A systematic quality assurance framework for the upgrade of radiation oncology information systems

In spite of its importance, no systematic and comprehensive quality assurance (QA) program for radiation oncology information systems (ROIS) to verify clinical and treatment data integrity and mitigate against data errors/corruption and/or data loss risks is available. Based on data organization, format and purpose, data in ROISs falls into five different categories: (1) the ROIS relational database and associated files; (2) the ROIS DICOM data stream; (3) treatment machine beam data and machine configuration data; (4) electronic medical record (EMR) documents; and (5) user-generated clinical and treatment reports from the ROIS. For each data category, this framework proposes a corresponding data QA strategy to very data integrity. This approach verified every bit of data in the ROIS, including billions of data records in the ROIS SQL database, tens of millions of ROIS database-associated files, tens of thousands of DICOM data files for a group of selected patients, almost half a million EMR documents, and tens of thousands of machine configuration files and beam data files. The framework has been validated through intentional modifications with test patient data. Despite the ‘big data’ nature of ROIS, the multiprocess and multithread nature of our QA tools enabled the whole ROIS data QA process to be completed within hours without clinical interruptions. The QA framework suggested in this study proved to be robust, efficient and comprehensive without labor-intensive manual checks and has been implemented for our routine ROIS QA and ROIS upgrades.     

Prospective validation of a core curriculum progress assimilation instrument for radiation oncology residentship

ObjectivesTo develop a tool that could assess residents’ knowledge beyond simple information gathering and evaluate its reliability.MethodsAn assessment tool of 40 objective questions and at least one essay-based question was developed to assess residents’ comprehension of general radiation oncology accordingly to validated training curricula beyond level 2 in the Bloom scale. With randomized content, questions were developed such as to be classified as at least 2 in the Bloom scale, so that reasoning and not only information gathering could be assessed. Criteria validation was made using the Classical Test Theory to describe difficulty and discrimination of each item. Reliability was tested by internal consistency using the Cronbach alpha test.ResultsBetween 2016 and 2019, 24 residents were assessed. Six different versions of the test were made with a total of 240 objective questions and 18 essay-based questions. Five of the six versions were deemed valid and reliable. Comparisons between 1st (PGY-1) and 3rd (PGY-3) year residents were made. Consistently, PGY-3 residents had scores 150% higher than PGY-1 residents. Only two different PGY-3 reached the most complex level of answers in the essay-based questions. The results demonstrated that the major part of the acquired knowledge and retention occurs in the first six months of training rather than in all the following period.ConclusionThe instrument can be considered valid. This developed instrument also raised the hypothesis that residents may not assess and analyze their acquired knowledge beyond the application level.     

Medical physics graduate education in Mexico and its relation to the advances in radiation oncology

AimTo evaluate the state of graduate education in medical physics and progress in radiation oncology (RO) equipment in Mexico since 2000, when conferring degrees from two master’s-degree programs in Medical Physics began.BackgroundMedical physics is a Health Profession and there are international recommendations for education, training, and certification. Both programs follow these education guidelines. The most common clinical occupation of graduates is in RO services. Techniques in Mexican RO include traditional and high-precision procedures.MethodsAcademic and occupational information about the programs and their graduates were obtained from official websites. Graduates were invited to respond to a survey that requested information about their present job. We obtained data on RO equipment and human resources from public databases and estimated staffing requirements of medical physicists (MPs).ResultsMedical physics programs have graduated a total of 225 MPs. Half of them work in a clinical environment and, of these, about 90 work in RO services. MPs with M.Sc. degrees constitute 36% of the current MP workforce in RO, estimated to be 250 individuals. Survey responses pointed out the main merits and limitations of the programs. The number of MPs in RO has increased fivefold and the number of linacs sixfold in 15 years. The present number of MPs is insufficient, according to published guidelines.ConclusionAll MPs in RO services with advanced modalities must be trained following international recommendations for graduate education and post-graduation clinical training. Education and health institutions must find incentives to create more graduate programs and clinical residencies.     

