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We evaluated the association between a KRAS mutational status and various clinicopathologic features including the metastatic pattern in patients with metastatic or recurrent colorectal cancer (MRCRC). The concordance rates of the KRAS status between primary tumor sites and paired metastatic organs were also analyzed.
The KRAS mutational status in codons 12, 13, and 61 from formalin-fixed sections of both primary tumors and related metastases was determined by sequencing analysis. One hundred forty-three Korean patients with MRCRC with available tissues (resection or biopsy) from both primary tumors and related metastatic sites were consecutively enrolled.
The KRAS mutation rate was 52.4% (75/143) when considering both the primary and metastatic sites. When the relationship between the KRAS status and initial metastatic sites at the time of diagnosis of MRCRC was analyzed, lung metastasis was more frequent as the initial metastatic site in patients with the KRAS mutation than in patients without the KRAS mutation (45.3% vs. 22.1%; P = 0.003). However, liver (37.3% vs. 70.6%; P < 0.001) or distant lymph node metastases (6.7% vs. 19.1%; P = 0.025) were less frequent as the initial metastatic organ in patients with the KRAS mutation than in patients without the KRAS mutation. The discordance rate of KRAS mutational status between primary and paired metastatic sites other than the lung was 12.3% (13/106). Compared with primary tumor sites, the KRAS discordance rate was significantly higher in matched lung metastases [32.4% (12/37)] than in other matched metastatic organs (P = 0.005).
Organs initially involved by distant metastasis were different according to the KRAS mutational status in MRCRC patients. The concordance rate (87.7%) of the KRAS mutation status at metastatic sites other than the lung was generally high compared with primary tumor sites; however, lung metastasis had a high rate of KRAS discordance (32.4%).
Keywords:KRAS mutation; Lung metastasis; Discordance; Colorectal cancer
Colorectal cancer (CRC) is the most common gastrointestinal cancer, and one of the leading causes of cancer deaths worldwide [1]. Recently, the incidences of CRC have been increasing in Asian countries including Korea [2]. Metastatic or recurrent colorectal cancer (MRCRC) has a poor prognosis. Many recent studies have demonstrated that MRCRC with KRAS mutant-type (MT) are resistant to anti-epidermal growth factor receptor (EGFR) agents such as cetuximab or panitumumab, which showed efficacy as monotherapy or in combination with cytotoxic agents in MRCRC patients with a wild-type (WT) genotype in KRAS codons 12 and 13 [3-6]. KRAS mutational analysis of primary or metastatic tumor tissues is recommended for all MRCRC patients receiving anti-EGFR chemotherapy.
The KRAS mutation is known to occur in about 40% of all CRC cases [7]. The activating mutation of KRAS induces stimulation of the RAS/MAPK signaling pathway independent of EGFR, subsequently followed by dysregulated cell growth, proliferation, and survival [8]. However, the actual differences in clinical behaviors between tumors with WT and MT KRAS, except resistance to anti-EGFR agents, remain controversial. There have been some reports showing that MT KRAS tumors have a poorer prognosis than WT KRAS tumors; however, such a relation between KRAS status and prognosis in CRC was not verified in other reports [9-13]. Recently, it has been reported that the recurrence pattern after the curative resection of CRC is determined according to the KRAS mutational status, showing the positive correlation of KRAS mutation with lung relapse [14,15]. Furthermore, some reports demonstrated a different prognosis and clinical presentation with respect to the mutation types of the KRAS gene [16,17]. However, these findings need to be confirmed by additional studies.
In addition, WT KRAS tumors are not always sensitive to EGFR-targeted therapy. Many studies have focused on the downstream signaling pathways of EGFR with the goal of identifying other predictive factors for patients resistant to anti-EGFR agents. BRAF or PIK3CA mutation and PTEN loss were suggested as other biomarkers predicting a lack of response to anti-EGFR agents [18-21]. Since the BRAF mutation or PTEN loss are rare [22], other mechanisms of resistance to anti-EGFR agents are expected to play a substantial role. Although the KRAS mutation is believed to be an early event in the carcinogenesis of CRC [23] and it has been demonstrated that the KRAS mutational status is highly concordant between primary tumors and related metastases [14,15,24-28], some recent studies have produced contradictory results in regards to the KRAS mutational status [11,29-31]. Especially, most previous studies on the concordance of the KRAS mutation status were conducted on easily available hepatic metastatic tissues [24,26,28]. Therefore, if the discordant rate is different according to the respective metastatic organs, it may also contribute to a poor response to anti-EGFR agents.
Therefore, this study was performed to determine whether there are differences in clinical behavior such as metastatic patterns according to the KRAS mutational status in MRCRC patients. Additionally, the concordance rates of KRAS mutation status between primary sites and respective metastatic organs were also evaluated.
Study population
Among patients with histologically confirmed colorectal adenocarcinoma who had been treated or followed up at medical oncology clinics of Seoul National University Bundang Hospital (SNUBH) between April 2010 and February 2011, 151 MRCRC patients who had undergone surgical resection or biopsy of both primary tumors and related metastatic sites were consecutively enrolled. Eight patients were excluded because of a failure in the process of KRAS mutational analysis on either primary or metastatic site, thus 143 patients were finally included in this study. The clinical data on enrolled patients was retrieved from the CRC database maintained at SNUBH [32], and additional data collection was retrospectively supplemented after a review of the electronic medical record (EMR). This study was approved by the institutional review board of SNUBH.
Preparation of tumor DNA and sequence analysis of KRAS gene
Formalin-fixed paraffin-embedded primary tumor and metastatic tissue specimens were chosen for each patient and all specimens were microdissected manually under the supervision of experienced gastrointestinal pathologists. After manual microdissection, > 60% of the sample area was shown to contain tumor cells as estimated from the H&E-stained slides. The DNA was extracted using a chelating ion exchange resin (InstaGene Matrix, Bio-Rad). For mutation analyses in codons 12, 13, and 61 of the KRAS gene, extracted tumor DNA samples were subjected to automated sequencing using an ABI 3130xl Genetic Analyzer (Applied Biosystems) and the data was analyzed with GeneMapper Software Version 4.0 (Applied Biosystems). Primer sequences for exon 1 were 5'-AACCTTATGTGTGACATGTTCTA-3' (forward) and 5'-TGGTCCTGCACCAGTAAT-3' (reverse); for exon 2, 5'-ACTGTAATAATCCAGACTGTGTT-3' (forward) and 5'-CCCACCTATAATGGTGAATATCT-3' (reverse). The polymerase chain reaction (PCR) conditions were as follows: one cycle of 95°C for 5 minutes; 34 cycles of 95°C for 30 seconds, 58°C for 30 seconds, and 72°C for 1 minute; and one cycle of 72°C for 10 minutes.
Determination of microsatellite instability (MSI) status
The MSI status of paired normal and tumor DNA samples was assessed using the Bethesda panel of 5 microsatellite markers. Sequencing was conducted using the same PCR system as the KRAS mutational analysis. The MSI status was classified as high frequency if ≥ 2 of 5 markers exhibited instability, as low frequency if one marker exhibited instability, and as stable if no markers exhibited instability.
Statistical analysis
The concordance rate of KRAS mutational status in primary tumors and related metastases was evaluated; the Kappa index was measured using Cohen's k-test, which can assess the concordance between categorical variables of the same individuals. The effect of KRAS mutational status on clinicopathologic parameters and initial metastatic sites were assessed using Pearson's chi square or Fisher's exact tests. Multivariate logistic regression analyses were performed to evaluate the effect of other clinicopathologic features on liver-only and lung-only metastases besides the KRAS status. The relationship between the discordant rates of the KRAS mutation status and various clinical parameters including respective metastatic sites was also evaluated using univariate (Pearson's chi square or Fisher's exact tests) and multivariate logistic regression analyses. In multivariate logistic regression analysis, the forward stepwise regression model including variables with a P-value < 0.10 in univariate analysis was used. Two-sided P-values of < 0.05 were considered significant. All analyses were performed using SPSS for Windows, version 17.0 (SPSS Inc., Chicago, IL, USA).
Patient characteristics
Of the 143 patients included in this study, 77 patients (53.8%) were male. The median age was 59 years (range, 20–83 years). Paired metastatic sites for KRAS analysis were liver (N = 47), lung (N = 37), peritoneum (N = 30), distant lymph nodes (LN) (N = 17), ovary (N = 11) and pancreas (N = 1), respectively. Most patients had stage IV disease (distant metastasis) at the time of initial CRC diagnosis (N = 101, 70.6%), and only 42 patients had recurred disease after curative resection for localized disease (stage I to III at the time of initial CRC diagnosis). The primary tumor sites were colon in 108 patients (76.5%) and rectum in 35 (23.5%). Other patient characteristics are shown in Table 1.
Table 1. Patient characteristics (N = 143) and the association between KRAS mutational status and clinicopathologic parameters
Frequency and types of KRAS mutation
The KRAS mutation was observed in 62 (43.4%) primary tumors and at 63 (44.1%) related metastatic sites. Seventy-five patients (52.4%) had the KRAS mutation in any place of the primary or metastatic sites. Of those 75 patients, 20 patients had a Gly12Asp mutation, 18 had a Gly13Asp mutation, 17 had a Gly12Val mutation, 9 had a Gly12Cys, 3 had a Gly12Ala, and other 3 patients had a Gly12Ser. In addition, 2 patients had a Gln61Leu mutation and Gly13Cys (N =1), Gln61His (N = 1), and Gln61Arg mutation (N = 1) were detected in the remaining 3 patients (Table 2). The incidence of codon 61 mutations was 5.3% among patients with the KRAS mutation (4 of 75 cases).
Table 2. Distribution of KRAS mutation types
Concordance of KRAS status in primary tumors and related metastases
KRAS status was concordant between primary and metastatic sites in 118 patients (82.5%; kappa = 0.645) (Table 3). Of the 25 discordant cases, 12 patients had the KRAS mutation in the primary tumors, and not in the metastatic sites; 13 patients had the KRAS mutation in the metastatic tumors, and not in the primary tumors. We analyzed the difference in discordance pattern according to clinical presentation (stage IV vs. recurred) at the time of initial MRCRC diagnosis and metastatic organs from which tissue specimens were obtained. There were no statistically significant differences in discordance patterns with respect to these parameters (Table 4).
Table 3. KRAS mutational status of primary tumors and paired metastatic sites
Table 4. Analyses of KRAS discordance patterns in KRAS discordant cases (N = 25)
Association between KRAS mutational status and clinicopathologic features
Clinical situations for the development of systemic metastasis in MRCRC patients were different according to the KRAS mutational status. In regards to the development of distant metastasis, systemic relapse from previously localized CRC (stages I to III) after complete surgical resection was more frequent in MT KRAS patients than in WT KRAS patients (38.7% vs. 19.1%); however, systemic metastasis was more frequent at the time of initial CRC diagnosis in WT KRAS patients than in MT KRAS patients (80.9% vs. 61.3%; P = 0.010).
There was no association between the KRAS status and other clinicopathologic features (gender, age, primary tumor location, histology, gross morphology, obstruction or perforation of primary tumors, and MSI) (Table 1).
KRAS mutational status and metastatic patterns
