COMP Report: A survey of radiation safety regulations for medical imaging x-ray equipment in Canada.

X-ray regulations and room design methodology vary widely across Canada. The Canadian Organization of Medical Physicists (COMP) conducted a survey in 2016/2017 to provide a useful snapshot of existing variations in rules and methodologies for human patient medical imaging facilities. Some jurisdictions no longer have radiation safety regulatory requirements and COMP is concerned that lack of regulatory oversight might erode safe practices. Harmonized standards will facilitate oversight that will ensure continued attention is given to public safety and to control workplace exposure. COMP encourages all Canadian jurisdictions to adopt the dose limits and constraints outlined in Health Canada Safety Code 35 with the codicil that the design standards be updated to those outlined in NCRP 147 and BIR 2012.

Unique sequence organization and small RNA expression of a "selfish" B chromosome.

B chromosomes are found in numerous plants and animals. These nonessential, supernumerary chromosomes are often composed primarily of noncoding DNA repeats similar to those found within transcriptionally "silenced" heterochromatin. In order to persist within their resident genomes, many B chromosomes exhibit exceptional cellular behaviors, including asymmetric segregation into gametes and induction of genome elimination during early development. An important goal in understanding these behaviors is to identify unique B chromosome sequences and characterize their transcriptional contributions. We investigated these properties by examining a paternally transmitted B chromosome known as paternal sex ratio (PSR), which is present in natural populations of the jewel wasp Nasonia vitripennis. To facilitate its own transmission, PSR severely biases the sex ratio by disrupting early chromatin remodeling processes. Through cytological mapping and other approaches, we identified multiple DNA repeats unique to PSR, as well as those found on the A chromosomes, suggesting that PSR arose through a merger of sequences from both within and outside the N. vitripennis genome. The majority of PSR-specific repeats are interspersed among each other across PSR's long arm, in contrast with the distinct "blocks" observed in other organisms' heterochromatin. Through transcriptional profiling, we identified a subset of repeat-associated, small RNAs expressed by PSR, most of which map to a single PSR-specific repeat. These RNAs are expressed at much higher levels than those arising from A chromosome-linked repeats, suggesting that in addition to its sequence organization, PSR's transcriptional properties differ substantially from the pericentromeric regions of the normal chromosomes.

Transgenerational inheritance of diet-induced genome rearrangements in Drosophila.

Ribosomal RNA gene (rDNA) copy number variation modulates heterochromatin formation and influences the expression of a large fraction of the Drosophila genome. This discovery, along with the link between rDNA, aging, and disease, high-lights the importance of understanding how natural rDNA copy number variation arises. Pursuing the relationship between rDNA expression and stability, we have discovered that increased dietary yeast concentration, emulating periods of dietary excess during life, results in somatic rDNA instability and copy number reduction. Modulation of Insulin/TOR signaling produces similar results, indicating a role for known nutrient sensing signaling pathways in this process. Furthermore, adults fed elevated dietary yeast concentrations produce offspring with fewer rDNA copies demonstrating that these effects also occur in the germline, and are transgenerationally heritable. This finding explains one source of natural rDNA copy number variation revealing a clear long-term consequence of diet.

Effects of dim light at night in C57BL/6J mice on recovery after spinal cord injury.

Spinal cord injury (SCI) can cause long-lasting locomotor deficits, pain, and mood disorders. Anatomical and functional outcomes are exacerbated by inflammation after SCI, which causes secondary damage. One promising target after SCI is manipulating the circadian system, which optimizes biology and behavior for time of day - including neuroimmune responses and mood-related behaviors. Circadian disruption after SCI is likely worsened by a disruptive hospital environment, which typically includes dim light-at-night (dLAN). Here, we hypothesized that mice subjected to SCI, then placed in dLAN, would exhibit worsened locomotor deficits, pain-like behavior, and anxiety-depressive-like symptoms compared to mice maintained in light days with dark nights (LD). C57BL/6J mice received sham surgery or moderate T9 contusion SCI, then were placed permanently in LD or dLAN. dLAN after SCI did not worsen locomotor deficits; rather, SCI-dLAN mice showed slight improvement in open-field locomotion at the final timepoint. Although dLAN did not alter SCI-induced heat hyperalgesia, SCI-dLAN mice exhibited an increase in mechanical allodynia at 13 days post-SCI compared to SCI-LD mice. SCI-LD and SCI-dLAN mice had similar outcomes using sucrose preference (depressive-like) and open-field (anxiety-like) tests. At 21 dpo, SCI-dLAN mice had reduced preference for a novel juvenile compared to SCI-LD, implying that dLAN combined with SCI may worsen this mood-related behavior. Finally, lesion size was similar between SCI-LD and SCI-dLAN mice. Therefore, newly placing C57BL/6J mice in dLAN after SCI had modest effects on locomotor, pain-like, and mood-related behaviors. Future studies should consider whether clinically-relevant circadian disruptors, alone or in combination, could be ameliorated to enhance outcomes after SCI.

