Recent acute shortage of medical radioisotopes prompted investigations into alternative methods of production and the use of a cyclotron and ¹⁰⁰Mo(p,2n)(99m)Tc reaction has been considered. In this ...context, the production yields of (99m)Tc and various other radioactive and stable isotopes which will be created in the process have to be investigated, as these may affect the diagnostic outcome and radiation dosimetry in human studies. Reaction conditions (beam and target characteristics, and irradiation and cooling times) need to be optimized in order to maximize the amount of (99m)Tc and minimize impurities. Although ultimately careful experimental verification of these conditions must be performed, theoretical calculations can provide the initial guidance allowing for extensive investigations at little cost. We report the results of theoretically determined reaction yields for (99m)Tc and other radioactive isotopes created when natural and enriched molybdenum targets are irradiated by protons. The cross-section calculations were performed using a computer program EMPIRE for the proton energy range 6-30 MeV. A computer graphical user interface for automatic calculation of production yields taking into account various reaction channels leading to the same final product has been created. The proposed approach allows us to theoretically estimate the amount of (99m)Tc and its ratio relative to (99g)Tc and other radioisotopes which must be considered reaction contaminants, potentially contributing to additional patient dose in diagnostic studies.
This study presents a summary of the dosimetry calculations performed for three technetium agents most commonly used in nuclear medicine diagnostic studies, namely sestamibi™, phosphonates and ...pertechnetate, labeled with cyclotron-produced technetium. Calculated patient doses were compared to those that would be delivered by the same radiotracers labeled with technetium obtained from a generator produced in a reactor. The main difference is that technetium from a generator is pure, i.e. contains only (99m)Tc and its decay product (99g)Tc, while in a cyclotron a large number of other stable and radioactive isotopes are created. In our calculations only technetium radioisotopes (ground and isomeric states) were considered as they will be included in the radiotracer labeling process and will contribute to the patient dose. Other elements should be removed by chemical purification. These dose estimates are based on our theoretical calculations of the proton-induced reaction cross sections and radioisotope production yields. Thick targets of enriched (three different compositions) and natural molybdenum, and three initial beam energies (16, 19 and 24 MeV) were considered for irradiation times of 3, 6 and 12 h with a beam current of 200 µA. The doses were calculated for injection times corresponding to 0, 2, 8, 12 and 24 h after the end of beam.
Cyclotron production of 99mTc through the (100)Mo(p,2n)99mTc reaction channel is actively being investigated as an alternative to reactor-based (99)Mo generation by nuclear fission of (235)U. Like ...most radioisotope production methods, cyclotron production of 99mTc will result in creation of unwanted impurities, including Tc and non-Tc isotopes. It is important to measure the amounts of these impurities for release of cyclotron-produced 99mTc (CPTc) for clinical use. Detection of radioactive impurities will rely on measurements of their gamma (γ) emissions. Gamma spectroscopy is not suitable for this purpose because the overwhelming presence of 99mTc and the count-rate limitations of γ spectroscopy systems preclude fast and accurate measurement of small amounts of impurities. In this article we describe a simple and fast method for measuring γ emission rates from radioactive impurities in CPTc. The proposed method is similar to that used to identify (99)Mo breakthrough in generator-produced 99mTc: one dose calibrator (DC) reading of a CPTc source placed in a lead shield is followed by a second reading of the same source in air. Our experimental and theoretical analysis show that the ratio of DC readings in lead to those in air are linearly related to γ emission rates from impurities per MBq of 99mTc over a large range of clinically-relevant production conditions. We show that estimates of the γ emission rates from Tc impurities per MBq of 99mTc can be used to estimate increases in radiation dose (relative to pure 99mTc) to patients injected with CPTc-based radiopharmaceuticals. This enables establishing dosimetry-based clinical-release criteria that can be tested using commercially-available dose calibrators. We show that our approach is highly sensitive to the presence of 93gTc, 93mTc, 94gTc, 94mTc, 95mTc, 95gTc, and 96gTc, in addition to a number of non-Tc impurities.
