Sierra Nevada reference conditions: A dataset of contemporary reference sites and corresponding remote sensing-derived forest structure metrics for yellow pine and mixed-conifer forests.

Contemporary reference sites in California's Sierra Nevada represent areas where a frequent, low-intensity fire regime - an integral ecological process in temperate dry forests - has been reintroduced after several decades of fire suppression. Produced by an intact fire regime, forest structural patterns in these sites are likely more resilient to future disturbances and climate, and thus can provide reference conditions to guide management and ecological research. In this paper, we present a set of 119 delineated contemporary reference sites in the Sierra Nevada yellow pine and mixed-conifer zone along with a suite of key remote sensing-derived forest structure metrics representing conditions within these sites. We also provide a set of summary figures for individual reference sites and sites grouped by dominant climate class. We identified restored frequent-fire landscapes using a combination of fire history, burn severity, management history, and forest type datasets and we delineated individual polygons using catchment basins, fire perimeters, and imagery. Reference sites ranged in size from 101-966 ha with a mean size of 240 ha. Where available (for 59 sites), we used airborne lidar datasets to characterize a suite of key forest structure metrics within reference sites. Across all 119 sites, we provide a set of forest structure metrics produced by the California Forest Observatory. Reference sites were categorized based on their dominant climate class to assist users in identifying the most climatically relevant reference conditions for their project or study area. We encourage the use of the reference sites and associated forest structure datasets for guiding ecologically focused forest management and research in the Sierra Nevada.

Reduced Theta Power During Memory Retrieval in Depressed Adults.

BACKGROUND: Major depressive disorder (MDD) is associated with poor recollection, but the neural mechanisms responsible for this deficit are unclear. Recollection is supported by interactions between the hippocampus and cortex that appear to be mediated by oscillatory activity in the theta band (4-7 Hz) and that are elicited during source memory retrieval. Therefore, we tested the hypothesis that evoked theta power during source memory retrieval would be reduced in MDD, as this would provide a physiological basis for deficient recollection in adults with depression. METHODS: Morlet wavelets were applied to event-related potentials collected from 24 unmedicated adults with MDD and 24 healthy control adults during the retrieval of source and semantic memories. Whole-scalp analyses focused on group differences in evoked theta power. RESULTS: There were no group differences in behavior. Nevertheless, from 400 to 799 ms, theta power was broadly reduced in adults with depression versus healthy adults. This reduction was observed during source and semantic retrieval. Parietal midline electrodes showed significantly reduced theta power during source-but not semantic-retrieval in adults with depression versus healthy adults in this interval. Furthermore, theta power over parietal midline sites from 400 to 799 ms was more strongly related to source memory accuracy in healthy adults versus adults with depression. CONCLUSIONS: Relative to healthy control adults, adults with depression showed reduced theta power during memory retrieval and a weaker relationship between parietal midline theta power and source memory accuracy. These findings indicate that abnormal theta signals may contribute to memory deficits in adults with MDD.

Three-dimensional partitioning of resources by congeneric forest predators with recent sympatry.

Coexistence of ecologically similar species can be maintained by partitioning along one or more niche axes. Three-dimensional structural complexity is central to facilitating resource partitioning between many forest species, but is underrepresented in field-based studies. We examined resource selection by sympatric northern spotted owls (Strix occidentalis caurina), a threatened species under the US Endangered Species Act, and nonnative barred owls (S. varia) in western Oregon, USA to explore the relative importance of canopy heterogeneity, vertical complexity of forest, and abiotic features to resource selection and identify potential differences that may facilitate long-term coexistence. We predicted that within home range selection of understory densities, measured with airborne lidar, would differ between species based on proportional differences in arboreal and terrestrial prey taken by each owl species. We used discrete choice models and telemetry data from 41 spotted owls and 38 barred owls monitored during 2007-2009 and 2012-2015. Our results suggested that while both species used tall canopy areas more often than low canopy areas, spotted owls were more commonly found in areas with lower tree cover, more developed understory, and steeper slopes. This is the first evidence of fine-scale partitioning based on structural forest properties by northern spotted owls and barred owls.

