text:
A Systematic Review Of Genetic Polymorphisms and Breast Cancer Risk
Alison M. Dunning, Catherine S. Healey, Paul D. P. Pharoah, M. Dawn Teare, Bruce A. J. Ponder and Douglas F. Easton
Alison M. Dunning
Catherine S. Healey
Paul D. P. Pharoah
M. Dawn Teare
Bruce A. J. Ponder
Douglas F. Easton
DOI: Published October 1999
Studies investigating the relationship between common genetic variants and cancer risk are being reported with rapidly increasing frequency. We have identified 46 published case-control studies that have examined the effect of common alleles of 18 different genes on breast cancer risk. Of these, 12 report statistically significant associations, none of which were reported by more than one study. However, many of the studies were small: 10 of the 46 had 80% power or greater to detect a rare allele homozygote relative risk <2.5. We therefore combined the results of individual studies to obtain more precise estimates of risk. Statistically significant differences in genotype frequencies were found in three case-control comparisons of unselected cases. These were for CYP19 (TTTA)n polymorphism [(TTTA)10 carrier odds ratio (OR) = 2.33; P = 0.002], the GSTP1 Ile105Val polymorphism (Val carrier OR = 1.60; P = 0.02), and the TP53 Arg72Pro polymorphism (Pro carrier OR = 1.27; P = 0.03). In addition, the GSTM1 gene deletion was found to be significantly associated with postmenopausal breast cancer (null homozygote OR = 1.33; P = 0.04). There was also some evidence that homozygotes for the PR PROGINS allele are protected against breast cancer, although this result was of borderline statistical significance. For polymorphisms in BRCA1, COMT, CYP17, CYP1A1, NAT1, and NAT2, the best estimate of risk either from the individual studies or the meta-analyses was sufficiently precise to exclude a relative risk of 1.5 or greater. For the polymorphisms in EDH17B2, ER, CYP2D6, CYP2E1, GSTT1, HSP70, and TNFα, the risk estimates, although nonsignificant, were insufficiently precise to exclude a moderate risk (>1.5). Precise estimation of the risks associated with these and other as yet untested genes, as well as investigation of more complex risks arising from gene-gene and gene-environment interactions, will require much larger studies.
Breast cancer is a common disease in Western societies, with a lifetime prevalence of 1 in 12 in the United Kingdom (1) and 1 in 8 in the USA (2) . Although 10–15% of breast cancer cases have some family history of the disease, only 5% can be explained by rare, highly penetrant mutations in genes such as BRCA1 and BRCA2 (3) First-degree relatives of breast cancer patients have a 2-fold increase in risk over the general population (4) , most of which cannot be accounted for by BRCA1/2 (5) . Although some of the familial risk may be due to shared environment, there may be other common, low-penetrance genetic variants which alter predisposition to breast cancer.
A frequently used experimental design for identifying common low-penetrance alleles is the association study (6) . In this design, polymorphic genotype frequencies are compared between groups with different phenotypes. The aim is to study polymorphisms that may either be causally related to disease risk or are in strong linkage disequilibrium with disease-causing variants. Phenotypes investigated can be either continuously variable, such as serum lipid levels, or discrete, such as disease cases versus matched controls, in which instance the study design is a classic case-control study. The simplest polymorphisms to use are biallelic, which most commonly arise from a SNP,4 and give rise to three different genotype classes: the common allele homozygote, the heterozygote, and the rare allele homozygote. Multiallelic, repeat length polymorphisms (microsatellites), such as the (TTTA)n polymorphism in CYP19, can also be used, but these usually give rise to many genotypes. Genotypes often are grouped to simplify analysis, but this is valid only if a rational grouping strategy can be applied. Furthermore, the higher mutation rate in microsatellites is likely to lead to weaker associations unless the polymorphism itself is functional (e.g., the androgen receptor polyglutamine tract and prostate cancer risk). Genetic association studies using populations are more powerful than linkage studies within pedigrees for identifying low-penetrance alleles, which by definition may not be expressed in multiple members of a single family (7) . However, at present, association studies can be carried out only on candidate genes.
There are a variety of ways of presenting gene polymorphism data in relation to breast cancer risk, depending on the nature of the polymorphism. In the case of simple biallelic polymorphisms, allele frequencies in cases and controls can be compared using the χ2 test to ascertain statistical significance. However, this method does not produce an easily interpretable measure of the magnitude of breast cancer risk and also lacks statistical power compared with some alternatives. A more appropriate method is to compare genotype frequencies of the three possible genotypes among cases and controls. The relative risk of breast cancer for each genotype is then estimated by the OR. The baseline group is usually the common allele homozygote, which by definition has an OR (and relative risk) of 1. Depending on the allele frequencies, the number of rare allele homozygotes may be very small, particularly in small studies, and the associated OR will have a wide confidence interval. Under these circumstances, it is common to combine the heterozygotes and rare-allele homozygotes and calculate the rare allele carrier OR. However, this risk estimate is valid only if the genetic model is dominant, an assumption that should not be made without appropriate evidence. For multiallelic polymorphisms, it is common to group alleles together and analyze the data in the same way as for a biallelic polymorphism.
The first low-penetrance breast cancer susceptibility locus identified by the association approach was the HRAS1 minisatellite (8) . This has more than 30 alleles, of which 4 are common, whereas the rest, which have a combined frequency of ≈0.06, are classified as "rare." These rare alleles have been found to be associated with a 1.9-fold increased relative risk of breast cancer (and increased risk of other cancers) and are estimated to account for 9% of all breast cancer incidence. However, the molecular mechanism underlying this association remains unclear. The HRAS1 locus has been reviewed extensively (8 , 9) and so will not be considered further here.
Association studies have also been performed on other genes with putative involvement in breast cancer susceptibility. The candidate genes studies thus far can be divided into three main groups: genes for proteins with roles in steroid hormone metabolism; genes coding for carcinogen metabolism enzymes; and common alleles of genes that have been identified through family studies such as TP53 and BRCA1. The candidate gene polymorphisms reviewed here are listed in Table 1<$REFLINK> .
Genetic polymorphisms investigated in relation to breast cancer risk
Steroid Hormone Metabolism Genes.
Several factors alter exposure to endogenous hormones, and many of these, such as age at menarche, age at first pregnancy, number of pregnancies, and age at menopause, alter breast cancer risk (10) . Hence, genes involved in the metabolism of sex hormones are strong candidates for breast cancer susceptibility genes. Those in the sex hormone biosynthesis pathway may affect production of, and thus exposure to, the most active estrogen; estradiol. Genes in this pathway include CYP17, CYP19, and the gene for 17β-hydroxysteroid dehydrogenase type 2.
The bioavailability of hormones is partially controlled by catabolism, and catechol estrogens (2 hydroxy-estrogens) are the major breakdown products of estrogens. COMT is a phase II enzyme that methylates catechol-estrogens during their conjugation and inactivation. It has two forms: one membrane-bound and the other cytosolic; both are expressed in breast tissue and share a polymorphism associated with differences in methylation activity.
The sex hormones control the activation of responsive genes by first binding to specific receptors and forming complexes that can in turn bind to sequences in the promoters of downstream, hormone-responsive genes. Thus, steroid hormone receptor genes, such as ER, PR, and AR, are candidates for breast cancer susceptibility genes.
Carcinogen Metabolism Genes.
Several enzymes have evolved for the detoxification of xenobiotic compounds, and their gene expression is induced in response to the presence of the compound (e.g., polycyclic aromatic hydrocarbons found in tobacco smoke). The actions of phase I and phase II enzymes render susceptible compounds more soluble and more readily excreted and ought to reduce cancer risk. However, the more soluble products of some compounds are even more potent carcinogens than the less soluble form. Hence, a genetic change that increases the expression of the gene or the activity of the protein produced may increase the amount of reactive carcinogen formed and, thus, increase the risk of cancer.
Two phase I enzymes, CYP1A1 and CYP2D6, are induced by, and act on, carcinogens found in tobacco smoke. Both have polymorphic differences in either inducibility or activity. CYP2E1, an enzyme that metabolizes ethanol, is also a candidate because epidemiological studies suggest that breast cancer risk is increased with alcohol consumption (11) .
The GST family are phase II enzymes that detoxify carcinogens and their reactive intermediates, such as those produced by CYP1A1, by facilitating their conjugation to glutathione and subsequent excretion. For both GSTM1 and GSTT1 [reviewed by Rebbeck (12)] , a high percentage of the Caucasian population are homozygous for null alleles (up to 60 and 20%, respectively) and have no detoxifying GST activity. Levels of DNA adducts, sister-chromatid-exchange, and somatic genetic mutations may be increased in carriers of GSTM1 and GSTT1 null genotypes (12) .
The N-acetyl transferases, NAT1 and NAT2, are also phase II enzymes, and they participate in the detoxification of the arylamines, some of the main carcinogenic components of tobacco smoke, and also the amines produced during the cooking of meat (13 , 14) . However, the action of NATs on these carcinogens can produce electrophilic ions that may induce point mutations in DNA. Polymorphism in both genes results in two phenotypes: slow acetylators who are homozygous for low-activity alleles, and fast acetylators who carry one or more high-activity alleles.
Common Alleles of High-Penetrance Genes.
