text:
- Research article
- Open Access
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Clinically significant association between the maximum standardized uptake value on 18F-FDG PET and expression of phosphorylated Akt and S6 kinase for prediction of the biological characteristics of renal cell cancer
- Tomoya Mizuno†1,
- Takao Kamai†1Email author,
- Hideyuki Abe†1,
- Setsu Sakamoto2,
- Kazuhiro Kitajima2, 3,
- Daisaku Nishihara1,
- Hideo Yuki1,
- Tsunehito Kambara1,
- Hironori Betsunoh1,
- Masahiro Yashi1,
- Yoshitatsu Fukabori1,
- Yasushi Kaji3 and
- Ken-Ichiro Yoshida1
© Mizuno et al.; licensee BioMed Central. 2015
- Received: 29 October 2014
- Accepted: 20 February 2015
- Published: 10 March 2015
The relationship between the clinicopathological features and molecular changes associated with standardized uptake value (SUV) determined by Positron emission tomography (PET) with [18F] fluorodeoxyglucose (18F-FDG PET) in human renal cell carcinoma (RCC) has not been elucidated. On the other hand, overactivation of the phosphatidylinositol 3'kinase (PI3K), serine/threonine kinase Akt, and mammalian target of rapamycin (mTOR) pathway has been detected in a variety of human cancers, including RCC. So far, little is known about the relationship between the SUV and these proteins in human RCC. Thus, it is important to study the relevance of SUV with clinicopathological features in human RCCs from a molecular point of view.
Seventy-seven consecutive patients with RCC who underwent nephrectomy and pretreatment determination of the maximum SUV (SUVmax) by 18F-FDG PET were analyzed. We investigated the relationship between the SUVmax, phosphorylated-Akt (Ser-473) (pAkt(Ser-473)), phosphorylated-Akt (Thr-308) (pAkt(Thr-308), and phosphorylated-S6 ribosomal protein (Ser-235/236) (pS6) protein levels in the primary tumor and various clinicopathological features.
The average SUVmax of the primary tumor was 6.9 (1.5 to 40.3). A higher SUVmax was correlated with higher expression of pAkt(Ser-473), pAkt (Thr-308), and pS6 protein in the primary tumor. A higher SUVmax and increased expression of pAkt (Ser-473), pAkt (Thr-308), and pS6 of the primary tumor was associated with less tumor differentiation, a higher pT stage, regional lymph node involvement, microscopic vascular invasion, and distant metastasis, as well as with early relapse following radical nephrectomy in patients who had localized or locally advanced RCC without distant metastasis (cTanyNanyM0) and with shorter overall survival in all patients.
A higher SUVmax on 18F-FDG PET is associated with elevated tumor levels of pAkt and pS6 protein and with aggressive behavior and metastatic potential of RCC, as well as with early relapse following radical nephrectomy and shorter overall survival. These findings suggest that SUVmax may be useful for predicting the biological characteristics of RCC.
- Renal cell carcinoma (RCC)
- Positron emission tomography (PET)
- [18F]fluorodeoxyglucose (18F-FDG)
- Maximum standardized uptake value (SUVmax)
- Akt
- S6 ribosomal protein
Renal cell carcinoma (RCC) is the most common solid cancer of the kidney and accounts for about 3% of adult malignancies. RCC is one of the top 10 causes of cancer deaths in industrialized countries and its incidence has consistently increased over the past few decades [1]. Localized RCC is usually treated surgically, but almost 30% of patients with limited disease at the time of resection develop metastasis within 3 years [2,3]. Clear cell RCC is a type of renal cancer that is extremely vascular with a high metastatic potential, and a high percentage of patients with clear cell RCC already have metastases at diagnosis or else relapse after nephrectomy [2,3]. Metastasis involves the spread of tumor cells from the primary lesion to a distant site [4], and it is the major cause of cancer death. RCC patients with distant metastasis have a poor prognosis and their 5-year survival rate is less than 10% [2,3].
Increased glucose uptake is a key alteration associated with the high glycolytic rate of cancer cells (the Warburg effect) [5], and reprogramming of energy metabolism can now be viewed as one of the "hallmarks of cancer" [6]. Oxidative phosphorylation is impaired in RCC, resulting in a metabolic shift to aerobic glycolysis [7]. The phosphatidylinositol 3'kinase (PI3K), serine/threonine kinase Akt, and mammalian target of rapamycin (mTOR) pathway is abnormally active in a number of human cancers, including RCC [8], and interruption of this pathway by targeted therapy has antiproliferative, pro-lethal, antiangiogenic, and pro-apoptotic effects, and are more effective against RCC than previous cytokine therapy or chemotherapy [9].
Positron emission tomography (PET) can be performed using [18F]fluorodeoxy-glucose (18F-FDG PET) to assess fundamental alterations of cellular glucose metabolism [10]. The maximum standard glucose uptake value (SUVmax) is the most common semiquantitative parameter determined by 18F-FDG PET and a decrease of SUVmax is associated with the response to numerous anticancer therapies [11]. 18F-FDG PET has been suggested as a noninvasive pharmacodynamic marker for the response to novel targeted anticancer agents in patients with advanced RCC [12-14]. It has been shown that inhibition of Akt disrupts transcription of glucose transporter protein-1 (GLUT1) and its translocation to the plasma membrane to promote glucose utilization independent of an effect on cell proliferation [15]. Thus, it has been proposed that 18F-FDG PET could be used as a pharmacodynamic biomarker for assessing the efficacy of inhibition of the PI3K/Akt/mTOR pathway by targeted therapy [10]. However, little is known about the relationship between the clinicopathological features and molecular changes associated with SUVmax in human RCCs. To our knowledge, this is the first reported study in which we examine the relationship between SUVmax and phosphorylated-Akt (Ser-473) (pAkt (Ser-473), phosphorylated-Akt (Thr-308) (pAkt (Thr-308), and phosphorylated-S6 ribosomal protein (Ser-235/236) (pS6) expression levels in human RCC. Our findings might lead to new insight on the value of SUVmax as a tumor biomarker in RCC from a molecular point of view.
Patients and samples
Data collection of patient and tumor characteristics
No. of patients
Age (yrs)
63.1 (39–83)
Sex (male/female)
follow-up times (months)
19 (3–43)
Histology (clear cell/cell/sarcomatoid differentiation)
Histological Fuhrman grading (G1/G2/G3/G4)
pT stage (T1/T2/T3/T4)
pN stage (T0/N1/N2)
Microscopic vascular invasion (v0/v1)
Metastasis (M0/M1)
Radical nephrectomy
with cavotomy with thrombectomy for > T3b tumor
with RPLND* for > N1 tumor
Postoperative adjuvant therapy with interferon (IFN)-alpha (3, 5, or 6 million units of natural human IFN-alpha two or three times weekly), sorafenib (400 to 800 mg/day), or sunitinib (25 to 50 mg/day for 4 weeks, followed by two weeks off therapy) was usually provided if patients had extra-renal involvement (metastatic disease) and was continued until progression occurred. The doses of these agents were decreased if the patient developed grade 3/4 toxicity.
Performance and evaluation of 18F-FDG PET /CT
Whole-body imaging using a combined 18F-FDG PET/CT scanner (Biograph, Sensation 16, Siemens Systems) and evaluation of the images were performed according to our previously reported methods [20,21]. Whole-body CT covered a region ranging from the meatus of the ear to the mid-thigh. The 64-detector-row helical CT scanner had a gantry rotation speed of 0.5 sec, a table speed of 24 mm per rotation, 120 kVp, 40 mA, and a slice thickness of 2.5 mm. The PET imager of the combined system had an axial view of 16.2 cm (per bed position) with an interslice interval of 3.75 mm and FWHM of 5 mm in one bed position. Imaging from the meatus of the ear to the mid-thigh was achieved with six to seven bed positions. The transaxial field of view and pixel size of the PET images reconstructed for fusion was 58.5 cm and 4.57 mm, respectively, with a 128 × 128 matrix. To avoid artifacts caused by the urinary tract, patients were asked to drink 1000 ml of water at 1–2 h prior to image acquisition and to empty the bladder just before the start of imaging. Bladder catheterization was not done and intravenous or oral contrast medium was not used. After fasting for at least 4 h, patients received an intravenous injection of 18F-FDG (4.0 MBq/kg). Blood glucose was checked in all patients before performing 18F-FDG PET, and no patient had a blood glucose level >160 mg/dl. About 50 min later, CT scanning was conducted and whole-body emission PET scanning was performed with acquisition for 3 min per bed position using the three-dimensional acquisition mode. Attenuation-corrected PET images were reconstructed with an ordered-subset expectation maximization iterative reconstruction algorithm that employed eight subsets and three iterations. Images obtained by 18F-FDG PET or CT and fused 18F-FDG PET/CT images were generated for review on a workstation (AZE Virtual Place Version 3.0035).
18F-FDG PET images and CT scans were interpreted by two experienced radiologists and decisions were made by consensus. 18F-FDG PET data were used to reconstruct coronal, axial, and sagittal images as is typically done for clinical assessment. When focal 18F-FDG PET uptake with a higher intensity than that of the surrounding tissues was seen at a site unrelated to physiologic/nonpathologic processes, metastatic RCC was suspected. Metastasis was diagnosed when abnormal focal 18F-FDG PET uptake on PET images corresponded to an abnormal mass on CT scans. The mean activity of the region of interest (ROI) was calculated (MBq/g)/(injected dose (MBq)/body weight (g)) where MBq is mega-Becquerel and g is grams. The SUV was determined according to the standard formula, with activity in the volume of interest (VOI) being calculated as Bq/ml divided by the injected dose in Bq/kg. In each patient, the average SUV was calculated from all images obtained about 1 h after tracer injection. SUVmax was defined as the maximum activity within the VOI. To obtain the highest SUVmax in patients with multiple metastatic tumors, the values of each lesion detected on CT scans were compared.
Western blotting
