Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases—as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple—but not all—immune-mediated diseases (SNP-wise PCPMA<0.01). We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.
Over the last five years we have found over 100 genetic variants predisposing to common diseases affecting the immune system. In this study we analyze 107 such variants across seven diseases and find that almost half are shared across diseases. We also find that the patterns of sharing across diseases cluster these variants into groups; proteins encoded near variants in the same group tend to interact. This suggests that genetic variation may influence entire pathways to create risk to multiple diseases.
Copyright: © 2011 Cotsapas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The human immune-mediated diseases are the result of aberrant immune responses. These immune responses may lead to chronic inflammation and tissue destruction, often targeting a specific organ site. The outcome of this process is immune-mediated inflammatory and autoimmune disease, affecting approximately 5% of the population .
Extensive clinical and epidemiologic observations have shown that immune-mediated inflammatory and autoimmune diseases can occur either in the same individual or in closely related family members. This clustering of multiple diseases appears more frequently than expected if disease processes were independent. As each of the immune-mediated inflammatory and autoimmune diseases has strong genetic influences on disease risk –, the observed clustering of multiple diseases could be due to an overlap in the causal genes and pathways , .
The patterns of clustering of diseases across the population are complex  – each disease has a prevalence between 0.01%–3%, so direct assessment of co-aggregation within individuals or families does not result in the very large samples required for genetic or epidemiological investigation. Thus it is unsurprising that to date, these observations have yet to be translated into determinants of the shared molecular etiologies of disease.
Recent GWA studies in immune-mediated and autoimmune diseases have identified 140 regions of the genome with statistically significant and robust evidence of presence of disease susceptibility loci. A subset of these loci have been shown to modulate risk of multiple diseases , , –. In addition, there is evidence that loci predisposing to one disease can have effects on risk of a second disease , although the risk allele for one disease may not be the same as for the second .
Together, these observations support the hypothesis of a common genetic basis of immune-mediated and autoimmune diseases . There is now the ability to estimate both the number of loci contributing to risk of multiple diseases and the spectrum of diseases that each locus influences. In addition, grouping variants by the diseases they influence should provide insight into the specific biological processes underlying co-morbidity and disease risk.
In this report, we systematically investigate the genetic commonality in immune-mediated inflammatory and autoimmune diseases by examining the contributions of associated genomic risk regions in seven diseases: celiac disease (CeD), Crohn's disease (CD), multiple sclerosis (MS), psoriasis (Ps), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D). We find that nearly half of loci identified in GWAS studies of an individual disease influence risk to at least two diseases, arguing for a genetic basis to co-morbidity. We also find several variants with opposing risk profiles in different diseases. Supporting the idea that common patterns of association implicate shared biological processes, we further demonstrate that loci clustered by the pattern of diseases they affect harbor genes encoding interacting proteins at a much higher rate than by chance. These results suggest that multi-phenotype mapping will identify the molecular mechanisms underlying co-morbid immune-mediated inflammatory and autoimmune diseases.
We first test our hypothesis of common genetic determinants by examining evidence of association of genetic variants in known immune-mediated and autoimmune disease susceptibility loci to multiple disease phenotypes. We collated a list of 140 single nucleotide polymorphisms (SNPs) representing reported associations to at least one immune-mediated disease at genome-wide significance levels. Where data for the reported SNP itself were not available in our GWA studies (Table 1), we chose a proxy in high linkage disequilibrium to the reported marker (r2>0.9 in HapMap/CEU). We did not consider SNPs in the human Major Histocompatibility Complex (MHC) from this analysis, as its role in many of these diseases is well-established and the classically associated alleles in the HLA region are not well captured by SNPs . We were able to acquire data for either the reported SNP or a good proxy in 107 of 140 cases, and assembled genotype test summaries for these from previously described GWA studies representing over 26,000 disease cases (Table 1).
We have developed a cross-phenotype meta-analysis (CPMA) statistic to assess association across multiple phenotypes. The CPMA statistic determines evidence for the hypothesis that each independent SNP has multiple phenotypic associations. Support for this hypothesis would be shown by deviations from expected uniformity of the distribution of association p-values, indicative of multiple associations. The likelihood of the observed rate of exponential decay of −log10(p) is calculated and compared to the null expectation (the decay rate should be unity) as a likelihood ratio test (see Materials and Methods for details). This CPMA statistic has one degree of freedom, as it measures a deviation in p-value behavior instead of testing all possible combinations of diseases for association to each SNP.
A total of 47 of the 107 SNPs tested have evidence of association to multiple diseases (SNP-wise PCPMA<0.01; expectation roughly 1 by chance; binomial probability of observing this result p = 3×10−64). This highly significant result confirms widespread sharing of genetic loci between immune-mediated inflammatory and autoimmune diseases. Further, these "multi-phenotype" SNPs include many loci not previously known to be shared across diseases, as well as new predictions of association for previously known shared loci (Table 2).
Table 2. SNPs associated with multiple phenotypes.
Although our CPMA statistic is agnostic to effect direction in each disease, a subset of the 47 multi-phenotype (CPMA positive) SNPs appeared to have strong allelic effects in opposite directions in different diseases . A total of 9 SNPs had strong evidence of such directional association (an association p<1×10−4 with at least one protective and one risk effect; lower panel in Table 2). This suggests that shared associations have complex effects on disease outcomes and may be of particular importance in pathogenic processes.
We next examined the patterns of association across 47 multi-phenotype SNPs to determine evidence of either a global autoimmune process or biological pathways influencing sets of diseases. On visual inspection of these data we found a striking patterning of associations across diseases: only one SNP (rs3184504, in an exon of SH2B3) exhibited evidence of association to all seven diseases; the others appeared to associate only to subsets of diseases (Table 2).
To formalize the analysis of association patterns across diseases, we determined specific patterns of associations across SNPs by computing SNP-SNP distances based on the level of association to each disease followed by hierarchical clustering to group them (Figure 1A; see Materials and Methods section for clustering details). SNPs in loci encoding proteins known to interact clustered together: for example, the independent effects at IL12B and IL23R, which encode subunits of a ligand-receptor pair are in the same region of the dendrogram. We next partitioned the dendrogram "tree" into four clusters and summarized the cumulative association of each cluster to each disease by combining our underlying dataset of association p-values per cluster, per disease using Fisher's omnibus test (Figure 1B; see Materials and Methods for details). Each cluster had a different pattern of associations across diseases; these patterns suggest that the clusters represent distinct co-morbid mechanisms.
Figure 1. Patterns of association across diseases correlate with protein-protein interactions.
A: 47 SNPs with evidence of association to multiple diseases (Pcpma<0.01) fall into groups clustered by the pattern of association across diseases. Clusters are numbered arbitrarily. B: Clusters show different patterns of association across diseases. We summarize the differential disease effects of each cluster with a cumulative association statistic (Fisher's method for combining p values). These patterns are different for each cluster, suggesting each represents a different co-morbid mechanism. Note that these figures are based on the same underlying association statistics the clustering in the first panel is derived from. C: proteins encoded within the linkage disequilibrium scope around SNPs in the same cluster interact either directly or via common intermediates. Three of our four clusters have significant protein inter-connectivity (permuted P<0.05; see Materials and Methods and  for details).
Our underlying hypothesis has been that phenotype-driven clusters represent distinct molecular mechanisms. This leads to the prediction that components of these clusters/pathways are encoded in associated loci; in other words, proteins encoded around SNPs in the same cluster should interact. We test this prediction by looking for connectivity between proteins encoded around SNPs within each cluster as described elsewhere . Briefly, we define a genomic region around each SNP in terms of linkage disequilibrium and consider any protein overlapping that region. We then ask if proteins encoded around SNPs in the same cluster interact using protein-protein interaction maps, excluding interactions between proteins in the same region (see Materials and Methods and ). We find that three of the four clusters we define by patterns of association have significant connectivity (Figure 1C; permuted P<0.05) by this method, suggesting that these represent distinct molecular mechanisms affected by genetic risk variants. Two of these groups of interacting proteins are also preferentially expressed  in immune cell subtypes compared to other tissue types (Figure S1), supporting our hypothesis that these represent true pathways underlying pathogenesis.
Immune-mediated inflammatory and autoimmune diseases have been known to cluster in families, suggesting a strong genetic component to risk. The genes in the human MHC (HLA complex) have been associated with disease risk, suggesting a common immune pathway. Less clear is whether other genetic variants associated with individual diseases also form common pathways/mechanisms for autoimmunity. Recent results from GWA studies suggest that common genetic mechanisms may underlie the observed clustering of multiple autoimmune diseases within a person or family. In this work we have tested the hypothesis that immunologically relevant genetic variation will either (1) underlie risk to all immune-mediated diseases, implicating a global immunological process; (2) influence risk to a discrete subset of diseases, implicating molecular entities underlying that co-morbidity; or (3) modulate risk for only one disorder thereby implying a disease-specific process.
A central goal of complex disease genetics is to uncover the pathways perturbed in disease and shed light on the underlying cellular processes. Despite a wealth of molecular insight into immune function few key pathways underlying genetic susceptibility to immune-mediated diseases have been elucidated. To identify these processes in immune-mediated inflammatory and autoimmune disease, we tested genetic variation contributing to seven diseases. We observed an overwhelming abundance of commonality across these phenotypes, assorting into cohesive phenotype-genotype groups that appear to underlie co-morbidities. By analyzing loci known to associate to at least one disease, we are able to identify groups of diseases that should be considered as a unified phenotype and analyzed together. We further demonstrate that this approach generates novel biological insights into pathogenesis, often difficult to obtain from genomic studies of single traits .
We have described a novel statistic, CPMA, which assesses evidence for multiple associations to a marker. Rather than perform a meta-analysis, which would only detect association to all phenotypes (or suffer from heterogeneity) or test all combinations of phenotypes which would increase the multiple testing burden, we look for deviation in the distribution of association p values. Our statistic thus detects markers associated to at least some, but not necessarily all, phenotypes; we note that this is a single degree of freedom test, providing high power to reject the null hypothesis. This power comes at the price of not knowing to which phenotypes the marker is associate; we overcome this with our clustering analysis, which resolves groups of markers associating to the same diseases. Thus our analytic strategy is able to both detect shared associations and identify the relevant phenotypes.
Our approach appears capable of distinguishing distinct genetic effects in the same locus in addition to validated shared associations. For example, it is now clear that the two signals in the IL2/IL21 locus on chromosome 4q27 are distinct, with T1D mapping to IL2 and other diseases to IL21 . Our analysis detects this difference, clustering the two SNPs representing these associations separately (Figure 1, labeled "IL2" and "IL2/IL21", respectively). Conversely, previous reports of an overlap in association between T1D and celiac disease  were in regions encoding genes highly expressed in T lymphocytes (RGS1, PTPN2 and CTLA4 in celiac; PTPN2 and CTLA4 in T1D). Our analysis identifies all these regions as CPMA-positive and highlights the second associations in T1D and celiac shown by Smyth et al., indicating that our approach could be used to prioritize marginal associations for replication. We also observe other potential associations. For example, rs2816316 on near RGS1 exhibits evidence of association to MS; rs2542151 and rs1893217 on near PTPN2 has modest association to psoriasis. These last observations, whilst suggestive, require further investigation given the known effects of these regions on other diseases.
In summary, our multi-disease approach is applicable beyond the immune-mediated inflammatory and autoimmune diseases, to current studies of related traits in pharmacology, metabolic and psychiatric disease and in genetic studies of cellular phenotypes such as gene expression. For most studies of the genetic basis of complex human phenotypes, the pathogenic processes are still far from understood and biological pathways may be identified using these methods. Ultimately, these results will contribute to an improved molecular nosology of mechanistic definitions and, ultimately, towards improving clinical care and human health.
All data were drawn from previously published genome-wide association studies from consortia with appropriate ethics oversight from their respective institutional review boards. As only summary data from a small number of markers across the genome were used here no further ethical issues arise.
Data were obtained from previously described case/control GWA studies of celiac disease , Crohn's disease , multiple sclerosis , psoriasis , rheumatoid arthritis , systemic lupus erythematosus  and type I diabetes  as shown in Table 1. We note that, with the exception of psoriasis, in these cohorts diagnosis of a second immune-mediated disease is a criterion for exclusion, thereby minimizing co-morbidity as a source of bias in our study.
For our analysis we selected 140 independent SNPs (r2<0.2) with reported associations to an immune-mediated disease in a genome-wide association scan and replicated in independent samples in that disease to combined genome-wide significance . We then chose proxies for those SNPs present on the major versions of Affymetrix and Illumina genome-wide genotyping platforms ; 107 SNPs had sufficient data coverage to be included. Where possible we used the SNP originally reported; if data were unavailable for that marker, we chose a high LD proxy (HapMap/CEU r2>0.9) to represent the region.
This statistic therefore measures the likelihood of the null hypothesis given the data; we can reject the null hypothesis if sufficient evidence to the contrary is present. We note that, because we only estimate a single parameter, our test is asymptotically distributed as . This gives us more statistical power than relying on strategies combining association statistics, which would consume multiple degrees of freedom.
To compare the patterns of association for multi-phenotype SNPs we first calculate SNP-SNP distances and then use hierarchical clustering on that distance matrix to assess relative relationships between SNP association patterns.
Calculating distances based directly on p values or the underlying association statistics is problematic, as each contributing study has slightly different sample sizes and therefore different statistical power to detect associations. Thus, distance functions based on numeric data – which incorporate magnitude differences between observations – would be biased if studies have systematically different data. Normalization procedures can account for such systematic differences but may fail to remove all bias. To reduce the impact such systematic irregularities might have on our comparison, we bin associations into informal "levels of evidence" categories. We define four classes (1<p<0.05, 0.05<p<0.001, 0.001<p<1×10-6, 1×10−6<p) and thus reduce our data to a SNP x disease matrix where entries are categorical variables describing these classes. We then calculate the Euclidean distances between pairs of SNPs using Gower's method for categorical data , which accounts for the discrete nature of the data.
To compare the distance relationships between SNPs we use hierarchical agglomerative clustering. This process joins single entities (in this case, SNPs) or groups of entities together if certain criteria are met. Successive rounds of clustering are preformed in an iterative way until all groups are joined, resulting in a tree of relationships where similar entities cluster on the same branches. In this analysis we cluster SNPs based on the Gower distance matrix using Ward's method for joining entities . In contrast to linkage clustering methods, Ward's method seeks to minimize the information lost during the clustering process, calculated as the error sum of squares (ESS). The higher the ESS the more information is being lost due to inaccuracy of grouping entities together. This method thus seeks compact, spherical clusters of data which are maximally similar.
All distance and clustering analysis was done using the StatMatch and stats packages in the R programming language .
and Scum follows the distribution with 2N degrees of freedom.
We use previously described methodology  to assess whether proteins encoded around SNPs in each cluster interact. Briefly, we first compile lists of all proteins that an association may affect by defining locus boundaries around each SNP in terms of linkage disequilibrium and including all proteins overlapping this region. We then use a high-confidence protein-protein interaction map ( as modified in ) to ask whether proteins encoded around SNPs in each cluster interact either directly or via a common intermediary and assess the significance of such observations relative to the local structure of the protein-protein network as described elsewhere , using 4000 permutations. These data and methodology are publicly available for download and via a webserver (http://www.broadinstitute.org/mpg/dapple).
Complete SNP-wise association data. Here we present the complete dataset on which we base our analysis. All data have been previously published as detailed in the main manuscript and in the key below, and are based on chi-square (1 df) or Z association statistics. Where not provided, we computed Z scores as the square root of the cognate chi-squared statistic. Sign was assigned with reference to the minor allele declared in the psoriasis GWAS (chosen arbitrarily). SNP - marker name. CHR – chromosome. POS - physical position (hg18). major_al - major SNP allele. minor_al - minor SNP allele. RA.Z - association Z score for rheumatoid arthritis (Stahl et al.Nat Genet 2010) . RA.P - association p value for rheumatoid arthritis (Stahl et al.Nat Genet 2010) . PS.Z - ditto for psoriasis (Nair et al. Nat Genet 2009) . PS.P - ditto for psoriasis (Nair et al. Nat Genet 2009) . MS.Z - ditto for multiple sclerosis (De Jager et al. Nat Genet 2009) . MS.P - ditto for multiple sclerosis (De Jager et al. Nat Genet 2009) . SLE.Z - ditto for systemic lupus erythematosus (Gateva et al. Nat Genet 2009) . SLE.P - ditto for systemic lupus erythematosus (Gateva et al. Nat Genet 2009) . CD.Z - ditto for Crohn's disease (Barrett et al. Nat Genet 2008) . CD.P - ditto for Crohn's disease (Barrett et al. Nat Genet 2008) . CeD.Z - ditto for celiac disease (Hunt et al. Nat Genet 2008) . CeD.P - ditto for celiac disease (Hunt et al. Nat Genet 2008) . T1D.Z - ditto for type I diabetes (Barrett et al. Nat Genet 2009) . T1D.P - ditto for type I diabetes (Barrett et al. Nat Genet 2009) . Disease - disease in which the SNP was originally reported: AITD autoimmune thyroid disease; AS ankylosing spondylitis; BD CD Crohn's disease; MS multiple sclerosis; PS psoriasis; SLE systemic lupus erythematosus; T1D type 1 diabetes; UC ulcerative colitis. cpma.p - p value for CPMA statistic (chi-squared, 1 df). Genes - nearby notable genes.
Enrichment in immune tissue expression for interacting genes encoded close to SNPs in (A) cluster 1 and (B) cluster 4. Following Rossin et al. we looked for preferential expression of significant network genes in tissue subsets. Of the genes encoded around SNPs in clusters 1 and 4 (as defined in Figure 1), we found that those participating in significant networks are enriched in expression (purple circles) in immune tissues (red bars). Other genes encoded around those SNPs are not enriched in the same tissues (black circles). Thus interacting genes encoded around SNPs associated to the same immune diseases are preferentially expressed in immune tissues. Interacting genes for the remaining significant group, cluster 2, were not enriched.
Conceived and designed the experiments: C Cotsapas, BF Voight, DA Hafler, SS Rich, MJ Daly. Performed the experiments: C Cotsapas, BF Voight, E Rossin, BM Neale, MJ Daly. Analyzed the data: C Cotsapas, BF Voight, E Rossin, K Lage, MJ Daly. Contributed reagents/materials/analysis tools: BF Voight, K Lage, BM Neale, C Wallace, GR Abecasis, JC Barrett, T Behrens, J Cho, PL De Jager, JT Elder, RR Graham, P Gregersen, L Klareskog, KA Siminovitch, DA van Heel, C Wijmenga, J Worthington, JA Todd, DA Hafler, SS Rich, MJ Daly. Wrote the paper: C Cotsapas, BF Voight, JA Todd, DA Hafler, SS Rich, MJ Daly.
1. Vyse T, Todd J (1996) Genetic analysis of autoimmune disease. Cell 85: 311–318.
2. Barrett JC, Hansoul S, Nicolae D, Cho J, Duerr RH, et al. (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 40: 955–962.
3. Graham R, Cotsapas C, Davies L, Hackett R (2008) Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet 40: 1059–1061.
4. Hunt KA, Zhernakova A, Turner G, Heap GAR, Franke L, et al. (2008) Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet 40: 395–402.
5. De Jager PL, Jia X, Wang J, De Bakker PIWd, Ottoboni L, et al. (2009) Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet 41: 776.
6. Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, et al. (2009) Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways. Nat Genet 41: 199–204.
7. Stahl EA, Raychaudhuri S, Remmers EF, Xie G, Eyre S, et al. (2010) Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 42: 508–514.
8. Criswell L, Pfeiffer K, Lum R, Gonzales B, Novitzke J, et al. (2005) Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes. The American Journal of Human Genetics 76: 561–571.
9. Wandstrat A, Wakeland E (2001) The genetics of complex autoimmune diseases: non-MHC susceptibility genes. Nature immunology 2: 802–809.
10. Eaton W, Rose N, Kalaydjian A, Pedersen M, Mortensen P (2007) Epidemiology of autoimmune diseases in Denmark. Journal of Autoimmunity 29: 1–9.
11. Maier L, Lowe C, Cooper J, Downes K, Anderson D, et al. (2009) IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production. PLoS Genet 5: e1000322.
12. Plenge RM, Cotsapas C, Davies L, Price AL, De Bakker PIWd, et al. (2007) Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet 39: 1477–1482.
13. Remmers EF, Plenge RM, Lee AT, Graham R, Hom G, et al. (2007) STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. The New England Journal of Medicine 357: 977–986.
14. Fung EY, Smyth DJ, Howson JM, Cooper JD, Walker NM, et al. (2009) Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus. Genes Immun 10: 188–191.
15. Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, et al. (2008) Shared and distinct genetic variants in type 1 diabetes and celiac disease. The New England Journal of Medicine 359: 2767–2777.
16. Sirota M, Schaub MA, Batzoglou S, Robinson WH, Butte AJ (2009) Autoimmune disease classification by inverse association with SNP alleles. PLoS Genet 5: e1000792.
17. Zhernakova A, van Diemen C, Wijmenga C (2009) Detecting shared pathogenesis from the shared genetics of immune-related diseases. Nat Rev Genet 10: 43–55.
18. de Bakker PIWd, Mcvean G, Sabeti PC, Miretti MM, Green T, et al. (2006) A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. Nat Genet 38: 1166–1172.
19. Rossin E, Lage K, Raychaudhuri S, Xavier R, Tatar D, et al. (2011) Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology. PLoS Genet 7: e1001273.
20. Khanna H, Davis EE, Murga-Zamalloa CA, Estrada-Cuzcano A, Lopez I, et al. (2009) A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nat Genet 41: 739–745.
21. Todd JA (2010) Etiology of type 1 diabetes. Immunity 32: 457–467.
22. Dubois PCA, Trynka G, Franke L, Hunt KA, Romanos J, et al. (2010) Multiple common variants for celiac disease influencing immune gene expression. Nature Publishing Group 42: 295–302.
23. Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, et al. (2009) A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systematic lupus erythematosus. Nat Genet 41: 1228–1233.
24. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, et al. (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41: 703.
25. Hindorff L, Sethupathy P, Junkins H, Ramos E, Mehta J, et al. (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proceedings of the National Academy of Sciences 106: 9362.
26. Johnson AD, Handsaker R, Pulit S, Nizzari M, O'Donnell CJ, et al. (2008) SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics 24: 2938–2939.
27. Gower J (1971) A general coefficient of similarity and some of its properties. Biometrics 27: 857–874.
28. Ward J Jr (1963) Hierarchical grouping to optimize an objective function. Journal of the American Statistical Association. pp. 236–244.
29. Team RDC (2010) R: A Language and Environment for Statistical Computing. Vienna, Austria.
30. Lage K, Karlberg EO, Størling ZM, Ólason PÍ, Pedersen AG, et al. (2007) A human phenome-interactome network of protein complexes implicated in genetic disorder. Nat Biotechnol 25: 309–316.