Effects of dim light at night in C57BL/6 J mice on recovery after spinal cord injury.

Spinal cord injury (SCI) can cause long-lasting locomotor deficits, pain, and mood disorders. Anatomical and functional outcomes are exacerbated by inflammation after SCI, which causes secondary damage. One promising target after SCI is manipulating the circadian system, which optimizes biology and behavior for time of day - including neuroimmune responses and mood-related behaviors. Circadian disruption after SCI is likely worsened by a disruptive hospital environment, which typically includes dim light-at-night (dLAN). Here, we hypothesized that mice subjected to SCI, then placed in dLAN, would exhibit worsened locomotor deficits, pain-like behavior, and anxiety-depressive-like symptoms compared to mice maintained in light days with dark nights (LD). C57BL/6 J mice received sham surgery or moderate T9 contusion SCI, then were placed permanently in LD or dLAN. dLAN after SCI did not worsen locomotor deficits; rather, SCI-dLAN mice showed slight improvement in open-field locomotion at the final timepoint. Although dLAN did not alter SCI-induced heat hyperalgesia, SCI-dLAN mice exhibited an increase in mechanical allodynia at 13 days post-SCI compared to SCI-LD mice. SCI-LD and SCI-dLAN mice had similar outcomes using sucrose preference (depressive-like) and open-field (anxiety-like) tests. At 21 dpo, SCI-dLAN mice had reduced preference for a novel juvenile compared to SCI-LD, implying that dLAN combined with SCI may worsen this mood-related behavior. Finally, lesion size was similar between SCI-LD and SCI-dLAN mice. Therefore, newly placing C57BL/6 J mice in dLAN after SCI had modest effects on locomotor, pain-like, and mood-related behaviors. Future studies should consider whether clinically-relevant circadian disruptors, alone or in combination, could be ameliorated to enhance outcomes after SCI.

Health Canada Safety Code 35: awareness of the impacts for diagnostic radiology in Canada.

Health Canada Safety Code 35 brings Canada's diagnostic imaging radiation output and protection standards to an international level. This Safety Code is comprehensive and will have broad implications for most health care facilities. This Safety Code outlines quality control procedures that will ultimately reduce patient dose while providing the best quality diagnostic images, all within a safe working environment. However, the Safety Code has some important omissions and errors of which radiologists should be aware, especially if they act as radiation safety officers. We hope that highlighting these issues will be the beginning of an ongoing dialogue between Health Canada, radiologists, medical physicists, and technologists that will not only bring awareness of Safety Code 35 but will provide a basis for updating, correcting, and improving future revisions of the Safety Code.

Assessment of patient doses in CR examinations throughout a large health region.

Optimization and standardization of radiographic procedures in a health region minimizes patient exposure while producing diagnostic images. This report highlights the dose variation in common computed radiography (CR) examinations throughout a large health region. The RadChex cassette was used to measure the radiation exposure at the table or wall bucky in 20 CR rooms, in seven hospitals, using CR technology from two vendors. Exposures were made to simulate patient exposure (21 cm polymethyl methacrylate) under standard conditions for each bucky: 81 kVp at 100 cm for anteroposterior abdomen table bucky exposures (180 cm for posteroanterior chest wall bucky exposures), using the left, the right, or the center automatic exposure control (AEC) cells. Protocol settings were recorded. An average of 37% variation was found between AEC chambers, with a range between 4% and 137%. A 60% difference in dose was discovered between manufacturers, which was the result of the manufacture's image processing algorithm and subsequently corrected via software updates. Finally, standardizing AEC cell selection during common chest examinations could reduce patient dose by up to 30%. In a large health region, variation in exam protocols can occur, leading to unnecessary patient dose from the same type of examination. Quality control programs must monitor exam protocols and AEC chamber calibration in CR to ensure consistent, minimal, patient dose, regardless of hospital or CR vendor. Furthermore, this report highlights the need for communication between radiologists, technologists, medical physicist, service engineers, and manufacturers required to optimize CR protocols.

A TRiP RNAi screen to identify molecules necessary for Drosophila photoreceptor differentiation.