When the relationship between KRAS status and initial metastatic sites at the time of diagnosis of stage IV disease or recurrence (in the cases of initial stages I to III) was analyzed (N = 143), patients with MT KRAS had a higher rate of initial lung metastasis (45.3%) than patients with WT KRAS (22.1%; P = 0.003). However, a higher percentage of liver or distant LN metastases was detected in patients with WT KRAS when compared to patients with MT KRAS (70.6% vs. 37.3%, P < 0.001 for liver; 19.1% vs. 6.7%, P = 0.025 for LN). Peritoneal or ovarian metastases showed no significant difference according to the KRAS mutational status (P-values > 0.05) (Table 5). Regarding other initial metastatic sites including bone (N = 3), kidney (N = 2) and so on, comparison could not be made due to too few cases.
Table 5. Association between initial metastatic or recurred sites and KRAS mutational status (N = 143)a
KRAS mutational status in patients with initial distant metastasis confined to a single organ at the time of diagnosis of stage IV or recurred disease was also analyzed (N = 113). A higher rate of lung-only metastasis was observed in MT KRAS cases (41.0%) compared with WT KRAS cases (11.5%; P < 0.001). Liver-only metastasis was more frequently observed in WT KRAS cases (65.4%) than in MT KRAS cases (27.9%; P < 0.001). However, the frequencies of developing metastasis only confined to distant LN, peritoneum or other organs were not significantly different between patients with WT and MT KRAS (Table 6).
Table 6. Analysis of metastatic patterns among patients with single organ-only metastasis (N = 113)a
Analyses of the clinical predictive factors for liver- or lung-only metastasis in patients with initial distant metastasis confined to a single organ (N = 113) were performed including other clinical variables [gender, age (< 65 vs. ≥ 65 years), clinical situations for the development of systemic metastasis (stage IV at the time of initial CRC diagnosis vs. recurred after curative resection of stage I - III CRC), primary tumor sites (colon vs. rectum), histologic grade, MSI, etc.] along with the KRAS status. Multivariate logistic regression analysis was carried out using variables with P-values < 0.10 in univariate analysis. KRAS status remained predictive for both liver-only and lung-only metastases [odds ratio (OR) = 0.24; 95% confidence interval (CI), 0.10 – 0.55; P = 0.001 for liver-only metastasis and OR = 4.20; 95% CI, 1.43 – 12.33; P = 0.009 for lung-only metastasis, respectively] in the multivariate analysis. Recurred cases had increased risk of developing lung-only metastasis and decreased risk of developing liver-only metastasis compared with initial stage IV cases. Rectal cancer patients had increased risk of developing lung-only metastasis compared with colon cancer patients; however, the primary tumor location was not predictive for liver-only metastasis in the multivariate analysis (Table 7).
Table 7. Multivariate logistic regression analysis on the correlation between clinical parameters including KRAS status and liver- or lung-only metastasesa
Discordance rates of KRAS status according to the respective metastatic sites
We evaluated the discordance rates of KRAS mutation status between primary tumors and paired tissues from various metastatic organs (Table 8). The lung was the most frequent site showing KRAS discordance (32.4%; 12/37); however, the discordant rate at metastatic sites other than the lung was 12.3% (13/106) (P = 0.005; Table 8). When the discordance rates of the KRAS status between primary tumors and respective metastatic sites (lung, peritoneum, distant LN or ovary) were compared with the discordance rate between primary tumors and hepatic metastatic tissues (10.6%), pulmonary metastasis only showed a significantly higher discordance rate of KRAS mutation status (32.4%; P = 0.014). However, no difference in the discordance rate of KRAS status for the other metastatic organs [peritoneum (13.3%), LN (11.8%), or ovary (18.2%)] was observed relative to liver metastasis (P-values > 0.05; Table 8). One patient with tissues acquired from a primary tumor (colon) and related pancreatic metastatic site showed concordance of KRAS status (KRAS mutant; Gly12Cys).
Table 8. The discordant rates of KRAS mutation status between primary tumors and respective metastatic sitesa,b
Additional analyses were performed to reaffirm whether the discordance rates of KRAS status were influenced by other various clinicopathologic factors such as primary tumor location, type of primary or metastatic tumor specimens (biopsied vs. resected), and the presence of chemotherapy (± radiotherapy) before obtaining primary or metastatic tumor specimens, along with the metastatic organs. In univariate analyses, rectal cancers showed an increased KRAS discordance rate when compared with colon cancers (28.6% vs. 13.9%; P = 0.047), and biopsied primary tumor specimens showed a trend for an increased discordant rate when compared with resected primary tumor specimens (40.0% vs. 15.8%; P = 0.073). However, the site of metastatic organs (lung vs. liver) only affected discordant KRAS status in multivariate logistic regression analysis (OR = 4.03; 95% CI, 1.27 – 12.80; P = 0.018) (Table 9).
Table 9. Univariate and multivariate analyses on the association between clinical parameters and the discordance rates of KRAS mutation statusa
To the best of our knowledge, this is the first large-scale study in which a KRAS mutational analysis was performed between primary tumors and corresponding metastases in Asian MRCRC patients. Overall, a high concordance rate of KRAS status was observed in Korean MRCRC patients, as had been previously reported in Western populations. We observed significant differences in initial metastatic patterns according to the KRAS mutational status. MT KRAS tumors developed lung metastases more frequently as the initial metastatic site; however, liver and distant LN were more frequently involved as the initial metastatic sites in WT KRAS tumors. Additionally, the degree of concordance in KRAS mutational status was significantly different according to the sites of related metastatic organs, where the lung was the most frequent metastatic site showing the discordance of KRAS status.
Our study demonstrated that the clinical presentation of CRC varied according to the KRAS mutational status. KRAS mutational status was shown to affect the presenting pattern of distant metastasis in MRCRC patients. Recurrent cases after curative treatment for localized diseases were more common in MT KRAS patients; however, systemic metastasis was more frequent at the time of initial CRC diagnosis in WT KRAS patients (Table 1). One previous study showed that the risk of recurrence was significantly higher for MT KRAS than WT KRAS tumors in patients with localized CRC [10]. If localized CRC patients with MT KRAS had more chances of recurrence, then the MT KRAS cases would be selected and thus a higher frequency of MT KRAS in recurrent CRC patients would be expected than in patients with stage IV disease at the time of initial CRC diagnosis. However, as our patient cohort is relatively small, our assumption needs to be further investigated in future large studies.
In the present study, organs initially involved by distant metastasis were shown to be different according to the KRAS mutational status. Patients with MT KRAS had an initial lung metastasis more frequently than patients with WT KRAS. In contrast, the WT KRAS patients had liver or distant LN metastases more frequently as the initial metastatic sites. However, other metastatic sites such as the peritoneum were not affected by KRAS status (Table 5). When the analyses were conducted on patients with initial distant metastasis confined to a single organ, the results were similar except for distant LN metastasis (Table 6). However, since the number of cases with LN-only metastasis was small (N = 6), the difference of percentages (7.7% vs. 3.3%) might not have reached statistical significance. Although the MT KRAS tumors showed a trend for more frequent development of peritoneum-only metastasis (13.5% vs. 27.9%; P = 0.062), it was not statistically significant (Table 6). In the multivariate analysis, KRAS status, primary tumor site, and clinical situations for the development of systemic metastasis were significant predictors for liver-only and/or lung-only metastases (Table 7). The reason why the clinical situations of developing systemic metastasis influenced the initially involved metastatic organs (liver or lung) is not clear; this may be related to the process of patient enrollment to this study as patients with available tissues from both primary and paired metastatic sites were only included. During this process, recurred CRC patients with tissue-available lung metastasis might be selectively included. However, even after adjusting for these clinical variables, the KRAS mutational status was an independent predictive factor for both liver-only and lung-only metastases in our study. A previous study, which analyzed the KRAS status in primary tumors of CRC patients, showed that there were more MT KRAS tumors in patients with lung metastasis than in patients with liver metastasis [14]. Based on this finding, they suggest that KRAS-mutated primary CRC tumors can recur with lung metastasis more frequently than with liver metastasis. Although the KRAS mutational status was regarded as positive if KRAS was mutated in any place of primary tumors or related metastases in the present report, our results also support their suggestion. Furthermore, when the analysis was conducted based on the KRAS status of primary tumor, the result of our study was also the same as above. Our work along with previous studies strongly suggests that the sequence of organs involved by systemic metastasis is influenced by KRAS mutational status in CRC patients.
Our results are generally consistent with previous studies that have reported a high concordance rate of KRAS mutation (about 90%) between primary and metastatic tumors [14,15,24-28]. Paired metastatic tissues in previous studies were mostly derived from the liver [24,26,28] because these tissues were easily available from hepatic metastasectomy [33,34]. However, reports on the degree of KRAS concordance of other metastatic organs other than the liver have been very limited. Our study evaluated the KRAS status of metastatic tissues from various organs besides liver. The degree of KRAS mutational concordance was different according to the related metastatic sites, with a significantly higher rate of discrepancy in lung metastases (32.4%) when compared with other metastatic organs (12.3%) or liver (10.6%) (P-values < 0.05; Table 8). Although some studies have recently demonstrated a relatively high degree of discordance, with a discordance rate of up to 50% [11,29-31], there has been no report showing the site-specific KRAS discordance, as was shown in this study. The mechanism behind the discordant KRAS mutational status is still not exactly known [31,35,36]. Sampling errors, heterogeneity within primary tumors, and the development of mutations during the process of metastasis may be the causes of this discordance. The reason why lung is the most frequent site where the KRAS discordance takes place is also unknown. In the present study, we analyzed the pattern of KRAS discordance (i.e. from WT in primary tumors to MT in related metastatic sites or vice versa); as the sample size was small (N = 25), the KRAS discordance pattern did not show any relation to clinical situations for the development of systemic metastasis (stage IV vs. recurred) or metastatic organs from which tumor specimens were obtained. Among 12 cases with KRAS-discordant lung metastasis, 6 cases (50%) had the change of KRAS status from WT in a primary tumor to MT in the lung and 6 cases (50%) had vice versa; there was no statistically significant difference in the discordance pattern between the lung and other paired metastatic organs (Table 4). Therefore, the underlying causes of KRAS discordance need to be further evaluated in future large studies.