Mutations in the TP53 and BRCA1 genes are associated with a high lifetime risk of breast and other cancers (15 , 16) . TP53 is a tumor suppressor gene whose protein is produced in response to DNA damage through radiation or genotoxic agents, resulting in cell cycle arrest in G1 and induction of pathways leading to DNA repair or apoptosis. Mutation in the TP53 gene results in decreased p53 activity, which may lead to failure of cells with DNA damage to arrest and thus to continue to replicate with damaged DNA. In the case of BRCA1, where the protein function is still uncertain, the majority of confirmed mutations generate truncated proteins that are likely to have severely reduced activity. It has been hypothesized that amino acid substitutions outside the major functional domains may confer more moderate breast cancer risks. The majority of these substitutions are rare (17) , and putative functional effects remain unconfirmed. However, it has been possible to test empirically the risks associated with the common polymorphisms.
Some of the genes discussed above have been assessed in multiple studies, whereas attempts to replicate the findings of other studies have yet to be reported. Here we have attempted to identify all of the published reports. Because most of these are based on small sample sizes, we have combined the results where possible in meta-analyses to obtain more precise estimates of risk. We discuss the implications of these findings and highlight areas where further work could be carried out profitably.
Literature Search.
Published studies were identified using the Medline (National Library of Medicine, Washington DC) and BIDS databases for 1983–July 1998, using the search terms "breast-neoplasms" and "polymorphism(s)." We also searched for studies on each specific candidate gene: for example, for CYP17 the terms "CYP17" and "breast neoplasm" were used. In addition, the bibliographies of studies identified by the electronic searches were hand searched. Eligible studies were those that compared genotypic or allele frequencies of candidate genes in a series of breast cancer cases with a series of non-breast cancer controls using genomic DNA. Studies in which tumor DNA was used from cases with genomic DNA from controls were excluded. Studies of HRAS alleles and breast cancer risk were also excluded because these have been reviewed extensively by other authors (8 , 9) .
Meta-analysis.
Whenever possible, raw data from comparable studies were analyzed jointly, using likelihood methods. Analyses were based on logistic regression and were carried out using the program S Plus. Each study was treated as a separate stratum, and the (control) allele or carrier frequencies in each study were permitted to be distinct, enabling studies with very different population frequencies to be considered jointly. For those metabolic polymorphisms associated with a specific phenotype, the principal analyses combined genotypes by phenotype classes (for example, poor metabolizer, slow acetylator). For all other polymorphisms, ORs were compared for each genotype. Genotype-specific ORs were estimated assuming that the genotype frequencies in controls were consistent with Hardy-Weinberg equilibrium (18) . Likelihood ratio tests (with degrees of freedom equal to number of genotypes − 1) were then used to test whether the ORs differed significantly from 1. If significant evidence of an association was found, a test for heterogeneity was performed. Ninety-five percent confidence intervals were calculated by direct examination of the likelihood surface. Joint analysis by subgroup (e.g., menopausal status) could only be performed if studies reported results for each subgroup. Specific analysis considering confounding factors such as age was not possible because raw data were not available.
We identified 46 eligible studies (19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64) , which are listed in Table 2<$REFLINK> . Although the basic study designs were all the same, a wide variety of sources of both cases and controls were used. Most reported studies were quite small: the median number of cases and controls combined was 391 (range, 58–1431).
Description of association studies of genetic polymorphisms and breast cancer risk
The results of the individual studies are given in Table 3<$REFLINK> , which shows the relative risk of breast cancer associated with the different polymorphisms as estimated by the OR and 95% confidence interval. To present these data in a coherent and easily comparable manner, we have given the genotypic risks. If these were not reported by individual studies, wherever possible, we have estimated the appropriate ORs and confidence intervals from the published raw data.
Table 2A
Genetic risks of breast cancer by gene and study
Although 18 genes have been studied, few investigators have reported significant risks, and where significant results have been reported, these have often not been confirmed by other studies of the same polymorphism. The associations that have been reported as significant by at least one study are discussed below.
The COMT Val158 Met polymorphism has been investigated in three studies. Thompson et al. (60) , found a significantly increased risk of premenopausal breast cancer in COMTMet carrier women, with a nonsignificantly reduced risk of postmenopausal cancer. However, an earlier study had reported the opposite (although nonsignificant) effects for the same genotype, i.e., a reduced risk of premenopausal cancer and an increased risk of postmenopausal breast cancer (39) , and a third study found no effect in unselected cases (51) . Conflicting results have also been reported in four studies of the 1931T→C polymorphism in the CYP17 promoter. Fiegelson et al. (30) found an increased risk of breast cancer for the CYP17C carrier in a subgroup analysis of 40 advanced cases, a finding not confirmed in three other studies (29 , 35 , 62) . A possible role for CYP19 in breast cancer has been suggested by Haiman et al. (32) and Kristensen et al. (37) reported an increased risk for carriers of the (TTTA)12 alleles; however, another group reported a statistically significant inverse association for this allele (55) , and our own unpublished data have failed to confirm a significant risk (65) . Haiman et al. also found a significantly increased risk for carriers of the rare (TTTA)10 allele (32) , but again this finding has not been confirmed by others (55 , 65) . Of two studies of the estrogen receptor gene polymorphism, CCC325CCG, one found a significantly elevated risk for the G carrier (42) , but a subsequent, larger study failed to confirm this result (58) .
One or more of four different polymorphisms in CYP1A1 have been assessed in four different studies, two of which have investigated the role of these polymorphisms in Caucasians and African Americans separately. The only significant result reported was in the study of Taioli et al. (59) , who found an increased breast cancer risk for African-American women who were CC homozygote for the 3′UTR T→C (T6235C). In contrast, the other study of African-American women found a nonsignificantly reduced breast cancer risk associated with this genotype (23) . Of five studies of the GSTM1 gene deletion, only one found that null individuals were at significantly increased risk (34) , and in subgroup analysis, this effect was restricted to postmenopausal breast cancer. Charrier et al. (26) also found a significantly increased risk of breast cancer in the subgroup of patients diagnosed over the age of 50.
Other Genes.
A significant effect of the Arg72Pro polymorphism in TP53 has been reported by Sjalander et al. (56) , who found that TP53Arg/Pro heterozygotes were at increased risk, as were TP53Pro carriers. Pro homozygotes were also at increased risk, although the confidence intervals were wide and the effect was not statistically significant. Two other studies of the same polymorphism had found no significant effect (43 , 61) . The genes HSP-70 and TNF-α have been investigated by one group, which found significantly increased risk for rare allele carriers of both genes (see Table 3<$REFLINK> ). However, this study was small, and their results have not been confirmed or refuted by other groups.
Comparable data from more than one study that could be combined were available for 25 different combinations of polymorphism and patient subgroups. The results of these analyses are given in Table 4<$REFLINK> . Statistically significant differences in genotype frequencies were found in three case-control comparisons of unselected cases. These were for CYP19 (TTTA)n polymorphism [(TTTA)10 carrier OR = 2.33; P = 0.002], the GSTP1 Ile105Val polymorphism (Val carrier OR = 1.60; P = 0.02), and the TP53 Arg72Pro (Pro carrier OR = 1.27; P = 0.03). In addition, the GSTM1 gene deletion was found to be significant in postmenopausal breast cancer (null homozygote OR = 1.33; P = 0.04). There was also some evidence that homozygotes for the PR PROGINS allele are protected against breast cancer, although this result was of borderline statistical significance.
Table 3B
Results of joint analysis
Gene-Environment Interaction.
Although there is little epidemiological evidence that cigarette smoking is associated with breast cancer, studies have assessed the possible interaction between polymorphisms in the genes that encode carcinogen-metabolizing enzymes, CYP1A1, NAT2, CYP2E1, and GSTM1, with smoking (20 , 21 , 40 , 41 , 44 , 50 , 54) . None of these studies found an overall increase in breast cancer risk with the variant genotypes, but some reported interactions with smoking. Ambrosone et al. (20) found an increase in risk in "light" smokers who carried the Val462 allele. In contrast, Ishibe et al. (41) found no interaction with the Ile462Val polymorphism but did find an increased risk in current smokers who were C carriers of the T6235C polymorphism. For NAT2, Ambrosone et al. (21) found an association between smoking >15 cigarettes per day and risk that was limited to slow acetylators, but two subsequent larger studies found that cigarette smoking was not appreciably associated with breast cancer among either fast or slow acetylators (40 , 50) . CYP2E1 genotype and smoking has been investigated in one study (54) , which found a risk of premenopausal breast cancer in smokers who were also carriers of the DraI cutting site in intron 6. However, this result was only statistically significant after adjustment for other risk factors, and the confidence intervals were wide. A lack of interaction between GSTM1 genotype and cigarette smoking has been reported by Kelsey et al. (44) .