We performed Western blotting of samples from all resected primary tumors. Tumor samples and normal control samples were carefully dissected to remove stromal tissue. In order to allow for inter-individual variation in the expression of pAkt (Ser-473), pAkt (Thr-308), and pS6, tumor tissue samples and the corresponding non-neoplastic samples obtained from the same patient were compared as described previously [16,22]. In brief, 10 μg of cytosolic protein was separated by SDS-PAGE (4-12% gel), and was transferred to a polyvinylidene difluoride membrane (iBlot Gel Transfer Stacks PVDF, Mini; Life Technologies, Carlsbad, CA). After the membrane was blocked, the bound proteins were probed with the following primary antibodies: a rabbit anti-human antibody targeting pAkt (Ser-473) (Cell Signaling Technology, Inc; PhosphoPlus Akt (Ser-473) Antibody Kit; # 9270, Danvers, MA), a rabbit anti-human antibody for pAkt (Thr-308) (Cell Signaling Technology, Inc; Phospho-Akt (Thr308) Antibody Kit; # 2965, Danvers, MA), a rabbit anti-human antibody targeting pS6 (2 F9, Cell Signaling Technology, Inc; # 4856), and an antibody for beta-actin (Millipore; # 1501R Bedford, MA). Hela cells were used as the positive control [16,22]. The membranes were washed and incubated with horseradish peroxidase-conjugated secondary antibodies. After protein bands were visualized by chemiluminescence, each membrane was scanned for densitometry with a PDI imaging scanner (Agfa Japan, Tokyo) and the data were analyzed with NIH Image software (ImageJ for Mac OS, version 1.47). Expression of pAkt (Ser-473), pAkt (Thr-308), and pS6 was calculated relative to that of beta-actin in the tumor tissue specimens and corresponding non-neoplastic specimens. For quantification of protein levels, the relative amount of pAkt (Ser-473), pAkt (Thr-308), and pS6 in tumor tissue specimens was expressed as a ratio of the optical density for the tumor specimen to that for the corresponding non-neoplastic specimen (set at 1.0) by densitometric analysis, as described previously [16,17]. The mean values for tumor and non-neoplastic tissues were calculated from three experiments [16,17].
To confirm the data obtained by Western blotting, immunohistochemistry was performed with the same antibodies utilized for Western blotting on representative tumors from the 5 patients, as described previously [23].
Statistical analysis
Western blotting data were analyzed by the Mann–Whitney U test for comparisons between two groups (TNM stage, microscopic vascular invasion, serum CRP, and systemic treatment effect), while the Kruskal-Wallis test was used to compare data on histological grade among three groups [16,17]. Spearman's rank correlation coefficient analysis was performed to determine the relations between SUVmax and the expression of pAkt (Ser-473), pAkt (Thr-308), or pS6, as well as Karnofsky performance status and tumor size [16,24]. The Kaplan-Meier method was used to estimate survival and differences were assessed by the log-rank test [16,17]. The impact on survival of SUVmax, pAkt (Ser-473), pAkt (Thr-308), and pS6 expression, tumor grade, pT stage, regional lymph node involvement, microscopic vascular invasion, and distant metastasis was assessed by Cox proportional hazards analysis using univariate and multivariate models. In all analyses, a P value of less than 0.05 was considered significant. Data were analyzed with commercially available software.
SUVmax and expression of pAkt and pS6 in the primary tumor
Relationship between SUVmax and pAkt/pS6K protein densitometry results and pathological parameters
SUVmax in the primary tumor
Western blotting in primary tumor
pAkt (Ser-473)
pAkt (Thr-308)
pS6K (Ser-235/236)
mean ± S.D
P value
mean ± S.D
P value
mean ± S.D
P value
mean ± S.D
P value
6.97 ± 5.96
3.91 ± 3.01
2.83 ± 2.13
2.43 ± 1.58
Histological differentiation (Fuhrman grade)
2.72 ± 0.66
1.54 ± 0.57
1.21 ± 0.36
1.13 ± 0.15
3.90 ± 2.33
2.57 ± 2.03
2.03 ± 1.57
1.86 ± 1.08
8.80 ± 3.79
5.16 ± 2.73
3.46 ± 1.85
2.81 ± 1.23
18.67 ± 10.23
8.09 ± 3.49
6.00 ± 2.71
5.19 ± 2.07
pT stage
3.77 ± 2.02
2.43 ± 1.74
1.93 ± 1.49
1.75 ± 0.95
10.91 ± 6.82
5.83 ± 3.24
4.00 ± 2.27
3.31 ± 1.79
Microscopic vascular invasion
3.33 ± 1.46
2.08 ± 1.22
1.67 ± 1.14
1.60 ± 0.78
9.01 ± 6.55
4.97 ± 3.23
3.50 ± 2.28
2.91 ± 1.72
pN stage
5.58 ± 5.80
3.13 ± 2.54
2.41 ± 2.00
2.04 ± 1.31
12.38 ± 2.59
7.38 ± 2.45
4.68 ± 1.64
4.14 ± 1.56
Metastasis (cM stage)
4.56 ± 3.59
2.55 ± 2.03
2.07 ± 1.69
1.81 ± 1.52
12.10 ± 6.78
7.04 ± 2.53
4.57 ± 2.03
3.85 ± 1.16
cell histology
clear cell carcinoma
4.94 ± 3.15
3.16 ± 2.44
2.28 ± 1.68
2.03 ± 1.19
non-clear cell carcinoma
9.44 ± 5.04
4.43 ± 3.36
3.21 ± 2.11
3.41 ± 2.24
16.54 ± 9.37
8.56 ± 1.88
6.17 ± 2.02
3.95 ± 1.59
Karnofsky performance status below 80% (n=19) showed higher p-SUVmax than that above 80% (n=58) (13.61 ± 7.47 vs 4.84 ± 3.29, P = 0.000052).
Higher SUVmax and elevated expression of pAkt and pS6 of the primary tumor was associated with its aggressive and metastatic profiles
A higher p-SUVmax was related to less tumor differentiation, local invasion, regional lymph node involvement, microscopic vascular invasion, distant metastasis, and non-clear cell histology (non-ccRCC) (Table 2).
Similarly, increased expression of pAkt (Ser-473) pAkt (Thr-308), and pS6 in the primary tumors was correlated with less differentiation, local invasion, regional lymph node involvement, microscopic vascular invasion, distant metastasis, and non-ccRCC (Table 2).
Regarding with the relationship between the p-SUVmax and the highest SUVmax of the metastatic tumors (m-SUVmax), there was a tendency toward correlation (r2 = 0.17, P = 0.0568). On the other hand, the highest m-SUVmax was not significantly correlated with the expression of pAkt (Ser-473) (r2 = 0.04, P = 0.3835), pAkt (Thr-308) (r2 = 0.05, P = 0.3526), or pS6 in the primary tumor (r2 = 0.01, P = 0.9803).
A higher SUVmax and increased expression of pAkt and pS6 of the primary tumor was associated with early relapse following radical nephrectomy and with shorter overall survival
Cox regression analysis for various potential prognostic factors in recurrence-free survival
Recurrence-free survival in cN0M0 cases
Unfavorable/favorable characteristics
No. of Patients
Relative risk
95% confidential interval
P value
Univariate (U)
4.283 - 64.472
Multivariate (M)
0.021 - 142.351
pAkt (Ser473)
1.688 - 50.514
0.062 - 367.647
pAkt (Thr308)
1.621 - 45.612
0.069 - 397.026
0.466 - 34.272
3.320 - 33.119
1.836 - 529.228
1.920 - 31.753
0.187 - 151.279
1.016 - 24.035
0.156 - 35.559
cell type
2.634 - 18.876
0.091 - 11.577
RCC is characterized by impaired oxidative phosphorylation and a shift to aerobic glycolysis, which is a form of metabolic reprogramming known as cancer cell glycolysis (or the Warburg effect). An increase of glycolysis generates the adenosine triphosphate (ATP) needed for rapid proliferation and also enhances fatty acid synthesis by diminishing the phosphorylation of acetyl CoA carboxylase (a rate-limiting step of fatty acid synthesis) in order to provide energy for rapid tumor growth [7]. 18F-FDG PET has been widely used to detect malignancy and predict the prognosis, as well as being employed for tumor staging/restaging and in therapeutic decision-making and monitoring [10,11].
The aim of the present study was to investigate whether 18F-FDG PET could be used for noninvasive assessment of the biological characteristics of human RCC by comparing the relevance of SUVmax with clinicopathological features in human RCCs from a molecular point of view. In this study, we investigated the following: 1) relationship between p-SUVmax and expression of pAkt (Ser-473), pAkt (Thr-308), and pS6 protein in the primary tumor; 2) whether the p-SUVmax predicted relapse of organ-confined or locally advanced RCC without distant metastasis (cTanyNanyM0) after radical nephrectomy; and 3) whether the p-SUVmax or m-SUVmax predicted the response of metastatic lesions (cTanyNany M1) to cytokine/immunotherapy and/or molecular targeting therapy after radical nephrectomy.
Relationship between SUVmax of the primary tumor and clinicopathological features
The p-SUVmax was positively correlated with Karnofsky performance status and tumor size, and was also correlated with less tumor differentiation, local invasion, regional lymph node involvement, microscopic vascular invasion, distant metastasis, and non-ccRCC histology. Furthermore, the p-SUVmax was positively correlated with the expression of pAkt (Ser-473), pAkt (Thr-308), and pS6 protein in the primary tumor, and the levels of these protein were also closely related to less differentiation, local invasion, regional lymph node involvement, microscopic vascular invasion, distant metastasis, and non-ccRCC histology.
Overactivation of the PI3K-Akt-mTOR pathway has been reported in various human cancers, including RCC [9]. mTOR forms mTOR complex (mTORC)1 and mTORC2 by binding to the regulatory associated protein of mTOR (Raptor) and the rapamycin-insensitive companion of mTOR (Rictor), respectively, and these two complexes have different intracellular functions. mTORC1 is activated by PI3K-Akt and it phosphorylates S6K1 and 4EBP1, thereby promoting translation and protein synthesis. Both this study and our previous investigations showed that pS6, the best-characterized downstream effector of mTORC1, is upregulated in primary renal tumors with metastasis [16,17], indicating that pS6 might influence the progression of RCC.
mTORC2 regulates the actin cytoskeleton and also possesses PDK2 activity that phosphorylates Ser-473 at the carboxy-terminus of Akt, which is essential for activation of Akt [25]. Activation of Akt may increase cell viability after inhibition of mTORC1, or could potentially the production of increase vascular endothelial growth factor (VEGF) because PI3K/Akt signaling induces tumor angiogenesis by regulating VEGF via both HIF1α-dependent and -independent mechanisms [26]. It has been reported that HIF1α expression is dependent on both raptor and rictor, whereas HIF2α expression only depends on rictor, with HIF2α and mTORC2 being more important in RCC [8,27]. We previously reported that tumors showing higher expression of pAkt (Ser-473) protein were resistant to treatment with interferon alpha and sorafenib, and that higher tumor levels of pAkt (Ser-473) were associated with shorter overall survival [16]. Similarly, Jonasch et al. reported that an increase of pAkt (Ser-473) expression revealed by microarray analysis was associated with worse survival of patients treated with sorafenib and interferon alpha [28]. Furthermore, we recently reported that assessing the expression of pAkt (Ser-473) in resected specimens might be useful for predicting the response of locally advanced RCC to neoadjuvant therapy with axitinib [23]. These findings suggest that pAkt (Ser-473) might be a key molecule in the progression of RCC and could be a potential biomarker for assessing the efficacy of targeted inhibition of the PI3K/Akt pathway. However, the role of pAkt (Thr-308) in RCCs has not been fully elucidated. So, we examined the expression for both pAkt (Ser-473) and pAkt (Thr-308) by co-expression analysis using surgically resected samples.
