Background/Objectives: Particle arc therapy (PArc) is an emerging radiotherapy technique with the potential to improve dose conformity and organ-at-risk (OAR) sparing, while also enhancing biological effectiveness through favourable dose-averaged linear energy transfer (LETd) distributions. This scoping review aimed to evaluate the current evidence on PArc, including dosimetric, biological, and delivery-related outcomes, and to identify key limitations and future research directions. Methods: Following the PRISMA-ScR 2018 guidelines, a systematic search was conducted across MEDLINE, Scopus, and Google Scholar in December 2025, identifying 74 relevant studies. Eligible studies included peer-reviewed articles reporting treatment planning, dosimetric, biological, or delivery outcomes, with comparisons to conventional particle therapy techniques. Data were extracted and synthesised qualitatively due to heterogeneity in study designs, reported metrics, and outcome definitions. Results: Relative to conventional particle therapy techniques, PArc generally demonstrated maintained target coverage, enhanced conformity (median relative improvement in conformity index: 6.3%), and more variable dose homogeneity. Improved OAR sparing and reduced integral dose (median relative reduction in integral dose: 10.5%) were commonly observed, although these benefits were sometimes accompanied by an increased low-dose bath, reflecting a trade-off between low-dose and intermediate-high-dose regions. Reductions in intermediate-to-high dose volumes were often associated with improved modelled biological outcomes, including reduced predicted normal tissue complication probabilities and secondary cancer risk. Enhanced LETd distributions were reported, with redistribution of high LETd from surrounding healthy tissue to the tumour volume, particularly in studies of carbon-ion arc therapy and radioresistant tumours. Robustness findings were mixed, with trade-offs among conformity, homogeneity, delivery efficiency, and LETd enhancement, and strong dependence on tumour site, delivery strategy, and evaluation method. Delivery efficiency was also variable, depending on machine capabilities and optimisation strategies. Conclusions: PArc shows significant potential to improve radiotherapy outcomes; however, the current evidence is largely limited to in silico studies. Further research is required to establish standardised methodologies and evaluation frameworks, integrate biological optimisation, and validate findings through prospective clinical studies before routine clinical implementation can be achieved.

PURPOSE:This study explores the feasibility of dose-escalated proton beam therapy (dPBT) for Locally Advanced Pancreatic Cancer (LAPC) patients by modelling common patient scenarios using current clinically-adopted practices. METHODS:Five patient datasets were used as simulation phantoms, each with six tumour sizes, to systematically simulate treatment scenarios typical in LAPC patients. Using the Raystation treatment planning system, robustly-optimised dPBT and stereotactic ablative radiotherapy (SABR) treatment plans were created with a 5 mm margin allowing for intra- and inter-fraction anatomical changes, following clinically-adopted protocols. Safe dose-escalation feasibility is assessed with dose metrics, tumour control (TCP) and normal tissue complication probabilities (NTCP) for average and worst-case intra-fraction motion scenarios. Significance testing was performed using a paired student's t-test. RESULTS:Dose-escalation feasibility is largely dependent on tumour size and proximity to critical structures. Minimal therapeutic benefit was observed for patients with >4.5cm tumours, however for tumours ≤4.5cm dPBT TCPs of 45%-90% compared to SABR TCPs of 10%-40% (p<0.05). The worst-case scenario dPBT TCP was comparable to SABR. Hypofractioned dPBT further improved this result to >90% (p<0.05) for tumours ≤4.5cm. CONCLUSION:Safe dPBT is feasible for patients with targets up to 4.5 cm in size and see a significant therapeutic benefit compared to the current standard of care in SABR. A patient-specific approach should be taken based on tumour size and surrounding anatomy.

