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In the current pandemic times, medical physicists may not be aware that there is an interesting story on two significant discoveries related to the coronavirus. One is the invention of polymerase chain reaction (PCR) and the other is the first electron microscopic observation and identification of the coronavirus. Both of them were disregarded by the reviewers and major journals declined to publish these discoveries. These days, PCR, for example, is a widespread method for analyzing DNA, having a profound effect on healthcare, especially now during the Covid-19 pandemic. Prejudice or perhaps ignorance prevail in every aspect of our society, and there is no exception in scientific research. We need to, however, learn from these two stories and be open-minded about novel discoveries and findings – as they may be just disruptive in the “right” way to lead to an unexpected breakthrough.

Hoi Yan Wong,1 Loredana G Marcu,2,3 Eva Bezak,1,3,4 Nayana Anupam Parange1,3 1Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia; 2Faculty of Informatics & Science, University of Oradea, Oradea 410087, Romania; 3Cancer Research Institute and School of Health Sciences, University of South Australia, Adelaide, SA 5001, Australia; 4Department of Physics, University of Adelaide, Adelaide, SA 5005, AustraliaCorrespondence: Nayana Anupam Parange Tel +61 8302 2585Email nayana.Parange@unisa.edu.auAbstract: There are important differences concerning health outcomes between the Australian population living in rural/remote regions and the urban population. Health care provision in remote areas, particularly in regions with a low number of inhabitants, is not without challenges. Aboriginal, rural and remote communities are therefore affected, as they face various obstacles in accessing health services, owing to geographical settings, difficulties in transportation to nearby hospitals, limited or inexistent local qualified personnel. The implementation of point-of-care testing could be a plausible solution to these challenges, as various point-of-care services that have been successfully put into action worldwide indicate towards positive clinical outcomes. Point-of-care units have a real potential in reducing morbidity and mortality in all population groups. This article aims to review the published literature on point-of-care testing around the world, with a focus on health economics and the feasibility of its implementation in Australian rural and remote regions.Keywords: health economics, remote areas, point-of-care testing, cost-effectiveness

Background: Several studies have investigated cardiac dose reduction when utilizing the deep inspiration breath hold (DIBH) technique in patients undergoing radiotherapy for left-sided breast cancer. This paper aims to recommend potential selection criteria based on a retrospective single institute study of free breathing (FB) and DIBH computed tomography (CT) simulation planning scans. Methods: Dosimetric comparisons were performed retrospectively for 20 patients correlating the dose reduction and patient anatomical factors (anatomical variation of chest shape, chest wall separation, total lung volume (TLV) and others). Results: Paired t-tests demonstrated significant cardiac dose reduction for most patients but not all. Minimal cardiac dose reduction was observed for three patients using their DIBH plan, with one patient receiving a higher dose. Linear regression analysis identified a positive correlation between the patient&rsquo, s TLV (on the FB CT simulation scan) and the magnitude of dosimetric benefit received (0.4045 R2). Conclusion: The TLV measured on a FB plan could potentially be utilised to predict cardiac exposure and assist with patient selection for DIBH. This is important in resource allocation, as DIBH may be unnecessarily recommended for some patients with little dosimetric benefit.

Introduction. Lung cancer is a disease which, despite the advancements in treatment, still has a very poor 5-year survival rate. Stereotactic ablative radiation therapy (SABR) is a highly advanced, sophisticated, and safe treatment which allows patients with early stage lung cancer to be treated effectively without invasive procedures and with excellent clinical outcomes. Avoiding surgery minimises morbidity and recovery time, bettering patients’ quality of life. Furthermore, SABR allows patients unsuitable for surgery to still undergo curative treatment. Methods. We aimed to review SABR-related normal tissue toxicities reported in the literature. While many studies assess safety, clinical efficacy, and disease control of SABR for lung cancer, the number of comprehensive reviews that analyse SABR-related side-effects is scarce. This integrative review summarises the toxicities reported in literature based on published clinical trials and tumour location (central or peripheral tumours) for available SABR techniques. Given that the majority of the clinical studies did not report on the statistical significance (e.g., p-values and confidence intervals) of the toxicities experienced by patients, statistical analyses cannot be performed. As a result, adverse events are compiled from clinical reports; however, due to various techniques and nonstandard toxicity reports, no meta-analysis is possible at the current stage of reported data. Results. When comparing lobectomy and SABR in phase III trials, surgery resulted in increased procedure-related morbidity. In phase II trials, very few studies showed high grade toxicities/fatalities as a result of SABR for lung cancer. Gross target volume size was a significant predictor of toxicity. An ipsilateral mean lung dose larger than 9 Gy was significantly associated with radiation pneumonitis. Conclusions. Based on the studies reviewed SABR is a safe treatment technique for lung cancer; however, further well-designed phase III randomised clinical trials are required to produce timely conclusive results and to enable their comparison and statistical analysis.

Jake C Forster,1,2 Wendy M Harriss-Phillips,1,2 Michael JJ Douglass,1,2 Eva Bezak1,3 1Department of Physics, University of Adelaide, 2Department of Medical Physics, Royal Adelaide Hospital, 3Sansom Institute for Health Research and the School of Health Sciences, University of South Australia, Adelaide, SA, Australia Background: The imbalance of angiogenic regulators in tumors drives tumor angiogenesis and causes the vasculature to develop much differently in tumors than in normal tissue. There are several cancer therapy techniques currently being used and developed that target the tumor vasculature for the treatment of solid tumors. This article reviews the aspects of the tumor vasculature that are relevant to most cancer therapies but particularly to vascular targeting techniques.Materials and methods: We conducted a review of identified experiments in which tumors were transplanted into animals to study the development of the tumor vasculature with tumor growth. Quantitative vasculature morphology data for spontaneous human head and neck cancers are reviewed. Parameters assessed include the highest microvascular density (h-MVD) and the relative vascular volume (RVV). The effects of the vasculature on the tumor microenvironment are discussed, including the distributions of hypoxia and proliferation.Results: Data for the h-MVD and RVV in head and neck cancers are highly varied, partly due to methodological differences. However, it is clear that the cancers are typically more vascularized than the corresponding normal tissue. The commonly observed chronic hypoxia and acute hypoxia in these tumors are due to high intratumor heterogeneity in MVD and lower than normal blood oxygenation levels through the abnormally developed tumor vasculature. Hypoxic regions are associated with decreased cell proliferation.Conclusion: The morphology of the vasculature strongly influences the tumor microenvironment, with important implications for tumor response to medical intervention such as radiotherapy. Quantitative vasculature morphology data herein may be used to inform computational models that simulate the spatial tumor vasculature. Such models may play an important role in exploring and optimizing vascular targeting cancer therapies. Keywords: cancer, head and neck, vasculature morphology, hypoxia, radiotherapy response

The radioprotective agent amifostine is a free radical scavenger that can protect cells from the damaging effects of ionising radiation when administered prior to radiation exposure. However, amifostine has also been shown to protect cells from chromosomal mutations when administered after radiation exposure. As apoptosis is a common mechanism by which cells with mutations are removed from the cell population, we investigated whether amifostine stimulates apoptosis when administered after radiation exposure. We chose to study a relatively low dose which is the maximum radiation dose for radiation emergency workers (0.25 Gy) and a high dose relevant to radiotherapy exposures (6 Gy). Mice were administered 400 mg/kg amifostine 30 min before, or 3 h after, whole-body irradiation with 0.25 or 6 Gy X-rays and apoptosis was analysed 3 or 7 h later in spleen and bone marrow. We observed a significant increase in radiation-induced apoptosis in the spleen of mice when amifostine was administered before or after 0.25 Gy X-rays. In contrast, when a high dose of radiation was used (6 Gy), amifostine caused a reduction in radiation-induced apoptosis 3 h post-irradiation in spleen and bone marrow similar to previously published studies. This is the first study to investigate the effect of amifostine on radiation-induced apoptosis at a relatively low radiation dose and the first to demonstrate that while amifostine can reduce apoptosis from high doses of radiation, it does not mediate the same effect in response to low-dose exposures. These results suggest that there may be a dose threshold at which amifostine protects from radiation-induced apoptosis and highlight the importance of examining a range of radiation doses and timepoints.

