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23 Oct 2013: Smits MLJ, van den Hoven AF, Rosenbaum CENM, Zonnenberg BA, Lam MGEH, et al. (2013) Correction: Clinical and Laboratory Toxicity after Intra-Arterial Radioembolization with 90Y-Microspheres for Unresectable Liver Metastases. PLOS ONE 8(10): 10.1371/annotation/559e04cc-b09c-4b5c-9405-56837f6d5627. https://doi.org/10.1371/annotation/559e04cc-b09c-4b5c-9405-56837f6d5627 View correction
To investigate clinical and laboratory toxicity in patients with unresectable liver metastases, treated with yttrium-90 radioembolization (90Y-RE).
Patients with liver metastases treated with 90Y-RE, between February 1st 2009 and March 31st 2012, were included in this study. Clinical toxicity assessment was based on the reporting in patient's charts. Laboratory investigations at baseline and during a four-month follow-up were used to assess laboratory toxicity according to the Common Terminology Criteria for Adverse Events version 4.02. The occurrence of grade 3–4 laboratory toxicity was stratified according to treatment strategy (whole liver treatment in one session versus sequential sessions). Response assessment was performed at the level of target lesions, whole liver and overall response in accordance with RECIST 1.1 at 3- and 6 months post-treatment. Median time to progression (TTP) and overall survival were calculated by Kaplan-Meier analysis.
A total of 59 patients, with liver metastases from colorectal cancer (n = 30), neuroendocrine tumors (NET) (n = 6) and other primary tumors (n = 23) were included. Clinical toxicity after 90Y-RE treatment was confined to grade 1–2 events, predominantly post-embolization symptoms. No grade 3–4 clinical toxicity was observed, whereas laboratory toxicity grade 3–4 was observed in 38% of patients. Whole liver treatment in one session was not associated with increased laboratory toxicity. Three-months disease control rates for target lesions, whole liver and overall response were 35%, 21% and 19% respectively. Median TTP was 6.2 months for target lesions, 3.3 months for the whole liver and 3.0 months for overall response. Median overall survival was 8.9 months.
The risk of severe complications or grade 3–4 clinical toxicity in patients with liver metastases of various primary tumors undergoing 90Y-RE is low. In contrast, laboratory toxicity grade 3–4 can be expected to occur in more than one-third of patients without any clinical signs of radiation induced liver disease.
Citation: Smits MLJ, van den Hoven AF, Rosenbaum CENM, Zonnenberg BA, Lam MGEH, Nijsen JFW, et al. (2013) Clinical and Laboratory Toxicity after Intra-Arterial Radioembolization with 90Y-Microspheres for Unresectable Liver Metastases. PLoS ONE 8(7): e69448. https://doi.org/10.1371/journal.pone.0069448
Editor: Natarajan Aravindan, University of Oklahoma Health Sciences Center, United States of America
Received: December 27, 2012; Accepted: June 7, 2013; Published: July 24, 2013
Copyright: © 2013 Smits et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
Intra-arterial radioembolization with yttrium-90 microspheres (90Y-RE) is an increasingly applied treatment option for patients with unresectable primary or secondary hepatic malignancies, refractory to systemic therapies. The treatment consists of intra-arterial administration of microspheres tagged with or containing yttrium-90 (90Y), a radioisotope that emits high-energy beta radiation. In contrast to the normal liver parenchyma, which mainly relies on the portal vein, intrahepatic malignancies mainly depend on the hepatic artery for their blood supply. [1] As a consequence, these tumors can be selectively targeted by instillation of 90Y-microspheres in the hepatic artery.
There is growing evidence for an overall beneficial effect of 90Y-RE regarding time to progression, overall survival and quality of life in salvage patients with either primary or metastatic hepatic malignancies.[2]–[4] The effect of 90Y-RE in terms of tumor response varies widely, with disease control rates (complete response+partial response+stable disease) ranging from 56% –100%. [4] Given the wide variety in tumor response rates, great effort is put into optimal patient selection through the identification of prognostic factors for a favorable outcome after 90Y-RE.[5]–[7] Improved selection may increase the efficacy of this therapy and prevent patients from futile treatment and unnecessary toxicity.
Although minimally invasive, 90Y-RE is not without adverse effects. Common adverse effects related to 90Y-RE are symptoms of the post-embolization syndrome, comprising fatigue, nausea, vomiting, abdominal pain, loss of appetite and fever.[7]–[10] In general, these symptoms appear on the day of treatment and last up to three days after treatment. [11] More serious complications can occur when an excessive radiation dose is applied to non-target tissue. An excessive dose to the healthy liver parenchyma, which can be due to either a high overall administered activity or an unfavorable tumor to non-tumor activity distribution ratio, can cause radiation induced liver disease (RILD). Alternatively, distribution of microspheres in organs other than the liver could cause serious morbidity and even mortality (e.g. radiation pneumonitis or gastric ulceration). These severe complications occur in less than 10% of patients.[12]–[14].
Laboratory toxicity in terms of elevated liver function tests and liver enzymes can be expected after 90Y-RE. It is important to monitor laboratory toxicity, because this may be an early indicator for RILD. Relatively little is known, however, about the normal range of laboratory toxicities following 90Y-RE in patients who do not develop RILD. The primary objective of this study was to investigate clinical and laboratory toxicity in patients with liver metastases, treated with 90Y-RE. Secondary objectives were assessment of tumor response and overall survival.
Materials and Methods
Patient Selection
Records of all liver metastases patients who were not participating in a clinical trial and had received a pre-treatment angiographic procedure for treatment with 90Y-RE at our institute between February 1st 2009 and March 31st 2012 were retrospectively analyzed. Patients that were eligible for 90Y-RE had unresectable liver dominant metastases and had progressive disease under systemic treatment, or were no longer treated systemically due to contraindications. The Medical Ethics Committee of the University Medical Center Utrecht waived the need for informed-consent and approved this study.
90Y-RE was carried out over two sessions: a pre-treatment diagnostic angiography and a treatment angiography. Patients were admitted to the hospital on the evening before angiography. They received 1.5 L per 24 h NaCl 0.9% intravenously for pre- and post-hydration. Pre-treatment diagnostic angiography started with selective visceral catheterization (celiac axis and superior mesenteric artery) in order to obtain an angiographic map of the patients' vascular anatomy. Specific extrahepatic vessels were coil-embolized to prevent 90Y-microspheres that were injected into one of the hepatic arteries, to be distributed to visceral organs other than the liver. Arteries that were actively searched for and embolized using coils included the gastroduodenal artery, the right gastric artery, and pancreaticoduodenal vessels and any other relevant arteries depending on the patient's specific anatomy. Subsequently, 150 MBq technetium-99m-labelled macro-albumin aggregates (99mTc-MAA) were injected into the hepatic artery to simulate the 90Y-microspheres distribution. Next, single photon emission computed tomography (SPECT) and planar nuclear imaging were performed. In order to assess whether part of the dose was deposited in abdominal organs other than the liver, the SPECT images were analyzed after fusion with computed tomography (CT). Planar nuclear imaging was used to calculate the lung shunt fraction; patients with a lung shunt <10% received the full dose of 90Y-microspheres, when lung shunt fraction was between 10%–15% or 15%–20% the dose of 90Y-microspheres was reduced with 20% and 40%, respectively. [15] Lung shunt fractions of >20% implied that no treatment could be given. If radioactivity was detected in non-target organs, such as pancreas, duodenum or stomach, further angiographic investigation was performed with additional coiling and/or a more distal injection position of 99mTc-MAA. [16] Patients stayed one night in the hospital for observation.
Treatment angiography was performed within two weeks after the pre-treatment angiography. Patients were readmitted to hospital the day before angiography, where they again received pre- and post-hydration. One hour before angiography, patients received a single intravenous dose of dexamethason (10 mg) and ondansetron (8 mg). The dose of radioactive resin microspheres (SIR-Spheres®, SIRTeX, Lane Cove, Australia) for each individual patient was calculated according to the body surface area method provided by the manufacturer. [15] The tumor volume and total liver volume were calculated by volumetric assessment of CT imaging. Subsequently, the dose of 90Y-microspheres was administered with the catheter tip in the hepatic artery or one of its branches, at the same position as used for the injection of 99mTc-MAA. The total liver weight (mliver) was derived from CT-volumetric measurements assuming a density of 1 kg/l. The net amount of administered radioactivity (Anet) (prepared activity minus residual activity in administration system and catheter) was calculated. The whole liver absorbed dose (Dliver), assuming a homogeneous distribution and full absorption of activity in the liver, was then estimated using the following Medical Internal Radiation Dose (MIRD) committee-based formula [17]:
Patients received 90Y-RE as a whole liver treatment in a single angiographic procedure (i.e. whole liver delivery), whole liver treatment in two sessions (i.e. sequential delivery) or as treatment of a single lobe (i.e. lobar treatment). In cases of sequential delivery, the aim was to perform both treatment sessions within a commonly accepted interval of 30–45 days. [11] The distribution of 90Y-microspheres was assessed with either bremsstrahlung SPECT or 90Y-positron emission tomography computed tomography (PET-CT). Our institution's radiation safety committee required all patients to stay in the hospital for a minimum of 12 hours after treatment.
Toxicity Assessment
Post-treatment, patients reported to the outpatient clinics at intervals of approximately four weeks. At these visits, physical examination and laboratory tests were performed. The following laboratory investigations were included in our analysis in order to assess laboratory toxicity: total bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, hemoglobin (Hb) and white blood cell count (leukocytes). Blood samples, taken up to four weeks prior to 90Y-administration and during a four months follow-up were used for toxicity analysis. Laboratory toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. [18] GGT, AST, ALT and Hb reference values were gender dependent. For each patient, baseline CTCAE grades and maximal CTCAE grades during follow-up were determined. In addition, new toxicity or progression of baseline toxicity to a higher CTCAE grade was grouped separately and will be referred to as "new toxicity". Patients, in whom data on baseline and/or follow-up laboratory investigations were not available in our center, were excluded from the laboratory toxicity assessment. The clinical toxicity assessment was based on the reporting of periprocedural complications, treatment-related symptoms (CTCAE grade 1–2) and serious adverse events (CTCAE grade 3–4), in the patient's charts.
Response Assessment
Baseline imaging was performed with CT or magnetic resonance imaging (MRI) of the liver. In addition, patients with (suspected) 18F-fluorodeoxyglucose (18F-FDG)-avid tumors received 18F-FDG-PET to assess the presence of extrahepatic metastases. Follow-up imaging was performed with CT or MRI of the liver (depending on the modality used for baseline imaging) at approximately 1, 3 and 6 months post-treatment. Response assessment was performed in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) on the level of target lesions (TL), whole liver (including non-target lesions) and overall response (including non-target lesions and extrahepatic disease) at 3 months (range 2.0–4.5 months) and 6 months (range 4.5–7.5 months) after the first 90Y-RE procedure. [19] Up to five target lesions per patient were identified by an observer (either MS or CR) and the maximal cross-sectional diameter of each target lesion was subsequently measured by the other observer. Observers were blinded for the identity and characteristics of the patient; date of imaging and whether it was a baseline or follow-up scan. Data on progression of non-target lesions, new liver lesions and progression of extrahepatic disease were extracted from radiologic reports. Patients who were lost to follow-up were regarded as having progressive disease (PD) on the 'overall response level' at the time of death. Median time to progression (TTP) was calculated for all response levels per Kaplan-Meier analysis.
Survival Analysis
Overall survival was defined as the interval between the date of (first) 90Y-RE treatment and the date of death or most recent contact (alive). Median overall survival (including corresponding 95% CI) was calculated through Kaplan-Meier survival-analysis. Statistical analyses were performed with SPSS Statistics 20.0 for windows (IBM SPSS, Chicago, IL). All percentages were rounded to the nearest whole number.
Between February 1st 2009 and March 31st 2012, a total of 73 consecutive patients (excluding patients participating in a prospective clinical trial) with liver metastases were considered eligible for 90Y-RE treatment at our institute and received a pre-treatment angiographic procedure with 99mTc MAA. A flowchart of the study design and patient treatment is presented in Figure 1. Fourteen patients (19%) could not be treated with 90Y-RE, due to persistent extrahepatic deposition (PED) of 99mTc-MAA (n = 11), rapidly progressive disease (n = 2) and a lung shunt fraction exceeding twenty percent (26%, n = 1). Fifty-nine patients received 90Y-RE treatment.
Flowchart displaying treatment selection and study design. *11 patients were non-evaluable for the laboratory toxicity assessment. Abbreviations: PED = persistent extrahepatic deposition; PD = rapidly progressive disease.
Baseline characteristics of these patients are presented in Table 1. The majority of the patients (30/59, 51%) had colorectal cancer liver metastases, six patients (10%) had neuroendocrine tumor (NET) liver metastases, and 23 patients (39%) suffered from liver metastases from various other primary tumors.
Treatment details are presented in Table 2. The majority of the patients received a whole liver treatment in one session (n = 38, 64%), with a selective administration of 90Y-microspheres in the left and right hepatic artery (n = 28) or administration in the proper (n = 9) or common hepatic artery (n = 1). In ten patients, whole liver treatment was performed selectively in sequential sessions (n = 10, 17%), with a median interval of 14 days (range 12–77 days) between both treatment sessions. Eleven patients received unilobar treatment (n = 11, 19%). The mean net administered activity was 1473 MBq (standard deviation 447) with an estimated mean liver-absorbed dose of 42.0 Gy (standard deviation 14.3). Post-treatment bremsstrahlung scintigraphy or 90Y-PET, revealed no extrahepatic deposition of radioactivity in any of the patients. Four patients were retreated with 90Y-RE after disease progression had occurred, with a median interval of 9 months (range 5–25 months) between the first and second treatment. Median time of hospital admission was 2 days (range 1–4 days). Fifty-four patients (92%) were discharged the day after treatment. The other five patients required longer hospitalization (one or two days extra), due to comorbidities such as renal insufficiency, diabetes mellitus or heart failure.
