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The aim of this study was to identify K-ras mutations as marker for isolated tumor cells in liver, lymph node, and bone marrow specimens of colorectal cancer patients. To detect these, a PCR-RFLP assay was used with a sensitivity exceeding that of routine histopathology by at least 1 order of magnitude. In addition, the ratio of mutated versus wild-type alleles was determined by an internal standard. Of 199 patients, 74 (37.5%) were found to bear a K-ras-positive tumor. Of these, 60 (81%) were mutated in codon 12 and 14 (19%) in codon 13 (P < 0.001). In addition, 14 organs were found K-ras positive, 13 of which were from 12 patients with a K-ras-positive tumor (16%) and 1 from a patient with a K-ras-negative tumor (0.8%). Eight patients exhibited liver involvement and 6 showed lymph node involvement. Remarkably, no bone marrow specimen was found K-ras positive (P < 0.017 versus liver involvement). Sequence analysis of tumor DNA revealed that GGT (Gly) was replaced by GAT (Asp; 35%), GTT (Val; 32%), AGT (Ser; 13%), GCT (Ala; 10%), TGT (Cys; 8%), and CGT (Arg; 2%) for codon 12, and by GAC (Asp) as the only type of mutation for codon 13. In colorectal carcinomas the ratio of K-ras mutated versus wild-type alleles ranged over 4 orders of magnitude (100-10−4, median: 10−2) and was correlated with both, residual tumor load (R1/2; P = 0.028) and distant metastasis (M1; P = 0.057). These results show that detection of K-ras mutated alleles by PCR-RFLP in patients with colorectal carcinoma may aid in the identification of isolated tumor cells. High ratios of K-ras alleles were correlated with certain negative prognostic parameters (R,M). In accord with its function as a primary filter for colorectal carcinoma cells, the liver was more often contaminated with K-ras-positive cells than bone marrow.
On a global scale, colorectal cancer (CRC) is one of the most common malignant diseases with higher incidence rates in Western industrialized countries than in Asia and South America. In Germany, >24,000 men and 28,000 women are diagnosed with CRC every year, and ∼30,000 patients succumb to this malignant disease. When these figures are related to the total incidence of malignancy, CRC ranks third after lung and prostate carcinoma for men and second after mammary carcinoma for women. Regarding mortality, CRC ranks second place for all of the malignancies in both sexes (1) . The 5-year overall survival rate declines with increasing cancer stage. In the early stages [Unio Internationale Contra Cancrum (UICC) I and II] the 5-year survival rate ranges from 70 to 90%, whereas the prognosis deteriorates in advanced stages (50% in UICC III and 5–25% in UICC IV). This implies that 20–30% of patients who are in early stages of cancer development and undergo resection with curative intent will suffer from metastatic recurrence.
Metastasis is caused by tumor cells that are shed into the blood or lymph vessels and are disseminated into peripheral organs before or during surgery. These so called isolated (disseminated) tumor cells (ITC) are tracked by immunohistochemistry, reverse transcription-PCR, and various other methods to assess their distribution and prognostic value (2 , 3) . The expression of carcinoembryonic antigen, cytokeratins, or guanylyl-cyclase C has been used as diagnostic marker for detecting ITC in organs such as lymph nodes (2) , blood, and bone marrow (3) . Up to now, several studies have been performed, but the metastatic potential of cells that are identified by cytokeratins or carcinoembryonic antigen in body compartments is still contested. Studies on cytokeratins/carcinoembryonic antigen from Greenson et al. (4) , Liefers et al. (5) , and Isaka et al. (6) showed that patients harboring ITC in lymph nodes have a worse prognosis than patients without ITC, whereas other investigations using the same biomarkers did not show a significant change in prognosis when ITCs were diagnosed in this tissue (7, 8, 9, 10, 11) . Another possibility for identifying ITCs or micrometastasis is the detection of nucleic acids, harboring tumor-specific gene mutations, which correspond to those in the primary tumor. In the development of sporadic CRC, K-ras mutations occur early and with high incidence (30–60%) in the multistep process of colorectal carcinogenesis (12) . Hot spots for mutations in codons 12, 13, and 61 of the K-ras gene can be used for convenient detection of tumor cells (13 , 14) . A relation between the presence of K-ras mutations in the primary tumor and a poor prognosis has been shown by some studies (15, 16, 17, 18, 19, 20) , but not by others (21 , 22) .
The liver functions as a primary filter for colorectal tumor cells shed into the blood and is the main target organ of CRC metastasis. However, there are only a few studies that have attempted to detect isolated tumor cells within this organ. De Kok et al. (23) probed for ITCs by seeking K-ras mutations in bile obtained intraoperatively from patients with known liver metastasis, but succeeded only in 20% of patients with K-ras mutated tumors. Schimanski et al. (24) investigated K-ras mutations in liver biopsies of patients at various CRC stages. A modified PCR-RFLP assay was used for detection, which had been originally established by Norheim-Andersen et al. (14) . With this method a third of all patients with K-ras mutated primary tumors were found to harbor ITCs showing K-ras mutation in the liver identical to the primary tumor (24) . A follow-up of these patients has demonstrated that the presence of ITCs in the liver has a negative bearing on tumor recurrence and patient survival.3
The aim of this prospective study was to extend these results, by comparing the incidence of ITCs in the liver with that in lymph nodes and bone marrow in a relevant number of patients. Furthermore, a quantitative PCR assay was used to investigate the relation between the extent of mutated K-ras alleles and parameters of tumor aggressiveness. Finally, we explored whether results on the presence of mutated K-ras alleles can vary between tumor regions and to what extent such a difference can contribute to misclassification of tumor K-ras mutation status.
Patients and Acquisition of Tissue Samples.
A total of 203 consecutive patients with colorectal carcinoma undergoing elective surgery at the municipal hospital of Nürnberg, Germany, were entered into this prospective, diagnostic study. Patients had been diagnosed with CRC by the responsible pathologist based on endoscopically resected tumor specimens (tumor resection was performed irrespective of the M status). After obtaining informed consent from the patients and on the basis of the decision of the ethical committee, the following tissue samples were collected: tumor (100–500 mg of a central non-necrotic part), mucosa (100–200 mg from the oral part of the resectate), lymph nodes (of para-aortic origin), and liver [two samples of 20–50 mg, taken by trucut biopsies from segments three (left lobe) and five (right lobe)]. The liver biopsies were directed toward tissue that appeared to be free of metastasis. Four patients were excluded from the study because their tissue samples were incomplete. In addition, bone marrow (2 ml from the iliacal crest) was obtained from 113 patients in the second part of the study. All of the tissues were shock frozen in liquid nitrogen and then stored at −80°C until analysis. All of the specimens surgically obtained were evaluated by Prof. Hans Peter Wünsch (Institute of Pathology, Municipal Hospital Nürnberg).
Cell Cultures.
Three human CRC cell lines (HT-29, HDC-8, and SW-620), and one mammary carcinoma cell line (MDA-MB231) were used as controls for PCR-RFLP and generating standards for quantitative PCR. HT-29 cells (DZSM No. ACC 299; K-ras wild type) were grown in Mc Coy's medium (Sigma, Munich, Germany), SW-620 cells (American Type Culture Collection No.CCL-227; K-ras codon 12 mutated) were grown in Leibowitz L15 medium, HDC-8 (established previously by Brüderlein et al.; Ref. 25 ; K-ras codon 12 mutated) and MDA-MB 231 cells (American Type Culture Collection No. HTW-26; K-ras codon 13 mutated) were grown in RPMI 1640. Media supplemented with 15% fetal bovine serum (Sigma) and l-glutamine (2 mm), were used to cultivate the cells under standard conditions (humidified atmosphere, 5% CO2 in air, 37°C).
Sensitivity Assays.
Serial dilutions of K-ras mutated (HDC-8; MDA-MB-231) in wild-type cells (HT-29) were based on cell counts and ranged from 1:0 to 1:106 K-ras mutated to wild-type cells. For serial dilutions in mucosa and liver, the weight of these tissues was used by assuming that 100 mg of tissue corresponded with 108 cells.
DNA Isolation.
Tissues were disrupted in lysis buffer (2 ml of buffer QRL1 from Qiagen, Hilden, Germany) using a 5 ml homogenizer (Braun, Melsungen, Germany). DNA was isolated using the DNA/RNA-isolation kit from Qiagen according to the manufacturer's recommendations. In brief, proteins were precipitated by an equal volume of QRV1 buffer. Thereafter nucleic acids were pelleted by adding 0.8 volumes of isopropanol to the clear supernatant. The nucleic acid pellet was dissolved in QRL1 and QRV2 buffers (ratio 1:9) and loaded onto a column. Under these conditions, RNA is retained on the column and the eluate can be collected for later DNA isolation. RNA was washed on the column (buffer QRW) and then eluted with preheated (45°C) QRU buffer. RNA was pelleted by adding an equal volume of ice cold isopropanol and centrifuging at 15,000 × g (30 min; 4°C). The pellet was washed twice with 70% ethanol and finally air-dried. Thereafter, the eluate was loaded onto the column, and the DNA was treated in an analogous way with QC wash buffer, preheated (45°C) QF elution buffer, 0.7 volumes iso-propanol, and 70% ethanol. The amount of isolated nucleic acids was determined spectrophotometrically (Gene Quant II; Pharmacia, Freiburg, Germany).
Detection of K-ras Mutations.
Detection of K-ras mutations in codons 12 and 13 was performed by PCR-RFLP on all available tissues of the 199 CRC patients as described before (24) . Briefly, 300 ng of DNA were used as a template for the first PCR, which consisted of a 50 μl volume containing 0.35 units of Red-taq DNA polymerase, 5 μl 10× Red-taq PCR reaction buffer (Sigma-Aldrich, Steinheim, Germany), 0.2 μm deoxynucleotide triphosphates (MBI Fermentas, St. Leon-Roth, Germany), and 0.2 μm of the oligonucleotide primers Ras A and Ras B (see Table 1⇓ ). For amplification, a DNA Engine PTC200 (MJ Research, Watertown, MA) thermocycler was used under the following conditions, initial denaturation (4 min at 95°C), followed by 30 cycles of denaturation (1 min at 94°C), annealing (1 min at 52°C), and elongation (2 min at 72°C). After the last cycle, a final extension (5 min at 72°C) was added, and thereafter, the samples were kept at 4°C. The first PCR generated an amplicon of 166-bp length.
The Ras A (sense) primer (Table 1⇓ , mismatched bases are underlined) was designed to introduce a restriction site for BstXI (MBI Fermentas) and XcmI (New England Biolabs, Schwalbach, Germany) into the wild-type amplicon. Because of this altered sequence, BstXI (5′-CCANNNNNNTGG-3′) and XcmI (5′-CCANNNNNNNNNTGG-3′) cut the amplicon only if the first two bases of codons 12 or 13 (italicized bases) were wild-type.