Medical physics aspects of the synchrotron radiation therapies: Microbeam radiation therapy (MRT) and synchrotron stereotactic radiotherapy (SSRT)

Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25–75 micron-wide microplanar beams separated by wider (100–400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified.SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper.     

Radiotherapy as treatment option in biliary cancer patients: a national survey of AIRO (Italian Association of Radiation Oncology) Gastroenterology Group

BackgroundThe aim is to find out how many radiation oncology centres treat biliary duct carcinoma (BDC), what treatments they offer and whether they would be interested in developing prospective trials.Materials and methodsA questionnaire was posted to all 220 Italian Radiation Oncology Centres. The survey consisted of 31 eligibility questions in a combination of multiple and forced choice formats addressing the following parameters: characteristics of the centre, numbers of BDC patients treated, treatment options, radiotherapy parameters (target definition, schedule, technique, dose constraints) and interest in developing future randomized trials.ResultsNo major differences emerged in BDC management, whatever the site, and whether it was resectable or not. Discrepancies in routine clinical practice were, however, observed with lack of agreement on expansion margins, dose constraints and treatment schedules for the stereotactic technique and palliative treatments.ConclusionsThe present survey attempted to fill the gaps in the role of radiotherapy in patients with BDC. Since lack of prospective randomized studies and disease rarity have mitigated against an evidence-based approach, patients with BDC should be enrolled in prospective studies. The above-mentioned results should also emphasize the need to combine analysis of treatment results from all Italian centres in order to create predictive models.     

Quality control for biomarker determination in oncology: the experience of the Italian Network for Quality Assessment of Tumor Biomarkers (INQAT)

Biomarker analysis and evaluation in oncology is the product of a number of processes (including managerial, technical and interpretation steps) which need to be monitored and controlled to prevent and correct errors and guarantee a satisfactory level of quality. Several biomarkers have recently moved to clinical validation studies and successively to clinical practice without any definition of standard procedures and/or quality control (QC) schemes necessary to guarantee the reproducibility of the laboratory information. In Italy several national scientific societies and single researchers have activated -- often on a pilot level -- specific external quality assessment protocols, thereby potentially jeopardizing the clinical reality even further. In view of the seriousness of the problem, in 1998 the Italian Ministry of Health sponsored a National Survey Project to coordinate and standardize the procedures and to develop QC programs for the analysis of cancer biomarkers of potential clinical relevance. Twelve QC programs focused on biomarkers and concerning morphological, immunohistochemical, biochemical, molecular, and immunoenzymatic assays were coordinated and implemented. Specifically, external QC programs for the analytical phase of immunohistochemical p53, Bcl-2, c-erb-2/neu/HER2, and microvessel density determination, of morphological evaluation of tumor differentiation grade, and of molecular p53 analysis were activated for the first time within the project. Several hundreds of Italian laboratories took part in these QC programs, the results of which are available on the web site of the Network (www.cqlaboncologico.it). Financial support from the Italian Government and the National Research Council (CNR) will guarantee the pursuit of activities that will be extended to new biomarkers, to preanalytical phases of the assays, and to revision of the criteria of clinical usefulness for evaluating the cost/benefit ratio.     

A strategy capitalizing on synergies: the Reporting Structure for Biological Investigation (RSBI) working group

In this article we present the Reporting Structure for Biological Investigation (RSBI), a working group under the Microarray Gene Expression Data (MGED) Society umbrella. RSBI brings together several communities to tackle the challenges associated with integrating data and representing complex biological investigations, employing multiple OMICS technologies. Currently, RSBI includes environmental genomics, nutrigenomics and toxicogenomics communities, where independent activities are underway to develop databases and establish data communication standards within their respective domains. The RSBI working group has been conceived as a "single point of focus" for these communities, conforming to general accepted view that duplication and incompatibility should be avoided where possible. This endeavour has aimed to synergize insular solutions into one common terminology between biologically driven standardisation efforts and has also resulted in strong collaborations and shared understanding between those in the technological domain. Through extensive liaisons with many standards efforts, several threads have been woven with the hope that ultimately technology-centered standards and their specific extensions into biological domains of interest will not only stand alone, but will also be able to function together, as interchangeable modules.     

