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Despite the low contribution of heavy ions to the total fluence in the space radiation environment, their radiobiological effect on the human body is extremely high. In this article, we investigated the radiation field which resulted from the interaction of galactic cosmic rays (GCRs), specifically some heavy ions and energies, typically encountered in space with a realistic multilayer sample of the International Space Station (ISS) Columbus module’s shielding wall. The quality factor, Q, and the normalized dose equivalent, H, derived from microdosimetric measurements for C, Ne, and Si ions behind different spacecraft wall configurations and materials are presented in this article. Particularly, carbon fiber, polyoxymethylene, and perspex with same areal density compared to currently used aluminum were investigated.

This paper draws lessons from the Ebola Virus Disease epidemic to suggest how health systems research can be strengthened to assist better with preparedness for and mitigation of future public health emergencies The epidemic killed more than 11 000 people in West Africa between February 2014 and January 2016 The causes of the epidemic and the response to the outbreak harbour many lessons concerning how health systems were overwhelmed and need to be re-designed in order to cope with future public health emergencies and limit their escalation From these lessons, it is possible to identify the most significant systemic issues that must be addressed to ensure health systems can exhibit greater resilience in the face of similar events in the future The paper goes on to consider the current capacity of health systems research (HSR) to assist with the management of these issues and to suggest that critical systems thinking and practice could empower health systems researchers and practitioners in a manner that would give them much greater potency The research has additional importance now that Covid-19 has demonstrated that pandemics are not ‘black swan’ events © 2021 John Wiley & Sons, Ltd

Obesity is a serious, chronic, and progressive disease associated with physiological dysfunctions that interact with circadian clock activity. Vertical gastrectomy (VG) is currently the most freque...

Purpose Stereotactic radiosurgery (SRS) can be delivered with a standard linear accelerator (linac). At institutions having more than one linac, beam matching is common practice. In the literature, there are indications that machine central axis (CAX) matching for broad fields does not guarantee matching of small fields with side ≤2 cm. There is no indication on how matching for broad fields on axis translates to matching small fields off axis. These are of interest to multitarget single‐isocenter (MTSI) SRS planning and the present work addresses that gap in the literature. Methods We used 6 MV flattening filter free (FFF) beams from four Elekta VersaHD® linacs equipped with an Agility™ multileaf collimator (MLC). The linacs were strictly matched for broad fields on CAX. We compared output factors (OPFs) and effective field size, measured concurrently using a novel 2D solid‐state dosimeter “Duo” with a spatial resolution of 0.2 mm, in square and rectangular static fields with sides from 0.5 to 2 cm, either on axis or away from it by 5 to 15 cm. Results Among the four linacs, OPF for fields ≥1 × 1 cm2 ranged 1.3% on CAX, whereas off axis a maximum range of 1.9% was observed at 15 cm. A larger variability in OPF was noted for the 0.5 × 0.5 cm2 field, with a range of 5.9% on CAX, which improved to a maximum of 2.3% moving off axis. Two linacs showed greater consistency with a range of 1.4% on CAX and 2.2% at 15 cm off axis. Between linacs, the effective field size varied by

Objective Radiotherapy for gynaecological cancer is associated with multiple adverse effects. This randomised controlled trial evaluated the impact of a combined nurse- and peer-led psycho-educational intervention on psychological distress, preparation for treatment, quality of life, psychosexual function, unmet needs and vaginal stenosis. Methods Eligible women had a confirmed diagnosis of gynaecological cancer, scheduled to receive radiotherapy with curative intent, aged ≥18 years, and able to read and write English. Participants randomly assigned one-to-one to either four nurse-led consultations plus four peer-led telephone sessions, or to usual care. Participants completed study measures at baseline, immediately before first radiotherapy (FU1), and four weeks (FU2), three (FU3), six (FU4), and 12 months (FU5) post radiotherapy. The primary outcomes were psychological distress at FU1 and FU2 measured by the Hospital Anxiety and Depression Scale. Results Of 840 eligible participants, 625 were approached and 319 (51%) consented; 158 assigned to intervention, 160 to usual care with 1 withdrawing before randomisation. Between-groups differences for primary outcomes were trivial- and small-sized, (both p > 0.05). Notable effects on secondary outcomes favouring the intervention at FU2 included preparation for treatment (sensory/psychological concerns, d = 0.57; and procedural concerns, d = 0.52) and specific needs domains (sexuality needs, d = 0.38; and health system and information needs, d = 0.41). Conclusions There was no evidence that a nurse- and peer-led intervention had a beneficial effect on psychological distress compared to usual care. However, improved treatment readiness and lower health system and sexuality needs indicate the intervention may have addressed outcomes known to be important to this population.

We describe the unusual case of a clinically significant subdural haematoma without any underlying cause in a term baby delivered by an elective caesarean section, which required surgical evacuation. We review the literature and describe the presentation, investigation and management options in infants with this infrequent condition.

Background Accidental awareness during general anaesthesia (AAGA) is a complex and rare outcome to investigate in surgical patient populations, particularly obstetric patients. We report the protocol of the Direct Reporting of Awareness in Maternity patients (DREAMY) study, illustrating how the research was designed to address practical and methodological challenges for investigating AAGA in an obstetric cohort. Methods This is the trial protocol of a prospective, multicentre cohort study of patients undergoing obstetric surgery under general anaesthesia. Accidental awareness during general anaesthesia will be detected using three repetitions of standardised direct questioning over 30 days, with responses indicating memories during general anaesthesia verified using structured interviews. Reports will be adjudicated, then classified, in accordance with pre-defined and pre-validated structures, including the Michigan Awareness Classification tool. Quantitative data will be collected on general anaesthesia conduct for all participants. This descriptive study is being conducted in England and aims to recruit a minimum of 2015 patients. Results The DREAMY study was prospectively registered (ClinicalTrials.gov Identifier: NCT03100396) and ethical approval granted. Participant recruitment began in May 2017 and one year follow up concluded in August 2019. Publication of the results is anticipated in 2020. Conclusions The DREAMY study will provide data on incidence, experience and implications of AAGA for obstetric patients, using a robust methodology that will reliably detect and translate subjective AAGA reports into objective outcomes. In addition, the study is expected to improve vigilance for AAGA in participating hospitals and encourage adoption of recommendations for support of patients experiencing AAGA.