For the first restriction, 10 μl of the first PCR reaction were digested with 10 units of either BstXI for codon 12 detection (55°C, 4 h), or XcmI for codon 13 detection (37°C, 4 h), in a total volume of 20 μl, according to the manufacturer's recommendations. Two μl of this first digest were used as a template for the second PCR in which primer Ras C (Table 1)⇓ was used instead of Ras B, thus creating a restriction site in both mutant and wild-type amplicons for enzymes BstXI and XcmI. The second PCR was run under the same conditions. Because of the nested antisense primer (Ras C), the second PCR generated a fragment of 152 bp. For the second restriction, 10 μl of the second PCR were digested under the same conditions as for the first digest.
A sample of the second digest (18 μl) was run on a polyacrylamide gel (Roth, Karlsruhe, Germany), stained with ethidium bromide and analyzed under UV-light using a video densitometer (Herolab, Wiesloch, Germany). Amplicons of mutated DNA were cut only once into fragments of 134 bp and 18 bp, whereas amplicons of wild-type DNA were cut twice into fragments of 106-, 28-, and 18-bp length.
DNA from cell lines HDC-8, MDA-MB231, and HT-29 was used as standards to control for the efficacy of the restriction enzymes. Autoclaved, double-deionized water was used as a negative control. To discriminate mutant bands from background, the aperture of the video camera was increased such that faint bands from K-ras wild-type controls disappeared. Only bands that remained visible after this background reduction were counted as mutant bands.
DNA Sequencing.
Bands of 134 bp length, indicating mutated DNA, were excised from 3% high resolution agarose gels (Sigma-Aldrich). The amplicons were purified using the Qia Quick gel extraction kit according to the manufacturer's recommendations (Qiagen). In brief, the gel slice was dissolved by adding 6 volumes of QG buffer and incubating at 50°C for 10 min. Thereafter 1 volume of isopropanol was added, and the sample was loaded onto a column. After washing with QG and PE buffers, the DNA was eluted with Tris buffer [10 mm Tris-Cl (pH 8.5)]. A sample of the purified amplicon (12.8 μl) was used for sequencing, which was performed with 4 μl of the Big Dye Terminator Cycle Sequencing Ready Reaction kit (ABI, Weiterstadt, Germany) according to the manufacturer's recommendations and 3.2 μl of sequencing primer RasSeq (Table 1)⇓ . The reaction resulted in a product of 110 bp, which was analyzed on an ABI 310 Sequencer for point mutations of the respective amplicon.
Preparation of the Internal Standard.
DNA from cell lines SW-620, K-ras mutated in codon 12, and MDA-MB231, K-ras mutated in codon 13, were used to prepare internal standards for each mutation analyzed. As shown in Fig. 1⇓ , the two primer pairs, IS-A and IS-B (sequences are shown in Table 1⇓ ), were used, amplifying human K-ras gene fragments of 162 bp (A) and 115 bp (B) in length. Primer IS-A(3′) and IS-B(5′) each contained a restriction site for the enzyme HindIII (underlined sequence). The amplified fragments were separated on a 2% high-resolution agarose gel (Sigma). After staining with ethidium bromide, the corresponding fragments were excised and extracted with the Qia quick gel extraction kit (for details see above). The two fragments (0.5 μg each) were incubated with 5 units HindIII (MBI Fermentas) at 37°C for 4 h. The resulting fragments (A′ and B′) with sticky ends were cleaned with the PCR purification kit (Qiagen) and then ligated (0.25 μg each) by incubation with 0.5 units of T4-ligase (Boehringer, Mannheim, Germany) at 16°C for 12 h. The resulting amplicon (C, 263 bp) was again isolated from a 2% agarose gel. For additional amplification the primer pair, IS-C, was used, resulting in a 244-bp oligomer (D). In comparison with the K-ras wild-type sequence it contained a 10-bp deletion and was used as internal standard in the subsequent experiments.
The age of patients was compared by calculating the mean and SD of the respective subgroups. In addition, the nonparametric Wilcoxon test was applied (26) . The contingency x2 test, and where appropriate, the Cochran-Armitage test for a linear trend were used to compare all of the other patient and tumor characteristics by group. Ps < 0.05 were considered significant.
Sensitivity of the PCR-RFLP.
To define the sensitivity of the method used, dilutions of K-ras-mutated HDC-8 colon carcinoma cells were prepared in normal colonic mucosa (Fig. 2A)⇓ and liver (Fig. 2B)⇓ tissues. The sensitivity of the PCR-RFLP assay was determined for ratios of mutated to wild-type cells ranging from 1:1 to 1:106. A discernible difference of mutated bands against background was found for dilutions of one K-ras mutated cell in 103 mucosa cells and 104 liver cells. For higher dilutions, a difference against background was found only exceptionally, as e.g., shown in Fig. 2B⇓ . Similar results were obtained when K-ras codon 12 mutated HDC-8 cells or K-ras codon 13 mutated MDA-MB231 mammary carcinoma cells were diluted in K-ras wild-type HT-29 colon carcinoma cells (data not shown).
Quantitative PCR-RFLP Assay.
To quantitate the ratio of mutated cells within samples that were K-ras positive in the qualitative assay, a serial dilution of internal standard ranging from 280 fg to 9 pg was added to the PCR reactions. For standardization the quantitative PCR was first applied to a dilution of HDC-8 cells in liver (mentioned above). The correlation obtained between the internal standard and the HDC-8 cell dilution (r = 1.0; P < 0.01) is shown in Fig. 3⇓ . This relation was the basis for quantitating all of the mutated samples as shown in Fig. 4⇓ .
Patients Characteristics.
The characteristics of 199 patients with 201 colorectal carcinomas are given in Table 2⇓ . The age of these patients ranged from 29 to 89 years. The mean age of male patients (65 years; n = 116) did not differ significantly from that of female patients (68 years; n = 83).
Within the large bowel, the majority of tumors were found in the rectum (42%), followed by the sigmoid (26%), and the lowest number was detected in the descending colon (2.5%). No significant gender difference was observed.
Classification of Tumor Stage, Nodal Involvement, and Distant Metastasis.
The majority of carcinomas were classified as tumor stage T3 (63%), with the remaining tumor stages being together observed less frequently (37%). There was no significant gender difference.
As assessed by histology, 59% of all of the tumors did not show tumor cell dissemination into regional lymph nodes. About 20% were ranked into the classes N1 (three or less involved lymph nodes) or N2 (more than three lymph nodes positive for tumor cell infiltration), respectively. Again, there was no significant gender difference.
Clinical metastasis (M) was found in 18% of all patients; again, there was no significant gender related difference.
UICC Status and Additional Histopathologic Parameters.
According to the UICC status, the higher percentage of patients was grade II (36%) followed by grade III (27%), and grades I (19%) and IV (18%). Relative to this distribution, there was no significant gender difference. The majority of patients were resected successfully, i.e., no residual tumor could be detected histologically at the margins of the resection (R0; 83%). From those patients with residual tumor load (R), the R2 status (15.6%) prevailed over those with R1 status (1.5%). The majority of the tumors were classified into histological grades G2 (81%) and G3 (18%). Histology of the surrounding tumor tissue showed that only a minority of tumors (24%) had eroded venous vessels (V). There was a significant increase in the ratio of tumors associated with venous arrosion and tumor-size according to the Tumor-Node-Metastasis system (T1: 0/6, 0%; T2: 4/44, 9%; T3: 31/126, 25%; T4: 14/24, 58%; P = 0.006). In contrast to vascular invasion, the majority of tumors (88%) showed lymphatic vessel invasion (L).
K-ras Mutations in Tumor Samples.
The distribution of tumors within the colorectum relative to their mutation status is shown in Fig. 5⇓ . Seventy-four of 201 (37%) tumors were mutated in K-ras codons 12 and 13. This ratio was relatively constant in four of six parts of the colorectum, with the exception of the cecum (54% mutated tumors) and the descending colon (20% mutated tumors). Both deviations are probably due to the few tumors found within these regions of the colorectum.
Sixty of 74 tumors (81%) with a K-ras mutation were mutated in codon 12 and 14 (19%) in codon 13 (P < 0.001). Interestingly, the percentage of codon 13-mutated tumors was highest in the cecum, followed by the ascending colon (25%), and lowest in the left part of the colorectum (P = 0.054, test for trend).
The respective type of mutation is described in Table 3⇓ . Most prevalent were the mutations GGT→GAT (Gly→Asp; 35%) and GGT→GTT (Gly→Val; 32%) for codon 12 and GGC→GAC (Gly→Asp; 19%) for codon 13.
All of the tumors were additionally analyzed by a quantitative PCR assay. When determining the ratio between mutated and wild-type alleles, 54 of 74 (73%) had a ratio of K-ras mutated alleles ≥1%. Conversely, 20 of 74 tumors (27%) had a ratio of K-ras mutated cells <1%. There was no significant difference in this distribution when codon 12 and 13 mutations were compared. However, patients ≥80 years of age (n = 4) had a significantly higher ratio of K-ras positive alleles than younger patients (P = 0.037). With an increasing ratio of ras mutated cells there was a trend for an association with nodal involvement (P = 0.11), as well as for patients with venous invasion (P = 0.10). Finally, patients with residual tumor load (R1/2; P = 0.028) and patients with distant metastasis (M1; P = 0.057) were significantly correlated with a high percentage of K-ras-mutated tumor cells.
K-ras Mutations in Extratumoral Tissues.
An overview on patients with a K-ras mutation in mucosa, liver, and/or lymph node samples is shown in Table 4⇓ . From the 15 patients listed, 11 were male and 4 female. Their mean age did not differ significantly from that of the total collective. Twelve patients had a codon 12 mutation in their carcinoma, 1 patient a codon 13 mutation, and 2 patients were apparently wild-type. The latter 2 patients were included because 1 had a codon 12 mutation in normal-appearing mucosa and the other a codon 12 mutation in a lymph node. Gels from 2 of the male patients with codon 12 mutations are shown in Fig. 6⇓ .
Sequence analysis of both tumor and corresponding tissue confirmed an identical mutation in the nontumor tissue for 11 of these patients. Two patients exhibited an unrelated mutation in normal-appearing mucosa (tumor: wild-type and AGT, mucosa GAT and GCT, respectively). Another one had an unrelated mutation in normal-appearing mucosa (tumor: GAT, mucosa: GTT), whereas the lymph node mutation corresponded to the primary lesion.
There were more liver DNA samples with K-ras mutations (n = 8) than lymph node (n = 6) and bone marrow DNA samples (n = 0). These differences were significant when comparing the number of positive bone marrow samples with that of the liver (P < 0.004) and the lymph nodes (P < 0.02).
