Targeted Alpha Therapy for Glioblastoma: Review on In Vitro, In Vivo and Clinical Trials.

Glioblastoma (GB), a prevalent and highly malignant primary brain tumour with a very high mortality rate due to its resistance to conventional therapies and invasive nature, resulting in 5-year survival rates of only 4-17%. Despite recent advancements in cancer management, the survival rates for GB patients have not significantly improved over the last 10-20 years. Consequently, there exists a critical unmet need for innovative therapies. One promising approach for GB is Targeted Alpha Therapy (TAT), which aims to selectively deliver potentially therapeutic radiation doses to malignant cells and the tumour microenvironment while minimising radiation exposure to surrounding normal tissue with or without conventional external beam radiation. This approach has shown promise in both pre-clinical and clinical settings. A review was conducted following PRISMA 2020 guidelines across Medline, SCOPUS, and Embase, identifying 34 relevant studies out of 526 initially found. In pre-clinical studies, TAT demonstrated high binding specificity to targeted GB cells, with affinity rates between 60.0% and 84.2%, and minimal binding to non-targeted cells (4.0-5.6%). This specificity significantly enhanced cytotoxic effects and improved biodistribution when delivered intratumorally. Mice treated with TAT showed markedly higher median survival rates compared to control groups. In clinical trials, TAT applied to recurrent GB (rGB) displayed varying success rates in extending overall survival (OS) and progression-free survival. Particularly effective when integrated into treatment regimens for both newly diagnosed and recurrent cases, TAT increased the median OS by 16.1% in newly diagnosed GB and by 36.4% in rGB, compared to current standard therapies. Furthermore, it was generally well tolerated with minimal adverse effects. These findings underscore the potential of TAT as a viable therapeutic option in the management of GB.

DNA Double Strand Break and Response Fluorescent Assays: Choices and Interpretation.

Accurately characterizing DNA double-stranded breaks (DSBs) and understanding the DNA damage response (DDR) is crucial for assessing cellular genotoxicity, maintaining genomic integrity, and advancing gene editing technologies. Immunofluorescence-based techniques have proven to be invaluable for quantifying and visualizing DSB repair, providing valuable insights into cellular repair processes. However, the selection of appropriate markers for analysis can be challenging due to the intricate nature of DSB repair mechanisms, often leading to ambiguous interpretations. This comprehensively summarizes the significance of immunofluorescence-based techniques, with their capacity for spatiotemporal visualization, in elucidating complex DDR processes. By evaluating the strengths and limitations of different markers, we identify where they are most relevant chronologically from DSB detection to repair, better contextualizing what each assay represents at a molecular level. This is valuable for identifying biases associated with each assay and facilitates accurate data interpretation. This review aims to improve the precision of DSB quantification, deepen the understanding of DDR processes, assay biases, and pathway choices, and provide practical guidance on marker selection. Each assay offers a unique perspective of the underlying processes, underscoring the need to select markers that are best suited to specific research objectives.

Modeling the effect of daughter migration on dosimetry estimates for unlabeled actinium-225.

BACKGROUND: Actinium-225 (225 Ac) is an alpha emitting radionuclide which has demonstrated promising results in Targeted Alpha Therapy (TAT). A concern with 225 Ac is that the decay energy can break the bond to the targeting vehicle, resulting in the release of free alpha-emitting daughter radionuclides in the body. PURPOSE: The aim of this work is to develop a compartment model to describe the movement of unlabeled 225 Ac in a human where the daughter isotopes of 225 Ac have unique biokinetics. METHOD: The ICRP Occupational Intake of Radionuclides reports were used to construct a compartment model for the 225 Ac decay chain where the daughter isotopes of 225 Ac are assigned their own unique transfer coefficients (TCs) between compartments. Computer simulations were performed for unlabeled 225 Ac uniformly placed in the plasma and only the dose from alpha particles was considered. Absorbed doses to normal organs were determined for the liver, kidneys, bone, soft tissue, active marrow, and blood. Simulations were performed for the case when: (1) the daughters have unique biokinetics and (2) the daughters decay at the site of 225 Ac. RESULTS: When the daughters have unique biokinetics, the organs that receive the highest absorbed dose are the liver (male: 1466.6 mGy/MBq, female: 1885.7 mGy/MBq), bone (male: 293.6 mGy/MBq, female: 403.6 mGy/MBq) and kidneys (male: 260.8 mGy/MBq, female: 294.0 mGy/MBq). These doses were compared to the case when the daughters of 225 Ac decay at the site of 225 Ac. There was a 13.5% increase in kidney dose, a 0.8% decrease in liver dose, and <0.1% decrease in bone dose calculations when the daughters have unique biokinetics compared to assuming the daughters decay at the site of 225 Ac. CONCLUSIONS: The kidneys received a large dose estimate (260-295 mGy/MBq) as well as a considerable change in dose of +13.5% when the daughters have unique biokinetics compared to assuming the daughters decay at the site of 225 Ac. Therefore, to accurately determine the kidney dose from unlabeled 225 Ac in a human, the biokinetics of the daughter isotopes should be considered.