Ulster County residents could elect to bypass legislators and task a local committee with redrawing county lines.
A forum was held on Wednesday, Oct. 24 from 7 p.m. to 9 p.m. to advocate for this proposal, which has received unanimous approval from the eleven members of the Ulster County Charter Revision Commission (CRC). These commissioners included Gerald Benjamin, Rod Futerfas, Thomas Kadgen and Dare Thompson. The group among a small audience in the College Terrace at SUNY New Paltz. They served as proponents for this amendment in their shared discussion.
This forum was organized by the League of Women Voters of the Mid-Hudson Region, a nonpartisan political organization. They invited CRC members to discuss and explain this proposal as a panel.
The purpose of this proposal is to avoid gerrymandering, a practice that supposedly serves to manipulate district boundaries in order for one party to withhold political favor over others.
This proposal was created in 2001. However, when it was first set forth, Benjamin, who served on both the original and current commission, forgot to specify for this proposal to "go directly to ballot." The state legislature then obtained authority over whether or not the ballot would be submitted to voters, according to Benjamin.
If passed, seven county residents will be selected to serve on this commission, with geographic and racial diversity in mind, according to the proposal. The county legislature and county executive would select four commissioners, who would then appoint the remaining three members. Additionally, elected officials, municipal employees and officers of a political committee would not be able to become commissioners, as this proposal is intended to exclude political influence from the process of reviewing and redrawing county legislative districts.
These members would be chosen in 2021, who would then have two years to produce a map of the 23 Ulster County districts, according to Kadgen. These district boundaries are also required to be redrawn, with each U.S. decennial census, in order to ensure fair and equal representation of all residents.
The adoption status of this proposal will ultimately be decided by the majority vote of Ulster County residents on Nov. 6.