A comparison of the ratio of K-ras mutated versus wild-type cells in tumors that gave rise to ITCs with that of primaries without detectable ITCs showed no significant difference. However, the ratio of mutated cells was significantly lower in liver and lymph node tissues (P = 0.04) than in their corresponding primary tumors. This indicates that specimens from distant organs were in fact taken from normal-appearing tissue.
Fifty-seven of the 74 patients (77%) with K-ras mutation were clinically diagnosed as M0. Of these, 3 patients (5.3%) were found to carry K-ras mutated alleles in normal-appearing tissue. Conversely, from the 17 of 74 patients (23%) diagnosed clinically as M1, the majority (n = 9; 53%) were found to carry K-ras-mutated alleles in normal-appearing tissue.
K-ras Heterogeneity in Tumors.
Tumors are likely to represent multiple clones, some of which could differ in their K-ras mutation status. To assess the possible influence of this on the results of the PCR-RFLP assay used, a series of 18 patients was used to compare the assay results for five different parts of the tumor. As shown in Table 5⇓ , analysis of the standard central sample of 18 tumors resulted in 8 K-ras-mutated and 10 wild-type tumors. Additional analysis of 4 peripheral samples per tumor, respectively, showed that 1 of the 8 mutated tumors was heterogeneous, as 2 of the 5 samples from this tumor were wild-type. Similarly, 1 of the 10 wild-type tumors was heterogeneous, as 1 of the 5 samples of this tumor was mutated. Thus, the increased diagnostic expense contributed to a 6% increase in tumors diagnosed K-ras positive and to assessing 11% of all tumors as representing multiple clones.
This prospective study investigated the incidence of ITCs in liver, lymph nodes, and bone marrow of 199 evaluable patients as determined by PCR-RFLP detection of mutations in K-ras codons 12 and 13. One K-ras-mutated allele/106 wild-type alleles could be detected by this method. However, it was not possible to quantitate reliably or sequence alleles below one mutated allele/104 wild-type alleles (Fig. 2)⇓ . This sensitivity exceeds that of conventional histopathology by at least 1 order of magnitude. The latter method routinely detects ratios of tumor and normal cells ranging from 1:102 to 1:103 as was shown in an experimental study on human tumor cells growing in the liver of nude rats (27) . Therefore, 1 in 7 (14%) K-ras mutated liver specimens would have been missed in this study by conventional histopathology, and 4 in 7 (57%) samples would have been at the limit of detection.
ITCs in Extratumoral Tissues.
The three tissues examined for ITC showed significant differences in the incidence of K-ras-mutated cells. According to its function as a primary filter for hematogenic spread of colorectal tumors, the liver showed a significantly increased incidence of ITCs compared with the bone marrow (11% versus 0%). When contrasting the liver tissue incidence of ITCs with that of a previous study (26%),3 it is unclear why the detection rate varied by 15%. With regard to detecting ITCs in liver, with or without concomitantly known metastasis, the variation was low in the former (53% versus 54%) but high in the latter group of patients (5% versus 17%; P = not significant). Reasons for this difference could be attributed to the following: (a) the evaluation of the PCR-RFLP assay was altered to exclude bands that could not be readily discriminated from background; (b) patients of this study were in a clinically less advanced stage than in the previous survey;3 (c) the polymerase used in this study produced a slightly higher background than that used before, thus obscuring the presence of faint positive bands; and (d) the differences observed are not significant and may be related to the relatively few patients investigated.
Combined analysis of the present and the former study on patients with ITCs in clinically inconspicuous liver, however, yields a mean incidence of 14% and, thus, indicates a notable percentage of patients with distinctly elevated probability of developing early metastasis.3 The identification of a subgroup of clinically inconspicuous patients with ITCs implies that a suitable therapy could be found to counteract their increased risk to develop overt metastasis. A comparison of the detection rates of hematogenic and lymphogenic spread showed that the former prevailed over the latter, but this difference was not significant. The incidence of K-ras mutations found in lymph nodes (7%) may be because tissue from the para-aortic region was selected for this analysis and thus corresponds, if positive, to stage M1. This, in turn, could indicate that the lymphatic colorectal carcinoma spread is no longer confined to the surgically resected area and would imply an increased risk of developing early metastasis. Combined analysis of both hematogenic and lymphogenic spread shows that 4 of those 12 patients with ITCs identified in liver or lymph nodes (33%) would merit an upgrade in their histopathological staging, and, therefore, could be designated as "i" according to Hermanek (28) . In contrast, analysis of bone marrow samples did not contribute to knowledge about ITCs. The reason for this failure probably is that the detection limit of the PCR-RFLP method used was higher than the presumably very low concentration of K-ras-mutated cells in the bone marrow of patients investigated. Nevertheless, it can be deduced that a possible contamination of bone marrow with K-ras-mutated cells was below that of the liver and/or the lymph nodes, and, therefore, could be regarded of minor importance. To improve the sensitivity of the method, it appears necessary to enrich epithelial cells to detect K-ras mutations in bone marrow. Such a procedure, however, has resulted in detection of a high percentage of mutations, which are unrelated to that of the primary tumor (29) and, therefore, their relevance can be questioned.
Other groups have reported on K-ras mutations detected in tumor drainage blood (30) . Such results may have potential to define the level of risk to develop metastases at distant sites and for selecting adjuvant therapies. Although of interest, this procedure has two potential drawbacks: first, it determines the temporal concentration of ITCs, which is prone to fluctuation, due to the nature of the blood compartment. Second, cancer cells found in this compartment may be ineffective in homing into distant organs, as estimated by Barbera-Guillem et al. (31) , who found that only 0.68% of all malignant cells present in the blood are able to home into an organ and that only 19% of these cells will be able to grow into tumor nodules. In contrast with blood, organs such as liver, lymph nodes, and possibly bone marrow harbor tumor cells that have undergone a preselection and are potentially able to form micrometastasis. Furthermore, ITCs contaminating peripheral organs might have accumulated over time and, thus, represent a result of various phases of tumor cell shedding, which is independent of the actual blood concentration.
To differentiate between ITCs and micrometastasis, a quantitative PCR-approach seemed advisable for the subgroup of patients with K-ras-mutated primary carcinomas. Our results on both primary tumor and normal-appearing tissue of target organs of metastasis indicate that few tumors were monoclonal with regard to K-ras mutation, as has also been reported by others (32) . The majority of primary tumors contained at least 1% of K-ras mutated alleles. This, in turn, was the upper limit for most of the tissues with metastatic load (12 of 13).
K-ras Mutation and Tumor Aggressiveness.
The quantitative results also demonstrate that a high ratio of K-ras-mutated primary tumor cells is significantly related to increased aggressiveness, as evinced by the significant relationship with residual tumor load and distant metastasis. Also, a trend exists for a relationship with nodal involvement and venous invasion. Although a final evaluation can only be conducted after knowledge of the patient outcome, these results correlate very nicely with experimental findings that mutations of the Kirsten ras gene may contribute to malignancy predominantly through effects on angiogenesis, invasion, and metastasis (33) .
No relationship was found between the type of mutation and histological parameters of tumor aggressiveness. In concordance with other groups, G:C to A:T transitions prevailed over G:C to T:A transversion mutations (34) . The percentage of all G:C to A:T transition mutations (58%) corresponds well to that collated by others for p53 gene mutations in colorectal carcinoma (63%; Ref. 35 ). Reasons for this base exchange include the formation of guanine adducts (e.g., O6-methylguanine and N2,3-ethenoguanine; Refs. 35 , 36 ) at the transcribed strand, leading to mispairing with thymine, as well as of deamination of cytosine on the coding strand, which leads to uracil mispairing with adenine. In addition, formation of 1,N2-ethenoguanine that has only been detected in vitro thus far can direct misincorporation of thymine, which would explain the transversion mutation (G:C to T:A; Ref. 37 ).
Multiple Tumor Samples and Heterogeneity.
Although 85% of tumors showed heterogeneity toward their K-ras status (here defined as a ratio of mutated:wild-type cells below 1), our results on tumor sampling indicate that only 6% of these tumors were misclassified by analyzing a single sample taken from the center of the tumor. This indicates a sufficient reliability and sensitivity of the PCR-RFLP test procedure and could be a solid reason to screen only one tumor sample in future studies, as well as only those tissues that are derived from patients with K-ras-positive tumors. This deduction is corroborated by the fact that only 1 of 434 investigated tissues was found positive for a K-ras mutation, although the primary tumor was K-ras negative.
Our results demonstrate that detection of K-ras-mutated cells by PCR-RFLP identifies tissues contaminated with ITCs of the primary carcinoma. The ratio of K-ras mutated versus wild-type cells was higher in tumor than in K-ras-positive tissues and was significantly correlated with residual tumor load and distant metastasis. In accord with its function as a primary filter for colorectal carcinoma cells shed into the blood, the liver was found positive for K-ras-mutated cells more often than the bone marrow. The reliability and sensitivity of the method implies that future studies involving K-ras detection for identification of ITCs can be restricted to tissues of patients with K-ras-positive primary tumors.
We thank Dr. Robert Owen for stylistic improvements of the manuscript. The manuscript is dedicated to the late Prof. Christoph Gebhardt.
Grant Support: Else Kröner-Fresenius-Stiftung.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Requests for reprints: Martin Berger, Unit of Toxicology and Chemotherapy, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Phone: 49-6221-423310; Fax: 49-6221-423313; E-mail: M.Berger{at}Dkfz-Heidelberg.de
↵3 U. Linnemann, C. C. Schimanski, C. Gebhardt, and M. R. Berger. Prognostic value of disseminated colorectal tumor cells in the liver: Results of follow-up examinations. Int. J. Colorectal Dis., in press.
- Received November 8, 2002.
- Revision received August 29, 2003.
- Accepted October 20, 2003.


