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The peak season for colds, flu, and RSV infection runs from late fall to spring. Preventing exposure is still the best defense, especially if very young, elderly, and immunocompromised patients are to avoid serious complications. [ABSTRACT FROM AUTHOR]

Abstract Background Although there have been reported benefits of health education interventions across various health issues, the key to program effectiveness is participation and retention. Unfortunately, not everyone is willing to participate in health interventions upon invitation. In fact, health education interventions are vulnerable to low participation rates. The objective of this study was to identify design features that may increase participation in health education interventions and evaluation surveys, and to maximize recruitment and retention efforts in a general ambulatory population. Methods A cross-sectional questionnaire was administered to 175 individuals in waiting rooms of two hospitals diagnostic centres in Toronto, Canada. Subjects were asked about their willingness to participate, in principle, and the extent of their participation (frequency and duration) in health education interventions under various settings and in intervention evaluation surveys using various survey methods. Results The majority of respondents preferred to participate in one 30–60 minutes education intervention session a year, in hospital either with a group or one-on-one with an educator. Also, the majority of respondents preferred to spend 20–30 minutes each time, completing one to two evaluation surveys per year in hospital or by mail. Conclusion When designing interventions and their evaluation surveys, it is important to consider the preferences for setting, length of participation and survey method of your target population, in order to maximize recruitment and retention efforts. Study respondents preferred short and convenient health education interventions and surveys. Therefore, brevity, convenience and choice appear to be important when designing education interventions and evaluation surveys from the perspective of our target population.

Objectives: To establish the variation in film dosimetry usage in radiotherapy centres across the United Kingdom. To identify consensus and highlight areas of potential improvement to enhance radiotherapy dosimetry verification with film., Methods: A survey questionnaire was designed by members of the Institute of Physics and Engineering in Medicine Interdepartmental Dosimetry Audit Group via Microsoft Forms and distributed to all Heads of Radiotherapy Physics in the United Kingdom. The survey was open from June 19, 2023, to July 31, 2023., Results: Forty responses were received from the 62 radiotherapy centres in the United Kingdom, of which 58% were currently using film dosimetry and a further 7 were keen to commence use. Many reported film use had decreased in recent years but was still valuable particularly for commissioning and implementing new techniques. The variation and consensus of methods for film dosimetry calibration, measurement, and application was established. A review of barriers to implementation and methods to reduce uncertainty were included in the assessment., Conclusions: A comprehensive assessment of film dosimetry usage in radiotherapy in the United Kingdom has been collated, which demonstrates a wide variation in methods, across typical clinical users, but maintains film as a valuable dosimetry option., Advances in Knowledge: This research provides a snapshot of current film dosimetry use across the United Kingdom. It examines the variation and consensus of practice to which individual users can compare their systems, and identifies opportunities to improvement in the accuracy of film dosimetry., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Evidence indicates that dysfunction of older Schwann cells and macrophages contributes to poor regeneration of more mature peripheral nervous system (PNS) neurons after damage. Since the underlying molecular factors are largely unknown, we investigated if CRYAB, a small heat shock protein that is expressed by Schwann cells and axons and whose expression declines with age, impacts prominent deficits in the injured, older PNS including down-regulation of cholesterol biosynthesis enzyme genes, Schwann cell dysfunction, and macrophage persistence. Following sciatic nerve transection injury in 3- and 12-month-old wildtype and CRYAB knockout mice, we found by bulk RNA sequencing and RT-PCR, that while gene expression of cholesterol biosynthesis enzymes is markedly dysregulated in the aging, injured PNS, CRYAB is not involved. However, immunohistochemical staining of crushed sciatic nerves revealed that more macrophages of the pro-inflammatory but not immunosuppressive phenotype persisted in damaged 12-month-old knockout nerves. These pro-inflammatory macrophages were more efficient at engulfing myelin debris. CRYAB thus appears to play a role in resolving pro-inflammatory macrophage responses after damage to the older PNS., Competing Interests: Disclosure statement The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective. To evaluate a new film for radiotherapy dosimetry, Gafchromic EBT4, compared to the current EBT3. To evaluate dose-response and verify test cases in MV external beam and HDR brachytherapy. Approach . Three lots (batches) of EBT4 and three lots of EBT3 films were calibrated at 6 MV over 0-1200 cGy range, using FilmQAPro software. Signal-to-noise of pixel value, reported dose (RD), and factors affecting dosimetry accuracy were evaluated (rotation of the film at scanning, energy response and post-exposure darkening). Both films were exposed to clinical treatment plans (VMAT prostate, SABR lung, single HDR source dwell, and 'pseudo' 3-channel HDR cervix brachytherapy). Film-RD was compared to TPS-calculated dose. Main results. EBT4 calibration curves had characteristics more favourable than EBT3 for radiation dosimetry, with improved signal to noise in film-RD of EBT4 compared to EBT3 (increase of average 46% in red and green channels at 500 cGy). Film rotation at scanning and post-exposure darkening was similar for the two films. The energy response of EBT4 is similar to EBT3. For all clinical case studies, EBT4 provided better agreement with the TPS-planned doses than EBT3. VMAT prostate gamma 3%/3 mm passing rate, EBT4 100.0% compared to EBT3 97.9%; SABR lung gamma 2%/2 mm, EBT4 99.6% and EBT3 97.9%; HDR cervix gamma 3%/2 mm, EBT4 97.7% and EBT3 95.0%. Significance. These results show EBT4 is superior to EBT3 for radiotherapy dosimetry validation of TPS plan delivery. Fundamental improvements in noise profile and calibration curve are reported for EBT4. All clinical test cases showed EBT4 provided equivalent or smaller difference in measured dose to TPS calculated dose than EBT3. Baseline data is presented on the achievable accuracy of film dosimetry in radiotherapy using the new Gafchromic EBT4 film., (© 2023 Institute of Physics and Engineering in Medicine.)

