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We analyzed the influence of 8 germinal polymorphisms of candidate genes potentially related to EGFR signalling (EGFR, EGF, CCND1) or antibody-directed cell cytotoxicity (FCGR2A and FCGR3A) on outcome of colorectal cancer (CRC) patients receiving cetuximab-based therapy.
Fifty-eight advanced CRC patients treated with cetuximab-irinotecan salvage therapy between 2001 and 2007 were analyzed (mean age 60; 50 PS 0-1). The following polymorphisms were analyzed on blood DNA: EGFR (CA repeats in intron 1, -216 G > T, -191C > A, R497K), EGF (A61G), CCND1 (A870G), FCGR2A (R131H), FCGR3A (F158V). Statistical analyses were conducted on the total population and on patients with wt KRas tumors. All SNPs were considered as ternary variables (wt/wt vs wt/mut vs mut/mut), with the exception of -191C > A EGFR polymorphism (AA patient merged with CA patients).
Analysis of skin toxicity as a function of EGFR intron 1 polymorphism showed a tendency for higher toxicity in patients with a low number of CA-repeats (p = 0.058). CCND1 A870G polymorphism was significantly related to clinical response, both in the entire population and in KRas wt patients, with the G allele being associated with a lack of response. In wt KRas patients, time to progression (TTP) was significantly related to EGFR -191C > A polymorphism with a longer TTP in CC patients as compared to others, and to CCND1 A870G polymorphism with the G allele being associated with a shorter TTP; a multivariate analysis including these two polymorphisms only retained CCND1 polymorphism. Overall survival was significantly related to CCND1 polymorphism with a shorter survival in patients bearing the G allele, and to FCGR3A F158V polymorphism with a shorter survival in VV patients (in the entire population and in KRas wt patients). FCGR3A F158V and CCND1 A870G polymorphisms were significant independent predictors of overall survival.
Present original data obtained in wt KRas patients corresponding to the current cetuximab-treated population clearly suggest that CCND1 A870G polymorphism may be used as an additional marker for predicting cetuximab efficacy, TTP and overall survival. In addition, FCGR3A F158V polymorphism was a significant independent predictor of overall survival.
Keywords:EGFR inhibitors; cetuximab; clinical outcome; colorectal cancer; polymorphisms
Despite the introduction of new treatments, the 5-year survival rate for metastatic colorectal cancer (mCRC) remains below 10% [1]. Cetuximab, an IgG1 monoclonal antibody (MoAb) targeting epidermal growth factor receptor (EGFR), has proven to be effective in providing clinical benefit in approximately 10% to 20% of patients [2-4]. EGFR is a transmembrane tyrosine kinase receptor that, following ligand binding, triggers two main signaling pathways: the RAS-RAF-MAPK pathway which is involved in cell proliferation, and the PI3K-PTEN-AKT pathway which controls cell survival and motility [5].
While the presence of a KRAS mutation permits identification of tumors that are insensitive to these treatments, only less than half of patients with a KRAS wild type (wt) tumor will benefit from treatments, suggesting a role for additional mechanisms of resistance [6-10]. It thus appears necessary to better define the subpopulation of patients who truly benefit from cetuximab. One approach to resolving this question may be the application of pharmacogenetics, as recently reviewed by Coate and co-workers [11]. Yet, gene polymorphisms may affect pharmacodynamics of anti-EGFR therapies such as cetuximab, by introducing inter-patient variability at the level of the EGFR target itself, the EGF ligand, as well as in the immunological mechanism called antibody-dependent cellular cytotoxicity (ADCC).
Four functional EGFR variants have been associated with EGFR regulation [12-14]: a (CA)n repeat polymorphism in EGFR intron 1, a G > A single nucleotide polymorphism (SNP) at codon 497, and two SNPs -216 G > T and -191C > A located in the promoter region. Modulation of the EGFR ligand EGF and of the downstream EGFR signaling, including the cyclin-D1 gene (CCND1), may also play a role in modulating cetuximab activity. Functional variants have been described in the EGF 5'-untranslated region (EGF 61 G > A) [15,16], and in the exon 4 of the CCND1 gene (870A > G) [17,18]. The ADCC, mediated through Fc receptors (FcγR) carried by immune cells such as macrophages and natural killer cells, plays an important role in the antitumor effect of IgG1 antibodies, such as cetuximab [19,20]. The effectiveness of ADCC may depend on the degree of activation of FcγR and constitutional polymorphisms have been demonstrated on genes encoding for these receptors: a histidine (H)/arginine (R) polymorphism at position 131 for FCGR2A and a valine (V)/phenylalanine (F) polymorphism at position 158 for FCGR3A [21].
In the present study, we investigated possible associations between these genetic variants and clinical outcomes of advanced CRC patients treated with cetuximab. Clinical end points were skin toxicity, clinical response, time to progression (TTP) and overall survival (OS).
Materials and methods
Fifty-eight patients with advanced colorectal carcinoma were included in this retrospective pharmacogenetic study. All were treated between December 2001 and November 2007. Forty-four patients were treated at the Hôpital La Timone and 14 at the Hôpital Nord (Marseille). The study was carried out with ethics committee approval and patients signed a specific informed consent for pharmacogenetic analyses. Patient characteristics are shown in Table 1. Formalin-fixed, paraffin-embedded tumor material was collected retrospectively for 50 patients. After histological control (HES) and macro-dissection to select tumor areas containing at least 50% tumor cells, DNA was extracted, and activating mutations of KRAS gene at codon 12 and codon 13 were analyzed by direct sequencing (Big Dye Terminator cycle sequencing kit, Applied Biosystems, Foster City, CA) on a 3130 genetic analyzer (Applied Biosystems). A KRAS mutation was detected in 32% of patients (16/50). The majority of patients (55%) received cetuximab as third-line therapy, and the associated chemotherapy was irinotecan for 71% of patients. Thirteen patients out of 58 had received previous therapy with bevacizumab for their metastatic disease. Cetuximab was administered i.v. over 2 hr at day1-day8-day15 (400 mg/m2 starting dose, 250 mg/m2 for subsequent doses, 21-day cycles). Treatment was administered until disease progression or unacceptable toxicity.
Table 1. Patient characteristics (N = 58)
Toxicity evaluation
Toxicity evaluation focused on cetuximab-related toxicity, i.e. acneiform rash. The maximum observed toxicity grade was recorded for all patients (N = 58), according to NCI-CTCAE v3.0.
Efficacy evaluation
Best clinical response, assessed according to modified RECIST criteria, was assessable on 56 patients (2 patients were not evaluated because of early treatment interruption due to toxicity). Time to progression (TTP) and specific survival (cancer-related death) were computed from day-1 of cetuximab treatment. At time of analysis, 51 patients out of 56 assessable patients had progressed. Survival was recorded in 57 patients among whom 44 had died from their cancer and one had died from an independent cause. Median follow-up was 39.2 months (reverse Kaplan-Meier method).
Pharmacogenetic analyses
Germinal polymorphisms of EGFR, EGF, CCND1, FCGR2A and FCGR3A genes, potentially linked to cetuximab pharmacodynamics, were analyzed on DNA extracted from a 9 ml blood sample (Paxgene Blood DNA kit, Prenalytics). With the exception of the EGFR intron-1 polymorphism, all other variants were investigated using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method (Table 2). Electrophoresis separation was performed on a 3% agarose gel. The CA-repeats polymorphism in intron 1 of EGFR gene was analyzed by fluorescent genotyping on CEQ-8000 Beckman-Coulter, as previously described [22]. Due to the large number of genotypes (between 14 and 20 CA repeats), patients were split into 2 groups (patients with the sum of CA repeats ≤ 35 vs others). Wild-type and mutated cell lines were used as controls.
Table 2. Characteristics of the PCR-RFLP methods used
The Exact p values for Hardy-Weinberg equilibrium were tested on http://innateimmunity.net/IIPGA2. webcite All SNPs were considered as ternary categorical variables (wt/wt vs wt/mut vs mut/mut), with the exception of -191C > A EGFR polymorphism for which the only AA patient was merged with heterozygous patients. Non-parametric tests were performed for comparisons (Mann-Whitney or Kruskal-Wallis). Pearson chi-square tests were applied for categorical variables, including linkage disequilibrium analyses. A logistic model was applied for estimation of odds ratio (OR) associated with toxicity (1 = grade 2-3, 0 = grade 0-1) or response (1 = CR+PR, 0 = SD+PD). TTP and survival curves were plotted according to the Kaplan-Meier method. The influence of the various tested parameters on TTP and survival was assessed by means of Log Rank test, or Cox analysis (for continuous variables or multivariate analysis). For stepwise multivariate analyses, the probabilities for entry and removal were 0.05 and 0.10, respectively. Whatever the gene polymorphism and the clinical end-point, we firstly performed univariate analyses, and then included the significant genotypes (p ≤ 0.050 from univariate analyses) in a single multivariate analysis. In addition, for efficacy end-points (response, TTP and survival), we conducted additional univariate and multivariate analyses on the sub-population of KRas wt patients. The p value considered as statistically significant (p ≤ 0.05, two-sided test) was not corrected for multiple testing. Statistics were performed on SPSS software (v15.0).
Description of gene polymorphisms
Table 3 depicts the frequency of analyzed genotypes. Regarding intron 1 EGFR polymorphism, homozygous 16-16 CA repeats was the most frequent genotype (29.3%), followed by heterozygous 16-20 CA repeats (22.4%) and 16-18 CA repeats (10.3%). All bi-allelic genotypes agreed well with those predicted by the Hardy-Weinberg equilibrium. No linkage disequilibrium was observed between EGFR -216 G > T, -191C > A and R497K polymorphisms, nor between FCGR2A H131R and FCGR3A V158F polymorphisms. Tumoral K-Ras mutation status was not related to polymorphisms of genes linked to the EGFR pathway (EGFR, EGF, CCND1).