BACKGROUND:There is growing interest in embedding health-related quality of life (HRQoL) assessment and patient-reported outcome measures (PROMs) within clinical cancer care. This study evaluated the feasibility, acceptability, and usability of implementing an electronic PROM (ePROM) platform to measure HRQoL in children with cancer. PROCEDURE:A multicenter mixed-methods feasibility study was conducted over 12 months with children aged 5-12 years diagnosed with cancer, their parents, and their clinicians. Participants completed age-appropriate child self-report and parent-proxy report pediatric quality of life inventory (PedsQL) generic core scales using a web-based platform at key clinical milestones. Clinicians were provided with access to HRQoL outcomes. Parents and clinicians completed evaluation surveys, including the system usability scale (SUS), at 6 months to assess usability and acceptability. RESULTS:A total of 91 participants were enrolled, including 37 children, 37 parents, and 17 clinicians. Overall, 85% of all administered PROMs were completed by at least the child or parent respondent, yielding a total of 175 PROMs. Children completed 88% of scheduled PROMs, whereas parents completed 62%. Evaluation surveys were completed by 17 parents and 6 clinicians. The mean SUS score was 88.6 (standard deviation [SD] = 11.5), indicating high usability. All responding parents rated the platform as child friendly and said that the PROM captured important aspects of their child's HRQoL. CONCLUSIONS:Routine assessment of HRQoL using an ePROM platform was feasible, acceptable, and usable for children aged 5-12 years with cancer. Preliminary evidence suggesting clinical utility supports the need for future implementation-effectiveness studies.

BACKGROUND:Glioblastoma (GB) is an aggressive primary brain tumor with local recurrence rates exceeding 90% and a five-year survival rate of approximately 5%. Standard treatments such as surgical resection, external beam radiotherapy (EBRT), and chemotherapy often leave residual tumor cells that are resistant to therapy. Local targeted alpha therapy (TAT) with actinium-225 (225Ac) offers high-linear energy transfer (LET) cytotoxicity but is limited by short diffusion range and elevated intratumoral pressure. Convection-enhanced delivery (CED), which applies mild hydraulic pressure to drive bulk flow, may improve radionuclide penetration. PURPOSE:This study presents a computational model simulating the distribution of unlabeled 225Ac delivered via CED. The full 2 2 5Ac decay chain (parent + daughters) is included in the dosimetric calculations. By characterizing transport dynamics, full decay-chain dose deposition, and resultant clonogenic survival, the model explores both the therapeutic potential and limitations of CED-based alpha therapy. METHODS:A Python-based CED model was developed incorporating diffusion (diffusion coefficient = 1.0 × 10-5 cm2/s), bulk flow (velocity in surgical cavity = 7.0 × 10-5 cm/s; velocity in brain tissue = 5.0 × 10-5 cm/s), and radioactive decay in a radially symmetric brain geometry. Time-dependent activity profiles were imported into the Monte Carlo simulation platform TOol for PArticle Simulation (TOPAS) to calculate voxel-level dose distributions. Simulated dose per decay was converted to clinically relevant administered activity (MBq) and integrated over 50 days, adjusted for a relative biological effectiveness (RBE) of 5 (sensitivity range: 3, 7, and 10), and applied via the linear-quadratic model with tumor repopulation parameters (tumor cell doubling time Tp = 14-50 days; repopulation onset Tk = 0-50 days) to a probabilistic GB cell map. RESULTS:CED achieved therapeutic doses (≥ 2 Gy (RBE)/ MBq) to ∼1.43 cm from injection sites. A five-injection plan delivering a total of 10 MBq reduced the global survival fraction (SF) from 100% (no alpha therapy) to ∼3.4%, with further reductions to ∼2.0% and ∼1.4% at 20 MBq and 30 MBq, respectively. Residual clonogenic tumor cells were mainly located > 2 cm from injection sites. Sensitivity analysis identified injection site placement and total activity as the dominant efficacy factors, whereas varying the RBE had minimal effect. Early tumor repopulation (Tk ≤ 14 days) substantially reduced control in fast-doubling tumors. CONCLUSIONS:This study supports the feasibility of CED of 225Ac for GB, highlighting the need for optimized catheter placement, dosing, and scheduling to address its limited therapeutic radius and tumor repopulation. While results are promising, model assumptions require refinement, and experimental validation is essential to guide clinical translation.