The metal-oxide-semiconductor field-effect transistor (MOSFET) can be used as a dosimeter. It is robust, lightweight, cost-effective, is able to operate in real time with and without external bias, and also has a very small sensitive volume. Therefore, it is particularly suitable for in vivo dosimetry in modern radiation therapy and also as a patient dosimeter in diagnostic radiology. MOSFET sensitivity to ionizing radiation can be tailored to a specific application or a dose range. This is done by fabricating the radiation-sensitive volume of different thicknesses, or alternatively, by adjusting the external bias applied on the gate during irradiation. However, increased sensitivity comes at the cost of reduction in the MOSFET’s lifespan. This article investigated a way to maximize sensitivity while minimizing the reduction in lifespan. The MOSFETs we considered had a sensitive volume of thickness 0.68 or 1.0 $\mu \text{m}$ and different boron implantations under the gate. We then irradiated the MOSFETs by applying different positive biases on the gate. We assessed linearity of the dose-response relationship and sensitivity in photon beams that were produced using a megavoltage medical linear accelerator (linac) and an orthovoltage X-ray tube.

BACKGROUND: This article systematically updates the literature on changes in visual functions during the phases of the normal menstrual cycle in women. OBJECTIVES: To update Guttridge's 1994 review of visual structures and functions associated with the menstrual cycle and broaden the search through psychophysical, neuroimaging and neurobehavioral measurements covering 1994-2020. DESIGN AND SETTING: Narrative review conducted in a neurosciences and behavior laboratory in Brazil. METHODS: The PubMed, Cochrane Clinical Answers and Google Scholar databases were searched. After screening and applying the eligibility criteria, 32 articles were examined. Through this analysis, the following information was extracted: (1) geographical distribution of the study; (2) sample size (according to age and phase of the menstrual cycle); (3) type of measurements according to psychophysical, neuroimaging and neurobehavioral instruments; (4) vision testing model; (5) visual subcategory evaluated; (6) categories of processed visual stimuli; and (7) main findings. RESULTS: The menstrual phases give rise to significant changes in visual functions, including in relation to orientation and spatial attention, visual campimetry and visual sensitivity. These relate specifically to the follicular and luteal phases. CONCLUSIONS: These findings theoretically expand the effects of menstrual cycles on visual functions found by Guttridge (1994). Despite some inconsistencies in the studies analyzed, it was found that visual processing during the follicular and luteal phases of the normal menstrual cycle of healthy women can explain physiological, cognitive, behavioral and social modulations.

This systematic review aimed to verify the empirical evidence of the application of the eye tracking technique in depressive disorder. The PubMed, PsyInfo and Web of Science databases were used, using the following descriptors: ((Depression OR "Affective Disorders") AND ("Eye Tracking" OR Eye-Tracking OR "Eye Movements" OR "Eye Tracker" OR "Eye Gaze")). According to the eligibility criteria, sixteen relevant studies were identified and its methods, results and their main limitations were verified. The results suggest an increase in latency and reaction time to detect complex stimuli, e.g. the recognition of emotional facial expressions. In addition, greater numbers of fixations in stimuli of negative emotional content were observed. The findings demonstrate that changes in eye movement measurements in depressive disorder are associated with an attentional bias mechanism. It is concluded that Eye Tracking is a useful tool for psychophysiological assessment of depressive disorder. Esta revisão sistemática teve como objetivo verificar as evidências empíricas da aplicação da técnica de rastreamento ocular no transtorno depressivo. Foram utilizadas as bases de dados PubMed, PsyInfo e Web of Science, utilizando os seguintes descritores: ((Depression OR "Affective Disorders") AND ("Eye Tracking" OR Eye-Tracking OR "Eye Movements" OR "Eye Tracker" OR "Eye Gaze")). De acordo com os critérios de elegibilidade, foram identificados cinco estudos relevantes e verificados seus métodos, resultados e suas principais limitações. Os resultados sugerem um aumento na latência e no tempo de reação para detectar estímulos complexos, por ex. o reconhecimento de expressões faciais emocionais. Além disso, observou-se um maior número de fixações em estímulos de conteúdo emocional negativo. Os resultados demonstram que as alterações nas medidas dos movimentos oculares no transtorno depressivo estão associadas a um mecanismo de viés de atenção. Conclui-se que o rastreamento ocular é uma ferramenta útil para avaliação psicofisiológica do transtorno depressivo.

In their article, Berkowitz and Garrett (2020) argue that it is ethically and legally mandatory for physicians to obtain informed consent prior to performing an apnea test. They argue that without ...

In this paper, we address the problem of identification of maximum safe dose, where the maximum safe is defined as the highest dose that is non-inferior to the reference treatment (negative control) dose such that any other lower dose is also non-inferior to the reference dose. Statistical methodology for non-inferiority trial for several multiple treatments in establishing efficacy of new treatment readily available for multiplicity adjustment. We extend this methodology to identification of maximum safe dose in a toxicological experiment by incorporating the confidence set-based stepwise procedure using Fieller's confidence interval method under heteroscedasticity without multiplicity adjustment. Our simulation studies indicate that the familywise error rate (FWER) is properly controlled in a strong sense, and the power of our procedure depicts that power increases with increasing in sample size and the ratio of mean difference. Results from our studies support the theoretical findings.

MotivationRibosome profiling, or Ribo-seq, is the state of the art method for quantifying protein synthesis in living cells. Computational analysis of Ribo-seq data remains challenging due to the complexity of the procedure, as well as variations introduced for specific organisms or specialized analyses. Many bioinformatic pipelines have been developed, but these pipelines have key limitations in terms of functionality or usability.ResultsWe present riboviz 2, an updated riboviz package, for the comprehensive transcript-centric analysis and visualization of Ribo-seq data. riboviz 2 includes an analysis workflow built on the Nextflow workflow management system, combining freely available software with custom code. The package is extensively documented and provides example configuration files for organisms spanning the domains of life. riboviz 2 is distinguished by clear separation of concerns between annotation and analysis: prior to a run, the user chooses a transcriptome in FASTA format, paired with annotation for the CDS locations in GFF3 format. The user is empowered to choose the relevant transcriptome for their biological question, or to run alternative analyses that address distinct questions. riboviz 2 has been extensively tested on various library preparation strategies, including multiplexed samples. riboviz 2 is flexible and uses open, documented file formats, allowing users to integrate new analyses with the pipeline.Availabilityriboviz 2 is freely available at github.com/riboviz/riboviz.Supplementary information

