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The theranostic promise for neuroendocrine tumors in the late 2010s – Where do we stand, where do we go? (2018)
More than 25 years after the first peptide receptor radionuclide therapy (PRRT), the concept of somatostatin receptor (SSTR)-directed imaging and therapy for neuroendocrine tumors (NET) is seeing rapidly increasing use. To maximize the full potential of its theranostic promise, efforts in recent years have expanded recommendations in current guidelines and included the evaluation of novel theranostic radiotracers for imaging and treatment of NET. Moreover, the introduction of standardized reporting framework systems may harmonize PET reading, address pitfalls in interpreting SSTR-PET/CT scans and guide the treating physician in selecting PRRT candidates. Notably, the concept of PRRT has also been applied beyond oncology, e.g. for treatment of inflammatory conditions like sarcoidosis. Future perspectives may include the efficacy evaluation of PRRT compared to other common treatment options for NET, novel strategies for closer monitoring of potential side effects, the introduction of novel radiotracers with beneficial pharmacodynamic and kinetic properties or the use of supervised machine learning approaches for outcome prediction. This article reviews how the SSTR-directed theranostic concept is currently applied and also reflects on recent developments that hold promise for the future of theranostics in this context.
Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([\(^{68}\)Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [\(^{68}\)Ga]DOTATATE, we aimed to quantitatively investigate the biodistribution of [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([68Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden. Procedures: Of the 44 included patients, 36/44 (82%) patients demonstrated suspicious radiotracer uptake on [\(^{68}\)Ga]DOTATOC positron emission tomography (PET)/x-ray computed tomography (CT). Volumes of Interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUV\(_{mean}\)) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUV\(_{mean}\), maximum standardized uptake value (SUV\(_{max}\)), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman's rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden. Results: The median SUV\(_{mean}\) was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUV\(_{mean}\) 6.9, SUV\(_{max}\) 35.5, TBM 42.6g, and TBU 1.2%. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUV\(_{mean}\) increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUV\(_{mean}\) nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3%) vs. higher TBU (>7%), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET. Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [\(^{68}\)Ga]DOTATOC PET/CT. Potential implications include increased normal organ dose with [\(^{177}\)Lu-DOTA]\(^0\)-D-Phe\(^1\)-Tyr\(^3\)-Octreotide and decreased absolute lesion detection with [\(^{68}\)Ga]DOTATOC in high NET burden.
Purpose: We aim to provide an overview of the conventional single photon emission computed tomography (SPECT) and emerging positron emission tomography (PET) catecholamine analogue tracers for assessing myocardial nerve integrity, in particular focusing on \(^{18}\)F-labeled tracers. Results: Increasingly, the cardiac sympathetic nervous system (SNS) is being studied by non-invasive molecular imaging approaches. Forming the backbone of myocardial SNS imaging, the norepinephrine (NE) transporter at the sympathetic nerve terminal plays a crucial role for visualizing denervated myocardium: in particular, the single-photon-emitting NE analogue \(^{123}\)I-meta-Iodobenzylguanidine (\(^{123}\)I-mIBG) has demonstrated favorable results in the identification of patients at a high risk for cardiac death. However, cardiac neuronal PET agents offer several advantages inlcuding improved spatio-temporal resolution and intrinsic quantifiability. Compared to their \(^{11}\)C-labeled counterparts with a short half-life (20.4 min), novel \(^{18}\)F-labeled PET imaging agents to assess myocardial nerve integrity have the potential to revolutionize the field of SNS molecular imaging: The longer half-life of \(^{18}\)F (109.8 min) allows for more flexibility in the study design and delivery from central cyclotron facilities to smaller hospitals may lead to further cost reduction. A great deal of progress has been made by the first in-human studies of such \(^{18}\)F-labeled SNS imaging agents. Moreover, dedicated animal platforms open avenues for further insights into the handling of radiolabeled catecholamine analogues at the sympathetic nerve terminal. Conclusions: \(^{18}\)F-labeled imaging agents demonstrate key properties for mapping cardiac sympathetic nerve integrity and might outperform current SPECT-based or \(^{11}\)C-labeled tracers in the long run.
Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy (2018)
Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed. Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated. Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
Standardized reporting is more and more routinely implemented in clinical practice and such structured reports have a major impact on a large variety of medical fields, e.g. laboratory medicine, pathology, and, recently, radiology. Notably, the field of nuclear medicine is constantly evolving, as novel radiotracers for numerous clinical applications are developed. Thus, framework systems for standardized reporting in this field may a) increase clinical acceptance of new radiotracers, b) allow for inter- and intra-center comparisons for quality assurance, and c) may be used in (global) multi-center studies to ensure comparable results and enable efficient data abstraction. In the last two years, several standardized framework systems for positron emission tomography (PET) radiotracers with potential theranostic applications have been proposed. These include systems for prostate-specific membrane antigen (PSMA)-targeted PET agents for the diagnosis and treatment of prostate cancer (PCa) and somatostatin receptor (SSTR)-targeted PET agents for the diagnosis and treatment of neuroendocrine neoplasias. In the present review, those standardized framework systems for PSMA- and SSTR-targeted PET will be briefly introduced followed by an overview of their advantages and limitations. In addition, potential applications will be defined, approaches to validate such concepts will be proposed, and future perspectives will be discussed.
Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy (2018)
Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed. Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated. Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.
Volumetric and Texture Analysis of Pretherapeutic \(^{18}\)F-FDG PET can Predict Overall Survival in Medullary Thyroid Cancer Patients Treated with Vandetanib (2018)
Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET. Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated. Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.). Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.
Patterns of uptake of prostate-specific membrane antigen (PSMA)-targeted \(^{18}\)F-DCFPyL in peripheral ganglia (2017)
Objective: Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent \(^{18}\)F-DCFPyL. Methods: A total of 98 patients who underwent \(^{18}\)F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUV\(_{max}\)), and maximum standardized uptake value corrected to lean body mass (SUL\(_{max}\)) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUV\(_{max}\) and SUL\(_{max}\) values by the mean uptake in the ascending aorta (Aortamean) and the right gluteus muscle (Gluteusmean). Results: Overall, 95 of 98 (96.9%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4%), followed by the cervical ganglia (51/76, 67.1%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80%) and cervical 30/51 (58.8%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8%) of the analyzed stellate ganglia and in 45/76 (59.2%) of the celiac ganglia, whereas only 5/76 (6.6%) of the sacral ganglia demonstrated \(^{18}\)F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9%) and cervical ganglia (19/ 22, 86.4%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts. Conclusion: As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients' cancers must be understood. This is the first systematic evaluation of the uptake of \(^{18}\)F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research.
MI-RADS: Molecular Imaging Reporting and Data Systems – A Generalizable Framework for Targeted Radiotracers with Theranostic Implications (2018)
Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET) imaging agents for staging and restaging of prostate carcinoma or neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Both framework systems may contribute to increase the level of a reader's confidence and to navigate the imaging interpreter through indeterminate lesions, so that appropriate workup for equivocal findings can be pursued. Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e. if the reader is familiar with one system, the other system can readily be applied as well. In the present review we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a future role of the umbrella framework MI-RADS compared to other harmonization systems.
Subcellular storage and release mode of the novel \(^{18}\)F-labeled sympathetic nerve PET tracer LMI1195 (2018)
Background: \(^{18}\)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (\(^{18}\)F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. The favorable image quality with high and specific neural uptake has been previously demonstrated in animals and humans, but intracellular behavior is not yet fully understood. The aim of the present study is to verify whether it is taken up in storage vesicles and released in company with vesicle turnover. Results: Both vesicle-rich (PC12) and vesicle-poor (SK-N-SH) norepinephrine-expressing cell lines were used for in vitro tracer uptake studies. After 2 h of \(^{18}\)F-LMI1195 preloading into both cell lines, effects of stimulants for storage vesicle turnover (high concentration KCl (100 mM) or reserpine treatment) were measured at 10, 20, and 30 min. \(^{131}\)I-meta-iodobenzylguanidine (\(^{131}\)I-MIBG) served as a reference. Both high concentration KCl and reserpine enhanced \(^{18}\)F-LMI1195 washout from PC12 cells, while tracer retention remained stable in the SK-N-SH cells. After 30 min of treatment, 18F-LMI1195 releasing index (percentage of tracer released from cells) from vesicle-rich PC12 cells achieved significant differences compared to cells without treatment condition. In contrast, such effect could not be observed using vesicle-poor SK-N-SH cell lines. Similar tracer kinetics after KCl or reserpine treatment were also observed using 131I-MIBG. In case of KCl exposure, Ca\(^{2+}\)-free buffer with the calcium chelator, ethylenediaminetetracetic acid (EDTA), could suppress the tracer washout from PC12 cells. This finding is consistent with the tracer release being mediated by Ca\(^{2+}\) influx resulting from membrane depolarization. Conclusions: Analogous to \(^{131}\)I-MIBG, the current in vitro tracer uptake study confirmed that \(^{131}\)F-LMI1195 is also stored in vesicles in PC12 cells and released along with vesicle turnover. Understanding the basic kinetics of \(^{18}\)FLMI1195 at a subcellular level is important for the design of clinical imaging protocols and imaging interpretation.
