Toward high-throughput defect density quantification: A comparison of techniques for irradiated samples.

Transmission electron microscopy (TEM) is an established tool used for the investigation of defects in materials. Traditionally, diffraction contrast techniques-two-beam bright-field and weak-beam dark-field-have been used to image defects due to contrast sensitivity from weak lattice strains. Use of these methods entail an intricate tilt series of imaging using different diffracting vectors, g, to verify the g•b invisibility criterion relative to the different defect types and habit planes inherent to the material. Recently, the addition of down-zone imaging and STEM imaging has also proven to be effective imaging techniques for defect density analysis. Interest in nanocrystalline (NC) materials, spurred by their conjectured superior properties compared to their coarse-grain counterparts, has been thriving and the investigation of their defect morphologies is essential. Maneuvering within NC samples in the TEM adds another layer of difficulty making the aforementioned techniques not practical for application to specimens with complex microstructures. For this reason, we have devised a protocol for identifying NC grains optimally oriented for quantitative analysis using NanoMegas ASTAR automated crystal orientation mapping (ACOM) in the TEM. In this work, we conduct a series of experiments assessing the effectiveness of conventional two-beam bright-field, weak-beam dark-field, and down-zone STEM imaging. We also evaluate an ACOM-assisted multibeam imaging method and compare defect density results obtained using each technique in an irradiated nanocrystalline Au sample.

Achieving Radiation Tolerance through Non-Equilibrium Grain Boundary Structures.

Many methods used to produce nanocrystalline (NC) materials leave behind non-equilibrium grain boundaries (GBs) containing excess free volume and higher energy than their equilibrium counterparts with identical 5 degrees of freedom. Since non-equilibrium GBs have increased amounts of both strain and free volume, these boundaries may act as more efficient sinks for the excess interstitials and vacancies produced in a material under irradiation as compared to equilibrium GBs. The relative sink strengths of equilibrium and non-equilibrium GBs were explored by comparing the behavior of annealed (equilibrium) and as-deposited (non-equilibrium) NC iron films on irradiation. These results were coupled with atomistic simulations to better reveal the underlying processes occurring on timescales too short to capture using in situ TEM. After irradiation, NC iron with non-equilibrium GBs contains both a smaller number density of defect clusters and a smaller average defect cluster size. Simulations showed that excess free volume contribute to a decreased survival rate of point defects in cascades occurring adjacent to the GB and that these boundaries undergo less dramatic changes in structure upon irradiation. These results suggest that non-equilibrium GBs act as more efficient sinks for defects and could be utilized to create more radiation tolerant materials in future.

[Prognostic value of the metabolically active tumour volume]. / Valeur pronostique du volume tumoral métabolique sur la TEP au ((18)F)-fluorodésoxyglucose préthérapeutique pour le cancer de l'œsophage localisé.

PURPOSE: The purpose of this study was to assess the prognostic value of different parameters on pretreatment fluorodeoxyglucose [((18)F)-FDG] positron emission tomography-computed tomography (PET-CT) in patients with localized oesophageal cancer. PATIENTS AND METHOD: We retrospectively reviewed 83 cases of localised oesophageal cancer treated in our institution. Patients were treated with curative intent and have received chemoradiotherapy alone or followed by surgery. Different prognostic parameters were correlated to survival: cancer-related factors, patient-related factors and parameters derived from PET-CT (maximum standardized uptake value [SUV max], metabolically active tumor volume either measured with an automatic segmentation software ["fuzzy locally adaptive bayesian": MATVFLAB] or with an adaptive threshold method [MATVseuil] and total lesion glycolysis [TLGFLAB and TLGseuil]). RESULTS: The median follow-up was 21.8 months (range: 0.16-104). The median overall survival was 22 months (95% confidence interval [95%CI]: 15.2-28.9). There were 67 deaths: 49 associated with cancer and 18 from intercurrent causes. None of the tested factors was significant on overall survival. In univariate analysis, the following three factors affected the specific survival: MATVFLAB (P=0.025), TLGFLAB (P=0.04) and TLGseuil (P=0.04). In multivariate analysis, only MATVFLAB had a significant impact on specific survival (P=0.049): MATVFLAB<18 cm(3): 31.2 months (95%CI: 21.7-not reached) and MATVFLAB>18 cm(3): 20 months (95%CI: 11.1-228.9). CONCLUSION: The metabolically active tumour volume measured with the automatic segmentation software FLAB on baseline PET-CT was a significant prognostic factor, which should be tested on a larger cohort.

[Are extensive fields useful for radiotherapy of esophageal cancer?]. / Des marges extensives sont-elles nécessaires pour la radiothérapie du cancer de l'œsophage ?