Eleven patients (19%) were excluded from laboratory toxicity analysis, because data on laboratory investigations at baseline or during follow-up, within our defined intervals, were not available in our center. In the remaining 48 patients, there were values missing for some laboratory parameters, therefore the denominator was adjusted accordingly when calculating incidences. CTCAE grades at baseline, maximum CTCAE grades during follow-up and corresponding new toxicity are presented in Figure 2. Grade 3–4 toxicity at baseline was observed for GGT (16/47, 34%) and ALP (1/47, 1%). Grade 3–4 new toxicity was observed in 18 patients (38%), including following parameters: GGT (13/47, 27%), ALP (10/27, 21%), bilirubin (1/41, 2%), AST (1/47, 2%), ALT (1/47, 2%), and albumin (1/42, 2%). In addition, the incidence of grade 3–4 new toxicity was stratified according to treatment strategy. Ten out of 28 evaluable patients (36%) who received whole liver treatment in one session had grade 3–4 new toxicity, compared to five out of ten patients (50%) who received whole liver treatment in sequential sessions, and three out of ten patients (30%) who received unilobar treatment (Table 3).
Clustered bar-chart displaying the incidence of laboratory toxicity at baseline (BL), during follow-up (FU) and corresponding 'new toxicity' (NT) per laboratory value. CTCAE grades: blue = grade 1; green = grade 2; orange = grade 3; red = grade 4. Abbreviations: ALT = alanine amino-transferase; Hb = hemoglobin; AST = aspartate aminotransferase; AP = alkaline phosphatase; GGT = gamma-glutamyl transferase.
The following periprocedural complications were reported: allergic reaction to contrast agent (n = 6), arterial dissection (n = 2), nausea/vomitus during angiography (n = 1), delayed hemostasis at the access site requiring prolonged clamping (n = 1), inguinal hematoma at the access site (n = 1). Complications did not prevent any patients from receiving therapy. Back pain or abdominal pain during angiography was managed with fentanyl (37% of patients, range 50–200 mcg i.v.) and/or diclofenac (35% of patients, range 50–125 mg i.v.).
Clinical symptoms associated with the postembolization syndrome (CTCAE grade 1–2) were observed in the majority of the treated patients. This syndrome comprised the following symptoms (in order of frequency): fatigue and loss of appetite, pain/discomfort in the right upper abdominal quadrant requiring analgesics (paracetamol and/or diclofenac and/or morphine), nausea and vomitus, fever and general discomfort. In general, these symptoms started on the day of treatment and lasted up to two weeks after treatment. No grade 3–4 clinical toxicity was observed after 90Y-RE treatment and no serious treatment-related complications such as duodenal or gastric ulceration, radiation pneumonitis or RILD, were observed.
Target lesions-, whole liver- and overall response rates and TTP (for all patients and per tumor type) at 3- and 6-months are displayed in Table 4. Target lesion, whole liver and overall disease control rates (complete response+partial response+stable disease) at 3-months post-treatment were 35%, 21% and 19% respectively. Corresponding disease control rates at 6-months were 25%, 13% and 12%. Median TTP for all patients was 6.2 months (95% CI 2.2–10.0) for target lesions, 3.3 months (95% CI 2.8–3.8) for the whole liver and 3.0 months (95% CI 2.4–3.5) overall.
At the time of analysis, 49 patients had died and 10 patients were still alive. Median overall survival for the entire group of patients (n = 59) was 8.9 months (95% CI 7.2–10.6). The Kaplan-Meier survival curve is displayed in Figure 3. Median overall survival was 8.9 months (95% CI 6.9–10.9) for colorectal cancer liver metastases (n = 30), 40.3 months (0–107.9) for NET metastases (n = 6) and 7.8 months (95% CI 5.0–10.6) for other metastases (n = 23) (Figure 4).
The blue line represents patients with colorectal liver metastases (CRLM), the green line represents patients with neuroendocrine tumor (NET) liver metastases, and the red line represents patients with liver metastases from other primary tumors.
The primary objective of this study was to investigate treatment-related clinical and laboratory toxicity in patients with unresectable liver metastases, treated with 90Y-RE. Secondary objectives were to assess tumor response and overall survival. Clinical toxicity was confined to grade 1–2 symptoms of the post-embolization syndrome. No RILD or other grade 3–4 clinical toxicity was observed, whereas laboratory toxicity grade 3–4 was observed in 38% of patients. In this cohort, a disease control rate of up to 35% was obtained at 3-months post-treatment, and median overall survival was 8.9 months.
Tumor response rates vary widely in the 90Y-RE literature. [4] This may be explained in part by differences in methodology for response assessment. Various studies do not specify whether RECIST criteria have been followed. According to these criteria, tumor response should be differentiated in target lesion, liver and overall response. [19] In order to improve interpretability of overall response rates, studies should indicate whether patients had evidence of extrahepatic disease at baseline. Response rates are commonly divided into 3- and 6-months rates post-treatment. However, it should be clearly stated which imaging intervals are chosen to represent this 3- and 6-months measurements. In addition, it would be preferable to score target lesion response blindly, to assure objective measurements. In a comprehensive review of the 90Y-RE literature, twelve studies were identified that reported a 3-month disease control rate, ranging from 63–100%. [4] In most of these studies, the level on which response assessment had been performed was not specified. Assuming these are whole-liver disease control rates, our 3-month disease control rate was much lower: 21%. This difference could be attributable to differences in methodology of response assessment, as mentioned above. However, less stringent patient selection criteria and the heterogeneity of our cohort, including hyper- and hypovascular liver metastases from various primary tumors, could also have attributed to lower response rates.
Toxicity due to radiation to the liver has first been described after external radiation therapy. [20], [21] It was found that the liver is very sensitive to radiation and patients may develop radiation induced liver disease (RILD), months after an overdose of radiation. Histopathologically, RILD is characterized by veno-occlusive disease with congestion of the central veins and sinusoids.[21]–[24] The symptoms of RILD comprise fatigue, anicteric ascites, hepatomegaly, and elevated liver function tests (especially alkaline phosphatase). [23] High dose corticosteroids can be given to mitigate the course of this disease. It is however, hard to recognize RILD since it has a long latency time and many of its symptoms can also occur after non-complicated treatment with 90Y-RE. A better understanding of the physiological variation of treatment-related laboratory toxicity after 90Y-RE would be very helpful in discriminating early signs of RILD from transient laboratory abnormalities after treatment. Mild toxicity (grade 1–2) of liver function tests is common after 90Y-RE, occurring in up to 70% of the patients.[25]–[27] Reported incidences of grade 3–4 toxicity are much lower and vary widely across studies. Van Hazel et al. [2] observed no grade 3–4 toxicity in their study, Piana et al. [25] found an overall incidence of 7% and Kennedy et al. [8] reported an incidence of up to 20.5% for ALP. In the study of Piana et al., one patient died of RILD. [25] In our study we found higher incidences of laboratory toxicity, with new laboratory toxicity grade 3–4 occurring in up to 38% of the patients. However, we did not observe any serious treatment-related complications, nor did we observe any RILD. This indicates that serious laboratory toxicity regarding transaminases and liver function tests can occur as part of the physiological reaction of the liver to 90Y-RE treatment.
One of the factors complicating the interpretation of toxicity results is that abnormalities in liver function tests and transaminases could be the result of tumor progression instead of treatment-related toxicity. Moreover, results of toxicity are often incompletely reported in the 90Y-RE literature. Many studies do not specify how CTCAE scores for laboratory toxicity have been determined. This could inadvertently lead to an underestimation of treatment toxicity and it limits the comparability of studies. Therefore, we aimed to report our methods and results in an unambiguous and transparent fashion.
The most important limitations of this study were its retrospective design and the lack of standardization of laboratory investigations and reporting of clinical symptoms during physical examination. Therefore, our results in terms of the incidence of laboratory or clinical toxicity are likely to be underestimations of the real incidence of toxicity. Another limitation was the heterogeneity of our study population. However, this heterogenic group does reflect the typical population of patients referred for 90Y-RE treatment.
Fourteen of the 73 patients (19%) who received work-up angiography did not receive 90Y-RE. The majority of these patients (n = 11) were not eligible because of persisting extrahepatic deposition (PED) of 99mTc-MAA. This PED rate of 11/73 (15%) is much higher than the rates reported in the literature (ranging from 0% to 10%). [16], [28], [29] A likely cause of the high PED rate in this study is the relative large number of proximal injection positions (i.e. proper or common hepatic artery). Several studies have demonstrated that extrahepatic deposition can be solved/prevented by more distal injection positions (left/middle/right hepatic artery or even more selective). [16], [28], [30] We have changed our current practice accordingly and we rarely perform whole liver treatments from the proper hepatic artery anymore. In addition, our center and many others increasingly use c-arm cone beam computed tomography during the pre-treatment angiography to help prevent extrahepatic distribution and identify culprit vessels. [31], [32].
The whole liver approach has also been associated with increased toxicity. Seidensticker et al. have reported that a whole liver approach, in non-cirrhotic liver metastases patients, resulted in a higher number of liver-related CTCAE grade 3–4 events as compared to a sequential lobar approach. [14] We could not confirm this finding in our patients. In fact, the number of patients with CTCAE grade 3–4 laboratory toxicity was even lower in the whole liver approach group (36%) than in the sequential lobar group (50%). Selection bias, and confounding due to differences in baseline characteristics, may play a significant role in this matter. However, we do recognize the clinical importance, and we think that the question whether treating the whole liver at once increases toxicity, should be determined using a randomized controlled trial.
The majority of the patients (70%) treated in our cohort, received radio-embolization as salvage therapy. This illustrates that 90Y-RE is still regarded as a treatment option of last resort, for patients who have unresectable and chemorefractory liver tumors. The costs of radioembolization treatment (approximately €11.000 for one dose of SIR-spheres plus the costs of the procedure, the involved imaging, hospitalization and follow-up) need to be weighed against the potential benefit to the patient. [33] For this purpose, prospective comparative studies evaluating survival, tumor response, and quality of life after 90Y-RE are strongly warranted. In addition, it will become increasingly important to select those patients that will benefit most from this therapy. Performing radioembolization at an earlier stage in patients with liver metastases might for instance translate into improved tumor response rates and overall survival. Two large randomized controlled trials are currently ongoing, investigating the effect on overall survival (SIRFLOX study) and progression free survival (FOXFIRE study) of the addition of 90Y-RE to FOLFOX (fluorouracil, leucovorin, oxaliplatin) with or without bevacizumab as first-line treatment for patients with unresectable colorectal liver metastases. [34].
The risk of severe complications or grade 3–4 clinical toxicity in patients with liver metastases of various primary tumors undergoing 90Y-RE is low. In contrast, laboratory toxicity grade 3–4 was observed in more than one-third of the patients without any signs of RILD. This physiological reaction of liver enzymes to 90Y-RE therapy may mask early signs of toxicity due to RILD.
Author Contributions
Conceived and designed the experiments: MS AvdH CR MK MvdB. Performed the experiments: MS AvdH CR BZ ML JN MK MvdB. Analyzed the data: MS AvdH CR. Contributed reagents/materials/analysis tools: MS AvdH CR. Wrote the paper: MS AvdH CR BZ ML JN MK MvdB.
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- 26. Gulec SA, Mesoloras G, Dezarn WA, McNeillie P, Kennedy AS (2007) Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: the tumor selectivity of the treatment as a function of tumor to liver flow ratio. J Transl Med 5: 15.
- 27. Arslan N, Emi M, Alagoz E, Ustunsoz B, Oysul K, et al. (2011) Selective intraarterial radionuclide therapy with Yttrium-90 (Y-90) microspheres for hepatic neuroendocrine metastases: initial experience at a single center. Vojnosanit Pregl 68: 341–348.
- 28. Dudeck O, Wilhelmsen S, Ulrich G, Lowenthal D, Pech M, et al. (2012) Effectiveness of repeat angiographic assessment in patients designated for radioembolization using yttrium-90 microspheres with initial extrahepatic accumulation of technitium-99m macroaggregated albumin: a single center's experience. Cardiovasc Intervent Radiol 35: 1083–1093.
- 29. Smits ML, Nijsen JF, van den Bosch MA, Lam MG, Vente MA, et al. (2012) Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. Lancet Oncol 13: 1025–1034.
- 30.
Lam MG, Banerjee S, Louie JD, Abdelmaksoud MH, Iagaru AH, et al.. (2013) Root Cause Analysis of Gastroduodenal Ulceration After Yttrium-90 Radioembolization. Cardiovasc Intervent Radiol.
- 31. Louie JD, Kothary N, Kuo WT, Hwang GL, Hofmann LV, et al. (2009) Incorporating cone-beam CT into the treatment planning for yttrium-90 radioembolization. J Vasc Interv Radiol 20: 606–613.
- 32. Heusner TA, Hamami ME, Ertle J, Hahn S, Poeppel T, et al. (2010) Angiography-based C-arm CT for the assessment of extrahepatic shunting before radioembolization. Rofo 182: 603–608.
- 33. Garin E, Rolland Y, Boucher E, Ardisson V, Laffont S, et al. (2010) First experience of hepatic radioembolization using microspheres labelled with yttrium-90 (TheraSphere): practical aspects concerning its implementation. Eur J Nucl Med Mol Imaging 37: 453–461.
- 34. Sharma RA, Wasan HS, Love SB, Dutton S, Stokes JC, et al. (2008) FOXFIRE: a phase III clinical trial of chemo-radio-embolisation as first-line treatment of liver metastases in patients with colorectal cancer. Clin Oncol (R Coll Radiol) 20: 261–263.