Our study has some limitations. First, this study was performed at a single institution and all MRCRC patients diagnosed at our institution were not included. Instead, only MRCRC patients with both primary and paired metastatic tissues were consecutively included. In such a process, unrecognized biases might have influenced our study. Second, a KRAS mutational analysis was not repetitively conducted in cases with discordant KRAS status partly because of insufficient remaining tissue specimens for further examination. This might raise concerns about the sensitivity of the KRAS mutation analysis. We actually used traditional sequencing (Sanger) method with relatively low sensitivity for KRAS mutation analysis [37]. In addition, biopsied specimens of primary tumor showed a trend for higher discordance rate than resected specimens in this study (40.0% vs. 15.8%; P = 0.073), although no significance was shown in multivariate analysis. However, we used tumor cell enrichment by microdissection under the supervision of experienced pathologists to increase the sensitivity of the sequencing method. In addition, biopsy of primary tumors in our study was all performed by endoscopy. Actually, a biopsy of distant metastasis may be more problematic than endoscopic biopsy of primary tumors in context of tumor cell percentage [38]. In the present study, a small number of metastatic specimens (8/143) was obtained from needle biopsy and only 1 case had KRAS discordance [1/8 (12.5%) for biopsied metastatic specimens vs. 24/135 (17.8%) for resected metastatic specimens; P = 1.000]. Moreover, the concordance rates observed between primary and metastatic tissues including the liver only (89.4%) or all metastatic organs other than lung (87.7%) were similar to the concordance rates reported in previous studies. All these findings suggest that the high KRAS discordant rate of lung metastasis (32.4%) had not simply resulted from types of tumor tissue specimens (biopsied vs. resected) or less sensitive analytic methods performed at our institute. Instead, the results from our study reflect the real situation of clinical fields as the traditional sequencing (Sanger) analysis is the most frequent method used in the real clinical practice setting. More sensitive methods, such as real-time PCR for KRAS mutation analysis, are only used in the investigational setting and not widely spread in the clinical practice.
Despite these limitations, our study provides some clinically meaningful suggestions. The present study demonstrated that the KRAS mutational status was an independently predictive factor for organs initially involved by distant metastasis. This observation implies that surveillance strategies after curative surgery might be tailored to individual CRC patients according to the KRAS mutational status. Postoperative surveillance might be more focused on lung metastasis (i.e., chest computed tomography) in patients with MT KRAS than in patients with WT KRAS, when considering the chance of performing metastasectomy after the early detection of pulmonary metastasis. Our study also raised the hypothesis that the discordant rates of KRAS mutational status might be metastatic site-specific in CRC. Using the sequencing method, we found different discordant rates according to the metastatic sites. A high KRAS discordant rate in patients with lung metastasis, observed in our study, warrants further large validation studies.
The concordance rate of KRAS mutation in metastatic sites was generally high compared with primary tumor sites in Korean MRCRC patients, as had been previously reported in Western patients. Organs initially involved by distant metastasis were different according to the KRAS mutational status. Individually tailored postoperative surveillance strategies after curative CRC surgery according to the KRAS mutational status need to be further investigated in future studies. In addition, lung metastasis had a higher rate of KRAS discordance (32.4%) than other metastatic organs, suggesting a possibility of site-specific KRAS discordance in MRCRC patients. This observation should be clarified in further large studies.
End notes
This article was partly presented at the European Multidisciplinary Cancer Congress, Stockholm, Sweden, 23-27 September 2011.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
MJK carried out patient data collection and statistical analysis and drafted this manuscript. HSL and KUP participated in sequencing analysis, data collection and contributed to the interpretation of the data. JHK, YJK, DWK, SBK and JSK treated many of the enrolled patients and contributed to the interpretation of data. JHK and JOL assisted patient data collection and the statistical analysis of the study. SMB and JSL contributed substantially to the interpretation of data, and helped the statistical analysis. KWL conceived this study, participated in its design and coordination, treated many of enrolled patients, and helped to draft the manuscript. All authors read and approved the final manuscript.
We thank Medical Research Collaborating Center (MRCC) in Seoul National University Bundang Hospital for their kind assistance in the process of statistical analysis for this study.
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Ann Surg Oncol 2010, 17(2):572-578. PubMed Abstract | Publisher Full Text
Hutchins G, Southward K, Handley K, Magill L, Beaumont C, Stahlschmidt J, Richman S, Chambers P, Seymour M, Kerr D, et al.: Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer.
J Clin Oncol 2011, 29(10):1261-1270. PubMed Abstract | Publisher Full Text
Oliveira C, Velho S, Moutinho C, Ferreira A, Preto A, Domingo E, Capelinha AF, Duval A, Hamelin R, Machado JC, et al.: KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression.
Oncogene 2007, 26(1):158-163. PubMed Abstract | Publisher Full Text
Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, Dietrich D, Biesmans B, Bodoky G, Barone C, et al.: Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60–00 trial.
J Clin Oncol 2010, 28(3):466-474. PubMed Abstract | Publisher Full Text
Andreyev HJ, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ, Young J, Walsh T, Ward R, Hawkins N, et al.: Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.
Br J Cancer 2001, 85(5):692-696. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Cejas P, Lopez-Gomez M, Aguayo C, Madero R, de Castro Carpeno J, Belda-Iniesta C, Barriuso J, Moreno Garcia V, Larrauri J, Lopez R, et al.: KRAS mutations in primary colorectal cancer tumors and related metastases: a potential role in prediction of lung metastasis.
PLoS One 2009, 4(12):e8199. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Tie J, Lipton L, Desai J, Gibbs P, Jorissen RN, Christie M, Drummond KJ, Thomson BN, Usatoff V, Evans PM, et al.: KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer.
Clin Cancer Res 2011, 17(5):1122-1130. PubMed Abstract | Publisher Full Text
Modest DP, Stintzing S, Laubender RP, Neumann J, Jung A, Giessen C, Haas M, Aubele P, Schulz C, Boeck S, et al.: Clinical characterization of patients with metastatic colorectal cancer depending on the KRAS status.
Anticancer Drugs 2011, 22(9):913-918. PubMed Abstract | Publisher Full Text
De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, Lamba S, Arena S, Frattini M, Piessevaux H, et al.: Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab.
JAMA 2010, 304(16):1812-1820. PubMed Abstract | Publisher Full Text
Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, et al.: Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer.
J Clin Oncol 2008, 26(35):5705-5712. PubMed Abstract | Publisher Full Text
Laurent-Puig P, Cayre A, Manceau G, Buc E, Bachet JB, Lecomte T, Rougier P, Lievre A, Landi B, Boige V, et al.: Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer.
J Clin Oncol 2009, 27(35):5924-5930. PubMed Abstract | Publisher Full Text
Jhawer M, Goel S, Wilson AJ, Montagna C, Ling YH, Byun DS, Nasser S, Arango D, Shin J, Klampfer L, et al.: PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab.
Cancer Res 2008, 68(6):1953-1961. PubMed Abstract | Publisher Full Text
Loupakis F, Pollina L, Stasi I, Ruzzo A, Scartozzi M, Santini D, Masi G, Graziano F, Cremolini C, Rulli E, et al.: PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer.
J Clin Oncol 2009, 27(16):2622-2629. PubMed Abstract | Publisher Full Text
Tol J, Nagtegaal ID, Punt CJ: BRAF mutation in metastatic colorectal cancer.
N Engl J Med 2009, 361(1):98-99. PubMed Abstract | Publisher Full Text
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL: Genetic alterations during colorectal-tumor development.
N Engl J Med 1988, 319(9):525-532. PubMed Abstract | Publisher Full Text
Artale S, Sartore-Bianchi A, Veronese SM, Gambi V, Sarnataro CS, Gambacorta M, Lauricella C, Siena S: Mutations of KRAS and BRAF in primary and matched metastatic sites of colorectal cancer.
J Clin Oncol 2008, 26(25):4217-4219. PubMed Abstract | Publisher Full Text
Etienne-Grimaldi MC, Formento JL, Francoual M, Francois E, Formento P, Renee N, Laurent-Puig P, Chazal M, Benchimol D, Delpero JR, et al.: K-Ras mutations and treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy.
Clin Cancer Res 2008, 14(15):4830-4835. PubMed Abstract | Publisher Full Text
Santini D, Loupakis F, Vincenzi B, Floriani I, Stasi I, Canestrari E, Rulli E, Maltese PE, Andreoni F, Masi G, et al.: High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice.
Oncologist 2008, 13(12):1270-1275. PubMed Abstract | Publisher Full Text
Licar A, Cerkovnik P, Novakovic S: Distribution of some activating KRAS and BRAF mutations in Slovene patients with colorectal cancer.
Med Oncol 2011, 28(4):1048-1053. PubMed Abstract | Publisher Full Text
Knijn N, Mekenkamp LJ, Klomp M, Vink-Borger ME, Tol J, Teerenstra S, Meijer JW, Tebar M, Riemersma S, van Krieken JH, et al.: KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients.
Br J Cancer 2011, 104(6):1020-1026. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Albanese I, Scibetta AG, Migliavacca M, Russo A, Bazan V, Tomasino RM, Colomba P, Tagliavia M, La Farina M: Heterogeneity within and between primary colorectal carcinomas and matched metastases as revealed by analysis of Ki-ras and p53 mutations.
Biochem Biophys Res Commun 2004, 325(3):784-791. PubMed Abstract | Publisher Full Text
Park JH, Han SW, Oh DY, Im SA, Jeong SY, Park KJ, Kim TY, Bang YJ, Park JG: Analysis of KRAS, BRAF, PTEN, IGF1R, EGFR intron 1 CA status in both primary tumors and paired metastases in determining benefit from cetuximab therapy in colon cancer.
Cancer Chemother Pharmacol 2011, 68(4):1045-1055. PubMed Abstract | Publisher Full Text
Baldus SE, Schaefer KL, Engers R, Hartleb D, Stoecklein NH, Gabbert HE: Prevalence and heterogeneity of KRAS, BRAF, and PIK3CA mutations in primary colorectal adenocarcinomas and their corresponding metastases.
Clin Cancer Res 2010, 16(3):790-799. PubMed Abstract | Publisher Full Text
Choi S, Lee KW, Bang SM, Kim S, Lee JO, Kim YJ, Kim JH, Park YS, Kim DW, Kang SB, et al.: Different characteristics and prognostic impact of deep-vein thrombosis / pulmonary embolism and intraabdominal venous thrombosis in colorectal cancer patients.
Thromb Haemost 2011, 106(6):1084-1094. PubMed Abstract | Publisher Full Text
Van Cutsem E, Nordlinger B, Adam R, Kohne CH, Pozzo C, Poston G, Ychou M, Rougier P: Towards a pan-European consensus on the treatment of patients with colorectal liver metastases.
Eur J Cancer 2006, 42(14):2212-2221. PubMed Abstract | Publisher Full Text
Pawlik TM, Schulick RD, Choti MA: Expanding criteria for resectability of colorectal liver metastases.
Oncologist 2008, 13(1):51-64. PubMed Abstract | Publisher Full Text
Gattenlohner S, Etschmann B, Kunzmann V, Thalheimer A, Hack M, Kleber G, Einsele H, Germer C, Muller-Hermelink HK: Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy.
J Oncol 2009, 2009:831626. PubMed Abstract | PubMed Central Full Text
Watanabe T, Kobunai T, Yamamoto Y, Matsuda K, Ishihara S, Nozawa K, Iinuma H, Shibuya H, Eshima K: Heterogeneity of KRAS Status May Explain the Subset of Discordant KRAS Status Between Primary and Metastatic Colorectal Cancer.
Dis Colon Rectum 2011, 54(9):1170-1178. PubMed Abstract | Publisher Full Text
Plesec TP, Hunt JL: KRAS mutation testing in colorectal cancer.
Adv Anat Pathol 2009, 16(4):196-203. PubMed Abstract | Publisher Full Text
Aubin F, Gill S, Burkes R, Colwell B, Kamel-Reid S, Koski S, Pollett A, Samson B, Tehfe M, Wong R, et al.: Canadian Expert Group consensus recommendations: KRAS testing in colorectal cancer.
Curr Oncol 2011, 18(4):e180-e184. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Pre-publication history
The pre-publication history for this paper can be accessed here:

subset: commoncrawl


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Hotels in 40902 - Arjay KY
Only hotels in 40902 zip code are listed below. Search for cheap and discount hotel rates in Arjay, KY for your upcoming leisure or conference / group travel. We list the best 40902 hotels and motels so you can review the Arjay hotel list below to find the perfect lodging. Hotels in Bell county and area code 606 are also listed.
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Hello Mr. Tex,
I am new to this forum, so hopefully I'm not bothering you. I was in the Merchant Forum, and noticed a thread of your from almost a year ago that said you were trying to sell some Kendo Bogu. I know it's a long shot, but do you still have it by any chance? Please let me know!
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Originally written on Project Spurs | Last updated 11/30/12
San Antonio Spurs legend Bruce Bowen was hated by everyone who wasn't a fan of the team who's jersey he was wearing. He was a pest on defense and, even though he was respected by his peers, he was disliked for his play. From moving his arms around a player looking to pass to a hand to the face constantly, you can see he probably wasn't the first player on anyone else's Christmas list. To Spurs fans and his teammates, he was viewed as a great teammate. He was a guy who didn't ask for attention and took whatever job was asked of him from guarding the shortest fastest player to the tallest opposing player. Bowen also knows what great teammates are and knows there's a bond in a team that has to be built up to be successful. If you agree with that, then you shouldn't be too surprised about Bowen weighing in on the Rajon Rondo-Kris Humphries incident. How many guys in the league today are MORE CONCERNED with protecting a teammate, than ending the streak of a personal goal?LOVE RONDO!!! — Bruce Bowen (@Bowen12) November 29, 2012 Kevin Garnett may not be the most popular or well liked player in the league or to its fans, but he's beloved among his teammates and fans who bleed Celtic green. He is to the Boston Celtics what any San Antonio Spur is to his team: a player you hate on an opposing team but one that you'd love on yours, so you'd expect one of his teammates to stick up for him even for a mind touch foul. The Celtics may not be a young team, but they are a team with new pieces that are supposed to be major players in their success this year. The incident cost Rondo two games, but he knows the benefits of the camaraderie that will develop from the team will be worth it. Now the new Celtics know they have someone sticking up for them during any situation and it will pay off, especially in the playoffs. Rondo knew this and so did Bruce.
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John Zant
Muscle Beach Memories
Santa Barbaran Steve Morris honors the iconic weight-lifting hot spot with a garage full of memorabilia. Read story.
Thursday, July 31, 2014
Sports: S.B. Foresters
The S.B. Foresters Have the California Collegiate League's Best Record for the 18th Time in 20 Years. Read story.
Thursday, July 24, 2014
Sports: Sam Cathcart Turns 90
S.B. football coach reminisced about his life in sports and the time he faced death and destruction in World War II. Read story.
Wednesday, July 16, 2014
Sports: Peak Performances
S.B. Track Club stars score big in the heptathlon and decathlon at the U.S.A. Track & Field Championships. Read story.
Wednesday, July 9, 2014
Fútbol Musings
Some thoughts about the World Cup and a few other things. Read story.
Wednesday, July 2, 2014
World Cup Update
Californian Chris Wondolowski helps the U.S. keep on keeping on in the Group of Death. Read story.
Wednesday, June 25, 2014
World Cup Week One
S.B. soccer fans go wild after the stunning 2-1 victory by the U.S. over Ghana on Monday in the opening round of the World Cup. Read story.
Thursday, June 19, 2014
The World Cup
How far will the U.S. soccer team go, and what some S.B. international students have to say about their country's team. Read story.
Wednesday, June 11, 2014
Hoop Heroes
Past and present basketball superstars in the community "who have achieved and/or made significant contributions to the game of basketball" are honored at the Court of Champions dinner. Read story.
Thursday, June 5, 2014
Baseball Viewing Shutout
SportsNet LA is the exclusive TV outlet for more than 140 Dodgers games this season. Read story.
Thursday, May 29, 2014
Sports Roundup
John Zant talks volleyball, Amgen, basketball, and S.B. Athletic Round Table Hall of Famers. Read story.
Wednesday, May 21, 2014
UCSB's Shyan Vaziri Owns the Track
The Gaucho junior's progress to elite status in the 1,500 did not come overnight. "You build your aerobic base over time," he said. Read story.
Thursday, May 15, 2014
Star Athletes: Stamatia Scarvelis and Shane Hauschild
Stamatia Scarvelis and Shane Hauschild have secured their legacy as two of the best athletes to come out of Santa Barbara and Goleta. Read story.
Thursday, May 8, 2014
Amgen Tour Comes to Town
The cycling race covers more than 700 miles in eight stages and bills itself as "America's Greatest Race." Read story.
Wednesday, April 30, 2014
The Voice of the Gauchos
S.B. Sports Writer Philip Patton will be inducted into the Intercollegiate Athletics Hall of Fame on Saturday, April 26. Read story.


