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A genome wide association study of genetic loci that influence tumour biomarkers cancer antigen 19-9, carcinoembryonic antigen and α fetoprotein and their associations with cancer risk
- Meian He1,2,
- Chen Wu3,
- Jianfeng Xu2,4,5,6,
- Huan Guo1,
- Handong Yang7,
- Xiaomin Zhang1,8,
- Jielin Sun9,
- Dianke Yu3,
- Li Zhou1,
- Tao Peng10,11,
- Yunfeng He1,
- Yong Gao2,6,
- Jing Yuan1,
- Qifei Deng1,
- Xiayun Dai1,
- Aihua Tan2,
- Yingying Feng1,
- Haiying Zhang12,
- Xinwen Min7,
- Xiaobo Yang12,
- Jiang Zhu7,
- Kan Zhai3,
- Jiang Chang3,
- Xue Qin13,
- Wen Tan3,
- Yanling Hu14,
- Mingjian Lang7,
- Sha Tao14,
- Yuanfeng Li15,
- Yi Li7,
- Junjie Feng9,
- Dongfeng Li7,
- Seong-Tae Kim9,
- Shijun Zhang2,
- Hongxing Zhang15,
- S Lilly Zheng9,
- Lixuan Gui1,
- Youjie Wang1,
- Sheng Wei1,
- Feng Wang1,
- Weimin Fang1,
- Yuan Liang1,
- Yun Zhai15,
- Weihong Chen1,
- Xiaoping Miao1,
- Gangqiao Zhou15,
- Frank B Hu8,
- Dongxin Lin3,
- Zengnan Mo2,
- Tangchun Wu1
- 1MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- 2Institute of Urology and Nephrology, First Affiliated Hospital and Centre for Genomic and Personalised Medicine, Guangxi Medical University, Nanning, Guangxi, China
- 3State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- 4Fudan University Institute of Urology, Huashan Hospital, and Fudan-VARI Centre for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China
- 5Center for Genetic Epidemiology, Van Andel Research Institute, Grand Rapids, Michigan, USA
- 6Fudan-VARI Centre for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai, China
- 7Department of Cardiology, Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China
- 8Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
- 9Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
- 10Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- 11Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, Maryland, USA
- 12Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
- 13Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- 14Medical Scientific Research Centre, Guangxi Medical University, Nanning, Guangxi, China
- 15State Key Laboratory of Proteomics, Beijing Proteome Research Centre, Beijing Institute of Radiation Medicine, Beijing, China
- Correspondence to Dr T Wu, School of Public Health, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China; wut{at}mails.tjmu.edu.cn
- Received 31 July 2012
- Revised 6 November 2012
- Accepted 3 December 2012
- Published Online First 7 January 2013
Objective Tumour biomarkers are used as indicators for cancer screening and as predictors for therapeutic responses and prognoses in cancer patients. We aimed to identify genetic loci that influence concentrations of cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and α fetoprotein (AFP), and investigated the associations between the significant single nucleotide polymorphisms (SNPs) with risks of oesophageal squamous cell (OSCC), pancreatic and hepatocellular cancers.
Design We carried out a genome wide association study on plasma CA19-9, CEA and AFP concentrations in 3451 healthy Han Chinese and validated the results in 10 326 individuals. Significant SNPs were further investigated in three case control studies (2031 OSCC cases and 2044 controls; 981 pancreatic cancer cases and 1991 controls; and 348 hepatocellular cancer cases and 359 controls).
Results The analyses showed association peaks on three genetic loci for CA19-9 (FUT6-FUT3 at 19p13.3, FUT2-CA11 at 19q13.3 and B3GNT3 at 19p13.1; p=1.16×10−13–3.30×10−290); four for CEA (ABO at 9q34.2, FUT6 at 19p13.3, FUT2 at 19q13.3 and FAM3B at 21q22.3; p=3.33×10−22–5.81×10−209); and two for AFP (AFP at 4q11-q13 and HISPPD2A at 15q15.3; p=3.27×10−18 and 1.28×10−14). These explained 17.14% of the variations in CA19-9, 8.95% in CEA and 0.57% in AFP concentrations. Significant ABO variants were also associated with risk of OSCC and pancreatic cancers, and AFP variants with risk of hepatocellular cancer (p<0.05).
Conclusions This study identified several loci associated with CA19-9, CEA and AFP concentrations. The ABO variants were associated with risk of OSCC and pancreatic cancers and AFP variants with risk of hepatocellular cancer.
Significance of this study
What is already known on this subject?
Cancer antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and α fetoprotein (AFP) are used as indicators for cancer screening and as predictors for therapeutic responses and prognoses in cancer patients.
Plasma concentrations of CA19-9, CEA and AFP vary substantially in healthy individuals, as well as in cancer patients, suggesting the influence of both genetic and environmental factors.
What are the new findings?
This study identified three genetic loci associated with CA19-9, four loci with CEA and two loci for AFP concentrations.
The ABO variants were associated with risk of oesophageal squamous cell cancer and pancreatic cancers and AFP variants with the risk of hepatocellular cancer.
How might it impact on clinical practice in the foreseeable future?
Our findings provide new insight into genetic determinants of CA19-9, CEA and AFP in the population.
Our findings may enable early screening for cancer risk in the general population.
Tumour biomarkers are used as indicators for cancer screening and as predictors of therapeutic responses and prognoses in cancer patients.1–5 Cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and α fetoprotein (AFP) are the most commonly used tumour markers, with high sensitivity and specificity for the diagnosis and prognosis of several cancers.6 Plasma concentrations of CA19-9, CEA and AFP vary substantially in healthy individuals, as well as in cancer patients, suggesting the influence of both genetic and environmental factors.7–9
While genome wide association studies (GWAS) have identified many loci associated with cancers, none has investigated genetic determinants of plasma concentrations of CA19-9, CEA or AFP. These biomarkers increase dramatically in individuals with cancer compared with those who are cancer free. It is possible that the loci influencing tumour biomarker levels may be related to the risk of cancer. Identification of genetic factors for tumour biomarkers may aid in early detection of cancer risk, improve prediction of cancer prognoses and enable personalised treatment.
To identify the genetic loci that influence CA19-9, CEA and AFP tumour biomarkers, we carried out a two stage GWAS. The discovery stage included 3451 subjects; the validation stage 10 326 subjects. The associations between significant single nucleotide polymorphisms (SNPs) and the risks of oesophageal squamous cell cancer (OSCC), pancreatic cancer and hepatocellular cancer (HCC) were further investigated in three case control studies. The study design is summarised in figure 1.
In the present study, we performed a GWAS of two studies in the Chinese Han population, including the Dongfeng-Tongji cohort study (DFTJ cohort) and the Guangxi Fangchenggang Area Male Health and Examination Survey (FAMHES). All of the subjects were recruited at health check-ups and had no diagnosed cancer or other chronic diseases, including cardiovascular disease, diabetes, stroke or chronic hepatitis.
The DFTJ cohort study was launched between September 2008 and June 2010. A total of 31 000 retirees at Dongfeng Motor Corporation, Hubei, China, were invited. Approximately 87% (n=27 009) of the invited participants agreed and completed the baseline questionnaire, physical check-up examination and provided blood samples.10 We conducted the GWAS in 1461 individuals who did not have diagnosed cancer or other chronic diseases.
FAMHES was initiated in 2009 in Fangchenggang City, Guangxi, China.11 Briefly, participants enrolled in FAMHES had no prior history of cardiovascular disease, cancer or other major chronic diseases. Every participant in the study completed a physical examination in the Medical Centre of Fangchenggang First People's Hospital from September 2009 to December 2009, and provided a blood sample at the same time. Initially, 4364 healthy men were asked to attend this study and 4303 individuals (98.6%) consented, with an age span of 17–88 years. For this study, we included only those aged 20–69 years who reported Han ethnicity (n=2012).
A total of 8830 healthy subjects were included in the first validation set; all were selected from the DFTJ cohort. Another 1496 subjects (996 Han and 500 Zhuang Chinese) from FAMHES were used for the second validation set. The demographic and clinical information of all subjects in the present study is summarised in the online supplementary table S1. All of the participants provided informed consent and the ethics committees of Tongji Medical College and Guangxi Medical University approved this project.
The OSCC case control,12 pancreatic cancer case control13 and HCC case control14 studies have been described in detail elsewhere (including 2031 OSCC cases and 2044 controls; 981 pancreatic cancer cases and 1991 controls; and 348 chronic hepatitis B virus carriers with HCC and 359 chronic hepatitis B virus carriers without HCC).
Phenotype measurement
In the DFTJ cohort, we measured plasma levels of CA19-9, CEA and AFP levels with the Architect Ci8200 automatic analyser (Abbott Laboratories, Abbott Park, Illinois, USA) using Abbott Diagnostics reagents according to the manufacturer's instructions. The intra-assay coefficients of variation were 5.32%, 4.38% and 4.6% for CA19-9, CEA and AFP, respectively. In the FAMHES study, we measured serum CA19-9, CEA and AFP concentrations with electrochemiluminescence immunoassay on the COBAS 6000 system E601 (Elecsys module) immunoassay analyser (Roche Diagnostics, GmbH, Mannheim, Germany), with the same batch of reagents used according to the manufacturer's instructions. The intra-assay coefficients of variation were 3.4%, 4.8% and 2.7% for CA19-9, CEA and AFP, respectively.