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If you are interested in applying for the Region 15 One-Year Undergraduate Scholarship, you may apply here. There are three one-year scholarships valued at $500 each.
Eligibility Requirements:
Applicant must be an entering freshman in a Texas college or university in the fall of 2017. Applicant must have been accepted into the school's college of education. Applicant must major in a music degree program leading to Texas teacher certification with music as the primary teaching field.
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Reds boss Rafael Benitez identified Italy international Aquilani as his preferred replacement for Xabi Alonso, who joined Real Madrid for around £30million earlier this week.
Liverpool had a bid of around £20million for Aquilani accepted by Roma on Wednesday before the player headed to Merseyside for a medical and contract talks.
The now former Roma man is expected to be at Anfield on Saturday to witness his new team-mates take on Atletico Madrid in the club's final pre-season friendly before next weekend's big kick-off.
Aquilani dispelled fears over the ankle injury that needed surgery this summer and restricted his appearances for the Serie A club last season.
But considering he has only just returned to training, it seems unlikely he will be fit to face Tottenham next Sunday in the Barclays Premier League season opener at White Hart Lane.
Aquilani, 25, is believed to be earning around £80,000 a week.
- More about:
- AS Roma
- Atletico De Madrid
- Liverpool FC
- Rafael Benitez
- Xabi Alonso


