437. CRにおける最適な低被曝線量撮影系の検討

Objective To compare the difference of entrance dose between CR and amorphous silocon DR system in chest imaging, and to discuss their optimum exposure dose. Methods For CR and DR, different entrance dose was measured by dosimeter in chest phantom. The value of IQFinv was analyzed by CDRAD2. 0 software. Image quality difference between CR and DR was assessed by group t-test. The relationship between image quality and entrance dose was tested by using Pearson correlation analysis. The best IQFinv values in CR and DR system were achieved via ROC curve analysis, and the exposure dose was then calculated. Results There were direct correlation values between entrance dose and the value of IQFinv in CR and DR system, respectively( r =0. 893 ,0. 848 ,P < 0. 01 ) . The linear regression equation for DR was IQFinv =0. 0050 +3. 359, and for CR was IQFinv =0. 005D + I. 651 , where D was entrance dose. The difference of IQFinv value between CR and DR was significant(t = 5. 455 ,P < 0. 05). The best IQFinv value of the two groups from ROC analysis was 3.55. Conclusions With the entrance dose increased, the detection ability of contrast-detail was elevated in the two digital radiography systems. With equal entrance dose, the detection ability of DR in contrast-detail was superior to CR. With equal image quality, DR obviously decreased the radiation dose to the patients. Key words: Digital radiography; Image quality; Exposure dose; Quality control

OPC (Optical Proximity Correction) improves the feature CD (critical dimension) uniformity and pattern fidelity in general. However, since model calibration only takes CD measurements at optimum exposure dose and best focus condition, the correction result may not be desirable at non-optimum conditions due to significant sub-resolution process distortion. Certain specific patterns are prone to bridging or pinching (we refer this type of location as hotspot in this paper) when process drifts a little from optimum condition. Simulation based full-chip verification became the method of choice for capturing hotspots on post-OPC layouts prior to mask tape-out to save development time and cost. In this paper, a complete simulation and analysis flow using SiVL was experimented to capture hotspots for a 100nm node process. Calibrated process model and multiple optical models with different focus/threshold conditions were applied for simulation. The method and effectiveness of filtering and analyzing fatal errors from output error database was discussed. The analysis results were then correlated to actual wafer printing. A good match between prediction and experiment was found.

Induction of an adaptive survival response in B6C3F1 mice exposed to whole-body irradiation by low doses of X-rays (priming exposure) then to high doses of X-rays (challenge exposure) was examined. The adaptive survival response was determined by comparing the cloning efficiency of low dose-irradiated spleen T-lymphocytes to that of unprimed controls. Maximal expression of the adaptive survival response induced by exposure to low doses of X-rays occurred 7 hours after the priming exposure. The optimal low dose range for the induction of the adaptive survival response was 0.05-0.1 Gy. Thus, low dose X-irradiation induces the adaptive response in spleen T-lymphocytes of B6C3F1 mice as assessed by survival. The duration of this response is short, and there is an optimal low dose range. The Dq value for the primed cells was somewhat larger than that for the unprimed ones. Low dose exposure may enhance the capacity of spleen cells for repair during priming.

We provide here a user-friendly guide to find the optimumi-line (365 nm) photolithographic exposure dose of an arbitrary thickness of SU-8 on various substrate materials and thin film coatings used in MEMS, microsystems and microelectronics technologies: semiconductors, 2D materials (graphene and MoS2) plastics, glass, metals and ceramics.