SNP selection and genotyping
We did the GWAS scan on the DFTJ cohort using Affymetrix Genome-Wide Human SNP Array 6.0 chips and follow-up genotyping with the iPLEX system (Sequenom) and/or the TaqMan assay (Applied Biosystems). In total, we genotyped 906 703 SNPs among 1461 subjects. After stringent QC filtering, SNPs with minor allele frequency (MAF)<0.01, Hardy–Weinberg equilibrium <0.0001 and SNP call rate <95% were excluded. Individuals with call rates <95% were also not included for further analysis. In total, we retained 1452 subjects with 658 288 autosomal SNPs for the statistical analyses, with an overall call rate of 99.68%.
For the FAMHES GWAS, we used the Illumina Omni-Express platform to conduct the GWAS scan, and the iPLEX system (Sequenom) and/or the TaqMan assay (Applied Biosystems) for follow-up genotyping. QC procedures were first applied to 2012 individuals. A total of 1999 individuals passed the call rate of 95% and were included in the final statistical analysis. We then applied the following QC criteria to filter SNPs: p<0.001 for the Hardy–Weinberg equilibrium test, MAF<0.01 and genotype call rate <95%. In total, we retained 709 211 SNPs.
SNPs selected for validation were based on the following criteria: (1) p≤5.0×10−8 for all GWAS samples; (2) SNP with the lowest p value were selected when multiple SNPs showed a strong linkage disequilibrium (r2≥0.8); and (3) MAF≥0.05. Based on these criteria, a total of 17 SNPs for the three tumour biomarkers were selected for further validation. The primers and probes are available on request. Genotyping in the validation stage was performed according to the manufacturer's iPLEX Application Guide (Sequenom) and TaqMan assay Guide (Applied Biosystems). All genotyping reactions were performed in 384 well plates. Each plate included a duplicate for four subjects selected at random, as well as 6–9 negative controls in which water was substituted for DNA. The average genotyping concordance rate was 99.8%.
Statistical analysis
We evaluated population structure by principal component analysis (PCA) using the software package EIGENSTRAT 3.0,15 and generated a quantile–quantile plot using R 2.11.1 (http://cran.r-project.org/). We used the additive model by linear regression analysis to perform the GWAS, and PLINK 1.06 (http://pngu.mgh.harvard.edu/~purcell/plink/) for statistical analysis.16 The Manhattan plot of −log10 P was generated with Haploview (V.4.1).17 In the DFTJ cohort GWAS, we used MACH V.1.0 software (http://www.sph.umich.edu/csg/abecasis/mach/) to impute untyped SNPs using the linkage disequilibrium information from the HapMap (http://www.hapmap.org/index.html) phase II database (CHB+JPT as a reference set, 2007-08_rel22, released 2007-03-02). The IMPUTE program was used to infer the ungenotyped SNPs in the FAMHES GWAS.18 Imputed SNPs with high genotype information content (proper info>0.5 for IMPUTE and Rsq>0.3 for MACH) were kept for the further association analysis.
We used ProbABEL software to conduct the association studies with imputation data.19 The DFTJ cohort GWAS data from 1452 subjects and the FAMHES GWAS data from 1999 subjects were used to conduct a fixed effects meta-analysis with an inverse variance weighted method using metal software.20 We used the Cochran Q test to assess heterogeneity.21 The chromosome region was plotted using SNAP.22 Prior to the analysis, the three tumour biomarkers were nature log transformed to normalise the distribution.
For the association analyses of the GWAS scan and validation samples, we adjusted for age, sex, body mass index, smoking and drinking. For the GWAS analysis, the top two Eigen vectors were also adjusted as covariates in the linear regression analysis. We conducted a forward selection linear regression analysis with plasma CA19-9, CEA and AFP concentrations to further investigate the independence of top SNPs. We forced age, gender, body mass index, smoking and drinking into the regression model. SNPs with p<0.05 entered the final model. The proportion of the variation in CA19-9, CEA and AFP levels explained by the SNPs was measured by r2, which is the difference of the model sum of squares between models with and without the SNPs of interest divided by the corrected total sum of squares of the full model. We used both the simple and weighted count method to calculate the genetic risk score. These analyses were also performed using SAS V.9.1.3 (SAS Institute, Cary, North Carolina, USA).
The general characteristics and biochemical trait levels of all participate are shown in online supplementary table S1. Distributions of CA19-9, CEA and AFP levels are presented in online supplementary figure S1. Individual variations in plasma levels of the three biomarkers were broad, with 2.43%, 5.96% and 1.27% of participants exceeding the reported normal ranges for CA19-9 (37 U/ml), CEA (5 ng/ml) and AFP (25 ng/ml), respectively.
Principal component analysis showed minimal evidence for stratification in our study population (see online supplementary figure S2). The quantile–quantile plot revealed a good match between the distributions of the observed p values and those expected by chance (see online supplementary figure S3). The small genomic control inflation factor (λ) between 1.001 and 1.032 indicated a low possibility of false positive associations from population stratification. We derived p values in a scatterplot (figure 2) from the additive model in linear regression analyses. Except for the SNP of rs2251844 at the HISPPD2A locus (Q=7.49, p=0.006), we detected no heterogeneity at the other loci (p>0.05).
Results of the genome wide association study
Cancer antigen 19-9
The α (1,3) fucosyltransferase (FUT6)–fucosyltransferase 3 (FUT3) gene cluster at 19p13.3 showed a genome wide association with plasma CA19-9 concentrations (table 1, figure 2, and see online supplementary table S2). The SNP rs3760775 was the strongest signal in this locus (p=1.07×10−172). Two other SNPs (rs17271883 and rs3760776) in the same gene were also significantly associated with plasma CA19-9 levels (p=4.17×10−60 and 2.69×10−36, respectively). In addition, the fucosyltransferase 2 (FUT2)-CA11 locus at 19q13.3 was significantly associated with CA19-9 levels (figures 2, 3). SNP rs1047781 (combined p=7.83×10−176; table 1) in the exon of the FUT2 gene is a non-synonymous variant, and the change from the A to T allele led to a substitution from isoleucine to phenylalanine.
The SNP rs11880333 in the intron of CA11 was also associated with CA19-9 levels, with a combined p=1.56×10−27. The SNP rs265548 near the B3GNT3 gene at 19q13.1 reached a genome wide significance threshold (p=3.57×10−10), and was validated in replication sets 1 and 2.
We performed a forward selection linear regression analysis of the top SNPs using a combination of the two validation data sets. Four SNPs (rs17271883, rs3760775, rs1047781 and rs265548) were independently associated with CA19-9 levels and jointly explained 17.14% of the total variation in plasma CA19-9 levels (see online supplementary table S5). The association of these SNPs with CA19-9 concentrations was cumulative. The additive effect size was 2.25 U/ml of CA19-9 per one allele increment in the simple count genetic risk score (p for trend=7.08×10−194; see online supplementary figure S4). The additive effect size was 1.54 U/ml of CA19-9 using the weighted genetic risk score (p for trend=2.48×10−117; data not shown).
Carcinoembryonic antigen
We identified four loci associated with plasma CEA concentrations (figures 2, 3). The synonymous variant of rs8176749 in the ABO gene had the most significant p value (p=3.02×10−35) (table 1). The SNP rs8176720 in the exon of the ABO gene at 9q34.2 was also consistently associated with CEA concentrations (p=7.57×10−17). The GWAS discovery stage showed that the loci of FUT6 and FUT2 associated with CA19-9 levels were also associated with CEA concentrations; the p values for rs3760775 in FUT6 and rs1047781 in FUT2 were 9.10×10−21 and 1.25×10−68, respectively. However, the direction of the association for rs3760775 was the reverse of that for CA19-9 and CEA levels; the T allele of rs3760775 was associated with decreased CA19-9 levels but with increased CEA levels (table 1). FAM3B at 21q22.3 (rs441810, p=1.76×10−11) was the fourth locus associated with CEA levels (table 1, figure 2).
These top SNPs jointly explained 8.95% of the total variation in plasma CEA levels (see online supplementary table S6). The additive effect size was 0.19 ng/ml of CEA per one allele increment in the genetic risk score (p for trend=2.43×10−128; see online supplementary figure S4). We obtained similar results by using the weighted genetic risk score (β=0.20; p for trend=3.86×10−167; data not shown).
Alpha fetoprotein
Three loci were associated with AFP at a genome wide significance level. In the GWAS discovery stage, the p values for their strongest SNPs were 7.69×10−9 for rs12506899 in AFP, 5.09×10−8 for rs12579373 in CHST11 and 3.35×10−8 for rs2251844 in the HISPPD2A gene (table 1, figure 2). We validated two loci of AFP and HISPPD2A, but in both validation data sets we failed to do so for the SNP rs12579373 in CHST11 (table 1).