The effects of ionizing radiation on DNA methylation are of importance due to the role that DNA methylation plays in maintaining genome stability, and the presence of aberrant DNA methylation in many cancers. There is limited evidence that radiation-sensitivity may influence the modulation of DNA methylation by ionizing radiation, resulting in a loss of methylation. The BALB/c, CBA and C57Bl/6 strains are the most commonly utilized mouse strains in radiation research and are classified as radiation sensitive (BALB/c and CBA) or radiation resistant (C57Bl/6). We present here the first direct comparison of changes in repeat element DNA methylation (L1, B1 and Intracisternal A Particle; IAP) over time in these three mouse strains after high-dose radiation exposure. Using a high-resolution melt assay, methylation of the spleen repeat elements was investigated between 1 and 14 days after whole-body irradiation with 1 Gy X rays. Our study demonstrated that rather than a loss of methylation at the elements, all strains exhibited an early increase in L1 methylation one day after irradiation. In the most radiosensitive strain (BALB/c) the increase was also detected at 6 days postirradiation. The radioresistant C57Bl/6 strain exhibited a loss of L1 methylation at 14 days postirradiation. Less extensive changes to the B1 and IAP elements were detected at various time points, and pyrosequencing revealed that the responses of the strains were influenced by sex, with the male BALB/c and CBA mice exhibiting a greater response to the irradiation. The results of our study do not support the hypothesis that the most radiosensitive strains exhibit the greatest loss of repeat element DNA methylation after exposure to high-dose radiation. While the exact mechanism and biological outcome of the changes in DNA methylation observed here are still to be elucidated, this study provides the first evidence that radiation exposure elicits time-dependent changes in the methylation of repeat elements that are influenced by the genetic background, gender and the type of repeat element investigated. Furthermore, it suggest that any induced changes may not be persistent.

Head and neck cancer represents a challenge for radiation oncologists due to accelerated repopulation of cancer cells during treatment. This study aims to simulate, using Monte Carlo methods, the response of a virtual head and neck tumor to both conventional and altered fractionation schedules in radiotherapy when accelerated repopulation is considered. Although clinical trials are indispensable for evaluation of novel therapeutic techniques, they are time-consuming processes which involve many complex and variable factors for success. Models can overcome some of the limitations encountered by trials as they are able to simulate in less complex environment tumor cell kinetics and dynamics, interaction processes between cells and ionizing radiation and their outcome. Conventional, hyperfractionated and accelerated treatment schedules have been implemented in a previously developed tumor growth model which also incorporates tumor repopulation during treatment. This study focuses on the influence of three main treatment-related parameters, dose per fraction, inter fraction interval and length of treatment gap and gap timing based on RTOG trial data on head and neck cancer, on tumor control. The model has shown that conventionally fractionated radiotherapy is not able to eradicate the stem population of the tumor. Therefore, new techniques such as hyperfractionated/ accelerated radiotherapy schedules should be employed. Furthermore, the correct selection of schedule-related parameters (dose per fraction, time between fractions, treatment gap scheduling) is crucial in overcoming accelerated repopulation. Modeling of treatment regimens and their input parameters can offer better understanding of the radiobiological interactions and also treatment outcome.

The innovation of computational techniques serves as an important step toward optimized, patient-specific management of cancer. In particular, in silico simulation of tumour growth and treatment response may eventually yield accurate information on disease progression, enhance the quality of cancer treatment, and explain why certain therapies are effective where others are not. In silico modelling is demonstrated to considerably benefit from information obtainable with PET and PET/CT. In particular, models have successfully integrated tumour glucose metabolism, cell proliferation, and cell oxygenation from multiple tracers in order to simulate tumour behaviour. With the development of novel radiotracers to image additional tumour phenomena, such as pH and gene expression, the value of PET and PET/CT data for use in tumour models will continue to grow. In this work, the use of PET and PET/CT information in in silico tumour models is reviewed. The various parameters that can be obtained using PET and PET/CT are detailed, as well as the radiotracers that may be used for this purpose, their utility, and limitations. The biophysical measures used to quantify PET and PET/CT data are also described. Finally, a list of in silico models that incorporate PET and/or PET/CT data is provided and reviewed.

Aim Methods and materials Results Conclusion Personal information References, Aim: Stereotactic body radiation therapy (SBRT) is an increasingly important treatment option for delivering large localised radiation doses to non-brain legions. Non-conventional fractionation effects are a subject of radiobiological research; including...

Purpose. Despite the latest technological advances in radiotherapy, cancer control is still challenging for several tumour sites. The survival rates for the most deadly cancers, such as ovarian and pancreatic, have not changed over the last decades. The solution to the problem lies in the change of focus: from local treatment to systemic therapy. The aim of this paper is to present the current status as well as the gaps in radiotherapy and, at the same time, to look into potential solutions to improve cancer control and survival. Methods. The currently available advanced radiotherapy treatment techniques have been analysed and their cost-effectiveness discussed. The problem of systemic disease management was specifically targeted. Results. Clinical studies show limited benefit in cancer control from hadron therapy. However, targeted therapies together with molecular imaging could improve treatment outcome for several tumour sites while controlling the systemic disease. Conclusion. The advances in photon therapy continue to be competitive with the much more expensive hadron therapy. To justify the cost effectiveness of proton/heavy ion therapy, there is a need for phase III randomised clinical trials. Furthermore, the success of systemic disease management lies in the fusion between radiation oncology technology and microbiology.

As a result of advanced treatment techniques, requiring precise target definitions, a need for more accurate delineation of the Clinical Target Volume (CTV) has arisen. Mathematical modelling is found to be a powerful tool to provide fairly accurate predictions for the Microscopic Extension (ME) of a tumour to be incorporated in a CTV. In general terms, biomathematical models based on a sequence of observations or development of a hypothesis assume some links between biological mechanisms involved in cancer development and progression to provide quantitative or qualitative measures of tumour behaviour as well as tumour response to treatment. Generally, two approaches are taken: deterministic and stochastic modelling. In this paper, recent mathematical models, including deterministic and stochastic methods, are reviewed and critically compared. It is concluded that stochastic models are more promising to provide a realistic description of cancer tumour behaviour due to being intrinsically probabilistic as well as discrete, which enables incorporation of patient-specific biomedical data such as tumour heterogeneity and anatomical boundaries.