In the present study, increased expression of pAkt (Thr-308) in the primary renal tumor was also correlated with aggressive biological behavior and metastatic potential. Furthermore, expression of pAkt (Ser-473) and pAkt (Thr-308) in primary tumor tissue showed a strong positive correlation. Phosphorylation at two sites is required for full activation of Akt, since it is phosphorylated by PI3K-dependent kinase-1 (PDK1) at a threonine residue in the catalytic domain (Thr-308) and by PI3K-dependent kinase-2 (PDK2) at a serine residue (Ser-473) located in the carboxy-terminal hydrophobic motif [29]. Taken together, activation of both of pAkt (Ser-473) and pAkt (Thr-308) might be very important in the progression of RCC. Because SUVmax was positively correlated with the expression of pAkt (Ser-473), pAkt (Thr-308) and pS6, 18F-FDG PET might be a useful imaging modality for assessing the biological characteristics of RCC from a molecular point of view.
Usefulness of SUVmax of the primary tumor for predicting the prognosis
Tumors with a higher p-SUVmax showed earlier relapse after radical nephrectomy. The tumors with early relapse also displayed higher expression of pAkt (Ser-473), pAkt (Thr-308), and pS6. These findings suggest that the patients with a higher SUVmax of the primary renal tumor should be under active surveillance, even if the tumor is well or moderately differentiated or is a noninvasive T1 lesion.
As is often the case with the patients with metastatic RCCs who received systemic therapy, while the sizes and/or the numbers of some metastatic lesions decreased, those of other lesions increased or new lesions appeared. Furthermore, some of the patients who showed poorer response for first-line systemic therapy for metastatic lesions had sensitivity for second-line systemic therapy. These might help to explain why many patients with metastatic disease show better survival when they receive sequential therapy with multiple targeting agents and current best supportive care than was achieved with conventional immuno-cytokine therapy [9]. It is likely that the biological characteristics of the primary and metastatic tumors were not always identical. Gerlinger et al. reported that primary and metastatic lesions showed biological differences and suggested that intra-patient tumor heterogeneity meant treatment strategies should be re-considered on the basis of these differences [30]. Thus, we should not select the treatment strategy by assuming that the characteristics of metastatic tumors are the same as those of the primary tumor. Since we could not obtain samples of every metastasis, however, we had to predict the biological characteristics of the metastatic lesions by examining the surgically resected primary tumors. In the present study, there was a correlation between p-SUVmax and the highest m-SUVmax of the metastatic tumors, as well as between p-SUVmax and the expression of pAkt (Ser-473), pAkt (Thr-308), and pS6 protein in the primary tumor, indicating that the metastatic tumors with higher m-SUVmax might have higher protein expression for pAkt (Ser-473), pAkt (Thr-308) and pS6.
It has also been reported that a decrease of SUVmax is associated with the response to various anticancer therapies [11], and use of 18F-FDG-PET as a pharmacodynamic biomarker for assessing the efficacy of inhibiting the PI3K/Akt pathway has been proposed [10]. Namura et al. reported that the survival of patients can be predicted by evaluating the SUVmax of metastatic tumors using 18F-FDG PET [31]. In addition, Ueno et al. reported that 18F-FDG PET/CT could be used to evaluate the early response of metastatic RCC to treatment with tyrosine kinase inhibitors (TKIs), since tumor size and FDG uptake on 18F-FDG PET/CT after 1 month of treatment predicted progression-free survival and overall survival [13]. These findings suggest that the SUVmax of metastatic tumors might be a biomarker that provides useful information for clinical decision making. However, in Japan, 18F-FDG PET is approved for one examination as a method of staging RCC, but repeat imaging to evaluate the treatment effect is not covered by the Japanese health insurance system. Therefore, we could not examine the influence of radical nephrectomy or systemic treatment on metastatic lesions by repeating 18F-FDG PET. Accordingly, we should make efforts to assess the biological characteristics of metastatic tumors from data obtained by 18F-FDG PET prior to nephrectomy.
Regarding with 25 metastatic (M1) cases, the m-SUVmax, p-SUVmax, pAkt (Ser-473), pAkt (Thr-308) and pS6 expression levels in the primary tumors were not associated with the response for first-line systemic therapy (data not shown). When we divided the 25 M1 cases into two groups at median value of p-SUVmax at nephrectomy, Kaplan-Meier plots of survival for patients with low vs. high p-SUVmax showed no statistic difference for overall survival time, while the patients with higher m-SUVmax had a tendency toward shorter overall survival, suggesting that the SUVmax of each metastatic lesion is important for predicting the biological characteristics. The patients with higher pAkt (Ser-473) and pAkt (Thr-308) expression showed a shorter overall survival time, but pS6 had no impact. On the other hand, when we analyzed all 77 patients, the aggressive and metastatic potential with higher p-SUVmax and pAkt (Ser-473), pAkt (Thr-308) and pS6 expression levels in the primary tumors were associated with unfavoravle prognosis. Taken together, SUVmax, pAkt (Ser-473), pAkt (Thr-308) and pS6 might be biological markers in RCCs.
The present study was not randomized and evaluated a relatively small number of patients, while the follow-up period was too short to draw definite conclusions. Immunohistochemical study showed the positive staining in membrane and cytoplasm in cancer cells, but not in normal glomerulus and renal tubules. Although these findings supported the data obtained by Western blotting, we should investigate the relationship between SUVmax and the staining intensity and localization of pAkt (Ser-473), pAkt (Thr-308) and pS6. On the other hand, glucose transporters are responsible for 18F-FDG uptake by cancer cells and GLUT1 expression has been positively correlated with 18F-FDG uptake [32]. GLUT1 is thought to be a possible intrinsic marker of hypoxia, and it has been reported that GLUT1 expression is regulated by hypoxia via hypoxia inducible factor (HIF)-1 [33]. Upregulation of the HIF-1 pathway has been identified in RCC, and hypoxia is associated with higher 18F-FDG uptake [12]. HIF-1 is considered to support tumor growth by induction of angiogenesis via increased expression of VEGF and also by promoting anaerobic metabolism [34]. Akt inhibition disrupts transcription of GLUT1 and its translocation to the plasma membrane to promote glucose utilization independent of an effect on cell proliferation [15]. Accordingly, we should comprehensively investigate the role of HIF-1, GLUT1, Akt in RCC in the future. Obtaining such information may be important to elucidate the relationship between clinicopathological features and molecular changes associated with SUVmax, and will shed light on the clinical issue of whether 18F-FDG PET is a useful modality for therapeutic decision-making and monitoring.
A higher SUVmax on 18F-FDG PET is associated with elevated tumor levels of pAkt and pS6 protein and with aggressive behavior and metastatic potential of RCC, as well as with early relapse following radical nephrectomy and shorter overall survival. These findings suggest that SUVmax may be useful for predicting the biological characteristics of RCC.
The authors are special grateful to Dr. Kyoko Arai for her constructive suggestions regarding statistical analysis, and Hitomi Yamazaki and Mai Takahashi for her excellent technique in this study.
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- Ma WW, Jacene H, Song D, Vilardell F, Messersmith WA, Laheru D, et al. [18F]Fluorodeoxyglucose positron emission tomography correlates with Akt pathway activity but is not predictive of clinical outcome during mTOR inhibitor therapy. J Clin Oncol. 2009;27:2697–704.View ArticlePubMedPubMed CentralGoogle Scholar
- Furuya N, Kamai T, Shirataki H, Yanai Y, Fukuda T, Mizuno T, et al. Serum interferon alpha receptor 2 mRNA may predict efficacy of interferon alpha with/without low-dose sorafenib for metastatic clear cell renal cell carcinoma. Cancer Immunol Immunother. 2011;60:793–808.View ArticlePubMedPubMed CentralGoogle Scholar
- Kamai T, Tsujii T, Arai K, Takagi K, Asami H, Ito Y, et al. Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer. Clin Cancer Res. 2003;9:2632–41.PubMedGoogle Scholar
- Fuhrman SA, Lasky LC, Lmas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982;6:655–63.View ArticlePubMedGoogle Scholar
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- Kitajima K, Murakami K, Yamasaki E, Fukasawa I, Inaba N, Kaji Y, et al. Accuracy of 18F-FDG PET/CT in detecting pelvic and paraaortic lymph node metastasis in patients with endometrial cancer. AJR Am J Roentgenol. 2008;190:1652–8.View ArticlePubMedGoogle Scholar
- Betsunoh H, Fukuda T, Anzai N, Nishihara D, Mizuno T, Yuki H, et al. Increased expression of system large amino acid transporter (LAT)-1 mRNA is associated with invasive potential and unfavorable prognosis of human clear cell renal cell carcinoma. BMC Cancer. 2013;13:509. doi: 10.1186/1471-2407-13-509.View ArticlePubMedPubMed CentralGoogle Scholar
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