We aimed to explore the impact of ageing on 11C-Hydroxyephedrine (11C-HED) uptake in the healthy rat heart in a longitudinal setting. To investigate a potential cold mass effect, the influence of specific activity on cardiac 11C-HED uptake was evaluated: 11C-HED was synthesized by N-methylation of (−)-metaraminol as the free base (radiochemical purity >95%) and a wide range of specific activities (0.2–141.9 GBq/μmol) were prepared. \(^{11}\)C-HED (48.7±9.7MBq, ranged 0.2–60.4μg/kg cold mass) was injected in healthy Wistar Rats. Dynamic 23-frame PET images were obtained over 30 min. Time activity curves were generated for the blood input function and myocardial tissue. Cardiac 11C-HED retention index (%/min) was calculated as myocardial tissue activity at 20-30 min divided by the integral of the blood activity curves. Additionally, the impact of ageing on myocardial 11CHED uptake was investigated longitudinally by PET studies at different ages of healthy Wistar Rats. A dose-dependent reduction of cardiac 11C-HED uptake was observed: The estimated retention index as a marker of norepinephrine function decreased at a lower specific activity (higher amount of cold mass). This observed high affinity of 11C-HED to the neural norepinephrine transporter triggered a subsequent study: In a longitudinal setting, the 11C-HED retention index decreased with increasing age. An age-related decline of cardiac sympathetic innervation could be demonstrated. The herein observed cold mass effect might increase in succeeding scans and therefore, 11C-HED microPET studies should be planned with extreme caution if one single radiosynthesis is scheduled for multiple animals.
Predictive value of \(^{18}\)F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib (2018)
Introduction: Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKI). We aimed to assess the role of metabolic imaging using 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography/computed tomography (PET/CT) shortly before and 3 months after initiation of TKI treatment. Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after TKI treatment initiation. During follow-up, CT scans were performed every 3 months and analyzed according to Response Evaluation Criteria In Solid Tumors (RECIST). The predictive value for estimating progression-free (PFS) and overall survival (OS) was examined by investigating \(^{18}\)F-FDG mean/maximum standardized uptake values (SUVmean/max) of the metabolically most active lesion as well as by analyzing clinical parameters (tumor marker doubling times {calcitonin, carcinoembryonic antigen (CEA)}, prior therapies, RET (rearranged during transfection) mutational status, and disease type). Results: Within a median follow-up of 5.2 years, 9 patients experienced disease progression after a median time interval of 2.1y whereas the remainder had ongoing disease control (n=5 partial response and n=4 stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5y after TKI initiation. Pre-therapeutic SUVmean >4.0 predicted a significantly shorter PFS (PFS: 1.9y vs. 5.2y; p=0.04). Furthermore, sustained high 18F-FDG uptake at 3 months with a SUVmean>2.8 tended to portend an unfavorable prognosis with a PFS of 1.9y (vs. 3.5y; p=0.3). Prolonged CEA doubling times were significantly correlated with longer PFS (r=0.7) and OS (r=0.76, p<0.01, respectively). None of the other clinical parameters had prognostic significance. Conclusions: Pre-therapeutic \(^{18}\)F-FDG PET/CT holds prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. Low tumor metabolism of SUVmean < 4.0 prior to treatment predicts longer progression-free survival.
Background: Precise regional quantitative assessment of renal function is limited with conventional \(^{99m}\)Tc-labeled renal radiotracers. A recent study reported that the positron emission tomography (PET) radiotracer 2-deoxy-2-(\(^{18}\)F-fluorosorbitol (\(^{18}\)F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, (\(^{18}\)F-FDS is available via simple reduction from routinely used 2-deoxy-2-(\(^{18}\)F-fluoro-D-glucose ((\(^{18}\)F-FDG). We aimed to further investigate the potential of (\(^{18}\)F-FDS PET as a functional renal imaging agent using rat models of kidney diseases. Methods: Two different rat models of renal impairment were investigated: Glycerol induced acute renal failure (ARF) by intramuscular administration of glycerol in hind legs and unilateral ureteral obstruction (UUO) by ligation of the left ureter. 24h after these treatments, dynamic 30 min 18F-FDS PET data were acquired using a dedicated small animal PET system. Urine 18F-FDS radioactivity 30 min after radiotracer injection was measured together with co-injected \(^{99m}\)Tc-diethylenetriaminepentaacetic acid (\(^{99m}\)Tc-DTPA) urine activity. Results: Dynamic PET imaging demonstrated rapid (\(^{18}\)F-FDS accumulation in the renal cortex and rapid radiotracer excretion via kidneys in control healthy rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in ARF rats and UUO-treated kidneys. Measured urine radiotracer concentrations of (\(^{18}\)F-FDS and \(^{99m}\)Tc-DTPA were well correlated (R=0.84, P<0.05). Conclusions: (\(^{18}\)F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. Advantages of high spatiotemporal resolution of PET imaging and simple tracer production could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.
SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework (2018)
Reliable standards and criteria for somatostatin receptor (SSTR) positron emission tomography (PET) are still lacking. We herein propose a structured reporting system on a 5-point scale for SSTR-PET imaging, titled SSTR-RADS version 1.0, which might serve as a standardized assessment for both diagnosis and treatment planning in neuroendocrine tumors (NET). SSTR-RADS could guide the imaging specialist in interpreting SSTR-PET scans, facilitate communication with the referring clinician so that appropriate work-up for equivocal findings is pursued, and serve as a reliable tool for patient selection for planned Peptide Receptor Radionuclide Therapy.
Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach (2017)
C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.
Bildgebung der frühen linksventrikulären Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell (2017)
Einleitung: Die linksventrikuläre diastolische Dysfunktion (LVDD) ist bei Diabetikern noch vor Entwicklung einer klinisch apparenten Herzinsuffizienz eines der ersten Anzeichen einer kardialen Beteiligung. Daher soll in dieser Studie untersucht werden, ob die LVDD mit ECG-gated F-18-FDG PET in einem Diabetes-Rattenmodell dargestellt werden kann. Methodik: Es wurden F-18-FDG PET Scans in einem Typ-2-Diabetes Rattenmodell (ZDF fa/fa, n=6) und in ZL Kontrollen (n=6) vorgenommen (Alter, jeweils 13 Wochen). Unter Hyperinsulinemic-Euglycemic Clamp-Technik wurden 37 MBq 18F-FDG über die Schwanzvene appliziert. 15-35 Minuten nach Tracergabe wurden mittels eines Kleintier-PET-Scanners sowie unter EKG-Ableitung PET Scans angefertigt (16 frames/cardiac cycle). Die linksventrikuläre Ejektionsfraktion (EF) und die Peak Füllrate (PFR) wurden mittels einer geeigneten Software (Heart Function View) gemessen, wobei die Software an die Größe des Rattenherzes angepasst wurde. Ergebnisse: Im Alter von 13 Wochen entwickeln ZDF Diabetes-Ratten eine im Vergleich zu Kontrolltieren eine signifikante myokardiale Hypertrophie, bestätigt durch post-mortem Analyse des Herzgewichtes (994±78mg vs. 871±44mg in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.01). ECG-gated PET zeigte eine signifikante Abnahme der LV diastolischen PFR (10.4±0.5 vs. 11.8±0.4 EDV/sec in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.001), jedoch zeigte sich kein signifikanter Unterschied zwischen LVEF und der Herzfrequenz in den untersuchten ZDF Diabetes-Ratten und Kontrollen (LVEF: 60.0±4.5 vs. 63.7±4.1%, n.s. und HR: 305±25 vs. 323±24 bpm, n.s.). Schlussfolgerung: Im Diabetes-Ratten-Modell kann unter Verwendung eines ECG-gated FDG-PET Protokolls die diastolische Dysfunktion als Parameter der frühen diabetischen Kardiomyopathie nachgewiesen werden.
The novel PET probe 2-deoxy-2-18F-fluoro-D-sorbitol (18F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in two human volunteers. 18F-FDS was produced by a simple one-step reduction from 18F-FDG. On dynamic renal PET, the cortex was delineated and activity gradually transited in the parenchyma, followed by radiotracer excretion. No adverse effects were reported. Given the higher spatiotemporal resolution of PET relative to conventional scintigraphy, 18F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from 18F-FDG, 18F-FDS is virtually available at any PET facility with radiochemistry infrastructure.
Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMARADS- 3B Categories (2018)
Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has become commonly utilized in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa. Methods: PET/CT imaging with \(^{18}\)F-DCFPyL was carried out in 110 patients with PCa and lesions were categorized according to PSMA-RADS Version 1.0. 56/110 (50.9%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions and 22/56 (39.3%) patients had adequate follow-up to be included in the analysis. The maximum standardized uptake values (SUV\(_{max}\)) of the lesions were obtained and the ratios of SUV\(_{max}\) of the lesions to SUV\(_{mean}\) of blood pool (SUV\(_{max}\)-lesion/SUV\(_{mean}\)-bloodpool) were calculated. Pre-determined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine if they demonstrated evidence of underlying malignancy. Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were evaluable on follow-up imaging. 27/46 (58.7%) lesions demonstrated changes on follow-up imaging consistent with the presence of underlying PCa at baseline. These lesions included 24/32 (75.0%) PSMA-RADS-3A lesions and 3/14 (21.4%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up. Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and this information should be taken into when guiding patient therapy.
Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging (2018)
Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center. Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed. Results: The number of target lesions identified by each observer were as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least two individual observers (all four readers selected the same target lesion in 58/125 (46.4%) instances, three readers in 40/125 (32%) and two observers in 27/125 (21.6%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC=0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC=0.84), with a significant difference for ER (ICC=0.97) vs. IR (ICC=0.74, P=0.005). Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.