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Albemarle-Pamlico National Estuary Partnership - Ecological Flows
Evaluation of Ecological Flows in North Carolina & Virginia's Coastal Plain
Merchant's Millpond State Park, North Carolina. Photo by APNEP staff.
Timeframe: 2016 - 2018
APNEP's Ecological Flows Action Team has contracted with Dr. Michael O'Driscoll and Caitlin Skibiel of the Coastal Water Resources Center at East Carolina University to identify and collect ecological flow data for the Albemarle-Pamlico region's coastal plain, an area where established methods of determining ecological flow are limited. An ecological flow is defined as the volume of stream flow needed to maintain a healthy aquatic ecosystem. Understanding ecological flows helps ensure that aquatic ecosystems, and the human communities that depend on those ecosystems, receive enough water to remain functional and healthy. The overall goal of this project is to find, organize, and review currently available ecological flow data, which can then assist with analysis of ecological flows in the region and identify data gaps.
"I think that especially in the coastal plain, it's important to study ecological flows because of all the population growth upstream in the Raleigh-Durham area," explains lab technician Caitlin Skibiel, who has been working on this project with Dr. O'Driscoll. "It's all really interconnected." Growing populations use more water, removing it from waterways and lowering that waterway's flow volume, which can then decrease water availability downstream. Downstream water quality can also be affected, depending how the water is used for before it is returned to the system.
Within North Carolina's and Virginia's coastal plain, Skibiel is concerned specifically about low water flow increasing the effects of saltwater intrusion, where brackish or saltwater from the estuary reaches further upstream than it has historically. This saltier water can negatively impact freshwater ecosystems and cause issues for community water supplies.
Caitlin Skibiel is currently compiling data for the Coastal Plain Ecological Flows Evaluation, including identifying sources of surface and groundwater flow within the coastal plain of the APNEP region. This data will be coordinated with real-time and historical hydrologic discharge and water level, water quality, geomorphological, and meterological data. This data will then be centralized in a data storage and analysis platform, and analyzed in order to recommend: which river basins the Ecological Flows Team should focus on first, how to fill existing gaps in data, and applications to address further needs.
APNEP Comprehensive Conservation and Management Plan (CCMP) actions addressed:
E2.2: Develop and maintain an online resource that clearly conveys regional information in support of ecosystem-based management.
A3.3: Develop and refine ecological flow requirements for each major river.
D3.1: Develop and implement a strategy to improve decision-maker's understanding of the costs and benefits of environmental protection, restoration, planning, and monitoring.