The diagnosis and treatment of cancer patients requires access to imaging to ensure accurate management decisions and optimal outcomes. Our global assessment of imaging and nuclear medicine resources identified major shortages of equipment and workforce, particularly in low- and middle-income countries (LMIC). A microsimulation model of 11 cancers showed scale-up of imaging would avert 3.2% (2.46 million) of all cancer deaths caused by the modeled cancers between 2020-2030, saving 54.92 million life years. Scale-up of imaging, treatment and care quality would avert 9.55 million (12.5%) of all deaths caused by the modeled cancers, saving 232.30 million life years. Scale-up of imaging would cost $6.84 billion in 2020-2030 but yield global lifetime productivity gains of $1.23 trillion, a net return of $179.19 per $1 invested. Using a conservative human capital approach, scale-up of imaging would provide a net benefit of $209.46 billion and net return of $31.61 per $1 invested. Using the same model and a full income approach, combining scale-up of imaging and treatment and quality of care would provide a net benefit of $2.66 trillion, and a net return of $12.43 per $1 invested. These improved health and economic outcomes were seen across all countries and geographical regions. We propose actions and investment that would enhance access to imaging equipment, workforce capacity, digital technology, radiopharmaceuticals, and research and training programs in LMIC, to realise massive health and economic benefits and reduce the burden of cancer globally.

Workflow management systems represent, manage, and execute multistep computational analyses and offer many benefits to bioinformaticians. They provide a common language for describing analysis workflows, contributing to reproducibility and to building libraries of reusable components. They can support both incremental build and re-entrancy—the ability to selectively re-execute parts of a workflow in the presence of additional inputs or changes in configuration and to resume execution from where a workflow previously stopped. Many workflow management systems enhance portability by supporting the use of containers, high-performance computing (HPC) systems, and clouds. Most importantly, workflow management systems allow bioinformaticians to delegate how their workflows are run to the workflow management system and its developers. This frees the bioinformaticians to focus on what these workflows should do, on their data analyses, and on their science. RiboViz is a package to extract biological insight from ribosome profiling data to help advance understanding of protein synthesis. At the heart of RiboViz is an analysis workflow, implemented in a Python script. To conform to best practices for scientific computing which recommend the use of build tools to automate workflows and to reuse code instead of rewriting it, the authors reimplemented this workflow within a workflow management system. To select a workflow management system, a rapid survey of available systems was undertaken, and candidates were shortlisted: Snakemake, cwltool, Toil, and Nextflow. Each candidate was evaluated by quickly prototyping a subset of the RiboViz workflow, and Nextflow was chosen. The selection process took 10 person-days, a small cost for the assurance that Nextflow satisfied the authors’ requirements. The use of prototyping can offer a low-cost way of making a more informed selection of software to use within projects, rather than relying solely upon reviews and recommendations by others., Author summary Data analysis involves many steps, as data are wrangled, processed, and analysed using a succession of unrelated software packages. Running the right steps, in the right order, and putting the right outputs in the right places, is a major source of frustration. Workflow management systems require that each data analysis step be “wrapped” in a structured way, describing its inputs, parameters, and outputs. By writing these wrappers, the scientist can focus on the meaning of each step, and how they fit together, which is the interesting part. The system uses these wrappers to decide what steps to run and how to run these and takes charge of running the steps, including reporting on errors. This makes it much easier to repeatedly run the analysis and to run it transparently upon different computers. To select a workflow management system, we surveyed available tools and chose 4 in which we developed prototype implementations to evaluate their suitability for our project. We conclude that many similar multistep data analysis workflows can be rewritten in a workflow management system, and we advocate prototyping as a low-cost (both time and effort) way of making an informed selection of software for use within a research project.

Purpose. A radiotherapy system with a fixed treatment beam and a rotating patient positioning system could be smaller, more robust and more cost effective compared to conventional rotating gantry systems. However, patient rotation could cause anatomical deformation and compromise treatment delivery. In this work, we demonstrate an image-guided treatment workflow with a fixed beam prototype system that accounts for deformation during rotation to maintain dosimetric accuracy. Methods. The prototype system consists of an Elekta Synergy linac with the therapy beam orientated downward and a custom-built patient rotation system (PRS). A phantom that deforms with rotation was constructed and rotated within the PRS to quantify the performance of two image guidance techniques: motion compensated cone-beam CT (CBCT) for pre-treatment volumetric imaging and kilovoltage infraction monitoring (KIM) for real-time image guidance. The phantom was irradiated with a 3D conformal beam to evaluate the dosimetric accuracy of the workflow. Results. The motion compensated CBCT was used to verify pre-treatment position and the average calculated position was within −0.3 ± 1.1 mm of the phantom’s ground truth position at 0°. KIM tracked the position of the target in real-time as the phantom was rotated and the average calculated position was within −0.2 ± 0.8 mm of the phantom’s ground truth position. A 3D conformal treatment delivered on the prototype system with image guidance had a 3%/2 mm gamma pass rate of 96.3% compared to 98.6% delivered using a conventional rotating gantry linac. Conclusions. In this work, we have shown that image guidance can be used with fixed-beam treatment systems to measure and account for changes in target position in order to maintain dosimetric coverage during horizontal rotation. This treatment modality could provide a viable treatment option when there insufficient space for a conventional linear accelerator or where the cost is prohibitive.

This paper is a review of the development of the mechanical pulping process with focus on refiner-based processes. The intention is to provide an overview of the trends and the major advances in the development of the mechanical pulping (MP) process. The focus is on the development of the entire MP process, rather than the refiner as such. However, when discussing the MP process development, it is inevitable to consider the development of the refiner unit operation briefly. Processes for printing papers based on softwood is mainly discussed, but board processes are discussed briefly as well.

Many alternatives to surgical castration have been explored to induce short or long term infertility in male animals. Comparatively few have been carefully evaluated in very young production animals. A comparison of four treatments known to deplete testicular cells in rodents (heating, cooling, chemotherapy, radiation) was undertaken using ram lambs. Neither testicular cooling (0 °C) nor heating (45 °C) affected testis weights, tubule diameters or germ cell numbers. Low dose chemotherapy (Busulfan 4 mg/kg) treatment caused dramatic falls in white blood cells and platelets numbers which recovered within 3 weeks. Spermatogonia numbers were not significantly reduced (27% change). The impact of irradiation doses (0–15 Gy) delivered with high precision to the testis by a 6 MV photon beam was assessed by serial biopsies. Sertoli cell numbers were depleted by 90% at 3 weeks in 15 Gy treated testes. Spermatogonia were depleted 8 weeks after irradiation with 9 Gy, 12 Gy and 15 Gy. By 13 weeks, only in the 15 Gy treated testes were spermatogonia and Sertoli cell numbers lower. At 13 weeks testis atrophy resulted in 3/6 lambs irradiated with 12 Gy or 15 Gy. Irradiation of very young lambs clearly compromised testis function, thermal treatment was ineffective and busulfan treatment resulted in minimal effects.

