Impact of digitalization of mammographic units on average glandular doses in the Flemish Breast Cancer Screening Program

The impact of digitalization on the average glandular doses in 49 mammographic units participating in the Flemish Breast Cancer Screening Program was studied. Screen-film was changed to direct digital radiography and computed radiography in 25 and 24 departments respectively. Average glandular doses were calculated before and after digitalization for different PMMA-phantom thicknesses and for groups of 50 successive patients. For the transition from screen-film to computed radiography both phantom and patient dose data show a significant increase of dose with digitalization. For the transition from screen-film to direct digital radiography the evolution of the average glandular dose depends on the phantom thickness. For 20mm PMMA a significant increase in dose was found, for 45mm and 70mm PMMA there was a significant decrease in dose. The median average glandular dose of the patient dosimetry showed a smaller but significant decrease

Effects of Ionizing Radiation on the Size Distribution of Proteoglycan Aggregates Synthesized by Chondrocytes in Agarose

Effects of ionizing radiation on the structure and size-distribution of newly synthesized proteoglycan aggregates are studied in-vitro. Chondrocytes, isolated from embryonic chick sterna, are cultured for 7 days in a tri-dimensional agarose system. Single radiation doses of 10, 20 and 50 Gy are given before starting the culture. Digestion of the artificial agarose matrix liberates the newly synthesized proteoglycans. Spreading with cytochrome C allows electron microscopic investigations of the individual, newly synthesized molecules. The structure of aggregates synthesized by control and irradiated chondrocytes is comparable. However, radiation causes alterations in the size-distributions of the aggregate-populations. For the control cultures, an average aggregate contains 27 aggrecans per aggregate. 34 pro mille of the molecules contain more than 100 aggrecans per aggregate. Irradiation with 10 Gy doesn\u27t cause alterations. With radiation doses of 20 and 50 Gy, an average molecule contains 20 aggrecans. Only about 9 pro mille of the aggregates contain more than 100 aggrecans. Stimulation of lysosomal activity after irradiation could explain the observed alterations

Effects of Ionizing Radiation on Cartilage: Emphasis on Effects on the Extracellular Matrix

In this report, we review data dealing with radiation effects on cartilage. More specifically, we emphasize on alterations caused in the extra-cellular cartilage matrix. Although radiation studies predominantly describe the effect on the structure of DNA and on the mitotic activity of cells, alterations caused by the effect on the non-mitotic activity can also be important. Cartilage, having an extracellular matrix composed of 2 major components, aggrecan and collagen, provides a good model to study this kind of radiation effects. The following topics concerning literature data are summarized: effects on the amount of matrix synthesized, effects on the activity of certain enzymes and effects on the structure and morphology of the matrix. Some new findings concerning the radiation effect on the size distribution of aggrecan-aggregate populations, de novo synthesized by chondrocyte cultures, either derived from calcifying or from non-calcifying cartilage, are given

γ-H2AX foci as in vivo effect biomarker in children emphasize the importance to minimize x-ray doses in paediatric CT imaging

Objectives: Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting. Methods: From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring gamma-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models. Results: Despite the low CT doses, a median increase of 0.13 gamma-H2AX foci/cell was observed. Plotting the induced gamma-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose-response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13% respectively. Conclusion: CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols

The early diagenetic and PETROphysical behaviour of recent cold-water CARbonate mounds in Deep Environments (PETROCARDE)

