Correlation between IgA tissue transglutaminase antibody ratio and histological finding in celiac disease.

OBJECTIVES: Positivity of both immunoglobulin A anti-tissue transglutaminase (TTG) and anti-endomysium antibodies (EMA) has a positive predictive value of nearly 100% for celiac disease (CD). The objective of the present study was to evaluate whether patients of any age, with high pretest probability of CD and high titre of anti-TTG and EMA positivity, have a high probability of intestinal damage and may not require the biopsy for final diagnosis. METHODS: A retrospective analysis of 412 consecutively referred patients, age range 10 months to 72 years, who underwent small-bowel biopsy for suspicion of CD and positivity to both anti-TTG and EMA, was performed at 4 Italian centers. Biopsies were evaluated independently by 2 pathologists using Marsh modified classification; in cases of dissimilar results, a third pathologist examined the biopsy. The final histological finding diagnosis was expressed as the prevalent or highest score assigned by the pathologist board. RESULTS: Three hundred ninety-six patients (96.1%) had histological findings consistent with CD (grade 2 and 3a, 3b, or 3c of modified Marsh classification). An anti-TTG ratio ≥ 7 was able to identify with the 3 assays used (Celikey, anti-TTG immunoglobulin A, EuTTG) all of the patients with significant mucosal damage (Marsh ≥ 2) independent of age and sex; specificity and positive predictive value were 100%. An anti-TTG ratio >20 was more specific (99.8%) for identification of patients with villous atrophy (Marsh 3 a, b, or c). CONCLUSIONS: Patients with positivity of anti-TTG ≥ 7-fold cutoff, confirmed by positivity to EMA, have a high-degree probability of duodenal damage. In selected conditions, a duodenal biopsy may be avoided and a confirmed greatly positive anti-TTG result could be the basis to prescribe a gluten-free diet

57Co Production using RbCl/RbCl/58Ni Target Stacks at the Los Alamos Isotope Production Facility: LA-UR-14-22122

Introduction The Los Alamos Isotope Production Program commonly irradiates target stacks consisting of high, medium and low-energy targets in the “A-”, “B-”, and “C-slots”, respectively, with a 100MeV proton beam. The Program has recently considered the production of 57Co (t1/2 = 271.74 d, 100% EC) from 58Ni using the low-energy posi-tion of the Isotope Production Facility, down-stream of two RbCl salt targets. Initial MCNPX/ CINDER’90 studies predicted 57Co radioisotopic purities >90% depending on time allotted for decay. But these studies do not account for broadening of the proton beam’s energy distribution caused by density changes in molten, potentially boiling RbCl targets upstream of the 58Ni (see e.g., [1]). During a typical production with 230 µA average proton intensity, the RbCl targets’ temperature is expected to produce beam energy changes of several MeV and commensurate effects on the yield and purity of any radioisotope irradiated in the low-energy posi-tion of the target stack. An experiment was designed to investigate both the potential for 57Co’s large-scale production and the 2-dimensional proton beam energy distribution. Material and Methods Two aluminum targets holders were fabricated to each contain 31 58Ni discs (99.48%, Isoflex, CA), 4.76 mm (Φ) x 0.127 mm (thickness). Each foil was indexed with a unique cut pattern by EDM with a 0.254 mm brass wire to allow their position in the target to be tracked through hot cell disassembly and assay (see FIG. 1). Brass residue from EDM was removed with HNO3/HCl solution. The holders’ front windows were 2.87 and 1.37 mm thick, corresponding to predicted average incident energies of 17.9 and 24.8 MeV on the Ni [2]. Each target was irradiated with protons for 1 h with an average beam current of 218 ± 3 µA to ensure an upstream RbCl target temperature and density that would mimic routine production. Following irradiation, targets were disassembled and each disc was assayed by HPGe γ-spectroscopy. Residuals 56Co (t1/2 = 77.2 d, 100% EC) and 57Co have inversely varying measured nuclear formation cross sections between approximately 15 and 40 MeV. Results and Conclusion Distributions of 56,57,58,60Co were tracked as described in both irradiated targets. The distribution of activities matched expectations, with radioisotopes produced by proton interactions with the 58Ni target (56Co and 57Co) concentrated in the area struck by IPF’s rastered, annulus-shaped proton beam, and the distribution of radioisotopes produced by neutron-induced reactions (58Co and 60Co) relatively uniform across all irradiated foils. The potential range of such temperature variations predicted by thermal modeling (approx. ± 200 °C) corre-sponds to a density variation of nearly 0.2 g.cm−3, and a change in the average energy of protons incident on the low-energy “C-slot” of approximately 5 MeV, well-matched to the indi-rectly measured energy variation plotted in FIG. 3. No energy distribution in the plane per-pendicular to the beam axis has previously been assumed in the design of IPF targets. The effective incident energy measured by yields of 57Co and 56Co is, however, almost 5 MeV higher than those predicted using Anderson and Ziegler’s well-known formalism [2]. This discrepancy is supported by previous reports [3] and likely exacerbated compared to these reports by the large magnitude of energy degradation (from 100 MeV down to 30 MeV) in the IPF target stack. For more detailed discussion, refer to Marus et al.’s abstract, also reported at this meeting. While the experiments reported do confirm the potential for many Ci-scale yields of 57Co from months-long irradiations at the IPF, the level radioisotopic impurities 56Co and 58Co are concerning. Commercial radioisotope producers using U-150 (23 MeV) and RIC-14 (14 MeV) cyclotrons in Obninsk, Russia specify 56/58Co activities at levels <0.2% of available 57C