Predation is a central feature of ecological communities. Most theoretical and empirical studies of predation focus on the consequences of predators consuming their prey. Predators reduce prey ...population densities through direct consumption (a density-mediated interaction, DMI), a process that may indirectly affect the prey's resources, competitors, and other predators. However, predators can also affect prey population density by stimulating costly defensive strategies. The costs of these defensive strategies can include reduced energy income, energetic investment in defensive structures, lower mating success, increased vulnerability to other predators, or emigration. Theoretical and empirical studies confirm the existence of these induced costs (trait-mediated interactions, TMIs); however, the relative importance of intimidation (TMI) and consumption (DMI) effects remains an open question. We conducted a meta-analysis assessing the magnitude of both TMIs and DMIs in predator-prey interactions. On average, the impact of intimidation on prey demographics was at least as strong as direct consumption (63% and 51% the size of the total predator effect, respectively). This contrast is even more pronounced when we consider the cascading effects of predators on their prey's resources: density effects attenuated through food chains, while TMIs remained strong, rising to 85% of the total predator effect. Predators can thus strongly influence resource density even if they consume few prey items. Finally, intimidation was more important in aquatic than terrestrial ecosystems. Our results suggest that the costs of intimidation, traditionally ignored in predator-prey ecology, may actually be the dominant facet of trophic interactions.
Cyclotron production of (99m)Tc through the (100)Mo(p,2n) (99m)Tc reaction channel is actively being investigated as an alternative to reactor-based (99)Mo generation by nuclear fission of (235)U. An ...exciting aspect of this approach is that it can be implemented using currently-existing cyclotron infrastructure to supplement, or potentially replace, conventional (99m)Tc production methods that are based on aging and increasingly unreliable nuclear reactors. Successful implementation will require consistent production of large quantities of high-radionuclidic-purity (99m)Tc. However, variations in proton beam currents and the thickness and isotopic composition of enriched (100)Mo targets, in addition to other irradiation parameters, may degrade reproducibility of both radionuclidic purity and absolute (99m)Tc yields. The purpose of this article is to present a method for quantifying relationships between random variations in production parameters, including (100)Mo target thicknesses and proton beam currents, and reproducibility of absolute (99m)Tc yields (defined as the end of bombardment (EOB) (99m)Tc activity). Using the concepts of linear error propagation and the theory of stochastic point processes, we derive a mathematical expression that quantifies the influence of variations in various irradiation parameters on yield reproducibility, quantified in terms of the coefficient of variation of the EOB (99m)Tc activity. The utility of the developed formalism is demonstrated with an example. We show that achieving less than 20% variability in (99m)Tc yields will require highly-reproducible target thicknesses and proton currents. These results are related to the service rate which is defined as the percentage of (99m)Tc production runs that meet the minimum daily requirement of one (or many) nuclear medicine departments. For example, we show that achieving service rates of 84.0%, 97.5% and 99.9% with 20% variations in target thicknesses requires producing on average 1.2, 1.5 and 1.9 times the minimum daily activity requirement. The irradiation parameters that would be required to achieve these service rates are described. We believe the developed formalism will aid in the development of quality-control criteria required to ensure consistent supply of large quantities of high-radionuclidic-purity cyclotron-produced (99m)Tc.
Ecological and evolutionary processes are affected by forces acting at both local and regional scales, yet our understanding of how these scales interact has remained limited. These processes are ...fundamentally linked through individuals that develop as juveniles in one environment and then either remain in the natal habitat or disperse to new environments. Empirical studies in a diverse range of organisms have demonstrated that the conditions experienced in the natal habitat can have profound effects on the adult phenotype. This environmentally induced phenotypic variation can in turn affect the probability that an individual will disperse to a new environment and the ecological and evolutionary impact of that individual in the new environment. We synthesize the literature on this process and propose a framework for exploring the linkage between local developmental environment and dispersal. We then discuss the ecological and evolutionary implications of dispersal asymmetries generated by the effects of natal habitat conditions on individual phenotypes. Our review indicates that the influence of natal habitat conditions on adult phenotypes may be a highly general mechanism affecting the flow of individuals between populations. The wealth of information already gathered on how local conditions affect adult phenotype can and should be integrated into the study of dispersal as a critical force in ecology and evolution.
