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A method of incorporating risk aversion into the evaluation of the cost of nuclear accident is proposed, including a numerical application based on French data.

The European as low as reasonably achievable(ALARA) network regularly organises workshops on topical issues in radiation protection (RP). The topic of the 20th workshop was: 'ALARA for interventional radiology (IR) and nuclear medicine (NM)'. The objective was to examine the challenges faced when applying the optimisation principle (ALARA) in IR and NM and to consider how ALARA could be better implemented for patient and staff exposures. This memorandum provides a synthesis of the workshop sessions, and recommendations coming from the working groups discussion. Parallels are drawn with the recommendations arising from the 13th EAN workshop on 'ALARA and the medical sector (2011)' to consider how the optimisation challenges in IR and NM have evolved over the past decade. Current levels of exposure are presented along with operational practice and the challenges and opportunities for improvement, both in monitoring and practice. Whilst RP challenges remain, the application of ALARA appears more established in IR compared with experiences reported in 2011. The application of ALARA to emerging technologies in the NM setting is in need of further development to ensure that RP is considered at all stages in the development process of new radiopharmaceuticals. Besides the obvious technical and operational aspects, the importance of education and training, human factors and broadly the RP 'culture' were deemed fundamental to the success of the application of ALARA and where further emphasis is needed. All concerned parties, medical physics experts (MPEs), radiation protection experts, clinical staff, manufacturers and regulators have a role to play in the application of ALARA and this is discussed in the memorandum. Many of the recommendations from the 13th EAN workshop remain applicable today and overlap with the recommendations arising from the 20th workshop. This should prompt attention given that the use of IR and the development of novel radiopharmaceuticals for NM is only anticipated to increase with time., (© 2024 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

As part of the European RadoNorm research project, citizen science pilot projects focusing on the management of radon risk in houses have been implemented in four countries. This article describes the methodological basis, the development and the results of the French pilot project. Building on an initial review of existing literature, the pilot project aims to frame a 'participatory approach' aligned with the standards and recognized practices of citizen science. Particular attention was given to the management of data and the inclusion of ethical considerations. The focal point of the project was the process of radon building diagnosis which is supposed to be carried out whenever (high) radon concentrations are measured and should be prerequisite to mitigation works. As experience shows, however, this diagnosis is hardly implemented in France. To help remedy this situation, the pilot project recruited citizens already aware about radon from Pays Vesoul Val-de-Saône (East of France) to test an existing online self-evaluation guide for radon diagnosis, report on their operational experience and meet with radon/building experts. This enabled citizens to contribute to improvements in form and content to the guide and to ensure that it would be better fit for purpose. Comparison of the guide with experts' practices offered additional perspectives on what building diagnosis should entail. The pilot project produced rich and high-quality data that will nurture the evolution of the guide. The project demonstrated both the viability and the utility of applying the citizen science approach to radon post-measurement phases, with measurable benefits in bridging knowledge gaps and in encouraging behavioural changes. The results of using a citizen science approach in the field of radon management and research are encouraging, and they far outweigh the challenges involved in the implementation., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Andresz S et al.)