Drosophila rhabdomeric terminal photoreceptor differentiation is an extended process taking several days to complete. Following ommatidial patterning by the morphogenetic furrow, photoreceptors are sequentially recruited and specified, and terminal differentiation begins. Key events of terminal differentiation include the establishment of apical and basolateral domains, rhabdomere and stalk formation, inter-rhabdomeral space formation, and expression of phototransduction machinery. While many key regulators of these processes have been identified, the complete network of transcription factors to downstream effector molecules necessary for regulating each of these major events remains incomplete. Here, we report an RNAi screen to identify additional molecules and cellular pathways required for photoreceptor terminal differentiation. First, we tested several eye-specific GAL4 drivers for correct spatial and temporal specificity and identified Pph13-GAL4 as the most appropriate GAL4 line for our screen. We screened lines available through the Transgenic RNAi Project and isolated lines that when combined with Pph13-GAL4 resulted in the loss of the deep pseudopupil, as a readout for abnormal differentiation. In the end, we screened 6,189 lines, representing 3,971 genes, and have identified 64 genes, illuminating potential new regulatory molecules and cellular pathways for the differentiation and organization of Drosophila rhabdomeric photoreceptors.

Identification of Genes Involved in the Differentiation of R7y and R7p Photoreceptor Cells in Drosophila.

The R7 and R8 photoreceptor cells of the Drosophila compound eye mediate color vision. Throughout the majority of the eye, these cells occur in two principal types of ommatidia. Approximately 35% of ommatidia are of the pale type and express Rh3 in R7 cells and Rh5 in R8 cells. The remaining 65% are of the yellow type and express Rh4 in R7 cells and Rh6 in R8 cells. The specification of an R8 cell in a pale or yellow ommatidium depends on the fate of the adjacent R7 cell. However, pale and yellow R7 cells are specified by a stochastic process that requires the genes spineless, tango and klumpfuss To identify additional genes involved in this process we performed genetic screens using a collection of 480 P{EP} transposon insertion strains. We identified genes in gain of function and loss of function screens that significantly altered the percentage of Rh3 expressing R7 cells (Rh3%) from wild-type. 36 strains resulted in altered Rh3% in the gain of function screen where the P{EP} insertion strains were crossed to a sevEP-GAL4 driver line. 53 strains resulted in altered Rh3% in the heterozygous loss of function screen. 4 strains showed effects that differed between the two screens, suggesting that the effect found in the gain of function screen was either larger than, or potentially masked by, the P{EP} insertion alone. Analyses of homozygotes validated many of the candidates identified. These results suggest that R7 cell fate specification is sensitive to perturbations in mRNA transcription, splicing and localization, growth inhibition, post-translational protein modification, cleavage and secretion, hedgehog signaling, ubiquitin protease activity, GTPase activation, actin and cytoskeletal regulation, and Ser/Thr kinase activity, among other diverse signaling and cell biological processes.

Drosophila R8 photoreceptor cell subtype specification requires hibris.

Cell differentiation and cell fate determination in sensory systems are essential for stimulus discrimination and coding of environmental stimuli. Color vision is based on the differential color sensitivity of retinal photoreceptors, however the developmental programs that control photoreceptor cell differentiation and specify color sensitivity are poorly understood. In Drosophila melanogaster, there is evidence that the color sensitivity of different photoreceptors in the compound eye is regulated by inductive signals between cells, but the exact nature of these signals and how they are propagated remains unknown. We conducted a genetic screen to identify additional regulators of this process and identified a novel mutation in the hibris gene, which encodes an irre cell recognition module protein (IRM). These immunoglobulin super family cell adhesion molecules include human KIRREL and nephrin (NPHS1). hibris is expressed dynamically in the developing Drosophila melanogaster eye and loss-of-function mutations give rise to a diverse range of mutant phenotypes including disruption of the specification of R8 photoreceptor cell diversity. We demonstrate that hibris is required within the retina, and that hibris over-expression is sufficient to disrupt normal photoreceptor cell patterning. These findings suggest an additional layer of complexity in the signaling process that produces paired expression of opsin genes in adjacent R7 and R8 photoreceptor cells.

Spermatogenesis in haploid males of the jewel wasp Nasonia vitripennis.

