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Regularized regression analysis is a mature analytic approach to identify weighted sums of variables predicting outcomes. We present a novel Coarse Approximation Linear Function (CALF) to frugally select important predictors and build simple but powerful predictive models. CALF is a linear regression strategy applied to normalized data that uses nonzero weights + 1 or - 1. Qualitative (linearly invariant) metrics to be optimized can be (for binary response) Welch (Student) t-test p-value or area under curve (AUC) of receiver operating characteristic, or (for real response) Pearson correlation. Predictor weighting is critically important when developing risk prediction models. While counterintuitive, it is a fact that qualitative metrics can favor CALF with ± 1 weights over algorithms producing real number weights. Moreover, while regression methods may be expected to change most or all weight values upon even small changes in input data (e.g., discarding a single subject of hundreds) CALF weights generally do not so change. Similarly, some regression methods applied to collinear or nearly collinear variables yield unpredictable magnitude or the direction (in p-space) of the weights as a vector. In contrast, with CALF if some predictors are linearly dependent or nearly so, CALF simply chooses at most one (the most informative, if any) and ignores the others, thus avoiding the inclusion of two or more collinear variables in the model.
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Algoritmos , Área Bajo la Curva , Humanos , Modelos Lineales , Curva ROCRESUMEN
Chronic inflammation leads to bone loss and fragility. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) consistently promote bone resorption. Dietary modulation of proinflammatory cytokines is an accepted therapeutic approach to treat chronic inflammation, including that induced by space-relevant radiation exposure. As such, these studies were designed to determine whether an anti-inflammatory diet, high in omega-3 fatty acids, could reduce radiation-mediated bone damage via reductions in the levels of inflammatory cytokines in osteocytes and serum. Lgr5-EGFP C57BL/6 mice were randomized to receive diets containing fish oil and pectin (FOP; high in omega-3 fatty acids) or corn oil and cellulose (COC; high in omega-6 fatty acids) and then acutely exposed to 0.5-Gy 56Fe or 2.0-Gy gamma-radiation. Mice fed the FOP diet exhibited consistent reductions in serum TNF-α in the 56Fe experiment but not the gamma-experiment. The percentage osteocytes (%Ot) positive for TNF-α increased in gamma-exposed COC, but not FOP, mice. Minimal changes in %Ot positive for sclerostin were observed. FOP mice exhibited modest improvements in several measures of cancellous microarchitecture and volumetric bone mineral density (BMD) postexposure to 56Fe and gamma-radiation. Reduced serum TNF-α in FOP mice exposed to 56Fe was associated with either neutral or modestly positive changes in bone structural integrity. Collectively, these data are generally consistent with previous findings that dietary intake of omega-3 fatty acids may effectively mitigate systemic inflammation after acute radiation exposure and facilitate maintenance of BMD during spaceflight in humans.NEW & NOTEWORTHY This is the first investigation, to our knowledge, to test the impact of a diet high in omega-3 fatty acids on multiple bone structural and biological outcomes following space-relevant radiation exposure. Novel in biological outcomes is the assessment of osteocyte responses to this stressor. These data also add to the growing evidence that low-dose exposures to even high-energy ion species like 56Fe may have neutral or even small positive impacts on bone.