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HPLC Separation of Pharmaceutical Compounds with
ICP-MS Detection
Presented by Kaho Kwok of Northern Illinois University
High performance liquid chromatography (HPLC) has become a technique of choice for analytical separations of pharmaceutical compounds. Throughout the years, detection techniques for HPLC such as UV absorption, refractive index, and mass spectrometry have become common. However, there are drawbacks in these detection techniques. For instance, since the response of these detectors usually varies with the chemical structure of the compound of interest, internal standards are required for each analyte in order to obtain accurate quantitative results. Because inductively coupled plasma mass spectrometry (ICP-MS) rely on sample decomposition to convert analytes to atomic forms, such drawbacks can be minimized or eliminated. Sensitivity and selectivity can be enhanced by using ICP-MS as detector for pharmaceutical separations with HPLC. The analytical performance of our ICP-MS for non-metals (P, S, Cl, and F) detection will be presented. The performance of an HPLC system with ICP-MS detection for the separation of several pharmaceutical compounds containing non-metals will be presented. The ability to quantify impurities in these compounds with HPLC-ICP-MS will be discussed.

subset: commoncrawl


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Is Your Child's Online Privacy Being Compromised?
Many child safety advocates are working hard to improve safety online for kids. Part of this effort is from those working on COPPA (Children's Online Privacy Protection Act) to protect the privacy of children under the age of 13. Why does COPPA matter? Many websites that your child visits collect personal information and data about your child for the purposes of targeted advertising and messaging. Think about that. What kind of ads or messaging is your child being exposed to? What kind of influence may they have? Where does this personal information go? Is a profile being created about your...Read More


