were in the PFFR and 2888 in the EMV cohort. Black patients with PF were consistently younger than White patients (mean [SD] age at baseline, 57.9 [12.0] vs 68.6 [9.6] years; P Conclusions and relevance: In this cohort study of participants with PF, racial and ethnic disparities, especially among Black patients, were found in PF-related outcomes, including earlier onset of death. Further research is essential to identify and mitigate the underlying responsible factors.</p

The biology of color

Coloration mediates the relationship between an organism and its environment in important ways, including social signaling, antipredator defenses, parasitic exploitation, thermoregulation, and protection from ultraviolet light, microbes, and abrasion. Methodological breakthroughs are accelerating knowledge of the processes underlying both the production of animal coloration and its perception, experiments are advancing understanding of mechanism and function, and measurements of color collected noninvasively and at a global scale are opening windows to evolutionary dynamics more generally. Here we provide a roadmap of these advances and identify hitherto unrecognized challenges for this multi- and interdisciplinary field

The biology of color

Coloration mediates the relationship between an organism and its environment in important ways, including social signaling, antipredator defenses, parasitic exploitation, thermoregulation, and protection from ultraviolet light, microbes, and abrasion. Methodological breakthroughs are accelerating knowledge of the processes underlying both the production of animal coloration and its perception, experiments are advancing understanding of mechanism and function, and measurements of color collected noninvasively and at a global scale are opening windows to evolutionary dynamics more generally. Here we provide a roadmap of these advances and identify hitherto unrecognized challenges for this multi- and interdisciplinary field

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

An agent-based model of cattle grazing toxic Geyer's larkspur

<div><p>By killing cattle and otherwise complicating management, the many species of larkspur (<i>Delphinium</i> spp.) present a serious, intractable, and complex challenge to livestock grazing management in the western United States. Among the many obstacles to improving our understanding of cattle-larkspur dynamics has been the difficulty of testing different grazing management strategies in the field, as the risk of dead animals is too great. Agent-based models (ABMs) provide an effective method of testing alternate management strategies without risk to livestock. ABMs are especially useful for modeling complex systems such as livestock grazing management, and allow for realistic bottom-up encoding of cattle behavior. Here, we introduce a spatially-explicit, behavior-based ABM of cattle grazing in a pasture with a dangerous amount of Geyer’s larkspur (<i>D</i>. <i>geyeri</i>). This model tests the role of herd cohesion and stocking density in larkspur intake, finds that both are key drivers of larkspur-induced toxicosis, and indicates that alteration of these factors within realistic bounds can mitigate risk. Crucially, the model points to herd cohesion, which has received little attention in the discipline, as playing an important role in lethal acute toxicosis. As the first ABM to model grazing behavior at realistic scales, this study also demonstrates the tremendous potential of ABMs to illuminate grazing management dynamics, including fundamental aspects of livestock behavior amidst ecological heterogeneity.</p></div