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subset: commoncrawl


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I am totally getting into the Romance and Chick Lit genre now and Rebecca's books are the ones to get if you're thinking about trying it out. I've enjoyed both Return to Bluebell Hill and A Home In Sunset Bay a lot and writing a review to say that is just something I do to say thanks to the writers who allowed me to escape into a different world just for a few hours. Plus if one of you buys the book you'll make her day.
Enough is enough! The always perfect Laurie Chapman had jumped in her car and raced as fast as she could from London heading to Sunset Bay and (she hopes!) the open arms of her estranged sister… Mia Chapman loves running Dolly's Diner in the picture-perfect coastal Cornish town of Sunset Bay. Now that her and Grandma Dolly's dream is finally a reality Mia has never been prouder! Until Laurie suddenly turns up on her doorstep… How can she forgive the sister who walked away. Once upon a time Mia and Laurie were best friends. Back together after so long, the time has come for the sisters to figure out what went so wrong all those years ago – and whether they can ever put it right!
The book cover is absolutely divine. In fact it makes me wish Sunset Bay was a real place so I can go visit. If it is a real place, someone tell me soon! This blurb also has so much promise with it too. I love the way it gives you everything you need to know without giving away everything. I want to know why the sisters are estranged and what Laurie walked away from.
Overall this book was a lovely story full of a few twists and turns and unexpected moments. I honestly had some what the hell moments, very early on in the book, but they led me to some very lovely moments that made this book bloody brilliant. I really liked Mia, although the Cal things was very predictable. Laurie and Marco were great and the way they bonded was a wonderful growth in the story.
If you're looking for a lighthearted read you need to grab your hands on this little gem. It'll make you feel like you're coming home to an old friend.
Rating: 4/5 Stars
Links: Amazon UK Kindle | Goodreads | Twitter


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Sri Sri Natya
- Do you swing your hands and twirl around when you're happy?
- Do you express joy by jumping up and down and running across a room?
You express the happiness of your mind - by moving your body. You want to simply let go and dance! It's interesting that many dance movements have their roots in exercise. Indeed, dance is an extension of exercises, performed gracefully! The neck rotations and eye movements of Bharatnatyam* are exactly like Yoga Asanas.
The Sri Sri Natya was born by assimilating dance and yoga.
Note: * Bharatnatyam is an Indian classical dance form
Benefits of Sri Sri Natya
- Activates the right side of the brain - improves artistic abilities
- Improves co-ordination between limbs
- Lends grace, poise, and beauty
- Facilitates sound sleep
- Increases lung capacity
- Helps lose excess weight
This Five Day Course consists of 2 hr sessions each day and offers:
- Beautiful experiences through a combination of Dance, Music, Asanas and Meditation.
- All living beings have a natural tendency to express joy via movement, it is especially the case with human beings, dance being an expression of joy.
- The precise purpose behind Sri Sri Natya is to enable one and all to experience the joy of movement, or dance; and the healing effects of music.
- Sri Sri Natya enables one to enjoy the language of Indian classical art forms and to help everyone explore the spirit of dance and music, which is bliss. This workshop is meant to help one leave behind day to day life, and enter a world that is surreal.
- It is a joy to watch 150 - 450 people sway to music and express themselves through the language of Dance.
It was indeed a once in a lifetime experience. I thoroughly enjoyed all 5 days. It made me feel very young at heart (though I am 50 now). I felt very light and my heart was filled with enthusiasm and happiness. I never would have imagined that I will be dancing at this age in front of everybody without even the slightest inhibition! The course was so effective that it helped all of us totally unwind ourselves, forget all our worries, and I can definitely say it had a therapeutic effect in the stressful life most of us are leading these days. - Mythili Sridhar
Sri Sri Natya was one of the best gifts that I have received in my life. On the very second day of the course, I experienced absolute bliss and realized the 'SHIVA' within me - Lavanya Subramanian
I was hesitant in the beginning as I am a BP patient. My BP is quite normal now, and the heaviness in my chest has gone. I fell very active and enthusiastic. - Seshadri Jois
- I begin by saying that this is A MUST DO COURSE FOR ALL! When we danced with yogic postures to the tune of songs and music with divinity in mind, in a flash I realised that I am indeed divine! - Ravi Anantha Padmanaban


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She died quietly, she died the death of those who love stubbornly, angrily, jealously, secretly, and
elephantishly. At a neighbour's urge, she treated rheumatoid arthritis with crude oil. The therapy resulted in second-degree burns. On the inside of my eyelids I sketch her knees – two magical orbs of glass – and I rub them with devil's claw unguent. Prayer and displeasure spill softly in the room in which we are alone and furtive, for
where, why, and for whom does the devil
make unguent from his claw? She died quietly, to render loud some mornings that had tumbled down and stuck into me like hedgehogs. I sketch those mornings as a
crooked bicycle tyre. I push the bicycle uphill into the whitish dawn, I hurry to spill before her the smell of the lead from the newspaper, the smell of the pastry which is a crumbled sketch of her face on the inside of my eyelids. The way I close the distance between us is like the way her eyebrows come together in a frown, she pushes hard sugar cubes into my mouth, and I buzz in the garden for hours and I sip the sap of a liquorice. I sketch her as READ MORE…


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Ians Watches Batteries and Straps has over 300 watches on display for as little as £1.99 to £39.99 plus over 300 in backup stock. Straps from £2 also leather straps from £2.50 batteries from £1 and Genuine Swiss batteries from £2
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Clarkston Odour Treatment
Odour Treatment in Clarkston
Complete Trauma Cleaning provide a professional Odour Treatment service to business customers & individuals in Clarkston and the surrounding area.
Complete Trauma Cleaning offer a odour management, disinfection, infection control and deodorising service which can be utilized in a wide range of circumstance.
Following crime scene cleanup, void property clearances, waste removal or "hoarding cleanup", as well as sanitising the area to ensure it is free from biohazard risk such as residual body fluids which eliminates the risk of contamination to new occupants, we can also use environmentally friendly industrial deodorisers to remove any problem residual odours which may have arisen from body fluids or other contaminants such as rodent infestation or food waste.
We follow all appropriate health and safety legislation by performing full risk assessments and issuing method statements for the work carried out prior to the commencement of sanitising, infection control and / or deodorising.
We can also provide an infection control fogging service whereby a fine mist is pumped into the affected area which disinfects and eradicates all airborne or surface-based viral, bacterial and fungal infections.
Our disinfection fogging service uses disinfectants certified up to log kill 6 (99.999999%) and is suitable for use in the following locations:
- Transportation i.e buses, taxis and vehicles of any kind
- Trains, Planes, Buses, Taxis and Ships
- Hospitals and Clinics
- Swimming Baths and Sports Centres
- Veterinary Practices
- Prisons
- Workplaces
- Educational establishments, Nurseries and Playgroups
- Care Homes and Day Centres
- Gyms and Health Clubs
- Restaurants
- Hotels
- Offices
- Residential Properties
This allows us to not only meet but to exceed the 2010 Biocide Product Directive standards against Avian flu, A/H1N1 Swine flu, MRSA, C.difficile, Listeria, Paeruginosa, E-coli, S.Aureas, Enterococcus hirea, Bacillus subtillis, Asperigilus niger, Salmonella, Legionella pneumophilia and many more.
As well as offering Odour Treatment in Clarkston we also offer Odour Treatment to the nearby areas of Giffnock, Newton Mearns, Rutherglen, East Renfrewshire, East Kilbride, Barrhead, Cambuslang, City of Glasgow, Glasgow, Renfrewshire, Blantyre, Paisley, Renfrew, Bishopbriggs, Hamilton, Viewpark, Clydebank, Bearsden, Bellshill,
Some of the professional trauma cleaning, extreme cleaning and crime scene cleaning services we offer in the Clarkston area include (but are not limited to) the following:-


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Project aims to educate citizens about the impact of dog poop in Squalicum Watershed; recent "Poop Patrol" flagged 100 poops left behind in dog park.
The Clean Water program at RE Sources for Sustainable Communities recently launched the Squalicum Clean Water Project, a campaign that monitors water quality and educates citizens about how they can help prevent fecal coliform pollution in the Squalicum Watershed by picking up and properly disposing of dog poop.
Fecal coliform bacteria, an indicator of mammal or bird poop in the water, is found in many of Whatcom County's local creeks, lakes, and beaches. This bacteria indicates the likely presence of other disease-causing organisms including roundworms, E. coli, giardia, parvovirus, and more. When water is polluted with bacteria from poop, contact with the water or eating shellfish from the water can make you sick.
"Fecal coliform bacteria is a nationwide threat to water quality — it's one of the top non-point pollution sources," said Eleanor Hines, lead scientist with RE Sources for Sustainable Communities. "Our local testing over the last 18 months indicates that fecal coliform bacteria is consistently exceeding state water quality standards in the Squalicum Watershed. Focusing our education campaign on this non-point pollution source is a clear way to highlight the issue and encourage all citizens to improve their dog poop pickup practices."
To reach out to dog owners who may not realize the harmful impact that their dog's poop can have on the environment, RE Sources is hosting community events in parks and on trails this summer throughout the Squalicum Watershed.
"Poop Patrol" volunteers will be in local parks flagging dog poop piles left behind to help illustrate how widespread poor poop pickup practices are. "Tails on Trails" volunteers will visit parks and events to talk to community members and help them understand the importance and best practices of picking up, bagging, and putting dog poop in the trash — wherever they are.
Volunteers are still being recruited to help spread the word. Interested volunteers can email email@example.com or call 360-733-8307 x213.
Upcoming Poop Patrol and Tails on Trails events include a Poop Patrol outing at 10 a.m. on Saturday, June 25th at Cornwall Park, and a Tails on Trails event during the Bellingham Kids Traverse at 9:30 a.m. on Sunday, June 26th, at Squalicum Park. Volunteers can also schedule their own Poop Patrol or Tails on Trails events by emailing firstname.lastname@example.com.
During a recent Poop Patrol on Saturday, June 18th, at the off-leash dog park at Squalicum Park, volunteers flagged 100 abandoned piles of dog poop, illustrating the problem of poor pickup practices, and the threat of disease-causing bacteria running into our waterways. Photos from the event are at facebook.com/northsoundbaykeeper/.
"Whatcom County dogs generate 30,000 pounds of poop every day, and one dog's poop carries enough bacteria and viruses to pose a health risk to humans and pets," said Hines. "The Squalicum Clean Water Project is an opportunity to raise awareness about the threat of fecal coliform bacteria and how dog owners can protect their families, kids, pets, and neighbors downstream."
The Squalicum Clean Water Project was created in collaboration with the City of Bellingham's We Scoop campaign, launched in 2015 to connect with neighborhoods in the lower Squalicum Watershed — Columbia, Cornwall Park, and Birchwood.
RE Sources' Squalicum Clean Water Project is expanding on the City's program and connecting with neighborhoods in the upper watershed — Cordata, Meridian, King Mountain, Irongate, and Barkley.
Although the project is aimed at neighborhoods in the Squalicum Watershed, all Whatcom County residents are invited to participate, including people who don't own dogs. Citizens interested in helping to address the problem of fecal coliform pollution can sign the "Poop Pledge" and sign up to volunteer online at re-sources.org/pooppledge.
Media Contact: Eleanor Hines, Lead Scientist, firstname.lastname@example.com, 360-733-8307 x213
News > Press Releases >