Purpose To investigate the accuracy of the dosimetry of radiation fields produced by small ELEKTA cone collimators used for stereotactic radiosurgery treatments (SRS) using commercially available detectors EBT3 GafchromicTM film, IBA Stereotactic diode (SFD), and the recently developed detector DUO, which is a monolithic silicon orthogonal linear diode array detector. Methods These three detectors were used for the measurement of beam profiles, output factors, and percentage depth dose for SRS cone collimators with cone sizes ranging from 5 to 50 mm diameter. The measurements were performed at 10 cm depth and 90 cm SSD. Results The SRS cone beam profiles measured with DUO, EBT3 film, and IBA SFD agreed well, results being in agreement within ±0.5 mm in the FWHM, and ±0.7 mm in the penumbra region. The output factor measured by DUO with 0.5 mm air gap above agrees within ±1% with EBT3. The OF measured by IBA SFD (corrected for the over‐response) agreed with both EBT3 and DUO within ±2%. All three detectors agree within ±2% for PDD measurements for all SRS cones. Conclusions The characteristics of the ELEKTA SRS cone collimator have been evaluated by using a monolithic silicon high spatial resolution detector DUO, EBT3, and IBA SFD diode. The DUO detector is suitable for fast real‐time quality assurance dosimetry in small radiation fields typical for SRS/SRT. This has been demonstrated by its good agreement of measured doses with EBT 3 films.

The laparoscopic approach to tumour nephrectomy in children is controversial. We therefore reviewed our institution's cases of tumour nephrectomy (laparoscopic, open, and converted) to better understand which is suitable for this approach, what factors prevent it, and whether one can excise tumours greater than the CCLG recommendation of 300 ml.All tumour nephrectomies performed between 2002 and 2016 were identified using our surgical database. Further data were gathered from radiology and pathology databases. Those with nonrenal tumours or having a partial nephrectomy were excluded. Tumour maximum diameters, volumes, and ratios to contralateral kidneys were calculated. A Mann-Whitney U was used to compare the groups.Forty-three cases were included. Fifteen procedures were completed laparoscopically (35%), and a further 3 converted. The median age at surgery was 2.5 years (range 0-10) in the laparoscopic group and 2 years (range 0-15) in the open group. There was a significant difference (P0.05) between the laparoscopic and open groups for: median maximum diameter (10cm vs 12.25cm), median volume (155 ml vs 459 ml), maximum diameter ratio (1.22 vs 1.75), and volume ratio (3.8 vs 11.2).Tumours in the laparoscopic group were significantly smaller, but it was possible to excise tumours more than 300 ml. Difficulties in excision related to tumour size relative to the abdomen. Therefore, a ratio of tumour to contralateral kidney may be a better guide to safe excision than an overall volume cutoff. From our series, the laparoscopic approach is likely to be achievable if the volume ratio is ≤ 8.1.Level 3.

With the increase in complexity of brachytherapy treatments, there has been a demand for the development of sophisticated devices for delivery verification. The Centre for Medical Radiation Physics (CMRP), University of Wollongong, has demonstrated the applicability of semiconductor devices to provide cost-effective real-time quality assurance for a wide range of brachytherapy treatment modalities. Semiconductor devices have shown great promise to the future of pretreatment and in vivo quality assurance in a wide range of brachytherapy treatments, from high-dose-rate (HDR) prostate procedures to eye plaque treatments. The aim of this article is to give an insight into several semiconductor-based dosimetry instruments developed by the CMRP. Applications of these instruments are provided for breast and rectal wall in vivo dosimetry in HDR brachytherapy, urethral in vivo dosimetry in prostate low-dose-rate (LDR) brachytherapy, quality assurance of HDR brachytherapy afterloaders, HDR pretreatment plan verification, and real-time verification of LDR and HDR source dwell positions.

A feasibility study is presented on a newly developed microdosimetry system named Octobox, for its application in low dose rate, mixed radiation environments. A full characterization of the device was performed at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan, out-of-field of various heavy ion radiation fields — 290 MeV/u 12C, 230 MeV/u and 490 MeV/u 28Si and 400 MeV/u 20Ne ions, as well as a low dose rate 222Rn environment at the Australian Nuclear Sciences and Technology Organization (ANSTO). The device was shown to collect adequate statistics in a short period of time when compared to the MicroPlus probe with a single microdosimeter, while accurately measuring microdosimetric quantities and the corresponding average quality factor ( Q ¯ ) and dose equivalent (H) of the mixed radiation field. Good agreement of the microdosimetric spectra was also shown with Geant4 simulations for all presented ion fields. Based on the findings in this study, the Octobox is capable of being applied in mixed, low dose rate, radiation environments such as those encountered in space and aviation, as well as in underground mines for radiation protection purposes.

Introduction Patient rotation could greatly simplify radiation therapy delivery, with particularly important ramifications for fixed beam treatment with protons, heavy ions, MRI-Linacs, and low cost Linacs. Patient tolerance is often cited as a barrier to widespread implementation to patient rotation; however, no quantitative data addressing this issue exists. In this study, patient reported experiences of slow, single arc rotation in upright (sitting) and lying orientations are reported. Methods Fifteen patients currently or previously treated for cancer were slowly (~2 rpm) rotated in upright and lying orientations using an existing medical device. Patients were rotated 360° in 45° increments. Rotation was paused for 30 seconds at each angle to simulate beam delivery. Claustrophobia, anxiety and motion sickness were monitored via validated questionnaires. The Wilcoxon signed rank test was used to test for significant differences in anxiety and motion sickness before, during and after the study. Results No significant differences in anxiety or motion sickness were found between before and after the study, or upright and lying rotation (P > 0.05). The median percentage scores for anxiety and motion sickness immediately following the study were both 0. In general, anxiety and motion sickness scores were low throughout the study. All patients except one completed the study. Conclusions Slow, single arc rotation in upright and lying orientations was well tolerated in this study. These results support the need for further studies into the clinical implementation of patient rotation, which could have a major impact on the practice and cost of radiotherapy.