Although many in vitro chemosensitivity tests for anticancer agents have been reported, no scientific assessment of the optimum exposure time and dose of anticancer drugs for such tests has been established. We assessed the cytotoxicity of 4 anticancer agents (CDDP, CBDCA, ADM, MMC) by analyzing the relationships between the IC50 values and the drug exposure time in a study using PC-14 cells. The clinical AUC (Area Under the Curve) of each drug was compared with the dose giving 50% inhibition of the control level for cell growth (IC50) in a conventional MTT assay (C-MTT). A modified MTT assay, which involved washing out of the drugs and additional incubation (M-MTT) and a HTCA (Human Tumor Clonogenic Assay) was also carried out with PC-9 and PC-14 cells. The results suggested that all of 4 anticancer drugs were AUC-dependent agents. The HTCA was considered to be the assay giving results closest to the doses effective in clinical practice among the 3 assays tested, while the C-MTT gave a much higher AUC than the clinical AUC. It is suggested the reason is that in the C-MTT all the cells are viable at the end of drug exposure. Thus, not only viable cells with the potential of proliferate but also those without this potential are included in the results. On the other hand, viable cells with a proliferative potential are better assessed by the M-MTT, which has an additional incubation time. This study indicated that the C-MTT was unsuitable in vitro chemosensitivity tests for new AUC-dependent drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticosteroids are currently used routinely in the management of acute severe asthma. The optimal dose and route of administration continues to be debated. Some investigators have reported a greater benefit of higher doses of corticosteroids in the management of severe asthma, while others have not. To determine whether higher doses of systemic corticosteroids (oral, intravenous or intramuscular) are more effective than lower doses in the management of patients with acute severe asthma requiring hospital admission. Randomised controlled trials were identified from the Cochrane Airways Group Asthma Register. In addition, primary authors and content experts were contacted to identify eligible studies. Bibliographies from included studies, known reviews and texts were also searched. Studies were selected for inclusion in the review if they met the following broad inclusion criteria: described as randomised controlled trials, included patients with acute severe asthma, compared different doses of corticosteroids (any route) in 2 or more treatment arms, and had a minimum period of follow up of 24 hours. Two reviewers independently assessed the studies for inclusion and disagreement was resolved by third party adjudication. Data were extracted independently by two reviewers if the authors were unable to verify the validity of information. Missing data were obtained from authors or calculated from other data presented in the paper. The data were analysed as weighted mean differences (WMD) for primary pulmonary function outcomes using a fixed effects model. For the purposes of the review, three broad categories of corticosteroid dose (equivalent dose of methylprednisolone in 24 hours) were defined in advance: low dose (< or = 80 mg), medium dose (> 80 mg and < or = 360 mg) and high dose (> 360 mg). There were thus 3 main comparison groups: low versus medium dose, medium versus high dose and low versus high dose. Nine trials were included; a total of 344 adult patients have been studied (96 with low dose, 85 with medium dose and 163 with high dose corticosteroids). Only 6 trials provided sufficient data for the meta-analysis. There were no clinically or statistically significant differences detected in % predicted FEV1 among comparison groups after 24, 48 or 72 hours. At 48 hours, the weighted mean difference was -3.3% predicted (95% confidence interval -12.4 to + 5.8) for the low vs medium dose comparison, -1. 9% predicted (95% CI -8.1 to + 4.3) for the medium vs high dose comparison and + 0.5% predicted (95% CI - 7.8 to + 8.8) for the low vs high dose comparison. There appeared to be no significant differences in side effects or rates of respiratory failure among the varying doses of corticosteroids. No differences were identified among the different doses of corticosteroids in acute asthma requiring hospital admission. Low dose corticosteroids (< or = 80 mg/day of methylprednisolone or < or = 400 mg/day of hydrocortisone) appear to be adequate in the initial management of these adult patients. Higher doses do not appear to offer a therapeutic advantage.

