A Conceptual Framework to Integrate Biodiversity, Ecosystem Function, and Ecosystem Service Models.

Global biodiversity and ecosystem service models typically operate independently. Ecosystem service projections may therefore be overly optimistic because they do not always account for the role of biodiversity in maintaining ecological functions. We review models used in recent global model intercomparison projects and develop a novel model integration framework to more fully account for the role of biodiversity in ecosystem function, a key gap for linking biodiversity changes to ecosystem services. We propose two integration pathways. The first uses empirical data on biodiversity-ecosystem function relationships to bridge biodiversity and ecosystem function models and could currently be implemented globally for systems and taxa with sufficient data. We also propose a trait-based approach involving greater incorporation of biodiversity into ecosystem function models. Pursuing both approaches will provide greater insight into biodiversity and ecosystem services projections. Integrating biodiversity, ecosystem function, and ecosystem service modeling will enhance policy development to meet global sustainability goals.

The α-emitter astatine-211 targeted to CD38 can eradicate multiple myeloma in a disseminated disease model.

Minimal residual disease (MRD) has become an increasingly prevalent and important entity in multiple myeloma (MM). Despite deepening responses to frontline therapy, roughly 75% of MM patients never become MRD-negative to ≤10-5, which is concerning because MRD-negative status predicts significantly longer survival. MM is highly heterogeneous, and MRD persistence may reflect survival of isolated single cells and small clusters of treatment-resistant subclones. Virtually all MM clones are exquisitely sensitive to radiation, and the α-emitter astatine-211 (211At) deposits prodigious energy within 3 cell diameters, which is ideal for eliminating MRD if effectively targeted. CD38 is a proven MM target, and we conjugated 211At to an anti-CD38 monoclonal antibody to create an 211At-CD38 therapy. When examined in a bulky xenograft model of MM, single-dose 211At-CD38 at 15 to 45 µCi at least doubled median survival of mice relative to untreated controls (P < .003), but no mice achieved complete remission and all died within 75 days. In contrast, in a disseminated disease model designed to reflect low-burden MRD, 3 studies demonstrated that single-dose 211At-CD38 at 24 to 45 µCi produced sustained remission and long-term survival (>150 days) for 50% to 80% of mice, where all untreated mice died in 20 to 55 days (P < .0001). Treatment toxicities were transient and minimal. These data suggest that 211At-CD38 offers the potential to eliminate residual MM cell clones in low-disease-burden settings, including MRD. We are optimistic that, in a planned clinical trial, addition of 211At-CD38 to an autologous stem cell transplant (ASCT) conditioning regimen may improve ASCT outcomes for MM patients.

Therapeutic Efficacy of 213Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer.

Targeted alpha-particle therapy (TAT) might be a relevant therapeutic strategy to circumvent resistance to conventional therapies in the case of HER2-positive metastatic cancer. Single-domain antibody fragments (sdAb) are promising vehicles for TAT because of their excellent in vivo properties, high target affinity, and fast clearance kinetics. This study combines the cytotoxic α-particle emitter bismuth-213 (213Bi) and HER2-targeting sdAbs. The in vitro specificity, affinity, and cytotoxic potency of the radiolabeled complex were analyzed on HER2pos cells. Its in vivo biodistribution through serial dissections and via Cherenkov and micro-single-photon emission computed tomography (CT)/CT imaging was evaluated. Finally, the therapeutic efficacy and potential associated toxicity of [213Bi]Bi-DTPA-2Rs15d were evaluated in a HER2pos tumor model that manifests peritoneal metastasis. In vitro, [213Bi]Bi-DTPA-2Rs15d bound HER2pos cells in a HER2-specific way. In mice, high tumor uptake was reached already 15 min after injection, and extremely low uptake values were observed in normal tissues. Co-infusion of gelofusine resulted in a 2-fold reduction in kidney uptake. Administration of [213Bi]Bi-DTPA-2Rs15d alone and in combination with trastuzumab resulted in a significant increase in median survival. We describe for the very first time the successful labeling of an HER2-sdAb with the α-emitter 213Bi, and after intravenous administration, revealing high in vivo stability and specific accumulation in target tissue and resulting in an increased median survival of these mice especially in combination with trastuzumab. These results indicate the potential of [213Bi]Bi-DTPA-sdAb as a new radioconjugate for TAT, alone and as an add-on to trastuzumab for the treatment of HER2pos metastatic cancer.