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Live large and party like a rock star in this officially licensed Sexy KISS Demon adult womens costume. Rock Halloween in the black and silver mini dress, complete with matching belt, black bat-like cape, black wrist covers and black and silver boot covers.
…blood but instead it's the dreaded demon blood? It's scientifically proven that demon blood is darker and richer than conventional blood, perhaps because of all the souls consumed by demons. Consume this information and believe - get richer, darker fake Demon Blood to complete your costume like…
Hand out bags (of candy) on Halloween night when you wear the Bud Smoker Lab Coat. This white lab coat features a green graphic on the back along with a name plate.
Rescue a family from a burning building or simply get a cat down from a tree on Halloween when you wear this Fireman Coat Adult Costume. Black jacket features reflective material on the torso and arms.
For every little Genius M.D. there is the perfect laboratory jacket. This authentic 3-quarter length lab coat makes this the perfect instant costume. Comb your hair for a disciplined surgeon "look" or keep it crazy for that mad scientist flair - you decide!
Make sure you look the part when you leave for the royal gathering in the Medieval Kings Coat. This brown, polyester top features a lace-up closure on the front and both cuffs along with great shoulder details.
Terrify the neighbors with this creepy Demon Vampire Mask. Yellow skin, sharp teeth and grey hair give this mask a little something extra to complete a vampire costume!
Make Up Tips Terrorize the party this Halloween as a true demon with these Brown Demon Horns! These realistically detailed latex prosthetics will allow you to mingle undetected among the Hell dwellers. Attach in an instant with Spirit Gum Adhesive (sold separately). Remember to perfect the look with…
Beware the demon barber of Fleet Street! Men will quiver with fear as you brandish thisgiant razor blade...shave and a haircut, no way! Authentic looking faux weapon has a bloody finish, suggesting much hard use; lightweight plastic makes it a handy accessory to your costume crime.
…household lamps. Low wattage bulbs work well and you can add strobe lights for an additional effect! Put these up, sit back and enjoy watching the neighbors do double takes! Easy to set up, take down and store. This Halloween decoration features a en evil green demon that's sure to bring shivers!
Willard had rats but you can have bats. Creep them out with this black Squooshey Bat - great for trick or treat!
Go batty on Halloween when you wear these Bat Tights. This pair of nylon and spandex tights feature bat details that will go perfect with any witch or vampire costume.
Be the Count you've always wanted to be when you use the Bat Cape to complete your vampire costume on Halloween. This black cape features a tie closure and a large Gothic collar.
Show off your vampire style when you wear this silvery bat necklace - mysteriously alluring - it will draw attention to your neck!
Welcome your guest in a very special way when they go to hang their coat on the Coat Rack Monster Animated Decoration. This awesome prop features creepy sounds and motions along with the ability to control the volume.
Forget the medical license--get them to call you "Doctor" simply by slipping on this classic Doctor lab coat. This basic white lab coat is a stylish start to a humorous hospital costume sure to tickle their funny bones!
Giddyup out of that grave and go trick or treating when you wear the Horse Demon Adult Men's Costume. This black robe features a jagged hem and comes complete with a belt, gloves and hooded horse skull mask.
Go fast on Halloween when you decide to wear this Speed Demon Adult Mens Costume. The black and white checkered jumpsuit features racing patch emblems along with a red waist band.
Haunt the dreams of everyone in your neighborhood when you wear the Demon of Doom Child Costume. This black robe features a hood and belt, complete with gloves and a creepy skeleton half mask.
Creep out from the darkest shadows and scare up some Halloween fun in this Demon of Doom child costume. The long black robe features bell sleeves and an ornate skull shoulder and chest piece, complete with a black hood and grinning skull mask.
The high gloss-black hair includes the small ponytail in front and long crimped hair on the side. A flexible mesh base keeps you cool all night. The elastic band around the base keeps the wig snug and your hair out of the picture.
Deck out your house completely when you decorate using this Lace Bat Window Panel. This sheer fabric features bat and spider graphics -- it's sure to add a little something to your spooky scene!
Keep up your creepy look when you wear the Bat Bobble Headband. This black, plastic headband features feathery details along with black, green and purple bats.
Fly down from your cave and do the bat walk in this Bat Reputation Child Costume! Look spooktastic in faux velvet lace-up dress with purple tattered skirt, high collar, matching wings, and headpiece.


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Welcome to Calvary Lutheran Church in Brookfield, Wisconsin. If you are seeking a church home or simply looking to learn more about Jesus and what He has done for you, Calvary is here for you. It is not just a church; it is a fellowship of believers coming together to declare the glory of the Lord, and to celebrate Jesus as King. We strive to develop and nurture followers of Jesus Christ through our worship of God, preaching and teaching the Bible, caring for the needs of those in our church and our community, and reaching out around the world with the Gospel.
On the pages of this website, you'll find opportunities that will help you grow as an authentic Christian, as you build Christ-centered meaningful relationships, mature spiritually, and serve using your gifts and talents — in our church, our community, and around the world.
Come be part of Calvary Church — in worship services on Sundays and through activities and ministry during the week. Our prayer is that you will be blessed and strengthened by the power of Jesus and His life-saving Gospel message. We hope to see you soon!
- Saturdays at 5 pm
- Sundays at 9 am


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Book your room at Alpenclub Schliersee
Special Deal Double Room incl. free E-BikeMax Occupancy: 2 guests
Room (Alpenveilchen )Max Occupancy: 2 guests (up to 1 child, 1 infant)
Room (Alpenveilchen)Max Occupancy: 2 guests (up to 1 child)
Room (Alpenrose)Max Occupancy: 2 guests (up to 1 child)
Room (Enzian)Max Occupancy: 3 guests (up to 2 children, 1 infant)
Edelweiss RoomMax Occupancy: 2 guests (up to 1 child, 1 infant)
Special Deal Deluxe Room incl. Spa TreatmentMax Occupancy: 2 guests
Suite GruenseeMax Occupancy: 2 guests (up to 1 child, 1 infant)
Suite SpitzingseeMax Occupancy: 2 guests (up to 1 child, 1 infant)
Suite SchlierseeMax Occupancy: 2 guests (up to 1 child, 1 infant)
Get an overview of this hotel4-star hotel with full-service spa and restaurant
Situated in Schliersee, this spa hotel is within a 15-minute walk of Schliersee Pier and St. Sixtus Church. Markus Wasmeier Farm and Winter Sports Museum is 2.9 mi (4.7 km) away.
Hotel Features
Along with a full-service spa, this hotel has a restaurant and an indoor pool. Self parking is free. Additionally, a fitness center, a bar/lounge, and a spa tub are onsite.
Room Amenities
All 89 rooms provide conveniences like refrigerators and microwaves, plus WiFi and satellite TV. Other amenities available to guests include DVD players, room service, and coffee makers. Limited housekeeping is available.Information missing or incorrect? Tell us!
Hotel Amenities
Hotel Amenities
In addition to a full-service spa, Alpenclub Schliersee features an indoor pool and a spa tub. The hotel offers a restaurant. A bar/lounge is on site where guests can unwind with a drink. Public areas are equipped with high-speed wireless Internet access (surcharge).
This Schliersee hotel also offers a fitness center, a sauna, and a steam room. Onsite self parking is complimentary.
- Babysitting or childcare (surcharge)
- Supervised childcare/activities (surcharge)
- Arcade/game room
- Total number of rooms - 89
- Number of floors - 3
- Bar/lounge
- Breakfast available (surcharge)
- Conference space
- Elevator/lift
- Express check-in
- Express check-out
- Fitness facilities
- Front desk (limited hours)
- Full-service spa
- Laundry facilities
- Spa treatment room(s)
- Multilingual staff
- Restaurant
- Safe-deposit box at front desk
- Free self parking
- Sauna
- Spa services on site
- Spa tub
- Steam room
- Indoor pool
- Television in lobby
- WiFi (surcharge)
Family Friendly Amenities
- Indoor pool
- Laundry facilities
- Babysitting or childcare (surcharge)
- Arcade/game room
- Bowling alley on site
- Refrigerator
- Microwave
- DVD player
Available in all rooms: Wireless internet access (5 EUR per 24 hours surcharge)
Available in some public areas: Wireless internet access (5 EUR per 24 hours surcharge)
Free self parking
Room Amenities
- Phone
- DVD player
- Limited housekeeping
- Private bathroom
- Hair dryer
- Bathtub or shower
- Satellite TV service
- WiFi (surcharge)
- Cribs/infant beds available
- Refrigerator
- Coffee/tea maker
- Microwave
- Room service
Where to Eat
Buffet breakfasts are available for a surcharge and are served each morning.
Karmasee - This restaurant serves breakfast and dinner.
Room service is available.
Nearby Things to Do
An indoor pool and a spa tub are on site. Other recreational amenities include a sauna, a steam room, and a fitness center.
The recreational activities listed below are available either on site or nearby; fees may apply.
- Snowboarding nearby
- Downhill skiing nearby
- Sailing nearby
- Windsurfing nearby
- Mountain biking nearby
- Bicycle rentals nearby
- Hiking/biking trails nearby
- Bowling alley on site
- Cross-country skiing on site
Spa Services
Karma Spa has 3 treatment rooms including rooms for couples. Services include massages, facials, body wraps, and body scrubs. The spa is equipped with a sauna and a spa tub. A variety of treatment therapies are provided, including aromatherapy and Ayurvedic.
- Number of treatment rooms 3
- Couples treatment rooms
- Body wraps
- Body scrubs
- Aromatherapy treatments
- Ayurvedic treatments
- Sauna in spa
- Spa tub in spa
- Massages
- Body treatments
- Facial treatments
To make requests for specific accessibility needs, complete the "Special or Accessibility Requests" section of "Trip Preferences" when you book your hotel.
- Accessible path of travel
- Accessible parking
- In-room accessibility
Hotel Policies
Check-in time ends at 11:30 PM
Check-in time starts at 4 PM
Check-out time is 10 AM
Payment types
Children and extra beds
- Children are welcome.
- Cribs (infant beds) are available.
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
- A tax is imposed by the city: EUR 2 per person, per night
- Fee for buffet breakfast: EUR 15 per person (approximately)
- Fee for in-room wireless Internet: EUR 5 (for 24 hours, rates may vary)
- Fee for wireless Internet in public areas: EUR 5 (for 24 hours, rates may vary)
We should mention
Reservations are required for massage services and spa treatments. Reservations can be made by contacting the hotel prior to arrival, using the contact information on the booking confirmation.
National Rating
Hotelstars Union assigns an official star rating for properties in Germany. This property is rated 4 stars.