Lavigne et al. (39) looked for interactions between the Val158 Met polymorphism in the COMT gene and several factors including family history, menopausal status, smoking, alcohol, oral contraceptive use, and hormone replacement therapy. Helzlsouer et al. (34) also explored the possibility of interactions between GSTM1, GSTP1, and GSTT1 genotypes with family history, hormone replacement therapy, cigarette smoking, alcohol consumption, and body mass index. Although no overall effect was found in either study, both reported interactions with menopausal status and body mass index, and Helzlsouer et al. (34) additionally noted an interaction between GSTT1 and alcohol consumption. However, no studies attempting to confirm these quite complex interactions have yet been published.
Gene-Gene Interaction.
The possibility of gene-gene interactions have rarely been explored. One small study carried out genotyping in three genes: CYP1A1, GSTM1, and GSTT1 (23) . No interaction between these genes was found. The studies of Helzlsouer et al. (34) on the GST genes and Lavigne et al. (39) on COMT were carried out on the same populations. The increased relative risk of postmenopausal breast cancer for GSTM1Null and GSTP1Ile/Val/GSTP1Val/Val women of around 2 was found to be increased to a 3–4-fold increased risk if they were also COMTMet/Met. Again, no confirmatory studies have yet been published.
We have found a substantial number of reports of studies that have investigated candidate genes for low-penetrance breast cancer susceptibility alleles. Despite this research effort, there is no clear evidence that any of these polymorphisms are strongly associated with breast cancer risk. Of the individual studies, few of the reported associations have been statistically significant, and no significant association has been reported by more than one study. In some cases, this might be due to a lack of statistical power in individual studies. Even among the significant associations, the magnitude of the effect found is rarely greater than 2.5-fold increased risk. If the rare allele frequency is 0.2, 315 cases and 315 controls would be required to detect this magnitude of risk for a rare allele homozygote with 90% power at the 5% significance level: 10 of the 46 studies reported were larger than this.
We have attempted to reduce this lack of power by combining results in meta-analyses, but even the results of these need to be interpreted with some caution. Of the 25 associations tested in at least two studies, 4 were significant at the 5% level. One of these was significant only in a subgroup of cases (postmenopausal) and was not significant overall. Such subgroup-specific associations must always be treated with caution given that there is no clear a priori reason to suspect a subgroup effect. Moreover, only one of the associations has a significance levels of <1%. Given the number of polymorphisms being tested, a significance level of 10−4 or smaller would be required to provide strong evidence.
In any systematic review, a major cause for concern is the potential for publication bias. The most common scenario is the nonpublication of negative studies (i.e., those finding no significant association), resulting in bias of any meta-analysis away from the null. We cannot exclude this possibility for the three polymorphisms with significant results in the meta-analyses. For the polymorphisms for which we have found no evidence for an association between genotype and breast cancer risk, it is possible, but unlikely, that bias toward the null has occurred. There is an urgent need for databases into which the results of all association studies (positive and negative) with candidate genes can be entered to minimize the effects of publication bias.
Consistency of reporting added further complications to the meta-analysis; many studies do not describe the ethnicity of their study populations; therefore, we have combined samples on the assumption that any variant studied will have the same effect in all populations. This assumption may only be valid if the variant studied is truly functional with respect to breast cancer risk. If the variant is simply a neutral marker for some other functional variant, the assumption may be invalid because linkage disequilibrium relationships often differ between populations. In addition, there is no consensus nomenclature for SNPs: early reports often described the restriction enzyme site involved, but there are instances of multiple polymorphisms detected by the same restriction enzyme within a single gene (e.g., there are two polymorphisms creating MspI sites in CYP1A1). More recent studies usually identify the base substitution, but in introns and UTRs of genes, this can also be arbitrary. In Table 1<$REFLINK> , we presented the SNP and its general position (e.g., exon 3, intron 6, 3′UTR) for clarity, but workers will need to refer to the original articles for sufficient detail to replicate the DNA assays. The requirement for public databases of SNPs has recently been recognized (66) , and it is hoped these will then provide a standardized description. Furthermore, methodological difficulties have been caused by genes having several different polymorphisms in linkage disequilibrium with one another. For example, CYP1A1 has two SNPs in strong linkage disequilibrium with one another; these are the exon 7 Ile462Val and the 3′UTR T→C (T6253C) SNPs. Both have been shown to be significantly associated with risk of some neoplasms (although not breast cancer), but combining them in a meta-analysis would require a somewhat more complicated analytical approach.
Several studies have reported on putative gene-gene and gene-environment interactions. The results of these analyses should, however, be treated with caution. The problem of post hoc subgroup analyses and multiple hypothesis testing renders the interpretation of positive results difficult. Negative results also should be treated with caution because few studies will have had sufficient power to detect moderate interaction effects. For example, 1500 cases and 1500 controls would be required to detect an interaction between two genotypes each with a frequency of 0.1 and a relative risk of 1.1 but with a relative risk of 2.5 when combined. These analyses should, therefore, be treated as hypothesis generating rather than hypothesis testing.
Despite these concerns, we believe some firm conclusions can be drawn. For several polymorphisms, the best estimate of risk either from the individual studies or the combined meta-analyses is sufficiently precise to exclude a relative risk of 1.5. These include the polymorphisms in BRCA1, COMT, CYP17, CYP1A1, NAT1, and NAT2. This does not necessarily imply that a negligible fraction of breast cancer incidence is attributable to such genes. For example, the upper confidence interval for the CYP17 effect (1.39) would still correspond to a population-attributable fraction of ≈20%. We have, however, concluded that these polymorphisms contribute little to the familial aggregation of breast cancer: the same effect would correspond to a relative risk to siblings of cases of ≈1.01 [for details of calculation, see Easton (67)] , whereas epidemiological studies have found the relative risk to be ≈2-fold.
For other polymorphisms, the risk estimates, although nonsignificant, are insufficiently precise to exclude a moderate risk (>1.5), and larger studies are needed to obtain more precise risk estimates. These include polymorphisms in EDH17B2, ER, CYP2D6, CYP2E1, GSTT1, HSP70, PR, and TNFα. Finally, the polymorphisms in CYP19, GSTM1, GSTP1, and TP53 appear to be stronger candidates for low-penetrance breast cancer susceptibility genes, although they too need to be confirmed in larger studies. It is more likely, however, that the majority in variation in susceptibility to breast cancer is due to genes that have yet to be identified or tested. Candidate genes include those involved in DNA repair and micro- and macronutrient metabolism. In addition, gene-gene and gene-environment interactions may be important determinants of breast cancer risk. Such interactions would produce substantially increased risks in individuals with the right combination of factors, but large studies would be required to elucidate these effects. Further work is clearly needed to address these issues, but these studies will need to be substantially larger than the association studies published to date.
We thank Katie Blyth (Department of Pathology, University of Cambridge) for help in obtaining references.
↵1 This work was supported by the Cancer Research Campaign (CRC). B. A. J. P. is a Gibb Fellow of the Cancer Research Campaign.
↵2 These authors contributed equally to this study.
↵3 To whom requests for reprints should be addressed, at CRC Human Cancer Genetics Group, University Department of Oncology, Strangeways Research Laboratories, Worts Causeway, Cambridge CB1 8RN, UK.
↵4 The abbreviations used are: SNP, single nucleotide polymorphism; OR, odds ratio; COMT, catechol-O-methyltransferase; GST, glutathione-S-transferase; NAT, N-acetyl transferase; UTR, untranslated region.
Accepted July 12, 1999.
Received December 3, 1998.
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Dunning A. M., Chiano M., Smith N. R., Dearden J., Gore M., Oakes S., Wilson C., Stratton M., Peto J., Easton D., Clayton D., Ponder B. A. Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population. Hum. Mol. Genet., 6: 285-289, 1997.
Dunning A. M., Healey C. S., Pharoah P. D. P., Foster N., Easton D. F., Day N. E., Ponder B. A. J. Polymorphism in the steroid metabolism gene CYP17 and risk of breast cancer. Br. J. Cancer, 77: 2045-2047, 1998.
Feigelson H. S., Coetzee G. A., Kolonel L. N., Ross R. K., Henderson B. E. A polymorphism in the CYP17 gene increases the risk of breast cancer. Cancer Res., 57: 1063-1065, 1997.
Garrett E., Rowe S. M., Coughlan S. J., Horan R., McLinden J., Carney D. N., Fanning M., Kieback D. G., Headon D. R. Mendelian inheritance of a TaqI restriction fragment length polymorphism due to an insertion in the human progesterone receptor gene and its allelic imbalance in breast cancer. Cancer Res. Ther. Control, 4: 217-222, 1995.
Haiman C. A., Hankinson S. E., Speizer F. E., Hunter D. J. A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk. Proc. Am. Assoc. Cancer Res., 40: 194 1999.
Harries L. W., Stubbins M. J., Forman D., Howard G. C. W., Wolf C. R. Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis (Lond.), 18: 641-644, 1997.
Helzlsouer K. J., Selmin O., Huang H-Y., Strickland P. T., Hoffman S., Alberg A. J., Watson M., Comstock G. W., Bell D. Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer. J. Natl. Cancer Inst., 90: 512-518, 1998.
Helzlsouer K. J., Huang H-Y., Strickland P. T., Hoffman S., Alberg A. J., Comstock G. W., Bell D. A. Association between CYP17 polymorphism and the development of breast cancer. Cancer Epidemiol., Biomarkers & Prev., 7: 945-949, 1998.
Huober J., Bertram B., Petru E., Kaufmann M., Schmahl D. Metabolism of debrisoquine and susceptibility to breast cancer. Breast Cancer Res. Treat., 18: 43-48, 1991.
Kristensen V. N., Andersen T. I., Lindblom A., Erikstein B., Magnus P., Børresen-Dale A. L. A rare CYP19 (aromatase) variant may increase the risk of breast cancer. Pharmacogenetics, 8: 43-48, 1998.