The Council Directive 2013/59/Euratom has introduced binding requirements for the management of radon in the workplace in Member States of the European Union. How does it work in practice? In 2021, the European ALARA Network created a working group on ALARA for Radon at Work with the objective of collecting and sharing experiences from the field. A survey was developed to detail each step of the national regulations for the control of radon and to describe case studies showing implementation. This article presents a qualitative analysis of the answers received from seven countries. There are no two similar national regulations and, at each step, different provisions, protocols, techniques etc are applicable or recommended. This diversity contributes to the richness of the results and can inform about interesting and good practices, where 'good' is defined by what is appropriate in the nationally and locally prevailing circumstances. All national regulations follow a graded approach, which is a key component for the implementation of the optimisation (ALARA) principle, yet several potential weak points that may be challenging to ALARA have been identified and are discussed, namely the radon risk assessment, the focus on numerical values, uncertainties in the measurement, how to obtain economically efficient remediation, and the interface with other regulations. Strengthening collaboration between risk prevention and radiation protection actors could help to provide and build expertise on radon management in the workplace, especially when exposure is managed as a planned exposure situation., (© 2022 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Reflecting a change in funding strategies for European research projects, and a commitment to the idea of responsible research and innovation in radiological protection (RP), a collective of research institutes and universities have developed a prospective Strategic Research Agenda (SRA) for Social Sciences and Humanities (SSH) in radiological protection. This is the first time such a research agenda has been proposed. This paper identifies six research lines of interest and concern: (1) Effects of social, psychological and economic aspects on RP behaviour; (2) Holistic approaches to the governance of radiological risks; (3) Responsible research and innovation in RP; (4) Stakeholder engagement and participatory processes in RP research, development, policy and practice; (5) Risk communication; and (6) RP cultures. These topics were developed through broad stakeholder consultation, in conjunction with activities carried out in the framework of various projects and initiatives (EU H2020 CONCERT programme, the EU FP7 projects OPERRA, PREPARE and EAGLE, the 2015-2018 RICOMET series of conferences, and the 2014 and 2016 International Symposia on Ethics of Environmental Health); as well as through dialogues with members of the European radiation protection research communities. The six research lines open opportunities to integrate a range of key social and ethical considerations into RP, thereby expanding research opportunities and programmes and fostering collaborative approaches to research and innovation.

It is increasingly recognized that Alzheimer's disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of these molecular changes is a key aspect for the success of interventions aimed at slowing down rates of cognitive decline. Recent evidence indicates that of the two established methods for measuring amyloid, a decrease in cerebrospinal fluid (CSF) amyloid β 1-42 (Aβ 1-42 ) may be an earlier indicator of Alzheimer's disease risk than measures of amyloid obtained from Positron Emission Tomography (PET). However, CSF collection is highly invasive and expensive. In contrast, blood collection is routinely performed, minimally invasive and cheap. In this work, we develop a blood-based signature that can provide a cheap and minimally invasive estimation of an individual's CSF amyloid status using a machine learning approach. We show that a Random Forest model derived from plasma analytes can accurately predict subjects as having abnormal (low) CSF Aβ 1-42 levels indicative of AD risk (0.84 AUC, 0.78 sensitivity, and 0.73 specificity). Refinement of the modeling indicates that only APOEε4 carrier status and four plasma analytes (CGA, Aβ 1-42 , Eotaxin 3, APOE) are required to achieve a high level of accuracy. Furthermore, we show across an independent validation cohort that individuals with predicted abnormal CSF Aβ 1-42 levels transitioned to an AD diagnosis over 120 months significantly faster than those with predicted normal CSF Aβ 1-42 levels and that the resulting model also validates reasonably across PET Aβ 1-42 status (0.78 AUC). This is the first study to show that a machine learning approach, using plasma protein levels, age and APOEε4 carrier status, is able to predict CSF Aβ 1-42 status, the earliest risk indicator for AD, with high accuracy.