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MarkerPop and this week's challenge was mine to pick....so we're going with Pretty In Pink!!
I went with the Summer Cake image from Magnolia...that cake is just adorable! I colored it with Copic Markers: R35, R32, RV42, R21, E49, E47, YG63, YG61, YR68, YR07, Y38. I covered the frosting and candle flames with some You're So Fine Diamond Clear Cool Highlight Glitter. I fussy cut the cake and popped it up on foam tape.
Papers and brads are from My Mind's Eye's Sweetest Thing's Lavender and Tangerine's collections. I punched some vintage sheet music for a bit of a fun birthday theme touch!
The Winners Circle - Game #87 Shiny Spring
4 hours ago


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Baffled In Boston
--Excerpted from Gary's articles, including:
"The Man Who Would Be Ann" (published in Writer's Digest magazine)
I have this theory that I should always have ten writing projects started because nine of them are going to be disasters. So last March when I applied to replace Ann Landers at the Chicago Sun-Times, it wasn't because I was ready to flush the rest of my life down the toilet. Applying for the advice columnist job, to use a more pleasant analogy, was just planting one more seed in my garden. . . .
When I saw the newspaper's ad, in which the Sun-Times confessed that Ann was abandoning them and they wanted to replace her with someone who had "Guts, Guidance, and Good Advice," I didn't trouble myself with nitpicking questions like, "Do you really want this job, Gary?" . . .
Of course, I was not the only applicant. Twelve thousand hair stylists, taxi drivers, manicurists, bakers, candlestick makers … along with half the sex counselors and writers in America, joined the party. Though I was in the middle of writing two books with imminent deadlines, and preparing for a workshop, I stole the time to write a letter extolling my virtues to the Sun-Times. . . .
Mostly I promoted myself as a communicator. . . . I had written 20 books, 14 of which were good enough to be published. And the six dreadfully written unpublished ones piled in my closet only proved that I was familiar with rejection, failure, frustration and anguish, the very tragedies advice-seekers would write to me about.
I had also written a thousand articles, many of which took the form of advice to writers right here in Writer's Digest. I reasoned that if I could inspire writers to persevere in the face of grim publishing realities, helping people deal with alcoholism, family feuds and broken hearts would be as easy as typing.
A week after I mailed my resume, I got a letter from the Sun-Times. I thought it would be some variation on a rejection slip. Instead, I learned that I had made the first cut. A hundred and seven other people had also made the first cut, so it seemed a little early to invite the gang over for a celebration party.
The Sun-Times also sent along four sample letters addressed to "Dear So-and-So." I was to answer them before sundown the next day, a deadline which was particularly disheartening considering that I was near death with the flu.
One letter concerned AIDS and it left no room for humor. I saw it as a test. Would I know enough to scrap the jokes and also gather such sensitive information from reliable sources? I called the National Health Center and wrote a straightforward letter.
The other letters seemed to invite levity. One man said he had a gut feeling that his wife was having an affair with his brother on those nights when she was allegedly at "business-related dinners." He ended by saying he didn't want to be the last to know.
I wrote back, "The simple solution would be to invite your brother over for a game of pinochle every time your wife has one of those business-related dinners. If he continually declines with curious excuses like, "Gee, I'd love to, but tonight I have to wash my parakeet," then perhaps there is some basis for your fears."
My letters were good enough to get me into the final 22, and when I answered another set of four letters, I got a call from the Sun-Times.
"Welcome to the final seven," a woman said.
Now it was serious. Channel Seven came on Thursday, Channel Five on Friday . . . I spent entire days with the press. . . . The "Oprah Winfrey" show flew me to Chicago to do a program with the other finalists. . . . There were six of us, three women, three men. Number seven, "the mystery woman," had declined publicity. Poor her, we thought, she doesn't have a chance. After all, publicity was what this was all about. We became close quickly, the six of us. And why not? We were peering out at the world from the same goldfish bowl.
A week later I was in Chicago again. This time for "The Interview." Four editors surrounded me. . . . What do you think about abortion, they asked. What about divorce? What about this . . . about that? You wouldn't cut in line at an airport and embarrass us, the way Ann once did, would you? And by the way, you have to move to Chicago for this job, and we want you to know we're thinking of picking a man and a woman.
I told the Sun-Times I would move or share the job, but not both. If they decided on a man and a woman they could count me out. I didn't want to relocate just to become half of the new Ann Landers.
We'll let you know on May 18, they said.
When I got home the phone was ringing and it never really stopped. Have you heard anything, Gary? It wasn't just reporters and friends. It was friends of friends. It was men who had sat beside me on a bus one time, women who had the same optometrist as me. I enjoyed the attention but I was getting bored with hearing me report the same lack of news over and over.
The 18th of May came. The 18th went. And as that deadline receded farther and farther into the past, without explanation, I and the others took a turn for the worse. . . .A telephone network of Ann Landers finalists began communicating across the country. . . . We had a dozen theories a day. . . . "Any day now" turned into "any week now."
When the Sun-Times finally called, it was to tell me they had picked two people, neither of whom was me. The paper had selected the mystery woman, Diane Crowley, also from Massachusetts, and daughter of the original Ann Landers. Her partner was to be Jeffry Zaslow, a writer for the Wall Street Journal.
Though the contest was over, the adventure continued. I and two other finalists—Linda Stasi and Linda Moore—created "Almost Ann," a parody of advice columns, which was picked up by a major syndicate. . . . National Public Radio asked me to give occasional on-air advice for "All Things Considered". . . and a local radio station asked me to be its funny advice columnist.
And best of all, I've started writing a novel called Dear So-and-So [later published as Baffled In Boston]. It's a comedy about a guy who enters a contest to replace a famous advice columnist. It's one of the books I really want to write.
So that's four projects I've started as a result of not being the next Ann Landers. If I can get six more, perhaps one of them will work out for the best.
Instruction for Writers
Gary's invaluable, easy-to-use handbook helps you solve any and all writing problems — whether you are a student, business person or professional writer. Timeless!
"A crystallization of Gary Provost's writing wisdom... philosophy made practical."
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Are you an aspiring author? You are, aren't you! Well, here, Gary and Peter examine every secret, every facet of storytelling, from narrative hooks to fulfilling climaxes. With an outstanding array of examples, you can learn to master the cornerstones of great writing. Step by step. (An original Writer's Digest publication, it is now available to writers in ebook format from online booksellers.)
Master techniques of ripping stories from the headlines for fun and profit.
The Freelance Writer's Handbook contains a wealth of information on leads, query letters, markets and making money off of writing. This had been THE little manual for freelancers . . . back in the day.
The most popular of Gary's novels is now available as an eBook. AND is also now an AUDIBLE book. It's hilarious. It's so . . . Gary.
Gary's irreverent look at just about everything. Click to learn how this "underground hit" launched his unstoppable writing career.