Internal microdosimetry of alpha-emitting radionuclides.

At the tissue level, energy deposition in cells is determined by the microdistribution of alpha-emitting radionuclides in relation to sensitive target cells. Furthermore, the highly localized energy deposition of alpha particle tracks and the limited range of alpha particles in tissue produce a highly inhomogeneous energy deposition in traversed cell nuclei. Thus, energy deposition in cell nuclei in a given tissue is characterized by the probability of alpha particle hits and, in the case of a hit, by the energy deposited there. In classical microdosimetry, the randomness of energy deposition in cellular sites is described by a stochastic quantity, the specific energy, which approximates the macroscopic dose for a sufficiently large number of energy deposition events. Typical examples of the alpha-emitting radionuclides in internal microdosimetry are radon progeny and plutonium in the lungs, plutonium and americium in bones, and radium in targeted radionuclide therapy. Several microdosimetric approaches have been proposed to relate specific energy distributions to radiobiological effects, such as hit-related concepts, LET and track length-based models, effect-specific interpretations of specific energy distributions, such as the dual radiation action theory or the hit-size effectiveness function, and finally track structure models. Since microdosimetry characterizes only the initial step of energy deposition, microdosimetric concepts are most successful in exposure situations where biological effects are dominated by energy deposition, but not by subsequently operating biological mechanisms. Indeed, the simulation of the combined action of physical and biological factors may eventually require the application of track structure models at the nanometer scale.

Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model.

α-Emitting radionuclides deposit a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD). To evaluate this hypothesis, (211)At-labeled 1F5 monoclonal antibody (mAb) (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to (211)At-labeled 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor-bearing animals treated with doses of up to 48 µCi of (211)At-labeled anti-CD20 mAb ([(211)At]1F5-B10) experienced modest responses (0% cures but two- to threefold prolongation of survival compared with negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with (211)At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity was observed in the cured animals receiving 15 µCi of [(211)At]1F5-B10. These findings suggest that α-emitters are highly efficacious in MRD settings, where isolated cells and small tumor clusters prevail.

Designing ecological climate change impact assessments to reflect key climatic drivers.

Identifying the climatic drivers of an ecological system is a key step in assessing its vulnerability to climate change. The climatic dimensions to which a species or system is most sensitive - such as means or extremes - can guide methodological decisions for projections of ecological impacts and vulnerabilities. However, scientific workflows for combining climate projections with ecological models have received little explicit attention. We review Global Climate Model (GCM) performance along different dimensions of change and compare frameworks for integrating GCM output into ecological models. In systems sensitive to climatological means, it is straightforward to base ecological impact assessments on mean projected changes from several GCMs. Ecological systems sensitive to climatic extremes may benefit from what we term the 'model space' approach: a comparison of ecological projections based on simulated climate from historical and future time periods. This approach leverages the experimental framework used in climate modeling, in which historical climate simulations serve as controls for future projections. Moreover, it can capture projected changes in the intensity and frequency of climatic extremes, rather than assuming that future means will determine future extremes. Given the recent emphasis on the ecological impacts of climatic extremes, the strategies we describe will be applicable across species and systems. We also highlight practical considerations for the selection of climate models and data products, emphasizing that the spatial resolution of the climate change signal is generally coarser than the grid cell size of downscaled climate model output. Our review illustrates how an understanding of how climate model outputs are derived and downscaled can improve the selection and application of climatic data used in ecological modeling.

Rangeland management and fluvial geomorphology in northern Tanzania.