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surprise! we are in texas for christmas this year!
we have been planning a surprise visit to see ben's brother matt and his family for matt's 40th birthday, which just so happens to be on christmas day. i couldn't write about it, because he reads this blog and facebook, but after 3 days in a car caravaning with ben's mom & twin sister & her family, we arrived.
the surprise went off without a hitch and now we're here to enjoy ourselves. this break from stress, worry, and sadness is exactly what we needed.
it has been a big, loud, happy, messy, laughing, fabulous christmas. and the fun isn't over yet!
i'm so grateful for this crazy group of people, and all of my other loved ones.
happy christmas!
may your days be merry and bright.


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Chloe Buckley, a Carmel Valley girl now residing in Del Mar, throws water while blowing the tail during the Championship Final. That wave, on which she scored 7.71, put her in first place. The 19-year-old, second-generation North County native and student at MiraCosta College, has won the National Title in the Women's 18 and over division at the Surfing American USA National Championship at Lower Trestles in June. Her father Pete Buckley and brother Jack are her biggest fans and sponsors. Buckley is now surfing in the World Qualifying Series and is working to bring a World Championship home to North County. Courtesy photo
The Coast News has been delivering high-quality news, community voice and storytelling since its inception in 1987. Since then, the news organization has grown into a successful newsgroup covering a majority of San Diego's populous North County region.


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We have currently paused new affiliate registrations w.e.f. 5th May 2018 until further notice
while we work on developments and improvements to the FAP(Flipkart Affiliate Program) platform.
If you are an existing affiliate partner, you can continue promoting Flipkart URLs on your inventory as traffic, order & install attribution will be working as usual.


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The 45th President-Elect of the USA
The 45th President-Elect of the USA. At 2.52am Eastern Time today, Hillary Clinton called Donald Trump to congratulate him on winning the Presidency of the United States of America. The Republican Party also holds the majority in the Senate and the House of Representatives. Read Articles Here: Live Coverage SummaryContinue reading


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The central government is expected to offer more subsidies to providers of aged care services, with some regions to be selected for test runs of the program, the Shanghai Securities News reported Friday, citing vice civil affairs minister Dou Yupei. The State Council released a reform plan for the industry in September and the Ministry of Civil Affairs is working on policy details, Dou was quoted as saying.
– Contact HKEJ at [email protected]