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Back to School: DIY Locker Tote
Get ready for back to school with a quick and easy DIY Locker Tote to help keep your kid's academic belongings from overflowing. Small handles on each side are perfect for looping over the hooks on each side and the boxed bottom helps keep it wide open.
I'm Jenn from A Jennuine Life; since


text:
A Cultural Tradition of Filipino People, in Celebrating 18th Birthday "Debut"
A Cultural Tradition of Filipino People, in Celebrating 18th Birthday "Debut"
Submitted by Jamie Lou Dela Cruz
The Philippine debut celebrates a woman entering into her 18th year. It is when a young lady formally turned into an adult or legal age as she celebrates her birthday. In the celebration, the girl will be actually called as the "debutante", a young woman who is presented to society or it is usually at a formal ball event wherein several invited guests' as well as different significant persons were included in the said gathering.
At Fox Creek, Alberta, there was a girl named Ma. Patrisha Veronica Sta. Cruz Mendoza, daughter of Mr. Gilbert Mendoza, General Manager of Comfort Inn & Suites and Mrs. Adora Mendoza, works at the Devonian Hotel & Suites, who happens to celebrate her 18th birthday in their own Filipino traditional way or most commonly known as a "Debut". Many young Filipinas considered it as a momentous chapter of their life.
In the said event called "A Decade & Eight" birthday of Patrisha was held at the Fox Creek Community Legion Hall on May 3rd. It was started with the processional of the family members together with the celebrant. Moreover, warm welcome messages from the parents to their daughter as well as thanking and welcoming the guests were professed to begin the wonderful occasion.
Several honored guests' and/or visitors from different sectors of fox creek attended the party and witnessed the different way on how Filipinos celebrate the big event, the "Debut", such as 18 Roses from 18 male friends/relatives who happens to dance with the debutante one by one as well as having 18 candles from 18 chosen female friends/relatives and must give a speech or any birthday wishes for the celebrant.
Also, there were 18 persons who actually deliver some short messages for the debutante for the representation of 18 toasts. Moreover, a "Cotillion dance" was presented during the event, held by young Filipina women with their Escorts that demonstrate the wealth and prestige of the family.
This dance is a significant part of the occasion. Lastly, the celebrant brings the gathering to a close with a debutante's speech was upheld in which she shares her life experience and gratitude with her beloved guests.
The family of the debutante want to express their appreciation and thankful to all the Filipino Community together with their local friends for all the supports and helps to make this occasion a very successful one. Together with all the guests, family and friends who attended and witnessed this memorable event of Patrisha Mendoza.
Checkout a few videos on YouTube:
Patrisha Mendoza Cotillon
Patrisha Mendoza Debut
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Treasurer Scott Morrison was rushed into surgery for an undisclosed ailment. However, Mr Morrison is now on the mend after emergency surgery which was done in Canberra Hospital. The senior Liberal frontbencher posted the news on Facebook on Saturday. He thanked staff in the hospital's acute surgery ward, "including Kim and Mwa", and the emergency department, saying he was on the road to full recovery and "heading back to the Shire".
He said he expected to return to Parliament in just over a week.
"Was also nice to get a welfare visit from the boss (Malcolm Turnbull) yesterday afternoon [Friday] to make sure I was on the mend," he wrote. A spokesman for Mr Morrison would not say what he was treated for.
Despite the treasure having had to undergo emergency surgery which can be traumatising to most people, he received no mercy from the public. Social media erupted with tweets saying they wished the treasurer did not recover and that a heart would not be found if doctors tried to look for one.
We can rest assured that Scott Morrison's emergency surgery had nothing to do with his heart, unless doctors were trying to find it.
— Joe Furphy (@JosephFurphy) November 13, 2016
I do hope it's nothing trivial: "Scott Morrison on mend after emergency surgery" https://t.co/DJaF5CTRap via @theage
— Margaret Dahlstrom (@MargDahlstrom) November 13, 2016
This is breaking news, more details will follow.
Do you have any words for Mr Morrison?
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Apart from a coupe of people, there is a race going on here to get to the bottom most level of decency and humanity. The guy was sick – you don't have to like someone's political view to wish them well. You are inconsiderate scumbags. I'm not his biggest fan either, but he is a fellow human being and I am glad he is recovering.
Do you think he would care less if it was you ? bet He didn't wait in a queue at the A & E either . It's not a matter of just ' not liking him ' it's what he is doing to people . Taxing them out of retirement , leaving pensioners to struggle etc , that is why most people would prefer the uncompassionate uncaring man self serving man gets no sympathy .
Who cares? Do you think he"d send us good wishes? Dont give a dam about him he's a "nasty" man!! Pollies dont give a dam about our health, why should we give a dam about theirs!!! Notice they didnt say what it was, is that because the rest of us would have been patched up and sent home on a 2 year waiting list!!!!
Diet, you're probably quite right with your response to my overly harsh comment. Mate, it's just that it bloody infuriates
me when people make such senseless and inane posts … and especially when they don't have a grasp on spelling and grammar.
I WILL promise you to get down off my 'high horse' (somewhat) in future posts.


text:
Moorish Dismounted Christian Guard
2,074pages onAdd New Page
this wiki
this wiki
Being overthrown by their own palace guards is a risk faced by many rulers, and one way to prevent this is to hire guards from outside their own cultures, who cannot hope to wield power themselves. Thus the Sultans of the Moors hire Christian Knights to protect them. Their prowress in battle is an added bonus.
- Soldiers: 60
- Attack: 16
- Charge Bonus: 3
- Weapon Type: Melee
- Total Defence: 22
- Armour: 7
- Defence Skill: 9
- Shield: 6
- Hit Points: 1
- Recruitment Cost: 690


text:
+ Locations, Office Hours & Directions
As a cardiologist in New Milford, CT, Dr. William Cicio offers treatment plans for conditions affecting your heart & cardiovascular system, such as hypertension.
We invite you to write a review about your experience with Dr. Cicio.
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NOTE: Please contact the doctor's office to confirm your coverage before making an appointment.
Dr. William Cicio graduated from State University Of New York At Stony Brook, School Of Medicine in 1992.
Dr. Cicio has two offices in Connecticut and Pennsylvania where he specializes in Cardiology.
Dr. Cicio works with seventy doctors including Dr. Christian Leonardi and Dr. Michael Levine.
Dr. Cicio is a cardiologist in Williamsport, trained to deliver extensive treatment for the heart and cardiovascular system. Dr. Cicio may see patients for symptoms like shortness of breath, chest pains or dizziness, among others. Heart conditions that may be diagnosed and remedied by a cardiologist may include arrhythmia, angina, heart aneurysms, heart failure, coronary artery disease, congenital heart defects and rheumatic heart disease, to name a few.
State University Of New York At Stony Brook, School Of Medicine
Please Note: The information displayed below is sourced from the 2014 Medicare Physician and Other Supplier National Provider Identifier (NPI) Aggregate Report. It's important to remember that the statistics below are not inclusive of all patients treated by Dr. Cicio, but only those who participate in Medicare.
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text:
Healthy hair is more coveted than the perfect pair of jeans, but for some people, it's more elusive than a perfectly ripe avocado. There's no one food that will change what's already on your head, but your diet can have a lot to do with growing healthy, strong locks.
As much as I love trying the latest beauty products, my expertise is fixing us all from the inside out. The healthier you are on the inside, the healthier you'll look on the outside. Your hair is no exception. Try these foods below and you just may be tossing your hair like the Pantene girl.
Brown rice
"Whole grains" probably aren't the first thing you think of when you hear silicon. Yet this important compound is found in whole grains and is responsible for the growth and shine of your luscious locks. This mineral can keep your hair from thinning, and works to help improve circulation. This means more blood flow to your scalp, which in turn will encourage healthy hair growth.
You can pair whole grains like brown rice, farro or buckwheat with almost any lean protein and veggies to make a complete hearty and healthy meal, but try this bok choy and chicken stir fry to create a menu (and hair) that really shines.