57Co Production using RbCl/RbCl/58Ni Target Stacks at the Los Alamos Isotope Production Facility: LA-UR-14-22122

Introduction The Los Alamos Isotope Production Program commonly irradiates target stacks consisting of high, medium and low-energy targets in the “A-”, “B-”, and “C-slots”, respectively, with a 100MeV proton beam. The Program has recently considered the production of 57Co (t1/2 = 271.74 d, 100% EC) from 58Ni using the low-energy posi-tion of the Isotope Production Facility, down-stream of two RbCl salt targets. Initial MCNPX/ CINDER’90 studies predicted 57Co radioisotopic purities >90% depending on time allotted for decay. But these studies do not account for broadening of the proton beam’s energy distribution caused by density changes in molten, potentially boiling RbCl targets upstream of the 58Ni (see e.g., [1]). During a typical production with 230 µA average proton intensity, the RbCl targets’ temperature is expected to produce beam energy changes of several MeV and commensurate effects on the yield and purity of any radioisotope irradiated in the low-energy posi-tion of the target stack. An experiment was designed to investigate both the potential for 57Co’s large-scale production and the 2-dimensional proton beam energy distribution. Material and Methods Two aluminum targets holders were fabricated to each contain 31 58Ni discs (99.48%, Isoflex, CA), 4.76 mm (Φ) x 0.127 mm (thickness). Each foil was indexed with a unique cut pattern by EDM with a 0.254 mm brass wire to allow their position in the target to be tracked through hot cell disassembly and assay (see FIG. 1). Brass residue from EDM was removed with HNO3/HCl solution. The holders’ front windows were 2.87 and 1.37 mm thick, corresponding to predicted average incident energies of 17.9 and 24.8 MeV on the Ni [2]. Each target was irradiated with protons for 1 h with an average beam current of 218 ± 3 µA to ensure an upstream RbCl target temperature and density that would mimic routine production. Following irradiation, targets were disassembled and each disc was assayed by HPGe γ-spectroscopy. Residuals 56Co (t1/2 = 77.2 d, 100% EC) and 57Co have inversely varying measured nuclear formation cross sections between approximately 15 and 40 MeV. Results and Conclusion Distributions of 56,57,58,60Co were tracked as described in both irradiated targets. The distribution of activities matched expectations, with radioisotopes produced by proton interactions with the 58Ni target (56Co and 57Co) concentrated in the area struck by IPF’s rastered, annulus-shaped proton beam, and the distribution of radioisotopes produced by neutron-induced reactions (58Co and 60Co) relatively uniform across all irradiated foils. The potential range of such temperature variations predicted by thermal modeling (approx. ± 200 °C) corre-sponds to a density variation of nearly 0.2 g.cm−3, and a change in the average energy of protons incident on the low-energy “C-slot” of approximately 5 MeV, well-matched to the indi-rectly measured energy variation plotted in FIG. 3. No energy distribution in the plane per-pendicular to the beam axis has previously been assumed in the design of IPF targets. The effective incident energy measured by yields of 57Co and 56Co is, however, almost 5 MeV higher than those predicted using Anderson and Ziegler’s well-known formalism [2]. This discrepancy is supported by previous reports [3] and likely exacerbated compared to these reports by the large magnitude of energy degradation (from 100 MeV down to 30 MeV) in the IPF target stack. For more detailed discussion, refer to Marus et al.’s abstract, also reported at this meeting. While the experiments reported do confirm the potential for many Ci-scale yields of 57Co from months-long irradiations at the IPF, the level radioisotopic impurities 56Co and 58Co are concerning. Commercial radioisotope producers using U-150 (23 MeV) and RIC-14 (14 MeV) cyclotrons in Obninsk, Russia specify 56/58Co activities at levels <0.2% of available 57C