Researchers have independently documented the effects of land use on rivers and threats to river management institutions, but the relationship between changes in institutional context and river condition is not well described. This study assesses the connections between resource management institutions, land use, and rivers by integrating social science, geospatial analysis, and geomorphology. In particular, we measured hydraulic geometry, sediment size distributions, and estimated sediment yield for four rivers in northern Tanzania and conducted semistructured interviews that assessed corresponding resource management institutions. Communities managed rivers through both customary (traditional, nonstate) and government institutions, but the differences in the resource management policies and practices of the study rivers themselves were fairly subtle. Clearer differences were found at broader scales; the four watersheds exhibited substantial differences in land cover change and sediment yield associated with the location of settlements, roadways, and cultivation. Unexpectedly, these recent land use changes did not initiate a geomorphic response in rivers. The long history of grazing by domestic and wild ungulates may have influenced water and sediment supplies such that river channel dimensions are more resistant to changes in land use than other systems or have already adjusted to predominant changes in boundary conditions. This would suggest that not all rivers will have the anticipated responses to contemporary land use changes because of antecedent land use patterns; over long time scales (centuries to millennia), the presence of grazers may actually increase the ability of rivers to withstand changes in land use. Our findings point to a need for further interdisciplinary study of dryland rivers and their shifts between system states, especially in areas with a long history of grazing, relatively recent changes in land use, and a dynamic social and institutional context.

First measurements of radon-220 diffusion in mice tumors, towards treatment planning in diffusing alpha-emitters radiation therapy.

BACKGROUND: Diffusing alpha-emitters radiation therapy ("Alpha-DaRT") is a new method for treating solid tumors with alpha particles, relying on the release of the short-lived alpha-emitting daughter atoms of radium-224 from interstitial sources inserted into the tumor. Alpha-DaRT tumor dosimetry is governed by the spread of radium's progeny around the source, as described by an approximate framework called the "diffusion-leakage model". The most important model parameters are the diffusion lengths of radon-220 and lead-212, and their estimation is therefore essential for treatment planning. PURPOSE: Previous works have provided initial estimates for the dominant diffusion length, by measuring the activity spread inside mice-borne tumors several days after the insertion of an Alpha-DaRT source. The measurements, taken when lead-212 was in secular equilibrium with radium-224, were interpreted as representing the lead-212 diffusion length. The aim of this work is to provide first experimental estimates for the diffusion length of radon-220, using a new methodology. METHODS: The diffusion length of radon-220 was estimated from autoradiography measurements of histological sections taken from 24 mice-borne subcutaneous tumors of five different types. Unlike previous studies, the source dwell time inside the tumor was limited to 30 min, to prevent the buildup of lead-212. To investigate the contribution of potential non-diffusive processes, experiments were done in two sets: fourteen in vivo tumors, where during the treatment the tumors were still carried by the mice with active blood supply, and 10 ex-vivo tumors, where the tumors were excised before source insertion and kept in a medium at 37 ∘ C $37^\circ {\text{C}}$ with the source inside. RESULTS: The measured diffusion lengths of radon-220, extracted by fitting the recorded activity pattern up to 1.5 mm from the source, lie in the range 0.25 - 0.6 mm ${0.25-0.6}\nobreakspace {\text{mm}}$ , with no significant difference between the average values measured in in-vivo and ex-vivo tumors: L R n i n - v i v o = 0.40 ± 0.08 mm $L_{Rn}^{in-vivo}=0.40{\pm }0.08\nobreakspace {\text{mm}}$ versus L R n e x - v i v o = 0.39 ± 0.07 mm $L_{Rn}^{ex-vivo}=0.39{\pm }0.07\nobreakspace {\text{mm}}$ . However, in-vivo tumors display an enhanced spread of activity 2-3 mm away from the source. This effect is not explained by the current model and is much less pronounced in ex-vivo tumors. CONCLUSIONS: The average measured radon-220 diffusion lengths in both in-vivo and ex-vivo tumors are consistent with published data on the diffusion length of radon in water and lie close to the upper limit of the previously estimated range of 0.2 - 0.4 mm $0.2-0.4\nobreakspace {\text{mm}}$ . The observation that close to the source there is no apparent difference between in-vivo and ex-vivo tumors, and the good agreement with the theoretical model in this region suggest that the spread of radon-220 is predominantly diffusive in this region. The departure from the model prediction in in-vivo tumors at large radial distances may hint at potential vascular contribution, which will be the subject of future works.

Biodiversity loss reduces global terrestrial carbon storage.