text:
Q: Do most people do a decent job of creating their online
persona on LinkedIn?
Sammons: I come across poor quality profile images on
LinkedIn all the time. I've seen profiles with no headshot image to a logo as a
profile image, and everything in between.
Q: Why do you put so much emphasis on a LinkedIn photo?
Sammons: Your LinkedIn profile image sets the stage for
trust and likability. It follows you around throughout the entire network. When
you post a status update, it's there. When you like, share, or comment on
LinkedIn, it's there. When you participate in group discussions or send
personalized messages, your profile image is there.
Your LinkedIn profile is potentially going to be a first
stop for someone who is trying to learn more about you via a Google search. It
is a very important digital reputation asset. Within LinkedIn, profile views
are one of the top member activities.
Also, your profile image is an opportunity to make an
emotional connection with someone who finds you on LinkedIn. If your image is
outdated or low quality, it probably will not help you make that human
Q: What are some dos and don'ts for your LinkedIn profile
Sammons: Snapshots, cropped images, or logos also don't make
for professional profile images. And if your image is missing, you will have
absolutely no credibility on LinkedIn.
A high-quality profile image should be taken by a
professional photographer in a studio. It should be your head and some
shoulders—not your full body. Look straight ahead, making eye contact. The
image background should contrast nicely with what you're wearing, and you
should have a pleasant look on your face that is welcoming and personable.
Q: How often should you update your image?
Sammons: I've
found the two-year mark to be a good timeframe to refresh my profile image. If you
leave the same profile image out there for five years or more, you may not be
recognizable in person. Your profile image needs to look as close as possible
to the way you look today. You want for people to recognize you, especially
when you meet them in person.
me a stickler, but your profile image is something that can make or break you
on LinkedIn.
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text: Become a member! Join or Renew LAGBAC is the association of LGBT legal professionals and allies of Chicago and the surrounding area. Learn more Login Username or E-mail* Password* Only fill in if you are not human Keep me signed in Forgot your password? NewsLAGBAC's 30th Anniversary Gala – July 27, 2017Justice Theis hosted Meet the BenchJustice Reyes hosts 2nd installment of our Meet the Bench seriesEqual Employment Opportunity Officer – City of ChicagoCongratulations Cecilia and Stephanie! Upcoming EventsPride Kick-Off CLE and Reception – May 16, 2017LAGBAC's 30th Anniversary Gala – July 27, 2017Joffrey Ballet – Evening of Dance – May 5, 2017Dinner With Judge EhrlichOscars Watch Party


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Slurry Pumps
Minprovise supply Australia-wide the complete range of Wear Min-Tech slurry pumps and componentry. Our partnership with Wear-MinTech combined with our expertise in high wearing materials handling equipment allows us to offer the following service for slurry pump requirements:
- Aftermarket service exchange slurry pumps and components
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- Complete slurry pump replacements
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- New project application
Most wet-side components of slurry pumps ( i.e. impellers, inlet & back liners, volute bowls) have traditionally been made either from the Ni-Cr white cast irons ("Ni-Hards") or the eutectic composition of 27 % Cr white iron. Both of these alloys are sufficient for most slurry applications with Brinell hardness levels around 550 to 600 HB. However the inherent wear life of these alloys is limited when used in applications such as alumina extraction processes and SAG mill primary crushing duties for hard rock ores such as copper, gold, tungsten etc.
Wear minimisation Technologies (WMT) has developed a superior white iron alloy for such aggressive slurries, by increasing both the Chromium and Carbon content higher than those of either the Ni-Cr or the 27% Cr alloys. As a result, this alloy has a higher bulk hardness level above both the Ni- Cr and 27% Cr grades. Brinell hardness is given as 650+ HB minimum. This alloy conforms to AS 2027 Grade Cr 35.
This alloy has been field tested in several operational applications including:
SAG Mill discharge duty: Wet-side components have been installed in a copper mine and have been in continuous operation for over eight months ( in excess of 4000 hours service) with no requirement to change inlet liner or impeller upon routine inspection shut-downs.
Stope back fill applications for underground gold mine: The mine was using 27% Cr wet-side parts which were lasting two weeks before needing to be replaced. Once WMT alloy was installed twelve weeks service life was achieved (six times extra wear life over 27% Cr).
HD HDH Heavy Duty Slurry Pumps
The HD or HDH range of Wear-MinTech Pumps is designed for continuous pumping of highly abrasive slurries. Typical Applications include chemical process, heavy minerals, paper and pulp, mill discharge, sugar beet, cyclone feed, fly ash and slag granulation.
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Slurry Pump brochure
Wear Minimisation Technology Pty Ltd (Wear-MinTech) was established to provide an alternative supply to the Original Equipment Manufacturer for spare parts.
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【travel】travel collections (Travelog)
This is a summary of all the Logbooks (Travelogs) related to travel that we have available for the North Holland(Netherlands) area. Please go ahead and click on them if you want to read their contents. Does reading about travel in North Holland(Netherlands) make you want to go there too? In that case let's start planning your next trip!
2014-05-16 - 2014-07-19
2014-06-16 - 2014-06-16
2013-09-05 - 2014-06-28
2016-09-26 - 2016-09-27


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TeamGroup Elite Plus 8GB DDR3-1333MHz (TPKD38G1333HC901)
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Three Easy Children's Book Digital Illustration Tips Creating children's book digital illustrations can be daunting. I started digital illustrating when Adobe Photoshop was relatively new and a perfect creative device for me as an entry-level user. The technology advanced beyond my wildest expectations, with dozens of ways to achieve magical effects. While newer versions of Photoshop include ever-advanced features, I tend to use 3 key tools to… Read More
Create Magical Children's Book Illustrations
Make Magical Illustrations With Light Since I published I Want Cake! I started illustrating other authors' picture books. My Photoshop skills grew better and better as I learned more advanced techniques. Though illustration awards helped build my confidence, I wasn't 100% satisfied with my digital images — but I couldn't put my finger on the reasons why. I've generally relied on Photoshop filters to produce unique illustration results. Plugin filters such as color toning, cinematic looks, and… Read More
Storytelling Art
Storytelling Art — Transforming Photographs into Fantasy Images Five years ago I began creating children's book illustrations with Photoshop and discovered a new genre — Storytelling Art. That's because I had no formal training as an artist, but I was computer savvy from my medical science research work. Photoshop fascinated me — it seemed the perfect tool for illustrating, especially because I can't draw. I took photographs of… Read More