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Metta World Peace. Need I say more? Basketball brawler to model citizen. Okay, maybe not "model citizen," but close. How close?
This year he published a children's book titled, "Metta's Bedtime Stories" with the motive to "show everyone that you can always have a better day tomorrow, if you have a hopeful heart and keep positive thoughts." He has also made appearances on "Yo Gabba Gabba" and "Sesame Street." He has been a champion role model in raising mental health awareness, and he is an NBA champion (2010). He auctioned off his ring, and raised over $500k to benefit the Xcel University charity. And a portion of his book proceeds will go to Xcel University and The Artest Foundation, both non-profits dedicated to helping kids with mental illnesses.
But the thing is, he hasn't always been Mr. Perfect—in fact, he was quite the opposite. I'm sure many of us are familiar with the "Malice at the Palace." Remember that time a fan in Michigan chucked a beer in the face of Ron Artest who then stormed the bleachers and knocked the guy out? His teammates Stephen Jackson, Jermaine O'Neal and Ben Wallace charged up after him. The benches nearly cleared, and heavy handed consequences were laid down to players and fans. The most notable being that The League suspended Artest for the remainder of the season, totaling 86 games including 13 playoff appearances.
He did a Q&A shortly after, and when asked, "Why did you punch the shit out of the guy?" he answered with this:
"He fucking disrespected me. Ain't nobody gonna do that to me. I'm Ron Motherfucking Artest baby. I got an image to create [sic]."
Backtracking to the headline of this post, how does Ron Artest—fresh-faced and picking fights—turn into Metta World Peace? That don't rhyme.
I like to say it all started with a chance. In 2009, the Lakers traded Trevor Ariza (who the team arguably wouldn't have won a ring that year without) for Artest (who had a huge beef with Kobe Bryant the duration of the Lakers-Rockets playoff matchup). The Lakers were able to see past Artest's unpredictable past, and instead value him for his lock-down defense. Post-trade, Artest said it would be different with purple and gold on. To say that it was different is an understatement.
His four-year stint with the Lakers included his first championship ring, the NBA's J. Walter Kennedy Citizenship Award and a name change. Suddenly, instead of "Ron Motherfucking Artest," he transformed into mental health activist, Metta World Peace. And all it took was a trip to the City of Angels.
Now matured World Peace is returning home to New York to don blue and orange under the bright lights of Madison Square Garden. Though I will say that even though Metta has grown-up, he is not any less entertaining, just take a glance at his Twitter feed and you'll know exactly what I mean. All I gotta say is I want to thank my hood, I want to thank my psychiatrist and I GOT WHEATIES.
Metta, it's sad to see you leave Los Angeles. The interviews were priceless. You brought an unmistakable, one-of-a-kind flare to the purple and gold. I know they'll treat you well out there in NY, keep doing good and keep dreaming crazy.


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Sancton Parish Council has vacancies for three councillors.
A by-election will be held if 10 electors of the parish write to East Riding Council's chief executive by 6 April claiming an election.
If the chief executive does not receive such a request, the parish council will be informed that it may fill the vacancies by co-option, which means the council members will elect a new member from those who have expressed an interest in joining the council.
If you would like to discuss the role, contact the parish clerk, Mrs H Beckitt, Blacksmiths Cottage, King Street, Sancton YO43 4QP, call 01430 827321 or email firstname.lastname@example.com


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Iqaluit photo exhibit celebrates women and their families
Exhibition opens at Iqaluit museum
Iqaluit's Nunatta Sunakkutaangit Museum is showcasing an exhibition of photographs entered into the annual competition held by Qulliit Nunavut Status of Women Council.
The theme of the exhibition, which opened on Saturday, March 10, is "celebrating women and their families." The images include a 10-year-old girl and the first beluga she's harpooned, girls enjoying a snack of pieces of caribou head, children sliding on sealskins to help their mother by cleaning and softening them, and a woman's hand holding an ulu.
As well as showcasing the artistic talent of Nunavummiut, the executive director of Qulliit, Beth Beattie, told Nunatsiaq News that the competition is "a positive way of reminding people to think about women and their families," because women in the territory have important concerns for both themselves and their families about poverty, homelessness, violence and health.
She added that people outside the city often comment that events only happen in Iqaluit, so Qulliit tries to make it easy for people from all over the territory to participate in the photo competition.
They just need to send in digital images, then Beattie has them printed and framed. This year more than 30 entries were received from all three regions of the territory. That's a smaller number than in previous years.
The 10 prize-winning photos will be chosen later this month at the annual face-to-face meeting of Qulliit, which will be held this year in Rankin Inlet.
The exhibition continues at the museum in Iqaluit until April 1.


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We've worked with some amazing clients.
Take a look at how we helped these fantasic companies with their events.
Aplro hired our Zumex Orange Juicer and Oranges as part of an in house health and well-being event.
Aston Martin
We provided a cocktail bartender and glassware to Aston Martin Hagley for a 007 SPECTRE event with Belvedere Vodka.
Our mocktails went down a treat on some roadshows with Brother while they promoted using genuine ink cartridges.
Delegates at the BPS Annual Conference go crazy for the smoothie bar that we provide for Grunenthal.
Johnson & Johnson
Smoothies were in order for Johnson & Johnson to help promote their new smoother contact lenses.
Land Rover
We provided Land Rover with our full cocktail bar service for the launch of their new showroom in Stafford in 2015.
We helped the marketing team from Mars Ice Cream unwide after a busy conference with a cocktail making class.
We supplied an illuminated cocktail bar with flair bartenders for the launch of the new McLaren 570s in Birmingham.
The cocktail service from our fantastic rustic wooden bar went down a treat for the launch of the new MINI Clubman.
Macular Mojito's are always the most popular cocktail for delegates of Optrafair on the Optimed stand.
Poker Stars
We provided the team from Poker Stars with a full juice bar as part of a health and well being event.
Reed Recruitment
During their health and well-being event our smoothie bar really helped the staff from Reed "Love Mondays".
Think Tank
A molecular cocktail bar was installed at the Think Tank as part of their celebrations for British Science Week.
Top Cash Back
Our cocktail team provided Top Cash Back with some delicious cocktails for their summer staff party.
A 2m white branded cocktail bar and bartenders were provided for a James Bond themed event.
Transport For London
Staff at Transport For London were thrilled with the smoothie bar that we provided for there in health and well-being event.
We've worked with Tusker on a number of events, supplying a smoothie bar at their employee benifits shows around the UK.
An illuminated bar, bartender and cocktails were provided for the launch of the new Vauxhall Corsa.
Wedding Ideas
A full stocked cocktail bar was provided for the Wedding Ideas Magazine award winners party in Taunton.
Western Power
Cocktails and mocktails were provided as arrival drinks before a special gala dinner after a tough day of meetings.
We provided a cocktail bar and bartenders for this fantastic one day dance festival in Staffordshire.