Introduction: Antineoplastic drugs are widely used in the treatment of cancer. However, some are known carcinogens and reproductive toxins, and incidental low-level exposure to workers is a health concern. CAREX Canada estimated that approximately 75,000 Canadians are exposed to antineoplastic drugs in workplace settings. While policies and guidelines on safe handling of antineoplastic drugs are available, evidence suggests that compliance is low. In this paper, we identify barriers and facilitators for safe handling of antineoplastic drugs in workplace settings., Methods: We utilized a unique method to study public policy which involved compiling policy levers, developing a logic model, conducting a literature review, and contextualizing data through a deliberative process with stakeholders to explore in-depth contextual factors and experiences for the safe handling of antineoplastic drugs., Results: The most common barriers identified in the literature were: poor training (46%), poor safety culture (41%), and inconsistent policies (36%). The most common facilitators were: adequate safety training (41%), leadership support (23%), and consistent policies (21%). Several of these factors are intertwined and while this means one barrier can cause other barriers, it also allows healthcare employers to mitigate these barriers by implementing small but meaningful changes in the workplace., Conclusion: The combination of barriers and facilitators identified in our review highlight the importance of creating work environments where safety is a priority for the safe handling of antineoplastic drugs. The results of this study will assist policy makers and managers in identifying gaps and enhancing strategies that reduce occupational exposure to antineoplastic drugs.