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Bergstrom's Toxic Clean-Up
The Military Takes PR Lessons Before Town Meeting
By Karen Heikkala
November 1991; pages 6-7, 9; Volume 3, No. 2
Bergstrom Air Force Base's toxic clean up effort, now into its eighth year, will finally be opened for public scrutiny and comment on November 4th, at the LBJ Library from 7-10 pm. The Bergstrom effort began in 1983, when the Department of Defense initiated a world-wide operation designed to identify and clean up environmental problems on its bases. The military has kept the operation under a tight wrap, and only this summer has the national press reported on it. Despite articles in The New York Times and Newsweek this past summer, the Austin press has utterly failed to localize the issue.
At next week's meeting, Bergstrom personnel will solicit the public's concerns and comments on the base's environmental record before it's projected closure and reuse. Bergstrom's public-relations office claims that the military will take citizen's input seriously as it redrafts its new Environmental Impact Statement (EIS) on reuse options.
The low key publicity for the event, however, does not bode well for its effectiveness. Austin's own Environmental Affairs Department had heard nothing about it until Polemicist called them, and asked that we pass the word along as we worked in our story. In preparation for the upcoming meeting, Polemicist asked the Public Affairs Officer at Bergstrom to outline the current clean-up effort there. While he tried to appear helpful, he could not reveal any public information. "It's not that we don't want to talk to you. It's just that we have to make sure it's o.k. to talk to you."
Apparently the Colonel in charge of the clean-up is out of town. And where is he? At a two week training designed to teach military officials how to deal with the public about their clean up efforts. The colonel will be in PR training until two days after their public meeting on the 4th is over.
Watching the Waste
Pentagon officials and Bergstrom personnel have assured the city that they will clean up any known environmental problems, as well as any unknown problems discovered after they leave. Lenny Siegel, military coordinator of the National Toxic Campaign, however, notes that "the Federal government's track record for cleaning up is uneven around the country. Rather than always clean up sites, they sometimes have contained them, or covered them up. The bottom line is for citizen's groups to know what's out there and hold them accountable."
And there's plenty to scrutinize at Bergstrom AFB. According to Bergstrom's initial Environmental Impact Statement (EIS) on Proposed Base Closure, put together back in 1983, the Air Force identified 27 active, or potentially active areas with hazardous materials spilled or buried. Yet, in its more recent study, Bergstrom claims that only seven sites need cleaning, although it does not explain exactly what it has done with the rest.
The original study's sites included pipelines to radioactive sites, and containers and spills of petroleum fuels, solvents, radium, and pesticides. (See table below for all 27 sites.) Since Bergstrom started recording hazardous material disposals only 15 to 20 years ago, there are likely to be more old chemical spills and gasoline plumes still undiscovered. Furthermore, until this month, Bergstrom had been on the EPA's Resource Conservation and Recovery Act "significant non-complier" list, reserved for polluters that ignore continual warnings about storage tank maintenance and hazardous material handling practices. According to Samuel Coleman of the EPA, it is a status reserved for high-priority violations.
Behind Closed Doors
In August of 1990, Newsweek exposed the military's toxic disposal practices. It pointed out that "the military produces more tons of hazardous waste each year than the top five U.S. chemical companies combined." And it went on to call the Department of Defense, "America's most pervasive and protected polluter."
According to Newsweek, the military has for years enjoyed exemption from many of the environmental laws which regulate other hazardous-waste-producing industries. They have dumped carcinogens, acids, solvents, heavy metals and other toxic materials into carelessly constructed landfills and pits, and brushed off investigators. Protected by law from adequate enforcement measures, military officials easily covered up their reckless contamination throughout the seventies. The pleas of state agencies and environmental groups were largely ignored.
With the adoption of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) in 1980, State agencies began to gain some leverage over the Department of Defense in order to enforce their environmental regulations. But according to Jennifer Yezaek, an aide to Senator Benston, the law has been the focus of legal disputes, and it never in fact gave states the right to fine federal facilities for non-compliance. In late October, the Senate passed its own version of the Federal Facilities Compliance Act, intended to put some teeth into CERCLA. The new law will effectively allow states to levy fines against federal facilities that violate EPA regulations, if it makes its way through the final committee process.
CERCLA regulations instituted some military clean-up. The Department of Defense (DoD) did establish its own program in 1983 called the Installation and Restoration Program (mentioned above), which calls for a three phase process for identifying and restoring potentially contaminated sites. But, in traditional military fashion, officers have failed to inform the general public about this major project.
Indeed, not until this summer did news of this operation, the biggest engineering project DoD has ever undertaken, reach the pages of The New York Times.The department has promised to identify all hazardous sites strung out across their 25 million acres of land holdings and promised to remedy the situation. As of August 1991, says The Times, DoD has investigated 17,500 sites and identified 11,000 in need of restoration, and is still looking. To date, the Pentagon's Office of Inspector General estimates the cost could eventually be $100 billion to $200 billion, including the foreign bases.
The Money Trail
Despite these vast commitments to environmental spending, Friends of the Earth estimates that environmental spending for military bases for the fiscal year 1992 will actually be closer to $2.876 billion. Testing and monitoring sites is very expensive. The Times points out that drilling a well to take samples of polluted groundwater can cost $200,000. One soil sample can cost $500-$5,000.
Ironically, many of the contractors who helped create the mess are getting rich on the spoils. Bechtel National Inc., which built military installations for years for the government is now gelling much of its revenue from helping to clean them up. Raytheon Co., famous for the Patriot missile, is also looking at opportunities in the expanding market. Military-industrial officials told The Times that "the scattered environmental offices were not sharing information well, were suffering at times from duplicated efforts, and might not be supervising research or contractors closely enough. Unless such problems are corrected, they said huge sums of money could be wasted."
Walker, Haydell and Associates Engineering Firm is on contract to retest the sites that have been identified as toxic, including Bergstrom. Radian is also under contract with Bergstrom. Engineers dug several test wells and continue to monitor them, and have removed pesticides from an evaporation pit. So far, although they appear to have declared several sites "clean" and cleared them from further study, it is not clear how much cleaning has been completed. The public meeting will provide us with the space to ask exactly what we get and how much we pay for it.
Rivers of Jet Fuel
Bergstrom's phase-one study found 27 sites that needed attention. By the release of a phase-two Installation and Restoration Program study, enacted by Radian Engineering in 1989, the number had dwindled to seven. Field inspection documents clearing the other twenty sites were unavailable for Polemicist review. Many of the sites which remain on the list involve jet fuel and gasoline spills that have soaked into the ground or drained into Onion Creek. Here is a list of the seven remaining sites:
- In 1975 2,000-8,000 gallons of jet fuel spilled at site JP-4 and none were ever recovered. Groundwater samples contained carcinogenic chemicals. Soil samples found an organic vapor plume existing beneath tanks and appearing to be migrating southeast and southwest.
Bergstrom AFB occupies most of the upland recharge area to an alluvial aquifer that is separated from the deeper Edwards aquifer by a clay stratum, known as the Taylor marl. Discharges from Bergstrom flow via the South Fork Drainage Ditch into Onion Creek, or settle into the aquifer. Onion Creek, a high-quality aquatic life water supply (under Texas Water Commission standards) and a recreation area, receives approximately 70% of Bergstrom's runoff. In addition to petroleum hydrocarbons, the Radian study detected lead (known to cause mental impairment in children) and selenium, (linked to brain damage) in the creek's surface water and sediment.
An estimated 650-900 gallons per month of jet fuel apparently drained into this ditch prior to 1982. Though the Lower Colorado River Authority staff have been testing Onion Creek water since 1982 and state they have found nothing alarming, Radian evidence suggests that problems remain.
Pockets Full of Oil
One of the central threats to groundwater quality is Bergstrom's elaborate system of 74 underground storage tanks and the 25 above ground with a petroleum fuel capacity of 3 million gallons. The Texas Water Commission regulates the underground tanks, and Bergstrom oversees the raised tanks. In addition there is a 6,000 gallon underground tank that collects rinse water from paint stripping, considered a hazardous waste due to the heavy metals contained in it and the solvents used in the stripping process.
Radian tests showed high concentrations of total petroleum hydrocarbons in soil and ground water in a number of different sites. Where detected, rates ranged from over 500 parts per million to 6,200 parts per million. The City of Austin calls for remedial action when total petroleum hydrocarbons are greater than 100 parts per million.
Charles Finch, Texas Water Commission's field inspector for the last three years notes, "Those numbers are high, but Bergstrom is getting better. Compared to the number of underground tank violations they had in the last three years they have cleaned up their act considerably."
Texas Water Commission documents of 1990 show that past violations included negligent handling of their hazardous wastes, keeping unmarked drums of unidentified pesticides and explosive wastes for long periods, maintaining storage vaults without linings, etc. At one point, the base sent 35 hazardous rinse water shipments to Texas Industries, Inc. to be used as slurry in cement.
Now, technicians in Bergstrom's restoration program have narrowed their hazardous sites down to 5, excluding the South Fork Drainage Ditch and the evaporation pesticide pit from rehabilitation, according to the Walker, Haydell and Associates report. As already noted, the field inspection documents claiming them clean were not available to the public, and in fact the city admits that no one has really established the permanent environmental impact of these many years of solvent and fuel spills. Although the Walker is conducting further tests through well monitoring and soil samples, "the magnitude of effects on fauna, flora, and water quality where the aquifer discharges is unknown," the Walker report states.
The Airport Developmental Director's office reports that the city staff is currently creating a master plan (yet another in a time-honored Austin tradition) for Bergstrom's reuse as a city facility/airport. The city hopes that the base will be closed by 1993. However, according to staff, the master plan may or may not require the city to oversee environmental protection and renewal of the sites. The master plan will take 15-18 months to complete, and by next fall it will come before the City Council. If Austinites want to ensure that the cleanup abides by Austin water standards, then concerns about toxics must be pressed before any Council decision.
As Austinites make clear to City Council their commitment to water quality in the western hills, they must now decide whether to also fight for the quality of Onion Creek and its surrounding area. As the base closes, Del Valle will find itself much closer to Austin than before, and the Onion Creek area will be a prime target for development. New residents and old need clean water and safe recreational areas. Come to the meeting and ask the questions that will enable Austin to use this new facility safely and well.


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FASHION; Children Make the 60's New Again
By DEBORAH HOFMANN
Published: March 19, 1989
The generation gap may be narrowing, if children's accessories are any indication. Youngsters are complementing their neon novelty wear with emblems of the 1960's.
Both eras were in witty combination at a recent fashion show of 24 top children's designers at the Fashion Institute of Technology and sponsored by Children's Business, a trade magazine, and at the 30th annual International Kids Fashion Show at the Jacob K. Javits Convention Center, where nearly 900 dealers displayed their lines.
In schoolyards, the store-bought is seen alongside the improvisation. ''The hippie look is, like, totally amazing - John Lennon eyeglass frames, fringed jackets, patches with messages,'' said Jennifer Naliboff, 14 years old, a freshman at Midwood High School in Brooklyn. She and her friends scribble happy faces and peace symbols on white leather high-top sneakers and denim jackets. At Hunter Elementary School in Manhattan, Holly Nwogalanya , 9, wears the black felt beret of her parents' era, updated with colorful buttons.
''Anything about surfing is far out for big kids,'' said Yvonne Everett, 9, of Miami. ''But I can't relate to that yet.'' Her book bag is decorated with the once-ubiquitous yellow happy face.
''It was my idea to buy it,'' she added. ''But Mommy said O.K. She said it always made her feel good, too.'' Both the smiling face and the peace symbol are turning up on a children's line of button covers made by the Los Angeles company Click Its. Inspired by Cartoons
Two Manhattan hat designers exploit retrospective sources. Carol Amper Inc. makes beanie caps, for $22. Cozy velour hats by Kate Herman, of Etak, are inspired by cartoons and comics. Boys' styles include Jughead, Robin Hood, Rastafarian, Court Jester, Cat in the Hat and Cowboy styles. A gathered Minnie Mouse bowed beret is a favorite of young girls and mothers. They are elasticized and lined in cotton flannel and sell for under $40. Both makers are sold at Dinosaur Hill at 302 East Ninth Street, Shoofly at 506 Amsterdam Avenue near 84th Street and Space Kiddets at 46 East 21st Street.
What was once avant-garde has become conventional. Conservative children now wear sneakers unlaced, but the fashion elite have taken up shoelaces again.
Among the favored styles are Spring laces by Super Step in Somerville, Mass. A different shoelace is used for each pair of holes; the three-inch coils tuck into the holes. Having a dozen neon colors per shoe is said to be ''really flash.'' The laces are sold singly, out of fishbowls, or by the dozen, for $2.99, at Macy's, Bloomingdale's and athletic shoe stores. For girls, the company makes lacy wisps that are appearing on roller- and ice-skating rinks and sell for $2 a pair.
Today's sunglasses of choice are Roadies, made by Riviera. The fluorescent rubber frames add safety to skateboarding and sell for $15 at department stores including Macy's.
''Roadies are most excellent,'' said Michael Brawer, 11, of West Caldwell, N.J. ''The others are totally bogus.''
In appraising his son's gear, Michael's father, Steven, 38, a lawyer, echoes wistful parental peers. ''Michael has this totally cool look,'' he said. ''Secretly - I'm so stodgy now - I wish I could wear his wardrobe.''
Jamie Levatino Morris, 5 years old, wears a felt roller with velvet trim, one of the retrospective styles now in favor; A sneaker by Decoco, with Spring laces by Super Step (The New York Times/Sara Krulwich)