The Role of Telehealth in Ultrasound Training for Remote Learners: A Systematic Review.

Introduction: Remote learners and educators face geographic, professional, and personal barriers that affect their access to quality ultrasound education. The integration of telehealth in ultrasound education enables learners performing ultrasound to receive real-time instruction from an educator at a distant or remote site. However, to date, there has been poor understanding of the efficacy, benefits, shortcomings, and economic impact of telehealth education in comparison to in-person ultrasound training. The aim of this research was to assess current literature on telehealth in ultrasound education and hands-on training, its outcomes and impact, and requirements for future development. Methods: This review examined international literature on telehealth in ultrasound training. The primary author and second investigator were involved in the research and reached consensus on the eligibility criteria, search strategy, included articles, data extraction, and quality assessment. Results: A total of 23 studies were obtained from Medline, Emcare and Scopus. Key themes identified: Most studies saw an equivalent improvement in knowledge and skills through pre and postassessments in both in-person and telehealth sessions. Generally, learners felt comfortable performing ultrasound guided by a remote educator and felt their skills had been advanced across all studies. Educators reported positive feedback, however compared with learners, educators expressed less satisfaction with the telehealth session. Conclusions: This study demonstrated the feasibility of telehealth in ultrasound training for remote learners with little to no experience. Quality studies with comparable outcomes are needed to ascertain the safe and effective application of telehealth in ultrasound training.

Opportunities in Cancer Therapies: Deciphering the Role of Cancer Stem Cells in Tumour Repopulation.

Tumour repopulation during treatment is a well acknowledged yet still challenging aspect of cancer management. The latest research results show clear evidence towards the existence of cancer stem cells (CSCs) that are responsible for tumour repopulation, dissemination, and distant metastases in most solid cancers. Cancer stem cell quiescence and the loss of asymmetrical division are two powerful mechanisms behind repopulation. Another important aspect in the context of cancer stem cells is cell plasticity, which was shown to be triggered during fractionated radiotherapy, leading to cell dedifferentiation and thus reactivation of stem-like properties. Repopulation during treatment is not limited to radiotherapy, as there is clinical proof for repopulation mechanisms to be activated through other conventional treatment techniques, such as chemotherapy. The dynamic nature of stem-like cancer cells often elicits resistance to treatment by escaping drug-induced cell death. The aims of this scoping review are (1) to describe the main mechanisms used by cancer stem cells to initiate tumour repopulation during therapy; (2) to present clinical evidence for tumour repopulation during radio- and chemotherapy; (3) to illustrate current trends in the identification of CSCs using specific imaging techniques; and (4) to highlight novel technologies that show potential in the eradication of CSCs.

Impact of Aerobic Training on Cardiovascular Function, Fitness, and Patient Reported Outcomes During Anthracycline Chemotherapy: A Case Series in Women With Breast Cancer.