BACKGROUND:Targeted alpha therapy (TAT) with 225Ac-labelled radiopharmaceuticals is a growing therapeutic option for the treatment of various cancers. Due to the short range of alpha particles in tissue, the absorbed dose can be non-uniform on a microscopic scale. Therefore, understanding bone marrow toxicity in TAT requires small-scale dosimetry. METHOD:We developed a voxelised trabecular bone model, based off µCT slices, with a voxel size of (37 × 37 × 37) µm3. A small-scale dosimetry study was performed to assess the marrow toxicity from uptake of unlabelled 225Ac in the trabecular bone. The Particle and Heavy Ion Transport Code System (PHITS) was used to simulate the decays and score the absorbed dose to each voxel from the alpha and beta emissions of the 225Ac decay chain. RESULTS:For the alpha decays on the trabecular surface, 43 % of the marrow voxels were irradiated. The maximum voxel dose for the marrow was 1.1 Gy, and the mean non-zero voxel dose was 0.2 Gy (σ = 0.2 Gy). The beta-emissions from the trabecular surface irradiated all the marrow voxels, with a mean voxel dose of 3.9 mGy (σ = 1.7 mGy). CONCLUSION:Our model demonstrated a non-uniform absorbed dose profile to the red marrow due to alpha emissions on the trabecular bone surface. The alpha emissions irradiated less than half of the marrow voxels,while the beta emissions irradiated all marrow voxels. This could potentially suggest a lower marrow toxicity from alpha-emitters compared to beta-emitters when skeletal metastases are present.

PURPOSE:[225Ac]Ac-DOTATATE is a promising treatment option for patients with neuroendocrine tumors. A concern with 225Ac is that the decay energy can break the bond to the targeting vehicle, producing free daughter radionuclides in the body. Daughter migration is generally not considered in clinical dosimetry, and therefore its effect needs to be studied. METHODS AND MATERIALS:A compartment model for 225Ac and its daughters was developed, where each daughter isotope was assigned unique transfer coefficients. The model was applied to [225Ac]Ac-DOTATATE. Computer simulations were performed in Python for 2 scenarios: (1) the daughters decay at the site of [225Ac]Ac-DOTATATE decay; and (2) the daughters have unique biokinetics, where each decay of [225Ac]Ac-DOTATATE releases 221Fr off the DOTATATE peptide. Two extreme cases concerning intracellular degradation of [225Ac]Ac-DOTATATE were also examined: 1 in which it remains intact inside the tumor cells, and 1 with complete degradation followed by free 225Ac released back to plasma. Normal organ and tumor absorbed doses were determined in each case. In addition, the model-calculated cumulated activities of 221Fr and 213Bi were compared with recent measurements from a clinical trial. RESULTS:When modeling the unique daughter kinetics, the average absorbed dose to the kidneys and tumor was 517 (95% CI, 413-622) and 577 (95% CI, 134-1020) mGy/MBq, respectively, with daughter migration resulting in an average increase in the kidney dose of 10.2% (95% CI, 7.9%-12.5%), and an average decrease in the tumor dose of 22.9% (95% CI, 16.3%-29.4%). The model scenario including free 225Ac showed improved agreement with clinical trial data, specifically for the liver, suggesting a fraction of free 225Ac is produced in patients following the administration of [225Ac]Ac-DOTATATE. CONCLUSIONS:When performing dosimetry for [225Ac]Ac-DOTATATE, our study found that if daughter migration is ignored, the kidney dose is underestimated by ∼10%, and the tumor dose is overestimated by ∼23%. For accurate dosimetry, daughter biokinetics should be considered.