Purpose: To improve the quality of radiotherapy head and neck CT images through use of an additional image set reconstructed from the raw data of the primary scan, thus allowing parameters such as reconstruction field-of-view (FOV) and kernel to be optimised without impacting on the images used for treatment planning dose calculations., Methods: Using a Catphan image quality phantom and a Toshiba Aquilion LB CT scanner, qualitative and quantitative measurements were made for different reconstruction kernels and FOV diameters. The preferred FOV diameter and kernels were selected. Clinical images from six patients were reconstructed using those kernels (FC13, FC41, FC44, FC64) and the chosen FOV, 200 mm. The images were ranked to choose the kernel which gave best image quality for organ delineation. The scanner workflow was adjusted to produce for every scan a second image set using the chosen kernel and FOV. Finally, for 10 patient scans, image quality was compared for the two reconstructed images., Results: The second image set was produced using kernel FC44 and 200 mm FOV. The primary image set using 550 mm FOV and FC13 was unchanged and contours from the second image set merged onto the first. Oncologists reported increased confidence in contouring in all cases using the new procedure., Conclusion: Production of a second image set, using a reduced reconstruction FOV and a kernel which optimises contrast and sharpness, significantly improves the quality of head and neck CT images for contouring, and avoids any dose increase., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: A proportion of patients are not directly eligible for prostate brachytherapy (BT) due to pubic arch interference (PAI). Constraints in positioning sources behind the pubic arch due to linear, horizontal needle paths, may hamper effective irradiation of the target volume. This work evaluated the effect of prostate volume (V p ) and patient posture change on the amount of PAI, and demonstrated that steerable needles may broaden the inclusion criteria for patients with enlarged prostates and observed PAI., Material and Methods: Twenty-seven patients (V p > 60 cc) were included in this study. Access obstruction to the prostate was evaluated using diagnostic magnetic resonance imaging (MRI) scans, after six upward rotations of the pelvis and the prostate in 5 degree steps, to indicate the effect of patient posture change from supine to lithotomy position. For patients with PAI, we evaluated if the steerable needle could access the obstructed volume of the prostate., Results: The data showed no clear relation between V p and PAI. In 23 of the 27 patients, in which PAI was observed, 14 showed obstruction of the prostate of ≥ 10 mm in the supine position (mean PAI ± standard deviation: 15.2 ±3.8 mm). Anatomical rotation reduced PAI by 4.8 mm after every 10 degrees of upward rotation, still resulting in obstructions of 8.1 ±2.4 mm in 10 of the 14 cases after 15 degree rotation. The steerable needle enabled access to all the required coordinates of the prostate., Conclusions: The ability to steer along curved paths enables prostate BT in patients with enlarged prostates and PAI, and reduces the change of needing to abandon treatment., Competing Interests: This work has been funded by the European regional development fund under EU Interreg 2 Seas, grant: 2S04-022. The authors declare no conflicts of interest., (Copyright © 2022 Termedia.)

Purpose: Adaptive radiotherapy relies on rapid recontouring for replanning. Contour propagation offers workflow efficiencies, but the impact of using unedited propagated OAR contours directly during re-optimisation is unclear., Methods: Plans for ten head and neck patients were created on the planning CT scan. OAR contours for the spinal cord, brainstem, parotids and larynx were then propagated to five shading-corrected CBCTs equally spaced throughout treatment using five commercial packages. Two reference contours were created on the CBCTs by (1) a clinician and (2) a geometric consensus from the propagated contours. Treatment plans were re-optimised on each CBCT for each set of contours, and the DVH statistic differences to the reference contours were calculated. The spread of DVH statistic differences between the 5th and 95th percentiles was quantified., Results: The spread of DVH statistic differences was 3.7 Gy compared to the clinician contour and 3.3 Gy compared to the consensus contour for the brainstem (and PRV) and 2.4 Gy and 2 Gy for the spinal cord (and PRV), across all 5 auto-contouring solutions. The parotids and larynx showed differences of 3.7 Gy compared to the clinician and 0.9 Gy to the consensus contour, with the larger difference for the clinician possibly caused by uncertainty in the clinician standard due to poor image quality on the CBCTs., Conclusions: Propagated OAR contours can be used safely for adaptive radiotherapy replanning, however, where organ doses are close to clinical tolerance then the contours should be reviewed for accuracy regardless of the propagation software used., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Purpose: Adaptive radiotherapy relies of rapid re-contouring, online more so than offline. Intra-patient contour propagation via non-rigid registration offers a solution but can be of limited accuracy. However, the dosimetric significance of the inaccuracies is unknown. Here we evaluate the dosimetric reliability of contours generated by different commercially-available software packages., Method: Planning CT contours for ten head and neck cancer patients were propagated via five commercial packages to five CBCT scans acquired throughout treatment. The treatment plan was recalculated on each of the CBCTs for each set of propagated contours, and DVH parameters extracted for the spinal cord, brainstem, parotids and larynx. The propagated contours were compared to two gold standard contours: contours manually outlined and a consensus STAPLE contours generated from the propagated contours. Geometrical similarity was evaluated using mean distance to agreement (mDTA), Hausdorff distance, centroid agreement and Dice similarity coefficient. Dosimetric reliability was assessed against clinical constraints and comparing via the intraclass correlation coefficient (ICC)., Results: All propagated contours were similar to the STAPLE (mDTA < 1.0 mm) whilst larger differences were seen for the manual contours (mDTA < 3.0 mm). The dosimetric comparison showed that the propagated contours gave excellent dose estimates for most organs. The spinal cord reliability was moderate (ICC > 0.66)., Conclusions: Large differences in geometric metrics rarely had a statistically significant impact on DVH parameters for the OARs studied. For that reason, propagated contours on treatment CBCT images are suitable for estimating dose to the OARs., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. All rights reserved.)