Two SNPs (rs12506899 and rs2251844) explained approximately 0.57% of the total variation in plasma AFP levels (see online supplementary table S7). The additive effect size was 0.20 ng/ml of AFP per one allele increment in the genetic risk score (p for trend=1.67×10−17; see online supplementary figure S4). We obtained similar results by using the weighted genetic risk score (β=0.20; p for trend=1.61×10−17; data not shown). The full list of the SNPs associated with AFP levels<10−7 is shown in online supplementary table S4.
Associations between top SNPs in tumour biomarkers and different types of cancer risk
All of the SNPs in the ABO loci had nominally significant associations with OSCC risk (p<0.05, table 2). Among them, the SNP rs8176749 was in high linkage disequilibrium with rs8176672 (r2=0.90, D′=0.95). Conditional association analysis showed that the associations for rs8176749 and rs8176672 were not significant after mutual adjustment, suggesting that they are unlikely to be independent signals. Other top SNPs in ABO were not significant after adjustment for rs8176749 or rs8176672, indicating that other SNPs were not independent susceptibility markers for OSCC risk. The SNP of rs8176720 in the ABO gene also had a nominally significant association with pancreatic cancer risk (p=0.014, table 2).
To examine whether the ABO blood group was associated with the risk of OSCC and pancreatic cancer, we deduced the ABO blood group using two SNPs (rs8176746 and rs505922).23 The results indicated that the ABO blood group was significantly associated with OSCC risk. Compared with the O blood group, those with the A blood group had a significantly decreased risk of OSCC (OR=0.73, 95% CI 0.62 to 0.86; p<0.001); those with the B blood group had a marginally increased OSCC risk (OR=1.17, 95% CI 0.99 to 1.37; p=0.06). However, we did not find a significant association of ABO blood group with pancreatic cancer risk (see online supplementary table S8).
For the top SNPs in the AFP gene, there were significant associations between the SNP rs12506899 and the risk of HCC. Participants who carried the G allele had a decreased risk of HCC (table 2). SNP rs2251844 was not associated with HCC risk.
CA19-9 is a carbohydrate tumour associated antigen that is frequently unregulated in pancreatic cancer.24 The sialylated Lea carbohydrate structure is the carbohydrate antigenic epitope of CA19-9.25 Prior studies reported that variants in the Lewis (Le) gene (also known as FUT3) and the secretor (Se) gene (also known as FUT2) were associated with serum CA19-9 levels,26 ,27 and that the Le and Se enzymes participated in the synthesis of CA19-9. We also found an association between the B3GNT3 locus and CA19-9 levels. The B3GNT3 locates at 19p13.1 and encodes a member of the β-1,3-N-acetylglucosmaniyltransferase family that is the backbone structure of dimmeric sialyl Lewis a.28 Since the sialyl Lewis a is the carbohydrate antigenic epitope of CA19-9,25 it might be the potential mechanism underlying associations between variants in the B3GNT3 locus and CA19-9 concentrations.
CEA is a tumour associated antigen first reported by Gold and Freedman in 1965.29 Evaluation of CEA levels has become a useful complement to methods of detecting and staging tumours, following-up for recurrence or metastases, determining response to therapy and assessing prognosis in cancer patients.30 ,31 We found significant associations between ABO genotypes and plasma CEA levels. Our study also indicated that the genetic inferred ABO blood group was significantly associated with plasma CEA levels (see online supplementary table S9). Previous studies show that CEA and the blood A and B antigens share the same glycoprotein carrier molecules.32 ,33 This might explain the association between the ABO locus and CEA concentrations. FUT2 encodes a 1, 2 fucosyltransferase that catalyses the addition of a fucose to precursors to form the H antigen. The SNP rs1047781 in the FUT2 gene is a non-synonymous variant; the change from A to T allele leads to a substitution from isoleucine to phenylalanine. A functional study has found that this substitution inactivates fucosyltransferase.34
The third CEA locus is at 19p13.3, where multiple SNPs in a ∼21 kb region (between 5 781 302 and 5 802 801) had a significant association with CEA levels (p<5.0×10−8) in our GWAS discovery stage (figure 3). The most significant SNP (rs3760775, p=9.10×10−21) was between FUT3 and FUT6; both encode fucosyltransferases that catalyse the formation of Lewis antigens that share the same glycoprotein carrier molecule with CEA.32 Elevated FUT3/FUT6 concentrations might play an important role in the progression of adenocarcinoma.35 The fourth CEA level associated locus is at 21q22.3, which maps to the FAM3B gene. FAM3B is involved in glucose homeostasis and insulin regulation.36 The biological relationship between the FAM3B gene and CEA levels remains unclear.
AFP is a single chain glycoprotein with about 70 000 Da of molecular weight. Although barely detectable in healthy individuals,37 it increases in HCC.38 ,39 We found that the AFP locus had 'cis' effects on AFP levels; however, the biological relationship between the HISPPD2A loci and AFP levels remains to be investigated.
Tumour biomarkers are used as indicators for cancer screening and predictors for therapeutic response and prognoses. In the present study, we found that the AFP locus was not only associated with AFP levels but also with HCC risk. The effect direction was consistent. Studies indicate that AFP is not only a biomarker of HCC, but plays a direct role in the progression of HCC by inducing dysfunction and apoptosis of APCs and promoting the escape of HCC cells from immunological control and surveillance.1 ,2
Similarly, the ABO locus was not only associated with plasma CEA concentrations but also with the risk of OSCC and pancreatic cancer. This finding is consistent with those from other studies.40–45 To our knowledge, the present study was the first report of significant associations between SNPs in ABO gene loci and the OSCC risk. CEA and the blood A and B antigens share the same glycoprotein carrier molecules.32 ,33 The blood group was associated with the host immunological and inflammatory state in several reports,46 and might be related to carcinogenesis by involvement in the mediation of intercellular adhesion and membrane signalling.40 ,47
ABO antigens are secreted into the gastrointestinal tract by a functional FUT2 enzyme.48 Approximately 20% of individuals in different populations have no ABO antigen in their gastrointestinal secretions due to homozygous loss of functional mutations in the FUT2 gene,49 and these 'non-secretors' have decreased susceptibility to multiple pathogens, including Helicobacter pylori50 which has been linked to gastric adenocarcinoma.51 The current study found a consistent effect direction between the ABO locus–CEA levels and ABO locus–OSCC and pancreatic cancer risk, suggesting that CEA might not only be a tumour biomarker but also may be directly involved in the development of cancers.
In summary, the present GWAS of a large number of Chinese participants identified several novel loci associated with plasma concentrations of tumour biomarkers CA19-9, CEA and AFP. Our findings provide new insights into genetic determinants of these biomarkers in the population. They may enable early screening for cancer risk in the general population. Further studies are warranted to examine the potential structure and/or functional significance of these associations.
The authors would like to thank many colleagues for their hard work on the collection of epidemiological data, phenotypic characterisation of the clinical samples, and genotyping and analysis of the genome wide association data. The authors would also like to thank those who agreed to participate in the present study.
MH, CW, JX, HG, DL, ZM and TW contributed equally to this study.
Contributors MH, CW, JX, HG, DXL, ZM, FBH and TW: study concept and design. LZ, TP, YH, YG, JY, QD, XD, DFL, AT, YF, HYZ, XWM, XY, JZ, KZ, JC, XQ, WT, YLH, ML, ST, YFL, YL, JF, DFL, S-TK, SJZ, HXZ, SLZ, LG, YW, SW, FW, WF, YL, YZ, WC and XPM: acquisition of the data. MH, CW, JX, HG, LZ, SW, TP, YFH, YLH, LG and YFL: analysis and interpretation of the data. CW, JX, HY, XZ, JS, DY, JY, WC, GZ, DXL, ZM and TW: contributed reagents/materials/analysis tools. MH, CW, JX, XG and ZM: drafting of the manuscript. DXL, FBH and TW: critical revision of the manuscript for important intellectual content. TW, ZM and MH: obtained funding.
Funding This work was supported by grants from the National Basic Research Program grant (2011CB503800) and the Programme of Introducing Talents of Discipline to Universities to TW; the General Program of the National Natural Science Foundation of China (30945204, 30360124, 30260110, 81222038); the Guangxi Provincial Department of Finance and Education (2009GJCJ150); intramural funding from the Fudan-VARI Centre for Genetic Epidemiology and Fudan University Institute of Urology to ZM; and Program for New Century Excellent Talents in University and the General Program of the National Natural Science Foundation of China (81172751) to MH. The funders had no role in the study design, data collection, data analysis or interpretation of the data.
Complete interests None.
Ethics approval This study was conducted with the approval of the ethics committees of Tongji Medical College and Guangxi Medical University.
Provenance and peer review Not commissioned; externally peer reviewed.