The low dose radioadaptive response has been shown to be protective against high doses of radiation as well as aging-induced genomic instability. We hypothesised that a single whole-body exposure of low dose radiation would induce a radioadaptive response thereby reducing or abrogating aging-related changes in repeat element DNA methylation in mice. Following sham or 10 mGy X-irradiation, serial peripheral blood sampling was performed and differences in Long Interspersed Nucleic Element 1 (L1), B1 and Intracisternal-A-Particle (IAP) repeat element methylation between samples were assessed using high resolution melt analysis of PCR amplicons. By 420 days post-irradiation, neither radiation- or aging-related changes in the methylation of peripheral blood, spleen or liver L1, B1 and IAP elements were observed. Analysis of the spleen and liver tissues of cohorts of untreated aging mice showed that the 17–19 month age group exhibited higher repeat element methylation than younger or older mice, with no overall decline in methylation detected with age. This is the first temporal analysis of the effect of low dose radiation on repeat element methylation in mouse peripheral blood and the first to examine the long term effect of this dose on repeat element methylation in a radiosensitive tissue (spleen) and a tissue fundamental to the aging process (liver). Our data indicate that the methylation of murine DNA repeat elements can fluctuate with age, but unlike human studies, do not demonstrate an overall aging-related decline. Furthermore, our results indicate that a low dose of ionising radiation does not induce detectable changes to murine repeat element DNA methylation in the tissues and at the time-points examined in this study. This radiation dose is relevant to human diagnostic radiation exposures and suggests that a dose of 10 mGy X-rays, unlike high dose radiation, does not cause significant short or long term changes to repeat element or global DNA methylation.

Particle therapies are becoming increasingly available clinically due to their beneficial energy deposition profile, sparing healthy tissues. This may be further promoted with ultra-high dose rates, termed FLASH. This review comprehensively summarises current knowledge based on studies relevant to proton- and carbon-FLASH therapy. As electron-FLASH literature presents important radiobiological findings that form the basis of proton and carbon-based FLASH studies, a summary of key electron-FLASH papers is also included. Preclinical data suggest three key mechanisms by which proton and carbon-FLASH are able to reduce normal tissue toxicities compared to conventional dose rates, with equipotent, or enhanced, tumour kill efficacy. However, a degree of caution is needed in clinically translating these findings as: most studies use transmission and do not conform the Bragg peak to tumour volume; mechanistic understanding is still in its infancy; stringent verification of dosimetry is rarely provided; biological assays are prone to limitations which need greater acknowledgement.

Refereed/Peer-reviewed Background and Purpose: Proton therapy (PT) can reduce side effects for paediatric cranial malignancies. Despite the high number of paediatric patients treated with PT, radiation induced risk factors for second primary cancer (SPC) in out-of-field organs are unknown. This study estimated lifetime attributable risk (LAR) of SPC as a function of age and sex for out-of-field organs following passive scattering and scanning beam PT in paediatric brain tumours. Materials and Methods: Measured neutron dose equivalent spectra for scattered and scanning PT were sourced from literature. The physical distance of 12 measured organs from paediatric CT dataset-based phantoms (5, 9 and 13 years-of-age) were applied to Schneider et al.’s analytical model using MATLAB (R2020B) to calculate the organ-specific LAR of SPC. Results: Scanning beam PT demonstrated smaller LAR (per 10,000 person years) of SPC compared to scattering. This was prominent for more radiosensitive organs, including the lung (320 vs 50), breast (1000 vs 150) and thyroid (350 vs 75), but not for all (i.e., rectum and reproductive organs were

Refereed/Peer-reviewed Purpose: Science diplomacy in medical physics is a relatively young research field and translational practice that focuses on establishing international collaborations to address some of the questions biomedical professionals face globally. This paper aims to present an overview of science diplomacy in medical physics, from an international perspective, illustrating the ways collaborations within and across continents can lead to scientific and professional achievements that advance scientific growth and improve patients care. Methods: Science diplomacy actions were sought that promote collaborations in medical physics across the continents, related to professional and scientific aspects alike. Results: Several science diplomacy actions have been identified to promote education and training, to facilitate research and development, to effectively communicate science to the public, to enable equitable access of patients to healthcare and to focus on gender equity within the profession as well as healthcare provision. Scientific and professional organizations in the field of medical physics across all continents have adopted a number of efforts in their aims, many of them with great success, to promote science diplomacy and to foster international collaborations. Conclusions: Professionals in medical physics can advance through international cooperation, by building strong communication across scientific communities, addressing rising demands, exchange scientific information and knowledge.

There is a growing need for interventions to improve well-being in healthcare workers, particularly since the onset of COVID-19. Objectives: To synthesise evidence since 2015 on the impact of interventions designed to address well-being and burnout in physicians, nurses and allied healthcare professionals. Design: Systematic literature review. Data sources: Medline, Embase, Emcare, CINAHL, PsycInfo and Google Scholar were searched in May–October 2022. Eligibility criteria for selecting studies: Studies that primarily investigated burnout and/or well-being and reported quantifiable preintervention and postintervention outcomes using validated well-being measures were included. Data extraction and synthesis: Full-text articles in English were independently screened and quality assessed by two researchers using the Medical Education Research Study Quality Instrument. Results were synthesised and presented in both quantitative and narrative formats. Meta-analysis was not possible due to variations in study designs and outcomes. Results: A total of 1663 articles were screened for eligibility, with 33 meeting inclusion criterium. Thirty studies used individually focused interventions, while three were organisationally focused. Thirty-one studies used secondary level interventions (managed stress in individuals) and two were primary level (eliminated stress causes). Mindfulness-based practices were adopted in 20 studies; the remainder used meditation, yoga and acupuncture. Other interventions promoted a positive mindset (gratitude journaling, choirs, coaching) while organisational interventions centred on workload reduction, job crafting and peer networks. Effective outcomes were reported in 29 studies, with significant improvements in well-being, work engagement, quality of life and resilience, and reductions in burnout, perceived stress, anxiety and depression. Conclusion: The review found that interventions benefitted healthcare workers by increasing well-being, engagement and resilience, and reducing burnout. It is noted that the outcomes of numerous studies were impacted by design limitations that is, no control/waitlist control, and/or no post intervention follow-up. Suggestions are made for future research. Refereed/Peer-reviewed

Endometriosis is a common and painful gynaecological condition that takes an average of 6.4years to diagnose. While laparoscopic surgery is the recommend gold standard in diagnosis of endometriosis, transvaginal ultrasound (TVS) is able to assist surgeons in the planning and management of patients, especially when there is limited visualisation in the posterior compartment. Uterosacral ligaments (USL) are located in the posterior compartment and are one of the first and most common places that endometriosis deposits, The International Deep Endometriosis Analysis (IDEA) group consensus, which are the current guidelines for DE imaging, recommends a thorough ultrasound assessment to identify endometriotic disease. This includes an assessment of anatomic structures in the posterior compartment including the USLs. However, IDEA does not explicitly articulate specifics of USL imaging and measurements on ultrasound. The primary aim of this review is to determine is to identify ultrasound techniques and characteristics of USLs in the diagnosis of deep infiltrative endometriosis (DE). The secondary aim is to describe and summarise these findings into normal and pathological findings. A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A population, interventions, comparator, and outcome framework was used to define a search strategy. Articles were screened using Covidence review management system, and data was extracted by two authors using a standardised and piolet-tested form. Quality assessment was conducted using the Critical Appraisal Skills Programme (CASP). Medline, Embase and Scopus and Google Scholar were searched yielding 250 articles, with 22 being included in the review. Analysis of the data demonstrated inconsistent reporting of ultrasound techniques and characteristics of USLs. Most (20/22) papers described abnormal criteria of USLs, only 5/22 papers determined what the normal USL appearance is or what techniques (11/22) were applied. Even though reporting was heterogeneous, there was a high level of tertiary centre participation with gynaecological experienced operators, therefore was a high level of agreement. Through review of the current literature, this study has investigated ultrasound techniques and characteristics of USLs for the diagnosis of DE. All papers included in this review reported presence of pathological sonographic findings of the USLs when DE was presented therefore it is recommended that USL examination become a part of TVS exams when DE is clinically suspected. This study also demonstrated that there was lack of data and no agreement when it comes to measuring USLs with DE. Even so, the current evidence demonstrates that scanning the USLs, and locating, identifying, and describing USL thickening and endometriotic nodules in the various locations using the described techniques and characteristics in this review has clinical value in early diagnosis. Refereed/Peer-reviewed