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PHASE SIX: A Group Exhibition
Curated by: by Nate McLeod and Matthew Mark
Artists: Nate McLeod, Matthew Mark, Cassandra Paul, Tyler Los-Jones, and Larissa Tiggelers.
Main Space Exhibition Runs: April 29 - May 20, 2011.
Opening Reception: April 29, 2011, 7 - 10 PM
+15 Exhibition Runs: April 8 - May 31, 2011.
Opening Reception April 8, 2011, 7 - 8 PM.
- In conjunction with The New Gallery.
PHASE SIX is the sixth installment in a ten-part series of multidisciplinary events curated by Nate McLeod and Matthew Mark. The series is characterized by a lack of continuity between each event, and at times within the same event. Similar to "happenings", occurring most significantly in New York City in the late 1950s and early 1960s, these events are curated specifically with the intention of drawing an audience concerned with seeing the unexpected, rather than coming with a preconceived notion of what to expect.
THE WORKS: Group Exhibition
Reception: May 27th to May 28th, 2011
Reception Saturday May 28 from 6- 9pm
On the UAS Barewalls
Matthew Mark, Lindsay Wells, Stephen Nachtigall, Randy Gibson, Julien fournier, Ashely Huff, Matthew Brunning, Thomas Dahlgren, Kent Merriman Jr, Sara V.S
Online Archives


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Ignite your inner fire!
Good things flow from a strong core; a long lean torso, a healthy back, a positive flow of energy that benefits every aspect of your life. Now, one of the yoga world's top female teachers shows you an enlightened way to a powerful core. Unlike repetitive conventional abs work, Shiva's fluid yoga-based approach awakens your creativity and inner fire, building strength and grace in the same way that surfing, rock climbing, or dancing does -- while you're enjoying yourself, not counting the minutes until it's over.
Filmed at White Sands National Park, the program was directed by James Wvinner and shot in HD by Hollywood's Sion Michel (Memoirs of a Geisha). Beautiful, effective, inspiring. It's an abs workout you'll look forward to doing again and again.
Advanced Interval Cycling Workout
Yoga to the Rescue: Feel Good from Head to Toe
Yoga for Stress Relief
Step-By-Step: Session 2: Bending & Twisting Poses For Flexibility - Chalk Talk
Yoga for Stress Prevention
Yoga for Young Bodies: Hemalayaa


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Did you just roll out of bed, hungover, and realized it's Valentine's Day? Me, too. It's okay, though. I've got you. Here are some last minute V-Day saviors that will hopefully keep you out of the doghouse.
If you can find a banana, you're already half way there. Grab a sharpie and presto, you cheap bastard.
For just a few bucks, you can scoop up various candies and write a unique, cavity inducing, love letter.
Quick! Grab a photo frame from Grandma's, toss out the picture, & grab a marker.
This one's free. Go outside, find a stick, shave a side, and once again, pick up that marker.
This one is my personal favorite. If you're willing to spend a little more, you can eat the candy from a dollar store box of chocolates and replace them with little bottles of booze. Everyone loves liquor and it increases your chances of getting laid. Sooooo...
You can still win Valentine's Day, though. Papa John's is offering their adorable heart shaped pies for under $15. Big baller? You can add a side of brownies and get both for $15 at participating locations.
Are you a Valentine's Day cheapskate? What's the worst gift you've given/received?If you do all of the above, you'll save a shit ton of money AND make the guy (or girl) in your life very happy. If they don't appreciate these awesome cheapskate ideas, break up with them. They just weren't that into you in the first place.


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Behavior-Driven Testing Using Page Object Models
Does it feel like you spend half of every sprint fixing failing automated functional tests? Are programmers unwilling to work with automation code? Is test automation a maintenance nightmare? There is a better way. The Page Object Model (POM) is a powerful design pattern for building test...
Brian Hicks
5 Ways to Make Load Testing Work for You
While organizations understand the need for load testing, and many even have the necessary tools to manage it, they still fail to execute it well and "do the job" for end-users. Frustration at a poor user experience is increased by the IT organization's failure to explain...
Israel Rogoza
7 Sure-fire Ways to Ruin Your Test Automation
Test automation projects fail, but why? Could you stop it from happening? In this tongue-in-cheek talk, Seretta Gamba will share seven proven methods to disrupt or utterly ruin a test automation project, including letting a lone champion keep important knowledge to themselves, ignoring good..
Seretta Gamba
7 Fundamentals of a Successful Testing Team
You want to build an effective testing team, but you're asking yourself, "Where do I begin?" Greg Paskal, a quality assurance engineer with over thirty years of testing experience, shares seven keys to building a successful testing team. Learn the fundamentals every tester should know and how to build upon them to achieve an effective manual and automated testing strategy. Greg's minimal essential testing strategy (METS), coupled with his proven experience, will help you build an amazing testing organization.
Greg Paskal
7 Proven Ways to Ruin Your Test Automation
Test automation projects fail, but why? Could you stop it from happening? In this tongue-in-cheek talk, Seretta Gamba will share seven proven methods to disrupt or utterly ruin a test automation project, including letting a lone champion keep important knowledge to himself, ignoring good programming practices, setting impossible goals, and feigning support. Seretta's humorous recommendations will provide managers, testers, and automators alike with the early signs of an automation project in danger.
Seretta Gamba
A Tale of Continuous Testing
When the atmosphere is hostile to QA, and yet the demands on the QA Team are increasing, how do you transform a team where everything is tested and deployed manually, to an organization that delivers great software multiple times a day? Where do you start and how do you create the strategy for implementing Continuous Testing? Join David Lumpkin as he shares his company's journey to answer these questions and the team's evolution along the way.
David Lumpkin
Agile Dev West 2018
I Manage an Agile Team. Am I Obsolete?
Agile and Scrum Teams are self-organizing and self-managing. As a line manager, what's left to do? Traditionally, managers are responsible for the output of their teams. Sometimes they're even responsible for the for a team's delivery that they do not have direct oversight. This model is flawed. People are complex, a team of people is a complex system. May as well try to manage the weather. To get a handle on the complexity of teams, managers need to act differently in how they lead others.
Robert Pieper
A Case Study in Building a Culture of Continuous Improvement
Continuous improvement is the goal of agile teams. But what does it look like when we create a continuous improvement strategy beyond our agile teams and bring it to the company level? Working at Spotify, Kevin Goldsmith saw the benefits of its fantastic continuous improvement culture. When he joined Avvo as its new CTO, his primary goal was to help Avvo create that culture for itself. In this session, Kevin will show what Avvo has done to build a foundation for a continuous improvement culture.
Kevin Goldsmith
A Definition of Done for DevSecOps
[video:https://youtu.be/oQE8ysEvzaQ width:300 height:200 align:right]
Gene Gotimer
Agile Testing in Large Scale Organizations
Mary Thorn has had the opportunity in the past twenty years to work at many startups, creating several QA/test departments from scratch. For the past ten years, she has done this in agile software companies. Recently Mary moved from leading small agile test organizations to leading a large agile test organization where she has learned how to lead agile testers and agile testing in large contexts.
Mary Thorn
AI-Driven Testing as a Service: Fad, Fiction, or Future?
Advances in artificial intelligence (AI) and machine learning (ML) are leading to a new generation of software, which is becoming self-adaptive, autonomous, and smart. Academic researchers and industry practitioners are investigating how these new AI and ML technologies can be leveraged to improve software testing and testing services. A handful of testing-as-a-service (TaaS) vendors already offer services that use AI bots to perform some functional and performance testing. How well do they live up to their claims?
Tariq King
API Testing: How to Write Tests, Integrate into CI, and Track What You're Testing
Some developers and testers think that APIs, whether internally developed or not, should just work. Unfortunately, without a significant amount of focus on testing API services, one little flaw can spell disaster for your application—especially security vulnerabilities where hackers will target your application. Elise Carmichael discusses the risks of not fully testing APIs, how to be sure that all services are tested fully, and the types of negative testing you need to do on APIs.
Elise Carmichael
Agile Dev, Better Software & DevOps Conference East 2017
A Business-First Approach to DevOps Implementation
DevOps is a cultural shift aimed at streamlining intergroup communication and improving operational efficiency for development and operations groups. Over time, inclusion of other IT groups under the DevOps umbrella has become the norm for many organizations. But even broadening the...
Leon Fayer
A Lean Tour of Lean Software Development
Lean software development has been described as "better, faster, cheaper" and focused on "eliminating waste," but those are misnomers. Going after speed improvement and waste elimination can actually reduce the benefits you might otherwise get from lean. Ken Pugh describes what lean...
Ken Pugh
Agile Performance Holarchy (APH)—A Model for Scaling Agile Teams
A hierarchy is an organizational network that has a top and a bottom, and where position is determined by rank, importance, and value. A holarchy is a network that has no top or bottom and where each person's value derives from his ability, rather than position. As more companies seek the...
Jeff Dalton
Upcoming Events
|Apr 19
EPIC Experience
A Celebration of Agile Testing & Automation
|May 03
The Premier Event for Software Testing and QA Professionals
|Jun 07
Agile + DevOps West
The Latest in Agile and DevOps
|Oct 04
Software Testing Conference in Anaheim