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Ácidos Grasos Omega-3 , Animales , Ratones , Ratones Endogámicos C57BL , Osteocitos , Radiación Ionizante , Factor de Necrosis Tumoral alfaRESUMEN
Streaking artifacts in computed tomography (CT) scans caused by metallic dental implants (MDIs) can lead to inaccuracies in dose calculations. This study quantifies and compares the effect of MDIs on dose distributions using the collapsed cone convolution superposition (CCCS) and Monte Carlo (MC) algorithms, with and without correcting for the density of the MDIs. Ion chamber measurements were taken to test the ability of the algorithms in Pinnacle3 and Monaco to calculate dose near high-Z materials. Nine previously treated patients with head and neck cancer were included in this study. The MDI and the streaking artifacts on the CT images were carefully contoured. For each patient, a plan was optimized and calculated using the Pinnacle3 treatment planning system (TPS). Two dose calculations were performed for each patient: one with overridden densities of the MDI and CT artifacts and one without overridden densities of the MDI and CT artifacts. The plans were then exported to the Monaco TPS and recalculated for the same number of monitor units (MUs) using its MC dose calculation algorithm. The changes in dose to the planning target volume (PTV) and surrounding healthy tissues were examined between all the plans using VelocityAI. For the ion chamber measurements, when correct density information was used, Monaco was within 3% of the measured values, whereas the doses calculated in Pinnacle3 varied up to 7%. The CCCS algorithm in Pinnacle3 calculated only a significant decrease in PTV coverage for 1 patient when the densities were overridden. The MC algorithm in Monaco was able to calculate a significant change in PTV coverage for five of the patients when the density was overridden. Additionally, when healthy tissues affected by streaking artifacts were assigned the correct density, cumulative (from all the fractions) point doses increased up to 46.2 Gy. Not properly accounting for MDIs can impact both the high-dose regions (PTVs) and surrounding healthy tissues. This study demonstrates that if MDIs and the artifacts are not appropriately accounted for by contouring and assigning to them the correct density, there is a potential risk of compromising the quality of the plan regarding PTV coverage and dose to healthy tissues.
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Artefactos , Implantes Dentales , Neoplasias de Cabeza y Cuello/radioterapia , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Algoritmos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Método de Montecarlo , Dosificación Radioterapéutica , Tomografía Computarizada por Rayos XRESUMEN
How landscape context influences density-dependent processes is important, as environmental heterogeneity can confound estimates of density dependence in demographic parameters. Here we evaluate 19 populations in a shoaling temperate reef fish (Trachinops caudimaculatus) metapopulation within a heterogeneous seascape (Port Phillip Bay, Australia) to show empirically that shelter availability and population density interact to influence juvenile mortality, growth and condition. Although heterogeneity in shelter availability obscured the underlying patterns of density dependence in different ways, the combination of habitat and its interaction with density were two to six times more important than density alone in explaining variation in demographic parameters for juveniles. These findings contradict many small-scale studies and highlight the need for landscape-scale observations of how density dependence interacts with resource availability and competition to better understand how demographic parameters influence the dynamics of metapopulations in heterogeneous environments.
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Peces/crecimiento & desarrollo , Animales , Conducta Animal , Arrecifes de Coral , Densidad de Población , Especificidad de la EspecieRESUMEN
Uncertainties persist regarding the assessment of the carcinogenic risk associated with galactic cosmic ray (GCR) exposure during a mission to Mars. The GCR spectrum peaks in the range of 300(-1) MeV n to 700 MeV n(-1) and is comprised of elemental ions from H to Ni. While Fe ions represent only 0.03% of the GCR spectrum in terms of particle abundance, they are responsible for nearly 30% of the dose equivalent in free space. Because of this, radiation biology studies focusing on understanding the biological effects of GCR exposure generally use Fe ions. Acting as a thin shield, the Martian atmosphere alters the GCR spectrum in a manner that significantly reduces the importance of Fe ions. Additionally, albedo particles emanating from the regolith complicate the radiation environment. The present study uses the Monte Carlo code FLUKA to simulate the response of a tissue-equivalent proportional counter on the surface of Mars to produce dosimetry quantities and microdosimetry distributions. The dose equivalent rate on the surface of Mars was found to be 0.18 Sv y(-1) with an average quality factor of 2.9 and a dose mean lineal energy of 18.4 keV µm(-1). Additionally, albedo neutrons were found to account for 25% of the dose equivalent. It is anticipated that these data will provide relevant starting points for use in future risk assessment and mission planning studies.