The characterisation of a novel multi-strip silicon detector, the serial Dose Magnifying Glass, to incident 60 MeV mono-energetic proton beams, typical for ocular melanoma treatment, was performed by means of Geant4 simulations and experimental methods. Geant4 simulations were performed to determine the applicability and potential of the detector for proton beam range verification with high spatial resolution. Experimental characterisation was performed using the CATANA beam line to confirm the Monte Carlo feasibility study and determine the detector response to incident proton beams of 5 mm, 13 mm, 25 mm and 36 mm diameter, in addition to the detector response when PMMA slabs are positioned between the detector and the beam nozzle. Results indicate the suitability of the detector for proton beam range verification in proton therapy Quality Assurance.

In this work, we used the Monte Carlo-based Geant4 simulation toolkit to calculate the ambient dose equivalents due to the secondary neutron field produced in a new projected proton therapy facility. In particular the facility geometry was modeled in Geant4 based on the CAD design. Proton beams were originated with an energy of 250MeV in the gantry rooms with different angles with respect to the patient; a fixed 250MeV proton beam was also modeled. The ambient dose equivalent was calculated in several locations of interest inside and outside the facility, for different scenarios. The simulation results were compared qualitatively to previous work on an existing facility bearing some similarities with the design under study, showing that the ambient dose equivalent ranges obtained are reasonable. The ambient dose equivalents, calculated by means of the Geant4 simulation, were compared to the Australian regulatory limits and showed that the new facility will not pose health risks for the public or staff, with a maximum equivalent dose rate equal to 7.9mSv/y in the control rooms and maze exit areas and 1.3·10-1mSv/y close to the walls, outside the facility, under very conservative assumptions. This work represents the first neutron shielding verification analysis of a new projected proton therapy facility and, as such, it may serve as a new source of comparison and validation for the international community, besides confirming the viability of the project from a radioprotection point of view.

The C-13 methanol isotopologues 13CH3OH, 13CD3OD, and 13CHD2OH have individually served as the laser medium for an optically pumped molecular laser system used to generate far-infrared radiation. Once detected the frequencies of these laser emissions were measured using a heterodyne technique to a one-sigma fractional uncertainty no less than ± 5 parts in 107. In total, 60 far-infrared laser frequencies, ranging from 0.355 to 2.817 THz, have been measured for the first time. One of these laser emissions was discovered during this investigation and is reported with its polarization with respect to the CO2 pump laser, output power, and optimal operating pressure. In several cases, these measured laser frequencies are in excellent agreement with the calculated values, as determined through combination-loop relations, further confirming the proposed spectroscopic assignments.

Purpose: The purpose of this article is to present the first imaging experiments to demonstrate the functional equivalence between a conventional rotational gantry and a fixed-beam imaging geometry, and the feasibility of an iterative image-reconstruction technique under gravitational deformation. Methods and materials: Experiments were performed using an Elekta Axesse with Agility MLC and XVI, a custom-built rotating phantom stage, a Catphan QA phantom, and a porcine heart. For the imaging equivalence, a conventional cone beam computed tomography (CBCT) of the Catphan was acquired, as well as a set of 660 x-ray projections with a static gantry and rotating Catphan. Both datasets were reconstructed with the Feldkamp-Davis-Kress (FDK) algorithm, and the resultant volumetric images were compared using standard metrics. For imaging under gravitational deformation, a conventional CBCT of the Catphan and a set of 660 x-ray projections with a static gantry and rotating Catphan were also acquired with a porcine heart. The conventional CBCT was reconstructed using FDK. The projections that were acquired with the heart rotating were sorted into angular bins and reconstructed with prior image constrained compressed sensing using a deformation-blurred FDK prior. Deformation was quantified with B-spline transformation-based deformable image registration. Results: For imaging equivalence, the difference between the two Catphan images was consistent with Poisson noise. For imaging under gravitational deformation, the conventional CBCT porcine heart image (ground truth at 0 degrees) matched the static gantry, rotating heart reconstruction with a mean magnitude of

In the present work, we reported on the use of a new 2D array of diodes, the Duo, for dosimetry of small beams produced with a CyberKnife system, and shaped with a novel multi-leaf collimator, the InCise 2.

The goal of this work was to assess small-field output factors (OPF) on a newly commissioned linear accelerator (linac) using a ‘correction-less’ 2D monolithic array of diodes, the Duo, which has a spatial resolution of 0.2 mm. The results would validate a set of OPF extracted from the golden beam data (GBD) used to represent the dosimetric characteristics of that linac, an Elekta Versa HD (Elekta, Crawley), fit with an Agility multileaf collimator (MLC). The Duo acquired relative OPF in real time for square fields of nominal side 1, 2, 3 and 4 cm, for 6 MV with flattening filter (WFF) and 6 MV flattening filter free (FFF) photon energies. Results revealed at most a 1.0% difference in OPF when compared to baseline, and bolstered confidence in the acceptance and commissioning of the linac using local GBD as a baseline match.

Hyperthermia, the mild elevation of temperature to 40–43°C, can induce cancer cell death and enhance the effects of radiotherapy and chemotherapy. However, achievement of its full potential as a clinically relevant treatment modality has been restricted by its inability to effectively and preferentially heat malignant cells. The limited spatial resolution may be circumvented by the intravenous administration of cancer-targeting magnetic nanoparticles that accumulate in the tumor, followed by the application of an alternating magnetic field to raise the temperature of the nanoparticles located in the tumor tissue. This targeted approach enables preferential heating of malignant cancer cells whilst sparing the surrounding normal tissue, potentially improving the effectiveness and safety of hyperthermia. Despite promising results in preclinical studies, there are numerous challenges that must be addressed before this technique can progress to the clinic. This review discusses these challenges and highlights the current understanding of targeted magnetic hyperthermia.

Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in the treatment of cancer. It is a variation that relies on a particular form of enhanced selectivity to enable more effective cancerous cell death yet maintaining the integrity of healthy non-cancerous cells. It is yet to successfully make the major step into the wider medical community despite several encouraging trials. In this study, we investigate mEHT from an in vitro perspective. We demonstrate a supra-additive effect on 9 L gliosarcoma cells when exposed to mEHT in combination with MV X-ray radiation. The supra-additive effect is hypothesized to be induced by the mEHT mechanism that in turn causes apoptosis, membrane damage and an increase in rate of cell growth. This proves to be extremely advantageous in the case of the aggressive 9 L cell line as it is known to be radioresistant. However, the universal success of this multimodal treatment does not appear to be positive for all cell lines and requires further research. Due to the fundamental approach taken in this research, our results also provide a new prospect for mEHT to be a tool for sterilizing otherwise radioresistant cancers.