Refereed/Peer-reviewed Cancer stem cells are known to play a key role in tumour development, proliferation, and metastases. Their unique properties confer resistance to therapy, often leading to treatment failure. It is believed that research into the identification, targeting, and eradication of these cells can revolutionise oncological treatment. Based on the principle that what cannot be seen, cannot be targeted, a primary step in cancer management is the identification of these cells. The current review aims to encompass the state-of-the-art functional imaging techniques that enable the identification of cancer stem cells via various pathways and mechanisms. The paper presents in vivo molecular techniques that are currently available or await clinical implementation. Challenges and future prospects are highlighted to open new research avenues in cancer stem cell imaging.

Refereed/Peer-reviewed Purpose: Proton therapy (PT) is broadly accepted as the gold standard of care for pediatric patients with cranial cancer. The superior dose distribution of PT compared to photon radiotherapy reduces normal tissue complication probability (NTCP) for organs at risk. As NTCPs for pediatric organs are not well understood, clinics generally base radiation response on adult data. However, there is evidence that radiation response strongly depends on the age and even sex of a patient. Furthermore, questions surround the influence of individual intrinsic radiosensitivity (α/β ratio) on pediatric NTCP. While the clinical pediatric NTCP data is scarce, radiobiological modeling and sensitivity analyses can be used to investigate the NTCP trends and its dependence on individual modeling parameters. The purpose of this study was to perform sensitivity analyses of NTCP models to ascertain the dependence of radiosensitivity, sex, and age of a child and predict cranial side-effects following intensity-modulated proton therapy (IMPT) and intensity-modulated radiotherapy (IMRT). Methods: Previously, six sex-matched pediatric cranial datasets (5, 9, and 13 years old) were planned in Varian Eclipse treatment planning system (13.7). Up to 108 scanning beam IMPT plans and 108 IMRT plans were retrospectively optimized for a range of simulated target volumes and locations. In this work, dose-volume histograms were extracted and imported into BioSuite Software for radiobiological modeling. Relative-Seriality and Lyman-Kutcher-Burman models were used to calculate NTCP values for toxicity endpoints, where TD50, (based on reported adult clinical data) was varied to simulate sex dependence of NTCP. Plausible parameter ranges, based on published literature for adults, were used in modeling. In addition to sensitivity analyses, a 20% difference in TD50 was used to represent the radiosensitivity between the sexes (with females considered more radiosensitive) for ease of data comparison as a function of parameters such as α/β ratio. Results: IMPT plans resulted in lower NTCP compared to IMRT across all models (p < 0.0001). For medulloblastoma treatment, the risk of brainstem necrosis (> 10%) and cochlea tinnitus (> 20%) among females could potentially be underestimated considering a lower TD50 value for females. Sensitivity analyses show that the difference in NTCP between sexes was significant (p < 0.0001). Similarly, both brainstem necrosis and cochlea tinnitus NTCP varied significantly (p < 0.0001) across tested α/β as a function of TD50 values (assumption being that TD50 values are 20% lower in females). If the true α/β of these pediatric tissues is higher than expected (α/β ∼ 3), the risk of tinnitus for IMRT can significantly increase (p < 0.0001). Conclusion: Due to the scarcity of pediatric NTCP data available, sensitivity analyses were performed using plausible ranges based on published adult data. In the clinical scenario where, if female pediatric patients were 20% more radiosensitive (lower TD50 value), they could be up to twice as likely to experience side-effects of brainstem necrosis and cochlea tinnitus compared to males, highlighting the need for considering the sex in NTCP models. Based on our sensitivity analyses, age and sex of a pediatric patient could significantly affect the resultant NTCP from cranial radiotherapy, especially at higher α/β values.

Background There is limited access to life-saving antenatal ultrasound in low-resource rural and remote settings worldwide, including Australia, mainly due to shortages in skilled staff. Point-of-care ultrasound (PoCUS) offers a viable solution to this service deficit, however, rural clinicians face many barriers accessing training and professional development critical to advancing their clinical practice. Standards for PoCUS training and competency assessment are unclear. Regulation is lacking globally, allowing untrained and inexperienced clinicians to practice PoCUS clinically. Methods This prospective single cohort study aimed to evaluate antenatal PoCUS training workshops for General Practitioners (GPs) and Midwives/Nurses (M/Ns) from rural/remote Australia, assessing the impact of the training on trainees’ knowledge, confidence and translation of PoCUS into clinical practice. Two-day antenatal ultrasound workshops were delivered at the University of South Australia (UniSA) in 2018 and 2019 to 41 rural/remote clinicians . The training was designed and evaluated using the New world Kirkpatrick Evaluation Framework. Sixteen GPs and 25 M/Ns with mixed prior ultrasound experience were funded to attend. The course consisted of lectures interspaced with hands-on training sessions using high-fidelity simulators and live pregnant models. Pre- and post-knowledge assessments were performed. Post-workshop evaluation and follow-up surveys (3- and 6-month post-training) assessed the workshops and changes to trainees’ clinical practice. A 2-day follow-up training session was conducted 12 months after the workshops for 9 trainees. Results Pre/post knowledge testing demonstrated a 22% mean score improvement (95% CI 17.1 to 27.8, P Conclusion This study demonstrated intensive 2-day workshops can equip clinicians with valuable antenatal PoCUS skills, offering a viable solution to assist in the assessment and management of pregnant women in the rural/resource-poor setting where access to ultrasound services is limited or non-existent. Geographical isolation and lack of onsite specialist supervision poses an ongoing challenge to the continuing professional development of remote trainees and the implementation of PoCUS.