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Biomimética/instrumentación , Radiación Cósmica , Marte , Exposición Profesional/análisis , Vuelo Espacial/instrumentación , Recuento Corporal Total/instrumentación , Astronautas , Simulación por Computador , Diseño de Equipo , Análisis de Falla de Equipo , Medio Ambiente Extraterrestre/química , Humanos , Miniaturización , Modelos Estadísticos , Dosis de Radiación , Protección Radiológica/instrumentaciónRESUMEN
BACKGROUND: Population connectivity, which is essential for the persistence of benthic marine metapopulations, depends on how life history traits and the environment interact to influence larval production, dispersal and survival. Although we have made significant advances in our understanding of the spatial and temporal dynamics of these individual processes, developing an approach that integrates the entire population connectivity process from reproduction, through dispersal, and to the recruitment of individuals has been difficult. We present a population connectivity modelling framework and diagnostic approach for quantifying the impact of i) life histories, ii) demographics, iii) larval dispersal, and iv) the physical seascape, on the structure of connectivity and metapopulation dynamics. We illustrate this approach using the subtidal rocky reef ecosystem of Port Phillip Bay, were we provide a broadly-applicable framework of population connectivity and quantitative methodology for evaluating the relative importance of individual factors in determining local and system outcomes. RESULTS: The spatial characteristics of marine population connectivity are primarily influenced by larval mortality, the duration of the pelagic larval stage, and the settlement competency characteristics, with significant variability imposed by the geographic setting and the timing of larval release. The relative influence and the direction and strength of the main effects were strongly consistent among 10 connectivity-based metrics. CONCLUSIONS: These important intrinsic factors (mortality, length of the pelagic larval stage, and the extent of the precompetency window) and the spatial and temporal variability represent key research priorities for advancing our understanding of the connectivity process and metapopulation outcomes.
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Identifying how density and number-dependent processes regulate populations is important for predicting population response to environmental change. Species that live in groups, such as shoaling fish, can experience both direct density-dependent mortality through resource limitation and inverse number-dependent mortality via increased feeding rates and predator evasion in larger groups. To investigate the role of these processes in a temperate reef fish population, we manipulated the density and group size of the shoaling species Trachinops caudimaculatus on artificial patch reefs at two locations with different predator fields in Port Phillip Bay, Australia. We compared mortality over four weeks to estimates of predator abundance and per capita availability of refuge and food to identify mechanisms for density or number dependence. Mortality was strongly directly density dependent throughout the experiment, regardless of the dominant predator group; however, the limiting resource driving this effect changed over time. In the first two weeks when densities were highest, density-dependent mortality was best explained by refuge competition and the abundance of benthic predators. During the second two weeks, food competition best explained the pattern of mortality. We detected no effect of group size at either location, even where pelagic-predator abundance was high. Overall, direct density effects were much stronger than those of group size, suggesting little survival advantage to shoaling on isolated patch reefs where resource competition is high. This study is the first to observe a temporal shift in density-dependent mechanisms in reef fish, and the first to observe food limitation on short temporal scales. Food competition may therefore be an important regulator of postsettlement reef fish cohorts after the initial intense effects of refuge limitation and predation.
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Conducta Animal , Arrecifes de Coral , Peces/fisiología , Conducta Social , Animales , Modelos Biológicos , Densidad de PoblaciónRESUMEN
Predicting the consequences of predator biodiversity loss on prey requires an understanding of multiple predator interactions. Predators are often assumed to have independent and additive effects on shared prey survival; however, multiple predator effects can be non-additive if predators foraging together reduce prey survival (risk enhancement) or increase prey survival through interference (risk reduction). In marine communities, juvenile reef fish experience very high mortality from two predator guilds with very different hunting modes and foraging domains-benthic and pelagic predator guilds. The few previous predator manipulation studies have found or assumed that mortality is independent and additive. We tested whether interacting predator guilds result in non-additive prey mortality and whether the detection of such effects change over time as prey are depleted. To do so, we examined the roles of benthic and pelagic predators on the survival of a juvenile shoaling zooplanktivorous temperate reef fish, Trachinops caudimaculatus, on artificial patch reefs over 2 months in Port Phillip Bay, Australia. We observed risk enhancement in the first 7 days, as shoaling behaviour placed prey between predator foraging domains with no effective refuge. At day 14 we observed additive mortality, and risk enhancement was no longer detectable. By days 28 and 62, pelagic predators were no longer significant sources of mortality and additivity was trivial. We hypothesize that declines in prey density led to reduced shoaling behaviour that brought prey more often into the domain of benthic predators, resulting in limited mortality from pelagic predators. Furthermore, pelagic predators may have spent less time patrolling reefs in response to declines in prey numbers. Our observation of the changing interaction between predators and prey has important implications for assessing the role of predation in regulating populations in complex communities.