Natural ecosystems store large amounts of carbon globally, as organisms absorb carbon from the atmosphere to build large, long-lasting, or slow-decaying structures such as tree bark or root systems. An ecosystem's carbon sequestration potential is tightly linked to its biological diversity. Yet when considering future projections, many carbon sequestration models fail to account for the role biodiversity plays in carbon storage. Here, we assess the consequences of plant biodiversity loss for carbon storage under multiple climate and land-use change scenarios. We link a macroecological model projecting changes in vascular plant richness under different scenarios with empirical data on relationships between biodiversity and biomass. We find that biodiversity declines from climate and land use change could lead to a global loss of between 7.44-103.14 PgC (global sustainability scenario) and 10.87-145.95 PgC (fossil-fueled development scenario). This indicates a self-reinforcing feedback loop, where higher levels of climate change lead to greater biodiversity loss, which in turn leads to greater carbon emissions and ultimately more climate change. Conversely, biodiversity conservation and restoration can help achieve climate change mitigation goals.

Bringing the Nature Futures Framework to life: creating a set of illustrative narratives of nature futures.

To halt further destruction of the biosphere, most people and societies around the globe need to transform their relationships with nature. The internationally agreed vision under the Convention of Biological Diversity-Living in harmony with nature-is that "By 2050, biodiversity is valued, conserved, restored and wisely used, maintaining ecosystem services, sustaining a healthy planet and delivering benefits essential for all people". In this context, there are a variety of debates between alternative perspectives on how to achieve this vision. Yet, scenarios and models that are able to explore these debates in the context of "living in harmony with nature" have not been widely developed. To address this gap, the Nature Futures Framework has been developed to catalyse the development of new scenarios and models that embrace a plurality of perspectives on desirable futures for nature and people. In this paper, members of the IPBES task force on scenarios and models provide an example of how the Nature Futures Framework can be implemented for the development of illustrative narratives representing a diversity of desirable nature futures: information that can be used to assess and develop scenarios and models whilst acknowledging the underpinning value perspectives on nature. Here, the term illustrative reflects the multiple ways in which desired nature futures can be captured by these narratives. In addition, to explore the interdependence between narratives, and therefore their potential to be translated into scenarios and models, the six narratives developed here were assessed around three areas of the transformative change debate, specifically, (1) land sparing vs. land sharing, (2) Half Earth vs. Whole Earth conservation, and (3) green growth vs. post-growth economic development. The paper concludes with an assessment of how the Nature Futures Framework could be used to assist in developing and articulating transformative pathways towards desirable nature futures. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-023-01316-1.

Mesenchymal Stem Cell-mediated delivery of the sodium iodide symporter supports radionuclide imaging and treatment of breast cancer.

Mesenchymal Stem Cells (MSCs) migrate specifically to tumors in vivo, and coupled with their capacity to bypass immune surveillance, are attractive vehicles for tumor-targeted delivery of therapeutic agents. This study aimed to introduce MSC-mediated expression of the sodium iodide symporter (NIS) for imaging and therapy of breast cancer. Tumor bearing animals received an intravenous or intratumoral injection of NIS expressing MSCs (MSC-NIS), followed by (99m) Technetium pertechnetate imaging 3-14 days later using a BazookaSPECT γ-camera. Tissue was harvested for analysis of human NIS (hNIS) expression by relative quantitative-polymerase chain reaction. Therapy animals received an i.p. injection of (131) I or saline 14 days after injection of MSC-NIS, and tumor volume was monitored for 8 weeks. After injection of MSC-NIS, BazookaSPECT imaging revealed an image of animal intestines and chest area at day 3, along with a visible weak tumor image. By day 14, the tumor was visible with a significant reduction in radionuclide accumulation in nontarget tissue observed. hNIS gene expression was detected in the intestines, heart, lungs, and tumors at early time points but later depleted in nontarget tissues and persisted at the tumor site. Based on imaging/biodistribution data, animals received a therapeutic dose of (131) I 14 days after MSC-NIS injection. This resulted in a significant reduction in tumor growth (mean ± SEM, 236 ± 62 mm(3) vs. 665 ± 204 mm(3) in controls). The ability to track MSC migration and transgene expression noninvasively in real time before therapy is a major advantage to this strategy. This promising data supports the feasibility of this approach as a novel therapy for breast cancer.