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The Scotland international was adjudged to have been tripped by Danny Shittu in the area and Jordan Rhodes stepped up to move Rovers five points clear of the drop with two games to play.
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"I don't think we should be talking about that," he said when asked about the incident. "We should be talking about our second-half performance and how brave my players were. Some you get, some you don't.
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The true and original story of Rumpelstiltskin
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23-SWB, King's College London Strand, London, WC2R 2LS
Registered charity no. 1070013


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Suggested byand this is thread is for 40k chars vs other 40k chars to save clogging up the forum with random threads. If any Mod feels this should be in Off-Topic or anywhere else for that matter feel free to move it.
Round 1:
Leman Russ
Konrad Curze:
- Morals On
- Standard Gear
- No Prep
Next round begins after a majority vote as been decided.


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Closed Thread
Results 61 to 70 of 149
Thread: The Next Generation
Sunday, 6th May, 2012, 05:26 AM #61
Minor Trickster (Lvl 4)
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A FAD is a temporary trend, but one persons fab is another person Revelation. D&D needs to evolve & improve over the years, else everyone would still be using 3 little white books. If you dread change, stay with your current edition. No one really steals your old books & drinks your soft drinks in the dark of the night.So Long, and Thanks for All the Fish !
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Sunday, 6th May, 2012, 06:15 AM #62
Waghalter (Lvl 7)
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You have no idea what your talking about. Conan and "frodo" have each made more money and occupy more attention in RECENT video games, and movies than samarai shampoo and all the other **** fiction you mention put together.
Also just wondering if the OPs post is fair on these forums? I know I've gotten some warnings in the past so I just want to know if this is an acceptable type of post. Because it would be fun to start a similar thread targetting some other playstyles and preferences in an equally offensive manner.
Last edited by hanez; Sunday, 6th May, 2012 at 06:19 AM.
Sunday, 6th May, 2012, 06:45 AM #63
Orcus on an Off-Day (Lvl 22)
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the Jester
The Monster Project
Buy my first self-published weird sci-fi novel from Amazon here!
Sunday, 6th May, 2012, 07:42 AM #64
Waghalter (Lvl 7)
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I'm sure it's been pointed out by now on this thread, but a good chunk of the post is written under a false premise.
None of us here were alive when Conan, Gray Mouser, or even LotR were written. They were already old when any of us first heard of them. These things are timeless, not passe.
Just because you hadn't heard of something before now doesn't mean it's not worth hearing about. Youth just means there's a whole lot of things you've yet to experience.
You're right about one thing, though. DDN should (and almost certainly will) be able to approximate newer lore as well.
Sunday, 6th May, 2012, 07:50 AM #65
Thaumaturgist (Lvl 9)
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Extremely niche anime series is hardly 'new guard'. The only one mentioned that is relevant to the discussion is Harry Potter and it simply isn't high fantasy and doesn't belong in Dungeons & Dragons.
The newer popular fantasy are novels like A Song of Ice and Fire, The Wheel of Time, Sword of Truth, and The Inheritance Cycle and video games like Elder Scrolls, Dragon Age, Kingdoms of Amalur, Warcraft, and Guild Wars. Literally all of the newer fantasy plays on tropes created by their predecessors, even ones that are touted as different. The systems like the Vancian magic system echoes throughout all mediums of fantasy.
Vancian Magic - Television Tropes & Idioms
Tolkein still has more influence in the fantasy genre than J. K. Rowling will ever hope to have. His books are still being made into movies and video games, her works will only be a memory in 40 years.
Last edited by variant; Sunday, 6th May, 2012 at 07:54 AM.
Sunday, 6th May, 2012, 08:35 AM #66
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Sunday, 6th May, 2012, 08:52 AM #67
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The OP has some valid points, although I disagree with most of it.
If I'd run D&D any edition with the RAW, I'd get a lot less players. But the good thing is you can modify the rules relatively easily to suit any group, and the chances are someone else has already done this for you.
Yeah I think us old flatuli may sometimes insist on keeping something around too long (the whole Vancian magic disaster is one example to me) but you can option anything in or out in D&D as long as you do not totally kill the balance.
What could possibly happen is that the examples of what you can do with the system should include modern fantasy like Game of Thrones, the Pern books... LoTR is still modern to me.
And hey, I haven't even gotten around to read Dragonlance yet... I wonder if I will ever have the money to get the books, the possibility to convince my husband to buy them and the time to read them on top of my already long "must read" list...
Sunday, 6th May, 2012, 09:04 AM #68
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This is pretty simple in my eyes. D&D should draw inspiration from many different sources, old and new. Let the game evolve, but at the same time don't try to brush where it came from under the rug. The fact of the matter is that a great deal of all of this is aesthetics, it's the window dressing in your head and the presentation at the table. D&D is a big tent game, you can do a lot of different styles with the same mechanics. The game should acknowledge this and invite you to draw your inspirations from what you like. I sincerely hope that the text references movies, pulp, sword and sorcery, high fantasy, comics, manga, anime, video games, mythology, et c. It should be inclusive of peoples' taste, not exclusive.
"Each man, one way.
Each horse, one stance.
Each church, one buddha.
Each master to his own technique."
Sunday, 6th May, 2012, 03:52 PM #69
Grandmaster of Flowers (Lvl 18)
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Or, to paraphrase Cowboy Bebop: "And the work which has become a genre unto itself shall be called: Dungeons and Dragons".
They misremember the past?
They deliberately misrepresent the past?
I think that about covers it.
I'm playing Pathfinder this afternoon, a game considered by a lot of current gamers to be the true successor to D&D. My character bears no resemblance to anything out of the old guard of fantasy authors. What *does* she resemble? Hawkeye from the Avengers with a dash of Storm from the X-Men. This is what D&D does well. Mash things up. Even relatively recent things.
This is a misreading of 4e's market failure. 3e and Pathfinder are also "new guard" in terms of their tone and fidelity to older literary sources like Tolkien and Howard.No thanks. The "new guard" were given their chance and they dropped the ball.
This is untrue. Newer fantasy fans help explain the popularity of 3e and Pathfinder.Fans of the newer fantasy fiction failed to support the brand in sufficient numbers to make aiming the game at their tastes a worthwhile endeavor.
Except it was just an eclectic bunch of
shistuff two dudes really liked.
People will turn anything into orthodoxy, won't they? Even rule about about pretending to be elves....
I'm closing in on my mid-40s, and I can't say I'm immune to nostalgia. I want to see plenty familiar elements in 5e. Then again, I'll take Cowboy Bebop over Conan the Cimmerian any day of the week, and I'll be deeply disappointed if 5e eschews contemporary influences/references.They want nostalgia, and they're prepared to pay. If these guys had been around in 1974, in their mid-40s to mid-50s, they'd have *hated* D&D.
"You should probably put your bandit hat on now. Personally, I- I don't have one, but I modified this tube sock." - Ash, Fantastic Mr. Fox.
The Chronicle of Burne, and Some Others of Lesser Importance: Updated 05-17-2009! Current episode: Flight of the Philip.
The Port on the Aster Sea Our 4e setting. It's a heartbreaking work of staggering genius!
Sunday, 6th May, 2012, 04:03 PM #70
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I am 36, so not sure where I fall in the OP's mind. Most people I game with are between the ages of thirty and fifty.
With all due respect to the original poster, telling people to just go away isn't going to achieve anything. Either these folks are an important customer block or they aren't. WOTC getsto make the final call either way. Also, in D&D terms, telling people to go away usually results in a heavy penalty on your diplomacy roll.
But i think you are assuming a lot here. If the old generation goes away in a blink, that doesn't mean calls for vancian casting and other traditional D&D trappings will dissapear. Lots of people who started the ame quite recently like these things.


text:
Channel One wins $500,000
The money is much needed for the organization.
The money is much needed for the organization.
More and more are becoming victims as suspects tend to drain their accounts.
Semi did not stop after the accident
National magazine says Mayo is #1 for the first time in the history of its rankings
Jury selection is expected to resume Tuesday at the third trial of an Iowa man charged with killing his wife and unborn child.
The head of the St. Paul teachers union will step down after being elected to a national union leadership role.
Channel One Regional Food Bank is the winner of the first "All Star Fans Choose" grant.
The stolen Pit Bull from PAWS Humane Society in Charles City has been found safe.
Reported changes to Mason City's Transit System on July 23rd to accommodate RAGBRAI riders and regular riders.
The Saints and Bearcats both play next Tuesday.
A close look at the cell phone industry. Tips on when to upgrade and when to wait it out, and Insider knowledge on some ground breaking mobi…
Officials are monitoring cleanup of a fertilizer spill in northern Iowa that dumped hundreds of gallons of liquid.