Back to table of contents Previous article Next article Letter to the EditorFull AccessOptimal Risperidone Dose in Drug-Naive, First-Episode SchizophreniaVASSILIS P. KONTAXAKIS, , M.D., BEATA J. HAVAKI-KONTAXAKI, , M.D., SOPHIA S. STAMOULI, , M.D., and GEORGE N. CHRISTODOULOU, , M.D., F.I.C.P.M., F.R.C.PSYCH., VASSILIS P. KONTAXAKISSearch for more papers by this author, , M.D., BEATA J. HAVAKI-KONTAXAKISearch for more papers by this author, , M.D., SOPHIA S. STAMOULISearch for more papers by this author, , M.D., and GEORGE N. CHRISTODOULOUSearch for more papers by this author, , M.D., F.I.C.P.M., F.R.C.PSYCH., Athens, GreecePublished Online:1 Jul 2000https://doi.org/10.1176/appi.ajp.157.7.1178-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail An optimal therapeutic dose of a drug should be considered the dose at which a patient has a significant symptom reduction without unwanted side effects. Risperidone, a novel antipsychotic, is marketed with the suggestion of a rapid titration schedule (target dose of 6 mg/day by the third day) (1). However, recently a slower dose increase has been encouraged (1, 2). There is evidence that many patients (i.e., elderly patients, children, drug-naive patients) are sensitive to antipsychotic medication and need low therapeutic doses. To our knowledge, no information exists regarding the optimal risperidone dose in drug-naive, first-episode schizophrenia. The aim of our study was to provide this information.Our study group consisted of 17 drug-naive patients with first-episode schizophrenia (per DSM-IV criteria): 12 women and five men, with a mean age of 28.6 years (SD=5.6), consecutively admitted to Eginition Hospital, University of Athens, from April 1998 to March 1999. Written informed consent was obtained from the subjects and their relatives.All patients were openly treated with risperidone, given once daily in the evening, according to standard guidelines. Doses were gradually increased during an 8-week trial period (increased 1 mg/day per week for the first 3 weeks). Diazepam (mean=13.30 mg/day, SD=6.23) was co-administered to nine patients for agitation, anxiety, or insomnia. The patients’ psychopathology was assessed at baseline (drug-naive state), biweekly, and at endpoint by using the Positive and Negative Syndrome Scale (3). The optimal risperidone dose was defined as the dose at which either symptoms were reduced (at least 20% from baseline) or extrapyramidal side effects emerged. To assess improvement, we calculated the percentage of symptomatic change on the Positive and Negative Syndrome Scale, adjusted for minimum baseline ratings. The mean optimal daily risperidone dose was 2.70 mg/day (SD=0.89). All patients reached their optimal dose before developing extrapyramidal side effects. Four patients developed parkinsonism, and one developed akathisia at a mean daily risperidone dose of 5.20 mg/day (SD=1.60). Thirteen patients (76%) achieved an optimal response with a risperidone dose of up to 3 mg/day, with an average 60% (SD=21%) improvement in total Positive and Negative Syndrome Scale score at the end of the 8-week trial period. Four patients (24%) reached an optimal dose of 4–5 mg/day, with a mean 45% (SD=28%) improvement. None of the patients achieved optimal response at doses higher than 6 mg/day.Although confirmation is needed with the use of larger patient groups, this study’s findings suggest that “low and slow” increases of risperidone doses for treating drug-naive patients with first-episode schizophrenia are sufficient to minimize the risk of unwanted extrapyramidal side effects and reduce the risk of noncompliance with treatment.

The issue of determining likely outcomes after low dose exposure to radiation is complex and controversial. Currently, the linear no-threshold (LNT) model is used to justify the linear extrapolation of (adverse) outcomes from high doses, where effects are clearly seen, to low doses, where effects are very difficult to detect and even more difficult to ascribe to the measured radiation exposure. Among the factors hindering the development of a more precise system are the lack of reliable predictors of system health. While biomarkers indicating the health of individual cells or organisms exist, they fail at low doses due to the complexity of cause-effect relationships and the multiple factors contributing "stress" to the system as a whole (whether "whole" is a whole organism, a population or an ecosystem). Approaches to capture this complexity include adverse outcome pathway (AOP) analysis, which looks at multiple levels of organization from gene to ecosystem. In this commentary, we discuss the role of non-targeted effects (NTE) such as genomic instability and bystander effects. These mechanisms involve transmission of information between different levels of organization. In the case of BE, signals from exposed to unexposed cells or organisms coordinate response at higher levels of organization, permitting population responses to radiation to be identified and, potentially, mitigated. Genomic instability is more complex as it involves not only signaling but also trans-generational transmission of genetic or epigenetic changes and may lead to long-term adaptive evolution. GI may also be involved in memory or legacy effects, which contribute a further component to the dose effect measured in legacy sites. Our recent analysis of the contributions of memory and legacy effects to the total effect using data sets from Chernobyl and Fukushima (voles, birds and butterflies) suggests this type of analysis may help reduce uncertainties over laboratory-to-field extrapolations. A focus on novel but widespread NTE mechanistic pathways may open the way to successful prophylaxis and development of new biomarkers for better risk assessment after low dose exposures.