redpajama_set_name: RedPajamaCommonCrawl


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This is a procedure to inspect the large bowel, or colon (marked in yellow on the diagram). The procedure involves passing a thin tube into the bottom. Because this can be uncomfortable, the procedure is usually done under sedation. It is a low risk procedure but care has to be taken with the amount of sedation given.
In order for your doctor to get the best possible view and make the colonoscopy easier, your large bowel needs to be cleaned out. How this is done is explained on a separate page, detailing the preparation for colonoscopy. You need to have nothing to eat or drink for 4 hours before the procedure is done, however you make take medications with a sip of water.
Some medications may need to be stopped for up to a week before the procedure. These might include iron tablets, aspirin, clopidogrel, anti-inflammatory drugs. If you have significant heart disease, such as previous heart attacks or coronary stents, you will probably need to continue on your aspirin and/or clopidogrel, so please make sure you discuss this with your doctor.
If you have diabetes, valvular heart disease, a permanent pacemaker or are taking blood thinning medications such as warfarin, dabigatran or rivaroxaban it is important to discuss this with your doctor before you colonoscopy is organised as special arrangements may be necessary.
Before the procedure starts, intravenous sedation is given. If there is an area of abnormality seen, a biopsy may be taken. A polyp is a small growth attached to the bowel wall which over time can occasionally become a cancer. If polyps are found they are usually removed at the time of the examination. Most polyps can be burnt off by placing a wire snare around the base and applying an electric current. Removal of polyps carries a risk of bleeding and perforation.
When you wake up you may feel a little bloated. This is due to the gas that was inserted during the procedure. This will pass over the next hour or so. Very rarely, you may pass a small amount of blood.
You will remain in the hospital recovery area for 1-2 hours until the effects of the medication wear off. The results of the colonoscopy will be discussed with you during this time and a letter will be sent to your local doctor. Usually biopsy results are available after 3-5 days.
Because of the sedation given, it is very important that you do not drive a car, travel on public transport alone, operate machinery, sign legal documents or drink alcohol on the same day as the test. You should have a friend or relative take you home after the procedure and stay with you overnight.
Serious complications of colonoscopy are rare, occurring less than one in every thousand examinations. However complications can occur and include the following.
Intolerance of the bowel preparation: Some people develop dizziness, headaches, vomiting, dehydration & electrolyte imbalances.
Perforation (a hole or tear in the bowel wall): This is a very serious complication and often requires surgery to fix the problem. The surgery might involve a forming a colostomy (stoma).
Major bleeding from the bowel: This is more likely to occur if polyps are removed and occasionally at the time of a biopsy. Rarely, the colonoscopy itself can tear major blood vessels. It is possible if these serious complications occur that you may require a blood transfusion or surgery.
Sedation related: Whenever intra-venous sedation is given there is a risk of allergic reaction to the drugs or aspiration (pneumonia from inhaling gastric contents while sedated). Low blood pressure and low oxygen levels can occur but you will be closely monitored during the procedure and this can usually be rapidly corrected.
No procedure is perfect: Although colonoscopy is considered the most accurate way to examine the bowel, lesions (eg. polyps and cancers) can be missed. This is more likely to occur if the bowel clean out is not ideal.
Rare side effects can occur with any procedure. Death is a very remote possibility.
The colonoscope is completely cleaned between each patient to avoid the risk of transmission of serious infections such as HIV, hepatitis B or C.


Thank you for visiting the website of Schumacher-Kish Funeral and Cremation Services. It is our hope that our website will provide an additional level of service to those families in need. We have designed our site to not only provide a guide to our facilities and the services and products we can provide, but also to be a knowledgeable resource on such topics as planning or pre-planning a funeral and grief support.
We hope your visit will be helpful and informative. Should you need additional information or clarification on some of the site's content, please feel welcome to contact us and speak with one of our experienced directors.


You can make soap like these! If you can get 5 people to join you at your location (Nashville) you and your friends will get a hands-on experience in making handcrafted soap that does not contain detergents or harsh chemicals. You choose your own colors and scents and take home 5 pounds of soap to use, give as gifts or even sell! Email me at nomadhcsc@gmail.com and we can meet and discuss details and prices. I look forward to hearing from you.


text:
Q: PHP Oracle Query Data based on Array in table I have an oracle sql statement.
table data like this:
FORM_NO | PART_NO | CHUTTER_ID
1       | ABC     | 1,3,9,12,15

I have PHP variable
$get_q = "3";

Now I want to query:
$q = oci_parse($c1, "SELECT * FROM tb_test WHERE CHUTTER_ID IN '$get_q'");
oci_execute($q);

The result of query is empty.
Anyone know, how to solve this?

