A Geant4 Fano test for novel very high energy electron beams

Objective. The boundary crossing algorithm available in Geant4 10.07-p01 general purpose Monte Carlo code has been investigated for a 12 and 200 MeV electron source by the application of a Fano cavity test. Approach. Fano conditions were enforced through all simulations whilst varying individual charged particle transport parameters which control particle step size, ionisation and single scattering. Main Results. At 12 MeV, Geant4 was found to return excellent dose consistency within 0.1% even with the default parameter configurations. The 200 MeV case, however, showed significant consistency issues when default physics parameters were employed with deviations from unity of more than 6%. The effect of the inclusion of nuclear interactions was also investigated for the 200 MeV beam and was found to return good consistency for a number of parameter configurations. Significance. The Fano test is a necessary investigation to ensure the consistency of charged particle transport available in Geant4 before detailed detector simulations can be conducted

Fluence correction factor for graphite calorimetry in a clinical high-energy carbon-ion beam

The aim of this work is to develop and adapt a formalism to determine absorbed dose to water from graphite calorimetry measurements in carbon-ion beams. Fluence correction factors, kfl, needed when using a graphite calorimeter to derive dose to water, were determined in a clinical high-energy carbon-ion beam. Measurements were performed in a 290 MeV/n carbon-ion beam with a field size of 11 x 11 cm2, without modulation. In order to sample the beam, a plane-parallel Roos ionization chamber was chosen for its small collecting volume in comparison with the field size. Experimental information on fluence corrections was obtained from depth-dose measurements in water. This procedure was repeated with graphite plates in front of the water phantom. Fluence corrections were also obtained with Monte Carlo simulations through the implementation of three methods based on (i) the fluence distributions differential in energy, (ii) a ratio of calculated doses in water and graphite at equivalent depths and (iii) simulations of the experimental setup. The kfl term increased in depth from 1.00 at the entrance toward 1.02 at a depth near the Bragg peak, and the average difference between experimental and numerical simulations was about 0.13%. Compared to proton beams, there was no reduction of the kfl due to alpha particles because the secondary particle spectrum is dominated by projectile fragmentation. By developing a practical dose conversion technique, this work contributes to improving the determination of absolute dose to water from graphite calorimetry in carbon-ion beams

An Efficient and Reliable DNA-based Sex Identification Method for Archaeological Pacific Salmonid (Oncorhynchus spp.) Remains

Pacific salmonid (Oncorhynchus spp.) remains are routinely recovered from archaeological sites in northwestern North America but typically lack sexually dimorphic features, precluding the sex identification of these remains through morphological approaches. Consequently, little is known about the deep history of the sex-selective salmonid fishing strategies practiced by some of the region\u27s Indigenous peoples. Here, we present a DNA-based method for the sex identification of archaeological Pacific salmonid remains that integrates two PCR assays that each co-amplify fragments of the sexually dimorphic on the Y chromosome (sdY) gene and an internal positive control (Clock1a or D-loop). The first assay coamplifies a 95 bp fragment of sdY and a 108 bp fragment of the autosomal Clock1a gene, whereas the second assay co-amplifies the same sdY fragment and a 249 bp fragment of the mitochondrial D-loop region. This method\u27s reliability, sensitivity, and efficiency, were evaluated by applying it to 72 modern Pacific salmonids from five species and 75 archaeological remains from six Pacific salmonids. The sex identities assigned to each of the modern samples were concordant with their known phenotypic sex, highlighting the method\u27s reliability. Applications of the method to dilutions of modern DNA samples indicate it can correctly identify the sex of samples with as little as ~39 pg of total genomic DNA. The successful sex identification of 70 of the 75 (93%) archaeological samples further demonstrates the method\u27s sensitivity. The method\u27s reliance on two co-amplifications that preferentially amplify sdY helps validate the sex identities assigned to samples and reduce erroneous identifications caused by allelic dropout and contamination. Furthermore, by sequencing the D-loop fragment used as a positive control, species-level and sex identifications can be simultaneously assigned to samples. Overall, our results indicate the DNA-based method reported in this study is a sensitive and reliable sex identification method for ancient salmonid remains