Table 3. Distribution of gene polymorphisms
Impact of gene polymorphisms on toxicity
Maximum observed cetuximab-related acneiform rash was grade 0 in 7 patients, grade 1 in 14 patients, grade 2 in 28 patients and grade 3 in 9 patients, accounting for a total of 63.8% toxicity grade 2-3. This toxicity was not related to performance status or patient age, but was unexpectedly linked to patient gender, with a significantly greater toxicity in men as compared to women (77.8% vs 40.9%, p = 0.005).
A tendency was observed for greater cutaneous toxicity in patients bearing short CA repeats in intron 1 of EGFR gene, with 72.7% grade 2-3 in patients with CA sum ≤ 35 vs 47.8% in patients with CA sum > 35 (Figure 1, p = 0.058, OR = 2.91, 95% CI 0.95-8.92). No relevant relationship was observed for the other analyzed polymorphisms.
Figure 1. Relationship between cetuximab-related acneiform rash (maximum observed grade) and CA-repeats polymorphism in intron 1 of EGFR gene (CA sum ≤ 35 vs CA sum > 35). Chi-square test: p = 0.058. OR relative to patients with CA sum > 35 was 2.91 (95% CI 0.95-8.92).
Impact of gene polymorphisms on response
Best clinical response was CR in one patient, PR in 5 patients, stabilization in 11 patients and progression in 39 patients (i.e. 10.7% response rate, CR+PR). Even though response rate was greater in patients developing cutaneous toxicity (13.9% in patients with grade 2-3 vs 5.0% in patients with grade 0-1), this difference did not reach statistical significance (p = 0.30). In other respects, response rate was 15.2% in patients with non-mutated KRas tumors vs 0% in patients with KRas mutated tumors (p = 0.11).
Regarding gene polymorphisms, CCND1 polymorphism at position A870G was significantly related to clinical response (Figure 2, AA vs AG vs GG, p = 0.016). Interestingly, an analysis restricted to patients with KRas wt tumors confirms the predictive value of CCND1 A870G polymorphism on clinical response (AA vs AG vs GG, p = 0.027), with the presence of the G allele being associated with a lack of response (AA vs AG+GG, p = 0.007, OR relative to GG+AG patients was 39.0, 95% CI 2.67-569.7). No relevant relationship was observed for the other analyzed polymorphisms.
Figure 2. Relationship between best clinical response and CCND1 A870G gene polymorphism on the whole population. P value of chi-square test was 0.016 for AA vs AG vs GG, 0.004 for AA vs AG+GG and 0.73 for AA+AG vs GG. Response rate was 6.4% in AG+GG patients and 11.9% in AA+AG patients.
Impact of gene polymorphisms on TTP and specific survival
Median TTP was 2.8 months. TTP was not influenced by demographic or tumor characteristics, including K-Ras mutation status, with the exception of a slight influence of primary tumor localization (shorter TTP in patients with right colon primary cancer, p = 0.027). Univariate analyses showed that only -191C > A EGFR and A870G CCND1 genotypes were related to TTP. Figure 3 shows a trend for a longer TTP in homozygous EGFR -191CC patients relative to other patients (p = 0.050). CCND1 genotype had a significant impact on TTP, with a longer TTP in AA patients relative to GG patients and an intermediary TTP in heterozygous patients (p = 0.037, Figure 4). Kaplan-Meier analyses conducted in the sub-group of patients with KRas wt tumors reinforced the influence of both EGFR -191C > A (median 3.0 months in CC patients vs 2.6 months in CA+AA patients p = 0.030) and CCND1 A870G (medians 7.9, 3.0 and 2.6 months in AA, AG and GG patients, respectively, p = 0.024) genotypes on TTP. A multivariate stepwise Cox analysis including both gene polymorphisms (considered as previously), on the whole population, only retained CCND1 polymorphism (p = 0.057). This latter statistic became significant (CCND1 p = 0.035, EGFR not retained in the analysis) in a multivariate stepwise analysis conducted on patients with KRas wt tumors (relative risk of progression in GG patients relative to AA patients was 5.59, 95% CI 1.36-22.95; relative risk of progression in AG patients relative to AA patients was 2.32, 95% CI 0.66-8.17).
Figure 3. TTP probability according to EGFR -191C > A gene polymorphism on the whole population. Median TTP was 2.9 months in CC patients (43 patients, 38 events) vs 2.6 months in CA+AA patients (12 patients, 12 events); Log Rank test: p = 0.050.
Figure 4. TTP probability according to CCND1 A870G gene polymorphism on the whole population. Median TTP was 6.3 months in AA patients (7 patients, 6 events) vs 2.9 months in AG patients (35 patients, 31 events) vs 2.6 months in GG patients (12 patients, 12 events); Log Rank test: p = 0.037. Comparison of AA+AG patients (median TTP 2.9 months) vs GG patients gave a p value at 0.016.
Median specific survival was 8.4 months. Specific survival was influenced by neither demographic nor tumor characteristics, including K-Ras mutation status. However, patients previously treated by bevacizumab had a significantly shorter survival (median 4.9 months, 13 patients, 11 cancer-related deaths) than those who did not receive bevacizumab (median 9.8 months, 44 patients, 33 cancer-related deaths, p = 0.018). Univariate analyses revealed a significant influence of FCGR3A F158V polymorphism on survival (FF vs FV vs VV, p < 0.001), with the 6 VV patients having a markedly shorter survival (Figure 5). The influence of CCDN1 A870G polymorphism was at the limit of significance (AA vs AG vs GG, p = 0.050, Figure 6), with GG patients exhibiting the poorest survival. Other gene polymorphisms had no influence on specific survival. Univariate analyses conducted in the sub-group of patients with KRas wt tumors confirmed the impact of FCGR3A F158V polymorphism on survival (median 9.9, 9.0 and 2.9 months in FF, FV and VV patients, respectively, p = 0.003) and reinforced the significance of CCND1 A870G polymorphism (medians 9.9, 9.9 and 2.9 months in AA, AG and GG patients, respectively, p = 0.024). A multivariate stepwise analysis conducted on the entire population, including both gene polymorphisms considered as ternary variables along with bevacizumab pre-treatment (yes/no), revealed that CCND1 A870G (p = 0.044) and FCGR3A F158V (p = 0.006) polymorphisms were significant independent survival predictors (p = 0.014 for bevacizumab pre-treatment). Finally, this latter result was confirmed in a multivariate stepwise analysis conducted in the sub-group of patients with wt KRas tumors (p values were 0.021, 0.036 and 0.058 for CCND1, FCGR3A and bevacizumab pre-treatment, respectively).
Figure 5. Specific survival (cancer-related death) probability according to FCGR3A F158V gene polymorphism on the whole population. Median survival was 9.8 months in FF patients (29 patients, 21 events) vs 9.0 months in FV patients (20 patients, 15 events) vs 2.6 months in VV patients (6 patients, 6 events); Log Rank test: p < 0.001. Comparison of FF patients vs others was not significant (p = 0.31) whereas comparison of VV patients vs others gave a p value < 0.001.
Figure 6. Specific survival (cancer-related death) probability according to CCND1 A870G gene polymorphism in the whole population. Median survival was 9.9 months in AA patients (8 patients, 6 events) vs 9.0 months in AG patients (35 patients, 25 events) vs 4.7 months in GG patients (12 patients, 11 events); Log Rank test: p = 0.050. Comparison of AA+AG patients (median survival 9.0 months) vs GG patients gave a p value at 0.015.
Cetuximab has shown efficacy in patients with metastatic colorectal cancer in several phase II trials leading, in 2004, to FDA approval for the treatment of irinotecan-refractory metastatic colorectal cancer. Several retrospective and prospective studies have clearly demonstrated that KRAS mutation confers resistance to these patients [6-10,23,24] but the complete mechanism of cetuximab sensitivity remains only partially understood. The present study was conducted in patients receiving cetuximab before KRas-mutation testing was introduced as a requirement. As expected, no response rate was observed in mutated KRAS patients vs 15.2% in wt tumors, even though the difference did not reach significance. We presently analyzed 8 gene polymorphisms involving 5 relevant candidate genes potentially related to the pharmacodynamics of cetuximab, namely EGFR, EGF, CCND1, FCGR2A and FCGR3A, on 58 CRC patients receiving cetuximab-based therapy. Statistical analyses were conducted in the whole set of patients, as well as in the sub-group of 34 patients with wt KRas tumors, so as to reflect the current cetuximab-treated population.
Numerous studies have reported a relationship between favorable outcome of cetuximab-treated patients and related skin toxicity [2,3,25]. Accordingly, present data show a higher response rate in patients developing grade 2-3 cutaneous toxicity as compared to patients with grade 0-1 (14% vs 5%, respectively), even though not significant. Present results also show a tendency for an association between intron 1 EGFR polymorphism and cetuximab-related skin toxicity: the incidence of grade 2-3 toxicity was 1.5-fold greater in patients bearing short CA-repeats in intron 1 of EGFR gene (CA sum ≤ 35) as compared to others (p = 0.058, Figure 1). This observation concords well with previous studies by Amador et al. [26] and Graziani et al. [27] reporting that patients developing cutaneous rash after anti-EGFR therapies presented shorter CA-repeats in intron 1 of EGFR gene as compared to patients who did not develop rash. Experimental studies have reported an inverse correlation between the number of CA-repeats in the intron 1 of the EGFR gene and EGFR gene transcription [28-30]. It can thus be hypothesized that elevated ubiquitous EGFR expression (including skin and tumor) renders the cells more susceptible to anti-EGFR effects.
In addition to the influence of intron 1 polymorphism on EGFR gene transcription, EGFR gene presents two functional polymorphisms in the promoter region: the -216G/T polymorphism located in a Sp1 binding site [31,32], and the -191C/A polymorphism located 4 bp upstream of a transcription initiation site [31]. These two SNPs may thus have an impact on EGFR gene regulation. Present data obtained on patients with wt KRas tumors show a significantly longer TTP in homozygous EGFR -191CC patients relative to other patients (p = 0.030, univariate analysis). However, this genotype was not retained in a multivariate analysis.