Successful direct MHC class I Ag presentation is dependent on the protein degradation machinery of the cell to generate antigenic peptides that can be loaded onto MHC class I molecules for surveillance by CD8 + T cells of the immune system. Most often this process involves the ubiquitin (Ub)-proteasome system; however, other Ub-like proteins have also been implicated in protein degradation and direct Ag presentation. In this article, we examine the role of neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8) in direct Ag presentation in mouse cells. NEDD8 is the Ub-like protein with highest similarity to Ub, and fusion of NEDD8 to the N terminus of a target protein can lead to the degradation of target proteins. We find that appending NEDD8 to the N terminus of the model Ag OVA resulted in degradation by both the proteasome and the autophagy protein degradation pathways, but only proteasomal degradation, involving the proteasomal subunit NEDD8 ultimate buster 1, resulted in peptide presentation. When directly compared with Ub, NEDD8 fusion was less efficient at generating peptides. However, inactivation of the NEDD8-conugation machinery by treating cells with MLN4924 inhibited the presentation of peptides from the defective ribosomal product-derived form of a model Ag. These results demonstrate that NEDD8 activity in the cell is important for direct Ag presentation, but not by directly targeting proteins for degradation., (Copyright © 2022 by The American Association of Immunologists, Inc.)

The manuscript reports findings from a screening-level assessment of cancer risk from outdoor air in Aamjiwnaang First Nation. Ambient air pollution can contribute to cardiovascular/respiratory diseases, and certain types of cancer. Certain communities may be at higher risk to the negative health impacts due to their geographical proximity to pollution sources. Outdoor air concentrations were mapped and the Lifetime Excess Cancer Risks (LECR) associated with long-term exposure to known carcinogens were estimated. LECR results for both benzene and 1,3-butadiene were above one per million. The LECR for benzene was 6.4 per million when the Health Canada slope factor was applied and 12.0 when using the US EPA. For 1,3-butadiene the LECR estimate was 8.8 per million. This work provides a better understanding of environmental exposures and potential associated cancer risks for residents in the Aamjiwnaang community and highlights the need for further air monitoring and a more detailed risk assessment.

Setting: For First Nations people, human health and well-being are interconnected with a healthy environment. First Nations organizations commonly raise concerns regarding carcinogens in the environment; however, few case studies are available as guidance for working in a participatory and respectful way to help assess and address these concerns., Intervention: Through four community-led pilot projects executed over two years, we collaborated with 15 participants from four First Nations organizations across four provinces to identify concerns related to environmental carcinogens and to address those concerns through an integrated knowledge translation (KT) approach. We co-developed and implemented strategic KT plans for each pilot project, and conducted evaluation surveys and interviews with participants at multiple time points to assess process, progress, barriers and facilitators, and impact., Outcomes: The activities and outputs of the pilot projects are available at www.carexcanada.ca . Participants identified 18 concerns, and we co-developed 24 knowledge products. Tailored fact sheets for communities and briefing notes for leadership were deemed most useful; interactive maps were deemed less useful. Evaluation indicated that the collaborative projects were effective in addressing the concerns raised regarding exposures to carcinogens., Implications: The participant-led approach and multi-year funding to support capacity enhancement and face-to-face engagement were facilitators to project success. However, participants did face important barriers to collaborate which should be considered in future projects of this kind: the most important being a lack of resources (people and time), given competing and often more urgent priorities., (© 2021. The Author(s).)