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Create a stunning scene at your fairytale party with our fairytale props. Props, standees, and arches transport your guests to a fairytale kingdom to celebrate in. Use the royal throne prop for commemorative photos!
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To transform your fairytale party from a simple get together to a memorable event, use our fairytale props to create focal points and photo ops. For a large venue, our castle decorating kit takes guests to a far away kingdom where they can dance the night away. For a large or small space, our torch props add the illusion of castle walls while the sheild props are fun for kids' pictures. Coordinate fairytale props with your fairytale wall decorations to get more out of them. Using coordinated decorations allows you to create a scene that really wows guests without necessarily spending more money. Shop all of our fairytale party supplies for more ideas and inspiration!
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Kobi Farhi (Orphaned Land) - Interview
R'n'R : When and how music came into your life ?
KF : It's there since I was a little child, from home, and from Jaffa the city I grew on, music was always mixed as different cultures and religions are sharing this city. My first ever recording was made by my Grandma rip, and music was always a part of our daily life.
R'n'R : You often say that Turkey is your second country. Is there a reason ?
KF : I love the republic of Turkey and the great revolution that was made there by Ata Turk, just think it's a secular country with separation of religion and state and it's a Muslim country, I can only dream and wish that all Muslim countries would have followed this model, that would have given us the chance to play on those countries, today we can't do that, Turkey is the only one.
R'n'R : Who are your idols and your principal influences ?
KF : I really love rebels in Music, there are many of them, I find the ones from South America to be very fascinating, artists like Victor Jara, Mercedes Sosa, and Violetta Para. I also love Leonard Cohen very much.
R'n'R : Maybe it's an utopian way to think but do you think peace can come from the music ?
KF : Peace can come only if we change the worldwide education system, there is no other way I can think of.
R'n'R : Orphaned Land is known and loved in a lot of arabian countries. You must be proud of this.
KF : Yes, it is one of the greatest achievements of ours and a great lesson we've learned of how strong music can be in uniting so called enemies.
R'n'R : What memories do you keep of the Hellfest and Motocultor festivals in France ?
KF : Great shows, we played Hellfest 3 times and Motocultor 2 times, the best experience I remember is from Hellfest 2011 where we waved the flags of Israel and Lebanon with a Lebanese belly dancer who is our sister.
R'n'R : The album All Is One (2013) helped Orphaned Land in its worlwide notoriety. Do you agree ?
KF : I think that it started from our album Mabool already.
Click to watch the video of Mabool
R'n'R : What is your writing process in Orphaned Land ?
KF : We find a concept, and only then we compile the music like a puzzle, so we need that the music tells the story, only then lyrics are coming in. It's a complicated way, but that's how we are.
R'n'R : What is your Orphaned Land's favorite album and why ?
KF : I cannot say which one, it's changing, they are all my children.
R'n'R : Your cover of Hallelujah is incredible. The choirs are very moving. How came to you this idea to cover this song ?
KF : It was the choir's idea (Stimmgewalt is their name), they knew I like Leonard Cohen very much and they like him too, we did it one time and thought it could be great to record it.
Click to watch the video of Hallelujah with Stummgewalt
R'n'R : The cover of All Is One is optimistic but the lyrics are pessimistic. Does the cover represent a dream and the lyrics the reality ?
KF : Yes, the cover is just the Utopia, the lyrics are the reality.
Click to watch the official video of All Is One
R'n'R : Does the storm still rage inside again ?
KF : Always and forever.
R'n'R : Why Yossi Sassi left the band ?
KF : He wanted to focus more on a solo career.
R'n'R : Tell me more please about Orphaned Land's work with the great Steve Hackett. How did it happen ?
KF : Steve wrote me one day that he wanted me to participate in one of his new songs, I was in shock as I grew on his music with Genesis and I like his solo works too, I have his first solo album on vinyl. He offered to pay me or to play a solo for Orphaned Land in return. I thought to myself "What will I do with money? Buy a shirt?" obviously we wanted a solo from him, it is already recorded for our next album and it's an amazing solo! Perfection!
R'n'R : Can you talk about the new Orphaned Land album ? Is it ready and what is the title ?
KF : Not yet, we are recording it, and all i can say is that it'll be released either in November this year or in January 2018. More details will follow later. Sorry for being so discrete at the moment, I can say it's a strong concept album, 12 songs and more than 60 minutes.
Click to watch a video of Orphaned Land with Steven Wilson (M I ?)
Dave on Interview Vincent Cavanagh
Interesting reading. I am not surprised Vincent is thinking about the emotions o...
Crafton on The Bookends
Wonderful article and so well written, we thank you dearly!
halka on Tearing Down The Walls (2014)
Awesome review of an awesome album. Thanks! :-)
vadertu on Vandenberg's Moonkings - Breathing (Official Video)
great thanks!


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Meditation is a form of complementary and alternative medicine. There are numerous reasons to practice meditation. One common reason is for health related purposes. In fact, some people use this therapy to cope with illnesses. It is a great stress reliever that can be used to increase calmness and physical relaxation. Mediation can also improve practitioner's psychological balance in aiding with the treatment of Depression and Anxiety disorders such as conversion disorder. By practicing meditation, one can approach their thoughts and emotions more positively. It can refine practitioner's ability to focus their attention as well. Recently, the National Center for Complementary and Alternative Medicine (NCCAM) studies reveal that meditation can also improve attention-related abilities. This is very useful to those with Attention Deficit Hyperactivity Disorder or Attention Deficit Disorder.
According to the NCCAM, previous research has demonstrated that mindfulness meditation may reduce symptoms of anxiety and depression as well. This form of meditation focuses attention on breathing techniques to develop increased awareness of the present. A study was completed about meditation and it's affect on the brain utilizing a mindfulness-based stress reduction. The study's purpose is to distinguish specific brain regions of the participants. The results showed that "Brain images in the meditation group revealed increases in gray matter concentration in the left. The hippocampus is an area of the brain involved in learning, memory, and emotional control, and is suspected of playing a role in producing some of the positive effects of meditation." This proves that an underlying brain mechanism is associated with the mindfulness meditation in mental health. Overall, meditation can be great tool to help aid in treating mental illnesses. It would work best used in combination with other treatments. Meditation should not be used as a replacement for conventional care or as a reason to postpone seeing a doctor about a medical problem.


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Miami Beach
Miami Beach Holocaust Memorial Museum to host Holocaust Remembrance Day event
Hundreds of South Floridians will gather at the Holocaust Memorial on May 1, 6 p.m. to observe Yom HaShoah (Holocaust Remembrance Day) and to demonstrate solidarity with the people of Israel.
The annual Yom HaShoah program is a solemn commemoration of the six million Jewish victims of the Holocaust and pays tribute to those who survived.
This year, the program will also feature a special service to express unity with the people of Israel, who have recently experienced a renewed campaign of terrorism – including bus bombings and the brutal murder of five members of the Fogel family as they slept on March 11.
A number of community leaders will speak at the program, including Consul General of Israel to Florida and Puerto Rico Ofer Bavly.
Five survivors from the Miami area will present their memories and stories from their Holocaust experiences.
Address: The Holocaust Memorial, 1933-45 Meridian Avenue,, Miami Beach. In case of rain, the program will be held at Temple Emanu-El, 1701 Washington Avenue, Miami Beach.