A new primitive alligatorine from the Eocene of Thailand: relevance of Asiatic members to the radiation of the group

Despite the report of fragmentary remains from China, the fossil record of primitive Alligatorinae is unbalanced with most of its members reported from North America and Europe. Here, we describe cranial, mandibular, and some postcranial elements of a new alligatorine taxon from the Late Eocene of Krabi Basin, southern Thailand. Krabisuchus siamogallicus gen. et sp. nov. was a small animal probably not surpassing 2 m in total length. Despite deformation, the remains show a dorsally elevated cranium similar to Arambourgia gaudryi and Osteolaemus tetraspis. The new alligatorine is characterized by a very short snout and a blunt dentition in the posterior region. Krabisuchus siamogallicus is the first fossil alligatorine from Asia to be incorporated into cladistic analysis. Results indicate a close relationship of the newtaxon to Procaimanoidea, Arambourgia gaudryi, and Allognathosuchus polyodon, all of them being sister groups to the Alligator clade. Alligatorine were widespread as early as the Late Eocene across the northern hemisphere. Scenarios of alligatorine dispersal during the Palaeogene are discussed in comparison with the European and North American alligatorine fossil record. Basal alligatorines were probably land‐dwelling animals contrary to modern‐day crocodylians. Such a mode of life may have allowed this group to colonize vast territories, especially during periods of global warm climates. © 2010 The Linnean Society of London, Zoological Journal of the Linnean Society, 2010, 158 , 608–628.     

Lineage diversification and morphological evolution in a large-scale continental radiation: the neotropical ovenbirds and woodcreepers (aves: Furnariidae)

Patterns of diversification in species-rich clades provide insight into the processes that generate biological diversity. We tested different models of lineage and phenotypic diversification in an exceptional continental radiation, the ovenbird family Furnariidae, using the most complete species-level phylogenetic hypothesis produced to date for a major avian clade (97% of 293 species). We found that the Furnariidae exhibit nearly constant rates of lineage accumulation but show evidence of constrained morphological evolution. This pattern of sustained high rates of speciation despite limitations on phenotypic evolution contrasts with the results of most previous studies of evolutionary radiations, which have found a pattern of decelerating diversity-dependent lineage accumulation coupled with decelerating or constrained phenotypic evolution. Our results suggest that lineage accumulation in tropical continental radiations may not be as limited by ecological opportunities as in temperate or island radiations. More studies examining patterns of both lineage and phenotypic diversification are needed to understand the often complex tempo and mode of evolutionary radiations on continents.     

Intraspecific transfer of cantharidin within selected members of the family Meloidae (Insecta: Coleoptera)

The use of deuterium-labelled cantharidin (CAN-D(2)) to study details of cantharidin transfer in blister beetles indicates that the dynamics of organ-selective cantharidin accumulation may differ over time. Although the accessory glands absorb a high amount of CAN-D(2) in the short term, they ultimately accumulate less than the testes. Confirming previous studies, the last steps in the pathway of biosynthesis of cantharidin occur in the male's body distantly from the reproductive system but the ultimate product, cantharidin, is transported into the male reproductive tract via the membrane of the accessory glands. From there it first transfers preferentially to the epididimis and the vas deferens, followed by final deposition in the testes. Most, if not all, of the cantharidin passes internally within the sexual organs; hemolymph transport is not involved. In female meloids, cantharidin enters the genitalia from the male as a nuptial gift. High amounts are first absorbed by the spermatophoral receptacle followed by spreading through the ovaries and an ultimate accumulation in the eggs. The amount taken up by the ovaries remains considerably lower than that of the receptacle. Over time these two organs stop accumulating cantharidin, while the bursa copulatrix starts to incorporate the gift actively. The accumulated amount taken up by bursa is mainly supplied by the receptacle and ovaries suggesting that an internal transfer of cantharidin is used in females as the main transport route.     