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Civil War shipwreck in the way of Ga. port project
As a homespun war machine assembled by workers who likely had never built a ship before, the CSS Georgia represents the South's lack of an industrial base, Johnston said. The North, by contrast, was teeming with both factories and laborers skilled at shipbuilding. They churned out a superior naval fleet that enabled the Union to successfully cut off waterways used to supply Confederate forces.
Despite its functional failures, the shipwreck's historical significance was cemented in 1987 when it won a place on the National Register of Historic Places, the official listing of treasured sites and buildings from America's past. That gave the Georgia a measure of protection - dredging near the shipwreck was prohibited.
Still, a great deal of damage had already been done. The last detailed survey of the ship in 2003 found it in pieces and its hull apparently disintegrated. Erosion had taken a large toll, and telltale marks showed dredging machinery had already chewed into the wreckage.
Salvaging the remains will likely move slowly.
Divers will need to divide the site into a grid to search for artifacts and record the locations of what they find. The large sections or armored siding will likely need to be cradled gently by a web of metal beams to raise them to the surface intact, said Gordon Watts, an underwater archaeologist who helped lead the 2003 survey of the shipwreck.
The Army Corps' report also notes special care will be needed find and dispose of any cannonballs and other explosive projectiles remaining on the riverbed.
"If there is black powder that's 150 years old, and if it is dry, then the stability of it has deteriorated," Watts said. "You'd want to be as careful as humanly possible in recovering the stuff."
Once the remains of the Georgia are removed from the river and preserved by experts, the Army Corps will have to decide who gets the spoils. Morgan said ultimately the plan is to put the warship's artifacts on public display. But which museum or agency will get custody of them has yet to be determined.
Right now the Confederate shipwreck legally belongs to the U.S. Navy. More than 150 years after the Civil War began, the CSS Georgia is still officially classified as a captured enemy vessel.
U.S. Army Corps of Engineers' CSS Georgia page, http://www.sas.usace.army.mil/CSS/
The Associated Press


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In addition to a record-breaking number of graduates in the college – more than 800 undergraduates and nearly 100 graduate students – these graduating students are the first to earn a degree from the newly accredited College of Public Health and Human Sciences.
"Drag is more than just getting on stage in high heels and a gorgeous dress with makeup on my face," says CPHHS senior Luke Kawasaki. "I use drag to tell the world that gender queer and trans bodies are not something to be feared or ignored."
In comparison to bigger cities like Portland, or even Corvallis, Philomath supports a relatively small population and is set in a rural, forested location. But the frequent bustling of logging trucks and daily activity at local sawmills has some residents concerned about air quality.
Public health and human sciences students represent the future of health, and to recognize their achievements the college treated 325 high-achieving scholarship and fellowship recipients to two new events.
"As a researcher, my goal has been to promote full participation and active lifestyles for individuals with disabilities through evidence-based practice," JK says.
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Aransas Pass police look for man, woman involved in Bealls theft (Video)
ARANSAS PASS - Aransas Pass police are looking for a man and woman who stole from a department store in the 1900 block of W. Wheeler Avenue June 4.
Police responded to Bealls just after 8 p.m. after the couple were seen grabbing several items, then leaving in an unidentified vehicle.
The woman is described by police as heavyset and was wearing a tank top and shorts. The Hispanic man with her was wearing a white T-shirt and baggy shorts.
Anyone with information about this crime is encouraged to call Aransas Pass Police Department's Investigations Division or the Tri-County Crime Stoppers at 800-245-TIPS.
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Need Help? Call us at 1-800-566-8098.
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Fish Fillets
7 Feb 2011
|Fish fillets
|1⁄4 Cup (4 tbs)
|1 Quart
Wash the fillets thoroughly.
Combine the salt and water and immerse the fillets in the solution for 20 minutes, then drain.
Place the fillets in a single layer on a tray or baking sheet and freeze quickly.
Dip the frozen fillets in water just above freezing.
A thin coating of ice will form over the fillets.
Dip the fillets about 3 times for a smooth glaze.
Wrap each fillet carefully in freezer paper, then place in a freezer container large enough to hold all the fillets and seal.
Small fish may be glazed in this manner to prevent drying out.
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Fish Fillets Recipe


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Calallen keeps rolling
CORPUS CHRISTI - The 1-3 start Calallen endured to start the football season is a distant memory these days.
The Wildcats have returned to dominating form.
Utilizing a bombarding passing attack and taking advantage of four Kingsville turnovers, Calallen won its fifth consecutive ballgame Friday night, rolling over the Brahmas 55-14 during homecoming at Wildcat Stadium.
With the victory, Calallen (6-3, 5-1 in District 31-4A) assured itself of its 24th consecutive berth in the Class 4A playoffs. The prospect of that happening was in doubt after the first four games.
But there was no doubting the Wildcats on Friday. They totaled 399 yards of offense behind Dustin Vaughan's 270 passing yards, three touchdown passes and a rushing score.
"I knew it from the get-go that we had a chance to beat this team and we came out and did it," said Vaughan, who threw for 149 yards and two scores in the first quarter alone. "That's all that matters."
So dominant were the Wildcats, the officials let the game clock run almost continuously in the second half after Calallen broke from the locker room with a 42-7 lead.
"I said at the start of this season that we were a good football team. We were a team like we were in the 90s. And we are," Calallen coach Phil Danaher said. "We're starting to show it now, what we're capable of doing. We throw the ball well, we run the ball well, we power the ball, we kick well. I don't care what you say other than we're executing, we're hitting on cylinders. We're peaking at the right time."
The Brahmas (3-3, 4-5) fired the opening salvo, scoring on a 71-yard, 14-play that consumed more than six minutes. Kingsville quarterback Vando Gonzalez connected with Travis King on a 24-yard touchdown pass, the first of their two scoring hookups for the game.
But that final hookup between the Brahmas didn't come until Calallen had scored seven consecutive touchdowns, the first coming on Vaughan's 69-yard pass to a wide-open Jordan John on the Wildcats' first play from scrimmage.
"We were just hitting on all cylinders. The receivers were catching the balls, the line was doing a great job of blocking," Vaughan said. "You couldn't ask for a better game from them blocking from the offensive linemen. Everything was just working out. And our second team came out in the second half and did a great job."
The Wildcats intercepted Gonzalez four times -- Jared Wyatt had two of the picks and Jake Huddleston and Matt Garza had one each -- and they all led to Calallen TDs. Three of them came on Kingsville possessions in the first half. Vaughn cashed in by throwing TD passes to Adam Hoelscher and Hunter Whetsel and scoring on a 1-yard run.
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Krantz is the principal investigator (PI) of the project at The Children's Hospital of Philadelphia, along with co-PI Nancy B. Spinner, Ph.D., director of the Clinical Cytogenomics Laboratory at Children's Hospital. Both researchers also are faculty members at the Perelman School of Medicine of the University of Pennsylvania, which is partnering with Children's Hospital on three projects comprising the grant.
In addition to pinpointing gene variations that are the likely causes of a condition for which a patient is being studied, say the researchers, whole-genome sequencing will also uncover so-called "incidental findings." These findings are gene variants not related to a current condition, but having a bearing on an individual's future health. "We will investigate which of these incidental findings should be disclosed to a patient's family," said Spinner. "This is a complex issue that will benefit from the insights and contributions of the multidisciplinary team we have assembled for this program."
The first project under the grant, Clinical Genomics Studies, is co-led by Krantz and Spinner, and will enroll four cohorts of children in these disease groups: bilateral sensorineural hearing impairment, nuclear encoded mitochondrial respiratory chain disorders, sudden cardiac arrest and intellectual disability. "Each of these groups of disorders cannot be easily diagnosed with a gene-by-gene approach, so experts from several disciplines will develop tools for sequencing the patients' whole genomes and then interpreting the vast amounts of data," said Krantz. "Not all the gene mutations we find w
|Contact: John Ascenzi
Children's Hospital of Philadelphia


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Catalogue Number: 211-5400
- Features slide rule, spirit level, hammer, Phillips screwdriver & pliers
- Includes pliers, Allen keys, tape measure & spanners
- Black plastic case with tools mounted on a soft foam mat
Sorry, there are currently no sellers for this product.
Product Details
This Stanley 32-piece tool kit gives you a good range of tools to carry out DIY jobs around your home.
The tool kit comes in a black plastic case with 32 tools mounted on a soft foam mat. Tools include a slide rule, spirit level, hammer, Phillips screwdriver, pliers, Allen keys, tape measure and spanners.
With the Stanley 32-piece tool kit, you will be able to lay your hands on the tools you need to complete the job.
Product specifications
Product specifications
Key Information
|Tool box
|Pack Size
Additional Information
|What"s in the Box
|Includes: 32 pieces
|Product Height
|30.0 Centimetre
|Product Width
|360.0 Centimetre
|Product Depth
|265.0 Centimetre
|Product Weight
|2.85 Kilogram