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I don't know about you, but the holidays just snuck up on me! I swear I was JUST at the beach...
You're busy.
I know.
I'M busy. As a cook, December is my month. I stretch myself further than I think I can possibly stretch. I shine brighter than I think I could ever glow. More than anything, it's my month to really help others shine. To entertain, to celebrate, to wrap up their year, to provide for their loved ones through my food.
December is jam-crammed and you need to be doing a zillion other things than reading my words, so I'll cut to the chase: Holiday shopping! I shop all year long for my nears and dears. December comes around and I normally just have to wrap and put presents under the tree. This week I'm here to help you with your holiday shopping list. These are some my favorite (All Good) things that I am gifting this season.
For The Heart:
Big Love This is a big deal book. You know why? It's an open-hearted, open-minded, soul-filling, real-life inspirational book written by a man! Our positive thought leaders who write books like this are normally women - the Glennon Doyle, the Brené Browns, the Elizabeth Gilberts - they now have a contemporary in Scott Stabile. (And these powerhouse women have endorsed Scott and his book!) Buy this for someone you love this holiday. And buy a copy for yourself!
For The Ears:
The Long Awaited Album by Steve Martin and The Steep Canyon Rangers
It's no secret I love bluegrass music, and no secret I'm a fan of pretty much everything Steve Martin does. Watching his movie, The Jerk, at 7 years old as a little girl in Southwest Missouri, I never dreamed I'd spend 17 years of my adult life in this man's home, helping his chef, Andy, bring dinners and special occasions to life. The songwriting and musicianship on this album are stellar, and those Steep Canyon boys are dreamboats.
For the Morning:
I think every single one of us would benefit from starting our day reading these words as we sip our coffee or tea and take on the world. Fishs Eddy is one of my favorite stores in New York City and the new line of products by Cleo Wade are really special.
Believe it or not, I've never been to New Orleans, but I do know that chicory in your coffee is a 'thing' in NOLA and it is something I've adopted for myself. I mix in this little box with a pound of ground coffee beans and am rewarded with the sweet, smooth flavor of chicory and it stretches out my coffee grounds and makes them last longer. This is the perfect stocking stuffer for the coffee lover in your life.
For The Night:
As I was leaving a party that I had catered last year, the client gifted me this tin of tea. He said, "This is really special tea, my friend makes it and I only give it to really special people who will appreciate it." 2 things: 1. When I drink this tea, I recall my client's generous words and remind myself that I am special. It's a powerful nightly ritual. 2. It is REALLY SPECIAL (delicious and comforting) tea!
This organic, caffeine-free tea is the perfect way to wind down. The herbal blend was created to calm the nervous system and quiet the mind for restful sleep. It contains: organic Chamomile flowers, organic Peppermint leaf, organic Spearmint leaf, organic Lavender flowers, organic Lemon Verbena, organic Cornflowers, organic Rose petals, and organic Stevia. Remind someone how special they are and gift them this tea!
Peppermint Halo One of the greatest gifts I received this year was my favorite Canadian brand opening up a store in New York City! I was skeptical about this little magic wand of peppermint oil, but now I'm a believer. I roll it on at night to seal in my day and prepare me for sleep. I roll it on aches and pains, after workouts at the gym, after long days of cooking standing on my feet, and I use it for headaches. A great stocking stuffer for someone who needs a pep in their step!
For The Artist:
Art Feeds Floral Pullover
Art Feeds is one of my favorite organizations. And my hometown chapters in Carthage and Joplin, MO are especially important to me.
Their mission statement: ART FEEDS BELIEVES ALL CHILDREN ARE ARTISTS. WE EXIST TO feed CREATIVE DEVELOPMENT AND facilitate EMOTIONAL EXPRESSION IN CHILDREN THROUGH ART AND COMMUNITY. TO DO THIS, WE PROVIDE FREE THERAPEUTIC ART AND CREATIVE EDUCATION PROGRAMS WITHIN SCHOOLS & CHILDREN'S ORGANIZATIONS BY mobilizing TEAMS OF COMMUNITY MEMBERS TO BRING ALL FORMS OF ART INTO CLASSROOMS.
Talk about All Good Things, they are doing ALL the good things! Support the Arts and donate here! Or buy this sweatshirt (or other Art Feeds clothing from the site - there's really fun stuff on there) for the artist in your life. All proceeds benefit the organization.
For The Adventurer:
My friends Alice and Stacy are light bringers. They invented this SolarPuff. They brought their solar light to Haiti to aid with hurricane relief and they have been on the ground for the last two months in Puerto Rico literally bringing light where there has been no electricity from the hurricane destruction there. You can be a light bringer and donate to help get more solar lights to people that are in the dark and you can buy a light for someone in your life who hikes, camps, fishes, hunts, anyone going on an adventure that could use a waterproof solar light.
For The Kitchen:
Throughout 2017 I have partnered with Pomora olive oil; developing recipes, creating content for them, and sharing their oils with my audience. I have to be honest, I've fallen in love. Pomora olive oils elevate my dishes, the flavors inspire me to come up with tasty new dishes for my clients, and I feel like I have a real connection with my food because I have a real connection with the trees and growers who produce this oil. That's what sets Pomora apart from other oil brands. You adopt a tree and then reap the benefits from the olive harvest all year long. It's such a unique opportunity and an incredible gift to give the cooks in your life.
I love gingerbread. I love the warm spices that makeup gingerbread - ginger, cloves, cinnamon. They warm me up, they get me in the holiday spirit, and they lend themselves to savory and sweet applications. When you research gingerbread cake recipes, they are actually surprisingly similar. Ingredient lists all match, amounts all match. I knew I wasn't going to 'invent the wheel' by coming up with some new gingerbread cake recipe. Those recipes have been tried and tested, handed down through families and cooks, why change them?
Um... because you have this luxurious olive oil that swaps out easily with the butter and makes a velvety batter, that bakes up into a pillowy moist cake, and the sweet earthy notes of the olive oil DANCE with the sweet and exotic notes of the gingerbread spices. Make this cake for the holidays! Wrap it up and give it to your doorman, your housekeeper, office mates, teachers and instructors, your neighbor, make a little cake for SANTA and put it under the tree! And adopt a tree and gift yourself or someone you love a year's worth of this delicious oil!
Gingerbread Cake With Olive Oil
- 2.5 cups all-purpose flour
- 1.5 tsp baking soda
- 1 tsp ground cinnamon
- 1 tsp ground ginger
- 1/2 tsp ground cloves
- 1/2 tsp salt
- 1/2 teaspoon black pepper
- 1/4 cup plus 2 tablespoons extra-virgin olive oil
- 1/2 cup sugar
- 1 large egg
- 1 cup black strap molasses
- 1 cup hot water
- 1.5 cups powdered sugar
- 4 tablespoons lemon juice
Oil an 8x8-inch pan (Or 4 small tins to make individual cakes - I used a cleaned and dried empty soup can for one!). Preheat the oven to 350F.
In a medium bowl, whisk together the flour, baking soda, cinnamon, ginger, cloves, salt, and pepper. In a large bowl, whisk together the olive oil, sugar, and egg. In a small bowl, stir the molasses into the hot water until completely blended.
In the bowl of an electric mixer or with a handheld mixer, combine these 3 bowls, alternating dry ingredients, with the molasses water, with the egg, sugar, olive oil mixture until you have one smooth batter. Do not overmix.
Pour the batter into the prepared pan (or pans) and bake for 40 to 50 minutes, or until a toothpick inserted into the cake comes out clean and the cake has pulled away somewhat from the sides of the pan. Cool in the pan for 5 minutes.
Turn the cake(s) out onto a rack to cool. Slowly whisk the lemon juice into the powdered sugar to create a glaze. Smooth out any lumps. Drizzle over the cooled gingerbread. Let the glaze harden a bit before wrapping so it won't smear or stick.


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Wonder Gardens at Westfield Broward Mall
Plantation, FL 33388
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Sneaker Art Battle
Thursday, January 15, 2015 at 3 a.m.
CALLING ALL ARTISTS, EMERGING ARTISTS AND SNEAKER HEADZ FOR THE 2015 SNEAKER BATTLE HOSTED ON MARCH 21, 2015 FROM 4 - 8:30 PM AT WEST FIELD BROWARD MALL. Mon., Jan. 19, 2015...
The gallery at westfield broward
Thursday, December 18, 2014 at 3 a.m.
Committed to bringing culture to the community, the ever evolving Westfield Broward mall is pleased to announce the fifth exhibit at The Art Gallery at Westfield Broward on Thursday, December 18, 2014 from 6pm – 8pm featuring ...


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People with auto-brewery syndrome convert carbs into ethanol in their gut, becoming drunk without drinking alcohol. more...
November 13 , 1956 : The US Supreme Court upheld a decision that ended public bus segregation in Montgomery, Alabama. more...
Learn something new every day
More Info... by email
A corner bookcase is a great way to efficiently use a part of the room often neglected or otherwise left bare. Choosing the best corner bookcase starts with measuring the area in which you intend to place it so you can determine what size bookcase will work best in the space. Do not forget to measure the height of the room as well, since some bookcases can be quite tall. Once you have determined your space limitations, you should consider how much you are willing to pay for the unit, as the prices may vary significantly according to materials, brand, and so on.
The styles and designs available for a corner bookcase can vary significantly, and choosing the one that is best for you is largely a matter of preference. You can narrow down your search by deciding whether you want an enclosed or an open-air bookcase. An enclosed bookcase is a good option for keeping books and other items protected and stable, while an open-air bookcase tends to be less stable but eye-catching and aesthetically pleasing. An enclosed corner bookcase will also tend to be larger, so if the corner looks excessively bare, an enclosed bookcase is a great way to fill the space.
The materials used to build the bookcase will have a significant impact on the strength and durability of the corner bookcase, as well as the overall aesthetic appeal. It may help to research the different materials available; if you want a wooden bookcase, be sure to consider the various types of wood that will affect the way the bookcase looks. Some woods are naturally beautiful and strong, while others need painting or staining to ensure they are not susceptible to rot, mold, or other damage.
Consider whether you want the corner bookcase to include a small cabinet as well. This is useful for storing items that you do not necessarily want visible, as the books on the shelves will be. Some bookcases feature a small cabinet on the lowest part of the case for convenience and stability. You may also want to consider fully enclosed bookcases that feature hinged doors, usually made of wood and glass so the items within are visible. This is, again, a matter of preference, and the price of such a bookcase is likely to be higher than other, simpler models without cabinets, doors, or other added features.
One of our editors will review your suggestion and make changes if warranted. Note that depending on the number of suggestions we receive, this can take anywhere from a few hours to a few days. Thank you for helping to improve wiseGEEK!


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3 votes! This would be great, apps such as growlvoice can integrate with mighty text. I don't really like having to use chrome for messaging; growlvoice sits on the menubar, and shows notifications when new messages are received. no need to switch to another tab or open a new window to read the message, it is silently waiting for me in the menubar :) This is the one feature I'm really missing from google voice integration.verb0ze supported this idea ·