Background: Superior treatment responses by patients with human papillomavirus (HPV) positive head and neck squamous cell carcinoma (HNSCC),compared to patients with HNSCC from other causes, drive biomarker research to optimize treatment. Most HNSCC patients receive radiation therapy delivered as a fractionated course. Changing HPV status in HNSCC from apositive prognostic marker to a predictive one requires biomarkers that capture cellular radiation response to cumulative dose.Methods: Nuclear enlargement, γH2AX expression and micronuclei count,were studied in six HNSCC cell lines after 4 Gy fractionated X-irradiation. Results: All HNSCC cell lines displayed altered cellular responses, indicating increasing inability to repair radiation damage with subsequent radiation fractions.Increases in nuclear area were significantly greater among HPV positive cell lines(207% and 67% for the HPV positive and HPV negative groups, respectively). Conclusions: A different character of DNA repair dysfunction in the HPV positive group suggests greater chromosomal translocation with accumulated radiation dose. Refereed/Peer-reviewed

Mucin 1 is a transmembrane glycoprotein which overexpresses cancer-specific epitopes (MUC1-CE) on pancreatic ductal adenocarcinoma (PDAC) cells. As PDAC is a low survival and highly aggressive malignancy, developing radioimmunoconjugates capable of targeting MUC1-CE could lead to improvements in PDAC outcomes. The aim of this study was to develop and perform preliminary testing of diagnostic and therapeutic radioimmunoconjugates for PDAC using an anti-MUC1 antibody, C595. Firstly, p-SCN-Bn-DOTA was conjugated to the C595 antibody to form a DOTA-C595 immunoconjugate. The stability and binding affinity of the DOTA-C595 conjugate was evaluated using mass spectrometry and ELISA. DOTA-C595 was radiolabelled to Copper-64, Lutetium-177, Gallium-68 and Technetium-99m to form novel radioimmunoconjugates. Cell binding assays were performed in PANC-1 (strong MUC1-CE expression) and AsPC-1 (weak MUC1-CE expression) cell lines using Cu-64-DOTA-C595 and Lu-177-DOTA-C595. An optimal molar ratio of 4:1 DOTA groups per C595 molecule was obtained from the conjugation process. DOTA-C595 labelled to Copper-64, Lutetium-177, and Technetium-99m with high efficiency, although the Gallium-68 labelling was low. Lu-177-DOTA-C595 demonstrated high cellular binding to the PANC-1 cell lines which was significantly greater than AsPC-1 binding at concentrations exceeding 100 nM (p < 0.05). Cu-64-DOTA-C595 showed similar binding to the PANC-1 and AsPC-1 cells with no significant differences observed between cell lines (p > 0.05). The high cellular binding of Lu-177-DOTA-C595 to MUC1-CE positive cell lines suggests promise as a therapeutic radioimmunoconjugate against PDAC while further work is required to harness the potential of Cu-64-DOTA-C595 as a diagnostic radioimmunoconjugate. Refereed/Peer-reviewed

Paediatric cancer patients have a risk of late side effects after curative treatment. Proton radiation therapy (PRT) has the potential to reduce the incidence and severity of toxicities produced by conventional photon radiation therapy (XRT), which may improve the health-related quality of life (HRQoL) in children. This systematic review aimed to identify the evidence of HRQoL outcomes in childhood cancer survivors following XRT and PRT. Medline, Embase, and Scopus were systematically searched. Thirty studies were analysed, which described outcomes of 1986 childhood cancer survivors. Most studies (n = 24) described outcomes for children with a central nervous system (CNS) tumour, four studies reported outcomes for children with a non-CNS tumour, and two studies combined CNS and non-CNS diagnoses within a single cohort. No studies analysed routine HRQoL collection during paediatric radiation oncology clinical practice. There is insufficient quality evidence to compare HRQoL outcomes between XRT and PRT. Therefore, the current state of the literature does not conclude that PRT produces superior HRQoL outcomes for childhood cancer survivors. Standardised clinical implementation of HRQoL assessment using patient-reported outcomes is recommended to contribute to improvements in clinical care whilst assisting the progression of knowledge comparing XRT and PRT. Refereed/Peer-reviewed

Introduction This study aimed to assess the accuracy of transvaginal ultrasound (TVUS) for the mapping of endometriosis before surgery when performed by sonographers in an outpatient women's imaging centre. Methods A prospective longitudinal cohort study was performed. The study group comprised of 201 women who underwent a comprehensive TVUS assessment, performed by a sonographer. Laparoscopy was performed as the reference standard. Complete TVUS and surgical data were available for 53 women who were included in the final analysis. Results Endometriosis was confirmed at a surgery in 50/53 (94.3%) participants, with 25/53 (47.2%) having deep endometriosis (DE) nodules and/or endometriomas present. TVUS for mapping of DE had an overall sensitivity of 84.0%, specificity of 89.3%, PPV of 87.5%, NPV of 86.2%, LR+ of 7.85, LR- of 0.18, and accuracy of 86.8% (P < 0.001). Ovarian immobility had poor sensitivity for detecting localised superficial endometriosis, DE, adhesions, and/or endometriomas (Left = 61.9% and right = 13.3%) but high specificities (left = 87.5% and right = 94.7%). Site-specific tenderness had low sensitivities and moderate specificities for the same. All soft markers of endometriosis failed to reach statistical significance except for left ovarian immobility (P =

Refereed/Peer-reviewed

Refereed/Peer-reviewed Introduction: there is limited access to life-saving antenatal ultrasound in rural and low-resource settings largely due to shortages in skilled staff. Studies have shown healthcare practitioners can be upskilled in PoCUS through focused training, offering a viable solution to this deficit. However, standards for training and competency assessment are unclear and regulation surrounding practice is lacking. We aimed to review published literature examining antenatal PoCUS training programs, comparing teaching approaches and study methodologies. Methods: a search of electronic databases EMBASE, MEDLINE and Google Scholar was conducted. Original research articles evaluating antenatal PoCUS training of healthcare professionals worldwide were identified for analysis. Articles with limited detail on the PoCUS training intervention and those describing comprehensive diagnostic training programs were excluded. Evaluations were compared against the Kirkpatrick Evaluation Framework (KEF). Results: twenty-seven studies were included from an initial search result of 484 articles. There was considerable heterogeneity between the PoCUS training programs described. Course duration ranged from 3 hours to 2 years, with 11 of the 27 studies delivering obstetric-exclusive content. 44% trained multidisciplinary groups of health professionals. Long-term follow-up training and skills assessments were lacking in over half of the reviewed studies. Study quality and reporting detail varied, but overall beneficial outcomes were reported with 3/4s of the studies reaching upper KEF levels 3 and 4. Conclusion: PoCUS performed by upskilled healthcare professionals offers an attractive solution to the problem of inequitable access to antenatal ultrasound. A review of available literature highlighted a paucity of comparable high-quality studies needed to establish a stronger evidence base for antenatal PoCUS, and a need to standardise training and competency assessment. This review may inform educators, researchers and policy-makers on existing training formats and methodologies to assist in establishing best practice antenatal PoCUS training methods for safe service delivery by remote healthcare professionals.

There are important differences concerning health outcomes between the Australian population living in rural/remote regions and the urban population. Health care provision in remote areas, particularly in regions with a low number of inhabitants, is not without challenges. Aboriginal, rural and remote communities are therefore affected, as they face various obstacles in accessing health services, owing to geographical settings, difficulties in transportation to nearby hospitals, limited or inexistent local qualified personnel. The implementation of point-of-care testing could be a plausible solution to these challenges, as various point-of-care services that have been successfully put into action worldwide indicate towards positive clinical outcomes. Point-of-care units have a real potential in reducing morbidity and mortality in all population groups. This article aims to review the published literature on point-of-care testing around the world, with a focus on health economics and the feasibility of its implementation in Australian rural and remote regions. Refereed/Peer-reviewed