Lancaster J. M., Berchuck A., Carney M. E., Wiseman R., Taylor J. A. Re: "Progesterone receptor gene polymorphism and risk for breast and ovarian cancer.". Br. J. Cancer, 78: 277 1998.
Lavigne J. A., Helzlsouer K. J., Huang H-Y., Strickland P. T., Bell D. A., Selmin O., Watson M. A., Hoffman S., Comstock G. W., Yager J. D. An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer. Cancer Res., 57: 5493-5497, 1997.
Hunter D. J., Hankinson S. E., Hough H., Gertig D. M., Garcia Closas M., Spiegelman D., Manson J. E., Colditz G. A., Willett W. C., Speizer F. E., Kelsey K. A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer. Carcinogenesis (Lond.), 18: 2127-2132, 1997.
Ishibe N., Hankinson S. E., Colditz G. A., Spiegelman D., Willett W. C., Speizer F. E., Kelsey K. T., Hunter D. J. Cigarette smoking, cytochrome P450 1A1 polymorphisms, and breast cancer risk in the Nurses' Health Study. Cancer Res., 58: 667-671, 1998.
Iwase H., Greenman J. M., Barnes D. M., Hodgson S., Bobrow L., Mathew C. G. Sequence variants of the estrogen receptor (ER) gene found in breast cancer patients with ER negative and progesterone receptor positive tumors. Cancer Lett., 108: 179-184, 1996.
Kawajiri K., Nakachi K., Imai K., Watanabe J., Hayashi S. Germ line polymorphisms of p53 and CYP1A1 genes involved in human lung cancer. Carcinogenesis (Lond.), 14: 1085-1089, 1993.
Kelsey K. T., Hankinson S. E., Colditz G. A., Springer K., Garcia-Closas M., Spiegelman D., Manson J. E., Garland M., Stampfer M. J., Willett W. C., Speizer F. E., Hunter D. J. Glutathione S-transferase class μ deletion polymorphism and breast cancer: results from prevalent versus incident cases. Cancer Epidemiol., Biomarkers & Prev., 6: 511-515, 1997.
Ladero J. M., Benitez J., Jara C., Llerena A., Valdivielso M. J., Munoz J. J., Vargas E. Polymorphic oxidation of debrisoquine in women with breast cancer. Oncology, 48: 107-110, 1991.
Ladona M. G., Abildua R. E., Ladero J. M., Roman J. M., Plaza M. A., Agundez J. A., Munoz J. J., Benitez J. CYP2D6 genotypes in Spanish women with breast cancer. Cancer Lett., 99: 23-28, 1996.
Mannermaa A., Peltoketo H., Winqvist R., Ponder B. A. J., Kiviniemi H., Easton D. F., Poutanen M., Isomaa V., Vihko R. Human familial and sporadic breast cancer: analysis of the coding regions of the 17β-hydroxysteroid dehydrogenase 2 gene (EDH17B2) using a single-strand conformation polymorphism assay. Hum. Genet., 93: 319-324, 1994.
Manolitsas T. P., Englefield P., Eccles D. M., Campbell I. G. Re: "No association of a 306-bp insertion polymorphism in the progesterone receptor gene with ovarian and breast cancer.". Br. J. Cancer, 75: 1398-1399, 1997.
Mavridou D., Gornall R., Campbell I. G., Eccles D. M. TP53 intron 6 polymorphism and the risk of ovarian and breast cancer. Br. J. Cancer, 77: 676-677, 1998.
Millikan R. C., Pittman G. S., Newman B., Tse C. K., Selmin O., Rockhill B., Savitz D., Moorman P. G., Bell D. A. Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk. Cancer Epidemiol., Biomarkers & Prev., 7: 371-378, 1998.
Millikan R. C., Pittman G. S., Tse C. K., Duell E., Newman B., Savitz D., Moorman P. G., Boissy R. J., Bell D. A. Catechol-O-methyltransferase and breast cancer risk. Carcinogenesis (Lond.), 19: 1943-1947, 1998.
Peller S., Kopilova Y., Slutzki S., Halevy A., Kvitko K., Rotter V. A novel polymorphism in intron 6 of the human p53 gene: a possible association with cancer predisposition and susceptibility. DNA Cell Biol., 14: 983-990, 1995.
Pontin J. E., Hamed H., Fentiman I. S., Idle J. R. Cytochrome p450dbl phenotypes in malignant and benign breast disease. Eur. J. Cancer, 26: 790-792, 1998.
Shields P. G., Ambrosone C. B., Graham S., Bowman E. D., Harrington A. M., Gillenwater K. A., Marshall J. R., Vena J. E., Laughlin R., Nemoto T., Freudenheim J. L. A cytochrome P4502E1 genetic polymorphism and tobacco smoking in breast cancer. Mol. Carcinog., 17: 144-150, 1996.
Siegelmann-Danieli N., Buetow K. H. Constitutional genetic variation at the human aromatase gene (Cyp19) and breast cancer risk. Br. J. Cancer, 79: 456-463, 1999.
Sjalander A., Birgander R., Hallmans G., Cajander S., Lenner P., Athlin L., Beckman G., Beckman L. p53 polymorphisms and haplotypes in breast cancer. Carcinogenesis (Lond.), 17: 1313-1316, 1996.
Smith C. A., Moss J. E., Gough A. C., Spurr N. K., Wolf C. R. Molecular genetic analysis of the cytochrome P450-debrisoquine hydroxylase locus and association with cancer susceptibility. Environ. Health Perspect., 98: 107-112, 1992.
Southey M. C., Batten L. E., McCredie M. R. E., Giles G. C., Dite G., Hopper J. L., Venter D. J. Estrogen receptor polymorphism at codon 325 and risk of breast cancer in women before age forty. J. Natl. Cancer Inst., 90: 533-536, 1998.
Taioli E., Trachman J., Chen X., Toniolo P., Garte S. J. A CYP1A1 restriction fragment length polymorphism is associated with breast cancer in African-American women. Cancer Res., 55: 3757-3758, 1995.
Thompson P. A., Shields P. G., Fruedenheim J. L., Stone A., Vena J. E., Marshall J. R., Graham S., Laughlin R., Nemoto T., Kadlubar F. F., Ambrosone C. B. Genetic polymorphisms in catechol-O-methyltransferase, menopausal status and breast cancer risk. Cancer Res., 58: 2107-2110, 1998.
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Zheng W., Deitz A. C., Campbell D. R., Wen W. Q., Cerhan J. R., Sellers T. A., Folsom A. R., Hein D. W. N-acetyltransferase 1 genetic polymorphism, cigarette smoking, well-done meat intake, and breast cancer risk. Cancer Epidemiol., Biomarkers & Prev., 8: 233-239, 1999.
Zhong S., Wyllie A. H., Barnes D., Wolf C. R., Spurr N. K. Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis (Lond.), 14: 1821-1824, 1993.
Healey, C. S., Dunning, A. M., Durocher, F., Teare, D., Easton, D. F., and Ponder, B. A. J. Polymorphisms in the human aromatase cytochrome P450 gene (CYP19) and breast cancer risk. Carcinogenesis (Lond.), in press, 1999.
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Easton D. F. Cancer risks in A-T heterozygotes. Int. J. Radiat. Biol., 66: S177-S182, 1994.
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text:
BA10 – Occupancy permit
Form – application
BA9 – Application for occupancy permit
Application for occupancy permit
BA8 – Notice of cessation
8 March 2019 current version Notice of cessation
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Notice of completion
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BA2 – Application for building permit – uncertified
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8 March 2019 current version – Application for building permit – certified
Building Amendment Regulations 2014
The Building Amendment Regulations 2014 (the Amendment Regulations) were published in the Government Gazette on 24 April 2014 and came into operation on 25 April 2014. The Amendment Regulations are outlined in Industry Bulletin 039 .
New bushfire measures
Planning Minister John Day recently announced that the State Government had approved measures that would see the bushfire construction requirements of the Building Code of Australia, which includes deemed-to-satisfy compliance with Australian Standard AS 3959, apply from 1 May 2015.
Consultations on the review of Strata Titles and Emergency Services Acts
We wish to draw your attention to consultations being undertaken that are of relevance to the building industry. We have provided links to the consultation information below. As these reviews and subsequent consultations are not being carried out by the Building Commission, you will need to direct any submissions or questions to the relevant agency. Details of how to make a submission are...
4th Australian Lean Construction Conference
The 4th Australian Lean Construction Conference will be held at the Perth Convention and Exhibition Centre from 12-14 August 2014. Hosted by the Lean Construction Institute of Western Australia in collaboration with RFID for Energy, Mining and Construction, the theme of the 2014 event will be "Smarter and Leaner Projects in Australia". "The conference brings together global best practices from...
Weatherproofing of projections through metal roof surfaces
The Building Commission has met with manufacturers and installers of metal roofing products to discuss ways of improving the method of flashing to the high side of the roof penetration.
Review of Construction Contracts Act signed off
A key piece of legislation that supports security of payment in Western Australia's building and construction industry will be reviewed this year. Building Commissioner Peter Gow today announced that Professor Philip Evans of Curtin University has been appointed to review the Construction Contracts Act 2004 . "The Construction Contracts Act is part of a suite of new building legislation...
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Federal and state ministers have agreed to significant building regulation reforms to the National Construction Code (NCC).
Information for builders advertising house and land packages
If you are a builder who advertises house and land packages, you are responsible for ensuring that your advertising complies with the Australian Consumer Law (WA) (ACL). The following advice, Compliance issues regarding advertising by builders, is provided to builders on behalf of the Department of Commerce's Consumer Protection division. For more information, please contact Consumer Protection...
Feedback sought on emergency egress for all report
Please note: Feedback on the report mentioned in this news item has now closed. The page has been retained for archive purposes. The Australian Building Codes Board (ABCB) has released a Directions Report on Emergency Egress For All Occupants. The report discusses potential changes to the National Construction Code (NCC) to improve emergency egress from buildings for all occupants, including...
Business as usual for Home Indemnity Insurance
A new transitional arrangement with current providers of home indemnity insurance in Western Australia will mean that it is business as usual. The transitional arrangement gives the Government time to consider and consult on recommendations in the Economic Regulation Authority's Inquiry into Western Australia's Home Indemnity Insurance Arrangements , which was tabled in Parliament in September...
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text:
Q: Twilio: Webhook not calling specified URL on phone number Setting up to respond to SMS replies.  I've gone to my Active Numbers page, selected the number (I only have one), gone to the Messaging Service section (again only one service) and in "A message comes in", I've specified the URL of one of our HTTP Handlers.  It's a .Net Core handler that we use all the time.  It will try to process anything sent to its URL:
https://ourserver/lmw/core/filemanager?SC=SMS