Young workers, those under the age of 25, are considered a vulnerable working population, primarily due to their increased risk of injury. In this study we investigate if young workers may also be at an increased risk for occupational exposure to carcinogens. Using the 2006 and 2016 Canadian Census of Population and previously obtained CAREX Canada data, this study aimed to identify sectors and occupations that have high proportions of young workers and where potential exists for exposure to known and suspected carcinogens. Key groups where young workers are likely at a higher risk for occupational exposure to carcinogens were identified. Our work shows that young workers in construction, outdoor occupations, and farming are key groups that warrant further investigation. These specific groups are highlighted because of the large number of young workers employed in these sectors/situations, the high number of possible carcinogen exposures, and the potential for higher risk behavior patterns that typically occur in these types of jobs. While there is no data available to develop carcinogen exposure estimates specific to young workers, it is our perspective that young workers are likely at a higher risk for occupational exposure to carcinogens. Our findings identify opportunities to improve the occupational health and safety for this vulnerable population, particularly for young construction workers, farm workers, and outdoor workers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sweet, Telfer, Palmer, Fazel and Peters.)

Recognition of injuries in racing animals is essential to identify potential risk factors so actions can be taken to reduce or mitigate the cause of the injury to safeguard the animal. Racing greyhounds are subject to musculoskeletal injuries associated with athletic pursuit, in particular soft-tissue injuries, lacerations, and fractures. The objective of this study was therefore to determine risk factors for soft-tissue injuries, lacerations and fractures occurring during racing, using a cohort of greyhounds racing in New Zealand between 10th September 2014 and 31st July 2020. Dog-level, race-level and track-level risk factors for each outcome were assessed using mixed-effects multivariable logistic regression including trainer as a random effect. Throughout the study period there were 218,700 race starts by 4,914 greyhounds, with a total of 4,385 injuries. Of these, 3,067 (69.94%) were classed as soft-tissue injuries, 641 (14.62%) were reported as lacerations, and 458 (10.44%) were fractures. Greyhounds with a low racing frequency (racing more than 7 days apart) had 1.33 [95% confidence interval (CI): 1.06-1.67] times the odds of fracture compared to those racing more frequently. Older greyhounds had a greater odds of fracture compared with younger greyhounds. Racing every 7 days had a lower odds of soft-tissue injury compared with racing more than once a week. Dogs over 39 months had 1.53 (95% CI: 1.35-1.73) times the odds of sustaining a soft-tissue injury compared to the younger dogs. Greyhounds originating from Australia had a higher odds of fracture and laceration compared with New Zealand dogs. Better performing dogs (higher class) had a greater odds of fracture and laceration whilst maiden dogs had a higher odds of soft-tissue injury. Greyhounds starting from the outside box had a higher odds of fracture. There was considerable variation in the odds of soft-tissue injury at different racetracks. In conclusion, although the incidence of soft-tissue injuries was higher than other injury types, the repercussion of such injuries was less than those for fractures. The results from this study will help to inform intervention strategies aimed at reducing the rate of injuries in racing greyhounds, enhancing racing safety and greyhound welfare., Competing Interests: The current study uses historical data from the 2014–2020 racing seasons. Greyhound Racing New Zealand provided the spreadsheet from a database that is managed by an external statistics company. While the funders provided access to the database, they had no role in the design of the study, analysis of the data, interpretation of the data, writing of the manuscript, or in the decision to publish the results. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Palmer, Rogers, Stafford, Gal and Bolwell.)