PURPOSE: Study of the pattern of relapse for locally advanced oesophageal cancer and analysis of the local recurrences according to irradiated volume. PATIENTS AND METHODS: We performed a monocentric retrospective study of patients treated in the integrated centre of oncology (Angers, France). Two treatment strategies were used: concurrent chemoradiation alone or followed by surgery. Recurrences were classified as: locoregional, either isolated or associated with distant metastasis, and metastatic only. Locoregional relapses were subclassified as in-field, out-field, or mixed. RESULTS: Between March 2004 and October 2011, 168 patients were treated: 130 by chemoradiation, and 38 by chemoradiation followed by surgery. The median supero-inferior margins added to the gross tumour volume in order to create the planning tumour volume was 5cm (range: 0.5-21). Sixty-two percent of patients (n=104) relapsed: 82 locoregional relapses (49%), including 45 isolated relapses (27%) and 37 associated with distant metastasis relapses (22%), and 22 metastatic relapses (13%). From the 82 locoregional relapses, only four isolated relapses were exclusively out-field. CONCLUSION: With 5cm supero-inferior margins added to gross tumour volume, less than 3% of patients had an isolated out-field recurrence. However, half of the patients suffered in-field local recurrence and one third had metastases. These findings advocate for a limited prophylactic nodal irradiation. Trials are ongoing to assess dose escalation or surgery in order to increase local control.

Assessing Hydration in Children: From Science to Practice.

Raising children's awareness about their hydration status could be done through a noninvasive biomarker. Urine color (UC) has been validated as a biomarker of hydration in adults and children aged 8-14 years. The aim of this survey was to design and to evaluate the level of understanding and attractiveness of a self-assessment, UC-based hydration tool for children aged 6-11 years. The first phase of the survey consisted of face-to-face interviews during which 84 children identified those graphical elements necessary to understand the hydration message from 6 illustration-based designs containing the UC chart. The graphic elements selected were the basis to create 3 new designs. During the 2nd phase, the level of understanding and attractiveness of these 3 new designs was then evaluated via an online questionnaire by a total of 1,231 children in 3 countries. The design with the highest level of understanding was totally or partially understood by 76% of the participants, independent of age and gender. The levels of understanding, however, differed in the countries. In Indonesia, the levels of understanding of the 3 designs were comparable; whereas in both France (74%) and Mexico (78%), significantly more participants totally and partially understood one of the 3 designs. The levels of attractiveness of the 3 designs were comparable, independent of country, age, and gender. On average, 80% of all participants liked the 3 designs a bit or a lot. Only 14% did not like the designs, and 5% of participants had no opinion regarding attractiveness. These results indicated that three out of four children like and understand the correct hydration message from a strictly illustration-based tool containing the eight-point UC scale.

In situ transmission electron microscopy and ion irradiation of ferritic materials.

The intermediate voltage electron microscope-tandem user facility in the Electron Microscopy Center at Argonne National Laboratory is described. The primary purpose of this facility is electron microscopy with in situ ion irradiation at controlled sample temperatures. To illustrate its capabilities and advantages a few results of two outside user projects are presented. The motion of dislocation loops formed during ion irradiation is illustrated in video data that reveals a striking reduction of motion in Fe-8%Cr over that in pure Fe. The development of extended defect structure is then shown to depend on this motion and the influence of nearby surfaces in the transmission electron microscopy thin samples. In a second project, the damage microstructure is followed to high dose (200 dpa) in an oxide dispersion strengthened ferritic alloy at 500 degrees C, and found to be qualitatively similar to that observed in the same alloy neutron irradiated at 420 degrees C.

Pyruvate carboxylase deficiency--insights from liver transplantation.

Pyruvate carboxylase deficiency, complex form, presents in early infancy with lethal metabolic acidosis, resulting from ketoacidosis and lactic acidemia. Renal tubular acidosis, hyperammonemia, and citrullinemia complete the picture. In an infant with this disease, large amounts of glucose ameliorated the ketoacidosis, but worsened the lactic acidosis. Orthotopic hepatic transplantation completely reversed the ketoacidosis and the renal tubular abnormality and ameliorated the lactic acidemia. Concentrations of glutamine in cerebrospinal fluid were low and did not improve with liver transplantation.

Tolerability of enteric-coated didanosine capsules compared with didanosine tablets in adults with HIV infection.