Multiscale divergence between Landsat- and lidar-based biomass mapping is related to regional variation in canopy cover and composition.

BACKGROUND: Satellite-based aboveground forest biomass maps commonly form the basis of forest biomass and carbon stock mapping and monitoring, but biomass maps likely vary in performance by region and as a function of spatial scale of aggregation. Assessing such variability is not possible with spatially-sparse vegetation plot networks. In the current study, our objective was to determine whether high-resolution lidar-based and moderate-resolution Landsat-base aboveground live forest biomass maps converged on similar predictions at stand- to landscape-levels (10 s to 100 s ha) and whether such differences depended on biophysical setting. Specifically, we examined deviations between lidar- and Landsat-based biomass mapping methods across scales and ecoregions using a measure of error (normalized root mean square deviation), a measure of the unsystematic deviations, or noise (Pearson correlation coefficient), and two measures related to systematic deviations, or biases (intercept and slope of a regression between the two sets of predictions). RESULTS: Compared to forest inventory data (0.81-ha aggregate-level), lidar and Landsat-based mean biomass predictions exhibited similar performance, though lidar predictions exhibited less normalized root mean square deviation than Landsat when compared with the reference plot data. Across aggregate-levels, the intercepts and slopes of regression equations describing the relationships between lidar- and Landsat-based biomass predictions stabilized (i.e., little additional change with increasing area of aggregates) at aggregate-levels between 10 and 100 ha, suggesting a consistent relationship between the two maps at landscape-scales. Differences between lidar- and Landsat-based biomass maps varied as a function of forest canopy heterogeneity and composition, with systematic deviations (regression intercepts) increasing with mean canopy cover and hardwood proportion within forests and correlations decreasing with hardwood proportion. CONCLUSIONS: Deviations between lidar- and Landsat-based maps indicated that satellite-based approaches may represent general gradients in forest biomass. Ecoregion impacted deviations between lidar and Landsat biomass maps, highlighting the importance of biophysical setting in determining biomass map performance across aggregate scales. Therefore, regardless of the source of remote sensing (e.g., Landsat vs. lidar), factors affecting the measurement and prediction of forest biomass, such as species composition, need to be taken into account whether one is estimating biomass at the plot, stand, or landscape scale.

Small field dosimetry for the small animal radiotherapy research platform (SARRP).

BACKGROUND: Preclinical radiation biology has become increasingly sophisticated due to the implementation of advanced small animal image guided radiation platforms into laboratory investigation. These small animal radiotherapy devices enable state-of-the-art image guided therapy (IGRT) research to be performed by combining high-resolution cone beam computed tomography (CBCT) imaging with an isocentric irradiation system. Such platforms are capable of replicating modern clinical systems similar to those that integrate a linear accelerator with on-board CBCT image guidance. METHODS: In this study, we present a dosimetric evaluation of the small animal radiotherapy research platform (SARRP, Xstrahl Inc.) focusing on small field dosimetry. Physical dosimetry was assessed using ion chamber for calibration and radiochromic film, investigating the impact of beam focus size on the dose rate output as well as beam characteristics (beam shape and penumbra). Two film analysis tools) have been used to assess the dose output using the 0.5 mm diameter aperture. RESULTS: Good agreement (between 1.7-3%) was found between the measured physical doses and the data provided by Xstrahl for all apertures used. Furthermore, all small field dosimetry data are in good agreement for both film reading methods and with our Monte Carlo simulations for both focal spot sizes. Furthermore, the small focal spot has been shown to produce a more homogenous beam with more stable penumbra over time. CONCLUSIONS: FilmQA Pro is a suitable tool for small field dosimetry, with a sufficiently small sampling area (0.1 mm) to ensure an accurate measurement. The electron beam focus should be chosen with care as this can potentially impact on beam stability and reproducibility.