Males of hymenopteran insects, which include ants, bees and wasps, develop as haploids from unfertilized eggs. In order to accommodate their lack of homologous chromosome pairs, some hymenopterans such as the honeybee have been shown to produce haploid sperm through an abortive meiosis. We employed microscopic approaches to visualize landmark aspects of spermatogenesis in the jewel wasp Nasonia vitripennis, a model for hymenopteran reproduction and development. Our work demonstrates that N. vitripennis, like other examined hymenopterans, exhibits characteristics indicative of an abortive meiosis, including slight enlargement of spermatocytes preceding meiotic initiation. However, we saw no evidence of cytoplasmic buds containing centrioles that are produced from the first abortive meiotic division, which occurs in the honeybee. In contrast to other previously studied hymenopterans, N. vitripennis males produce sperm in bundles that vary widely from 16 to over 200, thus reflecting a range of cellular divisions. Our results highlight interesting variations in spermatogenesis among the hymenopteran insects, and together with previous studies, they suggest a pattern of progression from meiosis to a more mitotic state in producing sperm.

Genome Silencing and Elimination: Insights from a "Selfish" B Chromosome.

B chromosomes are non-essential components of numerous plant and animal genomes. Because many of these "extra" chromosomes enhance their own transmission in ways that are detrimental to the rest of the genome, they can be thought of as genome parasites. An extreme example is a paternally inherited B chromosome known as paternal sex ratio (PSR), which is found in natural populations of the jewel wasp Nasonia vitripennis. In order to ensure its own propagation, PSR severely biases the wasp sex ratio by converting diploid female-destined embryos into transmitting haploid males. This action occurs at the expense of the other paternally inherited chromosomes, which fail to resolve during the first round of division and are thus eliminated. Recent work has revealed that paternal genome elimination by PSR occurs through the disruption of a number of specific histone post-translational modifications, suggesting a central role for chromatin regulation in this phenomenon. In this review, we describe these recent advances in the light of older ones and in the context of what is currently understood about the molecular mechanisms of targeted genome silencing and elimination in other systems.

A 'selfish' B chromosome induces genome elimination by disrupting the histone code in the jewel wasp Nasonia vitripennis.

Intragenomic conflict describes a phenomenon in which genetic elements act 'selfishly' to gain a transmission advantage at the expense of the whole genome. A non-essential, selfish B chromosome known as Paternal Sex Ratio (PSR) induces complete elimination of the sperm-derived hereditary material in the jewel wasp Nasonia vitripennis. PSR prevents the paternal chromatin from forming chromosomes during the first embryonic mitosis, leading to its loss. Although paternally transmitted, PSR evades self-elimination in order to be inherited. We examined important post-translational modifications to the DNA packaging histones on the normal genome and the PSR chromosome in the fertilized embryo. Three histone marks - H3K9me2,3, H3K27me1, and H4K20me1 - became abnormally enriched and spread to ectopic positions on the sperm's chromatin before entry into mitosis. In contrast, other histone marks and DNA methylation were not affected by PSR, suggesting that its effect on the paternal genome is specific to a subset of histone marks. Contrary to the paternally derived genome, the PSR chromosome was visibly devoid of the H3K27me1 and H4K20me1 marks. These findings strongly suggest that PSR causes paternal genome elimination by disrupting at least three histone marks following fertilization, while PSR avoids self-elimination by evading two of these marks.

Male-Killing Spiroplasma Alters Behavior of the Dosage Compensation Complex during Drosophila melanogaster Embryogenesis.

Numerous arthropods harbor maternally transmitted bacteria that induce the preferential death of males [1-7]. This sex-specific lethality benefits the bacteria because males are "dead ends" regarding bacterial transmission, and their absence may result in additional resources for their viable female siblings who can thereby more successfully transmit the bacteria [5]. Although these symbionts disrupt a range of developmental processes [8-10], the underlying cellular mechanisms are largely unknown. It was previously shown that mutations in genes of the dosage compensation pathway of Drosophila melanogaster suppressed male killing caused by the bacterium, Spiroplasma [10]. This result suggested that dosage compensation is a target of Spiroplasma. However, it remains unclear how this pathway is affected, and whether the underlying interactions require the male-specific cellular environment. Here, we investigated the cellular basis of male embryonic lethality in D. melanogaster induced by Spiroplasma. We found that the dosage compensation complex (DCC), which acetylates X chromatin in males [11], becomes mis-localized to ectopic regions of the nucleus immediately prior to the killing phase. This effect was accompanied by inappropriate histone acetylation and genome-wide mis-regulation of gene expression. Artificially induced formation of the DCC in infected females, through transgenic expression of the DCC-specific gene msl-2, resulted in mis-localization of this complex to non-X regions and early Spiroplasma-induced death, mirroring the killing effects in males. These findings strongly suggest that Spiroplasma initiates male killing by targeting the dosage compensation machinery directly and independently of other cellular features characteristic of the male sex.