Organisms that shift their phenologies in response to global warming will experience novel photic environments, as photoperiod (daylength) continues to follow the same annual cycle. How different ...organisms respond to novel photoperiods could result in phenological mismatches and altered interspecific interactions. We conducted an outdoor mesocosm experiment exposing green frog (Rana clamitans) larvae, gray treefrog (Hyla versicolor) larvae, phytoplankton, periphyton, and zooplankton to a three‐month shift in photoperiod: an early‐season photoperiod (simulating April) and a late‐season photoperiod (simulating July). We manipulated photoperiod by covering and uncovering tanks with clear or light‐blocking lids to mimic realistic changes in daylength. We assessed amphibian life history traits and measured phytoplankton, periphyton, and zooplankton abundances. Green frog larvae and gray treefrog metamorphs were more developed under the early‐season photoperiod. Gray treefrog total length was also reduced, but photoperiod did not affect green frog total length. Although phytoplankton and periphyton abundances were not affected by photoperiod, copepod nauplii were in greater abundance under the early‐season photoperiod. Overall, this simplified aquatic community did not exhibit significant changes to structure when exposed to a three‐month shift in photoperiod. Temperate amphibians that breed earlier in the year may develop faster, which may have long‐term costs to post‐metamorphic growth and performance. Asynchronous shifts in zooplankton abundances in response to altered photoperiods could subsequently affect freshwater community structure. While photoperiod has been shown to individually affect freshwater organisms, our study using replicated outdoor wetland communities shows that the comprehensive effects of photoperiod may be less important than other cues such as temperature and precipitation.
We conducted a field‐based, mesocosm experiment exposing a simplified freshwater community (amphibians, phytoplankton, periphyton, and zooplankton) to a three‐month shift in photoperiod. Our results demonstrate that both amphibians developed faster and copepod reproduction increased under the early‐season photoperiod. Remarkably, our results suggest that this temperate freshwater community did not exhibit significant changes in structure despite being exposed to photoperiods representing two distinct seasons (spring and summer).
Predator-induced phenotypic plasticity is widespread in nature and includes variation in life history, morphology, and behavior. In organisms with complex life histories, predator-induced phenotypic ...plasticity in the larval period has been widely documented. Several models predict how organisms should alter their size at and time to metamorphosis in response to an increased risk of predation. A survey of empirical studies finds that these theoretical predictions are frequently met. However, no one model performs the best. Additionally, there are several results not predicted by any model. Predator-induced plasticity in metamorphic traits may be related to predator-induced changes in larval morphology and behavior. Predictions of predator effects on larval traits are generally met, except for direct costs of predator-induced morphological phenotypes. Future work should incorporate more detailed studies of growth rate, morphology, and behavior during the larval period, as well as studies of size-specific mortality rates in the presence and absence of predators.
Purpose
Image artefacts continue to pose challenges in clinical molecular imaging, resulting in misdiagnoses, additional radiation doses to patients and financial costs. Mismatch and halo artefacts ...occur frequently in gallium-68 (
68
Ga)-labelled compounds whole-body PET/CT imaging. Correcting for these artefacts is not straightforward and requires algorithmic developments, given that conventional techniques have failed to address them adequately. In the current study, we employed differential privacy-preserving federated transfer learning (FTL) to manage clinical data sharing and tackle privacy issues for building centre-specific models that detect and correct artefacts present in PET images.
