Comparing multiscale, presence-only habitat suitability models created with structured survey data and community science data for a rare warbler species at the southern range margin.

Golden-winged Warblers (Vermivora chrysoptera, Parulidae) are declining migrant songbirds that breed in the Great Lakes and Appalachian regions of North America. Within their breeding range, Golden-winged Warblers are found in early successional habitats adjacent to mature hardwood forest, and previous work has found that Golden-winged Warbler habitat preferences are scale-dependent. Golden-winged Warbler Working Group management recommendations were written to apply to large regions of the breeding range, but there may be localized differences in both habitat availability and preferences. Rapid declines at the southernmost extent of their breeding range in Western North Carolina necessitate investigation into landscape characteristics governing distribution in this subregion. Furthermore, with the increase in availability of community science data from platforms such as eBird, it would be valuable to know if community science data produces similar distribution models as systemic sampling data. In this study, we described patterns of Golden-winged Warbler presence in Western North Carolina by examining habitat variables at multiple spatial scales using data from standardized Audubon North Carolina (NC) playback surveys and community science data from eBird. We compared model performance and predictions between Audubon NC and eBird models and found that Golden-winged Warbler presence is associated with sites which, at a local scale (150m), have less mature forest, more young forest, more herb/shrub cover, and more road cover, and at a landscape scale (2500m), have less herb/shrub cover. Golden-winged Warbler presence is also associated with higher elevations and smaller slopes. eBird and Audubon models had similar variable importance values, response curves, and overall performance. Based on variable importance values, elevation, mature forest at the local scale, and road cover at the local scale are the primary variables driving the difference between Golden-winged Warbler breeding sites and random background sites in Western North Carolina. Additionally, our results validate the use of eBird data, since they produce species distribution modeling results that are similar to results obtained from more standardized survey methods.

Estimates of biomass reductions of ozone sensitive herbaceous plants in California.

Exposure to tropospheric ozone pollution impairs photosynthesis and growth in plants and this can have consequences for ecosystems. However, exposure-response research in the United States (U.S.) has historically focused on trees and crops, and less attention has been given to non-crop herbaceous species. We combined U.S. Environmental Protection Agency ozone monitoring data from the entirety of 2016 with published exposure-response relationships from controlled exposure experiments for twenty herbaceous plant species occurring in California. The U.S. Department of Agriculture PLANTS database was used to identify county-level occurrence data of these plant species. A kriged ozone exposure surface for 2016 was generated using data from monitoring stations in California and surrounding states, using Accumulated Ozone exposure over a Threshold of 40 ppb (AOT40) as an exposure metric. County-wide ozone exposure estimations were then combined with published exposure response functions for focal plants, and maps were created to estimate ozone-induced growth losses in the counties where the plants occur. Plant species had estimated annual growth losses from <1 % to >20 % based on exposure levels and sensitivity. Of the 20 species, 17 had predicted biomass loss >5 % in at least one county, emphasizing the vulnerability of herbaceous species at recent ozone concentrations. Butte, Nevada, Plumas, San Luis Obispo, and Shasta Counties, an area of about 31,652 km2, had the highest number of species (6) with >10 % estimated biomass loss, the loss threshold for European critical levels. White clover (Trifolium repens L.) was one of the most affected species with more than an estimated 10 % annual estimated growth loss over 59 % of the state. Overall, these estimated growth losses demonstrate potential for shifts in plant communities and negative effects on ecosystems. This study addresses critical policy needs for risk assessments on herbaceous species in a single year of ozone exposure.

Effectiveness and Safety of Romiplostim Among Patients with Newly Diagnosed, Persistent and Chronic Immune Thrombocytopenia in European Clinical Practice.

INTRODUCTION: Romiplostim has been approved in Europe since 2009 to treat patients with chronic primary immune thrombocytopenia (ITP). Using real-world data from seven European countries, we measured the effectiveness and safety outcomes within 24 weeks following romiplostim initiation by duration of ITP: less than 3 months ("newly diagnosed"), 3-12 months ("persistent"), and more than 12 months ("chronic"). METHODS: Adults with ITP and ≥ 1 romiplostim administration between 2009 and 2012 were included. Endpoints included durable platelet response, median platelet count, rescue therapy, bleeding and adverse events. We used inverse probability of censoring weighted estimators to estimate cumulative risk of each outcome. There were 64 newly diagnosed, 50 persistent, and 226 chronic ITP patients at romiplostim initiation. RESULTS: Durable platelet response at 24 weeks ranged from 32% [confidence interval (CI): 18-46%] in newly diagnosed patients to 53% (CI 37-68%) in persistent patients. Median platelet count during follow-up ranged from 88 (CI 80-96) × 109/L in chronic patients to 131 (CI 102-160) × 109/L in newly diagnosed patients. CONCLUSION: Regardless of ITP duration, over half of patients discontinued concomitant ITP medications. Few adverse events were observed. Although only approved for chronic patients, estimates of the romiplostim treatment effect were similar across patients being managed in European clinical practice, regardless of ITP duration at romiplostim initiation.

Sex differences in GBM revealed by analysis of patient imaging, transcriptome, and survival data.