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Vt. encourages more landowners to open to huntingThe Associated Press | November 05,2013BENNINGTON - The Vermont Department of Fish and Wildlife is encouraging landowners to make their properties available to hunters.
The department says amount of posted land has roughly doubled between 1971 and 2011, about 100,000 acres to between 200,000 and 230,000.
Hunting license sales have also been on the decline, from about 91,000 licenses sold in 1987 to about 73,500 in 2004.
The Bennington Banner reported that recent legislation has given landowners the option to use "hunting by permission" signs, which work similar to posted signs but are more inviting. The signs are still being worked on.MORE IN This Just In
A two car accident with injuries has narrowed traffic on Route 7 North towards the... Full StoryAn inmate at Marble Valley Correctional Facility died of an illness at Dartmouth-Hitchcock... Full StorySPRINGFIELD The Springfield Select Board took the first step toward endorsing the towns... Full Story
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Ready to watch this entire course?
Become a member and get unlimited access to the entire skills library of over 4,900 courses, including more Video and personalized recommendations.Start Your Free Trial Now
- Overview
- Transcript
- View Offline
- Understanding parallax
- Choosing the best photos
- Identifying planes
- Using Quick Selection, Quick Mask, and Refine Edge to create layers
- Adding a 3D camera to your scene
- Setting the depth and size of your composition
- Using multiple views
- Adding depth of field and Bokeh blur
- Setting ambient and directional light
Skill Level Intermediate
What kind of photos are going to work well for Motion Control? This is incredibly subjective. In some cases, it's going to be the pictures that your client gives you and says please make these move. However, you're probably being hired because of your good judgment and artistic sensibilities. So, if given a choice, you're going to want to have some input. Let's take a look at two pictures and talk about some of the pros and cons of using these images. I am in Adobe Bridge here, and this is a nice way to browse photos. You notice you get all the technical specs here on the right, and we'll talk about resolution in our next lesson.
I'm just going to take this image and View it Full Screen. I've got a nice Slideshow here. Notice I can move between the images, or if I just want to see a single image, the spacebar will open it up, and that's nice, it's very quick. This image has a lot of good things about it. We have a sense of perspective. What's nice here is that because we have an angle, we could take advantage of vanishing point exchange later to create a sense of movement around this house. Unfortunately, with this picture a lot of the objects are cut off. The car in the right here is chopped, so I'd likely need to remove it or replace it with more of a vehicle.
There is also not a lot of head room in the photo, so if I want to move down to this house, we're going to have to replace the sky and fill in additional details. On the left here, it gets pretty tight on this person. Remember, with video you often need to compensate for action safe and title safe, so you tend to pad the edges a bit, leaving room on the outside frame. This person is going to get smushed right up to the edge unless we extend the left edge here through cloning or scene replacement. Let's take a look at the next photo.
Now this image has a lot of action in it, which is good. We definitely have the sense of motion and which direction we're going to tell the story. I envision that the camera pans down from the sky here into the walking soldiers. What's nice is we have a definite sense of movement, and the camera can match that going ahead and panning across the action here to give you a sense of motion and perspective. Up front here, we have some stray action from the previous scene, and because that's not going to resolve, I'd likely crop the image or clone them out.
There are some flaws in this picture, here is soft focus, and that's indicative of the timeframe. So, make sure you give some thought as to where you're going to put your focus. With Bridge you can click and zoom to 100%, and this make it very easy to pan around the image and view the actual pixels, so you can evaluate. If dealing with historical photos, there is little guarantee that they're going to be tack sharp. In fact there's pretty much a guarantee that they won't. But even within a picture like this, some parts have better focus than others, and we'll have to keep that in mind as we choose to frame the shot.
So, evaluate the sources you have. To summarize, I always look for a sense of motion. This is going to help me tell what way the camera is going to move through the scene. Ideally, there's also some perspective. It might be an angle or just a sense of multiple layers stacked with foreground, mid-ground, and background. You're going to need that stacking if you really want to create a sense of movement, and you need that depth, hence Motion Control 3D. If you don't have any depth, that it's just simple pan and scan like a traditional Ken Burns style effect--and we've covered that in an earlier video here on lynda.com: Documentary Techniques with Photoshop and After Effects, and we go well into it there.
So take a look. For 3D Motion Control, perspective and depth are key.


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Is there any way to make them compatible?
Is there any way to make them compatible?
As a BraveNewCode customer, you have full access to our customer support documentation and dedicated support team through our forums. If you have not done so already, please login and post your question there to receive personal attention and to resolve your issue in a timely manner:
We look forward to seeing you there.
It's too bad they don't work together. I'm not a pro user. I would like to buy the pro version, but I'm never going to do that unless I can first get qtranslate and wptouch to work together. I know they are currently incompatible (using the latest versions of both). If I leave both activated, wptouch displays the default settings, no matter what I change in the backend.
As soon as qtranslate is deactivated, wptouch works as it should. Reactivating qtranslate once again displays the default wptouch settings when visiting with an iPhone.
The free version of WPtouch and WPtouch Pro are built differently to accommodate different levels of site needs. One is not merely an extension of the other.
One of our customers built and shared a plugin to enable WPtouch Pro and qtranslate to play nicely together. The link is available in our customer forums or directly from a support team member. So if you do decide to give WPtouch Pro a try, be sure to take advantage of the resources available to you.
In addition, every purchase of WPtouch Pro comes with a 7-day trial period during which, if you find the product not to be satisfactory, you may request a full refund for any reason.
This topic has been closed to new replies.


text: Kmart | Winter accessories clearance New price drops! Free shipping with shop your way max or free pick up Flag this deal What's the matter? Choose a reason Dead deal Duplicate Bad link Spam Inaccurate No value Alive again Edit deal lotuslove19 Jan 16, 2013 The prices are good mainly on the women's sizes.Thanks for the post. Reply Mawhen Jan 16, 2013 Great savings on end of the season stuff with plenty enough "season" to get some good use from items. Thanks! Reply helloamy1977 Jan 16, 2013 looks like the .60 ones are gone but they have 2 pair for .99 Reply MrBklynW Jan 16, 2013 awesome discount gloves. very nice find Reply blackfoot Jan 15, 2013 Looking to find some cheap gloves or mittens, thanks. Reply FibroMom Jan 15, 2013 Thank you, Kmart Queen! You have saved me MORE MONEY than you can imagine with your terrific deals! Thank you SO MUCH! :) Reply supercouponingmo Jan 15, 2013 Great post! There are some great deals here. Thanks. Reply EzzyLovesToSave Jan 15, 2013 Ready?...here it comes!...PINK ALET!....PINK ALERT!....PINK ALERT with SMOKIN Prices! Reply Jazmine_ilene Jan 15, 2013 very nice price for these gloves. perfect price to buy more than one pair =) Reply cid681 Jan 15, 2013 Darn, the prices are good mainly on the women's sizes. Reply poe601 Jan 15, 2013 Time to stock up, great selection and prices. Reply jkbane Jan 15, 2013 wow nice price drop Reply Load More Comments


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Milwaukee Bucks unveil new Robert Indiana-inspired floor
The Milwaukee Bucks are putting their hometown at the center of home court, with a giant M flanking each side of the midcourt line on a newly unveiled, art-inspired floor.
The Bucks unveiled the design for their new floor Tuesday evening at the Milwaukee Art Museum. It is inspired by Pop artist Robert Indiana's much-beloved 1977 MECCA floor. »Read Full Article(78)
Hank the Brewers dog to UW: Go, Bucky!
It's clear from the latest photo of Hank the Brewers dog where the ballpark pup's loyalties lie in Saturday night's matchup between the University of Wisconsin and Arizona.
Hank-watchers might take the red UW "Jump Around" shirt as a sign that the dog has already settled in to his new home, since Arizona is where the Milwaukee Brewers first met the stray dog last month. Hank was adopted by the family of a Brewers official, and has been getting acclimated to his new surroundings before the team starts the regular season Monday at Miller Park. »Read Full Article(6)
Florentine Opera's 'Julius Caesar' has hits, misses
Friday's Florentine Opera production of Handel's "Julius Caesar" scored both hits and misses.
The story of Julius Caesar and Cleopatra and the struggles between their cultures is both ancient and timely. Set by the composer in 48 B.C., the Florentine's production was set somewhere in the early or middle part of the 20th century and directed by Eric Einhorn. »Read Full Article(1)
Milwaukee Rep interns explore life onstage and off in Rep Lab
Ten plays for 10 bucks, featuring the 12 actors and two directors comprising the latest edition of the Milwaukee Repertory Theater's fabled intern program — many of whose graduates become stars? Pinch me, please, to make sure I'm awake.
But the Rep Lab — a creation of Rep Artistic Director Mark Clements, now in its fourth year — is no dream, even if many of this year's plays explore the difference between our dreamscapes and our everyday lives, and the related difference between our performing selves and who we actually are. »Read Full Article
Yellow Ostrich frontman Schaaf rooted in Wisconsin — and space
Seeking to create a bigger sound for the band's new indie-rock album, Yellow Ostrich frontman Alex Schaaf was influenced by the vastness of space, particularly the books of Carl Sagan and his landmark miniseries "Cosmos," of which the album shares a name.
But where Schaaf first found inspiration was far smaller in stature: Prairie du Chien, where the New York-based musician grew up the son of a butcher shop owner and a family living agent working for Crawford County. »Read Full Article


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Porcelain Beads Twisted Oval 16x9mm 15" strand
Our Price: $3.99
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Ask a question about this product
Why you'll LOVE this item:1 15-inch strand of Chinese porcelain beads. 16x9mm twisted ovals. A variety of colors on one strand Holes 1mm. Each bead is unique, colors will vary. Combine with our headpins, ear wires, organza cords, silver chains, and neck cords for instant wearable art.


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- Report: #913230
Report - Rebuttal - Arbitrate
Complaint Review: Sponsored Whips
Sponsored WhipsWilmington, Delaware Internet United States of America
Sponsored Whips sponsoredwhips.com, Patrick, Mitch FRAUD....Never performed services they promised...refuse to refund my $199.00. Internet
*REBUTTAL Individual responds: This is a False Statement
Ripoff Report
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Nearly 1 year later and still nothing. I have called and the few times I have spoken with somebody, they identified themselves as either Patrick or Mitch...they promised to return my calls but never do.
I send them emails, but they do not respond unless I become ANIMATED. Then I get a response saying let's schedule a time when we can talk...
I have now contacted an attorney who will serve them with a letter demanding a refund. We will see how far that goes.
Sponsored whips is a joke of an organization. They need to be shut down for fraud, internet and wire fraud and postal fraud....these characters need to go to prison...
Do not allow yourself to get screwed by these scam artists.
This report was posted on Ripoff Report on 07/17/2012 09:01 AM and is a permanent record located here: http://www.ripoffreport.com/r/Sponsored-Whips/internet/Sponsored-Whips-sponsoredwhipscom-Patrick-Mitch-FRAUDNever-performed-services-they-913230. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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#1 REBUTTAL Individual responds
This is a False Statement
AUTHOR: Paula at SW - (United States of America)
SUBMITTED: Tuesday, July 17, 2012POSTED: Tuesday, July 17, 2012
Here is PROOF of a refund:
A gentleman read some bad reviews and quickly wrote a bad one about us BEFORE his 30 days were up, but we saw this and he asked for a refund within his 30 days and wrote a retraction and STATES THE REFUND CAME IN!
here is a link:
Click above then look/scroll down to update #10 in ROR's site...
HE WAS IN his 30 period, and WAS refunded... He was scared we wouldnt honor it, posted here on ROR, but we DID honor our policy and NOT scared to admit this report is out there cuz it shows we ARE LEGIT!!
AGAIN FACTS!!! Not just complainers listing nonsense...
Companies will all ways have people not happy or satisfied its the way the biz world is.. and WE ARE a biz trying to make money to pay a staff, a office lease and GROW. We never have lied and said we are a charity.. so if our employees get paid from the "service fees" we charge show us how thats a "Scam"..
Also find me ONE post were some says: "they WORE all the logos, went to shows, and DID EVERYTHING we asked them to prove to sponsors they earned it, and they didnt get it... all the negative posts are SPAM by our competitors, non clients, and people who didnt follow our advice... sorry but true...
Facts are:
-Over 25,000 Facebook "likes" @ www.facebook.com/sponsoredwhips
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We Welcome ANYONE o swing by our office and see us and we will GLADLY explain and show our operation too you! or if you have a friend or relative that lives by us have them come by!!! :)
Are you an owner, employee or ex-employee with either negative or positive information about the company or individual, or can you provide "insider information" on this company?
Advertisers above have met our
strict standards for business conduct.