I send an SMS message to my personal number, reply "Help", and send that.  Nothing hits that URL.  I have it in the debugger and it catches anything I send it.  It just doesn't get hit by the reply to the SMS message.
What am I doing wrong?.. or did I misunderstand how this works?
EDIT:
I found an "Integration" section in the Messaging Service.  It was set to "Defer to sender's webhook"... which sounds right but I changed it to "Send a webhook -- Invoke an HTTP webhook for all incoming messages"... which sounds like the same thing.  Anyway, it didn't change a thing.  I'm still not receiving a post on the http handler.

A: Please note that "Help" is a special keyword when using messaging services.
According to the Twilio Help Center:

Twilio does not forward HELP/INFO messages to your incoming message webhook by default. However, if you use Advanced Opt-Out for Messaging Services, Twilio does forward HELP/INFO requests to your inbound webhook.

A: This is not a good answer but I wanted to close this out.  I started over and released my phone number and bought a new one.  I went to Active Numbers and selected the new phone. In "A message comes in", I put my webhook url in both primary and primary fails and saved that.
I then went to Messaging, Services, and selected my service.  In Integration, I clicked "Defer to sender's webhook" and then put the handler url in "Callback URL" and saved that.
I went to compliance and the first two were done but 3. Campaign Use Case was incomplete.  I completed that.
In Opt-out management, I edited that and put in some of my own text.
After doing all this, I replied to the message and got a response in the handler.  Not sure which one of these was the problem but doing it all over seemed to work.  Sorry I can't provide a better insight.

redpajama_set_name: RedPajamaStackExchange


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St. Valentine for the kids!
Carnival Kids Celebrates 20 Years!
Carnival Kids open their store in Mall of Sofia!


text:
Q: Calculating Time Difference Access Query I am trying to use a query to get a difference in time. Please see the attach screenshot for information. I am trying to find out the difference by sustracting "MapOriginalStart" from "Time". Both of them are formatted to "Short time"

A: Two simple tasks:
PM to AM conversion:
IIF([MapOriginalStart] > #12:00:00 PM#, [MapOriginalStart] - #12:00:00 PM#, [MapOriginalStart])
IIF([Time] > #12:00:00 PM#, [Time] - #12:00:00 PM#, [Time])

Time substraction:
(note that DateDiff, as referenced by @Christoph, does exist, but you can just as easily use the substraction operator -)
CDate(Abs([Time] - [MapOriginalStart]))

Note that you will probably run into trouble because you're probably not understanding time in Access properly. In Access, 12:51 AM is equal to 00:51 AM. That's a fact, and you will get incorrect results if you expect it to be greater than 10:00 AM

A: Erik is right. What you are looking for is:
TimeDiff: [MapOriginalStart] - [Time]

The result is a date value. Format that as h:nn to have it displayed as hours and minutes:
TimeDiffText: Format([MapOriginalStart] - [Time], "h\.nn")

For a decimal hour count, you can use:
Hours: DateDiff("s", [MapOriginalStart], [Time]) / 3600


text:
Open-File Report 03-79
Preliminary Preview for a Geographic and Monitoring Program Project: A Review of Point Source–Nonpoint Source Effluent Trading/Offset Systems in Watersheds
By Alexander Wood and Richard Bernknopf
Watershed-based trading and offset systems are being developed to improve policy-maker's and regulator's ability to assess nonpoint source impacts in watersheds and to evaluate the efficacy of using market-incentive programs for preserving environmental quality. An overview of the history of successful and failed trading programs throughout the United States suggests that certain political, economic, and scientific conditions within a temporal and spatial setting help meet water quality standards. The current lack of spontaneous trading among dischargers does not mean that a marketable permit trading system is an inherently inefficient regulatory approach. Rather, its infrequent use is the result of institutional and informational barriers. Improving and refining the earth science information and technologies may help determine whether trading is a suitable policy for improving water quality. However, it is debatable whether or not environmental information is the limiting factor. This paper reviews additional factors affecting the potential for instituting a trading policy.
The motivation for investigating and reviewing the history of offsets and trading was inspired by a project in the preliminary stages being developed by U.S. Geological Survey Western Geographic Science Center and the Environmental Protection Agency Region IX. An offset feasibility study will be an integrated, map-based approach that incorporates environmental, economic, and statistical information to investigate the potential for using offsets to meet mercury Total Maximum Daily Loads in the Sacramento River watershed. A regional water-quality offset program is being studied that may help known point sources reduce mercury loading more cost effectively by the remediation of abandoned mines or other diffuse sources as opposed to more costly treatment at their own sites. An efficient offset program requires both a scientific basis and methods to translate that science into a regulatory decision framework.
Download this report as a single PDF file (406 KB)
Download free PDF Reader software and to learn more about Adobe Acrobat Reader
Download a Microsoft Word version of the report (299 KB)
For questions about the scientific content of this report, contact Alexander Wood
This report is only available on the web


RUTH ANN "RUDY' PEARSON of Frankfort, Indiana, 93, Mother of Pastor Edwin Pearson, Frankfort Trinity UMC; died on Wednesday, December 23, 2015. Survivors include: daughter, Ann (Nick) Zafran of Frankfort; son, Ed (Nancy) Pearson of Frankfort; grandchildren, Nick (Heather) Zafran, Amy (Roddy) Norrod, Scott (Erin) Pearson, Kevin Pearson, and TJ Pearson; great-grandchildren, Matthew, Beatrix, and Cordelia.
A public visitation is set for Monday, December 28 from 12 p.m. until 2 p.m. at the Goodwin Funeral Home, 200 S. Main St., Frankfort, IN. A memorial service is anticipated for Monday, December 28 at 2 p.m. at the Goodwin Funeral Home, 200 S. Main St., Frankfort, IN.
Condolences may be shared with Pastor Edwin Pearson, 900 Cambridge Dr., Frankfort, IN 46041.
For more on the life and legacy of Mrs. Ruth Ann "Rudy" Pearson, click here.


text:
Coaching Doctors? First, Show Them the Evidence
By Margaret Cary, MD, MBA, MPH | Published 9/7/2017 9
What is it about physicians? The stereotype of the brilliant and bold surgeon who reigns over the operating room whose mantra is "A chance to cut is a chance to cure." The ever-smiling pediatrician wearing a bow-tie with a small elephant on his stethoscope. And the pipe-smoking psychiatrist, steeped in Freud and saying little. None of whom listens to anyone without an MD, and often not to them.
Many physicians have life and death in their hands—literally. As physicians, our training is to "fix it". Jerome Groopman shares with us that doctors usually get it right, but sometimes they don't.
"Most errors are mistakes in thinking. And part of what causes these cognitive errors is our inner feelings, feelings we do not readily admit to and often don't realize."
Show them the evidence
My work in coaching physicians lives at the interface of what they know—getting it right—and what they often don't realize, that being an effective executive leader requires additional skills and moving from linear to complex thinking. Once they realize the value of coaching in getting them there, they are ideal clients. Meet them where they live, in science. Show them the evidence, the research and they're ready to go.
Years ago, I coached an energetic, fearless surgeon who was failing badly in a new role. He was a skilled technician, performing procedures on desperate patients, often saving their lives after other surgeons had given up. He had been a rising star in an academic medical center where surgeons ruled and often were less than tactful with their colleagues, surgeons and non-surgeons alike.
I met this doctor after the CEO of a more cordial medical facility recruited him to be a department chair. Intra- and inter-professional relationships mattered at the new organization. Employees stayed forever, dedicated to the mission of putting patients first.
He was tasked to turn a failing department around, to update technologies and offer new services—big and important challenges. My coaching client had started his tenure by immediately making changes, without spending (one of the first books I asked him to read) or learning the new culture and its people. His approach came from the stereotypical academic medical center, which means it was long on telling and short on listening.
He had been hired to "turn the department around" and he was doing just that in the style of the organization he had been recruited from. That old methodology of succeeding wasn't working in the new system. He was bewildered by the switch in attitude toward him, by his colleagues complaining about him and his style. When I met him, I was the latest in a series of coaches, some of whom believed he was misguided and others who believed he was uncoachable—a lost cause.
During our coaching engagement, he grilled me at every step—what was the data? Where was it published? Without the proof of peer-reviewed articles, he seemed unenthusiastic and minimally engaged. A turning point came when I mentioned that Coursera offered a free online course in emotional intelligence, taught by Dr. Richard Boyatzis, an excellent and brilliant teacher with a world-class academic pedigree. Four weeks into the course my client said to me, "I didn't realize there was so much science, such a body of literature, in motivation and leadership."
And so our coaching continued, as did his questioning, with a difference. Now he had become deeply interested in the process. He met with each of his direct reports, apologized for his behavior and asked all for their suggestions on the future of the department. He began asking "what" questions and then listening for a maximum of three minutes before commenting. He learned to solicit opinions without appearing to attack the offerer. Eventually, and with the help of carefully chosen Harvard Business Review and medical journal articles, he learned to modulate his style to fit the organization and the importance of relationships.
Behavioral science is different from chemistry
I tell this story to illustrate the importance of evidence and of research to those who are schooled in hard science. Behavioral science is different from, say, chemistry, at least at the beginning levels. Variables in "soft sciences" are often measured in a more qualitative, or descriptive manner—measuring behavior, which is open to interpretation. In the "hard sciences" in which physicians train, variables are more amenable to a quantitative, or yes/no, manner of measuring things.
A quantitative conclusion is more concrete and often not open to interpretation. For example, "The elements combined to make a compound weighing 20 grams" compared with "When the subject was confronted with x he did y and the explanation is z." There are 20g whether you measure in ounces or kilograms; there are 20g whether you use a digital scale or a balance. On the other hand, the explanation of behavior has a lot to do with who explains it—what their training and assumptions are. The explanation is subject to variability depending on the observer, just like coaching, and that is what causes the physician to hesitate, to overthink. Just as they don't want to risk someone's life on untested treatments, they are trained to be deeply skeptical of interpretations that are not thoroughly understood.
To get physicians, and other clients, to invest in coaching, I often have to explain the theory and research behind the practice. It is not enough to point to the results and say "It works!" I have to show why they want to see the data and the interpretation. Doctors want to know the difference coaching can make in their success as leaders.
We know from research that client buy-in and readiness to change is essential for coaching to be successful. As individual coaches, how can we support physicians and other "hard-science-oriented" clients? As an executive coach for physicians, I typically start with 360 interviews to learn others' perceptions. Throughout our coaching engagement, I share articles and books—the evidence.
Since emotional intelligence is often a critical part of my clients' leadership development, if possible, I use the ability-based MSCEIT (Mayer-Salovey-Caruso Emotional Intelligence Test), a valid and reliable instrument that measures the taker's emotional intelligence in four dimensions (perceiving, understanding and managing emotions, and facilitating thought) and offers suggestions to improve the taker's emotional intelligence. Validity and reliability are foundations of the scientific method. The former refers to whether the test measures what it says it measures. The latter refers to the reproducibility of the test by other researchers. Physicians often are more trusting of instruments with these qualities.
Is Your Doctor Emotionally intelligent?
The Value of Coaching in Medicine
In the big picture, there's a lot to do. Earlier this year, Anthony Grant, Ph.D. (a prolific publisher on coaching), at the University of Sydney, published "The impact of leadership coaching in an Australian healthcare setting." The conclusion is that leadership coaching may facilitate goal attainment, foster resilience, and lead to greater ambiguity tolerance in those who are coached—all factors in preventing burnout and supporting personal growth. Dr. Atul Gawande proposed coaching for surgeons in a New Yorker article.
As one of my coaching clients told me,
"You've helped me expand my view of the world to think of consequences of my actions, take risks, and understand that it all comes down to relationships."
First posted on Library of Professional Coaching 11/21/2014 and on TDWI on 11/26/2014. It was updated on 09/05/2017.
medical education & medical students
Margaret Cary, MD, MBA, MPH
Website: https://thecarygroupglobal.com/
Margaret Cary, MD, MBA, MPH AKA Dr. Maggi, graduated from the University of California, Santa Barbara with a degree in zoology and a minor in polo. She exercised up to 23 polo ponies/day to put herself through college. Her MD is from Baylor College of Medicine, her Master's in Public Health (MPH) from UCLA, and her Master's in Business Administration from the University of Colorado, Denver. She completed her Family Medicine residency in Santa Rosa, through UCSF.
From an emergency room physician in a ski resort, Dr. Maggi has worked in nearly every aspect of health care, landing at her current post as CEO of The Cary Group Global. The Cary Group Global provides executive and leadership coaching and consulting to executives in health care and film and television production.
Dr. Maggi graduated from Georgetown University's Leadership Coaching program and holds a Professional Certified Coach (PCC) credential from the International Coach Federation. Her clients include
• Mayo Clinic,
• AMIA (American Medical Informatics Association),
• University of Massachusetts Medical School,
• Bon Secours Health System,
• Yale School of Medicine
• Weill Cornell College of Medicine,
• Georgetown University School of Medicine,
• Dubai Medical College,
• and other academic medical centers and research organizations.
Dr. Maggi is an expert at facilitating others' learning, from medical students to health system CEOs. Her client base consists of C-suite executives to VPs and department chairs, both new and experienced. She developed and led the Community of Champions, the national physician leadership development initiative at the Veterans Health Administration.
She has held many executive posts and practiced medicine in Santa Rosa and Mammoth Lakes, California; Denver, Colorado; London; and Kendal, UK.
Her research for Telemedicine and Telehealth: Principles, Policies, Performance, and Pitfalls (The Lancet's review) led her to the realization it's all about the people, the relationships, and asking questions. Her passion project is A Whole New Doctor, a leadership development and coaching program for medical students, staffed entirely with volunteers. A Whole New Doctor serves medical students from Georgetown University School of Medicine, Penn State College of Medicine, University of Nevada, Las Vegas School of Medicine, University of Virginia School of Medicine, Howard University College of Medicine and Hofstra Northwell School of Medicine.
Dr. Maggi is adjunct faculty at Georgetown University School of Medicine and has taught at the Harvard Macy Institute. She coaches TED Fellows and Global Good Fund Fellows and leads nonfiction writing workshops.
In addition to being a contributing author for The Doctor Weighs In, Dr. Cary also serves on the TDWI Editorial Board, where she medically reviews articles submitted for publication.
She is intellectually curious about nearly everything, a lifelong learner, animal lover, gardener, and always ready for adventure.
Nicole Alexander-Spencer says:
1/6/2021 at 10:24 pm
I would like more information about coaching.
Hanssen Tulia says:
I'm envious. Seems like every time I come back to your website you have a new interesting thing for me to read. How do you stay so motivated? Do you research all of these posts before posting?
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Each of the alumni below were a part of Art Club while they attended Sprayberry . Register if you would like to be listed below.
Looking for Sprayberry alumni who participated in Art Club but are not listed? Classmates.com® has hundreds of more Sprayberry alumni listed.