Sex differences in the incidence and outcome of human disease are broadly recognized but, in most cases, not sufficiently understood to enable sex-specific approaches to treatment. Glioblastoma (GBM), the most common malignant brain tumor, provides a case in point. Despite well-established differences in incidence and emerging indications of differences in outcome, there are few insights that distinguish male and female GBM at the molecular level or allow specific targeting of these biological differences. Here, using a quantitative imaging-based measure of response, we found that standard therapy is more effective in female compared with male patients with GBM. We then applied a computational algorithm to linked GBM transcriptome and outcome data and identified sex-specific molecular subtypes of GBM in which cell cycle and integrin signaling are the critical determinants of survival for male and female patients, respectively. The clinical relevance of cell cycle and integrin signaling pathway signatures was further established through correlations between gene expression and in vitro chemotherapy sensitivity in a panel of male and female patient-derived GBM cell lines. Together, these results suggest that greater precision in GBM molecular subtyping can be achieved through sex-specific analyses and that improved outcomes for all patients might be accomplished by tailoring treatment to sex differences in molecular mechanisms.

The prevalence and impact of transient species in ecological communities.

Transient species occur infrequently in a community over time and do not maintain viable local populations. Because transient species interact differently than non-transients with their biotic and abiotic environment, it is important to characterize the prevalence of these species and how they impact our understanding of ecological systems. We quantified the prevalence and impact of transient species in communities using data on over 19,000 community time series spanning an array of ecosystems, taxonomic groups, and spatial scales. We found that transient species are a general feature of communities regardless of taxa or ecosystem. The proportion of these species decreases with increasing spatial scale leading to a need to control for scale in comparative work. Removing transient species from analyses influences the form of a suite of commonly studied ecological patterns including species-abundance distributions, species-energy relationships, species-area relationships, and temporal turnover. Careful consideration should be given to whether transient species are included in analyses depending on the theoretical and practical relevance of these species for the question being studied.

Effect of controlled delivery of neurotrophin-3 from fibrin on spinal cord injury in a long term model.

The goal of this work was to assess the effect of the controlled delivery of neurotrophin-3 (NT-3) from an affinity-based delivery system in fibrin scaffolds on regeneration following spinal cord injury (SCI). A heparin-based delivery system (HBDS) was used to immobilize NT-3 within fibrin scaffolds via non-covalent interactions. The fibrin scaffolds were implanted in lesions immediately after injury in an adult rat model of SCI (complete ablation of a 2 mm segment of the cord at T9). Delivery of NT-3 was controlled by an affinity-based delivery system that limits drug loss by diffusion and releases the drug via cell-mediated processes. Twelve weeks after injury and treatment, animals treated with fibrin scaffolds and NT-3, with or without the delivery system, did not show functional improvement over saline controls. Substantial cavitation at edges of the lesion was present, and while neuronal fibers were present inside the lesion, traced corticospinal and dorsal sensory tracts did not regenerate into the lesion. Therefore, while previous studies indicate that the controlled delivery of NT-3 from fibrin scaffolds may increase the short term regenerative response, the continued degeneration of the cord, indicative of the severity of the injury, limits the long term regeneration stimulated by this treatment. Chronic or repeated treatments or a less severe injury model may prove useful in assessing the utility of controlled delivery systems for the treatment of spinal cord injury.

Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury.

Neurotrophins have been shown to promote axonal growth and regeneration after spinal cord injury. The therapeutic utility of neurotrophins may be enhanced by using a controlled delivery system to increase the duration of neurotrophin availability following injury. Such a delivery system can be incorporated into a bioactive scaffold to serve as a physical bridge for regeneration. This study assessed the effect of controlled delivery of neurotrophin-3 (NT-3) from fibrin scaffolds implanted in spinal cord lesions immediately following 2-mm ablation injury in adult rats. Nine days after injury, fibrin scaffolds containing the delivery system and NT-3 (1000 ng/mL) elicited more robust neuronal fiber growth into the lesion than did control scaffolds or saline (1.5- to 3-fold increase). Implantation of fibrin scaffolds resulted in a dramatic reduction of glial scar formation at the white matter border of the lesion. Hindlimb motor function of treated animals did not improve relative to controls at 12 weeks post-injury. Thus, controlled delivery of NT-3 from fibrin scaffolds enhanced the initial regenerative response by increasing neuronal fiber sprouting and cell migration into the lesion, while functional motor recovery was not observed in this model.

Controlled release of neurotrophin-3 from fibrin gels for spinal cord injury.

The goal of this work was to assess the feasibility of using affinity-based delivery systems to release neurotrophin-3 (NT-3) in a controlled manner from fibrin gels as a therapy for spinal cord injury. A heparin-based delivery system (HBDS) was used to immobilize NT-3 within fibrin gels via non-covalent interactions to slow diffusion-based release of NT-3, thus allowing cell-activated degradation of fibrin to mediate release. The HBDS consists of three components: immobilized linker peptide, heparin and NT-3. The linker peptide contained a Factor XIIIa substrate and was covalently cross-linked to fibrin during polymerization. This immobilized linker peptide sequesters heparin within fibrin gels, and sequestered heparin binds NT-3, preventing its diffusion. Mathematical modeling was performed to examine the effect of heparin concentration on the fraction of NT-3 initially bound to fibrin. In vitro release studies confirmed that heparin concentration modulates diffusion-based release of NT-3. Fibrin gels containing the HBDS and NT-3 stimulated neural outgrowth from chick dorsal root ganglia by up to 54% versus unmodified fibrin, demonstrating that the NT-3 released is biologically active. In a preliminary in vivo study, fibrin gels containing the HBDS and NT-3 showed increased neural fiber density in spinal cord lesions versus unmodified fibrin at 9 days.