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Register with us or sign in
We've had a lot of practice!
Oh, then a short yellow lily! You are the same height as me.
I imagined KEF being tall and blonde, now I know she is tall! I thought of a tall yellow lily, except there is already a lily here but she is pink.
Nutcutlet I thought of as a hazel tree, she's a bit of a tree expert and you can put hazelnuts in your nutcutlets.
Fairy I'd thought of dierama, Angel's Fishing Rod, could be used by a fairy too.
Orchid Lady is Tracey, she sounds fun and younger than some so I thought Snapdragon, used to play with them when I was a child.
It's lovely, my OH gave it to me fairly recently.
Good answer Dove, well thought out, but I associate Verdun with agastaches and grasses!
This is a hard one. But Chicky likes flowers and has chicklets which sort of makes me think of lupins. But I don't know if she's tall or short!
Dove's are silvery and soft, so I was thinking Stachys Byzantina, but I don't know if she likes it. She's just made a pond and that's more for dry places.
There have been several threads on this subject already and so many different opinions. I'm afraid I find Monty rather dull, his voice lulls me into sleep and he isn't not as knowledgeable as I would like, but I imagine he's a nice person.
Pouring here too.
Morning all.
We stayed in Aghios Nikolaos about 39 years ago! Must be that, because it was before I had children. I think my maths isn't good either, Clari, because I thought I was 27. We went to Spinalonga too, on a boat which I was nearly sick in because I ate something the hotel shouldn't have served the night before. It was October and was over 80°F and most of the beaches were deserted. When we got home we spent over 3 hours sitting on the platform at Gatwick station, about 45°F in our summer clothes in the night. First train was at 6am and everywhere was shut.
But we did have a lovely time in Crete. We hired a mini Fiat, like a bubble car, and the mountain roads were amazing, dirt tracks, wonderful scenery. The sea was clear and warm.
2 sons, DILs and adorable granddaughter and new baby came for lunch today, French Mothers Day. Lovely to see them all. Sons gave me a dipladenia.
Glad you had a good birthday Punkdoc. I looked up the Black Swan in Helmsley, looks yummy, lovely food photos. I know Helmsley, have an old school friend and an uncle in N. Yorks. We are going there in July. Love the Helmsley walled garden too.


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Leg Of Lamb, Yucatan-Style
|Ground cinnamon
|1⁄8 Teaspoon
|Ground pepper
|1⁄2 Teaspoon
|1 1⁄2 Teaspoon
|Salad oil
|2 Tablespoon
|Leg lamb
|6 Pound, boned and butterflied
|Grated orange peel
|1 Tablespoon
|Orange juice
|3 Tablespoon
|Grated lemon peel
|1⁄2 Teaspoon
|Packed cornbread
|1⁄2 Cup (8 tbs)
|Minced onion
|1 Tablespoon
Crush achiote by whirling to a powder in a blender (or grind achiote through a pepper mill set at medium grind.
Blend achiote (or chili and cinnamon) with pepper, salt, and salad oil.
Rub over all surfaces of lamb.
Blend thoroughly orange peel, orange juice, lemon peel, cornbread crumbs, and onion.
Spread mixture over inside of lamb, then reshape leg into a compact form and skewer or tie with heavy thread to hold.
To barbecue, bank about 20 low-glowing coals on each side of fire grill.
Place a drip pan in center.
Place meat on greased cooking grill about 6 inches above pan.
Cover barbecue and adjust dampers or drape a large piece of heavy-duty foil over meat.
Cook for about 2 hours or until meat thermometer inserted in thickest portion registers 140° for slightly pink meat; or cook until done to your liking.
After about 1 hour, add 6 to 8 briquets to each side.
Let roast stand in a warm place for about 20 minutes, then garnish with parsley and radishes.


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Parent Organization: Allocations Board
Global Medical Brigades is a secular, international student-operated volunteer organization whose mission is to provide sustained health care to underserved communities throughout the world. Global Medical Brigades is a part of the larger organization known as Global Brigades, which is the world's largest student-led international relief program.
Along with affiliate groups at other distinguished universities, our BU team recruits student volunteers and medical professionals, gathers medicine and other supplies, and then travels overseas to perform these medical brigades. Our current emphasis is to help the impoverished villages of Honduras in collaboration with one of their country's most highly regarded nonprofits, Sociedad Amigos de los Ninos, led by Sister Maria Rosa Leggol, a recent nominee of the Nobel Peace Prize.
We will hold two trips per year at a time decided by the executive board. We will recruit dedicated students, nurses, residents, pharmacists, dentists and doctors to volunteer on each trip. Along with the medical brigades, students will participate in several community projects that aim to also better the quality of life in these impoverished areas. The cost is $750 for the week plus airfare, which typically can range from $600 - $900.


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September 18th, 2010. I remember waking up that morning and crossing my fingers as I looked out the window. Gloomy, rainy, and cold. Sigh….a beautiful venue, a beautiful couple, and an ugly day. Oh well, this is what we get living in Vancouver.
As we drove out to Carolyn's parent's home in Abbottsford, the clouds slowly began to separate, and the sun slowly started peaking through. I held my breath the whole way there, and by the time we arrived at their house, it was full blown sunny and even HOT! Praise God, the sun stayed throughout the ENTIRE DAY, and as soon as we left Swan-E-Set at the end of the day, it started pouring. Wow.
We had just shot Carolyn and Kevin's engagement session a few weeks ago, so they were still fresh in our minds and we were excited to see them commit to each other in the name of our Lord. It was a beautiful day, and Carolyn and Kevin and their wedding party looked so elegant and classy.
Dan and I had a blast, enjoy some favorites!
Starting the day off at Carolyn's parent's gorgeous home, she got ready in the master bedroom. As soon as I saw Carolyn's dress, I literally gasped out loud! Oh my GOSH, what an amazing dress!!
There was beautiful light all around. The bathroom served as an ideal spot to shoot! Beauty!It was our first time shooting out at Swan-E-Set…and it made me want to get married there! I can understand why it's such a popular venue!Carolyn and Kevin's wedding party was awesome. The venue had golf carts for everyone, and man did we all have fun on those!I still can't get over how sunny it was! We had to pull out our Norman (photog talk!) to over power the sun!Love it!We just wanted to keep shooting Carolyn and Kevin, they looked so good! I didn't want to put my camera down ;pA Dan shot…he always amazes me with his vision!I remember asking Carolyn and Kevin at their engagement session if they were going to have any Korean tea ceremonies or traditions, and they said no. Rather, their mom's walked down the aisle together, hand in hand, wearing traditional Korea dresses (I apologize for not knowing the correct terminology!) How cool, and how awesome to show that these two families are uniting as one. The bride and her father!Carolyn called her dad a 'joke-ster'…he's definitely a fun character! He waved all the way down the aisle, and the guests roared in laughter! Before the ceremony started, everyone was lead to sing two worship songs.The light here is stunningA few games throughout the night…Something else that I thought was super cool: The first dance wasn't with each other, rather the first dance was Carolyn dancing with her dad, and Kevin dancing with is mom. After about half way through the song, Carolyn and Kevin joined each other. Awesome. The end of the night consisted of a slide show, which included Kevin's proposal to Carolyn (recorded by a friend), and an 'Arts Cafe', in which various friends and family members performed songs and dance routines…and Kevin finished off the night singing a few songs to his lovely bride!
What an amazing day it was being surrounded by such friendly people!
Enjoy their slide show below!


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Dwight Jones
Jones Delivers State of the District Address
The nation's fifth-largest school district is facing tough challenges this year.
School District Aims For Financial Transparency
A new online portal lets you see how the Clark County School District is spending your tax dollars.
Voters Say No To Schools and Improvements
Voters went to the polls before and on Election Day and rejected a property tax increase designed to raise between $669-720 million.
Property Tax Favorable Among Likely Voters
The Clark County School District will have a very important question on the November ballot.
CCSD Report Shows Improvement
In a 123-page report, the Clark County School District outlined everything from class size to truancy rates.
Clark County School District Shows Improvemment
The nation's fifth-largest school district is making gains.
Lawmaker Wants $20m For English Language Lessons
A state lawmaker wants to spend $20 million for English language programs in Clark County schools.
Superintendent: School District "On The Right Course"
Superintendent Dwight Jones says despite challenges, the nation's fifth-largest school district is heading in the right direction.
November Ballot Question Could Lead To New Schools
The Clark County School District has been through some times since the Great Recession began five years ago.
Dwight Jones Welcomes Back Students
A brand new school year is underway in the Clark County School District and Superintendent Dwight D. Jones welcomed students back to class in a unique way.


text:
Item Code: POWR-F-ER419
Availability: In stock
Powr-Flite Upright Vacuum PF82HF Replacement Vacuum bags (3 Pack)
Green Klean Replacement vacuum bags use the highest quality Micro-Plus filter media including Melt-Blown inner liner in order to achieve filtration efficiencies up to 99.9%. Designed specifically for commercial use, they are always equal to, or exceed OEM quality. Better filtration means cleaner air, less dusting, longer secondary filter life, at considerable savings. Each bag is printed to easily identify the vacuum it fits.
These vacuum cleaner bags are not cheaply made, just cheap on your wallet. The vacuum cleaner bags are an excellent replacement for part number ER419 and strongly recommended by GoVacuum for use in your vacuum cleaner. If you have any questions about what vacuum cleaner bags will fit your vacuum cleaner or you need bulk pricing, please contact us.