Last week I bought this WSO course which was a "Deal of the Day". It is called The SUPER Traffic Method.
Today, I'm going to reveal to you the best form of traffic on the planet. In fact, this special source of traffic has helped me generate well over half-a-million dollars online to date!
And then I looked at his Warrior Plus profile picture. Almost 23'000 sales (it has surpassed it now).
I knew the guy knows what he's doing. I might learn a thing or two.
This is what made me want to buy the product.
I wasn't sure what I'm getting into to, but my curiosity got the better of me.
What's included in The SUPER Traffic Method course?
Once I accessed the page I got greeted by 5 videos and two downloadable files. The videos are about 1 hour 30 minutes long altogether.
Mindmap of steps needed to be done to implement his method.
A list of Affiliate & JV Groups.
What is The SUPER Traffic Method about?
It's about creating your own info products and selling them on sites like JVZoo, Warrior Plus & Clickbank.
He went through all the steps that you need to do to make the product, get it in front of affiliates that promote the product on your behalf to their followers/email lists, and everything in between that is important.
He even shows examples of his past product launches and how he made more than $70'000 with only one course.
The same course can be downloaded for free by following the link in one of the videos.
This is the course he made $70K with if you are curious.
While I think the videos could have been shorter by half, the main information is good.
If you haven't launched any info products yet, it will be a great introduction to the process.
Since I've launched some products myself, I already knew most of the stuff, but it helped me acknowledge the power of affiliates and how much pre-launch is needed.
When I launched my first product, I did the Rookie mistake by not having a pre-launch page and I didn't have any affiliates to promote it for me.
I had to do all the hard work myself, and the sales were slow in the beginning.
By buying this course you can avoid mistakes, and do everything right from the start.
Jeremy shows where to get affiliates, how to build connections and how to promote your product launch.
For $19 The SUPER Traffic Method is worth the price.
Have you already tried The SUPER Traffic Method? Or do you have any questions about it?


The likes of George Monbiot and Al Gore get pretty hysterical about global warming / cooling / dimming or whatever current theory is in vogue. The science is settled / the evidence is overwhelming they scream in an attempt to block any debate. In reality physicists, as a sub-section of the scientific community, are a lot less keen on the whole carbon and climate scare racket. Scientists are not usually unanimous on any subject which is complex.


What's this? Anglo push-back? The huge café that used to be a Chaldean eatery now has a sign that reads "Goody's Cafe" in yellow letters on a giant, red '50s-style sign pole.
This big, ranch-style wooden building takes up almost a block. It has a total glass frontage except for big chunks of river-stone wall at the corners and around the main entrance. And it looks like what it is: totally '50s, '60s moderne.
First time I came by here it was the Hammurabi Family Restaurant and looked pretty romantic. It was a warm night. People were out on the terrace that fronts the building, smoking hookahs, chatting, drinking tea, and watching soccer on a big outside TV screen set into the stone wall.
Everything was so different. A couple of the guys I talked to said that for $225 you could roast an entire side of lamb on the streetside terrace and throw a party right there. Man, I longed to have one of those. And they had real exotic food, like stuffed honeycombs and intestine, plus lamb tongue and lamb shank with rice, or cut-up marinated lamb hearts on a skewer, as well as the everyday shish kebab dishes.
So, I always wanted to come back. Sad to say, last time I came in, it was looking kinda down-at-heel. They had taken all the counter stools away, and the booths didn't look too cool. You felt the place wasn't firing on all cylinders.
And now this. Transmogrification to all-American diner. Gotta go in and see what's up. Plus, a late breakfast would go down well, even if it isn't honeycomb and intestines.
I get inside and straight away this gal Karla has brought the menu and some coffee. First thing you notice is the gleaming-new red booths and new rack of black bar stools, 13 of them running down this lo-ong counter. Black-and-white photos of '60s stars such as Marilyn, Elizabeth Taylor, Eastwood, Bronson, the Duke. Then you notice the massive stainless steel kitchen behind and one busy cook. And plenty of customers. That's good. Life coming back into the building.
Photos of stars from the 1950s and '60s hang on the walls at Goody's Café.
You also feel like you're time-warped back to the '60s. The menu is back there, too, in everything but price. One side is breakfast, the other side is lunch. Lunch is, like, eight-ounce cheeseburgers for six bucks; an eight-ounce buffalo burger goes for nine; and a top-sirloin steak dinner for ten.
But for me the breakfast side has it all. Omelets — like the Farmer's, with ham, bacon, sausage, tomato, onions, and cheeses — mostly go for $7. Or the three pancakes with two sausages and two eggs are only $5. And breakfast sandwiches such as the bacon, egg, and cheese are also $5.
At this point, greed takes over. The skillets get my vote. Mostly $8. Choices are: Texas Skillet (chicken), Philly (sirloin), Greek, Mexican (chorizo), or veggie.
Gotta be Philly, just because of the meat, even though it's a buck more than all the others at $9. Then I have to insist on bacon, too. Another $1.50. The cook, Bill, gets right on it. And before I've had three slurps of joe, Alex, the other guy here and Bill's brother, brings it sizzling — and I mean sizzling — to the brown Formica countertop.
Huh. The iron skillet sits on a wooden raft with a little mitten covering the handle. And it's jumping. The sizzle sends little jets of steam up from underneath like fumaroles. I had my eggs scrambled and got the biscuit. It's just been baked. It's fresh and hot, but I thought it was going to be biscuits and gravy. Dang. Should've gone for the pancakes. Miss that syrup, seeing we're playing damn the torpedoes and up the cholesterol.
Best thing? The racks of thin-sliced seasoned beef. They are so delicious, way tender, full of flavor, lashed by tons of sautéed onions, 'shrooms, chopped home fries, and I don't know what else. I squirt a big red pile of ketchup for home-fry dipping purposes. Karla keeps refilling my $1.99 coffee.
So, the Chaldeans turned it into the "Hammurabi" for eight years. They named it for an ancient Babylonian — an Iraqi lawmaker who was, like, the world's first to encode the idea of "innocent until proven guilty." Pretty cool guy. But with the economic downturn, seems they couldn't make Hammurabi happen anymore. And after a lot of soul-searching, Bill and Alex and their dad (who still owned the property) took back the operation and revived Goody's, the same Kozak's-style all-American diner they had given up eight years before.
So, is this a sign of push-back by the valley's comfort-food-loving base? "Well it hasn't been easy, getting people to come back," says Bill.
They do have competition. As I leave, I notice Hometown Buffet's set up right across the road, and Greek, Italian, Mexican places are clustered nearby.
"It was a big decision, starting it up again," says Alex.
Next time, I guess I'll try the Greek omelet. Why? Because I love feta. Turns out Bill and Alex and their dad are Greek-Americans. Who could know feta better?
Dec. 11, 2013 @ 3:14 p.m.
It just doesn't get any better than seeing the gorgeous "Mrs. Anita Pelaez" over at her and her husband "Captain Kutchie's" place..Some Folks Also Call Him.."The KutchMan others call him The Kutchmon!"…Most Just Call Him "The Most Interesting Man In The World"….(Anita and Kutchie Pelaez's Key West, Key Lime Pie Factory and Grill)…Just watching the lovely couple baking together all those Yummy Key Lime Pies at their Key Lime Pie Factory and Grill in Asheville. …It's always worth the trip to visit them in they're Historic Key Lime Pie Factory and Grill…It should be on everyone's bucket list for sure..And The World's Best Key Lime Pies!..YUM-YUM-YUM….."Talk About World Class" What An Understatement!…….AAHHHHH!….The Magic Of The Lovely.."Mrs. Anita Pelaez" And Her Delicious Key Lime Pies Baked With Pure Love…Always……40 Years And They're Still Going Strong….
….May GOD Continue Blessing "Anita And Kutchie Pelaez" and They're World Famous Key Lime Pie Factory And Grill Where The Personalities, Ovens And Smiles Are Always Warm And Inviting. "Kutcharitaville" You're The Best We Love You!….
....Just Think, Kutchie's Goody Goody Cheese Burgers, The Original Cheese Burgers In Paradise! ....That Alone Is Quite A Pretty Big Deal If You Ask Me. It's A Pretty Big Deal Even If You Don't Ask Me.