Feedbacks between conservation and social-ecological systems.

Robust ways to meet objectives of environmental conservation and social and economic development remain elusive. This struggle may in part be related to insufficient understanding of the feedbacks between conservation initiatives and social-ecological systems, specifically, the ways in which conservation initiatives result in social changes that have secondary effects on the environments targeted by conservation. To explore this idea, we sampled peer-reviewed articles addressing the social and environmental dimensions of conservation and coded each paper according to its research focus and characterization of these feedbacks. The majority of articles in our sample focused either on the effect of conservation initiatives on people (e.g., relocation, employment) or the effect of people on the environment (e.g., fragmentation, conservation efficacy of traditional management systems). Few studies in our sample empirically addressed both the social dynamics resulting from conservation initiatives and subsequent environmental effects. In many cases, one was measured and the other was discussed anecdotally. Among the studies that describe feedbacks between social and environmental variables, there was more evidence of positive (amplifying) feedbacks between social and environmental outcomes (i.e., undesirable social outcomes yielded undesirable environmental effects and desirable social outcomes yielded desirable environmental effects). The major themes within the sampled literature include conflict between humans and wild animals, social movements, adaptive comanagement, loss of traditional management systems, traditional ecological knowledge, human displacement and risks to livelihoods, and conservation and development. The narratives associated with each theme can serve as hypotheses for facilitating further discussion about conservation issues and for catalyzing future studies of the feedbacks between conservation and social-ecological systems.

Children's use of analogy during collaborative reasoning.

This microgenetic study examined social influences on children's development of analogical reasoning during peer-led small-group discussions of stories about controversial issues. A total of 277 analogies were identified among 7,215 child turns for speaking during 54 discussions from 18 discussion groups in 6 fourth-grade classrooms (N = 120; age M=10.0, SD=0.6). Use of analogy was found to spread among the children in discussion groups and occur at an accelerating rate, primarily because of the increasing use of novel analogies. Relational analogies with shared surface features triggered purely relational analogies during the next 2 speaking turns, showing a trend of relational shift. These results provide distinctive new evidence for the importance of social interaction in an aspect of cognitive development.

A System Calibration and Fast Iterative Reconstruction Method for Next-Generation SPECT Imagers.

Recently, high-resolution gamma cameras have been developed with detectors containing > 105-106 elements. Single-photon emission computed tomography (SPECT) imagers based on these detectors usually also have a large number of voxel bins and therefore face memory storage issues for the system matrix when performing fast tomographic reconstructions using iterative algorithms. To address these issues, we have developed a method that parameterizes the detector response to a point source and generates the system matrix on the fly during MLEM or OSEM on graphics hardware. The calibration method, interpolation of coefficient data, and reconstruction results are presented in the context of a recently commissioned small-animal SPECT imager, called FastSPECT III.

Use of radiolabeled hyaluronic acid for preclinical assessment of inflammatory injury and acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is accompanied by a dramatic increase in lung hyaluronic acid (HA), leading to a dose-dependent reduction of pulmonary oxygenation. This pattern is associated with severe infections, such as COVID-19, and other important lung injury etiologies. HA actively participates in molecular pathways involved in the cytokine storm of COVID-19-induced ARDS. The objective of this study was to evaluate an imaging approach of radiolabeled HA for assessment of dysregulated HA deposition in mouse models with skin inflammation and lipopolysaccharide (LPS)-induced ARDS using a novel portable intensified Quantum Imaging Detector (iQID) gamma camera system. METHODS: HA of 10 kDa molecular weight (HA10) was radiolabeled with 125I and 99mTc respectively to produce [125I]I-HA10 and [99mTc]Tc-HA10, followed by comparative studies on stability, in vivo biodistribution, and uptake at inflammatory skin sites in mice with 12-O-tetradecanoylphorbol-13-acetate (TPA)-inflamed ears. [99mTc]Tc-HA10 was used for iQID in vivo dynamic imaging of mice with ARDS induced by intratracheal instillation of LPS. RESULTS: [99mTc]Tc-HA10 and [125I]I-HA10 had similar biodistribution and localization at inflammatory sites. [99mTc]Tc-HA10 was shown to be feasible in measuring skin injury and monitoring skin wound healing. [99mTc]Tc-HA10 dynamic pulmonary images yielded good visualization of radioactive uptake in the lungs. There was significantly increased lung uptake and slower lung washout in mice with LPS-induced ARDS than in control mice. Postmortem biodistribution measurement of [99mTc]TcHA10 (%ID/g) was 11.0 ± 3.9 vs. 1.3 ± 0.3 in the ARDS mice (n = 6) and controls (n = 6) (P < 0.001), consistent with upregulated HA expression as determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) staining. CONCLUSIONS: [99mTc]Tc-HA10 is promising as a biomarker for evaluating HA dysregulation that contributes to pulmonary injury in ARDS. Rapid iQID imaging of [99mTc]Tc-HA10 clearance from injured lungs may provide a functional template for timely assessment and quantitative monitoring of pulmonary pathophysiology and intervention in ARDS.