Cyclin D1 is a downstream effector of EGFR signaling that regulates cell cycle. The CCND1 A870G gene polymorphism affects the splice donor site at the exon 4/intron 4 boundary, resulting in two different mRNA transcripts (a and b) [33]. Both the A allele and the G allele can encode these two transcripts. However, the A allele preferentially encodes transcript b, which results in a longer half-life cyclin D1 protein [33]. The impact of CCND1 A870G polymorphism on cancer progression has been studied in head and neck cancer patients, with conflicting results [34,35]. In our study, patients homozygous for the CCDN1 870AA genotype had a significantly greater response rate than AG or GG patients, both in the whole population and in patients with a wt KRas tumor (75.0% vs 7.1%, respectively in wt KRas patients). In addition, patients with the CCND1 870AA genotype had a significantly longer median TTP than GG patients, with AG patients having an intermediary TTP, both in the whole population and in patients with a wt KRas tumor (median TTP were 7.9, 3.0 and 2.6 months, in AA, AG and GG wt KRas patients, respectively). Of note, in patients with wt KRas tumors, CCND1 polymorphism also influenced specific survival, with a significantly shorter survival in GG patients. The positive influences of CCND1 870A allele are thus consistent with one another, even though they do not concord with the sole published study having analyzed the impact of CCND1 A870G polymorphism on the outcome of advanced colorectal cancer patients receiving cetuximab therapy [36]. In this latter study, conducted on a limited sample of 39 patients, the 870 G allele had a favorable impact on survival [36].
In addition to direct anti-EGFR effect, IgG1 mAbs such as cetuximab mediate anti-tumor effects by the ADCC mechanism. Fragment C of the mAb binds to the Fc receptors (FcR) carried by immune cells, thus triggering tumor cell lysis. Functional polymorphisms on two FcR genes (FCGR2A, FCGR3A) affecting the affinity of FcR for fragment C have been identified [37,38]. These polymorphisms may thus influence ADCC efficiency [39,40]. Even though some studies have reported significant associations between these polymorphisms and clinical efficacy of rituximab [41], trastuzumab [42] or cetuximab [43,44], data conflict regarding which alleles are linked to favorable patient outcome. In the present study, we report a significant influence of FCGR3A F158V polymorphism on survival both in the whole population and in patients with a wt KRas tumor, with VV patients presenting a dramatically shorter survival. The favorable influence of the FCGR3A 158F allele was also reported in a study by Zhang et al. [43] and a study by Pander et al. [45], but not in the study from Bibeau et al. [44]. These discrepancies related to the impact of FCGR3A 158F/V polymorphism on cetuximab efficacy are difficult to account for but could be due to the relatively limited sample size of these studies.
We observed that none of the 13 patients pre-treated with bevacizumab had a response to cetuximab and that this subgroup had a significantly decreased specific survival as compared with non-pretreated patients (9.8 months vs 4.9 months, p = 0.018). This difference remains statistically significant in a multivariate analysis adjusted for age, sex, PS status and KRas status (data not shown). This negative influence of bevacizumab pre-treatment cannot be imputed to patient characteristics which were not significantly different between bevacizumab pretreated patients and non-pretreated patients, although it must be noted that 42% of bevacizumab pretreated patients carried KRAS mutated tumors vs 29% in non-pretreated patients (p = 0.48). Importantly, a multivariate analysis including bevacizumab pretreatment revealed that CCND1 A870G and FCGR3A F158V polymorphisms both remained significant independent predictors of patient survival (whole population and KRas wt tumors).
The retrospective design of this study, conducted on a relatively small number of patients, may place intrinsic limitations on the present original data. However, results obtained in the sub-group of wt KRas patients, corresponding to the current cetuximab-treated population, clearly suggest that CCND1 A870G polymorphism may be used as an additional marker for predicting cetuximab efficacy, TTP and overall survival. Of note, FCGR3A F158V polymorphism and CCND1 A870G polymorphism were significant independent predictors of overall survival in patients with wt KRas tumors. Such promising observations deserve further confirmation in a prospective study conducted on a larger population of CRC patients receiving cetuximab-based therapy.
Conflict of interests
we declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Authors' contributions
Manuscript writing: LD, GM and MCEG
Review: LD, MCEG, GM
Investigators: LD, EN, JFS, MG
All authors read and approved the final manuscript
We are grateful to Assistance Publique-Hôpitaux de Marseille. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sector.
Final responsibility for the decision to submit for publication: L. Dahan
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Amador ML, Oppenheimer D, Perea S, Maitra A, Cusatis G, Iacobuzio-Donahue C, Baker SD, Ashfaq R, Takimoto C, Forastiere A, Hidalgo M: An epidermal growth factor receptor intron 1 polymorphism mediates response to epidermal growth factor receptor inhibitors.
Cancer Res 2004, 64(24):9139-43.
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Graziano F, Ruzzo A, Loupakis F, Canestrari E, Santini D, Catalano V, Bisonni R, Torresi U, Floriani I, Schiavon G, Andreoni F, Maltese P, Rulli E, Humar B, Falcone A, Giustini L, Tonini G, Fontana A, Masi G, Magnani M: Pharmacogenetic profiling for cetuximab plus irinotecan therapy in patients with refractory advanced colorectal cancer.
J Clin Oncol 2008, 26(9):1427-34. PubMed Abstract | Publisher Full Text
Buerger H, Gebhardt F, Schmidt H, Beckmann A, Hutmacher K, Simon R, Lelle R, Boecker W, Brandt B: Length and loss of heterozygosity of an intron 1 polymorphic sequence of egfr is related to cytogenetic alterations and epithelial growth factor receptor expression.
Cancer Res 2000, 60(4):854-7. PubMed Abstract | Publisher Full Text
Buerger H, Packeisen J, Boecker A, Tidow N, Kersting C, Bielawski K, Isola J, Yatabe Y, Nakachi K, Boecker W, Brandt B: Allelic length of a CA dinucleotide repeat in the egfr gene correlates with the frequency of amplifications of this sequence--first results of an inter-ethnic breast cancer study.
J Pathol 2004, 203(1):545-50. PubMed Abstract | Publisher Full Text
Gebhardt F, Zänker KS, Brandt B: Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat in intron 1.
J Biol Chem 1999, 274(19):13176-80. PubMed Abstract | Publisher Full Text
Johnson AC, Ishii S, Jinno Y, Pastan I, Merlino GT: Epidermal growth factor receptor gene promoter. Deletion analysis and identification of nuclear protein binding sites.
J Biol Chem 1988, 263(12):5693-9. PubMed Abstract | Publisher Full Text
Kageyama R, Merlino GT, Pastan I: Epidermal growth factor (EGF) receptor gene transcription. Requirement for Sp1 and an EGF receptor-specific factor.
J Biol Chem 1988, 263(13):6329-36. PubMed Abstract | Publisher Full Text
Betticher DC, Thatcher N, Altermatt HJ, Hoban P, Ryder WD, Heighway J: Alternate splicing produces a novel cyclin D1 transcript.
Oncogene 1995, 11(5):1005-11. PubMed Abstract
Izzo JG, Papadimitrakopoulou VA, Liu DD, den Hollander PL, Babenko IM, Keck J, El-Naggar AK, Shin DM, Lee JJ, Hong WK, Hittelman WN: Cyclin D1 genotype, response to biochemoprevention, and progression rate to upper aerodigestive tract cancer.
J Natl Cancer Inst 2003, 95(3):198-205. PubMed Abstract | Publisher Full Text
Matthias C, Branigan K, Jahnke V, Leder K, Haas J, Heighway J, Jones PW, Strange RC, Fryer AA, Hoban PR: Polymorphism within the cyclin D1 gene is associated with prognosis in patients with squamous cell carcinoma of the head and neck.
Clin Cancer Res 1998, 4(10):2411-8.
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Zhang W, Gordon M, Press OA, Rhodes K, Vallböhmer D, Yang DY, Park D, Fazzone W, Schultheis A, Sherrod AE, Iqbal S, Groshen S, Lenz HJ: Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with Cetuximab.
Pharmacogenet Genomics 2006, 16(7):475-83. PubMed Abstract | Publisher Full Text
Shields RL, Namenuk AK, Hong K, Meng YG, Rae J, Briggs J, Xie D, Lai J, Stadlen A, Li B, Fox JA, Presta LG: High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R.
J Biol Chem 2001, 276(9):6591-604.
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J Clin Invest 1997, 100(5):1059-70. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
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Clin Cancer Res 2004, 10(18 Pt 1):6248-55. PubMed Abstract | Publisher Full Text
van Royen-Kerkhof A, Sanders EA, Wijngaarden S, van Roon JA, Voorhorst-Ogink M, Walraven V, Gerritsen A, van Dijk MA, Kuis W, Rijkers GT, Keler T, Leusen JH, van de Winkel JG: Flow cytometric determination of FcgammaRIIa (CD32) polymorphism.
J Immunol Methods 2004, 294(1-2):135-44.
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Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P, Watier H: Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene.
Blood 2002, 99(3):754-8. PubMed Abstract | Publisher Full Text
Musolino A, Naldi N, Bortesi B, et al.: Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2-neu-positive metastatic breast cancer.
J Clin Oncol 2008, 26(11):1789-96. PubMed Abstract | Publisher Full Text
Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, Chang HM, Borucka E, Lurje G, Sherrod AE, Iqbal S, Groshen S, Lenz HJ: FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab.
J Clin Oncol 2007, 25(24):3712-8. PubMed Abstract | Publisher Full Text
Bibeau F, Lopez-Crapez E, Di Fiore F, Thezenas S, Ychou M, Blanchard F, Lamy A, Penault-Llorca F, Frébourg T, Michel P, Sabourin JC, Boissière-Michot F: Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan.
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Pre-publication history
The pre-publication history for this paper can be accessed here:


text: Security All the passwords you should change because of Heartbleed, in one handy graphic Image Credit: WallpaperStock April 12, 2014 8:51 AM Harrison Weber 0 The Heartbleed security flaw was fixed in the newest version of OpenSSL, but you should still change your passwords on all of the sites affected by the bug. If you're still not sure which sites were affected, we have the perfect chart for you, created by the "digital forensic specialists" at LWG Consulting. Major sites ranging from Facebook and Google to Pinterest and Flickr were affected. Luckily, many financial institutions were not. Click here for the full size graphic. As we wrote yesterday, "Heartbleed arose inside a version of open-source OpenSSL cryptographic software. Information sitting inside the memory of a server should be encrypted, but a little bit of data could be pulled out under an attack. The vulnerability affected widely used infrastructure from cloud providers like Heroku and Amazon Web Services as well as networking hardware from vendors like Cisco and Juniper." Most recently, a report emerged alleging that the U.S. National Security Agency had known about Heartbleed for more than two years, and even exploited it. The NSA later denied the allegations.

subset: commoncrawl


text:
|Property type
|Minimum Stay
|2 nights
The house is located in the private community of Saw Creek Estates. Saw Creek is 30 minutes or less from Shawnee, Camelback ski area, and Bushkill waterfalls.
House has a beautiful view of ski and is just a walking distance. It also has a large front yard and is in a dead end so it is kid safe since not many cars pass through
House is three floors and there is a full bathroom on each floor and has 4 bedrooms. There 4 twin, 2 full, and a pull out mattress if needed.
My friends and I stayed here last year for four nights.
It is such a beautiful home, and Veronica was nothing short of amazing and helpful.
She answered any and all questions I had, and If I needed to ask her something while we were staying there she answered us almost immediately.
Would definitely stay here again!
Kristina Terranova
Great homely feeling great location definitely visiting again very soon. Very clean house comfortable stay.
When we walked into the house there was an overwhelming smell that smelt like a water pipe burst and wasn't properly cleaned up. There was a tub on the bottom floor which was also "out of order." The freezer and fridge were obviously not cleaned out and could of used a simple wipe down. It was obvious the house didn't have a quick clean up before we came. There were still balloons attached to the deck outside from a graduation party. Lastly, I specifically asked if there was a grill there and was told yes. There was a grill without propane and another grill without charcoal. This would of been fine but it bothers me that I asked the question and was not told that I had to provide charcoal or propane. Nothing is close in the Poconos (which is one of the relaxing perks), but we had to run out again (about an hour round trip) just for charcoal so we could cook. We did make the best of the situation and did have a good time, however a basic clean up and being up front about a few issues would of made it a better stay. If we were told about some things up front then this review would be a great one instead of a poor one. I feel like we did not get the house as advertised.
It was an amazing house for us to stay in. We had a great time. The community is friendly, the house was clean and prepared for us. The property is spacious and the backyard is open and great for yard games. We enjoyed it very much and will definitely think about returning soon.
The house was perfect for my group of friends and I. It was comfortable and had everything we needed. I definitely would like to stay here again in the future. Thank you!!!
The home is absolutely incredible. We spent the New Year Eve and day there. The location was amazing. The entire experience was the perfect retreat for our group. We will most definitely be returning to Bushkill and staying in this house!
Bushkill water falls;
Crossing premium outlets.
House sits on mountain ski and is only a five minute walk to amenities such as indoor or outdoor tennis courts, indoor racquetball courts, indoor or outdoor pool, indoor jacuzzi, fitness center, skiing, snack shop and restaurant.
|Rate Period
|Weekend Night
My Standard Rate
2 night minimum stay
|Property Damage Protection
|cleaning fee
Fri-Sun $500 plus $50 cleaning fee
Mon-Fri $175 per night plus $50 cleaning fee.
Holiday rates are higher*
First down payment is refundable if canceled 30 days before check in
Payment is usually accepted in the quoted currency (USD) unless the currency and the amount is specifically agreed in advance with the owner / advertiser.


text:
Looking Back At the Commodore 64 263
Posted by samzenpus
from the blast-from-the-past dept.
from the blast-from-the-past dept.
An anonymous reader writes "It's the 30th anniversary of the Commodore 64 this week — news that has made more than a few gaming enthusiasts feel their age. This story looks back at some of the peculiarities that made the machine so special — a true mass-market computer well into the era where a computer in every home was a novelty idea, not a near reality."


text:
CHENNAI: C.R. Visswanathan has been elected President of the Chennai Football Association in the elections held on Sunday under the supervision of the Tamil Nadu Football Association.
He beat his rival A. Ghulam Hussain by a margin of four votes (47-43). E. Sugumaran retained the Secretary's post with a handsome 50-40 win over P.S. Kanniyan, who had the backing of Mr. Visswanathan's group.
D.V. Sundar, the Joint Secretary of the Tamil Nadu Olympic Association, who was given the task of conducting the election said, "Everything went off smoothly. Everyone cooperated. In all 90 votes were polled," he said.
Other office bearers: Vice-Presidents: J.M. Fernando, M. Kumaresh, K. Madurai, V.M. Pugalendran; Treasurer: P.M. Radhakrishnan ; Assistant Secretaries: A. Anandan, S. Anandaraj, S. Kantharajan; Executive Committee: A.U. Celestine, I. Gandhi, Gnanaprakasam, T. Kalaivanan, S. Mohanraj, P. Munuswamy, B. Ravikumar David, R. Shanmugham, C.V. Shanthakumar, K. Thiyagarajan.


text:
Bill Stanford Auto
5 - 10 downloadsAdd this app to your lists
Tweets por @Appszoom
+ By SIBA Mobile Marketing LLC
For us, "customer service" means making your car buying experience as easy and enjoyable as possible. You'll find a number of ways that we make customer service the basis of buying and owning a car from our dealership. And now we've extended our service to this Android App. Before the sale you can browser our entire inventory and contact us about a test drive. After the sale you can schedule service visits, track your service history, and best of all, get notified immediately when we run another one of our great specials.
Comments and ratings for Bill Stanford Auto
- There aren't any comments yet, be the first to comment!


text:
Seminyak Hotels
See Seminyak hotels on a map
Popular with travellers from South Africa
- Most booked
Horison Seminyak Bali
Excellent 4.1 / 5 ( 230 reviews )
Most recent review
"Room was clean and spacious. Service was great as per your usual Bali standards. Convenient location yet quiet. Pool was a bit small if anything."
A Traveller, Apr 2015, AS
The Haven Bali Seminyak
Excellent 4.1 / 5 ( 285 reviews )
Most recent review
"Extremely enjoyable stay at The Haven Suites. Restaurants and shops are readily available around the hotel. Staff were friendly and helpful. Suite that we stayed in was spacious. Hotel even provides a shuttle service to the beach and has a small area for guests to relax in. Well done Haven"
A Traveller, Feb 2015, SG
Ping Hotel Seminyak Beach
Excellent 4.2 / 5 ( 241 reviews )
Most recent review
"Handy location. Ideal if you are only using it as a place to stay, not intending to spend time in the pool ... The area is tight. The pool is between the reception and the restaurant. The building is at the back of the street, hard for the sun to reach ... The beach is dirty. The shopping and res..."
A Traveller, May 2015, AU
Sense Hotel Seminyak
Excellent 4.0 / 5 ( 204 reviews )
Most recent review
"Seminyak was our last stop of a two week trip around Bali/Gili Islands. A couple we met on GIli Air suggested this hotel to us and I am so glad they did. We only booked for two days as we wanted to make sure it was what we wanted and within minutes of walking in the room, we knew we wanted to sta..."
A Traveller, Mar 2015, AS
W Retreat & Spa Bali Seminyak
Outstanding 4.7 / 5 ( 287 reviews )
Most recent review
"Definitely the best hotel in Seminyak. No other words needed. Will definitely stay here again."
A Traveller, May 2015, GB
The Kayana Villa
Outstanding 4.7 / 5 ( 76 reviews )
Most recent review
"I stayed at Kayana for 3D 2N on my own while waiting for my friend to join at a later date. Location of the villa is ideal, walking distance from many restaurants and boutiques. The staff are all very friendly, and hospitable. Every request is fulfilled quickly and efficiently. The rooms are very..."
A Traveller, Feb 2015, SG
Courtyard By Marriott Bali Seminyak
Excellent 4.6 / 5 ( 80 reviews )
Most recent review
"This is our 2nd time there cos we just love it there. Staffs r well trained and they remember repeat guests. But some area that needs improvements are: 1. Shower stall tiles should be rougher or mat should be provided. My husband slipped twice in the stall during our 3 nights stay there. 2. Kid..."
A Traveller, Apr 2015, SG
HARRIS Hotel Seminyak - Bali
Excellent 4.3 / 5 ( 79 reviews )
Most recent review
"Excellent new facili in Seminyak, Bali. Off seaon, so not crowded. Staff was courteous and even solicitous, and we thoroughly enjoyed our stay. They arranged for Dul, one of the desk clerks, to pick us up for an extra fee, but it got us through the airport vulture scene! We would stay there again..."
A Traveller, Mar 2015, GB
favehotel Seminyak
Good 3.8 / 5 ( 179 reviews )
Most recent review
"Comfy basic hotel at great location; close proximity to beach, convenience stores, eateries, massage parlors, bars, shops and more."
A Traveller, Apr 2015, SG
The Samaya Seminyak
Outstanding 4.8 / 5 ( 70 reviews )
Most recent review
"I would recommend this hotel to others. The staff were fantastic and always willing to help. The facilities were clean and well maintained. Thank you for a most enjoyable trip."
A Traveller, Jan 2015, US


text:
White Paper Download
Preparing for Profit
Outlook 2011 and Beyond
This white paper summarizes a webcast that brought back the expert panel from Preparing for the Recovery webcast to talk about how their predictions turned out and how the lessons learned will translate into growth strategies for the future.
Have a SAS profile? Log in to pre-fill the form.