A: You could write the test like this:
"SELECT * FROM tb_test WHERE ',' || CHUTTER_ID || ',' LIKE '%,$get_q,%'"

This appends commas to the value of CUTTER_ID so that it becomes something like:
,1,3,9,12,15,

Then it checks that the above matches this pattern:
%,3,%

where a % represents 0 to any number of characters. The additional commas are needed to make sure also 1 and 15 would be found with this method.
About your original query
Your query is invalid because the IN operator requires the right argument to be a bracketed list, like so (3), without quotes. But even if you would do that, you would get this expression:
CUTTER_ID IN (3)

which is like saying:
'1,3,9,12,15' IN (3)

But that does not make sense. You'd want to test the opposite:
3 in (1,3,9,12,15)

But alas, the database field CUTTER_ID is not suitable for such a construct. Luckily, the alternative with LIKE can work.
SQL Injection
Please note that if the value '3' in your example is derived from user input, then your code is vulnerable to SQL injection. To avoid this, bind the value via  oci_bind_by_name, like this:
$q = oci_parse($c1, "SELECT * FROM tb_test
                     WHERE ',' || CHUTTER_ID || ',' LIKE '%,' || :p1 || ',%'");
oci_bind_by_name($stid, ':p1', $get_q);
oci_execute($q);

Database design
Finally, a list of values in one database field is not a sign of a good database model. This is an example of a database that is not normalised. It does not even meet the first normalisation form.
If you have control over the database design, please consider changing it as suggested in the article linked above. It will improve the speed of your queries.

redpajama_set_name: RedPajamaStackExchange


text:
Beyond Antigua: Celebrating St. Patrick's Day in Montserrat
By: Cinzia Soro
I'm on a ferry travelling from one island to another to celebrate St. Patrick's Day. No, I'm not crossing the Irish Sea from Great Britain to Ireland, but heading across the warm waters of the Caribbean from Antigua to Montserrat
Adventure beckons
Here at Virgin Atlantic we value everyone's individuality, and coming from a foreign land myself, I'm always intrigued by the different cultures of the people I work with.
Back in March I had the opportunity to find out more about one of our Heathrow customer service agents, Shivonne Riley, whose beautiful smile expresses all the warmth and hospitality she inherits from her home country's culture. We've worked together at the airport for the last three years and she always talks proudly of her island, Montserrat, and its fascinating history and traditions. So last month I finally took a chance to experience it in person, and made the journey from Antigua to Montserrat for St. Patrick's Day, with Shivonne as my personal guide.
The other Emerald Isle
Part of the Leeward Islands chain, mountainous Montserrat lies around 27 miles southwest of Antigua. The island has been steadily rebuilding its economy after the devastating Soufrière Hills volcano eruptions of the mid-1990s – which left the southern half of the island uninhabitable – and tourists are now slowly beginning to return.
As soon as you drive around the lush landscape, it immediately becomes clear why it's known as the Emerald Isle of the Caribbean. Thanks to the volcano, the soil is rich and fertile, and all you can see are vivid green hills in every direction, tumbling down towards a ring of black-sand beaches and clear water.
During 'Green Week' in the middle of March, the island becomes greener than ever for the St. Patrick's Day festivities. But why does Montserrat celebrate St. Patrick's Day in the first place?
It all dates back to an 18th-century slave rebellion.
Back in the days of slavery Montserrat was mainly inhabited by Irish land owners who brought slaves from West Africa. Of course, they kept their traditions alive even when away from the motherland, so the Irish families would always celebrate St. Patrick's Day and get drunk and be merry.
On 17th March 1768 a group of slaves took advantage of these festivities to organise a revolt for freedom. Unfortunately, the plan was discovered by the Irish and suppressed, with nine people executed and more than thirty imprisoned and eventually banished from Montserrat. Despite being unsuccessful, the freedom fighters are still commemorated to this day for their efforts and sacrifices. The descendants of those families stayed on the island after the abolition of slavery in 1834 and keep the history of their ancestors close to their hearts.
A sense of camaraderie
Shivonne was born and raised in the neighborhood of St. Patrick's where it all happened, and where the commemorations used to take place every year on the 17th March.
After the catastrophic volcanic eruptions, the southern part of the island was evacuated, including St. Patrick's. Visits to the 'exclusion zone' are severely restricted as the volcano is still active and remains a constant threat. The after effects caused drastic changes to the island and its population, so Shivonne moved away to the UK like a lot of other Montserratians, while the St. Patrick's Day festival moved to Salem in the north, an area which was largely unaffected.
The essence of the commemoration remains, and it's still deeply felt by the community – not only by the people who still live here of course, but also by those like Shivonne who regularly make the trip back to the island at this time of year.
People of all ages are involved in the celebrations. Only 4,500 people currently live on the island, and there's a heartwarming sense of camaraderie. The week is filled with tours of cultural and historic sites, social hikes, and calypso and soca competitions, as well as an Afro Madras fashion show and even a car race in the restricted area, giving people another excuse to spend time together and enjoy the beautiful nature that is dominant in that part of the island. There are day and night parties, and performances by local and international bands, all culminating in the final day's main St. Patrick's event.
The last day starts early, with the 5 am 'jump up' (even if in 'island time' it's more like 9 am!). The meeting point is the secondary school, where a DJ on a truck with a huge sound system plays soca music – the most popular genre in this part of the world – followed by hundreds of people jumping, singing and dancing, bringing the 'fete' (their term for party) to the roads of Salem. As those raucous celebrations draw to a close, the official St. Patrick's parade begins.
People of all ages meet up in Salem centre. Some wear traditional clothes made from the national green, orange and white Madras fabric that represents a mix of African and Irish heritage. Others wear the Masquerades, colourful costumes originating from folk rituals, with tall head-gear, ribbons, small mirrors, bells and masks. The ritualistic dances and prominent masks are symbols of war, guardianship and fertility.
There are other groups wearing different traditional dresses from the African heritage, as well as school classes, modern dancers, steel pan performers, drummers and other percussionists. After parading through the roads of Salem, they perform on the stage at the Heritage Village.
Limin and soca
Sound systems line the streets, with people 'limin' and dancing to calypso, soca and reggae while enjoying drinks and local street food, in particular Montserrat's national dish: goat water; a thick goat meat stew served with crusty bread rolls.
The day ends with a big concert in Salem Park featuring international artists. This year's headliner is the soca/pop group Kes the Band from Trinidad and Tobago, who have people dancing until the sun comes up, not wanting the festival to end.
The whole festival is so authentic and true to its roots. While still being welcoming to visitors from the rest of the world, Montserratians feel no need to adapt it to attract tourists – it's about culture and island life, and keeping Montserrat's identity alive for the people who had to leave and settle abroad. Every year, everyone gets together to experience St. Patrick's Day, so this sense of belonging can be carried on into future generations.
It's a unique experience I'm honoured to be part of. Despite living through such difficult circumstances in both past and present times, Montserratians have always had the power and strength to just keep going, valuing their history and people, and cherishing spending quality time together.
On our way to the ferry for the trip back to Antigua, Shivonne makes sure we stop to drink some water at Runaway Ghaut – a deep ravine where fast-flowing rainwater runs into the sea. A nearby sign describes a local legend: 'If you drink from this burn, to Montserrat you will return'.
A 90-minute ferry service operates five days a week between Heritage Quay Pier in Antigua and Port Little Bay in Montserrat. For more info and booking visit ferry.mniaccess.com
There are also 2–4 daily flights that connect the islands with flymontserrat.com
Virgin Atlantic operates direct flights to Antigua from London Gatwick.
Cinzia Soro
Cinzia works in our Heathrow operations team and travels the world to experience living as a local, discovering new cultures and traditions as well as food and dance. Her ukulele always travels with her and helps spread positive vibes and connect with people along the way. Cinzia grew up in Sardinia and is on a mission to get everyone at Virgin Atlantic to visit her home country
More articles by Cinzia Soro
Categories: Our Places
Tags: Antigua Caribbean
Rowing the Atlantic: An extraOARdinary challenge
The Virgin Atlantic guide to Antigua
Where to go cycling in the Caribbean
Sweet success in Antigua: Discovering Betty's Hope


text:
require 'rails_helper'

