The Cingulate Island score (CIScore) is useful index for differentiating between dementia with Lewy body (DLB) and Alzheimer’s disease (AD) using regional cerebral blood flow (rCBF) SPECT. The Z score standing for medial temporal lobe (MTL) atrophy and the ratio of Z score between dorsal brain stem (DBS) to MTL are useful indices for differentiating between DLB and AD using MRI with VSRAD. The current study investigated the diagnostic ability by the combined use of rCBF SPECT and MRI in the differentiation between AD and DLB. In cases with 42 AD and 28 DLB undertaken Tc-99m-ECD SPECT and MRI, we analyzed differential diagnostic ability between AD and DLB among following conditions by single or combined settings. Namely, they were (1) the CIScore as a parameter of rCBF SPECT (DLB ≦ 0.25), (2) Z score value of MTL atrophy (DLB ≦ 2.05), (3) the ratio of Z score of DBS to medial temporal gray matter as a parameter of brain atrophy using VSRAD (DLB ≧ 0.38). Also, we analyzed them both including and omitting the elderly (over 75 years old). The accuracy of differential diagnosis in this condition was 74

PURPOSE:We evaluated the reproducibility calculating volume-based FDG-PET/CT parameters, i.e., metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in soft tissue tumors.MATERIALS AND METHODS:Fifty-three cases with soft tissue tumors were analyzed retrospectively. The conditions determining the lower limit of MTV were fixed value SUV 2.5 or 30% of SUVmax. To investigate the agreement of the measurements by two radiologists, %difference, the correlation coefficients and Bland-Altman plot were analyzed. We compared these parameters in both intra- and inter-operator for evaluating the agreement in the measurements.RESULTS:The values of % difference were excellent, 0.2-3.5%, in the intra-operator in all calculated volume-based parameters. In both inter- and intra-operator analysis, the values of % differences were lower in the parameters calculated by SUV 2.5 fixed value as a lower threshold compared with those calculated by 30% of SUVmax as a lower threshold. The correlation coefficient in MTV30% for inter-operator were 0.84 or 0.87, those were lower than values by the intra-operator evaluation. Nevertheless, the correlation coefficients were higher than 0.84 in every parameter. Particularly, correlation coefficient in the parameters calculated by SUV 2.5 fixed value was better than those calculated by 30% of SUVmax. The Bland-Altman plot analysis showed good agreement for all parameters, particularly in the intra-operator examinations. However, in the inter-operator study, some variances were noted in every condition.CONCLUSION:In conclusion, the reproducibility of measuring volume-based FDG-PET/CT parameters of soft tissue tumors was good, particularly, in the measurement by fixed lower limit value SUV 2.5 in the intra-operator.

Introduction Deep brain stimulation (DBS) is an effective treatment for advanced Parkinson’s disease (PD) with the targeting bilateral subthalamic nucleus or globus pallidus internus (STN or GPi-DBS). So far, detailed studies on the efficacy of unilateral STN-DBS for motor symptoms have been reported, but few studies have been conducted on unilateral GPi-DBS. Materials and Methods Seventeen patients with Parkinson’s disease (PwPD) who underwent unilateral GPi-DBS were selected. We conducted comparison analyses between scores obtained 6–42 months pre- and postoperatively using the following measurement tools: the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III, the Hoehn and Yahr stage, the presence/absence of dyskinesia, Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Geriatric Depression Scale (GDS), levodopa equivalent dose (LED), and cerebral blood flow by single photon emission computed tomography (SPECT). Patient backgrounds were compared between four cohorts with favorable (good responders, ≥50% improvement) and unfavorable (poor responders, <50% improvement) postoperative outcome. Results Significant improvement was observed postoperatively in the following: total MDS-UPDRS Part III scores during the off period, contralateral scores, ipsilateral scores, and axial scores. Similarly, the Hoehn and Yahr stages during the off period, and GDS also showed significant decrease. In contrast, LED, MMSE, and FAB remained unchanged while the number of patients who scored positive for dyskinesia decreased by 40%. Abnormal cerebral blood flow preoperatively seen in the cerebral cortex had normalized in the total score-based good responder cohort. In the ipsilateral score-based good responder cohort, cerebral blood flow increased in the contralateral frontal lobe including in the premotor cortex, contralateral to the DBS. Compared to the poor responders, postoperative good responders demonstrated significantly higher preoperative MMSE scores. Discussion Unilateral GPi-DBS therapy was effective in improving contralateral, ipsilateral, and axial motor symptoms of patients with advanced PD; in particular, it was found to be especially beneficial in PwPD whose cognitive function was unimpaired; the treatment efficacy rivaled that of bilateral counterparts up till at least 6 months postoperatively. Finally, normalization of preoperative abnormalities in cerebral blood flow and increased cerebral blood flow in the contralateral frontal lobe indicated the beneficial potential of this therapy on ipsilateral motor symptoms.