BACKGROUND: Chemotherapy for breast cancer can increase the risk of cancer therapy related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD, however, research to date has indicated high degrees of individual variability following exercise interventions in this population. AIM: This study aimed to explore the impact of regular, individualized aerobic exercise on CTRCD incidence (defined by global longitudinal strain [GLS]) during and immediately upon the completion of dose-dense anthracycline (DDAC) chemotherapy in 5 women with breast cancer. METHODS: Five women receiving DDAC with stage I-III breast cancer enrolled. Participants underwent resting echocardiography and exercise testing before, during, upon the completion of, and 3 months after the completion of DDAC treatment to measure GLS and aerobic fitness (VO2peak). Participants opted-in to an individualized 8-week aerobic exercise intervention (3 sessions per week, 24 sessions total) or standard care for the duration of their DDAC treatment. Data for each participant were presented descriptively. RESULTS: Four of the 5 participants completed the exercise intervention during DDAC treatment (adherence 79.2%-91.7%). Mild asymptomatic CTRCD occurred in 2 of the 4 exercising participants, of whom both were at an increased risk (one was >65 years of age and diagnosed with hypertension, with the other receiving trastuzumab prior to DDAC treatment). Varied responses in VO2peak were observed and did not align with changes in GLS. The only participant not to complete the exercise intervention reported poorer health related quality of life and increased cancer related fatigue at all measurement timepoints. CONCLUSION: This study details the individual variability in cardiovascular responses to exercise that can occur during DDAC treatment in women with breast cancer, which can inform exercise professionals and researchers when designing individualized exercise programs for this population.

Simple quantitative planimetric measurement of nigrosome-1 for clinical settings.

INTRODUCTION: Loss of MRI hyperintense signal in nigrosome-1 (assessed with susceptibility-weighted imaging) is a biomarker for Parkinson's disease (PD). Current clinical practice involves subjectively rating the appearance of nigrosome-1 which is challenging. The study aimed to test and compare a simple method for quantifying nigrosome-1 with the current subjective rating method. METHODS: Two experienced neuroradiologists measured area of hyperintense signal in nigrosome-1 (quantitative method) and rated nigrosome-1 appearance (as normal, attenuated, or absent; subjective method) in 42 patients encompassing the full spectrum of nigrosome-1 integrity (21 patients aged 55.5 ± 20.9 years with Essential tremor (ET) and a subset of 21 patients aged 69.6 ± 8.6 years with PD). Neuroradiologists were blinded to each other's measurements, clinical notes, and patient group. RESULTS: Both methods yielded a significant difference between the groups (PD vs ET; p < 0.001). Pooled (across sides) area of nigrosome-1 hyperintense signal was significantly smaller in the PD group (median = 2.1 mm2, range = 0-15.8 mm2) than ET group (median = 8.3 mm2, range = 0-15.7 mm2; p < 0.001). Inter-rater reliability was high to very high for both methods (subjective: weighted kappa = 0.640, p < 0.001; quantitative: W = 0.733, p = 0.004). Our primary hypothesis that area of nigrosome-1 hyperintense signal exhibits higher inter-rater reliability than subjective rating of nigrosome-1 appearance was not supported. CONCLUSION: The simple quantitative method, used with subjectively rated nigrosome-1 appearance, may improve confidence in longitudinal clinical reporting, when nigrosome-1 is attenuated. However, further work on the incremental diagnostic value of planimetry and bias, repeatability and reproducibility are needed before it can be recommended in clinical practice.

Antenatal ultrasound needs-analysis survey of Australian rural/remote healthcare clinicians: recommendations for improved service quality and access.