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the books of the Apocrypha and the Bible.
Current Cataloging Includes:
• 8 Apocrypha Comparison Citations
Tobit 6:1-12
• Use of witchcraft (v.4-8): Scripture condemns all forms of occult practice (Deuteronomy 18:10-12).
• The alleged "angel" Azarias is teaching this practice (ref. II Corinthians 11:14-15).
...(1)And as they went on their journey, they came in the evening to the river Tigris, and they lodged there. (2)And when the young man went down to wash himself, a fish leaped out of the river, and would have devoured him. (3)Then the angel said unto him, Take the fish. And the young man laid hold of the fish, and drew it to land. (4)To whom the angel said, Open the fish, and take the heart and the liver and the gall, and put them up safely. (5)So the young man did as the angel commanded him; and when they had roasted the fish, they did eat it: then they both went on their way, till they drew near to Ecbatane.
(6)Then the young man said to the angel, Brother Azarias, to what use is the heart and the liver and the gal of the fish? (7)And he said unto him, Touching the heart and the liver, if a devil or an evil spirit trouble any, we must make a smoke thereof before the man or the woman, and the party shall be no more vexed. (8)As for the gall, it is good to anoint a man that hath whiteness in his eyes, and he shall be healed. (9)And when they were come near to Rages, (10)The angel said to the young man, Brother, to day we shall lodge with Raguel, who is thy cousin; he also hath one only daughter, named Sara; I will speak for her, that she may be given thee for a wife. (11)For to thee doth the right of her appertain, seeing thou only art of her kindred. (12)And the maid is fair and wise: now therefore hear me, and I will speak to her father; and when we return from Rages we will celebrate the marriage: for I know that Raguel cannot marry her to another according to the law of Moses, but he shall be guilty of death, because the right of inheritance doth rather appertain to thee than to any other...
Tobit 12:1-11; 15
• Salvation by works (v.8-9): Scripture testifies that salvation is by grace through faith (ref. Ephesians 2:8-9)
• Contrary to verse 9 also, Scripture only testifies of the remission of sins via Christ's shed blood (ref. Matthew 26:28)
• The alleged "holy angel" Raphael is teaching these doctrines (ref. II Corinthians 11:14-15).
...(1)Then Tobit called his son Tobias, and said unto him, My son, see that the man have his wages, which went with thee, and thou must give him more. (2)And Tobias said unto him, O father, it is no harm to me to give him half of those things which I have brought: (3)For he hath brought me again to thee in safety, and made whole my wife, and brought me the money, and likewise healed thee. (4)Then the old man said, It is due unto him. (5)So he called the angel, and he said unto him, Take half of all that ye have brought and go away in safety.
(6)Then he took them both apart, and said unto them, Bless God, praise him, and magnify him, and praise him for the things which he hath done unto you in the sight of all that live. It is good to praise God, and exalt his name, and honourably to shew forth the works of God; therefore be not slack to praise him. (7)It is good to keep close the secret of a king, but it is honourable to reveal the works of God. Do that which is good, and no evil shall touch you. (8)Prayer is good with fasting and alms and righteousness. A little with righteousness is better than much with unrighteousness. It is better to give alms than to lay up gold: (9)For alms doth deliver from death, and shall purge away all sin. Those that exercise alms and righteousness shall be filled with life: (10)But they that sin are enemies to their own life. (11)Surely I will keep close nothing from you. For I said, It was good to keep close the secret of a king, but that it was honourable to reveal the works of God...
...(15)I am Raphael, one of the seven holy angels, which present the prayers of the saints, and which go in and out before the glory of the Holy One...
Judith 9:1-6
• Contradicting testimony (v.2-5): Compare with Genesis 34
• Specifically, Jacob condemned his sons, Levi & Simeon, for dealing with Shechem and Hamor deceitfully (Gen. 34:13), and for slaying both them and all the males of the city (Gen. 34:25-30). In addition, for this wicked act, God (through Israel) pronounced a prophetic judgment upon Levi & Simeon's bloodline (Gen. 49:5-7).
...(1)Judith fell upon her face, and put ashes upon her head, and uncovered the sackcloth wherewith she was clothed; and about the time that the incense of that evening was offered in Jerusalem in the house of the Lord Judith cried with a loud voice, and said, (2)O Lord God of my father Simeon, to whom thou gavest a sword to take vengeance of the strangers, who loosened the girdle of a maid to defile her, and discovered the thigh to her shame, and polluted her virginity to her reproach; for thou saidst, It shall not be so; and yet they did so: (3)Wherefore thou gavest their rulers to be slain, so that they dyed their bed in blood, being deceived, and smotest the servants with their lords, and the lords upon their thrones; (4)And hast given their wives for a prey, and their daughters to be captives, and all their spoils to be divided among thy dear children; which were moved with thy zeal, and abhorred the pollution of their blood, and called upon thee for aid: O God, O my God, hear me also a widow. (5)For thou hast wrought not only those things, but also the things which fell out before, and which ensued after; thou hast thought upon the things which are now, and which are to come. (6)Yea, what things thou didst determine were ready at hand, and said, Lo, we are here: for all thy ways are prepared, and thy judgments are in thy foreknowledge...
Ecclesiasticus 3:23-31
• Salvation by works (v.30): Scripture testifies that salvation is by grace through faith (ref. Ephesians 2:8-9)
...(23)Be not curious in unnecessary matters: for more things are shewed unto thee than men understand. (24)For many are deceived by their own vain opinion; and an evil suspicion hath overthrown their judgment. (25)Without eyes thou shalt want light: profess not the knowledge therefore that thou hast not.
(26)A stubborn heart shall fare evil at the last; and he that loveth danger shall perish therein. (27)An obstinate heart shall be laden with sorrows; and the wicked man shall heap sin upon sin. (28)In the punishment of the proud there is no remedy; for the plant of wickedness hath taken root in him. (29)The heart of the prudent will understand a parable; and an attentive ear is the desire of a wise man. (30)Water will quench a flaming fire; and alms maketh an atonement for sins. (31)And he that requiteth good turns is mindful of that which may come hereafter; and when he falleth, he shall find a stay...
Baruch 3:1-6
• Praying to the dead (v.4): Scripture condemns necromancy (Deuteronomy 18:10-12).
...(1)O Lord Almighty, God of Israel, the soul in anguish the troubled spirit, crieth unto thee.
(2)Hear, O Lord, and have mercy; for thou art merciful: and have pity upon us, because we have sinned before thee. (3)For thou endurest for ever, and we perish utterly.
(4)O Lord Almighty, thou God of Israel, hear now the prayers of the dead Israelites, and of their children, which have sinned before thee, and not hearkened unto the voice of thee their God: for the which cause these plagues cleave unto us. (5)Remember not the iniquities of our forefathers: but think upon thy power and thy name now at this time. (6)For thou art the Lord our God, and thee, O Lord, will we praise...
I Maccabees 1:51-58
• False prophecy (v.54): The "abomination of desolation" is an end-time prophetic event which has yet to occur (ref. Matthew 24:15-34) (Mark 13:14-30)
...(51)In the selfsame manner wrote he to his whole kingdom, and appointed overseers over all the people, commanding the cities of Juda to sacrifice, city by city. (52)Then many of the people were gathered unto them, to wit every one that forsook the law; and so they committed evils in the land; (53)And drove the Israelites into secret places, even wheresoever they could flee for succour.
(54)Now the fifteenth day of the month Casleu, in the hundred forty and fifth year, they set up the abomination of desolation upon the altar, and builded idol altars throughout the cities of Juda on every side; (55)And burnt incense at the doors of their houses, and in the streets. (56)And when they had rent in pieces the books of the law which they found, they burnt them with fire. (57)And whosoever was found with any the book of the testament, or if any committed to the law, the king's commandment was, that they should put him to death.
(58)Thus did they by their authority unto the Israelites every month, to as many as were found in the cities...
II Maccabees 12:39-45
• Praying to the dead (v.44-45): Scripture condemns necromancy (Deuteronomy 18:10-12).
• Doctrine of "Purgatory" (v.45): Scriptures asserts there is only Heaven and Hell (Matthew 25:46).
...(39)And upon the day following, as the use had been, Judas and his company came to take up the bodies of them that were slain, and to bury them with their kinsmen in their fathers' graves. (40)Now under the coats of every one that was slain they found things consecrated to the idols of the Jamnites, which is forbidden the Jews by the law. Then every man saw that this was the cause wherefore they were slain. (41)All men therefore praising the Lord, the righteous Judge, who had opened the things that were hid, (42)Betook themselves unto prayer, and besought him that the sin committed might wholly be put out of remembrance. Besides, that noble Judas exhorted the people to keep themselves from sin, forsomuch as they saw before their eyes the things that came to pass for the sins of those that were slain.
(43)And when he had made a gathering throughout the company to the sum of two thousand drachms of silver, he sent it to Jerusalem to offer a sin offering, doing therein very well and honestly, in that he was mindful of the resurrection: (44)For if he had not hoped that they that were slain should have risen again, it had been superfluous and vain to pray for the dead. (45)And also in that he perceived that there was great favour laid up for those that died godly, it was an holy and good thought. Whereupon he made a reconciliation for the dead, that they might be delivered from sin...
II Maccabees 14:37-46
• Glorification of suicide (v.41-42): Compare with I Corinthians 3:16-17 & I Corinthians 6:19-20
• Specifically, Scripture does not glorify suicide as a "manly" way to die (contra I Samuel 31:4 & I Chronicles 10:4, regarding king Saul)
• Depiction of evident demonization (v.45-46). Nowhere in Scripture is there testimony of a man physically remaining alive after all of his blood has left him -- nor does the vile act of throwing one's bowels upon their enemies glorify God, in any fashion.
...(37)Now was there accused unto Nicanor one Razis, one of the elders of Jerusalem, a lover of his countrymen, and a man of very good report, who for his kindness was called a father of the Jews. (38)For in the former times, when they mingled not themselves with the Gentiles, he had been accused of Judaism, and did boldly jeopard his body and life with all vehemency for the religion of the Jews. (39)So Nicanor, willing to declare the hate that he bare unto the Jews, sent above five hundred men of war to take him: (40)For he thought by taking him to do the Jews much hurt.
(41)Now when the multitude would have taken the tower, and violently broken into the outer door, and bade that fire should be brought to burn it, he being ready to be taken on every side fell upon his sword; (42)Choosing rather to die manfully, than to come into the hands of the wicked, to be abused otherwise than beseemed his noble birth: (43)But missing his stroke through haste, the multitude also rushing within the doors, he ran boldly up to the wall, and cast himself down manfully among the thickest of them.
(44)But they quickly giving back, and a space being made, he fell down into the midst of the void place. (45)Nevertheless, while there was yet breath within him, being inflamed with anger, he rose up; and though his blood gushed out like spouts of water, and his wounds were grievous, yet he ran through the midst of the throng; and standing upon a steep rock, (46)When as his blood was now quite gone, he plucked out his bowels, and taking them in both his hands, he cast them upon the throng, and calling upon the Lord of life and spirit to restore him those again, he thus died...


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Main St, Clane, Co. Kildare, W91 K1WH
At The Tigger restaurant and takeaway, Clane we offer authentic Chinese and Thai style cuisine. You'll find an extensive menu with dishes to suit every taste.
Read more about The Tigger | View Map of Area | Photos


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Olympic Games in Sochi !
Project is made by Yezerskaya Kristina ,Olenena Masha , Petrova Natasha , Viskova Olda. 2014
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Only for those of a special breed, Living a dream, a chance to succeed, Yesterday's hopes and desires coming true, Making your mark with records anew Proving hard work and the daily grind, Instructing the body, conditioning the mind Can capture a medal for the whole world to see, with Glamour and Pride for your country, As you stand aloft and you flag is flown high, there's Memories forever, and a tear in your eye, Enjoying the moment, the admiring looks, Securing you name in the history books. Current Events Poem by Ken Budden from Family Friend Poems
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The Olympic Games are the world's number one sport event. They are an important symbol for billions of people around the globe – a symbol of hope, peace and friendly cooperation between nations. They have been held since ancient times but let's talk about the future.
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Olympic Games 2014
Hosting country. Olympic traditions. Main Olympic symbols.
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Olympic awards in 2014 The emblem of the future Olympic Games
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New sports in Olympic Games. Equipment, special clothes. Clothes for our country team.
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The Opening Ceremony. Countries and competitors taking part in the Olympics. The most exiting events of the 2014 Olympic Games.
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Pierre de Coubertin said: "The most important thing in the Olympic Games is not to win but to take part, just as the most important thing in the life is not the triumph but the struggle. The essential thing is not to have conquered but to have fought well." It is the principle of the modern Olympic movement.