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Price beating policy
7 days replacement warranty
Genuine products
Two 5dBi External Detachable Antennas
Two high gain external antennas insure stronger transmission and reception capacity. The two detachable antennas can be rotated and adjusted in different directions to fit various operation environments. For even more demanding applications, the antennas can also be replaced with diverse indoor antennas or directional antennas (using standard RP-SMA connector) to show even greater flexibility and wider wireless coverage.
High Power for Strong Penetrability
With high transmission power, the TL-WN8200ND delivers up to 10 times the range of normal power USB adapter. Moreover, TL-WN8200ND is featured with its incredible and strong penetrability, making that you don't have to be physically tethered to the walls or floors to access the Internet.
High Receive Sensitivity for Reliable Signal
TL-WN8200ND features its high receive sensitivity, which could let you move further away from the access point while still maintaining the same wireless signal. In this case, using TL-WN8200ND means that you don't have to move the laptop like a divining rod, and you can easily pick up the network with its strong sensitivity.
Desktop-Style Design & 1.5m USB Extension Cable
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Overview of Vivotek IP8332
The Vivotek IP8332 combines clear megapixel resolution with an outdoor-ready housing and day/night functionality, providing a powerful surveillance tool. Video up to 1280x800 (1MP) resolution can be monitored, providing crisp, detailed footage which makes identification easy. The tough outdoor-ready casing is IP66-rated so can be mounted outdoors without the need for an additional weatherproof housing.
Usable video can be captured 24 hours a day with the camera's switchable infrared-cut filter, producing color video in normal light conditions and infrared-sensitive black and white footage when light levels drop. The camera also features integrated IR LEDs, illuminating objects up to 50ft away for true night vision.
Video can be recorded directly onto the camera when used with a MicroSD memory card, increasing reliability by eliminating external recording applications. Additionally, tamper detection software is built into the camera, which triggers recording or email notifications if the camera is covered, moved, obscured or spraypainted, reducing downtime. H.264 compression also helps to reduce recorded video file sizes, enabling smooth video streaming across low bandwidth networks.
Key features and benefits
- Capture greater image detail than a standard IP camera, making identification of people and objects easy
- Install the camera outdoors where conventional cameras can be damaged by weather conditions
- Monitor video 24 hours a day using the camera's day/night functionality and integrated IR lights
- Increase recording reliability and remove the need for external recording equipment with MicroSD card recording
- Maximize video recording capacity and stream smooth video over low-bandwidth networks with H.264 compression
- Bundled software provides surveillance for up to 32 Vivotek network cameras
Typical use
- The IP8332 is ideal for any outdoor security installation requiring megapixel image resolution combined with 24 hours surveillance in locations such as store fronts, loading bays, warehousing, storage yards and residential premises.
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- Software: Milestone Xprotect, SecuritySpy, Vivotek ST7501
- Network Video Recorders (NVRs): QNAP
Available models
- Vivotek IP8330 - VGA resolution outdoor camera with high frame rate and integrated IR lighting


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Browsing Mathematics and Computer Studies (Peer-reviewed publications) by Author "Flatley, Ronan"
Now showing items 1-2 of 2
A note on the computation of symmetric powers of hyperbolic forms and of trace froms on symbol algebras Flatley, Ronan (Scientific Advances Publishers, 2014)Let K be a field with characteristic different from 2 and let S be a symbol algebra over K. We compute the symmetric powers of hyperbolic quadratic forms over K. Also, we compute the symmetric powers of the quadratic trace ...
Trace forms of symbol algebras (Pre-published version) Flatley, Ronan (World Scientific Publishing Complany, 2012)Let S be a symbol algebra. The trace form of S is computed and it is shown how this form can be used to determine whether S is a division algebra or not. In addition, the exterior powers of the trace form of S are computed.


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Solid waste management firm mulls power plant
By Madelaine B. Miraflor
While the administration intensifies the implementation of Solid Waste Management Act (RA 9003) amid the country's worsening garbage problems, a solid waste management firm now considers building a waste-to-energy plant, but without the intention of really venturing into energy sector.
"It is going to be a waste disposal project," Metro Clark Waste Management Corp. (MCWM) President and Chief Executive Officer Rufo Colayco specified.
For MCWM, building a waste-to-energy plant is one of the solutions that can partly solve the country's worsening garbage problems.
"If you look at it as power generation project, there's the end. They should see it as waste disposal project that happens to have an electricity component," Rufo said, not discounting the fact that the electricity you can generate from this kind of renewable energy facility would surely cost higher.
MCWM Director for Technical Services Holger Holst said Philippine population has been growing at a rapid pace. This means that waste generation will also grow.
"Waste is not finished. That's for sure. Philippine population will double by 2050. You need so much area. We have to look for the next step how we can reduce the garbage. Reduction at 20 to 25 percent is not going to be enough," Holst said.
MCWM currently owns a world-class sanitary landfill within the Clark Special Economic Zone, some 80 kilometers north of Manila.
The sanitary landfill is located on a 100-hectare land, of which 70 hectares are dedicated for the landfill, 10 hectares for recycling facilities and 5 hectares for offices and other infrastructure. The remaining 15 hectares acts as environmental buffer.
The facility comes with recycling facilities, leachate storage and treatments pods as well an environmental buffer.
As per Rufo, the sanitary landfill is the only one in the Philippines that conforms to internationally accepted standards that substantially exceed the requirements of RA 9003.
Right now, the company serves 90 municipalities in Central Luzon.
Both Holst and Rufo agreed that waste-to-energy could be the future of their company in the Philippines but that might not happen until the government started seeing it the way they see it.
"You generate electricity when you burn the waste. But the cost of cleaning up is high. The cost of electricity the plant will generate is not that competitive compared to that of a coal-fired power plant," Rufo said.
"The last step is to have someone to sign a power purchase agreement with us but then they would look upon us as another power producer, which should not be the case. But I think the government will come around to seeing it that way," he added.
Rufo said that the key is for the government to recognize that this is not a power producing project but a waste disposal project to further reduce the cost of waste disposal in the country.
Holst said to sustain economic growth, the government must make waste management a priority.
"They have to do something. They have to make this higher priority. Based on ADB [Asian Development Bank], the government should invest 1.5 percent of gross domestic product [GDP] for waste management and we are far away from that," Holst said.
The government recently intensified its implementation of RA 9003, going after non-compliant companies as well as local government units (LGU).
This, after Environment Secretary Roy A. Cimatu promised to make the full implementation of RA 9003 as one of his top priorities soon after he assumed the DENR post in May last year.
As part of this effort, Cimatu even threatened to close down Boracay if a lot of companies and commercial establish in the islands will continue to defy the law.
Tags: Clark Special Economic Zone, garbage problems, Metro Clark Waste Management Corp., Philippine population, Rufo Colayco, solid waste management, Solid waste management firm mulls power plant, Technical Services Holger Holst, waste disposal project


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Welcome to the Never Say Die Weekly playlist! Updated every Friday. Regular artist takeovers. Dubstep ◘ Trap ◘ House ◘ Riddim ◘ Bass
16 songs
Listen to NSD Weekly [Dubstep • Trap • Bass] in full in the Spotify app