Pulsed Radiation Therapy With Concurrent Cisplatin Results in Superior Tumor Growth Delay in a Head and Neck Squamous Cell Carcinoma Murine Model.

PURPOSE: To assess the efficacy of 3-week schedules of low-dose pulsed radiation treatment (PRT) and standard radiation therapy (SRT), with concurrent cisplatin (CDDP) in a head and neck squamous cell carcinoma xenograft model. METHODS AND MATERIALS: Subcutaneous UT-SCC-14 tumors were established in athymic NIH III HO female mice. A total of 30 Gy was administered as 2 Gy/d, 5 d/wk for 3 weeks, either by PRT (10 × 0.2 Gy/d, with a 3-minute break between each 0.2-Gy dose) or SRT (2 Gy/d, uninterrupted delivery) in combination with concurrent 2 mg/kg CDDP 3 times per week in the final 2 weeks of radiation therapy. Treatment-induced growth delays were defined from twice-weekly tumor volume measurements. Tumor hypoxia was assessed by (18)F-fluoromisonidazole positron emission tomography imaging, and calculated maximum standardized uptake values compared with tumor histology. Tumor vessel density and hypoxia were measured by quantitative immunohistochemistry. Normal tissues effects were evaluated in gut and skin. RESULTS: Untreated tumors grew to 1000 mm(3) in 25.4 days (±1.2), compared with delays of 62.3 days (±3.5) for SRT + CDDP and 80.2 days (±5.0) for PRT + CDDP. Time to reach 2× pretreatment volume ranged from 8.2 days (±1.8) for untreated tumors to 67.1 days (±4.7) after PRT + CDDP. Significant differences in tumor growth delay were observed for SRT versus SRT + CDDP (P=.04), PRT versus PRT + CDDP (P=.035), and SRT + CDDP versus PRT + CDDP (P=.033), and for survival between PRT versus PRT + CDDP (P=.017) and SRT + CDDP versus PRT + CDDP (P=.008). Differences in tumor hypoxia were evident by (18)F-fluoromisonidazole positron emission tomography imaging between SRT and PRT (P=.025), although not with concurrent CDDP. Tumor vessel density differed between SRT + CDDP and PRT + CDDP (P=.011). No differences in normal tissue parameters were seen. CONCLUSIONS: Concurrent CDDP was more effective in combination PRT than SRT at restricting tumor growth. Significant differences in tumor vascular density were evident between PRT and SRT, suggesting a preservation of vascular network with PRT.

Effect of Irradiation on Tumor Microenvironment and Bone Marrow Cell Migration in a Preclinical Tumor Model.

PURPOSE: To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts. METHODS AND MATERIALS: Subcutaneous LLC tumors were established in C57BL/6 mice. Standard RT or PRT was given at 2 Gy/d for a total dose of 20 Gy using a 5 days on, 2 days off schedule to mimic clinical delivery. Radiation-induced tumor microenvironment changes were examined after treatment using flow cytometry and antibody-specific histopathology. Normal tissue effects were measured using noninvasive (18)F-fluorodeoxyglucose positron emission tomography/computed tomography after naïve animals were given whole-lung irradiation to 40 Gy in 4 weeks using the same 2-Gy/d regimens. RESULTS: Over the 2 weeks of therapy, PRT was more effective than SRT at reducing tumor growth rate (0.31 ± 0.02 mm(3)/d and 0.55 ± 0.04 mm(3)/d, respectively; P<.007). Histopathology showed a significant comparative reduction in the levels of Ki-67 (14.5% ± 3%), hypoxia (10% ± 3.5%), vascular endothelial growth factor (2.3% ± 1%), and stromal-derived factor-1α (2.5% ± 1.4%), as well as a concomitant decrease in CD45(+) bone marrow-derived cell (BMDC) migration (7.8% ± 2.2%) after PRT. The addition of AMD3100 also decreased CD45(+) BMDC migration in treated tumors (0.6% ± 0.1%). Higher vessel density was observed in treated tumors. No differences were observed in normal lung tissue after PRT or SRT. CONCLUSIONS: Pulsed RT-treated tumors exhibited slower growth and reduced hypoxia. Pulsed RT eliminated initiation of supportive mechanisms utilized by tumors in low oxygen microenvironments, including angiogenesis and recruitment of BMDCs.