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Rachel Riggio | Co-Founder, Chief Operations Officer
Rachel is a humanitarian with a mission to be a positive force in our world. She has faced many of life's obstacles with resilience and fortitude. Forced to persevere when faced with humbling life lessons such as the loss of a parent at age four, addiction, abuse, and childhood traumas; Rachel immersed herself in a period of rehabilitation. In tune with her life' s purpose, she has developed a strong drive to find and help those in need.
Rachel is a graduate of Santa Barbara City College were she earned a certificate in counseling. She has logged more than five hundred volunteer hours with the Daniel Bryant Youth and Family Treatment Center where she was recruited to head the program. Since 2006, Rachel has worked as a youth counselor specializing in group home settings and inpatient treatment for adolescents. After six years of working within the mental health system in California, she decided to expand her focus by creating an avenue to empower others to join a self sustaining community develop center that embodies all the spiritual and philosophical qualities she wants to see in our world.
Rachel uses the trials in her life to breathe compassion and healing into our world. She is wholeheartedly dedicated to the mission of the Red Road Foundation to creating opportunities for people to come together as a world community and aid in the lives of the neediest among us.
Garrett Riggio | Co-Founder, CMO, CFO
Garrett graduated from The University of Montana where he received a marketing degree with an emphasis in entrepreneurship. He played football for San Diego State University and the University of Montana. He would retire his football career early to pursue his passion for serving our world and co-found The Red Road Foundation. He currently own an operates a multitude of business and acts as a marketing and advertising consultant.
Garrett commented, "I've always felt a sense of responsibility to give love and aid to the people who need compassion in our world. I have been involved in community outreach programs and charity work for several years. I graduated high school with 450 hours of community service and graduated college with over a 1000. I've traveled to Tanzania, Africa to promote health and give supplies to the countless children in need after genocide. My newest experiences in Cambodia have been heart wrenching, yet rewarding in so many ways, these kids have changed my life. Living life to inspire creativity, Garrett Riggio follows his passions all around the world. He is ambitious and passion in all aspects of sales/marketing, consulting, and project management. He has built teams and brands from the ground up and consulted for billion dollar companies. His message is to be the change you wish to see in our world, which is why he lives every day making the dreams of others a reality. He strives to be a provider; his entrepreneurial spirit and commitment to improving global communities has led him to connect people via digital communities and social enterprise, as well as provide customer service to develop innovative products and refined services to provide new solutions for everyday problems to expand brand footprints.
"Dare to take the less beaten path, have courage to stand out and differentiate yourself, embrace your uniqueness, and be a catalyst for positive worldwide transformation."
Yorn Sreypov | Educational Director, English Teacher
Bachelor of Arts in Education & English at Southeast International Institute, Associate of Midwifery at Chenla University
In my decision to teach at The Red Road Foundation, I have several objectives. First of all, I want to share my knowledge and experiences with the next generation of children. In fact, I understand that sharing knowledge is the most important factor in improving the ability and skills of children. I am able to use my influence to help with motivating their willingness to study hard. This is very important in Cambodia, as after a generation of war, their parents have learned that survival is the main focus of life and have not yet been exposed to the benefits and opportunity that education brings. It is my passion to share knowledge and experiences that they may utilize to bring healing and education into our rural community.
I have studied and am a practicing midwife, as well. It is in accordance with my dream to become an educator who spreads knowledge that can aid mothers and children. Working with The Red Road Foundation has allowed me to play a crucial role to help and support Cambodian children. At TRRF, we have been serving Cambodian children, who have faced humbling life lesson such as loss of parents, living on the street, alcoholic parents, abuse, and barely having enough food to eat at the end of the day. Lastly, I love working with TRRF because I never stop learning and improving myself! I love to learn, and I do not want a day to pass where I don't learn something new. I work at TRRF because I understand that we play an important role in Cambodia, by giving our children an environment to facilitate education and personal growth, we strengthen our country. Through our efforts the children will be able to have a secure future and in turn be able to create a better future for my country. I believe that my work with Cambodian children will play an important part in building confidence and developing their lives, moreover; it will reinstate hope in their lives.
Hong Da | Project Manager
I have been working as a rice farmer and raising farm animals before I started working at The Red Road Foundation in 2015. I've always had the dream of meeting foreign people and speaking English. Since I started here, I have been able to accomplish that. I love meeting our volunteers from all over the world each week and working with them to make a difference in my community. Another reason why I work at The Red Road is because I understand that we play an important role in Cambodia in order to help the lives of children without opportunity, who are at risk of disease, living in poverty and being unable to afford medical help. I work for TRRF because I know we are changing lives and shaping the future of Cambodia. We offer a bridge that connects those who want to help in the west with the humble and grateful attitudes of those who live in poverty of the east. Furthermore; TRRF has been providing children in need with a safe place that they can prosper in. By giving them an environment to facilitate education and personal growth, the children will be able to have a secure future, and in turn be able to create a better future for my country. I know that many children are poor, sick and some who have lost their parents, they have not had the opportunity to learn and grow. I find strength in knowing that I play a part in bettering their lives. These children rely on TRRF and I am happy to help make a difference in their lives and in the future of Cambodia. I enjoy my work with children and playing a part in building their confidence and developing their lives so that they may reach their full potential.


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Subtotal: ( items in your basket)
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The S-Blade is the little brother of the successful X-Tra-Dry aimed at the ambitious road cyclist. With its quick release mounting, the S-Blade can be fitted on virtually any racing bike and the angle can be optimally adjusted. NEW for 2016: S-Blade Fixed model for a permanent fitting to the seatpost if a quick removal of the S-Blade is not needed.
Please check the stock availability notice on your item when placing your order. This item is: In stock.
Express Delivery Available If ordered before 8pm, delivered by courier next working day. Available on orders placed before 8pm (2pm weekends and Bank Holidays) for delivery next business day. Applies to most delivery addresses within mainland UK.
You will receive an email to confirm when your item has been sent.
You can also check the status of your order and individual items by accessing My Account details and following the prompts.
Please allow 10 working days from dispatch of your order before notifying us of any late deliveries.
It may be advisable to check with your neighbours to see if a parcel has been left with them, check any outhouses you might have where it may be left if it cannot fit through your letterbox and contact your local sorting office to see if the item has been returned to the depot as undelivered and awaiting collection.
Please see our returns policy.
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We accept bookings from the Professionals of the travel industry.
We conceptualized this page for them to be sure that if we start to work together it will be for a long time.
If you are already interested in selling our programs, send us an email to the address below, we will answer within 24 hours informing you of the special conditions we can provide you.
If you have your own program in the Philippines but you wish to deal with a serious Correspondent to ensure the full satisfaction of your clients, do not hesitate to get in touch with us.
We are ready to serve you.
This offer is available, too, for corporate and incentive Specialists.
We are also looking for "outbound" ready programs created by local travel agencies
wishing to promote their activities to our Filipino clientelle.
We are open 24 hours a day and 365 days a year.


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Chicago White Sox right-handed pitcher, Jorge Rondon, 28, will be playing his next season in NPB (Nippon Professional Baseball) with the Chunichi Dragons of the Central league, an announcement was made just today. According to the report, it's a one-year deal for Rondon, though other contract details (regarding annual salary) is still unknown at the moment… but will soon be released in a few days, he will most likely be used a reliever (while also making some starts) for the upcoming season.
The Venezuelan born Jorge Rondon played for 3 years there at the Major league level (with the Cardinals, Rockies, Orioles, and Pirates respectively). He currently owns a record of 0-1 along with an earned run average of 13.26 in 13 games played (19 innings pitched) in his big league career, as a reliever. He recently signed a minor league deal with the White Sox this December 13th after being designated for assignment by the Pittsburgh Pirates back in June 24th of this year.


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Hospital profile
This is a private hospital. Private hospitals charge patients for care (emergency department and admissions) and private health insurance can be used by patients to meet some or all of the costs. Visit the hospital's external webpage for more information.
This information is intended as a general guide only.
Please contact the hospital directly for the latest advice on the services available. In an emergency, dial 000.
Contact details
Bobbin Head Road
North Turramurra, NSW 2074
Lady Davidson Private Hospital websiteExternal link, opens in a new window.[http://www.ladydavidsonprivatehospital.com.au]


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Granite Geek Podcast
Podcast with Dave Brooks talking about some of his articles.
Listen on:
About Granite Geek
Dave Brooks has written a science/tech column since 1991 - yes, that long - and has written this blog since 2006, keeping an eye on topics of geekish interest in and around New Hampshire, from software to sea level rise, population dynamics to printing (3-D, of course). He moderates monthly Science Cafe NH discussions, beer in hand, and discusses the geek world regularly on New Hampshire Public Radio.
Brooks earned a bachelor's degree in mathematics but got lost on the way to the Ivory Tower and ended up in a newsroom. He has reported for newspapers from Tennessee to New England. Rummage through his bag of awards you'll find oddities like three Best Blog prizes from the New Hampshire Press Association and a Writer of the Year award from the N.H. Farm and Forest Bureau, of all places. He joined the Concord Monitor in 2015.