text:
Special Offer | Buy one frame, get one frame 50% off. use code: BOGO50
(11) reviews
- Gender:
- Female
- Material:
- Metal
- Color:
- Silver Black
- Spring Hinges:
- Yes
- Progressive Eligible:
- Yes
- Lens Width:
- Lens Height:
- Bridge Width:
- Arm Length:
- 52 mm
- 28 mm
- 17 mm
- 135 mm
Size MatchHow will I know if these frames fit?
Product DescriptionKam Dhillon 3047 Silver Black eyeglasses are modern and feminine. This semi-rimless frame has a structured brushed silver metal construction with stylized floral cutouts along the top and outer edges. The temples are a glossy black acetate with modest Kam Dhillon branding marked at each hinge.
About the BrandKam Dhillon eyewear is all about clean sophistication and class. From work to play these high end frames are suitable for every lifestyle. Made with lightweight acetate and stainless steel, the Kam Dhillon collection is dress-to-impress to a T.
Rates estimated for shipping to:
United States
United States
- Eyeglasses and Sunglasses Shipping is FREE for all orders! No minimum or coupon code required.
- Contact Lenses and Accessories UPS - $9.99 Shipping time 3-5 business days. Does not include handling time.
For free shipping on Contact Lens orders over $49 – Use code FSOVER49 at checkout.If you're not completely happy with your item, return it to us for FREE!
Within 365 day of purchase, you may return your order in its original condition. See Return Policy.
Within 365 day of purchase, you may return your order in its original condition. See Return Policy.
Site operated by Coastal Contacts Inc.
COPYRIGHT @ 2015 Coastal Contacts Inc. All rights reserved


text:
Memorial Day is a time to get together with friends and family for food, fun, and memories.
Nothing beats a big bowl of cool, creamy potato salad at your cookout.
Delicious recipes, party ideas, and cooking tips! Get a year of Allrecipes magazine for $7.99!
Watch a Real Mom make quick-and-easy pizza on the grill.
See how this nifty gadget cooks your pizza on the countertop.
Make a tantalizing, tasty BBQ pizza with smoked sausage and cheese.


text:
Florida nurse practitioners will have extra support in their efforts to lobby for the authority to prescribe controlled substances when the new legislative session starts in March. A recent state Senate report recommended giving NPs the expanded authority, and state Sen. Mike Bennett plans to introduce a bill on the issue. In addition, health reform has put an added emphasis on expanded access to care.
View Full Article in:Orlando Sentinel (Fla.) (tiered subscription model)
Published in Brief:


text:
The WAC Landmine Games
The traps to watch out for
Pete Fiutak
Landmine Games For Every Team
- 2009 CFN Preview |
East |
Big Ten |
Big 12 |
- Independents |
Mountain West |
Pac 10 |
Belt |
next to impossible for a team to get
up for every game over the course of
the long season. It's easy to be
jazzed for the big rival or the top
five team, but college kids can't
remain focused enough to play razor
sharp for one game and then
maintain the same high level again the next week for the also-ran. Below are
the very dangerous letdown games for
each team. These might be sandwich games, games a team and
the fans won't take seriously, the game after a big
rivalry, the game before a big game, or just a game that the
team just won't be stoked for and could turn into a painful
loss against a weaker opponent. If you find yourself
arguing that these games will be easy, you're jumping into the
same trap these teams might fall into. At the very least,
these could be tougher tests than your favorite team might
think. Sure, the team might win the game, but it might
be pushed very, very hard.
Boise State
- Nov. 6 at Louisiana Tech
This is a landmine because ... This is where the dream
season has the potential to die. Even if the Broncos
beat Oregon to start the season, and come up with
good road wins at Fresno State and Tulsa, they could
start to feel the effects of so much time away from
the blue turf in a deadly WAC battle in Ruston.
Boise State will have played three road games in
four weeks at this point and will have logged a ton
of frequent flier miles going to Tulsa, and back to
Boise, and then to Honolulu, and back to Boise to
face a nasty San Jose State team, and then it's off
to Ruston.
Fresno State
- Oct. 24 at New Mexico State
This is a landmine because ... Where's the clunker
going to come. When the lights are on, like they
will be against Wisconsin, Boise State, and
Illinois, Fresno State comes up with its A game and
tries for the splashy win. But can the program get
up for the lesser games? There was a home loss to
Hawaii last year, there was the close call against
NMSU two years ago, and there was the loss to Utah
State in 2006. Even though the Aggies have struggled
over the years, they lost the last three games
against Fresno by less than a touchdown.
- Oct. 17 at Idaho
This is a landmine because ... At home, Hawaii can play
with almost anyone. On the road, the Warriors are
completely different and it's always a roll of the
dice on which team will show up. Not only is the
trip to Moscow, Idaho a long one, but this is the
ultimate WAC sandwich game with Fresno State before
it and Boise State and at Nevada to follow.
- Sept. 5 at New Mexico State
This is a landmine because ... The Aggies, with their
new coaching staff, are going to come out jacked up
for the season opener. There isn't a game on the
schedule that Idaho will be the favorite, at least
until the season finale against Utah State, after
getting a week off, and there's a chance this might
be a winless campaign without a victory on opening
day. New Mexico State has problems, but it's at
home. Idaho really needed this game under its dome.
Louisiana Tech
- Oct. 31 at Idaho
This is a landmine because ... It's at the end of a
long section of road games. Stuck on the other side
of the country from the WAC, Louisiana Tech will be
on the plane a long time over the first half of the
season with road games at Auburn, Navy, Nevada, and
Utah State before having to travel to Idaho for a
Halloween day game. The Bulldogs won't just be
playing their third road game in four, but they'll
have Boise State, at LSU, and at Fresno State to
- Nov. 21 at New Mexico State
This is a landmine because ... It's the biggest
sandwich game on the slate. Nevada should be deep in
the hunt for the WAC title all season long, but it
has a brutal November to deal with starting with a
trip to San Jose State, followed up by a home game
against Fresno State, and then a date at New Mexico
State. Not only is the game in Las Cruces the second
road game in a stretch of three road games in four
weeks, but it comes six days before the WAC game of
the year at Boise State.
New Mexico
State - Sept. 5 vs. Idaho
This is a landmine because ... Yes, this is a dual
landmine game. Considering Idaho and New Mexico
State are among the two worst teams in the country,
and are expected to finish in the bottom of the WAC,
this is the trap game for each. The Aggies have
seven road games in the final ten, and they're not
going to be favored at home against Fresno State or
Nevada. The Utah State game might be dead even. The
Idaho game at home to kick things off is a must win,
or NMSU will be hard pressed to finish out of the
WAC basement.
San Jose
State - Sept. 26 vs. Cal Poly
This is a landmine because ... This is a different year
and a different Cal Poly team, head coach Rich
Ellerson is off to be the head man at Army, but
it'll still be dangerous. The Mustangs led the FCS
in total offense, scoring offense, and was second in
sacks. The multi-faceted option attack will be tough
for San Jose State to prepare for with USC, Utah,
and Stanford to start out the season.
Utah State
- Oct. 10 at New Mexico State
This is a landmine because ... Not only is this a
dead-even WAC game that Utah State needs to win to
have a shot of getting out of the conference cellar,
but it's the last part of a long road trip to kick
off the season. The Aggies play at Utah, at Texas
A&M, and at BYU before going to New Mexico State
(with a home opener against Southern Utah thrown
into the mix). Even if Utah State is the better
team, it could be cashed by the time it gets to Las


text:
Chatting with Keltie Knight on The Insider about yellow being one of the season's hottest colors.
Chatting with Keltie Knight on The Insider about yellow being one of the season's hottest colors.
I liked Jlo's look but still had a few opinions for The Insider.
I was back on KTLA talking about Shoedazzle's hottest fall trends.
I dressed Jeannie Mai for The View in Michelle Mason leather pants and a Finders Keepers bustier.
Avia Rosen captured this show of me fitting Orly Shani with designer, Johanna Johnson, at MHA Media in LA.
Che'nelle wanted a jumpsuit, so I put her in this insane one for a performance at New York Fashion Week.
Talking about fall trends while Ross Matthews takes over the world. The usual.
Prepping a fitting for Jeannie Mai with a ton of color for Fall.
A better look at this Bao Tranchi look I put on Che'nelle for her A-Nation performance.
All in a day's work!
Orly Shani and I swung by Iliza Shlesinger's podcast at The Laugh Factory to get some fashion pet peeves off our chests.
I dressed Orly Shani in Basler for The Emmy's.
Prepping our model for a Bello Magazine mod-themed shoot.
Orly Shani hosted the post show for the Emmy's on E!. I dressed her in a beaded gown to pick up the low lights at the after party.
PopSugar had me back on We Spy Style again for a new game… I love games!
I dressed Che'nelle in this romantic look by Bao Tranchi for her performance at the mega music festival, A-Nation, in Tokyo this summer.
I dressed James Maslow in Anthony Franco for the premiere of his new show.
Speaking to 18,000 people at the Staples Center for the FIDM graduation was humbling AND exciting!
Had the pleasure of visiting Lubov and Max Azria's home for their exclusive BCBG poolside fashion show.
Here are some stills from our Christmas in July segment.
I styled Camilla Luddington for an upcoming cover of Ocean Magazine in Palm Springs.
Simply Stylist interviewed me and found out whose closet I want to raid!
Nothing like a Christmas in July fashion segment with Debbie Matenopoulos!
There is nothing more therapeutic than speaking to prospective FIDM students.
Another successful makeover on Hallmark "Home and Family"!
I spoke to a crowd of 18,000 people at this year's FIDM graduation. I felt like a pop star, without the voice.
I dressed Emmy winner, Chandler Massey, for another record breaking win this year.
Orly Shani hosted the red carpet at this Maxim Event. I dress her in a heavy embellished gown and gunmetal heels.
I was on The Insider talking about the season's hottest monokinis.
I couldn't be happier with this look I styled on Che'nelle on a rooftop in Tokyo.
I dressed Che'nelle in these colorful separates for her music video, "Shananana", in Tokyo.
Loud Love Jewelry designer, Sarah Jackson, accompanied me to the Step Up Inspiration Awards.
I dressed Che'nelle in this avante grade white gown for a roof top music video shoot in Tokyo.
I dressed James Maslow for his appearance on Good Morning America in a soft grey H+M blazer.
I dressed Orly Shani in Ekaterina Kukhareva as guest host for E!'s Fashion Police.
I hosted a live event for Halston and Step Up at the Beverly Center in Los Angeles in honor of the Step Up Inspiration Awards.
I dressed James Maslow in Jacob Davis, Levi's, and Clade for Wango Tango.
My mom and I did a makeover for Mother's Day on a lucky Mother/Daughter duo on Hallmark "Home and Family". Check it out HERE!
I was on the KTLA Morning News showing all you moms which Shoedazzle purchases to make at any age.
I talked about the baby doll dress trend on The Insider last week.
Click HERE to learn where the trend started and who is wearing it!
Last week, I dressed James Maslow from Big Time Rush and Dancing with the Stars in 3 different looks. All of them included unique textures. Working with different textures allows men to switch up their look without taking a huge leap into unknown fashion territory.
For The Fabulist's promo shot, I dressed Orly Shani in this Peggy Hartano romper and paired it with a Supertrash belt and Steve Madden pumps.
People Magazine noted the look that Marcy Guevara and I created with Theia for Gabourey Sidibe at The Oscars this year. We love People Mag and this look!!
I recently started dressing my dear friend, Orly Shani, who we all know from the first season of Fashion Star. She is the new star of E!'s "The Fabulist" alongside Kristin Cavallari. Here are some looks we put together this past month:
Top: Bebe
Skirt: Bebe
Romper: Michelle Mason
Jacket: Michelle Mason
Top: Michelle Mason
Pants: Michelle Mason
Shoes: Bebe
Dress: Bariano Australia
Shoes: Jessica Simpson
Some screen grabs from a new nineties-inspired music video I styled for Che'nelle. Watch it HERE!
Marcy Guevara and I dressed Gabourey Sidibe in a custom Theia gown, paired with Dionea Orcini earrings and a Judith Leiber clutch. She presented at The Academy Awards and turned heads in orchid!
I dressed Orly Shani for her appearance at the Style Correspondent for E! at the Oscars.
Dress: Lorena Sarbu
Ear Cuff: Jenny Dayco
Hair/Makeup: Patrick Ta
Click HERE to check out this MakeUNDER I styled on Hallmark "Home and Family" with Debbie Matenopoulos.
Dress: Aidan Mattox
Shoes: DVF
Click HERE to watch Debbie Matenopoulos and me giving you the hottest trends for less on Hallmark "Home and Family".
I styled the always incredible, Che'nelle, for her Love Tour in Japan last month. We played with textures and juxtoposition.