(1) Background: This paper aims to present and discuss the most significant challenges encountered by STEM professionals associated with remote working during the COVID-19 lockdowns. (2) Methods: We performed a qualitative analysis of 921 responses from professionals from 76 countries to the open-ended question: "What has been most challenging during the lockdown for you, and/or your family?" (3) Findings: Participants reported challenges within the immediate family to include responsibilities for school, childcare, and children's wellbeing; and the loss of social interactions with family and friends. Participants reported increased domestic duties, blurred lines between home and work, and long workdays. Finding adequate workspace was a problem, and adaptations were necessary, especially when adults shared the same setting for working and childcare. Connectivity issues and concentration difficulties emerged. While some participants reported employers' expectations did not change, others revealed concerns about efficiency. Mental health issues were expressed as anxiety and depression symptoms, exhaustion and burnout, and no outlets for stress. Fear of becoming infected with COVID-19 and uncertainties about the future also emerged. Pressure points related to gender, relationship status, and ethnicities were also evaluated. Public policies differed substantially across countries, raising concerns about the adherence to unnecessary restrictions, and similarly, restrictions being not tight enough. Beyond challenges, some benefits emerged, such as increased productivity and less time spent getting ready for work and commuting. Confinement resulted in more quality time and stronger relationships with family. (4) Interpretation: Viewpoints on positive and negative aspects of remote working differed by gender. Females were more affected professionally, socially, and personally than males. Mental stress and the feeling of inadequate work efficiency in women were caused by employers' expectations and lack of flexibility. Working from home turned out to be challenging, primarily due to a lack of preparedness, limited access to a dedicated home-office, and lack of previous experience in multi-layer/multi-scale environments. Published version Funding has been received from the International Union for Physical and Engineering Sciences in Medicine (IUPESM) towards data analysis.

Objectives: Low exercise adherence is common amongst breast cancer (BC) patients. This study aimed to understand BC patients exercise identity and fears of exercise to identify barriers to exercise participation. Methods: Women (18 years plus) currently undergoing, or completed (in remission), chemotherapy for BC, and women (18 years plus) with no cancer history completed three validated questionnaires: Exercise Identity Scale (EI), Exercise Fear Avoidance Scale (EFAS) and Fear of Physical Activity/Exercise Scale – Breast Cancer. Results: 86 women were included (BC: n = 51 – non-cancer: n = 35). There were no significant differences between groups when comparing overall EI (p = 0.240; d=0.127) and EFAS (p = 0.060; d=0.203) scores. BC reported significantly higher scores on specific questions related to fear during exercise (EFAS 2,3, and 5; p =

Refereed/Peer-reviewed The continuously evolving field of radiotherapy aims to devise and implement techniques that allow for greater tumour control and better sparing of critical organs. Investigations into the complexity of tumour radiobiology confirmed the high heterogeneity of tumours as being responsible for the often poor treatment outcome. Hypoxic subvolumes, a subpopulation of cancer stem cells, as well as the inherent or acquired radioresistance define tumour aggressiveness and metastatic potential, which remain a therapeutic challenge. Non-conventional irradiation techniques, such as spatially fractionated radiotherapy, have been developed to tackle some of these challenges and to offer a high therapeutic index when treating radioresistant tumours. The goal of this article was to highlight the current knowledge on the molecular and radiobiological mechanisms behind spatially fractionated radiotherapy and to present the up-to-date preclinical and clinical evidence towards the therapeutic potential of this technique involving both photon and proton beams

Refereed/Peer-reviewed Women in Medical Physics and Biomedical Engineering (WiMPBME) is a Task Group established in 2014 under the International Union of Physical and Engineering Scientists in Medicine (IUPESM). The group’s main role is to identify, develop, implement, and coordinate various tasks and projects related to women’s needs and roles in medical physics and biomedical engineering around the world. The current paper summarizes the past, present and future goals and activities undertaken or planned by the Task group in order to motivate, nurture and support women in medical physics and biomedical engineering throughout their professional careers. In addition, the article includes the historical pathway followed by various women’s groups and subcommittees from 2004 up to the present day and depicts future aims to further these professions in a gender-balanced manner.

Objective. A systematic review of dosimetry in Targeted Alpha Therapy (TAT) has been performed, identifying the common issues. Approach. The systematic review was performed in accordance with the PRISMA guidelines, and the literature was searched using the Scopus and PubMed databases. Main results. From the systematic review, three key points should be considered when performing dosimetry in TAT. (1) Biodistribution/Biokinetics: the accuracy of the biodistribution data is a limit to accurate dosimetry in TAT. The biodistribution of alpha-emitting radionuclides throughout the body is difficult to image directly, with surrogate radionuclide imaging, blood/faecal sampling, and animal studies able to provide information. (2) Daughter radionuclides: the decay energy of the alpha-emissions is sufficient to break the bond to the targeting vector, resulting in a release of free daughter radionuclides in the body. Accounting for daughter radionuclide migration is essential. (3) Small-scale dosimetry and microdosimetry: due to the short path length and heterogeneous distribution of alpha-emitters at the target site, small-scale/microdosimetry are important to account for the non-uniform dose distribution in a target region, organ or cell and for assessing the biological effect of alpha-particle radiation. Significance. TAT is a form of cancer treatment capable of delivering a highly localised dose to the tumour environment while sparing the surrounding healthy tissue. Dosimetry is an important part of treatment planning and follow up. Being able to accurately predict the radiation dose to the target region and healthy organs could guide the optimal prescribed activity. Detailed dosimetry models accounting for the three points mentioned above will help give confidence in and guide the clinical application of alpha-emitting radionuclides in targeted cancer therapy.

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Refereed/Peer-reviewed Background: Glioblastomas (GBMs) are notorious for their aggressive features, e.g., intrinsic radioresistance, extensive heterogeneity, hypoxia, and highly infiltrative behaviours. The prognosis has remained poor despite recent advances in systemic and modern X-ray radiotherapy. Boron neutron capture therapy (BNCT) represents an alternative radiotherapy technique for GBM. Previously, a Geant4 BNCT modelling framework was developed for a simplified model of GBM. Purpose: The current work expands on the previous model by applying a more realistic in silico GBM model with heterogeneous radiosensitivity and anisotropic microscopic extensions (ME). Methods: Each cell within the GBM model was assigned an (Formula presented.) value associated with different GBM cell lines and a (Formula presented.) B concentration. Dosimetry matrices corresponding to various MEs were calculated and combined to evaluate cell survival fractions (SF) using clinical target volume (CTV) margins of 2.0 & 2.5 cm. SFs for the BNCT simulation were compared with external X-ray radiotherapy (EBRT) SFs. Results: The SFs within the beam region decreased by more than two times compared to EBRT. It was demonstrated that BNCT results in markedly reduced SFs for both CTV margins compared to EBRT. However, the SF reduction as a result of the CTV margin extension using BNCT was significantly lower than using X-ray EBRT for one MEP distribution, while it remained similar for the other two MEP models. Conclusions: Although the efficiency of BNCT in terms of cell kill is superior to EBRT, the extension of the CTV margin by 0.5 cm may not increase the BNCT treatment outcome significantly.

DNA double-strand breaks (DSBs) are fundamental to cell biology, from evolution to the latest gene-editing technologies. Yet, does an assay exist that truly quantitatively visualizes DSBs? Over-reliance on DSB detection by proxies can misguide interpretation of conventional assays, and more faithful DSB representatives await development.