1645 Background: Right ventricular failure is one of serious complication due to chronic respiratory failure. Although the lung transplantation is curative surgical methods for chronic respiratory dysfunction, few studies have reported about the course of right ventricular functional images before and after lung transplantation. In the present study, we evaluated the alteration of right ventricular function by monitoring FDG uptake of right ventricular myocardium before and after lung transplantation.\n Methods: Twenty patients who were undergone lung transplantation for the curative therapy of chronic refractory pulmonary failure were analyzed retrospectively. All patients were done FDG-PETCT before and after lung transplantation within 2 years. In the quantitative analyzes by on FDG-PET CT, both SUVmax of both ventricular myocardium and the ratios of SUV max between right ventricle myocardium and left ventricle myocardium (R/L ratio) were obtained. The data of 15 normal controls data were compared with patient9s data. Results: In the visual analysis, 6 of 20 patients showed increased right ventricular myocardial uptake. All these cases changed to be normal myocardial uptake after lung transplantation. In the semi-quantitative analysis, in the patients before the transplantation, the mean value of SUVmax in the right ventricle myocardium was 2.92±0.43 and the R/L ratio were 0.67±0.24. After lung transplantation, the mean value of SUVmax in the right ventricle myocardium was 2.04±1.27 and the R/L ratio was 0.53±0.14. They were significantly lower than those of pre-transplantation values. In the normal control, the value of SUVmax in the right ventricle myocardium was 1.96±0.75 and the value of R/L ratio was 0.52±0.28. Although both indexes of pre-transplantation patient’s values were significantly higher than those of normal controls values, there were no statistical significance between post-transplantation patient’s values and normal control values.\n Conclusions: In some cases with chronic respiratory failure, increased right ventricular myocardial FDG uptake was noted, which uptake decreased after lung transplantation. FDG-PET will be useful in monitoring the right ventricular overload in the chronic respiratory failure which can be relieved by pulmonary transplantation. \nClinical implication: Myocardial FDG-PET/CT examinations before and after the pulmonary transplantation will be useful for diagnosing right ventricular overload and its therapeutic-effect by lung transplantation.

Purpose The Cingulate Island Sign score (CIScore) by rCBF SPECT is used in the differentiation between Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) but has some false-positive AD cases. To resolve the problem, we developed new differential diagnosing method incorporating occipital lobe and para-hippocampal rCBF. Materials and methods In 27 DLB and 31 AD cases undertaken Tc-99 m-ECD SPECT, we evaluated the meanZscore in the bilateral superior, middle, inferior occipital gyri, cuneus, amygdala, hippocampus, and para-hippocampus. One criterion of DLB was defined as the case with CIScore lower than 0.27. The other criteria were the cases of following either or both two conditions were satisfied. (1) The number of occipital gyri with meanZscore higher than 1 is three or more. (2) The number of hippocampal regions with meanZscore higher than 1 is one or less. We compared the differential diagnostic ability among these four criterions. Results The diagnostic accuracy by CIscore was 69% and that of the occipital gyri analysis 84%, para-hippocampal regions analysis 76% and combined occipital gyri and para-hippocampal regions analysis 93%. Conclusion The new method by combined rCBF analysis of occipital gyri and para-hippocampal regions showed best diagnostic ability in differentiating DLB from AD.