57Co Production using RbCl/RbCl/58Ni Target Stacks at the Los Alamos Isotope Production Facility: LA-UR-14-22122

Introduction The Los Alamos Isotope Production Program commonly irradiates target stacks consisting of high, medium and low-energy targets in the “A-”, “B-”, and “C-slots”, respectively, with a 100MeV proton beam. The Program has recently considered the production of 57Co (t1/2 = 271.74 d, 100% EC) from 58Ni using the low-energy posi-tion of the Isotope Production Facility, down-stream of two RbCl salt targets. Initial MCNPX/ CINDER’90 studies predicted 57Co radioisotopic purities >90% depending on time allotted for decay. But these studies do not account for broadening of the proton beam’s energy distribution caused by density changes in molten, potentially boiling RbCl targets upstream of the 58Ni (see e.g., [1]). During a typical production with 230 µA average proton intensity, the RbCl targets’ temperature is expected to produce beam energy changes of several MeV and commensurate effects on the yield and purity of any radioisotope irradiated in the low-energy posi-tion of the target stack. An experiment was designed to investigate both the potential for 57Co’s large-scale production and the 2-dimensional proton beam energy distribution. Material and Methods Two aluminum targets holders were fabricated to each contain 31 58Ni discs (99.48%, Isoflex, CA), 4.76 mm (Φ) x 0.127 mm (thickness). Each foil was indexed with a unique cut pattern by EDM with a 0.254 mm brass wire to allow their position in the target to be tracked through hot cell disassembly and assay (see FIG. 1). Brass residue from EDM was removed with HNO3/HCl solution. The holders’ front windows were 2.87 and 1.37 mm thick, corresponding to predicted average incident energies of 17.9 and 24.8 MeV on the Ni [2]. Each target was irradiated with protons for 1 h with an average beam current of 218 ± 3 µA to ensure an upstream RbCl target temperature and density that would mimic routine production. Following irradiation, targets were disassembled and each disc was assayed by HPGe γ-spectroscopy. Residuals 56Co (t1/2 = 77.2 d, 100% EC) and 57Co have inversely varying measured nuclear formation cross sections between approximately 15 and 40 MeV. Results and Conclusion Distributions of 56,57,58,60Co were tracked as described in both irradiated targets. The distribution of activities matched expectations, with radioisotopes produced by proton interactions with the 58Ni target (56Co and 57Co) concentrated in the area struck by IPF’s rastered, annulus-shaped proton beam, and the distribution of radioisotopes produced by neutron-induced reactions (58Co and 60Co) relatively uniform across all irradiated foils. The potential range of such temperature variations predicted by thermal modeling (approx. ± 200 °C) corre-sponds to a density variation of nearly 0.2 g.cm−3, and a change in the average energy of protons incident on the low-energy “C-slot” of approximately 5 MeV, well-matched to the indi-rectly measured energy variation plotted in FIG. 3. No energy distribution in the plane per-pendicular to the beam axis has previously been assumed in the design of IPF targets. The effective incident energy measured by yields of 57Co and 56Co is, however, almost 5 MeV higher than those predicted using Anderson and Ziegler’s well-known formalism [2]. This discrepancy is supported by previous reports [3] and likely exacerbated compared to these reports by the large magnitude of energy degradation (from 100 MeV down to 30 MeV) in the IPF target stack. For more detailed discussion, refer to Marus et al.’s abstract, also reported at this meeting. While the experiments reported do confirm the potential for many Ci-scale yields of 57Co from months-long irradiations at the IPF, the level radioisotopic impurities 56Co and 58Co are concerning. Commercial radioisotope producers using U-150 (23 MeV) and RIC-14 (14 MeV) cyclotrons in Obninsk, Russia specify 56/58Co activities at levels <0.2% of available 57C