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3202 N. Mountainside Loop Road, Buckeye, AZ 85326 US Glendale Land for Sale
3202 N. Mountainside Loop Road, Buckeye, Arizona
Mountain Coves District at Verrado
Property Details
Listing Information
- Lot Size: 79288
- Style: Custom
- Schools: 79/216
- Taxes: $863
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Property Description
Nearly 2 acre mountainside custom home site located in Mountain Coves District at Verrado! Enjoy gorgeous city light and mountain views from your dream home. Private lot is located in a secluded cul-de-sac and backs a natural preserve. Verrado offers 20 neighborhood parks, village sport and health club, 18 hole public golf course, brand new schools, and a lively main street. There are no restrictions on builder or building. Property has not been assessed.
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Mission Moment July – 2017
(July 18, 2017)
Lung Association volunteer and lung cancer
survivor Lysa speaks out to protect healthcare.
Fight for Healthcare Continues: If the Senate passes the latest version of its healthcare bill, 32 millions of Americans would lose their health coverage. We can't let this happen and must keep the pressure on Senators to reject this bill. You can help! We are asking everyone to sign this petition to urge their Senators to vote "no" on this harmful bill. Please share the petition link in your social network and use #ProtectPatientsNow when you spread the word. With your help, we can protect healthcare for the millions with lung disease who depend on it.
House Poised to Vote on "Smoggy Skies Act" (H.R. 806): We expect the House of Representatives to vote on the Smoggy Skies Act (H.R. 806), during the week of July 18. This bill would delay ozone protections and permanently weaken the Clean Air Act. The American Lung Association sent a letter from health and medical organizations opposing the Smoggy Skies Act to House members and shared our ozone poll from earlier this year, which found that by a 2-to-1 margin, Americans support the U.S. Environmental Protection Agency's (EPA) more protective limits on smog.
Standing Up for Methane Standards: On July 10, Lung Association staff testified at a public hearing at the EPA to oppose delaying standards that would limit methane and other air pollutants. EPA has proposed a two-year delay of its current requirements for new and expanded oil and gas facilities to limit emissions of methane and other harmful air pollutants, including some carcinogens. EPA now is taking public comment on the proposed delay. The Lung Association opposes the delay and joined with representatives from other health and medical organizations to share the health impacts this delay particularly on the most vulnerable.
Healthy Air Partners Deliver Climate and Health Declaration to EPA Administrator: On June 19, the Lung Association joined 17 other national health and medical organizations to release an updated Declaration on Climate Change and Health, which highlights the health impacts of climate change and calls for bold action. That same day, CEOs and senior leaders of 13 national health and medical organizations, led by Lung Association National President and CEO Harold Wimmer, delivered the Declaration in person to Administrator Pruitt during a meeting at EPA Headquarters. The group talked with the administrator about the importance of EPA implementing and enforcing the Clean Air Act and the urgent need to reduce pollution that drives climate change. We also expressed our disappointment with EPA's recent decision to delay implementation of the more protective 2015 ozone standards. Check out the photo of the group here.
Legal Action Against EPA on the Ozone Standard Delay: On July 12, the American Lung Association, the American Thoracic Society, the American Public Health Association and others took legal action to stop the EPA's unnecessary delay in the implementation of the lifesaving 2015 ozone national air quality standard. The Lung Association and other organizations asked the U.S. Court of Appeals for the District of Columbia Circuit to throw out or block the delay by EPA. Here is the American Lung Association's press statement announcing this legal action.
Partnering with Nurses on Climate Change: Lung Association staff presented a plenary session on federal climate and clean air policy at the Association of Nurses for a Health Environment (ANHE) annual conference on June 13th in Washington, D.C. The conference was themed "Climate Change, Health, & Nursing: A Call to Action," and featured speakers including former EPA Administrator Gina McCarthy. Nearly 100 nurses from 12 different associations attended the training.
LUNG FORCE-Funded Researcher Connects Sugar and Lung Cancer: The American Lung Association's LUNG FORCE initiative has made a commitment to double our lung cancer research funding. One of the researchers that we have recently supported, Jung-whan Kim, PhD of the University of Texas at Dallas, published results from his study, "The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition" in the online journal, Nature Communications. Dr. Kim found that sugar serves as an energy supply in squamous cell carcinoma, a type of lung cancer almost always caused by smoking that accounts for 25 to 30 percent of all lung cancers. Currently, the available targeted therapies for squamous cell carcinomas are not effective. Dr. Kim's finding may help lead to new targeted therapies that may prove more effective for squamous cell lung cancer.
LUNG FORCE Hero: Rachel M. used to describe herself a mother, wife, military service member and career woman. Since April of this year, she has added something new – lung cancer patient with adenocarcinoma. Now she's partnering with LUNG FORCE to raise awareness, find a cure and bring about change.
2017 Volunteer and Staff Awards: The work of the American Lung Association would not be possible without a dedicated corps of volunteers and staff. In June, we recognized excellence among our volunteers and staff at a ceremony in Chicago, where we also presented, in conjunction with C. Everett Koop Foundation, the C. Everett Koop Unsung Heroes Award to an advocate for tobacco control who has made significant, but frequently unrecognized contributions to reduce the burden of tobacco use.
Back to School with Asthma: It may still be summer, but the start of the school year is just around the corner. Returning to school for a child with asthma can be challenging and stressful. The Lung Association is here to help. We have scores of tools and information for students, parents, including our Back-to-School Checklist to make sure you and your child are ready for a safe and healthy school year.
Improving Coverage for Asthma Care: The Lung Association's Asthma Care Coverage Project takes a comprehensive approach to track state Medicaid coverage and barriers to access in seven different areas of guidelines-based asthma care treatments and services. This year marks the first time that coverage and barrier information for all 50 states, District of Columbia and Puerto Rico is easily available. This project represents a unique opportunity to educate patients, providers and decision makers about the importance of coverage and access to asthma guidelines-based care in Medicaid to help improve asthma health outcomes for children and adults. Learn more.
Did you know that COPD is the third leading cause of death in the United States? The American Lung Association is a founding partner of the newly created COPD National Action Plan. Our EACH Breath Blog has details. While you're there, read our latest entry, "Support from Day One: Preparing for Lung Cancer Treatment," which helps guide patients and caregivers through treatment options following a lung cancer diagnosis.
Your generous support makes everything we do possible.
THANK YOU for all you do to support healthy air and healthy lungs. The lifesaving work of the American Lung Association is driven by an exceptional team of volunteers and staff across the country. We always have opportunities for those who share our passion for lung health to join in our work.
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text: Action Bros is an action packed online game that gives you the option to play in Single Player Mode or Multiplayer Mode. Better weapons and useful upgrades can be availed as the game play continues. Playing as the hero in the game you will have to complete the dangerous missions by defeating all the enemies that you face.


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Cruising's not for us. It's for old people. Who wants to be cooped up on a boat all day. It'll be really expensive….and so on and so on. That's why we chose not to go on a cruise.
But we were wrong.
We eventually decided to go because someone we knew actually got themselves a job on a cruise ship on a long-term contract so to offer moral support and some friendly faces we decided to look into a short haul cruise.
You can book really early
We booked early in September 2017 and our cruise wasn't due to take place until February 2018. The bonus of this is that as a thank you the cruise company, in this case, P&O gave us an allowance to spend on board of £80 EACH. Given that the cruise we'd chosen was only four days, that wasn't too bad. Booking this early also gave us the opportunity to choose exactly what kind of cabin we wanted. We were never going to go for the penthouse, luxury suites but again we didn't want to be cooped up in a tiny box with no windows. We chose a junior suite with a sea view and balcony and when we opened the door to it we were astonished at just how much space we had.
Now, this must come at a price, right?
Not really, we worked out that the whole thing cost about the same as we would spend on a week away in Portugal.
It's all-inclusive
Well, the food is. All we paid for were the drinks and I thought they'd be massively overpriced but what a pleasant surprise to find they were no more expensive than the average pub.
On our ship, the Oceana, which by ship terms at 2000 passengers is pretty small there were about four or five different restaurants to choose from.
In addition to the restaurants included in the price, the shows are also free to see and with two theatres both showing well-rehearsed, professional quality productions you'll be spoilt for choice.
The service is second-to-none
We were impressed on our arrival in Southampton that our cases were taken and we didn't see them again until we boarded and they were outside our door.
Take a seat at a bar or cafe and within seconds, you'll be asked what you'd like. There's no obligation to have anything of course, but the level of service is that high.
Sit down to dinner and orders are taken within moments. Food arrives almost without delay. If I had one tiny gripe then it would be that it's clear the food is not prepared to order, but if I was catering for 2000 people I wouldn't prepare it to order either!
There's a chance to dress up
I can't speak for every cruise but certainly, on this one there was a Gala night and men wore black tie and dinner jacket, women were in cocktail dresses or evening gowns. I don't know about you, but it's not often I get a chance to wear my DJ and bow-tie and I loved the glamour of the evening.
You can do a whistle-stop tour at each port
The cruise we chose docked at Bruges and Amsterdam and the stop generally gives you just enough time to disembark, get to the centre and tick off all the major sights you need to see to get a big 'been there' in your travel diary. If you're intent on seeing as many places as possible in a short space of time then cruising has to be the way to go.
It is surprisingly luxurious
We didn't pay a fortune for our brief dalliance into the world of cruising but the luxury you experience makes you feel like you've spent your entire life-savings; staircases wind luxuriously down to an atrium decorated in gold while a glass-windowed lift glides slowly up and down the floors.
An art gallery is available for viewing original works of art and bars stock expensive brands of liqueur. There are even shops on board with top name brands like Boss, Ralph Lauren, Ray-Ban and more to tempt you into parting with your money.
It's not just for old people
The image of cruising is that it is dedicated to the old and wealthy and cruise companies have worked hard to shed that image. The cross-section of passengers on board our recent trip was as broad as you'd expect to see on any holiday.
So, that was our first experience of cruising. Was it enjoyable? Definitely yes. Would we do it again? Definitely yes. Are we converted to die-hard cruisers? Mmm probably not, but it was an experience we'd certainly repeat, but next time go somewhere hot so we can make the most of the balconies and the upper decks.
Has this tempted you into giving a cruise a try?
Let me know.


