Applicability and usage of dose mapping/accumulation in radiotherapy

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on "commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications", we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of our discussions, we present a scheme where representative RT use cases are positioned, considering expected anatomical variations and the impact of dose mapping uncertainties on patient safety, which we have named the DMA landscape (DMAL). This tool is useful for future reference when DMA applications get closer to clinical day-to-day use. Secondly, we discussed current challenges, lightly touching on first-order effects (related to the impact of DIR uncertainties in dose mapping), and focusing in detail on second-order effects often dismissed in the current literature (as resampling and interpolation, quality assurance considerations, and radiobiological issues). Finally, we developed recommendations, and guidelines for vendors and users. Our main point include: Strive for context-driven DIR (by considering their impact on clinical decisions/judgements) rather than perfect DIR; be conscious of the limitations of the implemented DIR algorithm; and consider when dose mapping (with properly quantified uncertainties) is a better alternative than no mapping

Computational Detection and Functional Analysis of Human Tissue-Specific A-to-I RNA Editing

A-to-I RNA editing is a widespread post-transcriptional modification event in vertebrates. It could increase transcriptome and proteome diversity through recoding the genomic information and cross-linking other regulatory events, such as those mediated by alternative splicing, RNAi and microRNA (miRNA). Previous studies indicated that RNA editing can occur in a tissue-specific manner in response to the requirements of the local environment. We set out to systematically detect tissue-specific A-to-I RNA editing sites in 43 human tissues using bioinformatics approaches based on the Fisher's exact test and the Benjamini & Hochberg false discovery rate (FDR) multiple testing correction. Twenty-three sites in total were identified to be tissue-specific. One of them resulted in an altered amino acid residue which may prevent the phosphorylation of PARP-10 and affect its activity. Eight and two tissue-specific A-to-I RNA editing sites were predicted to destroy putative exonic splicing enhancers (ESEs) and exonic splicing silencers (ESSs), respectively. Brain-specific and ovary-specific A-to-I RNA editing sites were further verified by comparing the cDNA sequences with their corresponding genomic templates in multiple cell lines from brain, colon, breast, bone marrow, lymph, liver, ovary and kidney tissue. Our findings help to elucidate the role of A-to-I RNA editing in the regulation of tissue-specific development and function, and the approach utilized here can be broadened to study other types of tissue-specific substitution editing

Psychosocial and Ergonomic Factors, and Their Relation to Musculoskeletal Complaints in the Swedish Workforce

A random sample of 1 000 subjects (20–65 years old) from the national population of Sweden received a questionnaire; 70% (n = 695) replied, of whom 532 were occupationally active. Female gender, working with neck and/or body bent forward, arms above shoulders, and precision work tasks were predictors of musculoskeletal symptoms. Neck, shoulder, and upper back symptoms were more common in a strained situation at work (high demands, low control) (adjusted odds ratios [adjOR] 2.76, 2.80, and 2.26, respectively). Among females, neck and shoulder symptoms were more common in an iso-strain situation (high demands, low control and low social support) (adjOR 4.43 and 3.69, respectively), and low back symptoms were more common at low social support combined with a passive work situation (adjOR 3.35). No associations were found between iso-strain model and symptoms among males. In conclusion, iso-strain work situation was associated with neck symptoms among females, even when controlling for ergonomic factors

Psychosocial and Ergonomic Factors, and Their Relation to Musculoskeletal Complaints in the Swedish Workforce

A random sample of 1 000 subjects (20–65 years old) from the national population of Sweden received a questionnaire; 70% (n = 695) replied, of whom 532 were occupationally active. Female gender, working with neck and/or body bent forward, arms above shoulders, and precision work tasks were predictors of musculoskeletal symptoms. Neck, shoulder, and upper back symptoms were more common in a strained situation at work (high demands, low control) (adjusted odds ratios [adjOR] 2.76, 2.80, and 2.26, respectively). Among females, neck and shoulder symptoms were more common in an iso-strain situation (high demands, low control and low social support) (adjOR 4.43 and 3.69, respectively), and low back symptoms were more common at low social support combined with a passive work situation (adjOR 3.35). No associations were found between iso-strain model and symptoms among males. In conclusion, iso-strain work situation was associated with neck symptoms among females, even when controlling for ergonomic factors

The Effects of a Change in Work Organization Upon the Work Environment and Musculoskeletal Symptoms Among Letter Carriers

An organizational change among 82 postal workers was studied with the aim of evaluating the effects on the work environment, work ability, and musculoskeletal complaints. The study was undertaken in 2 suburbs of Stockholm, Sweden. Psychological work demands were estimated to be reduced at the 1-year follow-up but physical work demands had changed very little. In an observation study in a subgroup of older workers, the risk of overexertion at work and musculoskeletal complaints was reduced. In spite of that, most of the older participants (>35 years) had unchanged or increased musculoskeletal symptoms. This shows the need for early preventive measures

Applicability and usage of dose mapping/accumulation in radiotherapy

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on “commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications”, we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of our discussions, we present a scheme where representative RT use cases are positioned, considering expected anatomical variations and the impact of dose mapping uncertainties on patient safety, which we have named the DMA landscape (DMAL). This tool is useful for future reference when DMA applications get closer to clinical day-to-day use. Secondly, we discussed current challenges, lightly touching on first-order effects (related to the impact of DIR uncertainties in dose mapping), and focusing in detail on second-order effects often dismissed in the current literature (as resampling and interpolation, quality assurance considerations, and radiobiological issues). Finally, we developed recommendations, and guidelines for vendors and users. Our main point include: Strive for context-driven DIR (by considering their impact on clinical decisions/judgements) rather than perfect DIR; be conscious of the limitations of the implemented DIR algorithm; and consider when dose mapping (with properly quantified uncertainties) is a better alternative than no mapping.</p