RSpec.describe EventPolicy do
  before(:all) do
    @user = FactoryGirl.create(:scout)
    @record = FactoryGirl.create(:event)
    @record.users << @user
  end

  def self.options
    { policy_class: EventPolicy, policy_resource: FactoryGirl.build_stubbed(:event) }
  end

  permissions :index? do
    it_behaves_like 'user basic access'
  end

  permissions :show? do
    it_behaves_like 'user basic access'
  end

  permissions :calendar? do
    it_behaves_like 'user basic access'
  end

  permissions :new? do
    it_behaves_like 'user leader access'
  end

  permissions :edit? do
    it_behaves_like 'user leader access'
    it_behaves_like 'can access thier own'
  end

  permissions :destroy? do
    it_behaves_like 'adult admin access'
    it_behaves_like 'can access thier own'
  end

  permissions :create? do
    it_behaves_like 'user leader access'
  end

  permissions :update? do
    it_behaves_like 'user leader access'
    it_behaves_like 'can access thier own'
  end

  permissions :email_attendees? do
    it_behaves_like 'user leader access'
    it_behaves_like 'can access thier own'
  end

  permissions :sms_attendees? do
    it_behaves_like 'user leader access'
    it_behaves_like 'can access thier own'
  end

  permissions :add_signups? do
    it_behaves_like 'can access thier own'
    it_behaves_like 'adult leader access'
  end

end

redpajama_set_name: RedPajamaGithub


Congratulations to the following students from CP who are advancing to the Region audition! We are so proud of all our students who invested the time and energy to prepare for this experience.
Come to our annual Choir Family Picnic!
This year's theme is DECADES!
This is a great event to meet new friends and your Choir Sibling!
Family members are welcomed and encouraged!
*Wear something you are comfortable getting messy with. But feel free to dress up!
Join our PhotoCircle to share some of your sweet, crazy, and fun moments in choir!
Copyright © 2016, Cavalier Choir Boosters & The Woodlands College Park High School. All rights reserved.


text:
Oliver Inc. Purchase of Boutwell Packaging Represents Third Strategic Acquisition
Oliver Inc. announced it has acquired Boutwell Packaging. Boutwell is a manufacturer of high-quality folding carton and blister card packaging serving personal care, health care, automotive aftermarket, food and beverage, and consumer products markets.
Based in Fitchburg, Mass., Boutwell will continue delivering innovative packaging solutions from its current facility.
"Oliver is pleased to announce the acquisition of Boutwell to strengthen our position as a leading provider of custom paperboard packaging," said Dan Rodenbush, President and CEO of Oliver. "With the addition of the Boutwell team, we will increase our reach into key markets while expanding our capabilities and capacity. We are proud to welcome Boutwell to the Oliver family."
"Boutwell is excited to team up with Oliver," added Ward McLaughlin, CEO of Boutwell. "The combination of Boutwell and Oliver will generate value for our customers by expanding our ability to create unique, innovative, and sustainable world-class packaging."
Oliver has made significant investments in modern equipment, facilities, and people since Pfingsten became the majority shareholder in May 2016. The Boutwell transaction represents Oliver's third strategic acquisition and aligns with the company's strategy to create a leading provider of innovative, high-quality packaging solutions.
The transaction closed on March 31, 2021.
Source: Oliver Inc.
The preceding press release was provided by a company unaffiliated with Printing Impressions. The views expressed within do not directly reflect the thoughts or opinions of the staff of Printing Impressions.
The Week That Was (1/10/2021)
Printing Specialist Joins Ironmark Brand
Graphic Village Acquires OneTouchPoint Cincinnati
DMS Expands East with MSP Acquisition
Target Report: GPA Global Emerges as Consolidator


Canon MX340 Driver Download, Manual Setup, Scanner Driver.
Canon MX340 Software Driver Download & Manual Setup – The Canon MX340 is a multi-function tool for the budget plan aware customer. It's readily available for regarding ₤ 90 online, however, that does not imply they've stinted the requirements.
Certainly, the Canon could print, copy as well as scan, however, it additionally has a fax built-in and also an automatic record feeder. On top of that, the MX340 has Wi-Fi connection also. There's no big color LCD display, however, there is a 2 line display screen, which is fine, however in practice a little bit limiting. The automatic paper scanner could take care of 30 web pages each time at a resolution of 600 x 600, this is boosted to 1200 x 2400 when utilizing the flatbed.
In our examinations, the Pixma MX340 supplied appropriate efficiency. Its plain-text printing rate corresponded throughout COMPUTER as well as Mac systems, at 5.8 web pages each min as well as 5.7 ppm, specifically. On the COMPUTER, 4-by-6-inch shade images on letter-size media published at a price of 1.7 ppm. On the Mac, a near-letter-size picture took 2.5 mins to print (which exercises to concerning 0.3 ppm); a 7.5-by-9.9-inch picture checked at 600 dots each inch in 55 secs; a 4-by-6-inch picture checked at 1200 dpi in 90 secs; and also a solitary web page of message replicated in 21 secs (a price of 2.8 ppm).
This four-color device makes use of 2 ink cartridges, one black as well as the various other tri-colour, as well as these clips inconveniently when you've pivoted up to the scanner area into its 'bonnet-stand'. It has a well-damped launch, to make sure that when you close it, the leading area does not bang down into the print engine.


Why is hunting the way it is?
How does a reindeer protect itself from its enemies? Are humans doing anything to protect the elephants habitat? How does an elephant protect itself from its enemies? How can a dog protect itself from enemies? How many bones are in a African wild dog?