Aims Women treated with pelvic radiation therapy (PRT) for gynaecological or anorectal cancer report a high number of sexual problems and unmet post-treatment psychosexual information needs. Currently, there is suboptimal adherence to recommended rehabilitation aids, such as vaginal dilators, and a paucity of resources to facilitate post-radiation rehabilitation and reduce distress in this population. This randomised controlled trial aimed to evaluate the effectiveness of a study-developed psychosexual rehabilitation booklet in this setting. Materials and methods Eighty-two women scheduled for PRT to treat gynaecological/anorectal cancer were randomised to receive the intervention booklet (n = 44) or standard information materials (n = 38). Self-report questionnaires administered at pre-treatment baseline and at 3, 6 and 12 months post-treatment assessed adherence with rehabilitation aids, booklet knowledge, anxiety, depression and sexual functioning/satisfaction. Results Dilator adherence and booklet knowledge were significantly higher in the intervention group than in the control group (averaged over time points), with scores significantly increasing over time. Younger age and gynaecological cancer were significant predictors of greater dilator adherence. No significant group differences were found on psychological and sexual measures. Conclusions The psychosexual rehabilitation booklet was effective in educating women with gynaecological and anorectal cancers about PRT-related psychosexual side-effects and rehabilitation options, as well as promoting uptake of vaginal dilator use. Future research should elucidate the effectiveness of this booklet in women with greater psychological and sexual functioning needs.

Background Paediatric clavicle fractures are commonly seen in the emergency department (ED), and the current standard of care is to obtain a radiograph for all suspected clavicle fractures. We are yet to determine whether radiographs add valuable information to clinicians’ assessment and therefore if they are necessary in the management of paediatric clavicle fractures. Objective To determine whether clinicians can manage paediatric clavicle fractures without radiographs, first by determining the accuracy of clinicians in identifying the presence of a clavicle fracture, and second by evaluating the level of agreement (kappa (κ)) between the ultimate management of children with suspected clavicle fractures and clinicians’ blinded prediction prior to the radiograph. Methods This prospective study enrolled patients presenting to a paediatric ED with a suspected clavicle fracture. Prior to requesting a radiograph, clinicians completed a standardised form, where they predicted the presence of a fracture and their ultimate management based on their clinical findings, and rated their confidence. Results Of the 50 patients aged 7.2±3.9 years included, 40 (80%) had a radiologically proven clavicle fracture, and clinicians were able to accurately identify them (sensitivity 93%, positive predictive value 88%). There were five (50%) patients without a radiological fracture that were treated with broad arm sling. Clinicians’ prediction of ultimate management had the highest agreement with the ultimate management of the patient on leaving the ED, compared with clinicians’ prediction of the presence of fracture and the final radiograph findings: κ of 0.88 (95% CI 0.64 to 1), 0.67 (95% CI 0.36 to 0.98) and 0.62 (95% CI 0.30 to 0.94), respectively. Thirty-six (72%) of the clinicians felt comfortable treating without radiographs, and this was dependent on their level of training. Conclusions Clinicians can identify the presence of a fracture and tend to be overconservative in their management. Despite negative radiological findings, some patients were treated as though they had a fracture, based on clinical judgement. This adds evidence that radiographs are not routinely required for uncomplicated paediatric clavicle fractures.

This paper presents recent development of Silicon on Insulator (SOI) detectors for microdosimetry at the Centre for Medical Radiation Physics (CMRP) at the University of Wollongong. A new CMRP SOI microdosimeter design, the 3D mushroom microdosimeter is presented. Modification of SOI design and changes to the fabrication processes have led to improved definition of the microscopic sensitive volumes (SV), and thus to better modelling of the deposition of ionizing energy in a biological cell. The electrical and charge collection properties of the devices have been presented in previous works. In this study, the response of the microdosimeters in monoenergetic and spread out Bragg peak therapeutic 12C ion beam at Heavy Ion Medical Accelerator in Chiba (HIMAC, Japan) are presented. Derived relative biological effectiveness (RBE) in 12C ion radiation therapy matches the tissue equivalent proportional counter (TEPC) well, along with outstanding spatial resolution. The use of SOI technology in experimental microdosimetry offers simplicity (no gas system or HV supply), high spatial resolution, low cost, high count rates capabilities for beam characterisation and quality assurance (QA) in charged particle therapy.

INTRODUCTION: We tested the ability of the Assessment of New Radiation Oncology Technology and Treatments framework to determine the clinical efficacy and safety of intensity-modulated radiation therapy (IMRT) compared with 3-dimensional radiation therapy (3DCRT) for post-prostatectomy radiation therapy (PPRT) to support its timely health economic evaluation. METHODS: Treatment plans produced using FROGG guidelines provided dosimetry parameters for both techniques at 64 Gy and 70 Gy and were also used to model early and late outcome probabilities. Clinical parameters were derived from early toxicity and quality of life patient data, systematic literature review and expert opinion. Dosimetry parameters were correlated with the measures of clinical efficacy and safety. RESULTS: Data from two patient cohorts (29 and 27 respectively) were collected within the project timeframe, providing evidence for acute toxicity and quality of life, and dosimetric comparisons. Relative rates of tumour control probability (TCP) and normal tissue control probability (NTCP) modelling were readily derived from the planning exercise and demonstrated advantages in uncomplicated TCP for IMRT over 3DCRT, predominantly due to normal tissue sparing. The safety of IMRT delivery was demonstrated with TCP uncompromised by IMRT protocol violations, which achieved rectal sparing only by reducing minimum target dose and coverage. Conclusion: Sources of desk-top and patient-based evidence were successfully used to demonstrate potential improved clinical efficacy and safety of applying dose escalation using IMRT instead of 3DCRT in PPRT.