ABSTRACT Introduction Health‐related quality of life (HRQoL) is not routinely evaluated using patient‐reported outcome measures (PROMs) in paediatric radiation therapy (RT). This study aimed to identify barriers and facilitators to HRQoL implementation in paediatric RT clinical practice and requirements for a digital PROM platform, from the perspectives of healthcare professionals. Method Exploratory semi‐structured interviews were conducted with multidisciplinary clinicians from two hospitals providing care to paediatric RT patients. Interviews were transcribed verbatim, descriptively coded and analysed using content analysis. Consolidated Framework for Implementation Research (CFIR) was used as a theoretical framework for data collection, analysis and interpretation. Results Nine interviews were held with nurses ( n = 3), radiation therapists ( n = 3), radiation oncology registrars ( n = 2) and a consultant family therapist. Participants identified digital, clinical and child‐friendly features to inform platform development. All participants recognised the proposed digital platform to be of value by generating new information to support patient care. The perceived alignment with clinical workflows, potential to provide staff satisfaction and individual scope to act on PROM results were key facilitators. Clinical time pressures, transient staffing and reluctance for change were identified as potential barriers. Engagement of clinical staff and training in addressing psychosocial concerns were recommended to support clinical actioning of results and foster successful clinical uptake. Conclusion This study used CFIR to systematically identify requirements for a digital platform and barriers to routine patient‐reported HRQoL collection in the paediatric RT setting. The facilitators and complexities of PROM implementation can inform platform development and future implementation strategies.

Objectives Health-Related Quality of Life (HRQoL) assessment of children with cancer is not routinely performed in South Australia. Our goal was to co-design and evaluate a digital platform ‘Ripple’ for HRQoL collection and real-time clinical actioning in young patients. Methods Study 1 involved platform co-design with children, parents, and multi-disciplinary health professionals. The Ripple platform hosts validated PedsQL Generic Core score patient-reported outcome measures (PROMs) in child self-report and parent-proxy versions for children aged 5-12 years. Study 2 involved a 12-month multi-site hybrid implementation-effectiveness study to test the digital platform's feasibility in South Australian paediatric oncology and radiation oncology services. Children aged 5-12 years receiving treatment or follow-up care, a parent and their healthcare team were invited. Children and parents completed PROMs remotely or in clinic to align with clinical milestones. Clinicians were instantaneously notified of results. Preliminary results from Study 2 are presented. Results Study 1 included 20 participants (seven children, four parents and nine clinicians). In Study 2, 65 participants were recruited, including 28 children, 27 parents and 10 healthcare professionals. 54% of children were female and the median age at recruitment was 7 years. Children were diagnosed with a haematological malignancy (n=19), extracranial solid tumour (n=6) or central nervous system tumour (n=3). Compliance of children and parents completing the scheduled PROMs was 100% and 86%, respectively. Seven of nine clinicians had engaged with the PROM results. Of note, six patients required clinical follow-up based on a PROM entry due to emotional functioning responses (n=6), very low total score (n=2) or a significant decline from previous entry (n=2). Conclusion Early results show that patient-reported HRQoL assessment using a child-friendly digital platform is feasible in paediatric oncology clinical practice. Further research is needed to investigate whether PedsQL can support psychosocial assessment in this cohort.

INTRODUCTION:Health-related quality of life (HRQoL) outcomes are not routinely collected in paediatric radiation therapy (RT). This study co-designed and evaluated an electronic platform to support routine HRQoL assessment using patient-reported outcome measures (PROMs). METHODS:A digital platform was developed following a user-centred design approach. Development included planning with consumers and clinicians, identifying user needs through interviews and iterative design refinements. Alpha testing was performed with consumers. Beta testing involved directed tasks by children, parents and clinician participants to evaluate the developed platform. Thematic analysis of participant feedback was performed to identify refinements and shape clinical implementation strategies. RESULTS:Iterative alpha testing with end-users led to significant improvements in functionality and aesthetics. Beta testing involved 18 participants, including seven healthcare professionals, seven children and four parents. All participants successfully navigated the platform, completed tasks and interpreted PROM results. Participants described the platform as intuitive and child-friendly. Challenges included minor navigation issues on mobile devices. Suggestions for improvement included streamlined result visualisation and enhancements to the instructional material. Whilst parents and clinicians recognised the value of allowing parents to view their child's PROM results, considerations to ensure sensitivity were described. CONCLUSION:The electronic PROM platform was successfully developed to support HRQoL assessment of children undergoing RT. Future research is needed to evaluate the feasibility, usability and acceptability in clinical practice.