This study aimed to develop a silk fibroin (SF)-film for the treatment of chronic diabetic wounds. Silk fibroin was purified through a newly developed heating degumming (HD) process and casted on a hydrophobic surface to form SF-films. The process allowed the fabricated film to achieve a 42% increase in transparency and a 32% higher proliferation rate for BALB/3T3 fibroblasts compared to that obtained by conventional alkaline degumming treatment. Fourier transform infrared analysis demonstrated that secondary structure was retained in both HD- and alkaline degumming-derived SF preparations, although the crystallinity of beta-sheet in SF-film after the HD processing was slightly increased. This study also investigated whether conjugating insulin-like growth factor-1 (IGF-1) would promote diabetic wound healing and what the optimal dosage is. Using BALB/3T3 cells grown in hyperglycemic medium as a model, it was demonstrated that the optimal IGF-1 dosage to promote the cell growth was approximately 0.65 pmol. Further analysis of wound healing in a diabetic mouse model indicated that SF-film loaded with 3.25 pmol of IGF-1 showed significantly superior wound closure, a 13% increase at the 13th day after treatment relative to treatment with 65 pmol of free IGF-1. Improvement in diabetic wound healing was exerted synergistically by SF-film and IGF-1, as reflected by parameters including levels of re-epithelialization, epithelial tissue area, and angiogenesis. Finally, IGF-1 increased the epithelial tissue area and micro-vessel formation in a dose-dependent manner in a low dosage range (3.25 pmol) when loaded to SF-films. Together, these results strongly suggest that SF-film produced using HD and loaded with a low dosage of IGF-1 is a promising dressing for diabetic wound therapy.

Purpose: Cellular damage due to low dose of γ-radiation (≤0.1 Gy) is generally extrapolated from observing the effects at higher doses. These estimations are not accurate. This has led to uncertainties while assessing the radiation risk factors at low doses. Although there are reports on the radiation induced adaptive response, the mechanism of action is not fully elucidated, leading to the uncertainties. One of the outcomes of low dose radiation exposure is believed to be an adaptive response. The mechanism of adaptive response is not fully understood. Therefore, the study was undertaken to understand the role of hypoxia inducible factor (HIF) on radiation induced adaptive response.Materials and methods: Human breast cancer cell line MCF-7 cells pre-exposed to low dose γ-radiation (0.1 Gy; priming dose) were exposed to 2 Gy (challenging dose) 8 h after the priming dose and studied for the adaptive response. Cell death was measured by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was measured by fluorescence-activated cell sorting analysis. DNA damage was measured by alkaline comet assay. HIF transcription activity was assayed using transiently transfected plasmid having HIF consensus sequence and luciferase as the reporter gene.Results: Cells when exposed to 0.1 Gy priming dose 8 h prior to the higher dose (2 Gy; challenging dose) results in lower amount of radiation induced damages compared to the cells exposed to 2 Gy alone. Cobalt chloride treatment in place of priming dose also results in the protection to cells when exposed to challenging dose. There was up-regulation of HIF activity when cells were exposed to priming dose, indicating the role of HIF in radiation induced response.Conclusion: Results indicate the γ-radiation induced adaptive response. One of the mechanism proposed is up-regulation of HIF after low dose exposure, which protects the cells from damages when they are exposed to challenging dose of 2 Gy radiation.

Radiological protection is based on the assumption that any additional exposure to ionizing radiation produces an increased risk of stochastic adverse health effects. The ICRP has adopted linear no-threshold (LNT) dose-response relationships to derive health risks associated with low doses of radiation and this implies that the risks of cancer and hereditary effects are directly proportional to the dose received, no matter how small the dose. The LNT assumption has been criticised over the years both by those who consider that it underestimates the risk and by those who believe that it is overly conservative. A few years ago, most of the pressure on ICRP came from those who believed that the risks per unit dose adopted at low doses were too small, but in recent years the pressure has been coming from the opposite direction. Strictly speaking, ICRP feels that the most likely form of the dose-response relationship for low LET radiation is linear-quadratic (i.e. sub-linear at low doses), and for cancer they approximate this by two linear relations, that for the low dose region having a slope (risk per unit dose) half of that for the high dose region, represented by a DDREF of 2. Nevertheless, there are those (particularly in the US and France) who argue that there is no direct evidence for stochastic effects being produced by low doses of radiation, and that the appropriate dose-response relationship has a threshold dose below which no risk to health exists, or even that low doses of radiation are beneficial (`radiation hormesis').