A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics., (© 2021 The Authors. Journal of Microscopy published by JohnWiley & Sons Ltd on behalf of Royal Microscopical Society.)

In New Zealand, over two million dairy calves between four and seven days of age are sent to meat processing premises every year. There is a need to develop protocols for holistically assessing the welfare of calves sent to slaughter in the first week of life. This study aimed to determine the prevalence of potential animal-based indicators of the welfare state in bobby calves in lairage. The study observed calves in lairage between June and October 2016. Data collection involved assessing groups of calves in pens followed by non-invasive measurements on up to five calves within each pen. We made 23 visits to 12 meat processing premises with group-level observations made on 5910 calves in 102 pens, followed by a non-invasive examination of 504 calves. During the group level observations, none of the calves had their heads tilted or were panting, and coughing and play behaviour were observed in only 1% of pens. In contrast, at least one calf had faecal soiling in all the observed pens, with the percentage of calves affected in each pen ranging from 1% to 48%. In the individual observations, more than 60% of calves had signs of some degree of dehydration, and nearly 40% had some faecal soiling present. In addition, 24% of calves had a respiratory rate over 36 breaths per minute, considered higher than normal. The change in prevalence of some indicators-as time spent in lairage increased or as the calving season progressed-is worth further exploration. Identification of prevalent animal-based indicators facilitates better understanding of the welfare status of young calves in lairage, and these should be incorporated into more holistic calf welfare assessment schemes.

Due to the way occupational exposure limits (OELs) are set in Canada, workers across the country are not equally and adequately protected from harmful workplace exposures. This disparity is illustrated in the case of exposure to diesel engine exhaust (DEE). Based on the findings of a recent pan-Canadian and international scan of OELs for DEE, we recommend that Canada overcome these current disparities by moving towards harmonized, evidence-based OELs. To achieve this, Canada should adopt a centralized framework for setting OELs that considers the most recent scientific evidence as well as feasibility of implementation in the Canadian context. We assert that harmonizing OELs across Canada would allow for expertise and resources to be consolidated and is a crucial step to ensuring that all workers are consistently protected from harmful workplace exposures., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

While the role of ubiquitin in protein degradation is well established, the role of other ubiquitin-like proteins (UBLs) in protein degradation is less clear. Neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) is the UBL with the highest level of amino acids identified when compared to ubiquitin. Here we tested if the N-terminal addition of NEDD8 to a protein of interest could lead to degradation. Mutation of critical glycine residues required for normal NEDD8 processing resulted in a non-cleavable fusion protein that was rapidly degraded within the cells by both the proteasome and autophagy. Both degradation pathways were dependent on a functional ubiquitin-conjugation system as treatment with MLN7243 increased levels of non-cleavable NEDD8-GFP. The degradation of non-cleavable, N-terminal NEDD8-GFP was not due to a failure of GFP folding as different NEDD8-GFP constructs with differing abilities to fold and fluoresce were similarly degraded. Though the fusion of NEDD8 to a protein resulted in degradation, treatment of cells with MLN4924, an inhibitor of the E1 activating enzyme for NEDD8, failed to prevent degradation of other destabilized substrates. Taken together these data suggest that under certain conditions, such as the model system described here, the covalent linkage of NEDD8 to a protein substrate may result in the target proteins degradation.