Simple quantitative PCR approach to reveal naturally occurring and mutation-induced repetitive sequence variation on the Drosophila Y chromosome.

Heterochromatin is a significant component of the human genome and the genomes of most model organisms. Although heterochromatin is thought to be largely non-coding, it is clear that it plays an important role in chromosome structure and gene regulation. Despite a growing awareness of its functional significance, the repetitive sequences underlying some heterochromatin remain relatively uncharacterized. We have developed a real-time quantitative PCR-based method for quantifying simple repetitive satellite sequences and have used this technique to characterize the heterochromatic Y chromosome of Drosophila melanogaster. In this report, we validate the approach, identify previously unknown satellite sequence copy number polymorphisms in Y chromosomes from different geographic sources, and show that a defect in heterochromatin formation can induce similar copy number polymorphisms in a laboratory strain. These findings provide a simple method to investigate the dynamic nature of repetitive sequences and characterize conditions which might give rise to long-lasting alterations in DNA sequence.

The utilization of dual source CT in imaging of polytrauma.

Despite the growing role of imaging, trauma remains the leading cause of death in people below the age of 45 years in the western industrialized countries. Trauma has been touted as the largest epidemic in the 20th century. The advent of MDCT has been the greatest advance in trauma care in the last 25 years. However, there are still challenges in CT imaging of the polytrauma individual including time restraints, diagnostic errors, radiation dose effects and bridging the gap between anatomy and physiology. This article will analyze these challenges and provide possible solutions offered by the unique design of the dual source CT scanner.

Basic physics of ultrasound imaging.

The appearance of ultrasound images depends critically on the physical interactions of sound with the tissues in the body. The basic principles of ultrasound imaging and the physical reasons for many common artifacts are described.

Implementation of a new undergraduate radiology curriculum: experience at the University of British Columbia.

OBJECTIVES: The purpose of this study was to review and revise the undergraduate radiology curriculum at the University of British Columbia to improve radiology education to medical students and to meet the needs of a medical program with province-wide distribution. METHODS: We identified the radiology content of the curriculum from the Curriculum Management and Information Tool online database, from personal interviews with curriculum heads, and from published information. Undergraduates' and recent graduates' opinions were solicited by means of surveys. Information on radiology curricula at medical schools across Canada was gathered from email surveys and personal contacts with members of the Canadian Heads of Academic Radiology (CHAR). RESULTS: Review of our curriculum indicated that lack of a unified syllabus resulted in redundant content, gaps in knowledge, and lack of continuity in the curriculum. Results from the survey of programs across Canada indicated that most schools also lacked a formal radiology curriculum for medical students. By adapting the guidelines from the Association of Medical Student Education in Radiology, we revised our undergraduate radiology curriculum to emphasize integration and self-learning. The modified curriculum includes a combination of instructional technology, focused lectures in preclinical years, and in-context seminars in clerkship rotations. CONCLUSION: Most medical schools in Canada do not have a formal radiology curriculum for medical students. A structured curriculum is required to improve the quality of radiology teaching for medical students.

Radiation doses to patients receiving computed tomography examinations in British Columbia.

OBJECTIVE: To estimate the diagnostic reference levels and effective radiation dose to patients from routine computed tomography (CT) examinations in the province of British Columbia, Canada. METHODS: The patient weight, height and computed tomography dose index or dose linear product (DLP) were recorded on study sheets for 1070 patients who were referred for clinically indicated routine CT examinations at 18 radiology departments in British Columbia. Sixteen of the scanners were multidetector row scanners. RESULTS: The average patient dose varied from hospital to hospital. The largest range was found for CT of the abdomen, for which the dose varied from 3.6 to 26.5 (average 10.1) mSv. For head CT, the range was 1.7 to 4.9 (average 2.8) mSv; for chest CT, it was 3.8 to 26 (average 9.3) mSv; for pelvis CT, it was 3.5 to 15.5 (average 9.0) mSv; and for abdomen-pelvis CT, it was 7.3 to 31.5 (average 16.3) mSv. Reference dose values were calculated for each exam. These DLP values are as follows: head, 1300 mGy cm; chest, 600 mGy cm; abdomen, 920 mGy cm; pelvis, 650 mGy cm; and abdomen-pelvis, 1100 mGy cm. CONCLUSION: Among hospitals, there was considerable variation in the DLP and patient radiation dose for a specific exam. Reference doses and patient doses were higher than those found in similar recent surveys carried out in the United Kingdom and the European Union. Patient doses were similar to those found in a recent survey in Germany.