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That i get when i am trying the registration, with login no problems.
I am working with multisite, register from main site, have actually only one site, the main one
No other plugin runs
Fixed as suggested in some other note, i.e.
redirect = data.children('#simplemodal-login-redirect'); in the java file
Any other idea???


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Corrupt Core Redesign by Super-CuteWatch
©2012-2016 Super-Cute
Looking back on my old core designs I'm always so embarrassed by them... I'm currently trying to work on my same face/body type syndrome and thought redesigning these guys would be a great idea!
WHOA PORTAL ART HOW EXCITING this must be a surprise xD
WHOA PORTAL ART HOW EXCITING this must be a surprise xD
The irony is that there's cut lines where Rick disagrees with Space Core. Like, "You know what I hope is in space? Fire. I hope you go to space, and you catch on fire!" But you probably knew that, I'm guessing.
I feel like Rick should be saying "why not it's an adventure!
I used to pratice arcane arts on space =3
Oh gosh, your fact is PERFECT!
thank you so much!!
Just throwing something out there: I ship fact and adventure for no freakin reason and YOUR DESIGNS ARE NOT HELPING ME GET RID OF THIS SICKNESS OF FACTXADVENTURE! >
Other then that, i like it.
Especialy space, he looks cute.
Other then that, i like it.
Especialy space, he looks cute.
...I totally don't have a crush on fact. NOPE!
This is amazing. And you just made me ship the fact and space core. Which is bad cuz i shipped space core and curiosity core before this.
Fact: DO WANT
It looks like the hat is a little small
Why don't you draw One Direction stuff? Maybe One Direction cores? IDK. It's something to think about while you're not leaving the house ever.
Fact: This is brilliant.
I'm wondering if their core color should be a patch on their sleeves. Just a thought.
i love fact core!


text:
Obama considers new transparency rules
The Obama administration is determining how to require companies competing for government contracts to list their political contributions when submitting a contract bid, another effort to separate money from its influence, according to a draft executive order.
"To increase transparency and accountability to ensure an efficient and economical procurement process, every contracting department and agency shall require all entities submitting offers for federal contracts to disclose certain political contributions and expenditures that they have made within the two years prior to the submission of their offer," the order states in its current form. (Read the order.)
Related stories:
How outsourcing keeps America on top
Industry dealings could be more transparent in open-source tracking system
The White House has not released the order, which was obtained by Federal Computer Week. It's currently going through the standard review and feedback process, an administration official said today.
Although the order would leave many details up to the Federal Acquisition Regulatory Council, the administration wants company disclosures to include:
Companies would have to disclose the information if the total amount of contributions exceeded $5,000 in a year, according to the draft order. Furthermore, the Obama administration wants the contribution data made public through a searchable online database.
"Taxpayers deserve to feel confident that federal contracting decisions are based on merit alone and are not influenced by political favoritism," the administration official said.
The regulatory council has until December to adopt the rules.
The order furthers the president's reforms to government contracting policies, which began with his procurement reform memo in March 2009, soon after his presidential term began.
"The president is committed to bringing more accountability and transparency to a federal contracting system that has long needed reform," the official said.
The order also highlights various states' "pay-to-play" laws, some of which require companies to disclose contribution information. Others limit political contributions by contractor companies and particular officials at the companies.
"This state innovation toward better government should be encouraged, and the federal government should draw from the best practices developed by the states," the Obama administration's order states.
About the Author
Matthew Weigelt is a freelance journalist who writes about acquisition and procurement.
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Steve Kelman contends that a recent report on agencies' prize challenges tells only half the success story.
OMB's Data Center Optimization Initiative gives agencies new metrics and goals for fiscal 2018.
NSA and the CIA have revamped themselves in the past year. FCW asked officials how well Fort Meade and Langley are collaborating in cyberspace in pursuit of their separate missions.
The latest version of the Defense Department-wide Enterprise Service Management Framework places more emphasis on managing IT risk.
Despite GSA's efforts to accelerate the FedRAMP approval process, the lack of agency reciprocity puts the program's central goals at risk.
Got some early-career colleagues who are doing great things in federal IT? Nominate them for FCW's 2016 Rising Star awards.
The agency software inventories required under the draft category management policy will be treasure maps that lead to efficient, effective, streamlined buying and unprecedented savings.
As experts warned of the "dire" threats posed by outdated federal technology, lawmakers grilled top feds, debated workforce issues and inched closer to backing a $3.1 billion fix-it fund.
The agency is making strides in developing and deploying border technologies but still has some weaknesses.
This is Chicago style politics at its ugliest. Obama wants to know which party each vendor contributed to so he can reward his friends and punish his enemies. If Bush tried to do something like this while he was in office you know that the Democrates would have screamed bloddy murder, and Obama would have been hollering the loudest of them all. Just another blatent abuse of power that will get swept under the rug by the media.
Really? This is over the line and is being pushed for transparency reasons? Maybe because nothing else this administration has done has been transparent and the pre-election promises are being hailed cause the election is approaching. So If I am a contractor and give heavily to the GOP or Dems, depending on who is in office, could determine if the contract is awarded - don't you dare think this would not have an affect on contract awards. Give me a break!
The guidance from the President implies that political leaders are influencing the actions and decisions made by Contracting Officers and evaluation boards. Why should we violate the privacy of individuals and firms in order to address a problem that mey or may not exist? If it exists, than the problem should be addressed directly.
There is nothing good that can come out of this and it is political pandering at its worst. On the one hand you can read into this an attempt to try to brand contractors with a scarlett letter and effectively deny to them the same rights that others have. Who says you have to give up your basic citizen rights merely to sell to the government? Where in the FAR is that written? On the other hand, this can be seen as an attempt at political extortion. I.e. "Support my camapign if you want to keep doing government business". Either way, no one wins. Ill-conceived and utimately would do more harm than good.
Isn't it going to sort of hard to regulate this, since Contractors are not supposed to use appropriated funds for these type of activities in the first place? This will be an VERY interesting debate, especially if the Obama Administration eventually wishes to consider personal political contributions on the part of company owners or officers as part of the evaluation - contract award process.
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Asia Chartbook: Crises, Credit and Debt, 1835-2013
This Chartbook, which is a companion piece to Carmen M. Reinhart and Takeshi Tashiro (2013) "Crowding Out Redefined: The Role of Reserve Accumulation," focuses on nine Asian economies: China, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore and Thailand. Like its predecessor (Reinhart, 2010), it provides a pictorial history, on a country-by-country basis. In addition to public debt, we trace out the evolution of its composition between domestic and external borrowing. Total external debt (public and private) and domestic credit are also included through 2013. This combination gives a broad (but not complete) picture of a country's indebtedness. It should be ideally supplemented (where relevant) by indicators and trends in the shadow banking sector, as discussed in Shin (2013). It is also timeline of a country's creditworthiness and financial turmoil (including its history, if any, with IMF programs).
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- Ashoka Mody & Diego Saravia, 2009.
"From Crisis to IMF-Supported Program: Does Democracy Impede the Speed Required by Financial Markets?,"
Working Papers Central Bank of Chile
513, Central Bank of Chile.
- Ashoka Mody & Diego Saravia, 2008. "From Crisis to IMF-Supported Program; Does democracy impede the speed required by financial markets?," IMF Working Papers 08/276, International Monetary Fund.
- Carmen M. Reinhart, 2010. "This Time is Different Chartbook: Country Histories on Debt, Default, and Financial Crises," NBER Working Papers 15815, National Bureau of Economic Research, Inc.
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Archive for April 4th, 2012
the team: three
When you can no longer play. This is where the analogy breaks down. Because there'll come a point when we feel like we can't do it any more. We can't keep walking because it's just gotten too hard. The thing is, if God's done with your life, then He'll call you home. And if you're […]