The past and current trends in determining the DNA-damaging and carcinogenicity potential of environmental toxicants rely largely on treatment of rodents with single or multiple bolus doses. To simulate the human scenario where the exposure is generally continuous to low doses, we have developed polymeric implants embedded with carcinogens. When grafted subcutaneously, polymeric implants provide continuous (“24/7”) low dose exposure. In this study we report the effects of sustained low doses of a highly potent environmental carcinogen, dibenzo[a,l]pyrene (DBP) on DNA adduct accumulation. Different size DBP implants (10 – 20 mm long, 1.4 – 2.4 mm dia; 5% DBP load) were tested first in a pilot study using female A/J mice to optimize the implant surface area. Two 20-mm implants (1.4 mm dia), which produced maximal lung DNA adducts, were used subsequently. Groups of female A/J mice (n = 4 – 6) were grafted with sham or DBP implants. For comparison, animals were also treated in parallel with a bolus carcinogenic dose of DBP intraperitoneally (6 mg/kg) or vehicle alone. Animals from both the treatment groups were euthanized at different time intervals and selected tissues were collected. Analysis of the target (lung) DNA adducts by 32P-postlabeling showed qualitative identical adduct patterns by the two routes of administration; the sham treatments showed no detectable adducts. As expected, the bolus dose treatment resulted in higher DNA adducts (in adducts /109 nucleotides) (72 ± 18) compared with the implant group (33 ± 17) one week post-treatment. However, 3 weeks later, adduct levels in the implant group increased (54 ± 17) but a significant declined occurred in the i.p treatment group (19 ± 13). The adduct levels after 4 weeks in the implant group (66 ± 19) were somewhat higher than the 3 week group, suggesting that the adduct levels plateaued. The steady accumulation of DNA adducts was consistent with continuous release of DBP from the implant (about 10 µg/day based on in vitro release). The study is ongoing to determine if the low-dose continuous exposure which provides steady accumulation of DNA adducts in the target tissue will be tumorigenic. In summary, the steady-state adduct level reflect human exposure scenario and this approach will be ideal to determine both carcinogenicity and biological/pathological changes due to low-dose exposure as well as for screening potential chemopreventive agents. This exposure system has been used to determine efficacy of chemopreventive agents (accompanying abstracts by Aqil et al.; Gupta et al.) (Supported from CA-118114, KLCRP and Agnes Brown Duggan Endowment). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5557. doi:10.1158/1538-7445.AM2011-5557

An extensive clinical and epidemiological study of workers engaged in the manufacturing and formulation of aldrin and dieldrin, the Pernis study, provides occupational hygiene and biological monitoring data on individual exposures over the years of employment and provides the opportunity to investigate dose response relationships for these chemicals. The human epide miological mortality data on these workers, who were exposed to fairly substan tial lifetime average daily doses of aldrin and dieldrin, suggest that low dose exposures do not significantly increase human mortality and may even de crease the human mortality hazard rate. While hormesis from low dose expo sure to aldrin and dieldrin is not statistically significant, it is observed in the raw data and in the best fitting dose response models. The decrease in risk suggests increased survival time at low doses of aldrin and dieldrin. Using an upper bound on cancer potency based on mouse liver tumors, the U.S. Environmental Protection Agency (EPA) estimated that lifetime average daily doses (LADDs) of 0.0000625 and 0.00625 µg/kg body weight/day would correspond to increased cancer risks of 0.000001 and 0.0001, respectively. However, the best estimate from the Pernis epidemiological data is that LADDs of 0.0000625 and 0.00625 µg/kg body weight/day correspond to no increase in cancer risk and a decrease in the probability of mortality from all causes by the age of 70 years. At low doses of aldrin and dieldrin, the estimated decrease in mortality in a reference period of 70 years is more than 1000 times larger than the U.S. EPA's upper bound on the increase in the lifetime probability of cancer.

Applying ADA/ANSI Standard 1094: Impact of image adjustments and display device on subjective assessments

Is the Low-Thalidomide Dose MPT Regimen Beneficial?