Sub-recent cold-water carbonate mounds localized in deeper slope settings on the Atlantic continental margins cannot be any longer neglected in the study of carbonate systems. They clearly play a major role in the dynamics of mixed siliciclastic-carbonate and/or carbonate-dominated continental slopes. Carbonate accumulation rates of cold-water carbonate mounds are about 4 to 12 % of the carbonate accumulation rates of tropical shallow-water reefs but exceed the carbonate accumulation rates of their slope settings by a factor of 4 to 12 (Titschack et al.,2009). These findings emphasize the importance of these carbonate factories as carbonate niches on the continental margins. The primary environmental architecture of such carbonate bodies is well-characterized. However, despite proven evidences of early diagenesis overprinting the primary environmental record (e.g. aragonite dissolution) (Foubert & Henriet, 2009), the extent of early diagenetic and biogeochemical processes shaping the petrophysical nature of mounds is until now not yet fully understood.Understanding (1) the functioning of a carbonate mound as biogeochemical reactor triggering early diagenetic processes and (2) the impact of early diagenesis on the petrophysical behaviour of a carbonate mound in space and through time are necessary (vital) for the reliable prediction of potential late diagenetic processes. Approaching the fossil carbonate mound record, through a profound study of recent carbonate bodies is innovative and will help to better understand processes observed in the fossil mound world (such as cementation, brecciation, fracturing, etc. . . ).In this study, the 155-m high Challenger mound (Porcupine Seabight, SW of Ireland), drilled during IODP Expedition 307 aboard the R/V Joides Resolution (Foubert & Henriet, 2009), and mounds from the Gulf of Cadiz (Moroccan margin) will be discussed in terms of early diagenetic processes and petrophysical behaviour. Early differential diagenesis overprints the primary environmental signals in Challenger mound, with extensive coral dissolution and the genesis of small-scaled semi-lithified layers in the Ca-rich intervals. The low cementation rates compared to the extensive dissolution patterns can be explained by an open-system diagenetic model. Moreover, Pirlet et al. (2009) emphasizes the occurrence of gypsum and dolomite in another mound system (Mound Perseverance) in Porcupine Seabight, which might be also related with fluid oxidation events in a semi-open diagenetic system. Along the Moroccan margins, fluid seepage and fluxes in pore water transport affect the development of mound structures, enhancing extensive cold-water coral dissolution and precipitation of diagenetic minerals such as dolomite, calcite, pyrite, etc. (Foubert et al., 2008). Recent carbonate mounds provide indeed an excellent opportunity to study early diagenetic processes in carbonate systems without the complications of burial and/or later meteoric diagenesis

The R.V. Pelagia pre-drilling site survey at the Rockall and Porcupine cold water coral mounds provinces, European Atlantic margin. The CARBONATE project, ESF EuroMARC program

From 30 September to 22 October 2007 a cruise with the Royal NIOZ research vessel Pelagia was carried out within the framework of the ESF (EuroMARC) project CARBONATE. The goal of this cruise was to complete the existing data set of carbonate mounds present at the European Atlantic margin in order to be able to choose suitable coring sites to drill complete top to base sections through the carbonate mounds with the MeBo drilling device. This is a remotely operated drill that is placed at the sea floor and capable of drilling sediment cores with a maximum length of 85 metres. The drilling cruise, with the Irish research vessel Celtic Explorer, is planned to take place in the summer of 2008.During the Pelagia cruise 5 carbonate mound provinces were visited. The mounds were selected based on two main criteria:the mound provinces should represent different stages in mound developmentit must be possible to penetrate the mounds from top to base with the MeBo (expected maximum sequence thickness in the order of 75 m)The first area that was visited is located at the SE Rockall Bank margin. These mounds are characterised by abundant living cold water corals at their top. The second mound province that was visited is located at the SW Rockall Bank. Initially a large mound cluster known as Franken Mound was chosen for detailed studies. This mound, as well as smaller mounds in the vicinity, is dominated by dead corals and it is considered to be in what is often called the retirement stage. At theWand N margin of the Porcupine Bank two areas were visited. Most of the mounds occur as isolated structures. Only limited amounts of living cold water corals are present. The mounds in the last area that was visited are also referred to as the Magellan Mounds. This is a group of small (<100 m) mounds located in the Porcupine Seabight. These mounds are mostly fully buried and thus represent the final stage of mound development.At all sites a multibeam bathymetric survey was carried out. Subsequently a benthic lander was deployed which was equipped for a period of 2 to 4 days to measure near bed hydrography and sediment transport. This was followed by seismic and video surveys.The initial results of the cruise indicate that at all proposed drilling sites carbonate mounds with a total thickness that can be penetrated by the MeBo are present. The video observations did not reveal the presence of any rough terrain that may hamper the positioning of the MeBo at the seabed

Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging &gamma;-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the &gamma;-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and &gamma;-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses &ge;1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

Characterization of the c.190T>C missense mutation in BRCA1 codon 64 (Cys64Arg).

In the Milan area (Northern Italy), we identified a family characterized by a high prevalence of ovarian and breast cancer cases (5 out of 6 subjects, over 3 generations), and a predominant prevalence of ovarian lesions (4 out of 5 patients). Analysis of BRCA1 and BRCA2 genes allowed the identification of the missense c.190T>C mutation in codon 64 (Cys64Arg) of BRCA1. The aims of the present investigation were to characterize the functional implications of the c.190T>C mutation at the molecular level, and to search whether additional polymorphisms might be linked to the peculiar phenotypic features observed in the Italian pedigree. Molecular modelling studies suggested that substitution of the cysteine 64 with an arginine likely disrupts the architecture of the BRCA1 RING finger domain, responsible for the interaction with BARD1, essential for the tumor-suppressor activity of the BRCA1-BARD1 complex. By splicing site information analysis, exonic splicing enhancer site characterization, and analysis of transcript fragment length and sequence, we showed that the c.190T>C mutation was able to modulate the splicing of exon 5 in a fashion opposite to the c.190T>G transversion, responsible for the functionally-related Cys64Gly amino acid substitution. Genotyping of BRCA1 and BRCA2 in the Italian family revealed the presence of two significant polymorphisms: the cancer-associated c.2612C>T SNP in BRCA1, and the c.-26G>A SNP in the BRCA2 gene, acting as an ovarian cancer risk modifier in carriers of deleterious BRCA1 mutations. Analysis of these SNPs in a genotypically-unrelated Polish family, characterized by prevalent breast neoplasms in carriers of the c.190T>C mutation, revealed a genetic profile consistent with the hypothetic role of both polymorphisms

Microsatellite polymorphisms in DNA repair genes XRCC1, XRCC3 and XRCC5 in patients with gynecological tumors: Association with late clinical radiosensitivity and cancer incidence

This study investigates the association of microsatellite polymorphisms in XRCC1, XRCC3 and XRCC5 with the development of late radiation-induced radiotherapy reactions and examines the correlation between these microsatellites and cancer incidence. Sixty-two women with cervical or endometrial cancer treated with radiotherapy were included in the study. According to the CTCAEv3.0 scale, 22 patients showed late adverse radiotherapy reactions (grade 2 or more). PCR on lymphocyte DNA followed by automated fragment analysis was performed to examine the number of tandem repeat units at each locus. No significant association was found between the repeat length at any of the microsatellites in XRCC1, XRCC3 or XRCC5 and the incidence of late radiotherapy complications. Since higher odds ratios (ORs) were found for the rare XRCC1 [AC]11 and [AC]21 repeats (OR = 2.65, P = 0.325 and OR = 8.67, P = 0.093, respectively), the possible involvement of these small and large repeats in clinical radiosensitivity cannot be completely ruled out. When specific numbers of repeats were examined, no significant correlation was found between the microsatellite repeat length in XRCC1 and XRCC5 and cancer incidence. A weak correlation between XRCC3 [AC]16 homozygotes and cancer incidence was found (OR = 2.56, P = 0.055). A large-scale multicenter study of cancer patients with a high number of radiosensitive individuals is needed to clarify the value of rare polymorphic microsatellite repeats in XRCC1 and XRCC3 as a biomarker of clinical radiosensitivity or increased cancer risk