Introduction: This study aimed to determine the additional time needed to perform an endometriosis transvaginal ultrasound (eTVUS) compared to routine transvaginal ultrasound (rTVUS). Methods: A retrospective case–control study was performed. The study group included 199 eTVUS performed between September 2019 and September 2020. The control group comprised 105 consecutive rTVUS studies performed in the same time period. The time stamps on the ultrasound images of all cases in both groups were reviewed to determine the time taken to perform each study. Mean, median, minimum and maximum scan times for both groups were calculated as was percentage difference between scan times. A two-tailed, unpaired t-test of the normalised data and a Mann–Whitney U test assessing time difference of scans between two groups were performed with P value

Exercise improves measures of cardiovascular (CV) health and function. But as traditional measures improve gradually, it can be difficult to identify the effectiveness of an exercise intervention in the short-term. Left ventricular global longitudinal strain (LVGLS) is a highly sensitive CV imaging measure that detects signs of myocardial dysfunction prior to more traditional measures, with reductions in LVGLS a strong prognostic indicator of future CV dysfunction and mortality. Due to its sensitivity, LVGLS may offer useful method of tracking the effectiveness of an exercise intervention on CV function in the short-term, providing practitioners useful information to improve patient care in exercise settings. However, the effect of exercise on LVGLS is unclear. This systematic review and meta-analysis aimed to determine the effect exercise has on LVGLS across a range of populations. Included studies assessed LVGLS pre–post an exercise intervention (minimum 2 weeks) in adults 18 years and over, and were published in English from 2000 onwards. Study-level random-effects meta-analyses were performed using Stata (v16.1) to calculate summary standardized mean differences (SMD) and 95% confidence intervals (CI). 39 studies met selection criteria, with 35 included in meta-analyses (1765 participants). In primary analyses, a significant improvement in LVGLS was observed in populations with CV disease (SMD = 0.59; 95% CI 0.16–1.02; p = 0.01), however, no significant effect of exercise was observed in CV risk factor and healthy populations. In populations with CV disease, LVGLS could be used as an early biomarker to determine the effectiveness of an exercise regime before changes in other clinical measures are observed.

An investigation into the response of optical fibres to 16.5 MeV protons is presented here. A silica and a poly(methyl methacrylate) (PMMA) optical fibre was exposed to 16.5 MeV protons from a GE PETtrace cyclotron.The optical fibres were exposed to beam currents of 30nA – 270nA and the emission spectrum analysed. The silica fibre was the most sensitive and had two main peaks at 460 nm and 650 nm. The ratio between the peaks was observed to increase as irradiation of the fibres continued, where the 460 nm peak increased at a rate>4times the 650 nm peak. The rate of increase of the ratio between the peaks was observed to be constant at a constant target current and linear with target current. In the case of the PMMA fibre, significant spectral changes were observed during the exposure to 16.5 MeV protons. A simple method for estimating the effect of photodarkening and activation is presented here and indicated that the changes in the spectrum for the PMMA fibres may be due to photodarkening and activation. Refereed/Peer-reviewed

Aim: The negative impact of tumour hypoxia on cancer treatment outcome has been long-known, yet there has been little success combating it. This paper investigates the potential role of in silico modelling to help test emerging hypoxia-targeting treatments in cancer therapy. Methods: A Medline search was undertaken on the current landscape of in silico models that simulate cancer therapy and evaluate their ability to test hypoxia-targeting treatments. Techniques and treatments to combat tumour hypoxia and their current challenges are also presented. Results: Hypoxia-targeting treatments include tumour reoxygenation, hypoxic cell radiosensitization with nitroimidazoles, hypoxia-activated prodrugs and molecular targeting. Their main challenges are toxicity and not achieving adequate delivery to hypoxic regions of the tumour. There is promising research toward combining two or more of these techniques. Different types of in silico therapy models have been developed ranging from temporal to spatial and from stochastic to deterministic models. Numerous models have compared the effectiveness of different radiotherapy fractionation schedules for controlling hypoxic tumours. Similarly, models could help identify and optimize new treatments for overcoming hypoxia that utilize novel hypoxia-targeting technology. Conclusion: Current therapy models should attempt to incorporate more sophisticated modelling of tumour angiogenesis/vasculature and vessel perfusion in order to become more useful for testing hypoxia-targeting treatments, which typically rely upon the tumour vasculature for delivery of additional oxygen, (pro)drugs and nanoparticles Refereed/Peer-reviewed

Head and neck squamous cell carcinomas (HNSCC) resulting from oncogenic transformations following human papillomavirus (HPV) infection consistently demonstrate better treatment outcomes than HNSCC from other aetiologies. Squamous cell carcinoma of the oropharynx (OPSCC) shows the highest prevalence of HPV involvement at around 70–80%. While strongly prognostic, HPV status alone is not sufficient to predict therapy response or any potential dose de-escalation. Cancer stem cell (CSC) populations within these tumour types represent the most therapy-resistant cells and are the source of recurrence and metastases, setting a benchmark for tumour control. This review examines clinical and preclinical evidence of differences in response to treatment by the HPV statuses of HNSCC and the role played by CSCs in treatment resistance and their repopulation from non-CSCs. Evidence was collated from literature searches of PubMed, Scopus and Ovid for differential treatment response by HPV status and contribution by critical biomarkers including CSC fractions and chemo-radio sensitivity.While HPV and CSC are yet to fulfil promise as biomarkers of treatment response, understanding how HPV positive and negative aetiologies affect CSC response to treatment and tumour plasticity will facilitate their use for greater treatment individualisation. Refereed/Peer-reviewed

The aim of this article is to offer a view of the current status of women in medical physics and biomedical engineering, while focusing on solutions towards gender balance and providing examples of current activities carried out at national and international levels. The International Union of Physical and Engineering Scientists in Medicine is committed to advancing women in science and health and has several initiatives overseen by the Women in Medical Physics and Biomedical Engineering Task Group. Some of the main strategies proposed by the Task Group to attain gender balance are: (a) identify and promote female role models that achieve successful work-life balance, (b) establish programs to develop female leaders, (c) create opportunities for females to increase the international visibility within the scientific community, and (d) establish archives and databases of women in STEM Refereed/Peer-reviewed

Purpose: Intrinsic radioresistance and increased proliferation rates in head and neck cancers (HNCs) are associated with negative radiotherapy (RT) treatment responses. The use of gold nanoparticles (AuNPs) as radiosensitisers could enable total radiation dose reduction and lowered radiation‐toxicity. AuNP radiosensitisation may overcome hypoxia‐induced radioresistence and treatment‐induced accelerated repopulation of cancer cells in HNCs, improving radiotherapy outcomes. Methods: Tumour control was determined by considering individual cancer cell responses in probabilistic computational simulations using HYP‐RT software for clinical radiotherapy doses and fractionation schedules along with 3 different nanoparticle administration schedules. Antagonistic tumour hypoxia and rapid tumour regrowth due to accelerated repopulation of cancers cells were taken into consideration. Results: Simulations indicate that tumours that are conventionally uncontrollable can be controlled with AuNP radiosensitisation. In simulations where the absence of AuNPs required radiotherapy doses above standard clinical prescriptions, reoccurring AuNP administration allowed for radiation‐dose reductions below standard clinical dose prescriptions. For example, considering a 2 Gy per fraction radiotherapy schedule, tumour control was achieved with 57.2 ± 5.1 Gy (p =