Background Working from home during the Covid-19 pandemic was perceived differently by men and women working in STEM fields. The aim of this paper is to highlight the unexpected benefits generated by working from home during the pandemic. Methods Qualitative methodology was used to analyze data, collected via survey. The survey designed and conducted by WiMPBME targeted both males and females working in medical-related STEM fields (physics and engineering) and was answered by 921 individuals from 76 countries across all continents. This report analysed the responses to one open-ended question of the survey, namely: “What is the one positive that you have learnt/experienced as a result of working from home during this pandemic?”. Results 594 responded to the question of interest. Access to home office was reported by 72.2% of survey participants. Males were more likely than females to report no positives of working from home (62.9%). Females were more likely to cite quality time, physical and mental health as positive factors than males, and to mention children in their responses. The most commonly coded thematic unit for males was remote working, with many males reporting the feasibility of working from home. Increased work productivity, better time management and work organisation were other common themes highlighted by responders irrespective of gender. Conclusion The findings of the survey show the diversity of perceptions about remote working in STEM fields, while highlighting the importance of considering family dynamics, individual circumstances as well as gender when evaluating varied experiences of STEM professionals.

Cranial irradiation is associated with health-related quality of life (HRQoL) deficits in childhood cancer survivors. We investigated the relationship between radiation dose to brain substructures and HRQoL in children with brain tumors treated with proton beam therapy (PBT). Data were obtained from children in the Pediatric Proton/Photon Consortium Registry who received PBT for primary brain tumors between 2015 and 2021. HRQoL was assessed using PedsQL Generic Core questionnaires during the first week of PBT and annually thereafter. Standardized substructure segmentations and dosimetry data were correlated with parent-proxy reported HRQoL scores using Pearson correlations. Seventy-six patients were included, with median age 8.9 years (range 1.2–16.5) at diagnosis. Median follow-up was 5.0 years post-PBT and median prescribed dose was 54GyRBE. HRQoL scores were lower than normative population values during PBT, particularly in those who received craniospinal irradiation (CSI) (p < 0.05). Across the total cohort, higher mean doses to the whole brain, supratentorial brain, corpus callosum, left hippocampus, hypothalamus, optic chiasm, pituitary and thalamus correlated with worse HRQoL (r= -0.24 to -0.39), p < 0.05). In the CSI subgroup (n = 17), moderate-to-strong associations between dose to these structures and physical functioning (r= -0.50 to -0.79, p < 0.05) were observed. In children who received focal PBT (n = 59), weaker associations were observed between dose to the hypothalamus and pituitary, and HRQoL (r = -0.28 to -0.36, p < 0.05). Higher radiation doses to specific brain substructures were associated with poorer HRQoL outcomes after PBT. Minimizing dose to these areas during treatment planning may help preserve HRQoL in survivors.