Background: Frontline healthcare workers are critical to meeting the maternal, newborn and child health Sustainable Development Goals in low- and middle-income countries. The World Health Organization has identified leadership development as integral to achieving successful health outcomes, but few programs exist for frontline healthcare workers in low-resource settings., Methods: An 18-month pilot leadership development program was designed and implemented at Greater Accra Regional Hospital, a tertiary care facility in Ghana. A multi-modal training approach was utilized to include individual coaching, participatory discussions, role plays, and didactic sessions on leadership styles, emotional intelligence, communication, accountability and compassionate care., Results: A cross-section of 140 staff from 8 distinct hospital wards and 19 ranks were involved in various components of the leadership program from January 2014 to June 2015. At baseline, the primary leadership challenges and goals of the staff included: interpersonal communication, institutional logistics, compliance, efficiency and staff attitudes. Thirteen participants developed a total of 17 leadership projects to apply their training, many of which focused on improving challenges in organizational culture and systems through bettering leadership skills and interpersonal communication. The staff highly valued the program and found it beneficial to their work., Conclusions: Self-selected individual leadership projects mirrored areas of concern found in the needs assessment, indicating that the program was successful in achieving its goals. The on-site nature of the program was cost-effective and led to maximum staff participation despite clinical responsibilities. A longstanding relationship between the design team and the local hospital staff allowed for an exploration of approaches, many of which were new to the local context. Further research is needed on adapting the program to other settings in Ghana and integrating it into broader systems strengthening interventions. This pilot program was well received and warrants further adaptation and scale up.

As the cost of DNA sequencing continues to fall, an increasing amount of information on human genetic variation is being produced that could help progress precision medicine. However, information about such mutations is typically first made available in the scientific literature, and is then later manually curated into more standardized genomic databases. This curation process is expensive, time-consuming and many variants do not end up being fully curated, if at all. Detecting mutations in the literature is the first key step towards automating this process. However, most of the current methods have focused on identifying mutations that follow existing nomenclatures. In this work, we show that there is a large number of mutations that are missed by using this standard approach. Furthermore, we implement the first mutation annotator to cover an extended mutation landscape, and we show that its F1 performance is the same performance as human annotation (F1 78.29 for manual annotation vs F1 79.56 for automatic annotation).

Quality Issue: Low-resource clinical settings often face obstacles that challenge the implementation of recommended evidence-based practices (EBPs). Implementation science approaches are useful in identifying barriers and developing strategies to address them., Initial Assessment: Ridge Regional Hospital (RRH), a tertiary referral hospital in Accra, Ghana experienced a spike in rates of neonatal sepsis and launched a quality improvement (QI) initiative that identified poor adherence to hand hygiene in the neonatal intensive care unit as a potential source of infections., Choice of Solution: A multi-modal change package of World Health Organization-recommended solutions was created to address this issue., Implementation: To ensure that the outputs of the QI effort were adopted within the organization, leaders at RRH and Kybele, Inc. used an implementation science framework called the 'Interactive Systems Framework for Dissemination and Implementation' (ISF) to create a package of locally acceptable implementation strategies. The ISF has never been used before to guide implementation in low-resource settings., Evaluation: Hand hygiene compliance rose from 67% to 92% overall, including a 36% increase during the night shifts-a group of healthcare workers with typically very low levels of compliance., Lessons Learned: The drastic improvement in adherence to hand hygiene suggests the potential value of the joint use of QI and implementation science to promote the creation and application of contextually appropriate EBPs in low-resource settings. Our results also suggest that using an implementation framework such as the ISF could rapidly increase the uptake of other evidence-based interventions in low-resource settings.