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Campus Stockton Teaching Alliance: Teach Direct
At Junction Farm, our commitment to training and recruiting outstanding practitioners is extremely important to us. We believe that the best way to inspire children to learn and give them the skills and knowledge to do this is through having teachers who have excellent teaching and learning skills.
We achieve this by working closely with Initial Teacher Education providers to collaborate in the training and development of trainee teachers.
So, if you have a degree, the desire to inspire children and promote lifelong learning by being a teacher, you can find out more information about the partnerships we work with using the links below.
In alliance with:
We also work with www.stockton.gov.uk/scitt
For any further information on what becoming a teacher might involve more generally, you can also visit https://getintoteaching.education.gov.uk/
We look forward to hearing from you.
Kind regards,
Karen Norton


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Slow performance and programs 'hanging' are signs that your PC's memory isn't sufficient: More programs running at the same time means more memory usage.
In addition, when installing new software there are often minimum memory requirements. Check the software's packaging for details.
Here's how you check your computer's available RAM on a Windows 10 PC:
Step 1 – Power up your PC
Step 2 – Type 'system information' into the search bar
Step 3 – Scroll down to installed Physical Memory (RAM)
In this example, the PC has 8 GB of 'Installed Physical Memory (RAM)'. Check the PC's instruction manual or search for your PC on the manufacturer's website to find out whether you are able to install more RAM to increase your PC's memory and the type of RAM required e.g. 240 pin DIMM DDR3.
Just under the total installed physical memory is the 'Available Physical Memory'. In the above example, 3.5 GB is available. This tells you that the programs currently running on the PC are using 4.5 GB.
Increasing the RAM often improves performance especially when more than one program is running at the same time. Extra memory is also relatively inexpensive and is easy to install. You will need to open the PC's case to get to the motherboard but your PC's user guide should walk you through the installation of additional RAM.
Amazon and eBay have a large number of RAM upgrade kit sellers at competitive prices.


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Tax Management Services
Assurance and Advisory Services
Estate and Trust Planning and Tax Preparation
IRS Representation
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Dave has this so ingrained in his head, that he's made me crazy with it. "Don't spoil your dinner." Dave's mom told him this enough that if it's a moment after lunchtime, we can't have a snack, sliver, or morsel! I've had to remind Dave on many occasions that I'm a grown woman and can certainly decide if I'm actually hungry of not. Laughing.
Mason on the other hand, well, he will spoil his dinner. Thanks to Dave and his moms words of wisdom, Mason is on the right track! Did you hear this gem as a kid? I did, but it didn't stay with me like it did for Dave. What is the one that stayed with you? Post a comment!


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She not only brings her extensive experience in law, but has the very valuable perspective of a parent of the same generation as the Academy's current cadets' parents and has served as an active Trustee for eighteen years.
Fork Union, Virginia (PRWEB) July 05, 2017
After twenty-two years as Chair of the Board of Trustees of Fork Union Military Academy, William J. Vakos, Jr., asked the Board to consider passing the responsibility on to the next generation of leadership. By unanimous vote, as of July 1, Paige Lester Pruett, takes over as the Chair of the Board of Trustees.
Paige Lester Pruett is the youngest child of E. H. "Jack" Lester, an alumnus of Fork Union Military Academy's Class of 1951. She grew up steeped in the legacy of the Academy and understands the positive role the Academy played in Jack Lester's life and his success as the founder of Knox Creek Coal Corporation in Grundy, Virginia.
Pruett graduated from the University of Virginia in 1993 with a B.A. in Economics and Foreign Affairs and earned her Juris Doctor from the University of Virginia's School of Law in 1996. Pruett then began her legal career with the prestigious firm of McGuireWoods LLP in Richmond, Virginia. In 2003, Pruett was named Senior Counsel at Dominion Resources Services Company, Inc., in Richmond, Virginia. In 2010, she began practicing law as a self-employed attorney, serving primarily as counsel to GE Digital.
Pruett was elected to the Fork Union Military Academy Board of Trustees in 1998. She has also served on the Board of Trustees and Foundation Board of Stuart Hall School in Staunton, Virginia, and is a past member of the Board of Trustees of Jacob's Ladder, Inc.
As Chair of the Finance Committee and Investment Sub-Committee, Pruett is a member of the Executive Committee of the Board. In addition, Pruett also currently serves as Chair of the Board of Trustees' Enrollment Task Force, which works closely with the Academy's staff to ensure that the Academy's marketing and communications strategy is appropriate and effective.
"Paige Lester Pruett was raised in the family of an alumnus who loved and generously supported Fork Union Military Academy," said the Academy's president, RADM J. Scott Burhoe. "She not only brings her extensive experience in organizational and human resources law, but has the very valuable perspective of a parent of the same generation as the Academy's current cadets' parents and has served as an active Trustee of the Academy for eighteen years."
William J. Vakos, Jr., will continue to serve as a member of the Board of Trustees and as a member of the Executive Committee. This will help provide a seamless transition in the leadership of the Board.
The father of a Fork Union Military Academy graduate (Bryan Vakos of the Class of 1990), William J. Vakos, Jr., was elected to the Board of Trustees in 1985. His record of service in the years since, and the quiet generosity of William Vakos and his wife Mary, in both their time and treasure, has been an invaluable source of strength for the Academy.
Throughout the terms of four school presidents, the careful and solid leadership of William Vakos has been a steadfast force in guiding the school forward. His unflappable courage and determination, his sharp knowledge and breadth of experience, and his expertise in building and development helped guide the Academy through an unprecedented era of growth and expansion of campus facilities.
During his twenty-two years as Chair, and his thirty-two years as a member of the Board of Trustees, William Vakos has overseen three decades of tremendous improvement for the campus of Fork Union Military Academy with the addition of the Estes Athletic Center, the Moretz Academic Center, the Estes Dining Hall, Pruitt Lake and Pavilion, the Veterans Memorial, the renovation of Hatcher Hall to add the lower level Academic Center, the E. H. Lacy outdoor track facility, a new wastewater treatment plant, a major addition to the Beatty Library, the Aquatics Center, the restoration of Wicker Chapel, and, the crown jewel of his board tenure-the completion of the Jacobson Hall barracks.
In the summer of 2016, Vakos was awarded the Academy's highest honor, the R. L. "Red" Pulliam Award for Distinguished Leadership, recognizing his "outstanding leadership and significant contributions toward the betterment of Fork Union Military Academy." The award's citation further states that his "leadership characteristics of integrity and service to the Academy, coupled with strong Christian morals and values, set this person apart from all others and make him a role model not only for the Corps of Cadets, but for his fellow man."