Methods
Altogether, 1413 patients with
68
Ga prostate-specific membrane antigen (PSMA)/DOTA-TATE (TOC) PET/CT scans from 3 countries, including 8 different centres, were enrolled in this study. CT-based attenuation and scatter correction (CT-ASC) was used in all centres for quantitative PET reconstruction. Prior to model training, an experienced nuclear medicine physician reviewed all images to ensure the use of high-quality, artefact-free PET images (421 patients’ images). A deep neural network (modified U2Net) was trained on 80% of the artefact-free PET images to utilize centre-based (CeBa), centralized (CeZe) and the proposed differential privacy FTL frameworks. Quantitative analysis was performed in 20% of the clean data (with no artefacts) in each centre. A panel of two nuclear medicine physicians conducted qualitative assessment of image quality, diagnostic confidence and image artefacts in 128 patients with artefacts (256 images for CT-ASC and FTL-ASC).
Results
The three approaches investigated in this study for
68
Ga-PET imaging (CeBa, CeZe and FTL) resulted in a mean absolute error (MAE) of 0.42 ± 0.21 (
CI
95%: 0.38 to 0.47), 0.32 ± 0.23 (
CI
95%: 0.27 to 0.37) and 0.28 ± 0.15 (
CI
95%: 0.25 to 0.31), respectively. Statistical analysis using the Wilcoxon test revealed significant differences between the three approaches, with FTL outperforming CeBa and CeZe (
p
-value < 0.05) in the clean test set. The qualitative assessment demonstrated that FTL-ASC significantly improved image quality and diagnostic confidence and decreased image artefacts, compared to CT-ASC in
68
Ga-PET imaging. In addition, mismatch and halo artefacts were successfully detected and disentangled in the chest, abdomen and pelvic regions in
68
Ga-PET imaging.
Conclusion
The proposed approach benefits from using large datasets from multiple centres while preserving patient privacy. Qualitative assessment by nuclear medicine physicians showed that the proposed model correctly addressed two main challenging artefacts in
68
Ga-PET imaging. This technique could be integrated in the clinic for
68
Ga-PET imaging artefact detection and disentanglement using multicentric heterogeneous datasets.
A mechanistic understanding of phenology, the seasonal timing of life history events, is important for understanding species’ interactions and the potential responses of ecological communities to a ...rapidly changing climate. We present analysis of a seven-year dataset on the breeding phenology of wood frogs (Rana sylvatica), tiger salamanders (Ambystoma tigrinum), blue-spotted salamanders (Ambystoma laterale), and associated unisexual Ambystoma salamanders from six wetlands in Southeast Michigan, USA. We assess whether the ordinal date of breeding migrations varies among species, sexes, and individual wetlands, and we describe the specific environmental conditions associated with breeding migrations for each species/sex. Breeding date was significantly affected by species/sex identity, year, wetland, and the interactions between species/sex and year as well as wetland and year. There was a great deal of variation among years, with breeding occurring nearly synchronously among groups in some years but widely spaced between groups in other years. Specific environmental triggers for movement varied for each species and sex and changed as the breeding season progressed. In general, salamanders responded to longer temperature lags (more warmer days in a row) than wood frogs, whereas wood frogs required longer precipitation lags (more rainy days in a row) than salamanders. Wood frogs were more likely to migrate around the time of a new moon, whereas in contrast, Ambystoma salamander migration was not associated with a moon phase. Ordinal day was an important factor in all models, suggesting that these amphibians require a latency period or similar mechanism to avoid breeding too early in the year, even when weather conditions appear favorable. Male wood frogs migrated earlier than female wood frogs, and male blue-spotted salamanders migrated earlier than female A. laterale and associated unisexual females. Larger unisexual salamanders migrated earlier than smaller individuals. Differences in species’ responses to environmental cues led to wood frogs and A. laterale breeding later than tiger salamanders in colder years but not in warmer years. This suggests that, as the climate warms, wood frog and A. laterale larvae may experience less predation from tiger salamander larvae due to reduced size differences when they breed simultaneously. Our study is one of few to describe the proximate drivers of amphibian breeding migrations across multiple species, wetlands, and years, and it can inform models predicting how climate change may shift ecological interactions among pond-breeding amphibian species.
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