Background: Multiple studies have defined the prognostic and potential predictive significance of the primary tumor side in metastatic colorectal cancer (CRC). However, the currently available data for early-stage disease are limited and inconsistent., Materials and Methods: We explored the clinicopathologic, treatment, and outcome data from a multisite Australian CRC registry from 2003 to 2016. Tumors at and distal to the splenic flexure were considered a left primary (LP)., Results: For the 6547 patients identified, the median age at diagnosis was 69 years, 55% were men, and most (63%) had a LP. Comparing the outcomes for right primary (RP) versus LP, time-to-recurrence was similar for stage I and III disease, but longer for those with a stage II RP (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.52-0.90; P < .01). Adjuvant chemotherapy provided a consistent benefit in stage III disease, regardless of the tumor side. Overall survival (OS) was similar for those with stage I and II disease between LP and RP patients; however, those with stage III RP disease had poorer OS (HR, 1.30; 95% CI, 1.04-1.62; P < .05) and cancer-specific survival (HR, 1.55; 95% CI, 1.19-2.03; P < .01). Patients with stage IV RP, whether de novo metastatic (HR, 1.15; 95% CI, 0.95-1.39) or relapsed post-early-stage disease (HR, 1.35; 95% CI, 1.11-1.65; P < .01), had poorer OS., Conclusion: In early-stage CRC, the association of tumor side and effect on the time-to-recurrence and OS varies by stage. In stage III patients with an RP, poorer OS and cancer-specific survival outcomes are, in part, driven by inferior survival after recurrence, and tumor side did not influence adjuvant chemotherapy benefit., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the haemopoietic, vascular and immune systems and is overexpressed in acute and chronic myeloid leukaemia progenitor cells. It belongs to the type I cytokine receptor family in which the α-subunits consist of two fibronectin III-like domains that bind cytokine, and a third, evolutionarily unrelated and topologically conserved, N-terminal domain (NTD) with unknown function. Here we show by crystallography that, while the NTD of IL3Rα is highly mobile in the presence of IL-3, it becomes surprisingly rigid in the presence of IL-3 K116W. Mutagenesis, biochemical and functional studies show that the NTD of IL3Rα regulates IL-3 binding and signalling and reveal an unexpected role in preventing spontaneous receptor dimerisation. Our work identifies a dual role for the NTD in this cytokine receptor family, protecting against inappropriate signalling and dynamically regulating cytokine receptor binding and function.

A short, monodisperse oligoethylene glycol-containing photocleavable lysine tag was developed to facilitate the efficient purification of hydrophobic and fibril-forming peptides. This new tag was used to prepare a modified Aβ 42 peptide with increased solubility and decreased propensity to aggregate in aqueous media. The solubilising tag was readily removed by irradiation with UV light and permitted the preparation and isolation of Aβ 42 in high purity and yield.

With the aim of preparing hypoxia-selective imaging and therapeutic agents, technetium(I) and rhenium(I) tricarbonyl complexes with pyridylhydrazone, dipyridylamine, and pyridylaminocarboxylate ligands containing nitrobenzyl or nitroimidazole functional groups have been prepared. The rhenium tricarbonyl complexes were synthesized with short reaction times using microwave irradiation. Rhenium tricarbonyl complexes with deprotonated p-nitrophenyl pyridylhydrazone ligands are luminescent, and this has been used to track their uptake in HeLa cells using confocal fluorescent microscopy. Selected rhenium tricarbonyl complexes displayed higher uptake in hypoxic cells when compared to normoxic cells. A (99m)Tc tricarbonyl complex with a dipyridylamine ligand bearing a nitroimidazole functional group is stable in human serum and was shown to localize in a human renal cell carcinoma (RCC; SK-RC-52) tumor in a mouse.

Imaging of activated platelets using an activation specific anti-GPIIb/IIIa integrin single-chain antibody (scFvanti-LIBS) conjugated to a positron emitting copper-64 complex of a cage amine sarcophagine chelator (MeCOSar) is reported. This tracer was compared in vitro to a (64)Cu(II) complex of the scFv conjugated to another commonly used macrocycle, DOTA. The scFvanti-LIBS-MeCOSar conjugate was radiolabeled with (64)Cu(II) rapidly under mild conditions and with higher specific activity than scFvanti-LIBS-DOTA. The utility of scFvanti-LIBS-MeCOSar as a diagnostic agent was assessed in vivo in a mouse model of acute thrombosis. The uptake of scFvanti-LIBS-(64)CuMeCOSar in the injured vessel was significantly higher than the noninjured vessel. Positron emission tomography (PET) was used to show accumulation of scFvanti-LIBS-(64)CuMeCOSar with high and specific uptake in the injured vessel. ScFvanti-LIBS-(64)CuMeCOSar is an excellent tool for highly sensitive in vivo detection of activated platelets in PET and has the potential to be used for early diagnosis of acute thrombotic events.