The Effects of Pulsed Radiation Therapy on Tumor Oxygenation in 2 Murine Models of Head and Neck Squamous Cell Carcinoma.

PURPOSE: To evaluate the efficacy of low-dose pulsed radiation therapy (PRT) in 2 head and neck squamous cell carcinoma (HNSCC) xenografts and to investigate the mechanism of action of PRT compared with standard radiation therapy (SRT). METHODS AND MATERIALS: Subcutaneous radiosensitive UT-SCC-14 and radioresistant UT-SCC-15 xenografts were established in athymic NIH III HO female mice. Tumors were irradiated with 2 Gy/day by continuous standard delivery (SRT: 2 Gy) or discontinuous low-dose pulsed delivery (PRT: 0.2 Gy × 10 with 3-min pulse interval) to total doses of 20 Gy (UT14) or 40 Gy (UT15) using a clinical 5-day on/2-day off schedule. Treatment response was assessed by changes in tumor volume, (18)F-fluorodeoxyglucose (FDG) (tumor metabolism), and (18)F-fluoromisonidazole (FMISO) (hypoxia) positron emission tomography (PET) imaging before, at midpoint, and after treatment. Tumor hypoxia using pimonidazole staining and vascular density (CD34 staining) were assessed by quantitative histopathology. RESULTS: UT15 and UT14 tumors responded similarly in terms of growth delay to either SRT or PRT. When compared with UT14 tumors, UT15 tumors demonstrated significantly lower uptake of FDG at all time points after irradiation. UT14 tumors demonstrated higher levels of tumor hypoxia after SRT when compared with PRT as measured by (18)F-FMISO PET. By contrast, no differences were seen in (18)F-FMISO PET imaging between SRT and PRT for UT15 tumors. Histologic analysis of pimonidazole staining mimicked the (18)F-FMISO PET imaging data, showing an increase in hypoxia in SRT-treated UT14 tumors but not PRT-treated tumors. CONCLUSIONS: Differences in (18)F-FMISO uptake for UT14 tumors after radiation therapy between PRT and SRT were measurable despite the similar tumor growth delay responses. In UT15 tumors, both SRT and PRT were equally effective at reducing tumor hypoxia to a significant level as measured by (18)F-FMISO and pimonidazole.

Hematopoietic stem and progenitor cell migration after hypofractionated radiation therapy in a murine model.

PURPOSE: To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model. METHODS AND MATERIALS: Lewis lung carcinoma tumors were established in C57BL/6 mice and irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with positron emission tomography/computed tomography (PET/CT) and measured daily with digital calipers. The HSPC and myelomonocytic cell content was assessed via immunofluorescent staining and flow cytometry. Functionality of tumor-associated HSPCs was verified in vitro using colony-forming cell assays and in vivo by rescuing lethally irradiated C57BL/6 recipients. RESULTS: Irradiation significantly reduced tumor volumes and tumor regrowth rates compared with nonirradiated controls. The number of CD133(+) HSPCs present in irradiated tumors was higher than in nonirradiated tumors during all stages of regrowth. CD11b(+) counts were similar. PET/CT imaging and growth rate analysis based on standardized uptake value indicated that HSPC recruitment directly correlated to the extent of regrowth and intratumor cell activity after irradiation. The BM-derived tumor-associated HSPCs successfully formed hematopoietic colonies and engrafted irradiated mice. Finally, targeted treatment with a small animal radiation research platform demonstrated localized HSPC recruitment to defined tumor subsites exposed to radiation. CONCLUSIONS: Hypofractionated irradiation resulted in a pronounced and targeted recruitment of BM-derived HSPCs, possibly as a mechanism to promote tumor regrowth. These data indicate for the first time that radiation therapy regulates HSPC content within regrowing tumors.