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New Arrivals from ROKA London.
DESCRIPTION: These simple and stylish backpacks are practical, bold and perfect for any season! Featuring a showerproof outer and waterproof base with cotton-webbing straps, which get really soft and comfy with use. Coloured and chunky metal zips provide character and charm, whilst the concealed chunky zip on the front pocket is super easy to dive in and out of , so that you can quickly grab any necessary items.
Lots of colours available.
Call for more info on 01225462111 to ask about the colours and sizes we have in stock.
STYLE: Bantry B Small
COLOUR: Teal
MATERIAL: Treated Nylon - Water resistant
WASHING INSTRUCTIONS: Wipe with wet sponge
SIZING: W: 29.6 x H: 32 x D: 9.6 cm
Please note that although we have tried to represent colours as accurately as possible, these can sometimes vary between computer screens.


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To Text or Not to Text
Believe it or not, my cellphone is still not capable of texting. It's not even on, most of the time. A cellphone for me, is my way, of getting in touch with people, when I need to. Don't call me. I'll call you. That sort of stuff. Besides, you can always reach me via a landline or better yet, e-mail.
My hubby tried to get me hooked on texting by getting my friend since my elementary days, Adi's Ninang Suzi, to text me once in awhile through his phone. No such luck. After a few attempts, I got tired from "failed text" attempts or super-delayed answers. Once I texted my friend out of boredom while waiting for my OB-Gyne. This was at about 9am in the morning. I got her reply late in the afternoon as that was the only time she got my message. At least, she figured correctly that I was done with the doctor.
Two things good about not texting: I don't need to murder my spelling or the English language nor do I get Bin Laden jokes which can get me in trouble if I happened to be in Belgium. This early, though, I've already identified the day when I will finally say: "Texting is for me." That's when Adi wants his own cellphone.[By Angelica Viloria | Friday, October 5, 2001]
Copyright © 2001-2015 by Angelica Bautista Viloria. All Rights Reserved.
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Arty Being Adorable!
Mom said she'd plant cat grass - I wonder if this is it?
What a magnificent tail!
Check out the Friday Ark at The Modulator
and The Carnival of the Cats on Sunday.
That is a magnificent tail. Wow!
It is such a purrty tail! You could win in a purtiest tail contest we bet.
That is a great tail Arty. We are really enjoying the pictures of all your plants too. My mum has promised to get on with planting stuff this weekend as it is Bank Holiday so she can't say she doesn't have time to do it!
Indeed, a gorgeous tail! That plant you're sniffin' looks a little on the prickly side however.
Indeed it is a magnifient tail you have! It is like a plumb!
Fabulous tail!


text: Latest News LATEST NEWS 2019 Sponsorship Forms- Updated on Website 2019 Membership Forms- Updated on Website MTPA elected a new president for 2019! Randy Pryor is looking forward to a great 2019 season. His… See More Share this:Click to share on Facebook (Opens in new window)Click to share on Twitter (Opens in new window)Click to print (Opens in new window)


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If you enjoy working out of your truck, it is important that it is built to handle different types of tasks. This might include hauling large cargo or going through some tough environments. The 2016 Ram 1500 can handle all of these challenges with ease, and it has other noteworthy aspects that denote it as more than just a work truck, but a sophisticated vehicle as well.
Plenty of Storage Options
Hauling stuff with the 2016 Ram 1500 doesn't have to be difficult at all, thanks to all of the space it offers. There is plenty of room on the interior for passengers, which can sit up to six people comfortably.
The RamBox Cargo Management System gives you the chance to store more things without you having to worry about sacrificing the space in your truck's bed. This storage system features a sealed design, so you don't have to worry about any personal items getting damaged during the drive.
Efficient Engine
You have the option of selecting the EcoDiesel Turbo Diesel engine, which is both powerful and efficient. On a full tank of gas, you can travel up to 728 miles on the highway. You don't have to fill up very often, helping you maximize your long-distance journeys with friends or family. This V6 engine is capable of putting out 240 horsepower and 420 pounds per feet of torque.
If you would like to see what this truck can do on the road, travel to Ram dealers in El Paso. They can help you find the right truck for all your work needs.


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There is one question that people tend to ask so they can get a sense of who you are. Mostly these people are employers who want to see how ambitious you are, but no matter how many times I get asked or I ask myself I still don't like the question.
Where do you see yourself in five years?
Five years is a long time, and don't get me wrong I'm a very ambitious person and hard working. I love my job and hope to say I will be with the same company for five years. So far I have been working in my current location for a little over three years now and still love every minuet.
However if you asked me five years if this is where I saw myself I would have said no. Back then I was working in and office job that I hated, living with my boyfriend and his family who I love but I am also very independent and an only child. Living in a house with more then myself and one other person was tough to get use to.
Now I am in a job that I love which at times can still be tough but the people I work with everyday make it amazing. I have a apartment with my no longer boyfriend but fiancee now and our little cat family Sophie and Wayne. As well I'm bring this site back which I am beyond excited about and will be spending lots of time making it everything I wanted back then and what I hope it will be now.
Looking back a lot can change, its hard to really answer where you will be in five years because things happen and your life changes.
I tend to look at celebrities and wonder if they themselves had a five year plan.
Victoria Beckham is working with Skype to go behind the scenes of her fashion line. I absolutely love Victoria Beckham partly because I am a 90's kid and grew up with girl power, platforms and zing zing zaa or aka the Spice Girls. But I wonder, back when she was just starting out as Posh Spice living in the house with the other girls if see even dreamed of where she was going to end up.
I am so excited for this collaboration with Skype to come. Also to be able to see how its all going to come together. Is it a documentary movie? It is interactive?
I can't wait to see you explain her thoughts on the fashion world and how and where she sees her fashion line going.
What are your thoughts on Victoria Beckham's fashion lines? Are you excited for this? Five years ago did you plan on being where you are now?