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Venice, Italy
My Rating
didn't realize it would all be prison cells...had thought there would be more of the doges palace...But was thrilled to cross the Bridge of Sighs and hear about Casanova
Venice, Italy
My Rating
Superb Guide...wonderful experience...probably the high point of our visit!
Venice, Italy
My Rating
Wonderful tour...Iphigenia was a TERRIFIC Guide! Great way to start the Venice visit!
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NYC Parks Events Calendar
Get up, get out, and do something! Just about any day of the year, you can find something fun, informative, and healthy to enjoy at an area park. Feel free to browse the listings below, or use the search tools to find an event that matches your interests and location.
Viewing 14,211–14,220 out of 17,844 events
from November 24, 2012 (x) to April 25, 2026
Thursday, June 18, 2015
Join The Battery Conservancy as a Horticulture Volunteer!
at Playground (in The Battery), Manhattan
9:30 a.m.–12:00 p.m.
Looking for gardening experience in one of New York City's most unique and dynamic downtown parks? Join The Battery Conservancy as a Horticulture Volunteer!
Category: Nature, Volunteer
Fledglings: Early Childhood Program
at Audubon Center at the Boathouse (in Prospect Park), Brooklyn
9:30 a.m.–10:30 a.m.
The program will include opportunities for mini nature-walks, animal encounters, nature play, and story time.
Category: Nature, Kids
Dance/Movement Class: Dances for a Variable Population
at Garibaldi Plaza (in Washington Square Park), Manhattan
9:30 a.m.–10:30 a.m.
Dances for a Variable Population is a distinctive dance workshop program appropriate for older adults of all ages and abilities.
Category: Accessible, Dance, Seniors
Shape Up NYC: Stretching, Toning, Relaxation
at Poe Park Visitor Center (in Poe Park), Bronx
10:00 a.m.–11:00 a.m.
The relaxation technique, somewhat like yoga, makes you feel as though you are floating on water. You may experience yourself drifting in and out of sleep during the gentle and quiet…
Greenbelt Tree Tots
at Greenbelt Nature Center (in Blood Root Valley), Staten Island
10:00 a.m.–10:45 a.m.
Join us for a dynamic exploration of the wonders of the forest. Through hands-on activities, observations, finger plays, games, and stories, children will become familiar with…
Category: Nature, Kids
Summer on the Hudson: Locomotive Lawn Live
at Locomotive Lawn (in Riverside Park South), Manhattan
10:30 a.m.–11:00 a.m.
Bilingual Birdies celebrates language and culture with fun-filled live music, dance, and puppetry! Concerts may be held in Spanish, French, Mandarin, Hebrew, or English.
Category: Education, Concerts, Festivals, Kids, Free Summer Concerts, Waterfront
Central Park Tour: Southern Welcome Tour
at Inside the Park at Fifth Avenue and 61st Street (in Central Park), Manhattan
11:00 a.m.–11:45 a.m.
Travel past the Pond and Gapstow Bridge, and on to the Dairy, with this tour of southern park highlights led by Central Park Conservancy tour guides.
Category: Education, Nature, History, Tours
Ocean Breeze Summer Fitness: Thrower Power
at Midland Beach Splash Plaza (in Franklin D. Roosevelt Boardwalk and Beach), Staten Island
11:00 a.m.–12:00 p.m.
Take free fitness classes outside this summer, brought to you by the staff of the new Ocean Breeze Track & Field Athletic Complex!
Category: Fitness, Outdoor Fitness
Goal Ball for Athletes with Visual Impairments
at Sunset Park Recreation Center (in Sunset Park), Brooklyn
11:00 a.m.–2:00 p.m.
Goal Ball is a paralympic sport for athletes with visual impairments. It is played by two teams of three using a ball with bells inside.
Category: Accessible, Sports
Waterfront Garden Tour
at Touchdown of the 103rd Street Footbridge (in Randall's Island Park), Manhattan
11:00 a.m.–12:00 p.m.
Join an experienced member of our Horticulture Department and learn about the flowers that are growing on the island along the waterside.
Category: Nature, Tours, Waterfront, Seniors
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Related Information
- Get information on upcoming events directly in your inbox by signing up for our Email Newsletters.
- Know about an event that's not on the calendar? Send us a tip!
- Planning an event and considering hosting it in a park? Make sure to read our Planning an Event page.


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Comments about BILLABONG BEATNIK CHILD BUTTON UP TOP:
Adorable top just cut extremely large & needed a lot of alterations.
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I love this top for it's versatile uses and style. Very girly tied up, layered with a tank, paired with denim and strappy sandals or can be worn more casually as a summer cover up.


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Book your TNN to KSA flights with Expedia and find last-minute Tainan to Kosrae airfare. Expedia offers discount airfare on multiple airline carriers that fly direct and indirect routes between TNN and KSA, with new flight deals and promotions almost daily. When you book your next trip from Tainan to Kosrae Intl. with Expedia, you can rest assured you're getting great ticket prices and excellent service from one of the world's most trusted travel providers.
Cheap Flights from Tainan to Kosrae
Cheap TNN to Kosrae flights
TNN to KSA Flight Schedule
Popular Flights from Tainan, Taiwan
Browse popular flight destinations from Tainan (TNN), and plan your next exciting trip. Expedia has cheap flights from Tainan on multiple airline carriers, so book your next trip today!
Top Tainan Flights to US Destinations
Top Tainan International Destinations
Popular Flights from Kosrae, Federated States of Micronesia
Browse popular flight destinations from Kosrae (KSA), and plan your next exciting trip. Expedia has cheap flights from Kosrae on multiple airline carriers, so book your next trip today!
Top Kosrae Flights to US Destinations
Top Kosrae International Destinations
TNN to KSA Route Map
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Hotels Near Tainan Airport
Top Kosrae Hotels
Hotels Near Kosrae Airport
KSA - Kosrae Intl. Airlines
Browse the most popular airlines servicing the Kosrae (KSA) airport. Visit their flights pages to learn more about the most popular routes these carriers fly.
Interesting Facts About Flights from Tainan to Kosrae (TNN to KSA)
(Source: FAA & BTS 2009 Databases)


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05 Suzuki Boulevard S40 discussion forum:
RE: Boulevard S40
|RE: Boulevard S40
|Stacy said 2005-07-17 06:18
Too big? Nah! I´m 6´06 and 230lbs and I´m looking at buying one. These are great motorcycles! These are not just "womans" or "beginners" bikes either. A great bike for the "experienced", "purist", "cruiser" and anyone who just enjoys riding. This is the only motorcycle out there that really interests me. Guess I´m not trying to compensate for any anatomical deficiencies. 8D
|Answer this message Show discussion overview
Enter a comment or answer to this messageWe invite you to introduce yourself by a few sentences if you are new to this discussion group. Enter your e-mail to join the forum and get notifcations of new messages. Or post your question, answer or comment as a guest. We have just improved this discussion forum and expect the number of users to increase.
More 2005 Suzuki Boulevard S40 informationOur discussion groups are intended for short messages. We also welcome more extensive motorcycle reviews.
Bikez also recommends that you check out the technical data and the riders' rating for the 05 Suzuki Boulevard S40. You can also rate it yourself. Use our efficient motorcycle classifieds to sell or buy this bike. Your motorbike gets a high quality presentation. Ads are free.
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Motorcycle catalogue and Motorcycle classifieds