text:
A carpenter from Nazareth
Prizing the Bible from the hand of Christianity
Incarceration, The Sexual Jungle, and the rape of humanity
The degree of civilization in a society can be judged by entering its prisons.
Dostoyevski, The House of the Dead
With this quote, Wilbert Rideau closes his treatise on rape in the US prison system. Written in 1979, The Sexual Jungle is a depressing account of man's inhumanity towards man behind bars. In a perverse power struggle hung on the twisted definition of what constitutes "masculinity", the physically powerful dominate over any who they can break. You either fight the system and face the terrible consequences, or you capitulate and become enslaved. This could mean anything from devoting yourself to one man and becoming his "wife", or being treated as a whore and passed around as a sexual slave. "Since the majority of prisoners don't own slaves, their need for sexual outlet creates a large market for potential profit. In an economic sense, a slave is capital stock, property that can be made to produce income, and prison pimps don't hesitate to put their whores to work hustling for profit." Justification for the behaviour is, "He can't protect himself. Hell - I just proved that. He can't make it in here and you know it. As his old man, I'll take care of him. He give me sex, I give him protection. That ain't no bad deal if you look at it right. Hell - it's more to his benefit than mine."
The inclusion of Dostoyevski's quote breaks down the high wall between prison and the outside world. What goes on behind bars is only a more sordid reflection of what takes place in society: The power struggle, and man's continuous domination of man, "to his injury." Rideau's key paragraph, aiming to explain why prisoners resort to the methods they do, is simply a broad explanation for any of man's actions. "Man's greatest pain, whether in life or in prison, is the sense of personal insignificance, of being helpless and of no real value as a person, an individual - a man." So, in order to validate their sense of manhood and individual worth, they channel "all of their frustrated drives into the pursuit of power, finding gratification in the conquest and defeat, the domination and subjugation of each other." These are the self-same frustrated drives that propel humanity in general. Capitalism is a competitive market. It is a fight for survival: Which company is going to get the business? Who is going to get the job? Employees must compete to win positions, and then have their work assessed and re-assessed in order to keep their jobs. Like a reverse parole board, his is not a bid for freedom, but a bid to remain enslaved.
In the prison system this power struggle manifests itself as violent rape of other men, but even then it is not seen as such.
The act of rape...is not sexual and not really regarded as "rape". Both prisoners and personnel generally refer to the act as "turning out", a nonsexual description that reveal the nonsexual ritualistic nature of what is really an act of conquest and emasculation, stripping the male victim of his status as a "man."
So it might be that we think it rather extreme to brand the treatment of humanity is a form of rape - and, yet it is an act of conquest and emasculation. There is no work that feeds the soul, it is all slavery. Factory work, retail, the military, the civil services - all are pressed into serfdom. Even in the fields in which employees believe they are doing some good they are so tied up with bureaucracy and statistical achievements that those who engage in these fields eventually feel the life draining out of them. It is all designed to prop up the system, cogs keeping the vast machine marching along.
Similar to the oppressed life behind bars, those who give themselves over to the system, who work for the system (and are only too willing to offer their credentials unsolicited - "I'm a doctor/teacher/social worker/nurse") find that once they are in that position they can be bought and sold as property. Authorities alter the system and there is nothing these workers can do about it. They must cooperate and enforce the changes whether they agree with them or not. If they do not co-operate they face the threat of losing their job. With people clamouring for work and the atmosphere of competition constructed by the system, there are plenty who are willing to take over. This is achieved by keeping work at a minimum and making it a competitive market.
Those who brush off this analysis as so much paranoia are those who choose to take the blue pill. More than a quarter of a century before the Warchowski brothers penned The Matrix, Ivan Illich had already made the observation that man had been "reinvented as a source of mechanical power."
Prisoners condemned to the galleys were not much use most of the time, since galleys were most of the time in port. Prisoners condemned to the treadmills produced rotary power to which any of the new machines could be hooked. Up to the early nineteenth century men in English prisons actually laboured on the treadmills to make machines work."
Ivan D. Illich, Tools For Conviviality
Why limit the power source to prisoners when the whole of mankind can be pressed in to service?
Workers find themselves turned out on to the streets when multi-million dollar corporations move their factories overseas to lands where labour is cheap. Obscenely, these same corporations go to great lengths to push their expensive products on to the population they have just turned out, thereby pressing their faces into the dirt of their own poverty. They work hard to make people feel worthless for not being able to afford the latest luxury item. They tempt them with "buy now, pay later" deals, and confine them to lifelong servitude as they work to pay off their ever-mounting debts. It is ironic that Apple chooses to have the forbidden fruit as their logo, a reminder of the first humans being turned out of paradise.
The poverty stricken turn to crime, or prostitution - further blurring the line between the free and the incarcerated. Eventually they too will find themselves thrown into prison, banged up for trying to survive a system that screwed them over in the first place. However, to end up in prison is merely a further way to maintain the status quo. Society has no intention of changing the prison system. It serves a purpose just the way it is. Just as the prison administration is content for things to remain the way they are within the prison walls, so the state is content for the prison system to remain. Authorities turn a blind eye. They want things to stay the same because the fear engendered by the prison system serves to keep the people obedient. Man is able to invent rules and laws which the rest of mankind must abide by under threat of reprisals (incarceration). The systematic rape of mankind, being held down and forced to engage in something you have not consented too. Taxes and fines can be extracted from a population who do not want to be processed, who do not want their fingerprints to be taken and their data to be fed into the system and stored. The prison system will kill a man, or break him. In this way it serves to achieve its ultimate goal and turn out the Compliant Citizen, a task that should have been accomplished in the first prison system we are ever introduced to in life - school. It's hard to read The Sexual Jungle and not look at your own children and think, "What kind of a world have I brought them in to?" Yet we send them to school and into the system to be processed. We set up college and university as a goal, and encourage them to carve out a career and become another cog in the whole monstrous machine.
A bullying mentality is learned in school. Older ones can take advantage of the younger. The younger have to take it because their turn will come. Once there was a term for it: Fagging. A small boy could give himself over to an older pupil, and in return for services rendered - shoes polished, errands run around the school, tea-making - he could receive certain advantages. Even if this practice has been abandoned, there is still a servile spirit encouraged, a heavy emphasis on paying one's dues, and to do unto others what was done to oneself.
Natascha Kampusch was kidnapped at the age of ten and held against her will for eight years until she made her escape a few days after her eighteenth birthday. Once free, she found herself the victim of a different form of incarceration. She was not allowed to leave the police station. She was not free to come and go as she pleased. She had to be processed. She could not process herself. She was not allowed to diagnose herself after her years of imprisonment, she had to be diagnosed by state appointed psychologists. The state would argue that this is for the best, that they are offering protection. Wolfgang Priklopil would make the same claim. In his twisted psyche he was looking after Natascha Kampusch when no-one else would. Priklopil often told her that her parents didn't want her and didn't care. The state insinuates the same thing. It is always on hand, watching over. It implies a parent's lack of care, their inability to protect. The State "cares". The National Health Service "cares". Parents? "Meh - not so much." The state has the monopoly on care, they have defined love. It has been decided democratically, and everyone else must comply. One must bend to the will of the nation.
So it is with this system: We must conform or face the consequences. Self-schooling is looked down upon. Self-diagnosis is scoffed at. We find ourselves enslaved to the state and beholden to the professional strata. We are not educated unless we have been through the school system. We are not healthy unless diagnosed by the medical profession. We are not safe unless policed.
One of the evil acts perpetrated by society is to use children as a bargaining tool. Behind the unspoken threat that children will be removed into care if you do not bend to the system, hospitals become houses of incarceration. Should families find themselves entangled in the medical system, parents are not free to leave the hospital on their own recognisance. They must wait to be processed.
Man cannot conceive of changing the system. There is no need to keep the system going the way it is - it is detrimental to humanity. An alternative needs to be found. Nobody needs to starve, and everybody could receive adequate housing. Instead, we would rather have warehouses full of obsolete product than hand it out in the street. Man changes our viewpoint in an instant as it suits him. He declares belief in the survival of mankind as a whole, but he cannot abide the thought of an individual getting something for nothing, without having earned it. So, he has warehouses full of obsolete junk he doesn't know what to do with because they contain metals that will bleed poisons into the earth, water, and atmosphere. He has landfills full of garbage, rivers overflowing with toxic waste, and prisons full of dangerous men. The whole sorry state is irreversible. The answer is to the incarceration problem is to empty the prison cells. Not all men are a menace to society. They rob and steal because the system is set up against them. They need money for food to survive. This is the system man has created.
Religion is not the answer. It is merely another method of dominance. "Do as we say, or bad things will happen to you." This method finds its roots in scripture as later generations of Israelites constructed a scenario to force people into subjugation. They had a system of laws, drawn up by man but claimed to be given by God. They suggested that in the past, under Moses, the people had not done what they were told and bad things happened. Today, government has assumed the position of God. They set the laws and exact punishment on the criminals.
We may choose not to believe in the Jesus story, but what can't be denied is that anyone who speaks out against the state and its systems will face humiliation. Today Jesus would not be executed - not directly - he would be thrown into the prison system and raped to death because there is a twisted concept of what is defined as a "man". What is more brutal, forty strokes less one followed by a crucifixion, or being attacked and raped by five men and then having a hand thrust into your rectum and a bloody mass of haemorrhoids ripped out? In reality, they both amount to the same thing: "Man dominating man to his injury."
We may not have time for the Bible's pronouncement of judgement upon mankind, but we may be interested to know that in the final analysis God rarely has to do anything. When Gideon's three-hundred men blow their horns and yell their battle cry, the men of Midian "set the sword of each one against the other in all the camp." Once the men of Ammon and Moab had united against the sons of Seir, "they helped each one to bring his own fellow to ruin." And in the pronouncement against Gog of the Land of Magog, "Against his own brother the sword of each one will come to be." In today's prison system men have taken this pronouncement and fulfilled it in the most humiliating way. And outside the prison walls men have succeeded in being no less ruthless in the conquest and emasculation of their fellow men.
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text:
Q: How should I setup Traefik on ECS?  In Short
I've managed to run Traefik locally and on AWS ECS but now I'm wondering how should I setup some sort of load balancing to make my two services with random IPs available to the public.
My current setup on ECS
[Internet]
    |
[Load balancer on port 443 + ALB Security group on 443]
    |
[Target group on port 443 + Security group from *any* port]
    |
[cluster]
    |
[service1 container ports "0:5000"]

While this works, I'd now like to add another container, eg. service2 also with random ports eg 0:8000. And that's why I need something like Traefik.
What I did
Here's Toml file:
[api]

address = ":8080"

[ecs]

clusters = ["my-cluster"]
watch = true

domain = "mydomain.com"

region = "eu-central-1"
accessKeyID = "AKIA..."
secretAccessKey = "..."