BACKGROUND AND PURPOSE:This work evaluates carotid atherosclerosis quantification from computed tomography angiography (CTA), by novice and expert human contours. Variability sources are critically assessed to establish the minimum performance of future machine learning (ML) tools. METHODS:We analyzed extra cranial carotid lesions, with no, mild, moderate, and severe atherosclerosis (n = 10/group). CTA datasets of 24 patients (n = 6/group) were re-sampled to 2.5 mm axial thicknesses. Lumen, calcific plaque, and soft plaque were manually contoured by three expert experienced clinicians (neuroradiologist, vascular neurologist, and vascular surgeon), a medical physicist (MP), and a radiographer. Contouring was repeated several months later for intra-operator variability and again after development of a protocol. Clinicians blindly ranked each other's contours for descriptive statistical analysis. RESULTS:Relative to internal carotid origin, plaque began a median of 3.75 mm inferior (Interquartile Range [IQR] 0.8-7 mm), extended 18 mm superior (IQR: 13.0-29.6 mm), with a median total length of 24.4 mm (IQR: 14.7-37.4 mm). Clinicians and non-clinicians contoured lumen and calcific plaque similarly (dice similarity coefficient [DSC]: 0.87/0.62 respectively), but varied greater for soft plaque (DSC: 0.21). Neuroradiologist contours were consistently smaller, from approaching the partial-volume artifact conservatively. Clinicians favored their own contours, most pronouncedly the neuroradiologist (standard deviation: 0.00). Establishing a contouring protocol was not found to improve the agreement between clinicians. CONCLUSIONS:CTA carotid pathology contouring inherently has limited clinician agreement due to small structure size and poor contrast. The reference-contour datasets produced by experienced clinicians are prone to inter-and intra-variability which must be carefully considered to ensure ML models developed from such datasets are not fatally flawed.

OBJECTIVE:To explore the perceptions of rural Australian clinicians towards antenatal point-of-care ultrasound (APoCUS) training and accreditation, investigating barriers and enablers to continuing professional development (CPD). METHODS:A prospective cross-sectional online survey of rural Australian clinicians (doctors, nurses, midwives) was undertaken in 2023, using non-probability sampling with self-selection/voluntary response. The survey targeted rural clinicians caring for pregnant patients. Thematic and descriptive analyses were performed with response frequencies grouped by role, work sector, APoCUS use and previous training experience. Fisher's exact test was used for association. RESULTS:Fifty-seven responses were analysed (41 midwives/nurses, 16 physicians/doctors). Two-thirds were performing APoCUS, half reported formal or on-the-job training, and none were accredited. Midwives/nurses had a poorer understanding of their scope of practice (eligibility to learn/perform APoCUS) and accreditation requirements. Interest in accreditation was high, particularly for the midwife/nurse cohort. The perceived benefits of accreditation surrounded improved patient care and services, scanning capability and professional satisfaction. The main barriers to pursuing accreditation were supervision for scanning and assessments, cost, time commitment and workforce shortages. Half of the respondents had access to employer-provided CPD funds, and most reported having to self-fund to meet professional registration requirements. CONCLUSION:Australian rural clinicians are driven to upskill and provide high-quality care to patients but face significant barriers to CPD and attaining accreditation, evidenced by low accreditation rates. Future efforts should focus on simplifying accreditation processes, improving access to qualified supervisors/mentors and raising awareness of training and accreditation opportunities while providing support and incentives for rural clinicians to facilitate access.

BACKGROUND:The concept of Relative Biological Effectiveness (RBE) enables to translate the clinical experience for photon treatments to proton beam therapy. However, uncertainties in the proton RBE across the spread-out Bragg peak (SOBP) (typically assumed to be 1.1) may lead to suboptimal treatment plans and unwarranted toxicity to organs-at-risk. Herein, we report a reliable analytical method to determine the proton RBE in vitro along the SOBP and distal fall-off region. The 3D microtissue cassette enables the high throughput assessment of biological assays including clonogenic assay and γ-H2AX assay following a single proton irradiation. RESULTS:Proton RBE values determined using the standard clonogenic assay at 90 %, 50 % and 10 % of cell survival were calculated to be 1.3, 1.5 and 1.6, respectively. This was found to be consistent with the RBE determined using the γ-H2AX for double-strand DNA break repair (1.58 for 10 % cell survival). In addition, we also observed that the high spatial resolution of the cassette can distinguish the minute but significant γ-H2AX foci changes (number, area) in response to small differences in proton radiation dose fraction. SIGNIFICANCE:The results validate the reliability of the 3D printed cassette in addressing critical radiobiological issues. This methodology enables high throughput irradiation workflow and consequently reduce the time and resource burden for clinical facilities. This approach could be readily extended to investigate the radiobiological unknown of other emerging radiation therapy modalities based on charged particles.