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Discover the Edge Series of Commercial Floor Stripping Machines
The Conquest Edge Series of commercial floor stripping and scrubbing machines have been revolutionising the industry by offering chemical free stripping, massive time savings and deep scrubbing of what was traditionally described as very difficult floors. The rectangular oscillating head delivers astounding results that are sure to impress.
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The Doomsday Clock is an internationally recognized design that conveys how close we are to destroying our civilization with dangerous technologies of our own making. First and foremost among these are nuclear weapons, but the dangers include climate-changing technologies, emerging... Read More
Park is a PhD candidate in Geodetic Science, and one of the members of the Satellite Positioning and Inertial Navigation (SPIN) Laboratory at Ohio State University, where she has been a research associate for more than four years. She obtained her B.A. and M.S degrees in geoinformatics from the University of Seoul.
When North Korea conducted its second known nuclear bomb test on May 25, 2009, the country's leaders took extreme care to conceal the details of the event. They detonated the bomb a kilometer or so beneath the earth, so no radiation could escape; radiation clues could have enabled member countries of the Comprehensive Nuclear Test Ban Treaty Organization to more accurately determine the type and size of the bomb tested.


text: Share It MainStoriesGeorgia Hosts First Healthy Athletes Event and Provides Free Follow-up Care Georgia Hosts First Healthy Athletes Event and Provides Free Follow-up Care Giorgi Datunashvili, a Special Olympics athlete from Georgia, grins as Dr. Giorgi Dugashvili completes a dental exam during Georgia's first-ever Special Olympics Healthy Athletes clinic. Lynn Erickson | Oct 18, 2013 | Europe Eurasia: Georgia Giorgi Dugashvili, a dentist and new Special Olympics Special Smiles clinical director who completed his training at the 2013 Special Olympics World Winter Games in the Republic of Korea, immediately began planning for Healthy Athletes in his home country of Georgia after returning from the Games. On 28 September 2013, Dugashvili coordinated Georgia's first Healthy Athletes clinic, with 30 Special Olympics athletes completing dental examinations. During the screenings, 11 follow-up care items were identified and free follow-up care was provided on site. All aspects of this event - which also celebrated EKS Day - were completely locally funded. The host clinic, Tbilisi State Medical University Dental Clinic N1, and Tbilisi Medical University covered all of the associated fees. In addition, Dugashvili held seminars with his co-workers at the clinic prior to the event to educate them about how to provide health care to people with intellectual disabilities. Dugashvili shared, "I got involved with Special Olympics because it is very noble work. I am glad to contribute in any way that I can." About Me:Manager, Health Communications Read More Stories John Lucas: From Introvert to Spokesman in BrazilCaroline ChevatA Special Olympics athlete took part in the signing of an agreement between Special Olympics and the International Volleyball Federation.Special Olympics Saved my Life!Marquis Antwan GarnerJuan Atilio: Overcoming prejudiceLeilani GonzalezMaking a Difference in India and NepalDavid HircockThank You, Special Olympics LouisianaJude and Paula BernardAgreement in Italy Will Boost Inclusion and RespectMaureen RabbittBelgium Athlete Addresses Experts at European ForumMartha Jo BraycichMy Coaches Were There For MeCarla SimonBond Between Student and Coach Transforms Life of Special Olympics Swimmer at YMCACarolyn GessnerIn Malta, a Proud Mother Shares Her StoryNatasha MicallefAn "Awesome" Secret: The Universal Power of Unified SportsDavid EvangelistaDo You Have A Story to Share?Share Your Story More Stories


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Chemical Society Defends Policy on Open-Access Publishing
An anonymous e-mail message accusing the American Chemical Society of opposing open-access publishing in order to preserve the profitability of its journals — and, in turn, the bonuses that its top executives receive — has prompted a public...
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text: Posted March 10, 2014 If we would take Moses at 28, I don't see why we would trade down into the 2nd round to take him. Hmmmmm Generally, when you trade down, other teams give you picks to do so. Why not get the same guy AND the extra pick? That is the idea. Share this post Link to post Share on other sites


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Qsilica ProCollagen: first formula on the Australian market to contain Lipowheat™ Collagen: it's the most abundant protein in the human body, found in bones, muscles, tendons and, as most commonly known, the skin. However, did you know it also depletes as we age? "It's what gives our skin structural support," says naturopath Shelley Atkin. "When ...
Lifestream International has launched a high strength supplement, which may contribute benefits to a heart-healthy diet and lifestyle regimen. Formulated with widely researched, antioxidant-rich polyphenol, resveratrol, as well as tart cherry, Lifestream HEART HEALTH+ may help foster healthy sleep patterns, a habit which could lower stress levels. As with all Lifestream products, HEART HEALTH+ does ...
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"Shannon is not only highly effective at what she does, but she is a sheer joy to work with. She is a bright spirit that brings passion to every project that she works on. She is also a great writer and highly organized, and helped me garner great media for my book in the Australian and New Zealand markets."Kimberly Snyder, author of The Beauty Detox Solution and celebrity nutritionist
"I want to thank you for all the connections you've made on my behalf to promote my books. Your understanding of health and the natural way of life was clear on the first interview you did with me. I just wanted you to know how much I respect and appreciate all you do to get the word out, around the world, about healthy living. Thank you for everything."Mimi Kirk, raw food chef and author of LIVE RAW and LIVE RAW Around the World
"My joy in working with Shannon is her intuitive ability to take ideas beyond anything I could have imagined, and to do it with love, passion and joy. One of the keys in working with us in our institute is coming from the heart, and this by far is Shannon's greatest quality. She is our dear friend and trusted adviser."Lars Gustafsson, The BodyMind Institute
"Shannon has been a trusted, compassionate and incredibly professional contributor. I could leave it in her capable hands to come up with new and innovative stories each month as well as follow the brief to a high standard. Her knowledge on all things health and wellness is extensive and I will continue to work with her and recommend her for any future projects."Anji Bignell, Editor, Australian Natural Health and Nourish magazines
"Shannon is professional, punctual, detailed, delightful, full of integrity, inspiring, extremely friendly and so much fun to work with. It's evident that she loves what she does and puts her whole heart into it. I will definitely be working with Shannon again in the future and have already recommended her to every entrepreneur I know."Terra Rose Ganem, holistic health mentor
"Working with Shannon was a pure joy! She really put her heart and soul into the project and communicated every step of the way. More than just a great service provider, I would now consider her to be a friend. Highly recommended!"Katrina Zaslavsky, author of A Modern Woman's Guide to a Natural Empowering Birth
"Shannon managed communications with hundreds of journalists at our organization with grace and humor. She is a wonderful collaborator and is very self-motivated. Able to nimbly navigate between quickly changing priorities and maintain focus, Shannon remains calm under high pressure environments."Rose Kuo, Artistic Director, American Film Institute
"Shannon is an absolute genius when it comes to getting your message heard. Her writing touches people hearts and inspires action! Shannon is a total dream to work with, easy going yet focused, flexible yet not scared to voice something if it's heading in the wrong direction. If you want results and to share your message in authentic way, Shannon is your woman."Lisa Thompson, Fortune Events / Don Tolman