FLASH radiotherapy, or the administration of ultra-high dose rate radiotherapy, is a new radiation delivery method that aims to widen the therapeutic window in radiotherapy. Thus far, most in vitro and in vivo results show a real potential of FLASH to offer superior normal tissue sparing compared to conventionally delivered radiation. While there are several postulations behind the differential behaviour among normal and cancer cells under FLASH, the full spectra of radiobiological mechanisms are yet to be clarified. Currently the number of devices delivering FLASH dose rate is few and is mainly limited to experimental and modified linear accelerators. Nevertheless, FLASH research is increasing with new developments in all the main areas: Radiobiology, technology and clinical research. This paper presents the current status of FLASH radiotherapy with the aforementioned aspects in mind, but also to highlight the existing challenges and future prospects to overcome them. Refereed/Peer-reviewed

usc Research into machine learning (ML) for clinical vascular analysis, such as those useful for stroke and coronary artery disease, varies greatly between imaging modalities and vascular regions. Limited accessibility to large diverse patient imaging datasets, as well as a lack of transparency in specific methods, are obstacles to further development. This paper reviews the current status of quantitative vascular ML, identifying advantages and disadvantages common to all imaging modalities. Literature from the past 8 years was systematically collected from MEDLINE® and Scopus database searches in January 2021. Papers satisfying all search criteria, including a minimum of 50 patients, were further analysed and extracted of relevant data, for a total of 47 publications. Current ML image segmentation, disease risk prediction, and pathology quantitation methods have shown sensitivities and specificities over 70%, compared to expert manual analysis or invasive quantitation. Despite this, inconsistencies in methodology and the reporting of results have prevented inter-model comparison, impeding the identification of approaches with the greatest potential. The clinical potential of this technology has been well demonstrated in Computed Tomography of coronary artery disease, but remains practically limited in other modalities and body regions, particularly due to a lack of routine invasive reference measurements and patient datasets. Refereed/Peer-reviewed

The COVID-19 pandemic has forced many people, including those in the fields of science and engineering, to work from home. The new working environment caused by the pandemic is assumed to have a different impact on the amount of work that women and men can do from home. Particularly, if the major burden of child and other types of care is still predominantly on the shoulders of women. As such, a survey was conducted to assess the main issues that biomedical engineers, medical physicists (academics and professionals), and other similar professionals have been facing when working from home during the pandemic. A survey was created and disseminated worldwide. It originated from a committee of International Union for Physical and Engineering Sciences in Medicine (IUPESM; Women in Medical Physics and Biomedical Engineering Task Group) and supported by the Union. The ethics clearance was received from Carleton University. The survey was deployed on the Survey Monkey platform and the results were analyzed using IBM SPSS software. The analyses mainly consisted of frequency of the demographic parameters and the cross-tabulation of gender with all relevant variables describing the impact of work at home. A total of 921 responses from biomedical professions in 76 countries were received: 339 males, 573 females, and nine prefer-not-to-say/other. Regarding marital/partnership status, 85% of males were married or in partnership, and 15% were single, whereas 72% of females were married or in partnership, and 26% were single. More women were working from home during the pandemic (68%) versus 50% of men. More men had access to an office at home (68%) versus 64% for women. The proportion of men spending more than 3 h on child care and schooling per day was 12%, while for women it was 22%; for household duties, 8% of men spent more than 3 h; for women, this was 12.5%. It is interesting to note that 44% of men spent between 1 and 3 h per day on household duties, while for women, it was 55%. The high number of survey responses can be considered excellent. It is interesting to note that men participate in childcare and household duties in a relatively high percentage; although this corresponds to less hours daily than for women. It is far more than can be found 2 and 3 decades ago. This may reflect the situation in the developed countries only—as majority of responses (75%) was received from these countries. It is evident that the burden of childcare and household duties will have a negative impact on the careers of women if the burden is not more similar for both sexes. It is important to recognize that a change in policies of organizations that hire them may be required to provide accommodation and compensation to minimize the negative impact on the professional status and career of men and women who work in STEM fields. Refereed/Peer-reviewed

In recent years, artificial intelligence (AI) has increased its prevalence in society with the potential to transform many aspects of our lives. AI is considered to be not just one but a number of technologies. Based on a combination of machine learning, neural networks, deep learning and natural language processing, AI has been demonstrated to perform better than humans in certain circumstances. With the increase in size and complexity of available data, the application of AI and related technologies specifically to medicine and healthcare provides possibilities for contributing to significant improvements in patient outcomes with regards to diagnosis and treatments. Questions remain however as to the extent to which human beings will be replaced by AI. With its potential to be transformation in medicine and healthcare, in this topical debate Lois Holloway and Eva Bezak debate the important evolving field of AI. Refereed/Peer-reviewed

Improvements in the prognosis of pancreatic ductal adenocarcinoma (PDAC) rely on the development of effective treatments to target advanced disease. Mucin 1 (MUC1) is a transmembrane glycoprotein which is involved in the metastatic progression of PDAC and is a receptor-of-interest for targeted radionuclide therapy. The aim of this study was to determine the feasibility of MUC1-based targeted radionuclide therapy for PDAC, by evaluating the expression profile of MUC1 in different pancreatic cells and tissues using the C595 antibody. MUC1 expression was evaluated in four PDAC cell lines (PANC-1, BxPC-3, CAPAN-1 and AsPC-1) using flow cytometry and immunocytochemistry. Immunohistochemistry was performed on primary and metastatic PDAC, pancreatitis, pancreatic intra-epithelial neoplasia and normal pancreatic tissue samples to identify potential changes in C595-reactive MUC1 expression across different disease groups. C595-reactive MUC1 expression was found to varying degrees in the cell lines (11.5&ndash, 93.1%). A pixel analysis of the immunohistochemical staining demonstrated highest MUC1 expression in primary PDAC tissue (mean pixel value of 205.4), followed by other pancreatic cancer types (204.9), pancreatic intra-epithelial neoplasia (203.8), metastatic PDAC (201.5), chronic pancreatitis (198.1) and normal pancreatic tissue (191.4). The increased expression in malignant tissues and reduced expression in benign tissues indicate that C595-reactive MUC1 is a potential target for targeted radionuclide therapy of PDAC.

In the current pandemic times, medical physicists may not be aware that there is an interesting story on two significant discoveries related to the coronavirus. One is the invention of the polymerase chain reaction (PCR) and the other is the first electron microscopic observation and identification of the coronavirus. Both of them were disregarded by the reviewers and major journals declined to publish these discoveries. These days, PCR, for example, is a widespread method for analyzing DNA, having a profound effect on healthcare, especially now during the Covid-19 pandemic. Prejudice or perhaps ignorance prevail in every aspect of our society, and there is no exception in scientific research. We need to, however, learn from these two stories and be open-minded about novel discoveries and findings – as they may be just disruptive in the “right” way to lead to an unexpected breakthrough.

Head and neck squamous cell carcinomas (HNSCC) resulting from human papillomavirus (HPV) are increasing in incidence but demonstrate significantly better treatment response than HNSCC from other causes such as tobacco and alcohol. This study sought to identify differences in HNSCC, intrinsic to HPV status, in their response to radiation dose. Previously unexamined changes in radio-responsiveness following fractionated X-ray irradiation were compared between HPV positive and negative statuses of HNSCC. Six HNSCC cell lines, 3 of each HPV status, were investigated for radiosensitivity by clonogenic assay and modelled by response as a function of dose. Generational cultures of each cell line were developed to follow changes in radiosensitivity after repeated irradiations simulating fractionated radiation therapy. As a group, the HPV positive cell lines were more radiosensitive, but with changes following repeated fractions of dose, and modelling of response as a function of dose, both statuses displayed large radiobiological heterogeneity. These findings challenge current radiobiological assumptions of head and neck cancers as early responding tissue to radiation and may go some way in explaining difficulties reaching consensus in stratification of treatment by HPV status. Consequently, results from this study do not support stratifying radiation therapy by HPV status. Refereed/Peer-reviewed