Objective. Pancreatic adenocarcinoma (PDAC) is notoriously difficult to treat due to treatment-resistance and the pancreas' proximity to organs at risks (OARs). Tumour hypoxia further complicates treatment, with substantial intra- and inter-tumour heterogeneity limiting predictability of treatment response, and often requiring multimodal therapy. Proton beam therapy (PBT) with concurrent chemotherapy has been proposed as a promising alternative for patients with locally-advanced unresectable disease. This study aims to evaluate the impact of tumour hypoxia on PBT outcomes in PDAC, and whether concurrent chemotherapy can offset hypoxia-related reductions in local control. Approach. Thirty PBT treatment plans from previous work were utilised. An in silico model was developed to generate multiple hypoxia scenarios within plausible bounds reported in literature on PDAC. The effect of intra-fraction reoxygenation was modelled, followed by the addition of concurrent gemcitabine-based chemotherapy from clinical data. For each scenario, three-dimensional distributions of biologically effective dose, survival fraction, and tumour control probability were evaluated. Main results. Tumour hypoxia significantly reduced the weighted average TCP in larger internal target volumes, particularly where PBT dose was constrained by proximity to OARs. Intra-fraction reoxygenation improved TCP by up to 13.4% [95%CI:6.5, 20.4], and was most effective in tumours with high-grade hypoxia and dose-limited regions. Chemotherapy improved TCP by up to 21.9% [95%CI:20.1, 26.2], though its benefit mitigated dose-loss due to nearby OARs rather than directly mitigating hypoxia. Significance. These findings highlight the importance of considering hypoxia and spatial dose limitations when evaluating treatment efficacy with PBT. Quantifying tumour hypoxia and reoxygenation dynamics before and during treatment could offer insight into local control outcomes. Concurrent chemotherapy can enhance tumour control, but its effect is more influenced by surrounding anatomy than hypoxia, suggesting that while it improves local control, it is insufficient as a standalone treatment for locally-advanced PDAC.

Radioresistant cancers often exhibit upregulated DNA damage response (DDR) proteins including ataxia telangiectasia mutated (ATM), recovering more readily from radiation-induced DNA double-strand breaks (DSBs). ATM inhibitors (ATMi) are therefore being explored as adjuvants in radiotherapy to both enhance radiosensitivity and minimise normal tissue complications. The molecule AZD1390 has been developed as an inhibitor of ATM and is undergoing assessment in clinical trials. However, traditional markers of DNA DSB repair, such as γH2AX, represent stages of DDR downstream from the action of ATM. The ATMi AZD1390, developed by AstraZeneca, ultimately prevents phosphorylation of the H2AX histone variant. In order to quantify ATMi AZD1390 action, the novel and highly complementary assay SensiTive Recognition of Individual DNA Ends (STRIDE) was employed to directly quantify DSBs in comparison to γH2AX after X-ray irradiation of 4T1 cells. Findings revealed that ATM inhibition via AZD1390 delays DSB repair initiation and appears to play a greater role in suppressing DDR beyond ATM inhibition alone. In X-ray irradiated conditions, obfuscation of DSBs commenced between 30- to 45-minutes post-irradiation without AZD1390 versus 45 to 60-minutes for cells pretreated with AZD1390 and entirely prevented γH2AX in the majority of cells. STRIDE and γH2AX exhibited almost no co-localization indicating that they provide distinct and complementary information. DSB formation was also assessed in cells fixed pre-insult to minimise any biological response, providing unprecedented assessment of DSB formation. These results highlight the potential of STRIDE to accurately measure DNA damage response kinetics, paving the way for more precise mechanistic studies into the role of ATM in radiotherapy. ### Competing Interest Statement The authors have declared no competing interest. Tour de Cure, RSP-641-FY2023