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India-Russia Festival of Science & Culture
Kalinka, the dance ensemble from Russia at the DAE Convention Centre, Mumbai
Further strengthening the bond between the two countries, the Festival was organised jointly by the DAE Cultural Council, India and ROSATOM, Russia. It comprised of a spectrum of interesting science activities for the school children and a colourful extravaganza of Indian and Russian performing arts.
The science activities included drawing and painting competition, quiz contest and extempore, the winners of which have been rewarded with a trip to Russia. An interactive session with Mr. Mikhail Kornienko, the Russian cosmonaut, was well received by the youngsters. Career-orientation sessions by the Russian experts provided insight and inspiration to the students.
Kalinka, the dance ensemble from Russia, enthralled the audience with its sheer brilliance. It was hosted at two venues in Mumbai - at the Old Yacht Club, DAE Headquarters, as an exclusive session on 27th October and then at the DAE Convention Centre on 28th Oct as a part of the day long activities under the umbrella of the Festival.
Live streaming of the event through DAE Facebook reached more than 25k people.


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https://www.seac.cc/wp-content/uploads/2017/02/SolarBEAT_extension.jpg 2592 3456 Chris Tzikas https://www.seac.cc/wp-content/uploads/2016/09/logo_SEAC_rgb-300x138-300x78.png Chris Tzikas2017-02-21 15:47:132017-02-21 15:51:15SolarBEAT extended to 9 measurement locations
SolarBEAT extended to 9 measurement locations
SolarBEAT is the unique SEAC facility for BIPV and PVT system research. Since its start in 2014, 15 distinct projects have been executed here.
The interest for BIPV and PVT systems from supplier companies and their customers is growing substantially. Therefore SEAC now extended the SolarBEAT facility to enable the simultaneous accommodation of 9 independent projects.
The new positions will be fully operational from April 2017 onwards.
Are you interested in performance research for your solar PV or solar heat applications? Please contact us here.


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2 years ago - Posted by - stanley okonkwo
With the Blues hosting the Magpies today, club historian Rick Glanvill and club statistician Paul Dutton recount some of our past encounters...
Stamford Bridge has been a difficult ground for Newcastle over the decades. They have left with all the points on just three of their past 50 league visits over 63 years.
There were memorable 4-0 and 6-0 Blues victories the early 1980s, and equally one-sided matches in the 2000s. The 5-0 of November 2003 was a glimpse into the promised land under new owner Roman Abramovich.
There were five different goalscorers for Claudio Ranieri against Bobby Robson's men, three of them (Glen Johnson, Hernan Crespo, and Damien Duff) part of one of the most remarkable spending sprees in football that summer, and the other two (Frank Lampard and Eidur Gudjohnsen) already destined for legend status at the Bridge.
Chelsea's sixth successive victory started when dashing right-back Johnson lashed in his first goal for his new club, and Crespo tapped in a second before Andy O'Brien was dismissed for illegally depriving Adrian Mutu of a goalscoring opportunity. Lampard dispatched the penalty.
Duff later capped a brilliant display by picking up Shay Given's loose kick, leaving Stephen Caldwell for dead and drilling into the net, and Gudjohnsen completed a neat move with his head to make the final score 5-0.
Manutd v Westham: Ole Gunnar Team pdate0 comments


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Manuka + Superfoods
Honey has been prized as a delicacy for centuries and a valuable source of sustenance for people around the world. The sweet natural taste of honey can boost energy.
BIOSOTA Organics Manuka + SUPERFOODS collection was created for you to enjoy the natural taste of Manuka honey plus popular taste sensations for an innovative taste sensation.


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On July 28, 2010, the Federal Executive Council accepted the recommendation of the Committee on the Roadmap to the Adoption of International Financial Reporting Standards (IFRS) in Nigeria, that it will be in the interest of the economy for reporting entities in Nigeria to adopt globally accepted, high-quality accounting standards by fully adopting the IFRS in a phased transition. The Council further directed the Nigerian Accounting Standards Board (NASB), under the supervision of the Federal Ministry of Commerce and Industry, to the take necessary action to give effect to the Council's approval.
Section 55 (1) of the Companies Income Tax Act, Cap C21, LFN 2004 requires a company filing a return to submit its audited account to the Federal Inland Revenue Service (FIRS) while Sections 8, 52 and 53 of the Financial Reporting Council of Nigeria Act, 2011 gave effect to the adoption of IFRS. This implies that the audited accounts to be submitted to the FIRS after the adoption of IFRS shall be prepared in compliance with its standards. It is in line with the above that FIRS published guidelines on tax treatments to be given to each of the standards especially where there are deviations from Generally Accepted Accounting Practice (GAAP) after the adoption.
IFRS1: First time Adoption
A taxpayer shall prepare and present an opening IFRS statement of financial position at the date of transition to IFRS. This is the starting point for its accounting in accordance with IFRS.
A first time adopter of IFRS is required by the standard:
• to recognise all assets and liabilities whose recognition is required by IFRS;
• not to recognise items as assets or liabilities if IFRS do not permit such recognition;
• to reclassify items that it recognised in accordance with previous GAAP as one type of asset, liability or component of equity, but are a different type of asset, liability or component of equity in accordance with IFRS; and
• To apply IFRS in measuring all recognised assets and liabilities.
The new net asset based on the accounting balance shall not be adopted for minimum tax computation in the year of transition.
If the retained earnings of a taxpayer that had previously paid tax based on dividend for a particular tax year increases as a result of the adoption of IFRS, and additional dividends are paid after the transition period from the portion of the retained earnings that relates to the tax year, the taxpayer shall be subjected to additional tax based on dividend in line with Section 19 of CITA.
Where however, the taxpayer was previously assessed to tax for the tax year in line with Section 40 of CITA, the taxpayer will only pay tax on its dividends based on Section 19, where the cumulative amount of dividends declared from the profits/retained earnings relating to the tax year, exceeds the taxable profits previously reported in the tax computations.
Details of recognitions, de-recognitions and reconciliation must be forwarded to FIRS by the taxpayer including all adjustments to opening retained earnings.
All conversion cost (capital and revenue) shall be subject to verification by the FIRS before it can be allowed as qualified capital expenditure or revenue expenditure.
Extension of time to file returns
First time adopters of IFRS would on application in accordance with Section 26 (5) of FIRSEA (and provisions of Self-Assessment Regulations 2012) be granted three (3) months extension for filing of their first set of IFRS financial statements and related returns to allow sufficient time to overcome initial conversion problems.
IFRS compliant financial statement shall be included in tax returns in line with Financial Reporting Council of Nigeria (FRC) Act.
Tax returns under IFRS shall be in line with Section 55 of CITA and should include:
i. In respect of first time adopters;
• Statement of Financial Position as at the beginning of the earliest comparative period when a taxpayer applies an accounting policy retrospectively or makes a retrospective restatement of items in its financial statement.
• Statement comparing the tax effect of IFRS adoption with GAAP.
• Statement of reconciliations from GAAP to IFRS.
• Deferred tax computation.
ii. In respect of post-first time adoption:
Deferred tax computation.
A statement showing the adjustments made on income statement or total comprehensive income to arrive at assessable profit and total profit for tax purposes as the taxpayer may wish to adopt shall be included.
IAS 2: Inventories
Where allowable input VAT is included in the cost of inventories, it shall be disallowed for income tax purposes and treated separately as deductible from the output VAT as contained in the VAT Act.
When inventories are purchased with deferred settlement terms:
Cost of inventories shall be based on the cost indicated on the invoice inclusive of any imputed interest. Where such interest has been charged in the income statement it shall be disallowed for tax purpose. If however the interest has been separately shown on the face of the invoice, such interest shall not form part of the inventory.
Any inventory (e.g. returnable packaging materials) reclassified in line with IFRS as non-current asset shall continue to be treated as inventory in line with the existing tax practice.
Estimates or provisions shall not be allowable for tax purposes, and any write-down on stock based on estimated cost of completion shall be disallowed.
IAS 8: change in accounting policies, changes
in accounting estimates and correction of errors
Whereas IFRS provides for retrospective application of change in accounting policy, retrospective adjustment shall not be effected for first time adopters for tax purposes.
Taxpayers should submit a re-computation of income tax and deferred tax.
Taxpayers should disclose:
• All changes in estimates
• The basis of computation
• The statement to which it has been charged
Obsolete stock/inventories – FIRS may allow claims on obsolete stock where it is satisfied that such stock is indeed obsolete. Any verification/certification of destruction of obsolete stock/inventories carried out without the FIRS witnessing such shall not be accepted for tax purposes.
FIRS shall assess each correction of error on its merit and in line with the existing laws. Taxpayers shall provide detailed disclosure of the sources of the errors and the future tax effect of the errors.


