Patient-specific stopping power calibration for proton therapy planning based on single-detector proton radiography.

A simple robust optimizer has been developed that can produce patient-specific calibration curves to convert x-ray computed tomography (CT) numbers to relative stopping powers (HU-RSPs) for proton therapy treatment planning. The difference between a digitally reconstructed radiograph water-equivalent path length (DRRWEPL) map through the x-ray CT dataset and a proton radiograph (set as the ground truth) is minimized by optimizing the HU-RSP calibration curve. The function of the optimizer is validated with synthetic datasets that contain no noise and its robustness is shown against CT noise. Application of the procedure is then demonstrated on a plastic and a real tissue phantom, with proton radiographs produced using a single detector. The mean errors using generic/optimized calibration curves between the DRRWEPL map and the proton radiograph were 1.8/0.4% for a plastic phantom and -2.1/ - 0.2% for a real tissue phantom. It was then demonstrated that these optimized calibration curves offer a better prediction of the water equivalent path length at a therapeutic depth. We believe that these promising results are suggestive that a single proton radiograph could be used to generate a patient-specific calibration curve as part of the current proton treatment planning workflow

Fear of humans as apex predators has landscape-scale impacts from mountain lions to mice

Apex predators such as large carnivores can have cascading, landscape-scale impacts across wildlife communities, which could result largely from the fear they inspire, although this has yet to be experimentally demonstrated. Humans have supplanted large carnivores as apex predators in many systems, and similarly pervasive impacts may now result from fear of the human ‘super predator’. We conducted a landscape-scale playback experiment demonstrating that the sound of humans speaking generates a landscape of fear with pervasive effects across wildlife communities. Large carnivores avoided human voices and moved more cautiously when hearing humans, while medium-sized carnivores became more elusive and reduced foraging. Small mammals evidently benefited, increasing habitat use and foraging. Thus, just the sound of a predator can have landscape-scale effects at multiple trophic levels. Our results indicate that many of the globally observed impacts on wildlife attributed to anthropogenic activity may be explained by fear of humans

Artificial maturation of iron- and sulfur-rich Mars analogues: Implications for the diagenetic stability of biopolymers and their detection with pyrolysis gas chromatography–mass spectrometry

Acidic iron- and sulfur-rich streams are appropriate analogues for the late Noachian and early Hesperian periods of martian history, when Mars exhibited extensive habitable environments. Any past life on Mars may have left behind diagnostic evidence of life that could be detected at the present day. For effective preservation, these remains must have avoided the harsh radiation flux at the martian surface, survived geological storage for billions of years, and remained detectable within their geochemical environment by analytical instrument suites used on Mars today, such as thermal extraction techniques. We investigated the detectability of organic matter within sulfur stream sediments that had been subjected to artificial maturation by hydrous pyrolysis. After maturation, the samples were analyzed by pyrolysis–gas chromatography–mass spectrometry (py-GC-MS) to determine whether organic matter could be detected with this commonly used technique. We find that macromolecular organic matter can survive the artificial maturation process in the presence of iron- and sulfur-rich minerals but cannot be unambiguously distinguished from abiotic organic matter. However, if jarosite and goethite are present in the sulfur stream environment, they interfere with the py-GC-MS detection of organic compounds in these samples. Clay reduces the obfuscating effect of the oxidizing minerals by providing nondeleterious adsorption sites. We also find that after a simple alkali and acid leaching process that removes oxidizing minerals such as iron sulfates, oxides, and oxyhydroxides, the sulfur stream samples exhibit much greater organic responses during py-GC-MS in terms of both abundance and diversity of organic compounds, such as the detection of hopanes in all leached samples. Our results suggest that insoluble organic matter can be preserved over billions of years of geological storage while still retaining diagnostic organic information, but sample selection strategies must either avoid jarosite- and goethite-rich outcrops or conduct preparative chemistry steps to remove these oxidants prior to analysis by thermal extraction techniques

The UK children's publishing house: adapting to change for the multimedia market.

Reports the results of the first stage of research (in progress, 1997-2000), which aims to develop an understanding of the challenges facing publishers who have entered the children's multimedia market in the UK in the 1980s and 1990s. The findings of the first stage of the research amongst established UK publishers producing multimedia for children are described. These point to a number of factors that appear to be critical to the success of publishers in the multimedial market: modification of corporate culture, internal structures and processes; branding of the company's chosen multimedia identity; focusing on the added value element of multimedia products; promotion of organisational learning, innovation and creativity within the company; and sourcing necessary skills effectively. A second study will examine the perceptions of new media companies which have entered this market

The role of indirect genetic effects in the evolution of interacting reproductive behaviors in the burying beetle, Nicrophorus vespilloides

This is the final version. Available from Wiley via the DOI in this record.Data archiving:Data available from the Dryad Digital Repository: https://doi.org/10.5061/dryad.9rk5f69.Social interactions can give rise to indirect genetic effects (IGEs), which occur when genes expressed in one individual affect the phenotype of another individual. The evolutionary dynamics of traits can be altered when there are IGEs. Sex often involves indirect effects arising from first order (current) or second order (prior) social interactions, yet IGEs are infrequently quantified for reproductive behaviors.Here, we use experimental populations of burying beetles that have experienced bidirectional selection on mating rate to test for social plasticity and IGEs associated with focal males mating with a female either without (first order effect) or with (second order effect) prior exposure to a competitor, and resource defense behavior (first order effect). Additive IGEs were detected for mating rate arising from (first order) interactions with females. For resource defense behavior, a standard variance partitioning analysis provided no evidence of additive genetic variance – either direct or indirect. However, behavior was predicted by focal size relative to that of the competitor, and size is also heritable. Assuming that behavior is causally dependent on relative size, this implies that both DGEs and IGEs do occur (and may potentially interact). The relative contribution of IGEs may differ among social behaviors related to mating which has consequences for the evolutionary trajectories of multivariate traits.Natural Environment Research Council (NERC