A comparative study between open-face and closed-face masks for head and neck cancer (HNC) in radiation therapy

AimTo determine the setup reproducibility in the radiation treatment of Head and Neck (HN) patients using open face head and shoulder masks (OHSM) with customized headrest (CHR) versus standard closed head and shoulder masks (CHSM) and to determine the patient’s level of comfort and satisfaction for both masks.MethodsForty patients were prospectively randomized into two groups using simple random sampling. Group 1 was assigned with CHSMs, immobilized with a standard HR (SHR) while Group 2 was assigned with OHSMs, and immobilized with CHR. Cone beam computed tomography (CBCT) was taken the first 3 days, followed by weekly CBCT (prior treatment) with results registered to the planning CT to determine translational and rotational inter-fraction shifts and to verify accuracy. Mean (M) and standard deviation (SD) of the systematic and random setup errors of the 2 arms in the translational and rotational directions were analyzed, using Independent t-test and Mann–Whitney U test. Patient comfort was measured using a Likert questionnaire.ResultsThe vertical, lateral, longitudinal and Z/roll rotational shifts were not significantly different between the two masks. X/yaw and Y/pitch rotational shifts were significantly greater in Group 2 versus Group 1, for both systematic (p = 0.009 and 0.046, respectively) and random settings (p = 0.016 and 0.020) but still within three degrees. Patients reported higher neck and shoulder comfort (p = 0.020) and overall satisfaction (p = 0.026) using the OHSM with the CHR versus the CHSM with the SHR during CT simulation.ConclusionOpen masks provide comparable yet comfortable immobilization to closed masks for HN radiotherapy.     

Special wishes for the members of Antwerp Zoo; 65 years of history in pictures (1850-1914)

Antwerp Zoo in Belgium was founded in 1843 and is one of the oldest zoos in the world. It is part of the Royal Zoological Society of Antwerp (RZSA) which also manages Planckendael Wild Animal Park, De Zegge Nature Reserve, Flanders Congress and Concert Center and - since 2009 - Blankenberge Serpentarium - a reptile collection.During its almost 175 years existence the RZSA and Antwerp Zoo in particular went through periods with many highlights but also years with great difficulties. The early years till the start of World War I Antwerp Zoo went through a period that was important for the present zoological garden. The expansion and lay out of the park, the construction of buildings for visitors or to house animals, the offer for visitors to welcome them: much of it still exists or can still be noticed in the park or as part of the day to day operations of Antwerp Zoo and RZSA.For the young society, it was important to have a significant and satisfied membership. Members gave the RZSA not only a key appearance but their financial contributions were also needed for the further development of the gardens. To pamper the members from 1850 on a special annual wishing card was offered to them. This initiative came to an end in 1914. With a few exceptions all of them were very nicely illustrated with pictures of the animals, new constructions or other illustrations which illustrate the development of the zoological garden.The article describes in detail 62 (of 65) known wishing cards, analyzing the relevance of the illustrations for each year. Very often newly arrived species or new constructions are shown. As far as possible more details of these species were gathered. And the future existence of buildings and enclosures and the development of the gardens were also examined.We can conclude that the period before World War I was one with many highlights for Antwerp Zoo. The special whishing cards are very important historical documents and they continue to illustrate the evolution the Zoo went through during the first seventy years.     