The potential of dual-energy CT to reduce proton beam range uncertainties

PURPOSE: Dual‐energy CT (DECT) promises improvements in estimating stopping power ratios (SPRs) for proton therapy treatment planning. Although several comparable mathematical formalisms have been proposed in literature, the optimal techniques to characterize human tissue SPRs with DECT in a clinical environment are not fully established. The aim of this work is to compare the most robust DECT methods against conventional single‐energy CT (SECT) in conditions reproducing a clinical environment, where CT artifacts and noise play a major role on the accuracy of these techniques.METHODS: Available DECT tissue characterization methods are investigated and their ability to predict SPRs is compared in three contexts: (a) a theoretical environment using the XCOM cross section database; (b) experimental data using a dual‐source CT scanner on a calibration phantom; (c) simulations of a virtual humanoid phantom with the ImaSim software. The latter comparison accounts for uncertainties caused by CT artifacts and noise, but leaves aside other sources of uncertainties such as CT grid size and the I‐values. To evaluate the clinical impact, a beam range calculation model is used to predict errors from the probability distribution functions determined with ImaSim simulations. Range errors caused by SPR errors in soft tissues and bones are investigated. RESULTS: Range error estimations demonstrate that DECT has the potential of reducing proton beam range uncertainties by 0.4% in soft tissues using low noise levels of 12 and 8 HU in DECT, corresponding to 7 HU in SECT. For range uncertainties caused by the transport of protons through bones, the reduction in range uncertainties for the same levels of noise is found to be up to 0.6 to 1.1 mm for bone thicknesses ranging from 1 to 5 cm, respectively. We also show that for double the amount noise, i.e., 14 HU in SECT and 24 and 16 HU for DECT, the advantages of DECT in soft tissues are lost over SECT. In bones however, the reduction in range uncertainties is found to be between 0.5 and 0.9 mm for bone thicknesses ranging from 1 to 5 cm, respectively. CONCLUSION: DECT has a clear potential to improve proton beam range predictions over SECT in proton therapy. However, in the current state high levels of noise remain problematic for DECT characterization methods and do not allow getting the full benefits of this technology. Future work should focus on adapting DECT methods to noise and investigate methods based on raw‐data to reduce CT artifacts

A different appetite for sovereignty? Independence movements in subnational island jurisdictions

Local autonomy in a subnational jurisdiction is more likely to be gained, secured or enhanced where there are palpable movements or political parties agitating for independence in these smaller territories. A closer look at the fortunes, operations and dynamics of independence parties from subnational island jurisdictions can offer some interesting insights on the appetite for sovereignty and independence, but also the lack thereof, in the twenty-first century.peer-reviewe

Dose ratio proton radiography using the proximal side of the Bragg peak

Purpose: In recent years there has been a movement towards single-detector proton radiography, due to its potential ease of implementation within the clinical environment. One such single-detector technique is the dose ratio method, in which the dose maps from two pristine Bragg peaks are recorded beyond the patient. To date, this has only been investigated on the distal side of the lower energy Bragg peak, due to the sharp fall-off. We investigate the limits and applicability of the dose ratio method on the proximal side of the lower energy Bragg peak, which has the potential to allow a much wider range of water-equivalent thicknesses (WET) to be imaged. Comparisons are made with the use of the distal side of the Bragg peak. Methods: Using the analytical approximation for the Bragg peak we generated theoretical dose ratio curves for a range of energy pairs, and then determined how an uncertainty in the dose ratio would translate to a spread in the WET estimate. By defining this spread as the accuracy one could achieve in the WET estimate, we were able to generate look-up graphs of the range on the proximal side of the Bragg peak that one could reliably use. These were dependent on the energy pair, noise level in the dose ratio image and the required accuracy in the WET. Using these look-up graphs we investigated the applicability of the technique for a range of patient treatment sites. We validated the theoretical approach with experimental measurements using a complementary metal oxide semiconductor active pixel sensor (CMOS APS), by imaging a small sapphire sphere in a high energy proton beam. Results: Provided the noise level in the dose ratio image was 1% or less, a larger spread of WETs could be imaged using the proximal side of the Bragg peak (max 5.31 cm) compared to the distal side (max 2.42 cm). In simulation it was found that, for a pediatric brain, it is possible to use the technique to image a region with a square field equivalent size of 7.6 cm2, for a required accuracy in the WET of 3 mm and a 1% noise level in the dose ratio image. The technique showed limited applicability for other patient sites. The CMOS APS demonstrated a good accuracy, with a root-mean-square-error of 1.6 mm WET. The noise in the measured images was found to be σ =1.2% (standard deviation) and theoretical predictions with a 1.96σ noise level showed good agreement with the measured errors. Conclusions: After validating the theoretical approach with measurements, we have shown that the use of the proximal side of the Bragg peak when performing dose ratio imaging is feasible, and allows for a wider dynamic range than when using the distal side. The dynamic range available increases as the demand on the accuracy of the WET decreases. The technique can only be applied to clinical sites with small maximum WETs such as for pediatric brains