Callous-unemotional (CU) traits are early-emerging personality features characterized by deficits in empathy, concern for others, and remorse following social transgressions. One of the interpersonal deficits most consistently associated with CU traits is impaired behavioral and neurophysiological responsiveness to fearful facial expressions. However, the facial expression paradigms traditionally employed in neuroimaging are often ambiguous with respect to the nature of threat (i.e., is the perceiver the threat, or is something else in the environment?). In the present study, 30 adolescents with varying CU traits viewed fearful facial expressions cued to three different contexts ("afraid for you," "afraid of you," "afraid for self") while undergoing functional magnetic resonance imaging (fMRI). Univariate analyses found that mean right amygdala activity during the "afraid for self" context was negatively associated with CU traits. With the goal of disentangling idiosyncratic stimulus-driven neural responses, we employed intersubject representational similarity analysis to link intersubject similarities in multivoxel neural response patterns to contextualized fearful expressions with differential intersubject models of CU traits. Among low-CU adolescents, neural response patterns while viewing fearful faces were most consistently similar early in the visual processing stream and among regions implicated in affective responding, but were more idiosyncratic as emotional face information moved up the cortical processing hierarchy. By contrast, high-CU adolescents' neural response patterns consistently aligned along the entire cortical hierarchy (but diverged among low-CU youths). Observed patterns varied across contexts, suggesting that interpretations of fearful expressions depend to an extent on neural response patterns and are further shaped by levels of CU traits., Competing Interests: Authors have nothing to disclose., (© The Author(s) 2020.)

The aim of this study was to conduct a cross-sectional survey of racing greyhound trainers in New Zealand in order to provide an overview of their training practices. A survey regarding training practices was posted to all registered greyhound training license holders in New Zealand in August 2019. Data were collected from a convenience sample of 48 trainers (35.6%; n = 48/137) who completed the survey. Other than the differences in the number of greyhounds in race training, the training programmes described by public trainers and owner trainers were similar. Trainers reported that the primary reason for registering young dogs for racing and for qualifying for racing was the ability to meet time milestones. Young dogs had a median of six (interquartile range (IQR): 4-10) trials before they commenced their racing career. Trainers described training practices that aimed to prepare greyhounds for race-day. Regardless of whether the dogs raced once or twice a week, most training programmes demonstrated high specificity where training involved two periods of load cycles through high-intensity workload. Trainers racing their greyhounds once a week simulated the workload of trainers racing their greyhounds twice a week by introducing one high-intensity (speed) workout during the week. Training programmes were structured to condition the dogs to the physiological and metabolic requirements of sprint racing. This study highlights the importance of the need for an improved understanding of training and competition load in order to enable future research in the field of racing greyhounds.

The cysteine protease inhibitor Cystatin C (CST3) is highly expressed in the brains of multiple sclerosis (MS) patients and C57BL/6J mice with experimental autoimmune encephalomyelitis (EAE; a model of MS), but its roles in the diseases are unknown. Here, we show that CST3 plays a detrimental function in myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55 )-induced EAE but only in female animals. Female Cst3 null mice display significantly lower clinical signs of disease compared to wild-type (WT) littermates. This difference is associated with reduced interleukin-6 production and lower expression of key proteins (CD80, CD86, major histocompatibility complex [MHC] II, LC3A/B) involved in antigen processing, presentation, and co-stimulation in antigen-presenting cells (APCs). In contrast, male WT and Cst3 -/- mice and cells show no differences in EAE signs or APC function. Further, the sex-dependent effect of CST3 in EAE is sensitive to gonadal hormones. Altogether, we have shown that CST3 has a sex-dependent role in MOG 35-55 -induced EAE., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the variation between Catphan image quality CT phantoms, specifically for use in a future multi-centre image quality audit., Method: 14 Catphan phantoms (models 503, 504 and 604) were scanned on a Canon Aquilion Prime CT scanner using a single scan protocol. Measurements were made of noise in the uniformity section, visibility of low contrast targets and contrast, x-ray attenuation and CT number for 5 materials in the sensitometry section. Scans were also acquired using one phantom and varying reconstruction field of view, image slice thickness, effective tube-current-time product and iterative reconstruction settings to determine how the degree of inter-phantom variability compared with the magnitude of changes from scan parameter alteration., Results: Across all phantoms the mean CT value in the uniformity section was 7.0 (SD 0.9) range: 4.9-8.1 HU. For the different materials the CT numbers were air: -1004 ± 5, Polymethylpentene: -190 ± 2, Polystyrene: -42 ± 2, Delrin: 321 ± 5 and Teflon: 898 ± 8 HU. Consistency of low contrast targets through visual scoring was good. Measured contrast was lower (p < 0.001) with more variability for 504 versus 604 models. All phantoms produced identical tube current settings with x-ray tube current modulation, indicating no x-ray attenuation differences. The degree of change in image quality metrics between phantoms was small compared with results when scan parameters were varied., Conclusion: Catphan phantoms model 604 showed minimal differences and will be used for multi-centre inter-comparison work, with the consistency between phantoms appropriate for measuring possible variations in image quality., (Copyright © 2020. Published by Elsevier Ltd.)