BACKGROUND: A new enteric-coated (EC) didanosine (ddI) formulation (Videx EC; Bristol-Myers Squibb, Princeton, NJ, U.S.A.) may be better tolerated than the tablet form because it lacks the buffer component thought to be responsible for diarrhea and other gastrointestinal (GI) side effects. OBJECTIVE: To evaluate the frequency and magnitude of GI side effects (nausea, bloating, GI upset, diarrhea, abdominal cramps, gas [flatus]) before and after switching the formulation of ddI, in study subjects who were experiencing one or more GI symptom(s) of at least moderate severity. METHODS: A 6-week open label crossover study of current didanosine tablet users comparing daily symptom scores (7 point scale, 0 = absent to 6 = very severe) during weeks 1 to 2 (on tablets) to weeks 4 and 6 (on EC capsules). Formulation palatability and preference, lifestyle effects, and use of antidiarrheals or other medications for symptom relief were also assessed. RESULTS: GI symptom scores (7-day means) on tablets were diarrhea 2.11, gas 2.00, bloating 1.23, abdominal cramps 0.74, GI upset 0.69, nausea 0.66. After switching to EC (week 4 and week 6), mean scores decreased for diarrhea (mean scores 0.99 week 4, 0.79 week 6), gas (0.95, 0.79), bloating (0.49, 0.32), abdominal cramps (0.21, 0.05), GI upset (0.16, 0.14), and nausea (0.32, 0.22). Severity of all GI symptoms was significantly reduced after 4 weeks on EC capsules ( p <.01 by paired t- test). Negative impact of side effects on routine activities was significantly reduced (41% on tablet vs. 7% on EC; p <.01). All 42 study subjects preferred the EC form. CONCLUSIONS: According to patients' diary scores, switching to ddI in EC form significantly reduces nausea, bloating, GI upset, diarrhea, abdominal cramps, and gas for individuals who experienced GI side effects while taking the buffered tablet form. The striking tolerability advantages appear to support routine switching to EC for such patients and may suggest that widespread preferential selection of the EC form is appropriate to enhance didanosine tolerability and promote treatment adherence.

Comparison of SCH 39304 and its isomers, RR 42427 and SS 42426, for treatment of murine cryptococcal and coccidioidal meningitis.

SCH 39304 (304) and its isomers, SCH 42426 (426) and SCH 42427 (427), are new orally administered antifungal azole derivatives. In this study, we compared the efficacy of 304 with that of 426 and 427 in murine models of cryptococcal and coccidioidal meningitis. On day 18 postinfection with Cryptococcus neoformans, controls showed 80% mortality. The 50% protective doses calculated at this day were 0.56 mg of 304 per kg of body weight, 23.5 mg of 426 per kg, and 0.11 mg of 427 per kg. Controls with coccidioidal meningitis all succumbed, and treated mice at the same time point showed 50% protective doses of 10.8 mg/kg for 304, 200 mg/kg for 426, and 2.1 mg/kg for 427. We conclude that isomer 427 is five times as potent, whereas 426 is 1/50th as potent as 304 in these experimental mycoses.

Combined therapy with fluconazole and flucytosine in murine cryptococcal meningitis.

To assess the possible beneficial effects of combined therapy (fluconazole and flucytosine) in the treatment of cryptococcal meningitis in the immunocompromised host, we compared therapy with fluconazole and flucytosine, individually and combined, in the experimental murine model. BALB/c athymic (nu/nu) mice were infected intracerebrally with 150 to 300 CFU of Cryptococcus neoformans. In mortality studies, treatment was initiated 24 h postinfection and continued for 10 to 14 days with either fluconazole (1 to 15 mg/kg of body weight per day), flucytosine (60 to 120 mg/kg/8 h), both drugs, or 0.3% Noble agar (control). Combined therapy delayed mortality significantly when compared with controls and single-drug regimens. This was observed over a broad range of doses. Quantitative determinations of CFU in brain tissue demonstrated a significantly lower burden of C. neoformans in mice receiving combined therapy. The results indicate that combined therapy with fluconazole and flucytosine is superior to single-drug therapy.

Components of image intensive diagnosis. Codifying visual features for effusion cytology.

Components of visual assessment in the diagnosis of effusions were analyzed using relative operating characteristic. Diagnostic performance in the assessment of malignancy and the specification of metastatic origin was measured for two expert cytologists. The component of performance attributable to feature interpretation was measured in protocols which minimized the effects of clinical information and visual search in the decision process. Feature interpretation, as a process, contributed significantly to the evaluation of malignancy and marginally to the specification of metastatic origin. For each of these diagnostic tasks, the process of feature interpretation was codified in the construction of explicit models. The expert cytologists were asked to define a set of localized visual features that incorporate essential visual elements for diagnosis. These features were evaluated for a set of test cases, and regression models were constructed defining malignancy and metastatic origin. Relative operating characteristic analysis indicated that the predictive value of the models for diagnosis was very similar to the component of human performance attributable to feature interpretation.