Aims To report disease outcomes and late urinary toxicity profile. To assess the impact of changing technique and evolving quality assurance on genitourinary toxicity rates. Methods and materials One hundred eighty patients were treated with external beam radiation therapy and high-dose-rate brachytherapy (HDRB) for localized intermediate- and high-risk prostate cancer, between December 2002 and February 2012. The HDRB technique evolved over the period of this study, from 19.5 Gy/3 (n = 68), to 17 Gy/2 (n = 40), 18 Gy/2 (n = 39), and most recently 19 Gy/2 (n = 33). In the two fraction cohort, 68 patients underwent additional correction for catheter displacement before each fraction. Results With a median followup of 5.2 years, 5-year freedom from failure was 93.7% for intermediate, and 76.0% for high risk patients. The 3- and 6-year cumulative stricture incidence for all patients was 7.8% and 15.3%, respectively. There was no statistically significant difference in stricture rate for the four dose levels used nor between the three fractions and the two fraction technique overall. The 19 Gy/2 fractionation group had the lowest 3-year stricture rate (3.0%). The addition of correction for intrafraction catheter displacement did not result in a statistically significant difference in stricture rates, although the severity of strictures has been reduced. Conclusions Our biochemical control is consistent with other similar series. We found no increase in late urinary toxicity with a two fraction, two implant HDRB technique compared with three fractions. The HDRB dose did not correlate with stricture rates in our series. Correction of intra-fraction catheter displacement did not lead to a statistically significant reduction in stricture rates, although may have mitigated the effects of dose escalation.

Background Prior work estimating optimal treatment utilisation rates for cervical cancer has focused on radiotherapy or chemotherapy, using proportions of patients with clinical indications for specific treatment strategies which were obtained from the published literature. Objectives To estimate optimal uptake rates for surgery, radiotherapy, chemotherapy and chemo-radiotherapy for cervical cancer treatment in Australia and Canada, and to quantify the differences in the optimal and the observed treatment utilisation rates in a large cancer facility from each country. Methods A decision tree was constructed to reflect treatments according to guidelines and current practice (in 1999–2008) in each setting. Detailed patterns of care data from a large cancer facility in each country were obtained, and the observed stage distribution and proportions of patients with each clinical indication were used as inputs. Results The estimated overall optimal treatment rates for cervical cancer in Australia and Canada differed, largely due to the difference in the stage distribution at diagnosis in the two settings; 72% vs 54% with FIGO IA-IIA disease, respectively. The estimated optimal rates for surgery, radiotherapy, chemotherapy and chemo-radiotherapy in Australia were 63% (95% credible interval: 61–64%), 52% (53–56%), 36% (35–38%) and 36% (35–38%), respectively. The corresponding rates in Canada were 38% (36–39%), 68% (68–71%), 51% (49–52%) and 50% (49–51%), respectively. The absolute differences between the optimal and the observed rates were similar between the two settings; the absolute differences for chemotherapy and chemo-radiotherapy uptake were more pronounced (9–15% less than optimal) than those for surgery and radiotherapy uptake (within 5% of optimal). Conclusions This is the first study to use detailed patterns of care data in multiple settings to compare optimal and observed rates for all cervical cancer treatment modalities. We found optimal treatment rates were largely dependent on the overall stage distribution. In Australia and Canada, observed surgery rates, as measured in the two large cancer facilities, were similar to the estimated optimal rates, whereas radiotherapy, chemotherapy and chemo-radiotherapy appeared to be under-utilised.

Purpose: High dose rate (HDR) brachytherapy is a treatment method that is used increasingly worldwide. The development of a sound quality assurance program for the verification of treatment deliveries can be challenging due to the high source activity utilized and the need for precise measurements of dwell positions and times. This paper describes the application of a novel phantom, based on a 2D 11 × 11 diode array detection system, named “magic phantom” (MPh), to accurately measure plan dwell positions and times, compare them directly to the treatment plan, determine errors in treatment delivery, and calculate absorbed dose. Methods: The magic phantom system was CT scanned and a 20 catheter plan was generated to simulate a nonspecific treatment scenario. This plan was delivered to the MPh and, using a custom developed software suite, the dwell positions and times were measured and compared to the plan. The original plan was also modified, with changes not disclosed to the primary authors, and measured again using the device and software to determine the modifications. A new metric, the “position–time gamma index,” was developed to quantify the quality of a treatment delivery when compared to the treatment plan. The MPh was evaluated to determine the minimum measurable dwell time and step size. The incorporation of the TG-43U1 formalism directly into the software allows for dose calculations to be made based on the measured plan. The estimated dose distributions calculated by the software were compared to the treatment plan and to calibrated EBT3 film, using the 2D gamma analysis method. Results: For the original plan, the magic phantom system was capable of measuring all dwell points and dwell times and the majority were found to be within 0.93 mm and 0.25 s, respectively, from the plan. By measuring the altered plan and comparing it to the unmodified treatment plan, the use of the position–time gamma index showed that all modifications made could be readily detected. The MPh was able to measure dwell times down to 0.067 ± 0.001 s and planned dwell positions separated by 1 mm. The dose calculation carried out by the MPh software was found to be in agreement with values calculated by the treatment planning system within 0.75%. Using the 2D gamma index, the dose map of the MPh plane and measured EBT3 were found to have a pass rate of over 95% when compared to the original plan. Conclusions: The application of this magic phantom quality assurance system to HDR brachytherapy has demonstrated promising ability to perform the verification of treatment plans, based upon the measured dwell positions and times. The introduction of the quantitative position–time gamma index allows for direct comparison of measured parameters against the plan and could be used prior to patient treatment to ensure accurate delivery. C 2015 American Association of Physicists in Medicine.

Organic solvents can change CNS sensory and motor function. Eye-movement analyses can be important tools when investigating the neurotoxic changes that result from chronic organic solvent exposure. The current research measured the eye-movement patterns of men and women with and without histories of chronic organic solvent exposure. A total of 44 volunteers between 18 and 41 years old participated in this study; 22 were men (11 exposed and 11 controls), and 22 were women (11 exposed and 11 controls). Eye movement was evaluated using a 250-Hz High-Speed Video Eye Tracker Toolbox (Cambridge Research Systems) via an image of a maze. Specific body indices of exposed and non-exposed men and women were measured with an Inbody 720 to determine whether the differences in eye-movement patterns were associated with body composition. The data were analyzed using IBM SPSS Statistics version 20.0.0. The results indicated that exposed adults showed significantly more fixations (t = 3.82; p = 0.001; r = 0.51) and longer fixations (t = 4.27; p = 0.001, r = 0.54) than their non-exposed counterparts. Comparisons within men (e.g., exposed and non-exposed) showed significant differences in the number of fixations (t = 2.21; p = 0.04; r = 0.20) and duration of fixations (t = 3.29; p = 0.001; r = 0.35). The same was true for exposed vs. non-exposed women, who showed significant differences in the number of fixations (t = 3.10; p = 0.001; r = 0.32) and fixation durations (t = 2.76; p = 0.01; r = 0.28). However, the results did not show significant differences between exposed women and men in the number and duration of fixations. No correlations were found between eye-movement pattern and body composition measures (p > 0.05). These results suggest that chronic organic solvent exposure affects eye movements, regardless of sex and body composition, and that eye tracking contributes to the investigation of the visual information processing disorders acquired by workers exposed to organic solvents.