Solid Phase Micro Extraction: Potential for Organic Contamination Control for Planetary Protection of Life-Detection Missions to the Icy Moons of the Outer Solar System

Conclusively detecting, or ruling out the possibility of, life on the icy moons of the outer solar system will require spacecraft missions to undergo rigorous planetary protection and contamination control procedures to achieve extremely low levels of organic terrestrial contamination. Contamination control is necessary to avoid forward contamination of the body of interest and to avoid the detection of false positive signals which could either mask indigenous organic chemistry of interest or cause an astrobiological false alarm. Here we test a new method for rapidly and inexpensively assessing the organic cleanliness of spaceflight hardware surfaces using solid phase micro extraction (SPME) fibres to directly swab surfaces. The results suggest that the method is both time and cost efficient. The SPME-gas chromatography mass spectrometry (GC-MS) method is sensitive to common mid-weight, non-polar contaminant compounds, e.g. aliphatic and aromatic hydrocarbons, which are common contaminants in laboratory settings. While we demonstrate the potential of SPME for surface sampling, the GC-MS instrumentation restricts the SPME-GC-MS technique’s sensitivity to larger polar and non-volatile compounds. Although not used in this study, to increase the potential range of detectable compounds, SPME can also be used in conjunction with high performance liquid chromatography/liquid chromatography-mass spectrometry systems suitable for polar analytes [Kataoka et al., 2000]. Thus, our SPME method presents an opportunity to monitor organic contamination in a relatively rapid and routine way that produces information-rich data sets

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

A methodology to extract outcomes from routine healthcare data for patients with locally advanced non-small cell lung cancer

BACKGROUND: Outcomes for patients in UK with locally advanced non-small cell lung cancer (LA NSCLC) are amongst the worst in Europe. Assessing outcomes is important for analysing the effectiveness of current practice. However, data quality is inconsistent and regular large scale analysis is challenging. This project investigates the use of routine healthcare datasets to determine progression free survival (PFS) and overall survival (OS) of patients treated with primary radical radiotherapy for LA NSCLC. METHODS: All LA NSCLC patients treated with primary radical radiotherapy in a 2 year period were identified and paired manual and routine data generated for an initial pilot study. Manual data was extracted information from hospital records and considered the gold standard. Key time points were date of diagnosis, recurrence, death or last clinical encounter. Routine data was collected from various data sources including, Hospital Episode Statistics, Personal Demographic Service, chemotherapy data, and radiotherapy datasets. Relevant event dates were defined by proxy time points and refined using backdating and time interval optimization. Dataset correlations were then tested on key clinical outcome indicators to establish if routine data could be used as a reliable proxy measure for manual data. RESULTS: Forty-three patients were identified for the pilot study. The manual data showed a median age of 67 years (range 46- 89 years) and all patients had stage IIIA/B disease. Using the manual data, the median PFS was 10.78 months (range 1.58-37.49 months) and median OS was 16.36 months (range 2.69-37.49 months). Based on routine data, using proxy measures, the estimated median PFS was 10.68 months (range 1.61-31.93 months) and estimated median OS was 15.38 months (range 2.14-33.71 months). Overall, the routine data underestimated the PFS and OS of the manual data but there was good correlation with a Pearson correlation coefficient of 0.94 for PFS and 0.97 for OS. CONCLUSIONS: This is a novel approach to use routine datasets to determine outcome indicators in patients with LA NSCLC that will be a surrogate to analysing manual data. The ability to enable efficient and large scale analysis of current lung cancer strategies has a huge potential impact on the healthcare system

Solid phase micro extraction for organic contamination control throughout assembly and operational phases of space missions

Space missions concerned with life detection contain highly sensitive instruments for the detection of organics. Terrestrial contamination can interfere with signals of indigenous organics in samples and has the potential to cause false positive biosignature detections, which may lead to incorrect suggestions of the presence of life elsewhere in the Solar System. This study assessed the capability of solid phase micro extraction (SPME) as a method for monitoring organic contamination encountered by spacecraft hardware during assembly and operation. SPME-gas chromatography-mass spectrometry (SPME-GC-MS) analysis was performed on potential contaminant source materials, which are commonly used in spacecraft construction. The sensitivity of SPME-GC-MS to organics was assessed in the context of contaminants identified in molecular wipes taken from hardware surfaces on the ExoMars Rosalind Franklin rover. SPME was found to be effective at detecting a wide range of common organic contaminants that include aromatic hydrocarbons, non-aromatic hydrocarbons, nitrogen-containing compounds, alcohols and carbonyls. A notable example of correlation of contaminant with source material was the detection of benzenamine compounds in an epoxy adhesive analyzed by SPME-GC-MS and in the ExoMars rover surface wipe samples. The current form of SPME-GC-MS does not enable quantitative evaluation of contaminants, nor is it suitable for the detection of every group of organic molecules relevant to astrobiological contamination concerns, namely, large and/or polar molecules such as amino acids. However, it nonetheless represents an effective new monitoring method for rapid, easy identification of organic contaminants commonly present on spacecraft hardware and could thus be utilized in future space missions as part of their contamination control and mitigation protocols