Preclinical Evaluation of 225Ac-Labeled Single-Domain Antibody for the Treatment of HER2pos Cancer.

Human epidermal growth factor receptor type 2 (HER2) is overexpressed in various cancers; thus, HER2-targeting single-domain antibodies (sdAb) could offer a useful platform for radioimmunotherapy. In this study, we optimized the labeling of an anti-HER2-sdAb with the α-particle-emitter 225Ac through a DOTA-derivative. The formed radioconjugate was tested for binding affinity, specificity and internalization properties, whereas cytotoxicity was evaluated by clonogenic and DNA double-strand-breaks assays. Biodistribution studies were performed in mice bearing subcutaneous HER2pos tumors to estimate absorbed doses delivered to organs and tissues. Therapeutic efficacy and potential toxicity were assessed in HER2pos intraperitoneal ovarian cancer model and in healthy C57Bl/6 mice. [225Ac]Ac-DOTA-2Rs15d exhibited specific cell uptake and cell-killing capacity in HER2pos cells (EC50 = 3.9 ± 1.1 kBq/mL). Uptake in HER2pos lesions peaked at 3 hours (9.64 ± 1.69% IA/g), with very low accumulation in other organs (<1% IA/g) except for kidneys (11.69 ± 1.10% IA/g). α-camera imaging presented homogeneous uptake of radioactivity in tumors, although heterogeneous in kidneys, with a higher signal density in cortex versus medulla. In mice with HER2pos disseminated tumors, repeated administration of [225Ac]Ac-DOTA-2Rs15d significantly prolonged survival (143 days) compared to control groups (56 and 61 days) and to the group treated with HER2-targeting mAb trastuzumab (100 days). Histopathologic evaluation revealed signs of kidney toxicity after repeated administration of [225Ac]Ac-DOTA-2Rs15d. [225Ac]Ac-DOTA-2Rs15d efficiently targeted HER2pos cells and was effective in treatment of intraperitoneal disseminated tumors, both alone and as an add-on combination with trastuzumab, albeit with substantial signs of inflammation in kidneys. This study warrants further development of [225Ac]Ac-DOTA-2Rs15d.

Small-scale (sub-organ and cellular level) alpha-particle dosimetry methods using an iQID digital autoradiography imaging system.

Targeted radiopharmaceutical therapy with alpha-particle emitters (αRPT) is advantageous in cancer treatment because the short range and high local energy deposition of alpha particles enable precise radiation delivery and efficient tumor cell killing. However, these properties create sub-organ dose deposition effects that are not easily characterized by direct gamma-ray imaging (PET or SPECT). We present a computational procedure to determine the spatial distribution of absorbed dose from alpha-emitting radionuclides in tissues using digital autoradiography activity images from an ionizing-radiation quantum imaging detector (iQID). Data from 211At-radioimmunotherapy studies for allogeneic hematopoietic cell transplantation in a canine model were used to develop these methods. Nine healthy canines were treated with 16.9-30.9 MBq 211At/mg monoclonal antibodies (mAb). Lymph node biopsies from early (2-5 h) and late (19-20 h) time points (16 total) were obtained, with 10-20 consecutive 12-µm cryosections extracted from each and imaged with an iQID device. iQID spatial activity images were registered within a 3D volume for dose-point-kernel convolution, producing dose-rate maps. The accumulated absorbed doses for high- and low-rate regions were 9 ± 4 Gy and 1.2 ± 0.8 Gy from separate dose-rate curves, respectively. We further assess uptake uniformity, co-registration with histological pathology, and requisite slice numbers to improve microscale characterization of absorbed dose inhomogeneities in αRPT.