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Meath reach final after historic first shoot-out
Meath 1-19 Longford 2-16
History was created after a free-kick shoot-out decided this O'Byrne Cup semi-final at Páirc Tailteann yesterday.
It was the first time for a senior inter-county match to be decided in such a way and with no floodlights, proceedings ended in semi-darkness.
With normal and extra-time failing to separate the sides, the game went to free-kicks from the 45-metre line and it was the home team that prevailed, thanks to a Cillian O'Sullivan effort.
Mark McCabe had earlier pointed for the hosts while Sean McCormack was the only one to hit the target for Longford from their five efforts.
The game ended in a welter of excitement as Longford rallied from a four-point deficit with wing-back Michael Quinn snatching a goal before hitting over the equaliser, both scores coming in the final minute.
The grandstand finish was in sharp contrast to the fare served up in the opening half of the game at the end of which the visitors led 1-5 to 0-4.
Robbie Smyth struck for the Longford goal after Rian Brady had pounced on a mistake in the Meath defence. However, the midlanders should have been ahead by much more at that stage but their finishing was woeful at times.
In an effort to improve matters for an out-of-sorts Meath, Andy McEntee introduced Cillian O'Sullivan, James McEntee and Brian Power at the start of the second half. The changes had the desired effect as the Meath men recovered from a five-point deficit to go three clear with ten minutes of normal time remaining.
GAA Newsletter
Two further introductions, Sean Tobin and Joey Wallace, also left their mark, and it was Tobin from county champions Simonstown who netted with a sublime finish after taking a pass from O'Sullivan.
Meath, though, were unable to hold their lead and Robbie Smyth gained parity, 1-12 each, on 74 minutes. Smyth then spurned an opportunity to win it for his side in the last action of normal time.
With sub Daniel O'Neill popping over two points Meath gained the upper hand in extra-time to go three clear. Joey Wallace increased the lead two minutes from the end but the hosts still managed to relinquish their advantage in the final minute.
SCORERS - Meath: S Tobin 1-2 (1f), B McMahon 0-4 (1f), B Menton, T O'Reilly, J Wallace, D O'Neill 0-2 each, B Conlon, D Toner, B Brennan (f), M McCabe, J McEntee 0-1 each. Longford: R Smyth 1-4 (2f), M Quinn 1-1, S McCormack 0-4 (1f), D Reynolds, R Brady 0-2 each, R McEntire, J McGivney, D Quinn 0-1 each.
MEATH - A Colgan; S Lavin, L Moran, M Burke; D Keogan, B Conlon, S McEntee; B Menton, A Flanagan; P Kennelly, D Toner, G Reilly; B McMahon, B Brennan, T O'Reilly. Subs: B Power for Conlon, C O'Sullivan for Toner, J McEntee for Kennelly (all h-t), S Tobin for O'Reilly (50), J Wallace for Reilly (56), D O'Neill, for Moran (70), H Rooney for McMahon (72), S Glynn for S McEntee, M McCabe for Brennan, Toner for Keogan (all e-t),
LONGFORD - P Collum; P Fox, P McCormack, P Foy; M Quinn, B Gilleran, R McEntire; D Gallagher, A Farrell; B McKeon, S McCormack, D Reynolds; R Smyth, R Brady, D Mimnagh. Subs: P Gill for Reynolds (h-t), D McElligott for Gilleran, C Barry for Gallagher (both 48), J McGivney for McEntire (53), D Quinn for Mimnagh, S Donohoe for Fox, M Nally for Farrell (64), Farrell for Nally, Reynolds for Gill, Gilleran for Donohoe, Gallagher for Foy, J Matthews for Brady (all e-t).
REF - D Sheppard (Dublin)
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To the Editor,
Once upon a time there was a high school prom and a pretty Princess who was celebrating the removal of her braces. She wanted to look extra special in her simmering white gown so she went to a tanning salon. She did that twice even though she knew she could never tell her mother, the Queen. The Queen had a malignant melanoma removed from her leg the year before and instructed both of the princesses to stay away from tanning salons, and use sunscreen when going to the beach.
Fast forward the clock eight years. The Princess married her Prince and starting a new life as a wife in a small town an hour away from Grafton. She and her sister both went to a tanning salon with the bridesmaids. They sat in the bleachers at Fenway Park and Camden Yard, and rarely used sunscreen. They went camping and swimming on the Cape, and the coast of New Hampshire, and rarely used sunscreen. Two years after the wedding, a handsome young Prince was born. When the young Prince was five years old, a Baby Prince was born.
When the Baby Prince was two months old, a doctor sent the Princess to a special doctor to look at a mole on her back. There was an operation and the words Stage 3 Malignant Melanoma entered the family's vocabulary. All of the doctors agreed that the surgery was a success, and the Princess, her Prince and the two growing Princes resumed their happy lives.
Fast forward the clock four years. On a cold winter morning, the Princess called her doctor about a small lump on her ribcage. The vocabulary expanded again to include the word sebaceous and lymph nodes. More surgery followed by more hope, and a glimmer of springtime.
Last week, the Princess had the first ambulance ride of her life because what she thought was the flu, was not. Her head CT showed that multiple melanomas had spread to her brain; within a few days, her lungs, her liver and her abdomen were added to the list.
The Princess wants everyone who reads this story to Google MELANOMA, look at the pictures, read the warnings, and be very very afraid.
Once Upon a Time
To the Editor,


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