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Monday, August 6, 2012
Details should be forthcoming, but just quickly now, New York has been the WTC-9/11 Memorial, the West Village, the High Line, The Met Museum for lunch in the patrons dining room and a quick informed escorted selective tour, The Frick, The Neue Gallery for the Klimts, and another excellent (Viennese) lunch, an afternoon in the bowels of the Met in the archives with the files, books, records and costumes of the centuries, more walking and walking, a jaunt in Central park, mastering the subway, not mastering the heat and humidity, Williamsburg Brooklyn and the East River ferry back to Wall Street, a very relaxed night in a west village loft and nearby restaurant with two characters even Woody Allen could only dream of. And a sound system which I can without any hyperbole say is the best I've heard. He reviews.
The Book of Mormon was timely, lots of fun and lots of laughs in a South Park shock-em-in-the-aisles kinda way, with people waiting four hours in the hope of returns. And The Best Man, dedicated to its recently deceased writer Gore Vidal, a 1960s look at the hypocrisy and horse trading in politics is just as potent today. With punchy lines and quips, if not quite Wildean, and if tending now to be a bit preachy and overwritten, it is still compelling theatre driven by a great character performance by James Earl Jones, and the fascinating presence of Cybill taxi-driver Shepherd, whose erect controlled performance as Mrs Betrayed Canditate was of another style completely but I found I couldn't take my eyes off her. It was theatre that couldn't happen anywhere else in the world - the size of the theatre, that Broadway slickness of the scene changes, the usher(ettes) in campaign hats seating everyone with asides and the gift of the gab, the two crowded intervals, the audience its own self-aware entity, and then the jammed streets afterwards, the road blocked by a throng waiting for Ricky Martin over the street (after Evita), a hapless NYCPD cop bawling 'keep orrff the street please' every few minutes, guiding endless yellow cabs through the crowd, New York doing New York as if it were its own film set.
The hotel edges Washington Square Park, where we would mostly begin the day and end the night.
Not everyone heads to the fountain.
Labels: new york washington square park
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Rent from $85 ($500 retail) In stock
Listed by Catherine Claeys
Feel glamorous for your event in this BLACK gown which creates a trumpet silhouette, this Mon Cheri 216978 strapless Mikado dress has a pleated sweetheart neckline embellished with beading. The beading continues on the semi-open back. This gown features princess seams and the skirt finishes in a sweep train. Removable straps and a matching shawl are included. Disclaimer: The Picture above does show the green color however the dress is only available in BLACK.
Return policy: Vendor accepts returns within 24 hours of delivery in exchange to store credit. No refunds.
You are covered by the Poshare Money Back Guarantee if you received an item that is not as described in the listing. Review our Return Policy for details.
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Rent $150 $350 retail
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Schools League 2017
It's back…Schools League 2017!
After the success of last year's inaugural schools league, we're back again! This year there will be a warm-up event in Kingussie, before the 3 series races.
- 3 races
- Race bases: Deshar Primary School, Carrbridge Primary School, Kincraig Village Hall (see individual fixtures for details for each race).
- Primary and Secondary categories
- Individual and Team awards
- Best 3 scores to count for individuals
- Team = 4 best individual scores each week (+bonus points for parents and school staff!)
- Cost: £4/£3 non-member adult/junior, £3/£2 member adult/junior
Starts between 6.30pm and 7pm, all finished by 8pm (if you start early, you don't need to stay until 8pm, unless you want to see the final positions!).
We would like to encourage everybody taking part to become a member (cheaper entry fees, club mailing list, orienteering magazine, access to special offers). This is possible online, but please email Jess on with any questions. If you take part in the intro sessions (see other news item), then you will be signed up as a member already :)


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SCADA provides personal Consulting for the delivery of cost effective design and construction services for Private and Municipal Water and Wastewater Agencies. Gene Heyer am a CA licensed Control System Engineer, Certified Project Manager with over 30 years experience. References provided upon request.
633 Ramona Avenue,
Los Osos, California 93402
See other members in these categories
Engineering | Water |


text: Bevywise Networks is a highly vibrant and fast growing IoT startup. We are working on developing Software for the Internet of Things. We develop device agents that collects and communicate device status, servers that aggregates and store data and Intelligence Engine that analyse and interpret data for making precise decisions and simulator that helps you test and develop real devices. The development centre is located at Tirunelveli, India.


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Around Town
Christmas Cachets at the Post Office
A visit to the Bethlehem Post Office to send holiday mail has become an annual tradition for many families. You can select one of the "Christmas Cache" designs and hand-stamp your mail before sending your greetings off to friends and family.
The Bethlehem Post Office has introduced a new cachet design each year since 1938, and there are now 77 different festive embellishments available to decorate your holiday mail. Designs have been created by local residents, artists and children.
See the caches online.
The new 2013 design is a …?
Where: 34 East Street MAP
Hours: Fri. Dec 6 from 8 am - 8 pm,
and Sat. Dec. 7 from 8 am - 4 pm
Regina Laudis Abbey
The Abbey's 18th-century Neapolitan Crèche was given to the Abbey by artist and philanthropist Loretta Hines Howard, who also donated a similar Crèche to the Metropolitan Museum of Art. The figures, made of hand-carved wood, terra cotta, jute and porcelain, vividly portray the Holy Family, angels and the Three Kings, as well as merchants and peddlers, children, a lamplighter, a woman on her donkey transporting vegetables, and peasants and their farm animals.
The Lauren Ford Crèche is located in a small farm shed near the Lower Abbey Chapel. This Crèche, created by revered Connecticut artist Lauren Ford, is a charming rustic Nativity scene with figures of Jesus, Mary and Joseph dressed in New England clothes.
The Monastic Art Shop offers food, crafts, and beauty products; all fruit of the monastics' work on the land and in animal husbandry. Cheese, jams and jellies, herbal teas, flavored vinegars, herbs, and honey are available.
Where: 249 Flanders Road MAP
Hours: Daily 10 am - 4 pm
For more information, visit: http://abbeyofreginalaudis.org/
Bellamy-Ferriday House Tours
Bethlehem's beautiful eighteenth century Bellamy-Ferriday House & Garden will be festively decorated and open for tours and holiday cheer. Guides will be on hand to give tours and the family-friendly program will include games, prizes and surprises for children. Admission is free with a suggested $3 donation and/or a donation to the Bethlehem Food Bank. Scavenger hunt for kids of all ages and hot cider in the gift shop.
Where: 9 Main Street North
Hours:Sat. Dec. 7 from 10am - 4pm
For more information, visit:


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Student Experience and Wellbeing
The Student Experience & Wellbeing team work to support Durham students' education and personal development. Our work is co-ordinated and developed across the Colleges through engaging with students and college staff.
We work closely with Common Room members and leaders - helping these student organisations to provide the best, most inclusive experience possible for all students. Through providing training, resources, contacts and support to Common Rooms and other student organisations, we enable Durham students to have a truly transformative experience.
In partnership with local organisations, durham students and other University departments, we also work to raise awareness in key areas as they relate to students' educational and personal development needs, including:
- Drugs and alcohol
- Sexual violence and consent
- Living safely in the city
- Personal wellbeing and health
- Looking out for others
This page is under construction.
"The broader value of the collegiate way is something to do with how we collaboratively prepare to live lives that flourish for others as well as for ourselves…"
[Evans HM & TP Burt (eds), The Collegiate Way: university education in a collegiate context, Dordrecht: Sense Publishers, 2016, 88]
Useful Links
County Durham Drug & Alcohol Recovery Service
Useful Documents
- Living Out In Durham (Letter) (last modified: 8 October 2018)


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Individuals and organizations focused on improving the quality of Delmarva's social service delivery will gather at Delaware Technical & Community College, Owens Campus on Friday, May 13 for the 23rd annual Families in Crisis Conference.
This year's theme is "Vision of Hope: Helping Families Prepare for Today's Challenges and Tomorrow's World." Nurses, health care workers, and counselors can earn continuing education credits and gain valuable information from conference presentations, workshops, exhibits, and networking opportunities.
The conference begins at 8 a.m. with exhibits by area agencies; free health screenings for bone density, body mass, diabetes, blood pressure, and depression will be offered to participants from 8:30 a.m. to 1:30 p.m.
The keynote presentation on interpersonal and conflict resolution will be made by the Full Circle Theater group, and workshops on a variety of topics including cultural diversity, child abuse, chronic loss, bioterrorism, disabilities, self-defense, and addiction will be held in the morning and afternoon.
Cost for the conference, including meals, is $35 for the general public and $20 for all full-time students. Individuals with disabilities requiring accommodations must contact Lori Westcott at (302) 855-5988 by May 6.


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Elba High (EHS) Class of 1961 Alumni List
Help us Update the Elba High 1961 Class List by adding any names missing from the list below:
Registered Alumni
1961 Class List
Know Elba High Class of 1961 graduates that are NOT on this List? Help us Update the 1961 Class List by adding missing names.
The most popular movie of 1961 was 101 Dalmatians which has grossed over $153,000,000 since its release. The TV series Gunsmoke was the most popular show of 1961.
Reunions and Elba High School News
More 1961 alumni from Elba HS Elba, AL have posted profiles on Classmates.com®. Click here to register for free at Classmates.com® and view other 1961 alumni.
If you are trying to find people that graduated in '61 at EHS in Elba, AL, check the alumni list below that shows the class of 1961.
You can also find out what other graduates are doing now, share memories with other alumn, upload pictures from Elba and find other alumni.