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Motivated VA /Data Entry Specialist/ Web Research
Philippines - Last active: 22 hours ago - Tests: 7 - Portfolio: 1
As a former computer teacher for 8 years, I am well versed with the use of any MSoffice applications. I am an experienced data entry professional for almost 3 years. Also, a reliable web researcher and Virtual Assistant willing to learn new skills when needed. I am seeking for more challenging responsibilities to use my knowledge, skills and experiences as well as provide satisfaction to clients of excellent quality work within given time.
Social Media Manager | Email Marketing Manager | Online Researcher
Philippines - Last active: 22 hours ago - Tests: 10 - Portfolio: 6
Over the years, I have been inclined to works like email management, online research, social media management, coordination with other contractors, listing posting & management and etc. I have been using my expertise in; detail oriented, oral and written communication skills, customer service and internet research. My core competency is in my customer service skills, the way I treat people with great respect. I am seeking opportunities to satisfy clients with great results on my work responsibilities. I am accustomed using Google Spreadsheet, Mailchimp, Hootsuite and other online applications. I'm always willing to learn new applications when required by work.
- Virtual Assistant
- Google search
- Email Handling
- Email Marketing
- Email Technical Support
- Microsoft PowerPoint
- Microsoft Excel
- Internet research
- Blog Writing
- Google Docs
- Google Apps
- mailchimp
- Data Entry
- Social Media Marketing
- Article Writing
- Project management
- HootSuite
- Translation English Filipino
- Data Encoding
- Data scraping
- Microsoft Outlook Development
- Administrative Support
- Adobe PDF
- database management
- internet surveys
- TeamViewer
- Google Calendar Development
- Tumblr
- Calendar Management
- BPO Call Center
SMM/Creative Blogging and Article Writing and Video Freelancer
United States - Last active: 1 day ago - Tests: 4 - Portfolio: 1
I perform social media marketing strategies and content creation as well as creative blogging and article writing. My main goal is to promote a fantastic and personal dialogue between my employer's audience and my employer. I can write web content and creative copy. I also have much experience in video editing and production. Able to work well under deadlines. I am dedicated to producing high quality output and to maintaining an excellent, professional relationship with employer.
Graphic / Web Designer & Developer
Morocco - Last active: 22 hours ago - Tests: 2 - Portfolio: 14
UPDATE : Member of oDesk elite group "All-Star Freelancer Club" Hello! I'm Bilal, and I like making stuff, I'm a Graphic Designer & Front End Developer, based in Tetouan – Morocco. I studied web design & programming at the Institute Specialized in Applied Technologies in Tetouan, and have been an active member in the design community since 2009, I really love what I do and enjoy learning new techniques and new ways to help my clients and keep them happy. I like to keep my options open and I am always looking for new and exciting projects to tackle. Some past projects include: web design (including responsive design), UI Design (Including mobile apps & icon design), HTML5/CSS3 (Including PSD to HTML/CSS) , Wordpress & Tumblr themes, Social Media setup and design, custom web design, logo & branding, ads & banners and business card designs.
- Web design
- WordPress
- twitter bootstrap
- Tumblr
- psd to html
- Adobe Photoshop
- User interface design
- Logo Design
Groups: Pro Web Designers
Associated with: Blezzy Co
Freelance Writer and Editor, CMS expert.
Canada - Last active: 07/23/2013 - Tests: 10 - Portfolio: 4
I specialize in short writing tasks such as product descriptions, marketing brochures, advertising copy, and creative blog content. I am also versed in writing white papers, press releases, and creating full-length articles in addition to other long-form writing assignments. My eclectic work experience is conducive to writing from many varied perspectives in a variety of styles and formats. Thanks to my excellent organization and time management skills I am regularly able to complete tasks ahead of schedule. I am a Wordpress expert, and very competent with other CMS' such as Joomla and Drupal. If you have any concerns about whether I am the right person for the job send me a message and expect a prompt reply. I will not accept jobs that are outside of the scope of my abilities, and my fees are negotiable. I am open to fixed-price assignments that have well defined terms. Thanks you for your interest!
- Creative writing
- Blog Writing
- Article Writing
- Content Writing
- Technical writing
- Ghostwriting
- Search Engine Optimization (SEO)
- VirtueMart
- Joomla!
- eBook Design
- Google Docs
- WordPress
- Tumblr
- Transcription
- Adobe Photoshop
- Skype
- Microsoft Word
- Microsoft Publisher
- Copywriting
- Editorial Writing
- ebook Writing
Marketing, Design, and Web Development
United States - Last active: 12/20/2012 - Tests: 11 - Portfolio: 7
I am an experienced marketing professional, with almost a decade of web development, SEO, product placement, and design work to my credit. You will get excellent work produced from me simply because this is an area I enjoy to work on in my spare time. I have been at the forefront of Facebook and Twitter updates and strategies. No project is too big or too small! Please find my examples of work I've done, including website development, collateral development, Facebook page designs, image manipulation and creation, and more. I look forward to working on many projects at oDesk.
web copywriter, blogger, freelance writer | GloriSurban.com
Philippines - Last active: 08/26/2013 - Tests: 9 - Portfolio: 7
Fast, creative, professional. www.glorisurban.com Stories, fresh ideas, and a clear writing style make for effective content that inspires and sells. I combine all three so you can grow your business, enhance your influence, and make your blog an authority in your niche and your short stories the talk of the town. I'm Glori, provider of glorious content for small business blogs and websites and indie authors. "Looking for a writer to represent your company's image and on-line presence is not easy. Having a skillful writer like Glori is a wonderful thing. I would highly recommend her for your writing needs." - Ronsted Yuag of Skilled Therapy Compare What I Write About Niches I enjoy writing and blogging about include the following: 1. Personal Development (motivation, productivity, self-improvement, personality development) 2. Professional Development (lifestyle, career growth, entrepreneurship) 3. Health and Wellness (exercises, weight loss, diet, physical therapy) 4. Blogging and Freelance Writing 5. Network Marketing (social media, lead generation, personal branding) 6. Erotica (yep, you read that right) Let me take care of your content while you run your business.
- Article Writing
- Creative writing
- Blog Writing
- Social Media Marketing
- Tumblr
- Proofreading
- Copy editing
- Translation Filipino English
- Microsoft Word
- Content Management
- Internet research
- Market research
Groups: Article Samurai
Professional Photographer, Retoucher, Writer, Editor, Web Content
United States - Last active: 02/05/2010 - Tests: 1 - Portfolio: 1
Obtain a position where I can use my studio photography/lighting talents and experience in luxurious, design-filled lifestyle mediums to entice loyal consumers to fine tailored tradition. Additionally, to expand experience in photographic storytelling and editing.
Communications Specialist
United States - Last active: 10/21/2013 - Tests: 3 - Portfolio: 7
Well hello there. So nice of you to view my profile. I'm guessing you'd like to learn a bit about me. Pull up a chair, have a sip of tea and read on friend... I'm a strategic communicator with over three years of experience. I specialize in social media, blog writing, market research and WordPress. Since earning my graduate degree, I've combined my skills (professional and ninja) to tailor unique communication strategies for businesses, state agencies and nonprofits. I like to keep it short and sweet. If you'd like to view my portfolio, please hop over to my website, monicacthompson.com. Otherwise, if you like what you see don't be shy and shoot me a message!
Expert in writing, transcripts, translations, social media & SEO
Mexico - Last active: 1 month ago - Tests: 12 - Portfolio: 8
I write about: - Legal - Marketing - Gamble - Fashion - Business - Travel - Health - Coaching I manage: - Youtube - Linkedin - Blogger - Pinterest - Wordpress - Facebook - Twitter - Tumblr I can help you with: - Administrative help - Email responding - Power Point - Translation French - Spanish - Update social media - Data entry - Excel - Web Research - Analize and found the best keywords for your business - Moderate blogs and forums - Planning - Spanish Transcriptions - Google Docs - Translation English - Spanish I am a dedicated professional that knows that the most important thing in this life is the quality and I work to give you the best one.
- Blog Writing
- Content Writing
- Copywriting
- Transcription
- Translation Spanish English
- Translation English Spanish
- Creative writing
- Spanish
- Article Writing
- Search Engine Optimization (SEO)
- Data Entry
- Internet research
- Presentations
- Microsoft PowerPoint
- Microsoft Excel
- OpenOffice
- Physical Fitness
- Blog Commenting
- Ghostwriting
- Translation French Spanish
- YouTube Marketing
- WordPress
- Facebook Marketing
- Twitter Marketing
- Tumblr
- Administrative Support
- Social Media Marketing
- Data Analytics
- Website Analytics
- Content Management
- Legal research
- SEO Keyword Research
- Forum Moderation
- Business Continuity Planning


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New research suggests that antibiotic treatment could be asymptomatically inducing the transmission of the healthcare-acquired infection, C. difficile, contributing to the outbreaks that have recently been widely reported in hospitals and other settings. A team of scientists have successfully mirrored the infection cycle of C. difficile by generating a 'mouse hospital' with conditions mimicking the human environment in which C. difficile is transmitted.
The results have implications for infection control measures in the healthcare environment and open the door for the development of treatments and improved diagnosis of C. difficile.
At present, healthcare professionals manage the threat of C. difficile by observing stringent hygiene and isolation practices primarily by dealing with patients who exhibit the symptoms of infection - including diarrhoea and fever. But today's publication suggests that widening the targets of infection control in hospitals, to include all patients receiving antibiotic treatment - although logistically complex - is worth investigating.
"C. difficile is a highly resistant and highly infectious pathogen and resistant to many front line antibiotics," explains Dr Trevor Lawley, Wellcome Trust Sanger Institute researcher and lead author on the study. "Until now, animal studies have focussed on the observable, acute symptoms of C. difficile. But, to understand how this highly infectious pathogen spreads, investigating the entire cycle of transmission is absolutely vital. We looked at mice carrying C. difficile and observed that they shed low levels of spores and, crucially, they did not infect other mice."
"But when we treated mice with antibiotics, we saw a dramatic rise in the levels of spores shed - leading to what we have described as a 'supershedder state' and transmission of C. difficile among mice. Importantly, transmission occurs even
|Contact: Don Powell
Wellcome Trust Sanger Institute