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Conducta Animal/fisiología , Perciformes/fisiología , Conducta Predatoria , Animales , Organismos Acuáticos , Australia , Biodiversidad , Arrecifes de Coral , Ecosistema , Cadena Alimentaria , Mortalidad , Densidad de Población , Dinámica Poblacional , Conducta Predatoria/fisiología , Medición de Riesgo/métodos , Factores de Riesgo , ZooplanctonRESUMEN
Approaches to safety regulations-particularly radiation safety regulations-must be founded on the very best science possible. However, radiation safety regulations always lag behind the science for a number of reasons. First, the normal scientific process of peer-review, debate, and confirmation must ensure that the conclusions are indeed correct, the implications of the research are fully understood, and a consensus has been established. Second, in the U.S., there is a well-established, all-inclusive political process that leads to changes in radiation safety regulations. This process can take a very long time, as was demonstrated when the process was initiated to change the Code of Federal Regulations more than 20 y ago in response to International Commission on Radiation Protection Publication 26 and other recommendations. Currently, we find ourselves in a situation where the possibility of a terrorist radiological attack may occur and where the existing body of regulations provides very little guidance. Many international and national bodies, including several federal agencies, have provided recommendations on the appropriate levels of exposure for first-responders and first-receivers, as well as for the general public. However, some agencies provide guidelines based on very conservative dose limits which are not appropriate in situations where there is a substantial chance for the loss of lives and critical infrastructure. It is important that an emergency response is not hampered by overly cautious guidelines or regulations. In a number of exercises the impact of disparate guidelines and training in radiological situations has highlighted the need for clear reasonable limits that maximize the benefit from an emergency response and for any cleanup after the incident. This presentation will focus first on the federal infrastructure established to respond to radiological accidents and incidents. It will review briefly the major recommendations, both international and national, for responders and will attempt, where possible, to establish the scientific foundation for these guidelines. We will also stress the need to clearly and openly communicate the recommendations to the first-responders and the public so that no unnecessary anxiety or associated actions on their part impedes the ability to respond to a disaster. Finally, the use of these guidelines and recommendations by decision-makers at all levels will be discussed.
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Toma de Decisiones , Regulación Gubernamental , Protección Radiológica/legislación & jurisprudencia , Protección Radiológica/métodos , Liberación de Radiactividad Peligrosa , Ciencia , Terrorismo , Planificación en Desastres , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
The RS 2400's cylindrical X-ray source yields dose rates high enough to allow the irradiator to replace widely used gamma irradiators. Except for the leftmost 5 cm, beam uniformity is within 10% at the tube surface. At maximum operating parameters, the beam has HVL(1)=13.66 mm aluminum, HC=0.47, and hv(eq)=88.5 keV. Maximum dose rates to tissue are 65 Gy min(-1)+/-3.1% at tube surface, 37 Gy min(-1)+/-3.1% at center of canisters, 14.1 Gy min(-1)+/-6.5% for thin-shelled oysters, and 12.3 Gy min(-1)+/-6.2% for thick-shelled oysters.
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Irradiación de Alimentos , Ostreidae/efectos de la radiación , Esterilización/métodos , Animales , Irradiación de Alimentos/métodos , Irradiación de Alimentos/normas , Dosis de Radiación , Rayos XRESUMEN
In single-event Monte Carlo electron transport simulations, elastic scattering events dominate the changes in electron trajectories due to collisions. Classically, the polar scattering angle due to an elastic collision can be sampled efficiently from the screened Rutherford cross section. However, the screened Rutherford cross section fails for both high Z materials and when the incident electron energy becomes too low. Alternatively, improved simulation accuracy for electrons in all energy ranges and through all materials may be obtained by sampling directly from differential data derived from partial-wave-expansion method (PWEM) calculations based on theoretical atomic potential models. While sampling directly from wave calculations will yield simulation results to the best known physical accuracy, it comes at the cost of simulation time. This is due to a sampling process that is typically more involved when compared with using the screened Rutherford cross section. In this work we present a relationship capable of reproducing the moments of the differential cross section derived from PWEM calculations, resulting in good preservation of forward and backscattering peaks. The relationship is directly invertible and is as easily sampled as the Rutherford cross section. Most important, the data presented in this paper in combination with this relationship produce Monte Carlo simulation results which are comparable with those using the exact differential cross section from PWEM calculations for elements Z = 1 to 96 and for incident electron energies from 300,000 down to 50 eV.