text:
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Holcomb performs a track from his latest LP, Medicine.
GW checks in with daring acoustic fingerstylists Andy McKee, Jon Gomm and Daryl Kellie.
Can songwriting be affected by atmosphere? Yes, it most definitely can.
They've got the hair. They can rock tight pants. And lord knows, they've got the balls to think they can do justice to the songs of the legends. Yep, they're all-female tribute bands, and they are kicking ass across the globe. These six bands are made up of seasoned musicians who are not only serious about laying down an authentic performance of classic rock and metal, but they also bring their own artistry to the table.
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Children are one of our highest priorities at First Baptist Church, Laredo. The wonderful staff of paid professional nursery workers and volunteers lead our many programs. Our purpose is to help grow and develop our children spiritually. We do this through Bible teaching, crafts, music, and multimedia.
G.R.O.W. (God Rewards Our Work) is a fun outreach ministry that our church family looks forward to participating in week after week!
The Mother's Day Out program of First Baptist Church, Laredo is a Christian program. Our goal is to not only provide your child with a loving, nurturing, Christian environment, but one that is also fun-filled, safe, and developmentally appropriate.


text:
User Reviews for Tylenol Extra Strength
The following information is NOT intended to endorse drugs or recommend therapy. While these reviews might be helpful, they are not a substitute for the expertise, skill, knowledge and judgement of healthcare practitioners in patient care.
Learn more about Tylenol Extra Strength.
Reviews for Tylenol Extra Strength to treat Sciatica
No reviews have yet been submitted. Be the first to review this drug.
Learn more about Sciatica
Micromedex® Care Notes:
Related encyclopedia articles:
Symptoms and treatment for:
Mayo Clinic Reference:
More about Tylenol Extra Strength (acetaminophen)
Consumer resources
- Tylenol Caplet Extra Strength
- Tylenol Extra Strength
- Tylenol Extra Strength Cool Caplet
- Tylenol Extra Strength EZ
- Tylenol Gelcap Extra Strength
- Tylenol Geltab Extra Strength
- Other brands: Paracetamol, Mapap, Ofirmev, Q-Pap, More (48) »


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The Westin Resort & Spa, Puerto Vallarta
The Westin Resort & Spa, Puerto Vallarta
Hotel Guest Rating: 8.3/10
Paseo De La Marina Sur 205
Puerto Vallarta 48354
Welcome to the The Westin Resort & Spa, Puerto Vallarta
A private beach with pergolas, two outdoor pools, a hot tub and plush Heavenly Beds welcome Priceline guests to The Westin Resort & Spa, Puerto Vallarta, which also has a spa on-site and provides complimentary parking.
Hotel Features
The beachfront Westin Resort & Spa has 280 rooms in a series of buildings with various heights, surrounded by lush tropical foliage. The spacious accommodations feature balconies, colonial Mexican furnishings, plush Heavenly Beds and flat-panel TVs. Some rooms include ocean views. The resort has two palm-lined, outdoor pools, a swim-up bar, outdoor hot tub, three lighted tennis courts, kids' club, luxury spa, steam bath, sauna, souvenir shop, concierge desk, gym and business center. This is one sweet stretch of sand: the private beach has pergolas and offers water sports for additional fee. Dining includes a seafood/steak restaurant, Mexican restaurant with a rooftop terrace and indoor bar with seasonal live entertainment. Pets under 40 pounds are welcome for no additional fee. Note: The resort charges a fee for beach amenities, fitness center, tennis, spa, kids' club and high-speed internet access. Self-parking is free of charge.
Hotel Location
Westin Resort & Spa is about one-and-a-half miles south of Puerto Vallarta International Airport, and four miles north of Puerto Vallarta.
Guest Favorites
Priceline guests praise The Westin Resort & Spa, Puerto Vallarta as an "awesome hotel" with a "simply great atmosphere," "very friendly" staff and "tasty" breakfast, which altogether provide "one of the most amazing experiences" in the area.
The Westin Resort & Spa, Puerto Vallarta Amenities
- Baby sitting
- Baggage hold
- Balcony/Lanai/Terrace
- Business center
- Ceiling fan
- Child programs
- Coffee/Tea maker
- Connecting rooms
- Cribs
- Direct dial phone number
- Exercise gym
- Front desk
- Hairdryer
- High speed internet access for laptop in public areas
- High speed wireless
- Ironing board
- Lounges/bars
- Meeting rooms
- Minibar
- Ocean view
- Onsite laundry
- Parking
- Pool
- Restaurant
- Safe deposit box
- Separate tub and shower
- Shops and commercial services
- Smoke detectors
- Spa
- Steam bath
- Tennis court
- Voice mail
- Whirlpool
Hotel Information
Upon check-in photo identification and credit card are required. All special requests are subject to availability upon check-in. Special requests cannot be guaranteed and may incur additional charges.
Hotel Guest Reviews of the The Westin Resort & Spa, Puerto VallartaOur hotel ratings and reviews are from real hotel guests. Priceline.com ensures that its reviews are guests-only by proactively sending hotel surveys to customers after they've completed their hotel stays. In the post-stay surveys, priceline.com hotel customers are asked a number of questions about their stay and the hotel. On a scale of 1-10 with 10 being the best, the survey asks guests to rate their overall experience and specifically rate the hotel's cleanliness, staff and location. Priceline.com does not allow site visitors to post unsolicited hotel reviews.
May 30, 2015
Family Traveling with Young Children
May 5, 2015
April 22, 2015
March 13, 2015
January 17, 2015
November 5, 2014
October 31, 2014
October 30, 2014
September 4, 2014
Family Traveling with Young Children
It was a very nice big hotel, nice pools, gym but they didn't have a fridge already in room plus they would charge for everything it didn't even come w coffee or a fridge or wifi because they would charge things that u find for free at any other hotels there was always a charge at this hotel plus they always put a hold on your card of $100 when u get there and when u leave why? I don't even know. ...
August 22, 2014
Family Traveling with Young Children
I will definitely recommend this hotel as a good option. Its at 10 min away from downtown and malecon area so I needed to go by car but its a good option to take
(1 - 10 of 31 reviews)
- Raintrees Club Regina Puerto Vallarta from $216 (0.1mi)
- Vamar Vallarta Marina & Beach Resort from $67 (0.2mi)
- Villas Vamar from $96 (0.2mi)
- Melia Puerto Vallarta - All Inclusive from $184 (0.3mi)
- Flamingo Vallarta Hotel & Marina from $38 (0.4mi)
Most Popular Guest-Rated Hotels in Puerto Vallarta
- Casamagna Marriott Puerto Vallarta Resort & Spa
- The Westin Resort & Spa, Puerto Vallarta
- Fiesta Americana Puerto Vallarta - All Inclusive
Most Popular Business-Friendly Hotels in Puerto Vallarta
- Comfort Inn Puerto Vallarta
- Fiesta Americana Puerto Vallarta - All Inclusive
- Casamagna Marriott Puerto Vallarta Resort & Spa
Most Popular Romantic Hotels in Puerto Vallarta
- Casamagna Marriott Puerto Vallarta Resort & Spa
- Fiesta Americana Puerto Vallarta - All Inclusive
- The Westin Resort & Spa, Puerto Vallarta


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The LEGO Technic Idea Book: Wheeled Wonders: VehiclesPaperback Lego Technic Idea Book
List price $21.03
You save $7.53 35% off
Free delivery worldwide
Dispatched in 2 business days
When will my order arrive?
- Publisher: No Starch Press,US
- Format: Paperback | 144 pages
- Dimensions: 198mm x 252mm x 18mm | 458g
- Publication date: 1 November 2010
- Publication City/Country: Daly City, California
- Illustrations note: col. Illustrations
- Sales rank: 22,317
Product description
The LEGO(R) Technic Idea Book: Wheeled Wonders is a collection of hundreds of mechanisms for cars, trucks, motorcycles, and other vehicles that you can build based on their pictures alone. Each project uses color-coded pieces and is photographed from multiple angles, making it easy to see how the models are assembled without the need for step-by-step instructions. Every model illustrates a different principle, concept, or mechanism that will inspire your own original creations. You're encouraged to use these elements as building blocks to create your own masterpieces. The Technic models in Wheeled Wonders spin or move things, drag race, haul heavy gear, bump off walls, wind up and go, and much more. You'll discover how to build differential gears, implement steering and suspension, and design clutch and transmission systems to use in your own vehicles. This visual guide, the second in the three-volume LEGO Technic Idea Book series, is the brainchild of master builder Yoshihito Isogawa of Tokyo, Japan. Each title is filled with photos of Isogawa's unique models, all of which are designed to fire the imaginations of LEGO builders young and old. Imagine. Create. Invent. Now, what will you build? NOTE: The LEGO Technic Idea Book series uses parts from various Technic sets. If you don't have some of the pieces shown in a particular model, experiment by substituting your own parts or visit the No Starch Press website (nostarch.com) for a list of the special parts used in the book.
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Author information
Yoshihito Isogawa is a LEGO luminary with 42 years of experience. He began writing computer manuals while at the Tokyo University of Science and founded Isogawa Studio, Inc. soon after. He has twice won the grand prize in the Japan Manual Contest held by the Japan Technical Communicators Association and he has won outstanding performance awards many times. He currently lives in Tokyo.


text:
1.Does anyone know why my more buttons on my post aren't working? I can't seem to find settings to fix that. I'm new on WP.org and not familiar with HTML.
I made a test post here: http://dearlovely.com/letters
2. I've made my sidebar invisible, but now there seems to be an imaginary wall preventing me from center my text on pages. See this link for example: http://dearlovely.com/about