Productivity modifications to flour beetles (Coleoptera: Tenebrionidae) by gamma radiation (60Co) of one or both sexes and by the addition of radiated males or females to population

The effects on productivity by the addition of various numbers of radiated adult males or females to populations of two densities were determined for two species of flour beetles. Modifications in productivity after exposure to gamma radiation from⁶⁰Co included:

1. females of T. confusum were sterilized by an exposure between 2620 to 5230 R.
2. females of T. castaneum were not sterilized by 10, 200 R.
3. males were not sterilized by 10, 200 R.
4. sterile females may serve as depositories for normal sperm thereby reducing the productivity. Addition of such females to populations of flour beetles did not reduce the numbers of progeny.
5. since sterile females did not suppress population development, and since they destroy grain and cereal products, they should be eliminated from control programs featuring the sterile insect release technique.
6. population density decreased the numbers of progeny.

The use of the sterile insect release technique to control insects of stored grain products does not seem likely with present day sanitary standards since large numbers of insects need be added to effect control.     

Amplified product length polymorphism (APLP): a novel strategy for genotyping the ABO blood group

We present a simple rapid reproducible polymerase chain reaction based technique, termed amplified product length polymorphism (APLP), as a new strategy for primer design for ABO genotyping. The method involves the use of primers differing in length and permits the identification of the major ABO genotypes (A¹, A², B, O^A, O^G, and O²) according to the molecular size of the allele-specific amplified products. Ten different primers designed to analyze the variations in nucleotide positions 261, 297, 796, 802, and 1059–1061 of cDNA are mixed in one reaction, and the amplified products are resolved on a polyacrylamide gel. Of eight PCR fragments (132 bp, 120 bp, 108 bp, 98 bp, 88 bp, 80 bp, 72 bp, and 64 bp), two to five are amplified in the reaction according to ABO genotypes. The new technique has been successfully applied to the genotyping of 221 peripheral blood samples from Japanese and Germans whose ABO phenotypes had previously been determined; a novel A allele (A^G) was found in Japanese individuals. Received: 12 June 1996 / Revised: 15 August 1996     

Victims of the Early Toarcian anoxic event: the radiation and extinction of Jurassic Koninckinidae (Brachiopoda)

The significant mass extinction attributed to the Early Toarcian anoxic event had a severe impact on the phylum Brachiopoda. Beyond a serious decrease of species diversity, the extinction of the orders Spiriferidina and Athyridida is connected with this episode. The order Athyridida was represented by the family Koninckinidae in the Early Jurassic. The stratigraphical and geographical distribution of the three Early Jurassic koninckinid genera ( Koninckella, Koninckodonta, Amphiclinodonta ) shows a definite radiative pattern. The number of their nominal species increased from 2 to 17 from the Sinemurian to Early Toarcian; in the same time interval, their area increased from the Alpine region to the whole Mediterranean and the NW-European domains. This radiative evolution can be explained as the result of different factors: (1) morphological adaptation to muddy bottoms, (2) fundamental changes in the current pattern in the Tethys/Laurasian Seaway, and, possibly, (3) utilization of methane-based chemosynthesis as alternative food source. The radiation of koninckinids, leading from the cryptic habitats of the Tethyan rocky floors to the extensive muddy bottoms of the open European shelves, was abruptly terminated by the anoxic event in the Early Toarcian Falciferum Zone. The main causes of the extinction might be: (1) the excessive warming of Tethyan deep waters by thermohaline circulation, (2) the anoxic event, which was not survived by the spire-bearers, handicapped by their stiff, calcareous spiralia. Brachiopoda, Early Jurassic, Europe, extinction, Koninckinidae, radiation, Tethys.     