1487 Objectives: The unilateral lung transplantation is one of curative surgical methods for chronic respiratory dysfunction. However, few studies have reported about the course of respiratory function in the residual non-transplanted original lung. We evaluated the serial change of both transplanted lung and non-transplanted original lung function before and after unilateral lung transplantation using scintigraphy and CT volumetric. Methods: We analyzed retrospectively twenty-two lung patients who were undergone unilateral lung transplantation for the fundamental therapy of refractory pulmonary fibrosis. All patients were done both Tc-99m MAA perfusion scintigraphy and Kr-81m lung ventilation scintigraphy before and after lung transplantation. At the same time CT volumetric were done in each patient. After the operation, these examinations were evaluated annually within 2 years. On the both anterior and posterior planar images, the count ratios of non-transplanted lung to the transplanted lung (N/T ratio) were obtained. The CT volumetric study was also performed and the lung volume ratios of the non-transplanted lung to the transplanted lung (N/T volume ratio) were obtained using ZIO STATION (Zio software, Tokyo, Japan). Results: Before the transplantation, the mean values of N/T ratio were 0.89 on the anterior images and 0.91 on the posterior images. On the CT volumetric, the mean values of N/T volume ratio was 0.88. After the transplantation the mean value of N/T ratio was 0.43 and 0.42 after 1 year and the 0.29 and 0.31 after 2 year. The mean values of N/T volume ratio were 0.2 after 1 year and 0.1 after 2 year. After the unilateral lung transplantation, it was confirmed that both ventilation and perfusion remained in the non-transplanted lung despite the remarkable volume loss, but they declined over time. Conclusions: After the unilateral lung transplantation, both perfusion and ventilation were gradually and continuously decreased in non-transplanted lung. Both Tc-99m MAA perfusion scintigraphy and Kr-81m lung ventilation scintigraphy was useful tool for monitoring respiratory function in patients who would be undergone unilateral lung transplantation.

The aim of this multicenter prospective study was to compare the sensitivity of 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) with that of 67Ga single photon emission computed tomography (SPECT) for the identification of the site of greatest importance for the final diagnosis of the cause of fever of unknown origin (FUO). The study participants consisted of patients with an axillary temperature ≥ 38.0 °C on ≥ 2 occasions within 1 week, with repeated episodes for ≥ 2 weeks prior to providing consent, and whose final diagnosis after undergoing specific examinations, including a chest-to-abdomen CT scan, was uncertain. All the patients underwent FDG-PET/CT imaging first, followed by 67Ga-SPECT imaging within 3 days. The results of the FDG-PET/CT and 67Ga-SPECT examinations were reviewed by the central image interpretation committee (CIIC), which was blinded to all other clinical information. The sensitivities of FDG-PET/CT and 67Ga-SPECT were then evaluated with regard to identifying the site of greatest importance for a final diagnosis of the cause of the fever as decided by the patient’s attending physician. The clinical impacts (four grades) of FDG-PET/CT and 67Ga-SPECT on the final diagnosis were evaluated. A total of 149 subjects were enrolled in this study between October 2014 and September 2017. No adverse events were identified among the enrolled subjects. Twenty-one subjects were excluded from the study because of deviations from the study protocol. Among the 128 remaining subjects, a final diagnosis of the disease leading to the appearance of FUO was made for 92 (71.9%) subjects. The final diagnoses in these 92 cases were classified into four groups: noninfectious inflammatory disease (52 cases); infectious disease (31 cases), malignancy (six cases); and other (three cases). These 92 subjects were eligible for inclusion in the study’s analysis, but one case did not meet the PET/CT image acquisition criteria; thus, PET/CT results were analyzed for 91 cases. According to the patient-based assessments, the sensitivity of FDG-PET/CT (45%, 95% CI 33.1–58.2%) was significantly higher than that for 67Ga-SPECT (25%, 95% CI 15.5–37.5%) (P = 0.0029). The clinical impact of FDG-PET/CT (91%) was also significantly higher than that for 67Ga-SPECT (57%, P < 0.001). FDG-PET/CT showed a superior sensitivity to 67Ga-SPECT for the identification of the site of greatest importance for the final diagnosis of the cause of FUO.

Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are two major types of dementia. Due to shared signs and symptoms, accurate diagnosis of these dementia subtypes is a clinical challenge. We assessed the sensitivity and specificity of the combined use of neuropsychological testing and brain imaging data for the differential diagnosis of these conditions. The study population included 77 patients with either AD or DLB. Ala score was calculated from Mini-Mental State Exam subscores, and the cingulate island sign score (CIScore) was obtained from image analysis of brain perfusion single-photon emission computed tomography. Correlation between Ala score and CIScore values was observed in the subgroup of patients aged ≤79 years (r = 0.485, P = 0.002), and the scatter plot revealed that 70% of DLB patients were within the range of cut-off values for DLB. In the group aged ≥80 years, there was poor correlation between the Ala and CIScores (r = 0.285, P = 0.083), the average CIScore exceeded the cut-off value, and the scatter plot showed lower sensitivity, illustrating the challenge of discriminating AD from DLB in an older patient population. The concurrent use of Ala score and CIScore enhanced the specificity and the area under the curve in both subgroups, indicating the improved ability of these tests to aid in the differential diagnosis of AD from DLB. Our findings suggest that the use of these methodologies in routine medical practice may increase the sensitivity and specificity of the diagnosis of dementia subtypes.

Recent studies reported that high doses of short-acting loop diuretics are associated with poor outcomes in patients with heart failure (HF). Short-acting loop diuretics have been shown to activate the renin-angiotensin system (RAS) and have no favorable effects on cardiac sympathetic nervous system (SNS) activity. The goal of this study is to investigate the relationship between daily doses of furosemide and the outcomes of patients with left ventricular dysfunction (LVD) from the viewpoint of cardiac SNS abnormalities using iodine-123-labeled metaiodobenzylguanidine ((123)l-MIBG) myocardial scintigraphy. We enrolled 137 hospitalized patients (62.5 +/- 14.2 years old, 103 men) with LVEF < 45% who underwent (123)l-MIBG myocardial scintigraphy. A delayed heart-to-mediastinum ratio (delayed HMR) was assessed using (123)l-MIBG scintigraphy. Cardiac events were defined as cardiac death or re-hospitalization due to the deterioration of HF. Cox proportional hazard analysis was used to identify predictors of cardiac events. Cardiac events occurred in 57 patients in a follow-up period of 33.1 +/- 30 months. In a multivariate Cox proportional hazard analysis, delayed HMR and furosemide doses were identified as independent predictors of cardiac events (P = .0042, P = .033, respectively). Inverse probability of treatment weighting Cox modeling showed that the use of furosemide (>= 40 mg /day) was associated with cardiac events with a hazard ratio of 1.96 (P = .003). In the Kaplan-Mayer analysis, the cardiac event-free survival rate was significantly lower in patients treated with high doses of furosemide (>= 60 mg/day vs 40-60 mg/day vs <40 mg/day, the Log-rank test P < .0001). In a receiver-operating characteristic (ROC) analysis, the cut-off value for cardiac events was 40 mg/day of furosemide. The cardiac event-free rate was significantly lower in patients with delayed HMR <1.8 (median value) and receiving furosemide >= 40 mg/day than in other patients (the Log-rank test P < .0001). Significant differences in cardiac event rates according to furosemide doses among patients with delayed HMR <1.8 were observed among patients without beta-blocker therapy (P = .001), but not among those with beta-blocker therapy (P = .127). The present results indicate that a relationship exists between higher doses of furosemide and poor outcomes. The prognosis of HF patients with severe cardiac SNS abnormalities receiving high-dose short-acting loop diuretics is poor.