BACKGROUND: Ultrasound is the primary diagnostic tool in pregnancy, capable of identifying high-risk pregnancies and life-threatening conditions, allowing for appropriate management to prevent maternal and fetal morbidity and mortality. Women and babies from rural and remote Australia and low-resource areas worldwide experience poorer health outcomes and barriers to accessing antenatal care and imaging services. Healthcare clinicians working in these regions face significant challenges practising with limited resources and accessing training opportunities. OBJECTIVE: To perform an exploratory needs-analysis survey investigating the availability, accessibility and use of antenatal ultrasound in rural Australia, exploring rural clinicians' interest in and access to ultrasound training opportunities. METHODS: The survey tool for this cross-sectional study was designed and distributed as an anonymous online questionnaire targeting healthcare clinicians (doctors, nurses, midwives, clinic managers, Aboriginal healthcare workers) providing antenatal care in rural regions. Descriptive analysis was applied to quantitative data and thematic analysis was used to explore qualitative components. RESULTS: A total of 114 valid survey responses were analysed. Overall, 39% (43/111) reported ultrasound was not used when providing antenatal care to patients at their clinic, stating 'Lack of ultrasound equipment (73%,29/40) and inaccessibility of training opportunities (47%,19/40) as the main reasons. For those with ultrasound (61%,68/111), estimating due date (89%,57/64) was the main use, and limited training/skills to operate the equipment (59%,38/64) and inaccessibility/distance of training opportunities (45%,29/64) were the most commonly reported barriers. Clinicians described a lack of childcare options (73%,74/102), long distances to reach ultrasound services (64%,65/102), appointment (59%,60/102) and transport availability/times (46%,47/102) as the main obstacles to patient access. Increased attendance, compliance with care directives, parental bonding and improved lifestyle choices were described by respondents as positive outcomes of antenatal ultrasound use. CONCLUSIONS: Future efforts to combat inequitable service access must adopt a coordinated approach to meet the needs of pregnant women in low-resource settings. Providing portable ultrasound equipment, training in antenatal Point-of-Care ultrasound (PoCUS) with ongoing support/mentoring and accreditation of health professionals could strengthen rural workforce capacity. This, along with addressing the complex economic, environmental and socio-cultural barriers faced by patients, could improve service access and pregnancy outcomes in rural and remote communities.

How do practitioners prescribe exercise to patients with breast cancer? Professional perspectives on the key considerations for aerobic exercise in patients with breast cancer undergoing chemotherapy.

OBJECTIVES: This study aimed to understand the key factors experienced accredited exercise physiologists (AEPs) and medical professionals consider when prescribing/recommending aerobic exercise to patients with breast cancer undergoing chemotherapy. DESIGN: Modified Delphi Survey. METHODS: A four-round, two-phase survey was conducted. Following a Delphi approach, four cancer-specific AEPs, four oncologists, and one breast cancer surgeon (median 13-yr breast-cancer-specific experience) completed phase one. Eighty-four AEPs (median 5-yr experience) completed phase two. Phase one participants answered open- and close-ended questions regarding key considerations for aerobic exercise in patients with breast cancer undergoing chemotherapy, and what information should be collected to guide exercise prescription. All questions and considerations agreed upon in phase one (>70 % rating 7-9 on a 0-9 Likert Scale) were rated by AEPs in phase two. RESULTS: Key considerations for exercise assessment and prescription aligned closely with exercise guidelines for cancer survivors. Common strategies for exercise individualisation were identified by AEPs, including separating aerobic exercise into 5-to--9-minute bouts when required and avoiding exercising to complete exhaustion. Exercise intensity and duration should be adjusted throughout chemotherapy to improve tolerance and adherence. Novel considerations for subjective questioning and objective assessments to tailor exercise prescription were outlined. CONCLUSIONS: This study identifies how professionals approach exercise assessment and prescription in patients with breast cancer undergoing chemotherapy. Findings can guide AEPs in practice when prescribing tailored exercise to breast cancer patients undergoing chemotherapy and inform future guidelines.

Modelling the influence of radiosensitivity on development of second primary cancer in out-of-field organs following proton therapy for paediatric cranial cancer.

OBJECTIVE: Radiobiological modelling the risks of second primary cancer (SPC) after proton therapy (PT) for childhood cranial cancer remains largely unknown. Organ-specific dose-response risk factors such as radiosensitivity require exploration. This study compared the influence of radiosensitivity data (slope of ßEAR) on children's lifetime attributable risks (LAR) of SPC development in out-of-field organs following cranial scattering and scanning PT. METHODS: Out-of-field radiosensitivity parameter estimates for organs (α/ß and ßEAR) were sourced from literature. Physical distances for 13 out-of-field organs were measured and input into Schneider's SPC model. Sensitivity analyses were performed as a function of radiosensitivity (α/ß of 1-10 Gy) and initial slope (ßEAR) from Japanese/UK data to estimate the influence on the risk of radiation-induced SPC following scattering and scanning PT. RESULTS: Models showed similar LAR of SPC estimates for age and sex-matched paediatric phantoms, however, for breast there was a significant increase using Japanese ßEAR data. For most organs, scattering PT demonstrated a larger risk of LAR for SPC which increased with α/ß. CONCLUSION: Breast tissue exhibited the highest susceptibility in calculated LAR risk, demonstrating the importance for accurate data input when estimating LAR of SPC. ADVANCES IN KNOWLEDGE: The findings of this study demonstrated younger female patients undergoing cranial proton therapy have a higher risk of developing second primary cancer of the breast tissue. Long-term multicenter registries are important to improve predictive radiobiological modelling studies of side effects.

