In addition to naturally occurring sequence variation and spontaneous mutations, a wide array of technologies exist for modifying the mouse genome. Standardized nomenclature, including allele, transgene, and other mutation nomenclature, as well as persistent unique identifiers (PUID) are critical for effective scientific communication, comparison of results, and integration of data into knowledgebases such as Mouse Genome Informatics (MGI), Alliance for Genome Resources, and International Mouse Strain Resource (IMSR). As well as being the authoritative source for mouse gene, allele, and strain nomenclature, MGI integrates published and unpublished genomic, phenotypic, and expression data while linking to other online resources for a complete view of the mouse as a valuable model organism. The International Committee on Standardized Genetic Nomenclature for Mice has developed allele nomenclature rules and guidelines that take into account the number of genes impacted, the method of allele generation, and the nature of the sequence alteration. To capture details that cannot be included in allele symbols, MGI has further developed allele to gene relationships using sequence ontology (SO) definitions for mutations that provide links between alleles and the genes affected. MGI is also using (HGVS) variant nomenclature for variants associated with alleles that will enhance searching for mutations and will improve cross-species comparison. With the ability to assign unique and informative symbols as well as to link alleles with more than one gene, allele and transgene nomenclature rules and guidelines provide an unambiguous way to represent alterations in the mouse genome and facilitate data integration among multiple resources such the Alliance of Genome Resources and International Mouse Strain Resource.
PURPOSE:To estimate the uncertainty of a practical EBT2 film dosimetry approach that has been established at our institution and used for routine patient-specific plan verifications, particularly for SBRT and RapidArc, as well as planning system commissioning. Our technique is unique from other common dosimetry protocols with respect to calibration, irradiation and scanning.METHODS:Film dosimetry for patient-specific quality assurance of 29 patient plans were retrospectively reviewed. For each case, four films were irradiated; two for calibration and two for treatment plan. Each pair of two films were irradiated together in a phantom with one film transposed (rotated 180 degrees relative to the other) to compensate for asymmetric film response. After a minimum of 12 hrs post-irradiation, each film was scanned in four different orientations to mitigate non-uniform response of the scanner light and detector elements. The scanned 8 calibration and 8 plan images were averaged into one calibration and one plan film image, respectively. Each color channel of the calibration film was correlated to the reference dose matrix to produce a 3rd order polynomial calibration curve. Finally, each color channel of the plan film was converted to a dose map using the corresponding calibration curve. Average dose maps of the red and green channels were correlated to the treatment planning dose matrix, and the mean dose differences at the center of dose distributions (5×5mm̂2 area) as well as a gamma analysis were evaluated.RESULTS:The absolute dose differences were -0.8±1.7% (range=-4.5-3.0%). The gamma pass-rates (3%/3mm) were 94±7% (min.=74%). The pass rate increased to 99±3%(min.=87%) with the film scaled relatively to the plan doses.CONCLUSIONS:Based on a large number of cases, our approach appears to be robust to non-uniform film and scanner responses, and is shown to have an uncertainty (1SD) of less than 2% for absolute film dosimetry.
Purpose: It is essential for radiation oncology departments to have comprehensive patient safety and quality programs. Two years ago we undertook a systematic review of our safety/QA program. Existing policies were updated and new policies created where necessary. One crucial component of any safety/QA program is continually updating it based on current information, the ‘check’ and ‘act’ portions of the Deming Cycle. We accomplished this with a transparent variance reporting system and a safety/QA committee reviewing and acting on reported variances. Methods: With 5 radiation oncology centers in our institution, we needed to devise a system that would allow anyone to report a variance and provide our QA committee the ability to review variances system‐wide. We developed the system using web‐based tools. The system allows individuals to report variances, anonymously or named, specify the nature of the variance and indicate the tools used to identify the variance. Results: In 2011, 285 variances were reported, 102 were reported by physicists, 86 anonymously, 71 by therapists and 26 by dosimetrists. We realized the need to develop clear classifications for variances. We added a high priority category, defined as variances which resulted in or had the potential to result in harm to a patient or when a policy is purposely overridden. Of the 285 variances reported, 5 were high priority. We created a process variance category, defined as variances where a specific clinical process is not followed. Of the 285 reported variances 155 were process variances. Conclusions: Reporting of variances through a centralized database is central toward developing a robust patient safety/quality assurance program. Anonymous reporting fosters a non‐punitive environment, and promotes the ‘safety culture’. The goal of such a system is to review trends in clinical processes and ultimately to improve safety/quality by reducing variances associated with these processes.
The Mouse Genome Informatics (MGI; "http://www.informatics.jax.org":http://www.informatics.jax.org) group is comprised of several collaborating projects including the Mouse Genome Database (MGD) Project, the Gene Expression Database (GXD) Project, the Mouse Tumor Biology (MTB) Database Project, and the Gene Ontology (GO) Project. Literature identification and collection is performed cooperatively amongst the groups.In recent years many institutional libraries have transitioned from a focus largely on print holdings to one of electronic access to journals. This change has necessitated adaptation on the part of the MGI curatorial group. Whereas the majority of journals covered by the group used to be surveyed in paper form, those journals are now surveyed electronically. Approximately 160 journals have been identified as those most relevant to the various database groups. Each curator in the group has the responsibility of scanning several journals for articles relevant to any of the database projects. Articles chosen via this process are marked as to their potential significance for various projects. Each article is catalogued in a Master Bibliography section of the MGI database system and annotated to the database sections for which it has been identified as relevant. A secondary triage process allows curators from each group to scan the chosen articles and mark ones desired for their project if such annotation has been missed on the initial scan.Once articles have been identified for each database project a variety of processes are implemented to further categorize and index data from those articles. For example, the Alleles and Phenotype section of the MGD database indexes each article marked for MGD and in this indexing process they identify each mouse gene and allele examined in the article. The GXD database indexing process has a different focus. In this case articles are indexed with regard to the stage of development used in the study as well as the assay technique used. In each case the indexing gives an overview of the data held in the article and assists in the more extensive curation performed in the following step of the curation process. Indexing also provides each group with valuable information used to prioritize and streamline the overall curation process.The MGI projects are supported by NHGRI grants HG000330, HG00273, and HG003622, NICHD grant HD033745, and NCI grant CA089713.
The mouse is the premier model organism in human disease research because all of its life stages are accessible and there are myriad experimental tools for comparative analysis and specific manipulation of its genome. The Mouse Genome Informatics Database (MGI, http://www.informatics.jax.org ) supports biological knowledge building for the laboratory mouse by integrating and providing access to a wide range of data from DNA sequence to phenotype and disease associations. The integration of complex disease phenotypes, underlying genetic causes, and gene function information can be used to confirm human disease models and provide insight into disease mechanisms. We will illustrate the utility of MGI using hemochromatosis as an example. To describe phenotypic abnormalities and similarities to human disease in the mouse, we developed and utilize a vocabulary of mouse anomalies (the Mammalian Phenotype Ontology) and utilize the human disease terms provided in the Online Mendelian Inheritance in Man (OMIM). These standard terms provide a backbone for annotation, allowing both easy access and searching for researchers via web forms and computational access for data downloads.