Introduction/Background:Uterosacral ligaments (USL) are the most common sites of endometriosis. Transvaginal ultrasound (TVS) demonstrates high diagnostic accuracy for endometriosis of the USLs using standardised technique and characterisations. While high accuracy and reproducibility is established with these techniques by well-trained professionals, the question still remains if these techniques are reproducible in general settings. This study aims to assess the intra and interobserver agreement of TVS characteristics of USLs, between experienced and less experienced examiners in an Australian general ultrasound imaging practice, where sonographers are required to perform ultrasound for endometriosis. Methods:Forty-two patients, with and without known endometriosis, underwent ultrasound imaging of the USLs. Images were obtained of uterosacral ligaments and collated for interobserver survey. Six professional observers independently reviewed the images, classifying characteristics such as echogenicity, echotexture, contour, thickness, and presence of nodules. Interobserver reliability was assessed using Gwet's agreement coefficients (AC1), and the correlation between USL thickness and endometriosis was analyzed using Spearman's correlation. Results:Interobserver agreement for detecting USL endometriosis was substantial (AC1 = 0.63), with an overall agreement of (0.65) for the seven USL characteristics. Intraobserver agreement ranged from moderate (0.60) to almost perfect (0.96). Experience did not significantly affect intraobserver reliability. A strong positive correlation was found between USL thickness and endometriosis (r = 0.7965, P < 0.01). Conclusion:This study demonstrates high inter and intraobserver agreement among sonographers and radiologists in a general imaging department for identifying USL characteristics and diagnosing USL endometriosis. Both experienced and less experienced operators can reliably assess USLs Consistency was shown in identifying thickened uterosacral ligaments however, there is no consensus on where uterosacral ligament be measured. Even so, a thickened USL can prompt further extension of the pelvic scan to look for other endometriosis markers.

Cardiovascular (CV) disease accounts for one third of deaths in females, with hypertension (HTN) and type 2 diabetes mellitus (T2DM) risk factors for its development. Global longitudinal strain (GLS) is a strong prognostic indicator for future CV dysfunction and can be impaired in women with HTN and T2DM. This study aimed to determine if exercise impacts GLS in women with HTN or T2DM. A randomized crossover trial was conducted with 15 women (aged 64.1 +/- 4.7) diagnosed with HTN (n = 12) or T2DM (n = 3). Participants completed an 8-week exercise and 8-week non-exercising control period, separated by a 21.6 +/- 14.2-week washout period. Resting echocardiography and exercise testing were performed pre and post each arm to measure GLS and aerobic fitness (VO2peak). GLS (%) improved significantly following exercise (-16.8 +/- 1.5 to -18.4 +/- 1.8; p <= 0.001, d = 0.98), but not control (-17.2 +/- 2.0 to -16.9 +/- 1.4; p = 0.585, d = -0.14). Similarly, VO2peak (mL/kg/min) increased following exercise (18.0 +/- 2.1 to 19.2 +/- 2.6; p <= 0.001, d = 0.53), but not control (17.5 +/- 2.7-17.2 +/- 2.7; p = 0.269, d = -0.12). There were significant between-group differences for GLS (p <= 0.001, d = 1.02) and VO2peak (p = 0.011, d = 0.63). Aerobic exercise positively impacts GLS and VO2peak in women with HTN and T2DM. GLS may inform exercise professionals regarding the early effectiveness of an aerobic exercise intervention and infer a reduction in CV disease risk. The impact of aerobic exercise on global longitudinal strain (GLS), and other measures of cardiovascular (CV) function, was explored in women with hypertension and type 2 diabetes. Eight weeks of aerobic exercise significantly improved GLS (very large effect; d = 1.02) and aerobic capacity (moderate effect; d = 0.63) compared to control. Improvements observed in GLS and aerobic capacity were clinically meaningful. Significant reductions in systolic and diastolic blood pressure were also observed following exercise, but not control. GLS can measure the effectiveness of aerobic exercise on myocardial function in women at risk of developing CV disease.