Development of [225Ac]Ac-DOTA-C595 as radioimmunotherapy of pancreatic cancer: in vitro evaluation, dosimetric assessment and detector calibration.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy which may benefit from radioimmunotherapy. Previously, [177Lu]Lu-DOTA-C595 has been developed as a beta-emitting radioimmunoconjugate to target cancer-specific mucin 1 epitopes (MUC1-CE) overexpressed on PDAC. However, the therapeutic effect may be enhanced by using an alpha-emitting radionuclide such as Actinium-225 (Ac-225). The short range and high linear energy transfer of alpha particles provides dense cellular damage and can overcome typical barriers related to PDAC treatment such as hypoxia. Despite the added cytotoxicity of alpha-emitters, their clinical implementation can be complicated by their complex decay chains, recoil energy and short-range impeding radiation detection. In this study, we developed and evaluated [225Ac]Ac-DOTA-C595 as an alpha-emitting radioimmunotherapy against PDAC using a series of in vitro experiments and conducted a preliminary dosimetric assessment and cross-calibration of detectors for the clinical implementation of Ac-225. RESULTS: Cell binding and internalisation of [225Ac]Ac-DOTA-C595 was rapid and greatest in cells with strong MUC1-CE expression. Over 99% of PDAC cells had positive yH2AX expression within 1 h of [225Ac]Ac-DOTA-C595 exposure, suggesting a high level of DNA damage. Clonogenic assays further illustrated the cytotoxicity of [225Ac]Ac-DOTA-C595 in a concentration-dependent manner. At low concentrations of [225Ac]Ac-DOTA-C595, cells with strong MUC1-CE expression had lower cell survival than cells with weak MUC1-CE expression, yet survival was similar between cell lines at high concentrations irrespective of MUC1-CE expression. A dosimetric assessment was performed to estimate the dose-rate of 1 kBq of [225Ac]Ac-DOTA-C595 with consideration to alpha particles. Total absorption of 1 kBq of Ac-225 was estimated to provide a dose rate of 17.5 mGy/h, confirmed via both detector measurements and calculations. CONCLUSION: [225Ac]Ac-DOTA-C595 was shown to target and induce a therapeutic effect in MUC1-CE expressing PDAC cells.

A Systematic Review of LET-Guided Treatment Plan Optimisation in Proton Therapy: Identifying the Current State and Future Needs.

The well-known clinical benefits of proton therapy are achieved through higher target-conformality and normal tissue sparing than conventional radiotherapy. However, there is an increased sensitivity to uncertainties in patient motion/setup, proton range and radiobiological effect. Although recent efforts have mitigated some uncertainties, radiobiological effect remains unresolved due to a lack of clinical data for relevant endpoints. Therefore, RBE optimisations may be currently unsuitable for clinical treatment planning. LET optimisation is a novel method that substitutes RBE with LET, shifting LET hotspots outside critical structures. This review outlines the current status of LET optimisation in proton therapy, highlighting knowledge gaps and possible future research. Following the PRISMA 2020 guidelines, a search of the MEDLINE® and Scopus databases was performed in July 2023, identifying 70 relevant articles. Generally, LET optimisation methods achieved their treatment objectives; however, clinical benefit is patient-dependent. Inconsistencies in the reported data suggest further testing is required to identify therapeutically favourable methods. We discuss the methods which are suitable for near-future clinical deployment, with fast computation times and compatibility with existing treatment protocols. Although there is some clinical evidence of a correlation between high LET and adverse effects, further developments are needed to inform future patient selection protocols for widespread application of LET optimisation in proton therapy.