287 Purpose: Fractal dimension (D value) is an index of self-similarity and is considered to be useful indicator for homogeneity of tumor FDG uptake. There is a possibility that therapeutic effect can be divided into subgroups from the change of D value before and after cancer treatment. The study was done to investigate the usefulness of fractal analysis in FDG-PET/CT for diagnosing the therapeutic effect in non-small cell lung cancer (NSCLC). Materials and Methods: Seventy-two patients with NSCLC (47men and 25 women, age 59-84, mean age 65.5±10.7) were analyzed retrospectively. FDG-PET/CT examinations were done in the all patient before and after chemotherapies of various regimens. The chemotherapeutic effects were evaluated based on the change of FDG-uptake by PERCIST criterion. We also evaluated chemotherapeutic effects by the change of D values obtained by two kinds of Fractal analysis (Box counting method and Pixel counting method) on the FDG-PET MIP images. In the Fractal analysis, we calculated ΔD which is determined by the formula (D value of post-therapy) / (D value of pre-therapy) as parameters for evaluating the chemotherapeutic effect. Finally, we compared ΔD values among PMR, SMD and PMD group diagnosed by PERCIST criteria. Results: The values of ΔD were significantly higher in the PMD group compared with those in the PMR group. Namely, 1.41 vs. 0.83 by the evaluation with Box counting method and 2.78 vs. 0.84 by the evaluation with Pixel counting method. After chemotherapy, most of the PMR cases came to show the inhomogeneous FDG uptake and the most of PMD cases came to show the homogeneous FDG uptake. As for SMD group they showed various pattern and the values of ΔD were 0.96 by Box counting method and 2.38 by Pixel counting method. The association between the change of glucose metabolism and the change of homogeneity in FDG accumulation was suggested. Conclusions: In NSCLC before and after cancer therapy, fractal dimension decreased in the PMR group and tended to increase in PMD group. The change of fractal dimension (ΔD) by Box counting method or Pixel counting method in FDG uptake will be supplemental useful parameter for diagnosing cancer therapeutic effect in NSCLC

Purpose The International Study Group of Liver Surgery (ISGLS) proposed a definition and grading system for posthepatectomy liver failure (PHLF). We evaluated the usefulness of residual liver function estimation using 99mTc-galactosyl human serum albumin (99mTc-GSA) for the prediction of PHLF. Methods Patients with liver tumors (n = 136) and scheduled for hepatectomy underwent 99mTc-GSA scintigraphy. Based on their imaging data, the maximal GSA removal rate (GSA-Rmax)was calculated using multicompartment analysis. We also calculated GSA-Rmax in the predicted residual liver (GSA-RL) whose volume was determined on computed tomography (CT) scans. We compared the age, sex, 15-minute indocyanine green retention rate; albumin, bilirubin, hyaluronic acid, and type 4 collagen levels; the Child-Pugh classification; residual liver volume; residual liver percentage; GSA-Rmax; and GSA-RL in patients with and without PHLF. Univariate and multivariate logistic analyses were used for statistical assessments. Results Of 136 patients, 17 (12.5%) met the ISGLS criteria for PHLF (ISGLS-PHLF). There was a statistically significant difference in the age, albumin level, Child-Pugh classification, residual liver volume, residual liver percentage, GSA-Rmax, and GSA-RL between patients with and without PHLF. Based on multivariate analysis, GSA-RL and the residual liver volume were significant independent predictors of ISGLS-PHLF (P = 0.004 and P = 0.038, respectively). The odds ratio was 149423 for GSA-RL and 1.003 for the residual liver volume. Conclusions GSA-RL calculated using 99mTc-GSA scintigraphy was the most useful independent predictor for ISGLS-PHLF.