We're excited to share some new photos of the Oceanside Beach House. On a recent sunny fall day, Portland photographer David Papazian made the trip to Oceanside to shoot a handful of images. We think they turned out quite well. Let us know if you agree.
we made a quick visit to oceanside to check in on the construction progress over the last few months. the owners are doing most of the work themselves, and they've been moving along steadily on the interior. the spaces are starting to take shape, colors are getting introduced, and this little beach house is starting to come to life.
a quick reminder of what it once was.
we recently completed work on a small bathroom remodel with some pleasing results.
the existing dropped sheetrock ceiling was removed to expose the original wood decking. a carbonized bamboo cabinet provides a nice complement to the wood ceiling.
the existing shower compartment was replaced with a curbless all glass shower surround outfitted with a linear slot drain.
a duravit wall hung dual flush toilet is mounted on a background of simple white 3x6 tile in a stacked bond pattern.
a linear glass tile backsplash above the white quart countertop provides a hint of color. trimless mirrored doors conceal a wall to wall medicine cabinet.
linear porcelain tile provides a beautiful cost effective floor. a perimeter soffit conceals new piping and accommodates uplighting.
another bathroom remodel project is in the works. check back soon for the next small project update.
Just after the first WW, Enrnst May, Frankfurt's city architect initiated an ambitious project to house millions of soldiers returning to Germany, as well as thousands of war widows. May brought into his office a young but experienced Viennese architect, Grete Schütte-Lihotzky, to design a modern, rational, work kitchen.
The kitchen's organizing principle is similar to that of the design of galleys in ships and trains of the era. Its tiny size reflected a desire for efficiency and to save room for the living spaces of the flat.
The kitchen's innovative features included continuous work surfaces, a table for preparing food under a large window, storage bins with handles and spouts, an adjustable ceiling light, a movable stool, a concealed pass-through, drop-down ironing board, and cabinetry painted a deep blue to naturally repel flies.
Lihotsky apparently drew endless diagrams of how cooks move in a kitchen to understand how to maximize efficiency. The surfaces are at sitting height, so the cook didn't have to be on her feet the whole time.
Probably the biggest innovation was to take the dining table out of the kitchen. This simple galley working kitchen satisfied the modernists' concern with hygiene and made for a more efficient floorplan.
Not only was the layout of the kitchen innovative, but so was its construction and affordability. The cabinets were made without sides and backs to save cost, and special loans were made available to allow residents to buy a kitchen and pay it off with the monthly rent.
Over 10,000 versions of the frankfurt kitchen were installed within a four-year period. This small efficient kitchen became a standard in Europe throughout the 20th century.


The #1 song when you were born?
Why don't you post yours?
I guess David is about my age, since that was the #1 song when I was born. For Joan, it was a song I'm unfamiliar with: "Rumors are Flying", by Frankie Carle. Of course, we only hear the songs for the day we're born if our parents play them, or if we hear them on Oldies radio.
The #1 song on the day we were married, 6/16/68, is still appropriate: Herb Alpert's "This Guy's in Love With You." The song on the date we met, 1/13/67, is also still appropriate: the Monkees' "I'm a Believer".
WOW - thanks for the trip down Memory Lane Keith & Rita.
Sunshine Superman by Donovan was the rage the day we were married nearly 40 years ago.
Both mine and Kens..........Paper Dolls by the Mills Bros.
What song gets you in the cruisin' mood?
What is your favorite Holiday song?


A national travel/attraction web site today announced that Newport Aquarium was ranked the Best Aquarium in the country by reader voting. The web site - 10best.com - released the results of its inaugural "Readers' Choice Travel Awards." Each award was divided into a distinct attraction category.
On behalf of the Newport Aquarium cast and volunteers, thank you for voting for us and making Newport Aquarium #1. We set out each day to help our guests create wonderful memories with their families in a world-class facility. This ranking in some small way says we're succeeding. We're honored, but now we'll work extra hard to earn that vote again next year.
Newport Aquarium is an accredited member of the Association of Zoos & Aquariums (AZA), which means it's held to the absolute highest standards of animal care and exhibition.


text:
Course Review: Tallwoods Country Club, NSW
By Rohan Clarke
Nobody quite knew what to expect when Tallwoods Country Club acquired its seventh owner. Twelve months later and the much-loved course at Hallidays Point has undergone a massive facelift, restoring its place as one of the very best courses in regional New South Wales.
Once ranked as high as No.72 on Australia's Top 100 Courses, Tallwoods had fallen into receivership. Tumble weeds weren't exactly blowing down the fairways, but the conditioning of the wonderful layout designed by American architect Michael Hurdzan left a lot to be desired.
Tallwoods' fortunes changed when Barry Sale saw a 'For Sale' sign while visiting a sick friend on the NSW Mid North Coast. Sale's field of expertise was retail technology within the family business (Goodson Calculators Australia).
Enticed by the romance of owning a golf course, Sale purchased Tallwoods and began the mammoth task of resurrecting what James Fairfax originally built as the epicentre of a $54 million residential development. With his daughter, Susan Pace, as director of Tallwoods Country Club, they immediately ploughed more than $1 million into improvements on and off the course.
Tallwoods has long had a reputation for its tough par 3s.
The most noticeable sign is the bunkering. Tallwoods' green complexes were a feature of Hurdzan's original design and the poor state of the sand traps really detracted from the playing experience. Most bunkers had little sand and the hard clay bases resembled something out of a pottery kiln. In total, 63 bunkers have been renovated with new drainage and topped with a high-quality white fluffy sand to give the hazards a striking appearance.
New machinery has been provided for course maintenance, including fairway and greens mowers. A new irrigation system has been installed along with a new pumping shed. (Tallwoods hadn't used automated sprinklers for six years). A turf nursery has been created and more than $100,000 was spent initially on chemicals and fertilisers.
Elevation changes, often dramatic ones, are a Tallwoods hallmark.
As a result the greens are now the healthiest they've been in eight years, according to independent testing. All achieved with a greenkeeping staff that has increased to four fulltime groundsmen. In addition, a working bee of 13 volunteers gathers each fortnight to help restore Tallwoods, cleaning out rough areas and making the course more playable.
The new owners also delivered on their promise for a new fleet of 26 golf carts. New signage has been installed around a course that has some very steep descents from tees and greens. Long-time visitors would also notice the golf shop with a lot more stock.
After a complete renovation of the dining area, Tallwoods is open for breakfast, lunch and dinner seven days a week. Catering has been leased to brothers Greg and Darren Bultitude who have rebranded the restaurant 'The Kranky Goat'. Greg has returned as chef after a sabbatical overseas, restoring his sensational degustation to a menu that specialises in gourmet tapas plates, homemade pies and pizzas.
Many social clubs have now returned while 'vets' day each Monday attracts 60 players. Club membership has increased by about 25 percent to almost 350 golfers. This spring Tallwoods held its first FootGolf event.
Pace says it's been a very rewarding experience for the Sale family. "Dad and I were up here a couple of weeks ago and constantly the members are grabbing us. Just their compassion in saying thank you really means a lot to us. We get some really emotional members coming up saying 'Thank you for saving Tallwoods'."
The 10th green and 11th hole form a demanding corner of the golf course.
Meanwhile, Tallwoods has signed off on the construction of 16 luxurious on-site cabins, each with two bedrooms and two bathrooms. It's hoped eight cabins will be available as short-term accommodation by early 2020.
In addition, the Tallwoods residential masterplan includes an over-50s resort-style living complex, a hotel and retail shops. Management is working with a local town planner and Mid Coast Council on the finer details. It's anticipated 80 homes will be built in the seniors living development and 70 rooms in the hotel. The total cost to reinvigorate Tallwoods will exceed the original estimate of $5 million.
"We've proved ourselves over the past 12 months that we're not just here for the fun of it or to sell it. We really love Tallwoods," Pace says. "We all know that it's probably going to be a hard three years. But then we're looking to really start enjoying it. For us, we just want to get Tallwoods back to what it was."
Tallwoods is a harmonious mix of golf, housing and nature.
Tallwoods Country Club
Where: The Boulevard, Tallwoods Village, Hallidays Point NSW 2430
Web: tallwoods.com.au
Green fee: $55 with cart
Read here for Rohan Clarke's course review of Tallwoods Country Club from the beginning of 2019.
Australian Golf DigestBarry SaleCourse ReviewRohan ClarkeSusan PaceTallwoods Country Club
World golf's most famous resort has shared some sad news