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^Bookmarking that last comment for educational purposes. Wow.
I am the Wolf...Red
Backloggery | DeviantArt
Nintendo Network ID: CanisWolfred
Posts 361 to 380 of 621
^Bookmarking that last comment for educational purposes. Wow.
@FOREST_RANGER I really appreciate all that effort you put into your suggestions, thank you it really is helpful. As I said, I plan to go back to this at some point but for now I am preoccupied with a good number of works. And when I do plan to go back to real comic art, I'll do my own thing, some light hearted adventure to get me adjusted in proper pacing and scene captures. Maybe a quest for a certain cake perhaps?
I also have to say that your comic page does look more effective in capturing the reader and again, I really appreciate the effort you put just to prove a point.
Also, Just subbed the tutorial series you mentioned at the end, it will certainly help me in my skills.
Edited on by Karakato
Double Post/bump
Okay, so I made a line art for a random OC which stumped me for a with numerous revisions. I only have Proko to thank for sparking my interest in continuing her. Currently, she's at the WIP stage since I just wanted to keep my page updated within the month but what do you guys think so far:
I've been working on a certain form of art lately called Zentangle. It's pretty much doodling patterns, and it looks a lot more complicated than it really is.
The bottom one's the most recent; I really like the way it turned out.
8 Bit Forward
My Bio, by True_Hero, and another by Dark-Luigi. Oh, and a Kid Icarus one, too, created by Cyb3rnite.
deviantART Profile
Nintendo Network ID: NintenDash | Twitter: KiDasharus
I really like that last one. I remember I used to do that stuff before I even knew about it as a way to relieve stress before doing a big project. It's also good for getting in the right mindset for drawing and losens up your hand muscles...I should probably try that again.
Edited on by CanisWolfred
@CanisWolfred - Yeah. I'm doing Zentangle now to improve some of my drawing skills, then I'm going to go for bigger projects from there. But yeah, it's great for warming up for sure.
8 Bit Forward
My Bio, by True_Hero, and another by Dark-Luigi. Oh, and a Kid Icarus one, too, created by Cyb3rnite.
deviantART Profile
Nintendo Network ID: NintenDash | Twitter: KiDasharus
@3Dash yeah, the third Zentangle looked mesmerizing the moment I checked your page. I never tried that kind of method before, I always messed with a large blob of Kneaded eraser as a warm up. Weird yes, but it gets me pumped up for a reason.
Whoa, that zentangle made a knot in my brain @_@
I feel the urge to put that lineart into a coloring book haha
Twitter: SStaters
If any Pokémon-loving artists are interested someone's currently set up a project to try and get a different artist to draw every single Pokémon (I've claimed Whiscash because look at that face ). All the info's in this Google Doc, and just a heads up you seem to need a Twitter profile to follow his rules (and you can also check #Twitterdex to see pictures people have already finished). So go nuts and draw some Pokémon
Why not check out my webcomic? Maybe?
Twitter: Lindemannade
@RaReRux I'd love to be that great when doing Watercolor traditionally or digitally. Your work is just serene and I like how peaceful that nymph is.
Anyway, just finished an infograph on a certain case study I just crammed for, and I somehow managed to fit in a comic for some reason. I felt it could stand on its own so I uploaded it.
^That's surprisingly smart. I like it.
Also, I haven't had time to draw in weeks until yesterday...only to completely forget what I was trying to draw. I got a half-finished picture here, but I'm not even sure what it is. -_-;
Okay, decided to try out a new style after reigniting my interests in vector art. And since I'm a nut for Mega Man, I decided to do another robot master fan art:
Larger Image
Finished this picture of my hand the other day. It turned out pretty well, but it looks kinda smudgy in areas, even though I didn't shade using my fingers.
Also, I know Karakato saw this, but apparently I forgot to post it here. This was for my drawing class and uses six methods of drawing, so that's why it looks a bit odd. I used this as reference.
Top Left: Hatching with colored pencil
Top Right: Graphite powder
Middle Left: Pointillism with markers
Middle Right: Hatching with pencil
Bottom Left: Cross-hatching with pencil
Bottom Right: Scribbling with pencil
8 Bit Forward
My Bio, by True_Hero, and another by Dark-Luigi. Oh, and a Kid Icarus one, too, created by Cyb3rnite.
deviantART Profile
Nintendo Network ID: NintenDash | Twitter: KiDasharus
I've made another version of Majora's Mask:
What do you guys think of these? No one has responded to me yet to give me some feedback.
Edited on by Link-Hero
The mask looks great! I'm wondering what it would look like if you put the white outline one over the third one here?
Is this what you wanted?
So there are two Art Collaborations I'm taking part in and am asking whom among you are interested in joining in and showing off their creative talents. So the first one I'm joining is the Dragon Ball Collab. Basically, you can pick among the choices of all the characters from the OG DB to the Buu saga of DBZ. There are still a lot of spots left so there are still good characters to choose from. I myself chose Burter. If you are interested in joining, check out the link for more details.
The second Collab, is the Mega Woman Gender Swap Collab For anyone interested, there are 9 slots left. Sure the one's left are obscure, but they are still interesting enough in their own right and can provide a good creative challenge. I already submitted my entry (two drawings to be exact) and I'll just post one of them here:
Edited on by Karakato


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Professor Kate Conigrave
Conjoint Professor, Addiction Medicine, Head, Indigenous Substance Misuse Programs
Addiction Medicine, Central Clinical School
|+61 2 9515 8650
|+61 2 9515 5779
Biographical details
Kate is an Addiction Medicine Specialist and Public Health Physician based at Royal Prince Alfred Hospital. Her work combines treating individuals with alcohol, drug and tobacco problems; promoting the health of communities; and research and teaching.
Research interests
Kate's research focuses on reducing the impact of alcohol and drug use on health. She has a special interest in early detection and asssitance for alcohol problems, and on putting best evidence into day-to-day practice. Over the past 15 years Kate has worked in partnership with Aboriginal communities in research and health professional training initiatives to prevent or treat substance misuse.
Teaching and supervision
Kate teaches a wide range of health professional students, including in medicine and in public. She provides clinical training sessions to practising health professionals, including doctors and Aboriginal drug and alcohol professionals.
Kate was an editor of the book "Addiction Medicine" which was published internationally as a clinical guide for doctors and nurses. She was also one of six editors of the "Handbook of Aboriginal Drug and Alcohol Work" which was written to help Aboriginal and Torres Strait Islander health professionals working in the frontline of this challenging field.
Current research students
|Project title
|Research student
|Attitudes of Youth Towards Alcohol in Muslim Majority Countries (MMCs): Insights from Iraq.
|Mustafa AL ANSARI
Current projects
Kate leads teams on two NHMRC-funded research projects in the field of alcohol use and Indigenous Australians. These are being conducted in partnership with Aboriginal agencies and services, including the Aboriginal Drug and Alcohol Council, SA and Inala Indigenous Health Service. Team members also come from several other universities.
The first, aims to develop and test a tablet computer app to make it easier for Aboriginal and Torres Strait Islander people to recount their alcohol use for surveys or in a clinical setting. National surveys are used by governments to inform planning and funding decisions, so accurate data is important. This new app is being designed to help overcome language barriers in remote settings, and to overcome challenges in estimating alcohol consumption when people share alcohol or drink in non-standard drinking containers. The tablet computer app should provide a confidential and accessible way for communities to collect data on drinking. It is likely to also have clinical uses.
The second project, starting in June 2016, is a large trial of approaches to support Aboriginal community controlled primary health care services to optimise detection and treatment of alcohol problems. In any primary care service there are many barriers to doing this. In primary health care services for Indigenous Australians, there are extra challenges, including time pressures, and the complex health and social needs of patients. This project supports sharing of skills and expertise between services. Services will also receive support, opportunities for ongoing skills development and regular feedback on their performance. The approaches will be designed to provide a model for continuing quality improvement in routine clinical practice.
Awards and honours
Kate was part of a team which won two awards in 2014 for work led by Illawarra Aboriginal Medical Service. This involved setting up an alcohol home detoxification program (the 'A Clinic'). This included the 'Best Program' award from the Aboriginal Drug and Alcohol Network, NSW and award for Continuity of Care in Aboriginal Health, from the NSW Ministry of Health (NSW Aboriginal Drug and Alcohol Awards).
Kate received the Senior Scientist Award from the Australasian Professional Society on Alcohol and other Drugs in 2007
Substance abuse and addiction; Public health; Health practice; Alcohol; Indigenous health
Clinical Specialty
Addiction Medicine
Selected grants
- Better methods to collect self-report data on alcohol use behaviours from Aboriginal and Torres Strait Islander Australians; Conigrave K, Lee K, Room R, Chikritzhs T, Hayman N, Gray D, Wilkes E, Wilson S, Callinan S; National Health and Medical Research Council (NHMRC)/Project Grants.
- A model of outpatient alcohol withdrawal management for Aboriginal Australians; Conigrave K, Brett J; Foundation for Alcohol Research and Education/Research Support.
- Unmet healthcare needs and barriers to healthcare utilisation of young Aboriginal drug users in inner city Sydney: a pilot study; Conigrave K, Day C; Health Administration Corporation/Drug and Alcohol Research Grant.
- Set-up of the centre of excellence - indigenous substance misuse.; Conigrave K; Alcohol Education and Rehabilitation Foundation/Research Grant.
- Early intervention for hazardous alcohol use: an eight year follow-up; Conigrave K, Saunders J, Hall W; National Health and Medical Research Council (NHMRC)/Project Grants.
Selected publications
Handbook for Aboriginal Alcohol and Drug Work (University of Sydney, 2012)
Addiction Medicine (Oxford University Press, 2009)


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- Report: #240334
Report - Rebuttal - Arbitrate
Complaint Review: Zenni Optical
Zenni Optical27 Sunny Oaks Dr. San Rafael, California U.S.A.
Zenni Optical Rip-off; Poor quality products and very poor customer relations. San Rafael California
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Well, when it came time to order more glasses, I called and referenced the email. I was told that the representative that had told me I would get 50% off no longer worked there and was not authorized to offer that discount and they would not honor it. I asked to speak with the manager. The lady (who was very rude as soon as I told her what I wanted) told me she was the owner. I called my credit card company since they protect me from rip-offs when I purchase with their card. They advised me to order the second pair of glasses and then request the 50% off again since they could not do anything about the orginal purchase, being a little over a year old. I ordered glasses again and again, Zenni Optical would not honor their 50% off commitment. My credit card company credited me the 50%. I don't know if they sought recourse from Zenni Optical or not.
My titanium frame of my new glasses broke yesterday (Glasses were shipped on 11/26/06 and arrived in early December). So, my $68.00 titanium frame glasses (an extremely strong frame according to their website) lasted about 3 1/2 months. When I called, they said that frame is no longer available and I would have to order (and pay for) new glasses. FAT CHANCE!!! If the frame was still available, I could have purchased it for half price and installed my lenses in the new frame.
Side note. The first pair of glasses came apart where the bridge piece attaches to the frame on one side and according to a local eyeglass shop cannot be repaired (titanium can't be soldered or welded). They also said they broke because they were mismanufactured. The happened less than a month after I received the glasses but because of a death in the family and other more pressing problems, I resorted to my old pair of glasses and did not contact Zenni Optical for several months. At that time, they said the glasses were out of warrentee which is very understandable. However, I have now had 2 pair of Zenni optical glasses, both broke after a short time of use and customer service was lousy both times.
Beware. Zenni Optical is not someone you want to deal with.
Santa Barbara County, California
This report was posted on Ripoff Report on 03/22/2007 05:49 PM and is a permanent record located here: http://www.ripoffreport.com/r/Zenni-Optical/San-Rafael-California-94903/Zenni-Optical-Rip-off-Poor-quality-products-and-very-poor-customer-relations-San-Rafael-240334. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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