Background and Purpose: Assessment of dosimetric accuracy of radiosurgery on different treatment platforms., Material and Methods: Thirty-three single fraction treatment plans were assessed at thirty centres using an anthropomorphic head phantom with target and brainstem structures. The target being a single irregular shaped target, ~8 cc, 10 mm from the brainstem. The phantom was "immobilised", scanned, planned and treated following the local protocols. EBT-XD films and alanine pellets were used to measure absolute dose, inside both the target and the brainstem, and compared with TPS predicted dose distributions., Results: PTV alanine measurements from gantry-based linacs showed a median percentage difference to the TPS of 0.65%. Cyberknife (CK) had the highest median difference of 2.3% in comparison to the other platforms. GammaKnife (GK) showed the smallest median of 0.3%. Similar trends were observed in the OAR with alanine measurements showing median percentage differences of1.1%, 2.0% and 0.4%, for gantry-based linacs, CK and GK respectively. All platforms showed comparable gamma passing rates between axial and sagittal films., Conclusions: This comparison has highlighted the dosimetric variation between measured and TPS calculated dose for each delivery platform. The results suggest that clinically acceptable agreement with the predicted dose distributions is achievable by all treatment delivery systems., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The welfare and wastage of racing greyhounds is a topic of public concern. Little is published about the racing patterns of these dogs in New Zealand. The aim of this study is to describe the pattern of greyhound racing in New Zealand. Data on all race starts between 1 August 2011 and 25 March 2018 were supplied by Greyhound Racing New Zealand. A cohort was created containing dogs that had a racing career between 1 August 2013 and 31 July 2017. Data were collated within a customized Microsoft Access database from electronic records of all racing starts for every dog within the 2013-2016 racing seasons. For this cohort of racing dogs, there were 97,973 race starts across 22,277 races involving 2393 individual greyhounds. The median number of days between racing starts was 7 days (inter-quartile range (IQR): 4-10 days). The median career length was 424 days (IQR: 206-647 days) and the median number of racing starts throughout a racing career was 35 (IQR: 16-59 starts). Dogs of similar ability finished their career at a similar age.

Objective: The reconstruction kernel used for a CT scan strongly influences the image quality. This work investigates the changes in Hounsfield units (HUs) which can arise when altering the image reconstruction kernel for planning CT images and the associated changes in dose in the radiotherapy treatment plan if the treatment planning system (TPS) is not re-calibrated., Methods: Head and neck, prostate and lung CT images from four centres were used. For a specific scan, the base image was acquired using the original reconstruction kernel (used when the TPS was calibrated) and the treatment plan produced. The treatment plan was applied to all images from the other reconstruction kernels. Differences in dose-volume metrics for the planning target volume (PTV) and organs at risk (OARs) were noted and HU differences between images measured for air, soft tissue and bone., Results: HU change in soft tissue had the greatest influence on dose change. When within ±20 HU for soft tissue and ±50 HU for bone and air the dose change in the PTV and OAR was within ±0.5% and ±1% respectively., Conclusions: When imaging parameters were changed, if HU change was within ±20 HU for soft tissue and ±50 HU for bone and air, the change in the PTV and OAR doses was below 1%., Advances in Knowledge: The degree of dose change in the treatment plan with HU change is demonstrated for current TPS algorithms. This adds to the limited evidence base for recommendations on HU tolerances as a tool for radiotherapy CT protocol optimization., (© 2019 The Authors. Published by the British Institute of Radiology.)