This home has been remodeled and has a bright and open floor plan, with spacious living room and kitchen, activities area and desk area. Four private rooms and one large room for a couple or to be shared and two full baths. Large, gated yard, covered patio, fruit trees and plenty of space for gardening for the green thumbs.
Conveniently located right off the 405 Fwy and Beach Blvd — a short trip to many upscale shopping malls and the new Huntington Beach Senior Center.
Our RCFE homes are "all inclusive" where one flat rate covers all the typical living expenses from home cooked meals, doing laundry to bathing, cleaning, etc. For more info see "About Us"
Complete our form, and a representative will contact you.


Italian manufacturer of adhesives and sealants, Mapei Underground Technology Team (UTT) has seen a 4.36% increase in company sales in the Middle East in 2017 compared to 2016 after completing a number of high profile projects in the region.
Mapei UTT supplies protective coating for the concrete segments supplied to the Expolink consortium of Alstom, Acciona and Gülermak, for the Dubai Metro Route 2020 which will run through a 10m-wide, 2.5km long underground tunnel.
Chemicals for shotcrete to stabilize rock after blasting at the Shis to Khor Fakkan Roads & Tunnels project in Sharjah, a 23.2km dual carriageway near the edge of the Omani border are also supplied by Mapei. The road extends through mountainous terrain and passes through five rock tunnels with a total distance of 13km and will help ease traffic flow and ensure the safety of visitors traveling to and from Khor Fakkan and the wider emirate.
Also supplied with products from Mapei are; The Brenner Bass Tunnel, a 64km railway tunnel between Austria and Italy through the Eastern Alps that will be the longest underground rail link in the world; Cociv- Terzo Valico dei Giovi, a 53km high speed railway line between Genoa and Milan in Italy; Tunnel Euralpin Lyon-Turin, the new rail tunnel link between Lyon in France and Turin in Italy that is one of the largest rail projects in Europe; Grand Paris Express, metro line 14 in France; the Rogun Hydro Power Plant (HPP) Dam in Tajikistan, which at 335m high is the tallest in the world; the Mumbai Metro in India and the Quito Metro Line 1, a 22km tunnel through the capital of Ecuador.
Mapei UTT was created to supply a portfolio of dedicated products to match a variety of specifications in the construction industry.
"We are seeing a growing local demand for a range of products dedicated to underground construction as the industry looks at innovative design solutions for the travel and living demands of the regional population. We are providing products to projects in North-East Africa and Egypt, and our 28 research centres globally work with project design teams to find innovative new solutions to keep the Middle East construction projects the global benchmark," said Stefano Iannacone, Mapei Regional Director for the Middle East & East Africa.
Mapei Group is also acquiring Italian Fili & Forme Srl, a company with more than 10 years in the building industry using the Istrice brand that produces structural polymeric fibers for mortar and concrete reinforcement for use in the underground construction industry.
Only a few weeks ago Mapei opened a US$6.5 million production facility with new offices at the Dubai Investments Park, coinciding with its 10 year anniversary in the Middle East.
The newly-expanded facility has a 5,200m2 covered warehouse for larger storage capacity, and a new epoxy resin production line. The new offices cover more than 2,000m2 including a showroom and training centre.
Mapei has 1,000 regional customers and 128 employees of 25 nationalities at its regional headquarters. The company invests heavily in its highly-trained workforce hosting 120 training events for the Middle East team in 2017.
Established in 1937 in Milan, Italy, MAPEI now produces over 25,000 tonne of products per day, has over 66,000 clients and currently employs over 9,000 highly specialized professionals at its 75 plants in 54 countries worldwide.


Double strike has always been dangerous in Standard Pauper. Temur Battle Rage nicely illustrates why. With the perfect hand, we now have a Turn 3 kill in Standard Pauper, assuming your opponent doesn't interact with you during those three turns.
Turn 1: cast Akroan Crusader.
Turn 2: cast Rouse the Mob targeting the Crusader; cast Titan's Strength, again targeting the Crusader. This buffs the Crusader up to 6 power and creates 2 1/1 tokens with Haste. They deal 8 damage total.
Turn 3: cast Titan's Strength, targeting the Crusader; cast Temur Battle Rage, targeting the Crusader. This buffs the Crusader up to 4 power and creates 2 more 1/1 tokens with Haste. With the tokens from the previous round, they deal 12 damage total (4 first strike, 4 regular strike, 4 total from the tokens). For those playing along at home, 12 + 8 = 20, or the starting Life total of your opponent.
The same trick also works with Satyr Hoplite. But in this case, it's a 3/3 before buffs on Turn 2, and a 5/5 before buffs on Turn 3. You still deal 8 damage on Turn 2, but on Turn 3 you now deal a whopping 16 damage, bringing your total up to 24 damage.
Granted, either way this takes the perfect hand. You have to draw two copies of Titan's Strength, a copy each of Rouse the Mob and Temur Battle Rage, and three Lands, all of which must come into play untapped and two of which must be Mountains. You also need the Akroan Crusader or Satyr Hoplite in your opening hand, and for your opponent to be unable to interact with you during those three turns. You also get two Scry activations from Titan's Strength, for whatever that's worth.
Unlikely, yes. But certainly not outside the realm of possibility. And even with a slightly less ideal hand, a Turn 4 or 5 kill is even easier, particularly if you can pull off multiple buffs before casting Temur Battle Rage.
I suspect that this card alone will cause more rage than any other in the Standard Pauper cardpool once Fate Reforged is released.
A powerful card in Standard Pauper, for sure, and I bet we'll even see it come into some Classic Pauper decks, most notably Fiend combo.


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Good News2013-04-162013-04-16https://www.clarkcollegefoundation.org/wp-content/uploads/2018/09/clark-college-logo-2.pngClark College Foundationhttps://www.clarkcollegefoundation.org/wp-content/uploads/2018/09/clark-college-logo-2.png200px200px
Student newspaper takes home national honor
Members of The Independent student staff and faculty advisor Dee Anne Finken (left).
Members of the staff of The Independent, Clark College's award-winning news operation, returned from San Francisco with another award to their name and plenty of new insights and ideas about producing good journalism in a rapidly evolving media landscape.
Eleven Clark student journalists and their adviser attended the 29th annual Associated College Press conference February 28 to March 3, where they won a seventh-place "Best of Show" award among community colleges. They also attended more than 60 workshops on topics that included ethics, multimedia-news production, investigative reporting, social media and newsroom management.
News staffs from more than 100 colleges and universities—both two- and four-year—from throughout the United States attended. Independent adviser Dee Anne Finken said she was pleased that the students won recognition from among so many institutions. Since 2010, the Independent has won more than 40 statewide awards.
More important, Finken said, was the breadth and depth of learning that took place at the conference. "Our students dove right in and learned all types of new lessons," she said. "I think we're going to be seeing some cool new developments in the Indy as students begin to apply what they learned here."
Independent editor-in-chief Kyle Yasumiishi also said the trip was highly productive for his staff. "Clark College offers students many resources to help them succeed in school and the workplace," he said. "However, the field of journalism is rapidly changing and attending a conference like this is valuable because it keeps student journalists up to date about emerging jobs and opportunities that didn't exist 10 years ago and how to prepare for them."
Yasumiishi said he also valued the opportunity to network with fellow student journalists as well as professionals. "It's also inspiring to listen to keynote speakers who are leaders in their fields and on the forefront of the push to digital-first journalism," he said.
Finken was a panelist in a workshop that focused on assessment. She spoke at "Making the Grade: Innovative Strategies for Evaluating Student Work." "Finding ways to assess student work without engaging in pre-publication censorship is a long-running challenge for many of us who advise student journalists," she said. "I was pleased to be part of a group that continues to explore meaningful assessment tools."
When they were not attending workshops, students and their adviser took in some San Francisco sights, including Fisherman's Wharf, Ghirardelli Square, book and record stores and Chinatown. But overall, the trip was about learning, Yasumiishi said. "The key lesson I took away from the conference is to embrace the push to digital storytelling and multimedia journalism," he said. "Since nobody has yet developed a profitable model that will completely replace newspapers, college journalists have a golden opportunity to try new ways of delivering the news."
Photo: Left to right, back row, Margherita Nicotra, Kelli Borchers, and Jeff Knapp, second-from-back row, Madeline Bern, Evan Blatnik, and Bryce McQuivey, secondfrom-front row, Independent adviser Dee Anne Finken, Gabriella Benavides, and Sophia Coleman, front row, Kyle Yasumiishi, Michael Lusk, and Leisa Nunn.
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Exceptional Fundraising Award Bestowed on Clark College Foundation
Redefining PossibleNews
Monkeys, Mangoes and ModernizationNews


Tim Holtz DISTRESS GRIT PASTE Ranger TDA53422 at Simon Says STAMP!
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