Using stylized agent-based models for population-environment research: A case study from the Galápagos Islands.

Agent Based Models (ABMs) are powerful tools for population-environment research but are subject to trade-offs between model complexity and abstraction. This study strikes a compromise between abstract and highly specified ABMs by designing a spatially explicit, stylized ABM and using it to explore policy scenarios in a setting that is facing substantial conservation and development challenges. Specifically, we present an ABM that reflects key Land Use / Land Cover (LULC) dynamics and livelihood decisions on Isabela Island in the Galápagos Archipelago of Ecuador. We implement the model using the NetLogo software platform, a free program that requires relatively little programming experience. The landscape is composed of a satellite-derived distribution of a problematic invasive species (common guava) and a stylized representation of the Galápagos National Park, the community of Puerto Villamil, the agricultural zone, and the marine area. The agent module is based on publicly available data and household interviews, and represents the primary livelihoods of the population in the Galápagos Islands - tourism, fisheries, and agriculture. We use the model to enact hypothetical agricultural subsidy scenarios aimed at controlling invasive guava and assess the resulting population and land cover dynamics. Findings suggest that spatially explicit, stylized ABMs have considerable utility, particularly during preliminary stages of research, as platforms for (1) sharpening conceptualizations of population-environment systems, (2) testing alternative scenarios, and (3) uncovering critical data gaps.

High-resolution, single-particle digital autoradiography of actinide sources using microcapillary array collimators and the iQID camera.

Characterization of the homogeneity of thin actinide deposits prior to and after irradiation is important to ensure measurement of high-quality nuclear data in nuclear physics experiments. Autoradiography is frequently used to assess homogeneity, but geometric blur from source thickness, particle range, and source-detector gap can significantly degrade image resolution and introduce bias when estimating source uniformity and activity. We establish a method for minimizing geometric blur using a new autoradiography imaging technique with microcapillary array collimators and a new method to characterize the homogeneity of an imaged deposit. Also, we demonstrate that beta-/gamma-blind imaging is possible for alpha-particle autoradiography with ZnS:Ag scintillators and the ionizing-radiation quantum imaging detector (iQID), a digital autoradiography system with intrinsic spatial resolutions up to 20 µm for alphas. This iQID imaging approach can successfully discriminate alphas in the presence of a beta-gamma source in samples containing >106 dynamic range in activity. We apply this feature to characterize the uniformity of plutonium deposits before and after accelerator irradiation in the presence of a large beta-gamma background.

Mapping 241Am Spatial Distribution Within Anatomical Bone Structures Using Digital Autoradiography.

Digital autoradiography with the ionizing radiation quantum imaging detector is used at the US Transuranium and Uranium Registries for visualizing the microdistribution of alpha particles from Am and quantifying the activity. The radionuclide spatial distribution was investigated within cortical and trabecular regions of bone samples from US Transuranium and Uranium Registries case 0846. Multiple specimens from the humerus proximal end, humerus proximal shaft, and clavicle acromial end were embedded in plastic, and 100-µm-thick sections were taken and imaged using the ionizing radiation quantum imaging detector. The detector images were superimposed on the anatomical structure images to visualize Am distribution in cortical bone, trabecular bone, and trabecular spongiosa. Activity concentration ratios were used to characterize Am distribution within different bone regions. The trabecular-to-cortical bone and trabecular-spongiosa-to-cortical bone activity concentration ratios were quantified in both humerus and clavicle. The ionizing radiation quantum imaging detector results were in agreement with those obtained from radiochemical analysis of the remaining bone specimens. The results were compared with International Commission on Radiological Protection default biokinetic model predictions. Digital autoradiography was proven to be an effective method for microscale heterogeneous distribution studies where traditional counting methods are impractical.