Global status of medical physics human resource - The IOMP survey report.

PURPOSE: Realizing the need for periodic surveys about global medical physics human resource, the International Organization for Medical Physics (IOMP) performed a third survey following the previous two (2015 and 2018). The objective was to collect information about the current numbers of medical physicists (MPs) in individual countries, about their MP training, and accreditation pathways. METHODS: The survey was designed using Google Forms. Forms were distributed to national MP associations around the world. The data was collected during May-Nov 2022. MS Excel and SPSS software were used to perform descriptive statistics. RESULTS: 64 valid responses were received covering all continents. The largest numbers of MPs are in high income countries of Europe, Australia and North America, while the lowest numbers of MPs are seen in middle and low-income countries of Asia, Latin America and Africa. Among the respondents, 73% reported MP shortages in their countries. 69% reported the existence of an official MP training program which comprises university courses and in-service training. Furthermore, 85% of the respondents indicated the availability of MP university courses, primarily at the Master's degree level. Participation in research was between 10 and 30% of allocated work time for 42% and below 10% for 33% respondents. CONCLUSIONS: There are new findings on number of MPs per million population in different countries, with some expressing adequacy in the total number of MPs, but the data breakdown indicates a shortage in diagnostic X-ray physicists. Future surveys should also investigate in more detail data on outsourcing, and involvement in research.

In vitro characterisation of [177Lu]Lu-DOTA-C595 as a novel radioimmunotherapy for MUC1-CE positive pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) continues to be a malignancy with an unmet clinical demand. Development of radioimmunoconjugates which target cancer-specific receptors provides an opportunity for radioimmunotherapy of both metastatic and primary PDAC. In this study, we characterised the in vitro behaviour of a novel beta-emitting radioimmunoconjugate [177Lu]Lu-DOTA-C595 as a therapeutic agent against PDAC. [177Lu]Lu-DOTA-C595 is designed to target cancer-specific mucin 1 epitopes (MUC1-CE) overexpressed on most epithelial cancers, including PDAC. RESULTS: A series of in vitro experiments were performed on PDAC cell lines (PANC-1, CAPAN-1, BxPC-3 and AsPC-1) exhibiting strong to weak MUC1-CE expression. [177Lu]Lu-DOTA-C595 bound to all cell lines relative to their expression of MUC1-CE. [177Lu]Lu-DOTA-C595 was also rapidly internalised across all cell lines, with a maximum of 75.4% of activity internalised within the PANC-1 cell line at 48 h. The expression of γH2AX foci and clonogenic survival of PANC-1 and AsPC-1 cell lines after exposure to [177Lu]Lu-DOTA-C595 were used to quantify the in vitro cytotoxicity of [177Lu]Lu-DOTA-C595. At 1 h post treatment, the expression of γH2AX foci exceeded 97% in both cell lines. The expression of γH2AX foci continued to increase in PANC-1 cells at 24 h, although expression reduced in AsPC-1. Clonogenic assays showed a high level of cell kill induced by [177Lu]Lu-DOTA-C595. CONCLUSION: [177Lu]Lu-DOTA-C595 has favourable in vitro characteristics to target and treat MUC1-CE positive PDAC. Further investigations to characterise the in vivo effects and potential value of [177Lu]Lu-DOTA-C595 in other MUC1-CE expressing malignancies such as lung, ovarian and colorectal adenocarcinoma are warranted.

Workplace interventions to improve well-being and reduce burnout for nurses, physicians and allied healthcare professionals: a systematic review.

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.

Science diplomacy in medical physics - an international perspective.

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.

The current status of FLASH particle therapy: a systematic review.

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.

An Integrated Monte Carlo Model for Heterogeneous Glioblastoma Treated with Boron Neutron Capture Therapy.

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 α/ß value associated with different GBM cell lines and a 10B 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.

Cannot Target What Cannot Be Seen: Molecular Imaging of Cancer Stem Cells.

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.

Ultrasound Characteristics and Scanning Techniques of Uterosacral Ligaments for the Diagnosis of Endometriosis: A Systematic Review.

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.