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26 September 2014
Liberia champions childhood vaccines and Gavi at UN General Assembly
African leaders express support to the Vaccine Alliance with goal of reaching every child.
18 September 2014
Nepal becomes first country to introduce IPV with Gavi support
Nepal is one of 25 countries who have received approval to begin using IPV with Gavi support. Afghanistan and Pakistan are also planning to introduce IPV by end of next year.
25 June 2014
US summit on child survival puts spotlight on immunisation
Global health community celebrates progress and commits to maternal and child health at USAID event in Washington.
01 June 2014
Remembering Dr. Ciro de Quadros, advocate for vaccines
The global health community loses a hero and leader in the effort to eradicate polio, smallpox and measles
29 May 2014
Global summit looks to immunisation to save millions of lives
Canadian PM Harper calls on countries to invest politically, financially to improve maternal, newborn and child health
20 May 2014
European Commission announces increased pledge to GAVI Alliance as Replenishment begins
European Commission kickstarts GAVI Alliance Replenishment process with landmark contribution at high-level Brussels meeting.
Germany to host GAVI Alliance replenishment meeting in 2015
Announcement made at official launch of Alliance's replenishment process in Brussels.
Reasons to invest in the GAVI Alliance
From singers and Presidents to Ministers and advocates, GAVI Alliance supporters explain why they are backing the Alliance's vision for 2020
GAVI Alliance sets out opportunity to save up to six million lives through immunisation
The GAVI Alliance calls on donors to back ambitious plans to immunise an additional 300 million children against potentially fatal diseases between 2016 and 2020 and save a further five to six million lives.
09 May 2014
African business leaders and the GAVI Alliance discuss partnering up
CEO breakfast at WEF Africa puts spotlight on role of private sector partnerships in vaccinating children in Africa.
Ethics hotline
Concerned about the misuse of Gavi resources? Report it now.
© Gavi 2015
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The Rajasthan Royals skipper has an organised programme for his team, writes Peter Roebuck
Rajasthan Royals have established their base camp in Cape Town. As the South Africans and Australians played the third one-dayer on Thursday, the smartly-attired Royals cricketers sat in a nearby corporate box sucking in the atmosphere and watching the cricket.
Already the Indian Premier League (IPL) has flexed its muscles. Until a few days ago the box was due to be occupied by its long-standing owners. The Royals have changed all that. The offices on the second and third floor of the administrative block have been taken over and 90 free tickets were demanded to a match supposedly sold out. The big boys are in town.
Shane Warne, cricketer extraordinary, appeared in the media centre to catch up with old pals and fulfil his obligation to promote the tournament.
Slightly scandalous
Looking fit and slightly scandalous, the old trouper said he had not bowled a ball for 12 months and was unusually nervous. No sportsman, let alone a champion, wants to make a fool of himself. His hide is not quite as thick as it seems.
Talking about his team, Warne outlined an organised programme of preparation and reported that within a week the squad would be cut down from 27 to 18. Nine of the young Indians will be sent home but they'll live to fight another day.
Between them, IPL and ICL have changed the lives of thousands of young Indian cricketers, opening doors, persuading parents. It's not so long ago that talented lads were punished whenever their thoughts turned from study to the game of bat and ball.
Taking charge
Warne likes taking charge. Typically he has surrounded himself with advisors able to work with him, youngsters happy to listen to him and overseas cricketers with good track records.
Darren Berry, his team-mate and pal from Victoria, coaches the side and Jeremy Shape, the balding Englishmen previously known for is flat off-spin, serves as mentor. The Royals have also made shrewd signings.
Whilst others have thrown money around, Warne and his owners have played their cards carefully. Money has been spent on respected but obscure Australians and South Africans, nowadays including Tyrone Henderson, Lee Carseldine and Robert Quiney.
Warne and Graeme Smith are the only stars of this show, the rest are performers. Accordingly, it's been easier to turn them into a team as opposed to a collection of players seeking to justify or improve fat contracts.
Glitz and glamour
Warne also relishes the theatre that is also part and parcel of IPL. Apparently all eight teams will parade through Cape Town on the eve of the first match.
There will be a concert responding to all tastes with a wide range of African and Indian musicians and dancers, and several big Western name acts, including the Three Tenors, Snow Patrol and George Michael. Warne adds that Clint Eastwood and Morgan Freeman will walk across the field at the height of the opening ceremony. Some of it may be hype but the scale is impressive. IPL may be an Indian domestic competition but it is also a television extravaganza.
On Friday, as the cleaners swept away the debris of the night match, the Royals were back at Newlands. With Warne at the helm, they stretched muscles, sprinted between flags, worked on their fielding and went into the nets. A practice match against the Cape Cobras has been arranged for the weekend.
Everyone thought the last word had been written on Warne but the old rogue, the great competitor, is still around, catching the eye, embracing the spotlight, playing poker off the field and on it.


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- ITV Report
- ITV Report
Transplant patient stars in calendar
Live updates
Young man dies following car crash in Haverhill
A young man has died following a car crash on Homefield Road in Haverhill in Suffolk. His car struck a tree near the Moon Hall Lane junction around 11.45 this morning. Attempts to revive him failed and he was pronounced dead at the scene.
Police are asking any witnesses to come forward.
A1017 both ways closed due to accident, two vehicles involved between A1307 and B1057 Bumpstead Road.
Man charged with burglary in Haverhill
Police have charged a 32-year-old man following a burglary in Haverhill last week.
Alexander Hockett of Elmdon Place, Haverhill was arrested yesterday, Tuesday 27 August. He has been charged with the burglary of a residential property in Beaumont Vale between Tuesday 20 and Friday 23 August 2013.
He is due to appear at Bury Magistrates Court today. Police are reminding residents to lock doors and windows after a number of burglaries in the area.
Series of opportunist burglaries over Bank Holiday weekend
Police in Suffolk are appealing for help from the public after a series of burglaries in Haverhill over the Bank Holiday weekend.
Cash, jewellery and a Mercedes car with stolen in four raids. Most of the burglaries happened overnight and in two cases the thief gained entry through an open window.
Inspector Peter Ferrie said: "The spate of 'creeper' burglaries is directly targeting open or insecure doors and windows. I appeal to residents to ensure that they close and lock all ground floor doors and windows at night, otherwise they risk leaving an open invitation to a burglar."
Anyone with information about these crimes is asked to contact Suffolk Police on 101 or Crimestoppers anonymously on 0800 555 111.
Artist impression released following Suffolk burglary
Police have released artist's impressions of two men they would like to speak to in connection with a burglary in Haverhill in Suffolk.
Thieves claiming to work for a water company tricked their way into the home of an 80 year old man in Crowland Road, and stole around £1,000 worth of cash and jewellery.
Witness appeal following three burglaries in Haverhill
Suffolk Police are appealing for witnesses following three burglaries in Haverhill.
A wallet was stolen from a house in Yarmouth Road sometime between 11am and 11.15am on Friday 26 July.
A property in Strawberry Fields, Haverhill was entered sometime between midnight and 8am the same day through a garage. A handbag and wallet were stolen from within.
The third burglary happened between 6pm and 8.45pm on Friday 26 July a property in Harewood Terrace, Haverhill was entered. A handbag had been emptied and a purse stolen.
Haverhill stabbing information appeal
Police investigating an assault in Haverhill are appealing for information in relation to an incident that occurred in Harrow Road.
At around 10:55pm on Tuesday 9 July Suffolk Police were made aware of a man, aged in his thirties, who had presented himself at Addenbrooke's Hospital with stab wounds.
The incident is believed to have occurred between 9:30pm and 10pm and was originally thought to have happened in the vicinity of a toilet block within the Recreation Ground, near to Camps Road.
However, following enquiries this morning police believe it may be linked to a report of an altercation in a car park in Harrow Road.
Officers would like to hear from anyone who witnessed an altercation or has any details in relation to an incident in Harrow Road during these times.
The victim remains in hospital in a critical but stable condition though his injuries are no longer thought to be life threatening.
Man stabbed in Suffolk
A man is seriously ill in hospital after he was stabbed in Haverhill in Suffolk last night. The man, who is in his thirties, arrived at Addenbrookes Hospital in Cambridge at just before 11pm.
Police have not yet been able to get a full account of what happened. They have closed off Haverhill Recreation Ground, where the stabbing is thought to have taken place. Officers are also at an address in Montford Court.
Detectives want anyone who might have information on the incident to contact them.
Indecent exposure in Suffolk
Police are appealing for information after a man indecently exposed himself in Haverhill.
The incident occurred on Monday 29 April at 12.30pm near a small angling lake, known locally as the Newt Pond, in School Lane.
The victim, a 28-year-old woman, was walking along the footpath that runs beside the edge of the public area from the residential estate to the top of School Lane. As she was about 30 metres past the Newt Pond she noticed a man in the trees a few feet away from the path who was exposing himself.
The suspect is described as a white man of average height and stocky build, clean-shaven with short/shaven fair hair. He was wearing grey jogging bottoms and a red hooded top.
Lottery winner buys children's centre in Haverhill
A woman from Haverhill in Suffolk, who won 148 million pounds on the Euromillions lottery, is using some of her winnings to refurbish a children's play centre in the town, which had closed down.
Gillian Bayford and her husband won their millions last August. Gillian says it's important to give something back to the local community. You can see her story in full on ITV News Anglia tonight at 6pm.


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I can't download it. In fact, there is no download option, Am I wrong?
27th January 2007***
1: Info
2: Install
3: Playing
4: Credits
My second mod for oblivion,It adds a level 7 imperial to the Imperial office of commerce in the market district,He wearing Eleven armour,you must be at least 7 level to command him ;)
Just extract the 'Julian Ashcroft Companion.esp' to your Oblivion\Data folder, start the Oblivion launcher, click on Data Files
He will be roaming the Imperial office of commerce in the market district
Beretta(me):Plugin Creation
Partner mod team: For the tutorial and scripts i needed
if i missed you out please email me or email your feedback to,firstname.lastname@example.com
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I can't download it. In fact, there is no download option, Am I wrong?
nope, your right, the mods been dead for a while bythe looks of it
eh no i didnt...
lol ascroft got that from frlancer i see
Commander Julian Ashcroft will be taking the next ship to the shivering isles in a few weeks,Expect to meet him their in the realm on mania ;)
Actually I rated it up a little bit because personally...... I don't see anyone else making one. ;)
Kinda mod tho,its the beta remember ;) full release includes quests.
Cool downloading now, but wouldn't this be more of an add-on instead of a mod? From the description I don't see anything that makes a major gameplay change or some sort of campaign. Just looks like some extra npcs.
Promote Commander Julian Ashcroft on your homepage or blog by selecting a button and using the embed code provided (more).


text: I'm looking for an extended battery for my TyTN II. A while back I saw one with a back cover the allowed access to the GPS connection as well as the speaker and camera openings. It had a raised area where the larger battery was housed, with a indented area that matched the original thickness in the GPS/speaker/camera area. Unfortunately, I don't remember the capacity or brand. Can anyone point me to the brand? I don't believe it was Seidio or Mugen.