Although some studies have reported perceptual changes in psychosis, no definitive conclusions have been drawn about visual disturbances that are related to bipolar disorder (BPD). The purpose of the present study was to evaluate colour vision in BPD patients. Data were recorded from 24 participants: healthy control group (n = 12) and type 1 BPD group (n = 12). The participants were 20–45 years old and they were free from neurological disorders and identifiable ocular disease and had normal or corrected-to-normal visual acuity. Colour discrimination was evaluated using the Lanthony D-15d, Trivector and Ellipse tests, using a psychophysical forced-choice method. The relationship of visual measures to mood state and cognitive function was also investigated. The results showed that BPD patients had higher colour discrimination thresholds in the D15d (p p p

Introduction To compare outcomes of different salvage treatment modalities in patients with aggressive B-cell non-Hodgkin lymphoma (NHL) who remain FDG-PET positive after R-CHOP chemotherapy. Existing data on these patients with FDG-PET primary refractory disease are limited. Methods Patients with diffuse large B-cell lymphoma or grade 3 follicular lymphoma were retrospectively reviewed from the Prince of Wales Hospital databases. Eligibility criteria were: age≥18 years, treated with R-CHOP, with positive post-chemotherapy FDG-PET. Salvage treatment modalities were: radical radiotherapy (RT, dose≥30 Gy), high dose chemotherapy and autologous stem cell transplant (ASCT), or non-radical management. Survival was calculated from date of post-chemotherapy FDG-PET to last follow-up. Results Twenty-six patients from 2003-2015 met the inclusion criteria. Median age was 60 (range 19-84). Most had adverse baseline features: 21 (81%) stage III-IV, 24 (92%) bulky disease and nine (35%) skeletal involvement. Characteristics of PET-positivity post-chemotherapy were single site in 16 (62%), sites of prior bulk in 24 of 24, skeletal sites in five of nine, and able to be encompassed by RT in 21 (81%). Salvage treatment was: radical RT in 17 (65%), ASCT in four (15%) and non-radical in five (20%). Median follow-up of surviving patients was 31 months. Kaplan-Meier estimates of 3-year PFS and OS were 41% and 52%, respectively. By salvage modality, 3-year PFS was 51% for RT, 25% for ASCT and 20% for non-radical treatment, (P = 0.453); 3-year OS was respectively 65%, 25% and 40% (P = 0.173). Conclusion Patients with FDG-PET positive disease after R-CHOP for aggressive B-cell NHL are salvageable with radiotherapy.

Purpose This work aims to characterise a proton pencil-beam scanning (PBS) and passive double scattering (DS) systems as well as to measure parameters relevant to the relative biological effectiveness (RBE) of the beam using a silicon-on-insulator (SOI) microdosimeter with well-defined 3D sensitive volumes (SV). The dose equivalent downstream and laterally outside of a clinical PBS treatment field was assessed and compared to that of a DS beam. Methods A novel silicon microdosimeter with well-defined 3D SVs was used in this study. It was connected to low noise electronics, allowing for detection of lineal energies as low as 0.15 keV/μm. The microdosimeter was placed at various depths in a water phantom along the central axis of the proton beam, and at the distal part of the spread out Bragg peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the measured microdosimetric lineal energy spectra as inputs to the modified microdosimetric kinetic model (MKM). Geant4 simulations were performed in order to verify the calculated depth-dose distribution from the treatment planning system (TPS) and to compare the simulated dose-mean lineal energy to the experimental results. Results For a 131 MeV PBS spot (124.6 mm R90 range in water), the measured dose-mean lineal energy yD¯, increased from 2 keV/μm at the entrance to 8 keV/μm in the BP, with a maximum value of 10 keV/μm at the distal edge. The derived RBE distribution for the PBS beam slowly increased from 0.97 ± 0.14 at the entrance to 1.04 ± 0.09 proximal to the BP, then to 1.1 ± 0.08 in the BP, and steeply rose to 1.57 ± 0.19 at the distal part of the BP. The RBE distribution for the DS SOBP beam was approximately 0.96 ± 0.16 to 1.01 ± 0.16 at shallow depths, and 1.01 ± 0.16 to 1.28 ± 0.17 within the SOBP. The RBE significantly increased from 1.29 ± 0.17 to 1.43 ± 0.18 at the distal edge of the SOBP. Conclusions The SOI microdosimeter with its well-defined 3D SV has applicability in characterising proton radiation fields and can measure relevant physical parameters to model the RBE with sub-millimetre spatial resolution. It has been shown that for a physical dose of 1.82 Gy at the BP, the derived RBE based on the MKM model increased from 1.14 to 1.6 in the BP and its distal part. Good agreement was observed between the experimental and simulation results, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in proton therapy. This article is protected by copyright. All rights reserved.

New 10- $\mu \text{m}$ -thick silicon microdosimeters utilizing 3-D technology have been developed and investigated in this paper. The TCAD simulations were carried out to understand the electrical properties of the microdosimeters’ design. A charge collection study of the devices was performed using 5.5-MeV He2+ ions which were raster scanned over the surface of the detectors and the charge collection median energy maps were obtained and the detection yield was also evaluated. The devices were tested in a 290 MeV/u carbon ion beam at the Heavy Ion Medical Accelerator in Chiba (HIMAC) in Japan. Based on the microdosimetric measurements, the quality factor and dose equivalent out of field were obtained in a mixed radiation field mimicking the radiation environment for spacecraft in deep space.

Software engineering means developing software for a purpose. For systems that interact with a physical problem world, the proximate purpose is a desired behaviour of that problem world: the fundamental engineering task is to develop the system behaviour and specify the software that will evoke it. This chapter sketches a discipline for this task, in which behaviours are always understood as the result of interactions of a software machine and a physical problem world. Complex behaviour is designed in terms of simple constituent behaviours. The running behaviour instances form a dynamic tree in which control of the tree is exercised by the software machines at the nodes.