Introductions:[N-methyl-C-11]α-Methylaminoisobutyric acid (MeAIB) is an artificial amino acid radiotracer used for PET study, which is metabolically stable in vivo. In addition, MeAIB is transported by system A neutral amino acid transport, which is observed ubiquitously in all types of mammalian cells. It has already been shown that MeAIB-PET is useful for malignant lymphoma, head and neck cancers, and lung tumors. However, there have been no reports evaluating the usefulness of MeAIB-PET in the diagnosis of brain tumors. The purpose of this study is to investigate the efficacy of system A amino acid transport PET imaging, MeAIB-PET, in clinical brain tumor diagnosis compared to [S-methyl-C-11]-L-methionine (MET)-PET.Methods:Thirty-one consecutive patients (male: 16, female: 15), who were suspected of having brain tumors, received both MeAIB-PET and MET-PET within a 2-week interval. All patients were classified into two groups: Group A as a benign group, which included patients who were diagnosed as low-grade astrocytoma, grade II or less, or other low-grade astrocytoma (n=12) and Group B as a malignant group, which included patients who were diagnosed as anaplastic astrocytoma, glioblastoma multiforme (GBM), or recurrent GBM despite prior surgery or chemoradiotherapy (n=19). PET imaging was performed 20 min after the IV injection of MeAIB and MET, respectively. Semiquantitative analyses of MeAIB and MET uptake using SUVmax and tumor-to-contralateral normal brain tissue (T/N) ratio were evaluated to compare these PET images. ROC analyses for the diagnostic accuracy of MeAIB-PET and MET-PET were also calculated.Results:In MeAIB-PET imaging, the SUVmax was 1.20 ± 1.29 for the benign group and 2.94 ± 1.22 for the malignant group (p < 0.005), and the T/N ratio was 3.77 ± 2.39 for the benign group and 16.83 ± 2.39 for the malignant group (p < 0.001). In MET-PET, the SUVmax was 3.01 ± 0.94 for the benign group and 4.72 ± 1.61 for the malignant group (p < 0.005), and the T/N ratio was 2.64 ± 1.40 for the benign group and 3.21 ± 1.14 for the malignant group (n.s.). For the analysis using the T/N ratio, there was a significant difference between the benign and malignant groups with MeAIB-PET with p < 0.001. The result of ROC analysis using the T/N ratio indicated a better diagnosis accuracy for MeAIB-PET for brain tumors than MET-PET (p < 0.01).Conclusions:MeAIB, a system A amino acid transport-specific radiolabeled agents, could provide better assessments for detecting malignant type brain tumors. In a differential diagnosis between low-grade and high-grade astrocytoma, MeAIB-PET is a useful diagnostic imaging tool, especially in evaluations using the T/N ratio.Clinical trial registration:This trial was registered with UMIN000032498.

Objective We retrospectively analyzed activated BAT visualization on FDG-PET/CT in patients with various conditions and TH levels to clarify the relationships between visualization of BAT on FDG-PET/CT and the effect of TH. Methods Patients who underwent clinical FDG-PET/CT were reviewed and we categorized patients into 5 groups: (i) thyroid hormone withdrawal (THW) group; (ii) recombinant human thyrotropin (rhTSH) group; (iii) hypothyroidism group; (iv) hyperthyroidism group; and (v) BAT group. A total of sixty-two FDG-PET/CT imaging studies in fifty-nine patients were performed. To compare each group, gender; age; body weight; serum TSH, FT3, and FT4 levels; and outside temperature were evaluated. Results No significant visualization of BAT was noted in any of the images in the THW, rhTSH, hypothyroidism, and hyperthyroidism groups. All patients in the BAT group were in a euthyroid state. When the BAT-negative and BAT-positive patient groups were compared, it was noted that the minimum and maximum temperature on the day of the PET study and maximum temperature of the one day before the PET study were significantly lower in BAT-positive group than in all those of other groups. Conclusions Elevated TSH condition before RIT, hyperthyroidism, or hypothyroidism did not significantly impact BAT visualization of clinical FDG-PET/CT images.

Background: A number of previous studies have shown that myocardial viability can be assessed by positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG). However, there has been no multicenter study that verified the ability of this modality for diagnosing myocardial viability in Japan. We therefore conducted a prospective one arm’s unrandomized multicenter clinical trial in order to confirm the diagnostic ability of 18F-FDG for myocardial viability. Methods: This study included patients with heart failure and impaired left ventricular function where conventional myocardial perfusion scintigraphy was not contributive for the diagnosis of myocardial viability,and assessed the diagnostic ability of 18F-FDG for myocardial viability in these patients. The diagnostic ability was determined on the basis of post-coronary vascularization improvement in myocardial wall motion in a myocardial segment with 18F-FDG uptake (i.e., positive predictive value). We also assessed the safety of 18F-FDG.Results: Out of 49 patients who received 18F-FDG administration, 30 were included in the efficacy analysis set (mean age 64.4±14.6 years; 27 men and 3 women; mean follow-up period 228.6±74.5 days). The positive predictive value of 18F-FDG (95% two-sided confidence interval) in the 30 patients of the efficacy-analysis set was 63.9% (54.6-72.5%). Moreover, the proportion of patients with improved wall motion, on a per-patient basis, was 86.7% (26 of 30 cases). As for the safety, no serious adverse events occurred and the agent was well-tolerated.Conclusions: The identification of myocardial viability by 18F-FDG will be widely beneficial in predicting improvement in myocardial wall motion after coronary revascularization. No serious safety concerns associated with the use of 18F-FDG were observed.