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It was billed as the "Fight of the Century" – the match between world champion Manny Pacquiao and undefeated world champion Floyd Mayweather, Jr. When every dime is accounted for, revenue from last Saturday's fight at the MGM Grand in Las Vegas is expected to top $400 million. Unsurprisingly, that is a record. Honest fans paid approximately $100 for pay-per-view access, and the fighters will ultimately split a purse worth more than $300 million. In the end, Mayweather won by unanimous decision and, by every metric, the fight was a massive success for the athletes, their promoters, and the Vegas machine. It was also a big letdown for fans who had waited for an epic match-up that arguably should have happened five years ago.
Reports subsequently revealed that Pacquiao injured his shoulder in the months leading up to the fight. On Wednesday May 6, he underwent arthroscopic surgery in Los Angeles to repair a torn rotator cuff in his right shoulder. Despite the preexisting nature of the injury, Pacquiao denied any "injury to [his] shoulders, elbows, or hands that needed evaluation or examination" on his pre-fight questionnaire submitted to the Nevada State Athletic Commission. Pacquiao's camp denied making any misrepresentation, stating that Pacquiao and his adviser, Michael Koncz, inadvertently "checked the wrong box" on the questionnaire.
Following the injury disclosure, boxing fans teamed up with a few entrepreneurially-minded class action litigators to flood the federal courts with lawsuits alleging fraud and conspiracy by the fighters, their promoters, the television networks, and television providers. See, e.g., here and here.
Of local interest, on Monday, two Philadelphia residents joined the fray with a class action matter filed in the United States District Court for the Eastern District of Pennsylvania. Plaintiffs, Allan Gordon and Seth Lamb named Showtime and HBO, Mayweather Promotions, LLC, Pacquiao and his promoter, Top Rank, Inc., Top Rank's CEO and President, Bob Arum and Todd Duboef, respectively, and Michael Koncz, alleging that the defendants conspired to conceal Pacquiao's injury. Protesting what they call a "sham fight," Plaintiffs complain that Pacquiao injured his shoulder so severely that he could not train for a period of two weeks. Plaintiffs suit is summarized in Paragraph 13:
Defendants each engaged in blatantly self-interested and wrongful conduct which violated the contractual expectations and rights of pay-per-view purchasers who fully anticipated and contracted for access to view and observe an honest and fair boxing match played in compliance with all laws, regulations, and [Nevada Athletic Commission] rules.
Gordon and Smith each paid $99.99 to watch the match – Gordon from his secondary home in Hallandale Beach, Florida, and Smith from his home in Philadelphia. They assert statutory claims under the Pennsylvania Unfair Trade Practices and Consumer Protection Law (the "UTPCPL") and the Florida Deceptive and Unfair Trade Practices Act, both of which provide for remedies in addition to actual damages. In the case of the UTPCPL, for instance, a consumer can recover three times the amount of his or her actual damages and an award of attorneys' fees for a proven violation of any provision of the UTPCPL. In addition to their statutory claims, Plaintiffs assert common law claims for tortious interference with a contractual relationship, fraud, breach of contract, unjust enrichment, and civil conspiracy.
Plaintiffs ask the Court to certify the matter as a class action and to designate Plaintiffs as representatives of a class that Plaintiffs anticipate will exceed "hundreds of thousands" of pay-per-view subscribers. In reality, the class of potential plaintiffs could exceed five million.
Given the number of actions and potential class members, it is likely that present and future actions arising from the fight will be consolidated by the United States Judicial Panel on Multidistrict Litigation for the purposes of reducing expense and the toll on judicial resources. The MDL is a panel consisting of six federal judges from across the country (including Third Circuit Court of Appeals Judge and former First Lady of Pennsylvania, Marjorie Rendell), which serves to (1) determine whether civil actions pending in different federal districts involve one or more common questions of fact such that the actions should be transferred to one federal district for coordinated or consolidated pretrial proceedings; and (2) select the judge or judges and court assigned to conduct such proceedings.
In the interim, the chairman of the NSAC, Francisco Aguilar, has already promised an investigation by the state attorney general's office, implying that Pacquiao might be facing perjury charges.


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A complimentary shuttle bus service is available between the Exhibition grounds and Expo MRT Station (CG1).
Visitors may follow the IMDEX Asia directional signs and board our shuttle bus from the designated pick-up spot upon arrival at the Expo MRT Station.
The schedules for the shuttle bus services would be available at a later date.
Passengers please take note:
- Eating and drinking are prohibited on the shuttle bus
- Passengers are not permitted to carry bulky items on board the bus
- Passengers who behave in an unruly and/or unsafe manner on the bus or at the bus stop will be barred from boarding the bus


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Board of Directors
United Way's volunteer Board of Directors plays a critical role in setting the strategic direction of the organization and for strict oversight on all the organizations operations. They donate their time, advocate for United Way in the community, and in many ways are our bridge to the community.
United Way of Indian River County
2016-2017 Board of Directors
Chair Susan Adams
Marsh Landing Restaurant
Chair Elect Erin Grall
Grall Law Group
Secretary Jennifer Peshke
Law Offices of Jennifer D. Peshke, P.A.
Treasurer Karl Williams
Marine Bank and Trust
Gregory Rogolino, CIC Chair
Past Chair Randy Riley
Florida Community Bank
E. Fred Augenstein
The Ad Agency
Jan S. Beck
Troy Corporation
Dr. David Becker
John F. Beckert
Christopher Bieber
CenterState Bank
Anthony Guettler
Gould Cooksey Fennell
Miranda Hawker
Indian River County Health Department
Katie Kirk
Daland Corp.
Margo Lind
Melissa Medlock, CPA, P.A.
Beth Mitchell
Sebastian River Area Chamber of Commerce
Jeffrey Petersen
Merrill Lynch
Alan S. Polackwich, Sr.
Jeffrey Schlitt
Schlitt Services
Jonathan Schwiering
Vero Insurance
Jeff Smith
Clerk of the Circuit Court
Colonel Martin Zickert
USAF, Retired


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Represents part of Cherokee County
502 Coverdell Legislative Office Building
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Beaches and Mayport area:
Best Western Mayport
2389 Mayport Rd
Atlantic Beach, FL 32233-2715 (904) 435-3500 60 rooms, 2 floors, Built 7 years ago (2001), Check In: 3:00 PM, Check Out: 12:00 PM High-speed Internet in public areas ($), Pool, Hot tub, Fitness room, Free parking
Comfort Inn Mayport
2401 Mayport Road (A1A), Atlantic Beach
(closest, right down the street from my departure dock)
Comfort Inn Oceanfront
1515 North First Street, Jacksonville Beach
Days Inn Oceanfront
1031 South First Street, Jacksonville Beach
Holiday Inn Express and Suites
2040 A1A Mayport Road Atlantic Beach Florida 904 435 0700
Capt Dave can also recommend other places near the departure dock to stay, just ask.
If you are staying in Jacksonville, please remember this town is very spread out. You can be in Jacksonville and yet be 35 miles from my departure dock. Please consult my Map & Directions page with a link to Mapquest.com for directions


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How I've Made Money Online: Paidviewpoint (Video)
PaidViewPoint Paidviewpoint has been an "extra money-maker" for me over the years. The survey site is an awesome way for you to monetize your free time without doing anything too strenuous. If you are looking for a way to make a couple extra bucks in your free time this video is for you. The video is the 5th installment […]Read more


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Translate 7000 words English to Russian
This project was awarded to maximrahr for $30 CAD.Get free quotes for a project like this
Project Budget$30 - $70 CAD
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We need a native Russian to translate 7000 words into Russian.
Only native and serious translators,
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Deadline: 4 days (The first 3500 days in 2 days and the rest within the next 2 days)
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