Molecular phylogeography and systematics of the arid-zone members of the Egernia whitii (Lacertilia: Scincidae) species group

We assembled a molecular phylogeny for the arid-zone members of the Egernia whitii species group to test Pianka's [Zoogeography and speciation of Australian desert lizards: an ecological perspective, Copeia (1972) 127-145] hypothesis that habitat specificity to the three major arid-zone vegetation communities is the primary cause of lizard speciation within the arid interior of Australia. This hypothesis predicts that species should exhibit phylogeographic structuring concordant with the major arid-zone vegetation types. Sequence data were obtained from four of the five arid-zone members of the E. whitii species group, and from across the ranges of the ecologically generalized E. inornata and E. multiscutata and the more specialized E. striata. We targeted a fragment (696 base pair (bp)) of the mitochondrial genome comprising the 3' half of the ND4 gene. We analysed the data using parsimony, maximum likelihood and Bayesian methods. Our phylogeny confirms the monophyly of the arid-zone members of the species group, although the phylogenetic relationships among species were not fully resolved. Although our topology does not support the recognition of the existing subspecies within E. multiscutata, there is a substantial phylogeographic break between South Australian/Victorian (Clade 1) and Western Australian (Clade 2) populations. We found considerable phylogeographic structure within E. inornata, with six major clades identified. However, these clades were not concordant with the distribution of habitat types in the arid-zone. Phylogeographic structure was also observed in the more specialized E. striata, although our analysis revealed close phylogenetic affinities between the sympatric species E. striata and E. kintorei. Shimodaira-Hasegawa topology tests were equivocal in regard to whether the phylogeographic structure within E. striata was in accordance with Pianka's predictions. Although our data failed to provide strong support for the suggestion that ecological and habitat factors are responsible for the diversification of arid-zone lizards, most E. inornata and E. striata populations had similar habitats, indicating that adaptation to particular habitats may have some role in the speciation of lizards in the Australian arid-zone.     

Genetic isolation and cryptic variation within the Lycaena xanthoides species group (Lepidoptera: Lycaenidae)

Species exist as biological entities with patterns of discontinuous phenotypic variation. However, the distinctness of taxa is called into question when morphological intermediates exist in areas of sympatry, reflecting either gene flow among variants of a species or hybridization between different species. Studying the partitioning of genetic variation provides a means to discern between the two possibilities. We used genetic and morphometric approaches to investigate the degree of isolation among the three members of the Lycaena xanthoides species group. Lycaena xanthoides, L. editha, and L. dione are predominantly allopatric and have been treated both as three separate species and as a single polytypic species. Using 618 bp of the mitochondrial gene COII, we found little phylogenetic resolution, but significant among-taxa genetic variance partitioning. Divergence among these taxa has been relatively recent, as evidenced by relatively low pairwise sequence divergence. Also, the existence of two well-supported clades within L. xanthoides sensu stricto, concordant with the Transverse Ranges of southern California, indicates divergence within this taxon, and a possible cryptic species. Significant morphological differentiation between L. editha and L. xanthoides supports the hypothesis that these taxa represent separate gene pools. Populations occurring in a narrow zone where the two species' ranges approach are characterized by intermediate morphology, suggesting incomplete morphological divergence or recent hybridization. These findings highlight the utility of genetic data in inferring species boundaries and the identification of cryptic lineages.     

Molecular evidence for a fourth species within the Isotoma viridis group (Insecta, Collembola)

For identification of single species within the Isotoma viridis group, we present polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) as a fast and efficient DNA-based molecular method. We used five PCR primers amplifying the cytochrome oxidase II (COII) region (760 bp) of the mitochondrial DNA. The sequences clearly separated four species ( I. viridis , I. riparia , I. anglicana and I. caerulea ) out of samples from Norway, Sweden, Germany and Switzerland. Examination of genetic variation and phylogenetic relationship did not support the separation of two colour pattern forms of I. viridis into distinct species. For RFLP, several restriction enzymes were tested for their ability to produce not only species-specific restriction fragment patterns but to discriminate more than one species per enzyme used with as few cleavage sites as possible. Such a design should render a clear fragment pattern when performing a double digest. These demands appear to be fulfilled best by the combination of the restriction enzymes Mfe I, Nci I and one of Aci I, Bst EII, Nde I, or Sfc I. From the enzymes tested in a previous study, Ase I proved to be reliable, whereas Mbo I can no longer be recommended.