Optimized I-values for the use with the Bragg additivity rule and their impact on proton stopping power and range uncertainty

Purpose: Novel imaging modalities estimate patient elemental compositions for particle treatment planning. The mean excitation energy (I-value) is a main contributor to the proton range uncertainty. To minimize their impact on beam range errors and quantify their uncertainties, the currently used I-values proposed in 1982 are revisited. The study aims at proposing a new set of optimized elemental I-values for use with the Bragg additivity rule (BAR) and establishing uncertainties on optimized I-values and the BAR. // Methods: We optimize elemental I-values for the use in compounds based on measured material I-values. We gain a new set of elemental I-values and corresponding uncertainties, based on the experimental uncertainties and our uncertainty model. We evaluate uncertainties on I-values and relative stopping powers (RSP) of 70 human tissues, taking into account statistical correlations between tissues and water. The effect of new I-values on proton beam ranges is quantified using Monte Carlo simulations. // Results: Our elemental I-values describe measured material I-values with higher accuracy than ICRU-recommended I-values (RMSE: 6.17% (ICRU), 5.19% (this work)). Our uncertainty model estimates an uncertainty component from the BAR to 4.42%. Using our elemental I-values, we calculate the I-value of water as 78.73+/-2.89 eV, being consistent with ICRU 90 (78+/-2 eV). We observe uncertainties on tissue I-values between 1.82-3.38 eV, and RSP uncertainties between 0.002%-0.44%. With transport simulations of a proton beam in human tissues, we observe range uncertainties between 0.31% and 0.47%, as compared to current estimates of 1.5%. // Conclusion: We propose a set of elemental I-values well suited for human tissues in combination with the BAR. Our model establishes uncertainties on elemental I-values and the BAR, enabling to quantify uncertainties on tissue I-values, RSP as well as particle range. This work is particularly relevant for Monte Carlo simulations where the interaction probabilities are reconstructed from elemental compositions

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.

BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures. RESULTS: A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals. CONCLUSIONS: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .)

Estimating arthropod survival probability from field counts: a case study with monarch butterflies

Survival probability is fundamental for understanding population dynamics. Methods for estimating survival probability from field data typically require marking individuals, but marking methods are not possible for arthropod species that molt their exoskeleton between life stages. We developed a novel Bayesian state‐space model to estimate arthropod larval survival probability from stage‐structured count data. We performed simulation studies to evaluate estimation bias due to detection probability, individual variation in stage duration, and study design (sampling frequency and sample size). Estimation of cumulative survival probability from oviposition to pupation was robust to potential sources of bias. Our simulations also provide guidance for designing field studies with minimal bias. We applied the model to the monarch butterfly (Danaus plexippus), a declining species in North America for which conservation programs are being implemented. We estimated cumulative survival from egg to pupation from monarch counts conducted at 18 field sites in three landcover types in Iowa, USA, and Ontario, Canada: road right‐of‐ways, natural habitats (gardens and restored meadows), and agricultural field borders. Mean predicted survival probability across all landcover types was 0.014 (95% CI: 0.004–0.024), four times lower than previously published estimates using an ad hoc estimator. Estimated survival probability ranged from 0.002 (95% CI: 7.0E−7 to 0.034) to 0.058 (95% CI: 0.013–0.113) at individual sites. Among landcover types, agricultural field borders in Ontario had the highest estimated survival probability (0.025 with 95% CI: 0.008–0.043) and natural areas had the lowest estimated survival probability (0.008 with 95% CI: 0.009–0.024). Monarch production was estimated as adults produced per milkweed stem by multiplying survival probabilities by eggs per milkweed at these sites. Monarch production ranged from 1.0 (standard deviation [SD] = 0.68) adult in Ontario natural areas in 2016 to 29.0 (SD = 10.42) adults in Ontario agricultural borders in 2015 per 6809 milkweed stems. Survival estimates are critical to monarch population modeling and habitat restoration efforts. Our model is a significant advance in estimating survival probability for monarch butterflies and can be readily adapted to other arthropod species with stage‐structured life histories