Also I've added the host entry in /etc/hosts:

127.0.0.1 service1.mydomain.com
127.0.0.1 service2.mydomain.com

And the relative labels on the containers and I can curl service1.mydomain.com/status and get a 200.
Now my last bit is just the following question:

*

*How should publish all this to the internet? AWS ALB? AWS Network LB? Network Bridge/host/other?

A: AWS ALB vs AWS Network LB depends on who do you want to handle SSL.

*

*If you have a wildcard certificate and all your services are subdomains of the same domain ALB may be a good choice

*If you want to use Let's encrypt with traefik Network LB may be a better choice
In both case your setup will look something like this :
    [Internet]
        |
      [LB]
        |
    [Target group]
        |
    [Traefik]
    |       |
[service1] [service2]

In both case, easiest way to get this is to make traefik ecs services to auto register to the target group.
This can be done at service creation (network configuration section) and can not be done later. Link to documentation
Screen of configuration console


Falling of hair is a normal process. Hair drops out because a new one has developed and grown underneath it. A healthy adult may shed between 50 to 100 hairs in each day. Excessive hair loss may be due to various reasons such as pregnancy, anemia, circulatory problems, thyroid disorders and hormonal problems. Mental disturbance, stress or strain are also sometime cause hair fall as the people suffering from mental strain often found short of vitamin B.
A good balanced diet is essential for healthy hair. High protein diets especially those containing gelatin and cysteine resulting increased growth of hair. Lacks of fatty acids, iron deficiency, zinc deficiencies are leading to hair fall.
Massage the scalp every day 10- 15 minute with your finger tips so as to reach every root of the hair is important for healthy hair. Very few of us know that we have with us a natural hair tonic hidden at the root of our hair. It is the tiny bulb at the root of hair known as papilla. Papilla provides nourishment to each hair by secreting a greasy substance. While massaging, this nourishing grease spread all over the hair and also increases blood circulation.
Then brushes the hair and this also further spread nourishing grease and cleanse the dirt and dust from hair. Do not wash immediately after massage as massage stimulates blood vessels and warms up the area and need cooling for one hour. For extremely dry hair, massage with warm olive oil is beneficial. Massaging after adding one vitamin E capsules in coconut oil also reported better result. Avoid vigorous massage after oiling as this may cause weakening the Papilla.
Cleanse the hair is the next step. The following simple steps to be followed.
Do not apply chemical based shampoo excessively. Use only a mild shampoo with out containing alcohol. Avoid over shampooing which will remove the vital natural oils.
Use a conditioner every time after shampooing. Conditioners soften the hair while adding nutrients and give the hair a shine.
Eat plenty of protein containing foods, complex carbohydrate, fresh fruits, dark green leafy vegetables, eggs, liver and oily fish for healthy hair. Also avoid fried foods, starches and sugary foods.


2 thoughts on "Unneeded vs unneeded"?
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text:
Ravens vs. Titans NFL Predictions Against the Spread? 11/5/17
Drew Sharper
Ravens vs. Titans Pick
Will the Tennessee Titans take a step toward controlling the AFC South when they play host to the Baltimore Ravens today at 1PM ET?
According to oddsmakers at Bovada.lv, Tennessee is favored at home, as the Titans are getting odds of -3.5 points against the Ravens. The over/under total for the contest has been set at 43 points. The home team has won two straight meetings in this series, and the Titans are 5-2 against the spread in the last seven encounters. The public betting in this one has Tennessee getting 64 percent of the wagers at home. Today's game takes place at Nissan Stadium in Nashville, Tennessee. The contest will air live on CBS.
The Titans are coming off a 12-9 OT win over the Browns in Week 7 before taking their bye. Tennessee is 4-3 on the season and 3-4 against the spread. Given the ACL injury to Deshaun Watson at Houston and the Colts putting Andrew Luck on IR, the AFC South seems to be wide open for the Titans. Tennessee has had its offensive struggles this season, averaging just 22.6 points and 333.6 yards per game. Marcus Mariota has been battling a hamstring injury over recent weeks but is believed to have healed up in the bye week. He has thrown for 1,301 yards and four touchdowns this year while also rushing for 124 yards and three scores. Mariota is hopeful to get first-round pick Corey Davis in the lineup this week. He has appeared in just two games this year because of a hamstring injury. Tight end Delanie Walker may not play because of an ankle injury. However, DeMarco Murray and Derrick Henry are both healthy in the backfield. The two have combined for over 700 rushing yards. Defensively, Tennessee is giving up 24.7 points and 340.1 yards per game.
The Ravens are coming off a 40-0 thrashing of the Miami Dolphins in Week 8 to improve to 4-4 on the season. Baltimore is 4-4 against the spread as well, going 2-2 ATS on the road. The Ravens haven't been able to move the ball much this year as well, averaging just 295.1 yards and 21.3 points per game. Joe Flacco suffered a concussion on a nasty hit last week, but is expected to play today. He has 1,290 passing yards with six touchdowns and eight interceptions. Alex Collins is leading the offense with 478 rushing yards while Javorius Allen has 356 yards on the ground. Defensively, Baltimore is holding opponents to 18.5 points and 331.1 yards per game. However, they are allowing 132.8 rushing yards per contest. The unit has 19 sacks and 12 interceptions this season.
Bet on Ravens vs. Titans
At some point the Titans have to get on track, don't they? Tennessee seems to have too much talent to not take a step forward. Mariota seems to be healthy and should be able to use his arms and his legs against Baltimore. That should also help their duo of impressive backs. Baltimore doesn't have an offense that can consistently move the ball, so the Titans won't need many scores to cover. The Titans have covered in six of their last seven at home and I think they do it again today.
NFL WEEK 9 PREDICTION: TENNESSEE TITANS -3.5
Need More winners against the spread? Get $60 worth of FREE premium member picks. Instant Access here.


SALT LAKE CITY — In a pair of resolutions passed last week by the State School Board, Utah's top education officials made their position on the Utah Core Standards clear and called on Utah's governor and lawmakers to support the transition to new college- and career-readiness standards.
The resolutions, which were posted Tuesday on the State Office of Education website, were made partly in response to criticisms that have dogged the state office since Utah's adoption of the Common Core State Standards in 2010.
"There seems to be some confusion surrounding the Common Core so the intent was to help clarify some of the misconceptions about that," said David Crandall, vice chairman of the State School Board.
The Common Core is a series of academic benchmarks aimed at preparing students for higher education. They have been voluntarily adopted by 46 states but have come under fire by conservative groups who view the standards as an intrusion into local control by the federal government.
In Utah, the Common Core standards for mathematics and English language arts are included in the Utah Core Standards, the statewide educational benchmarks established by the democratically elected State School Board.
The Common Core is a series of academic benchmarks aimed at preparing students for higher education.
"The executive authority over education for the state rests with the State Board of Education," Crandall said. "That's the reason that we put that in (the resolution), to make it clear to the public that it is an executive responsibility that we have to adopt the standards for the state."
But opponents of the standards have called on lawmakers to intervene and end the state's participation in the Common Core. In the resolution passed last week, the school board states that school officials held public discussions and studied the standards prior to their adoption and urges lawmakers to resist "erroneous" information spread by critics.
"Be it resolved that the Utah State Board of Education calls upon the governor of the state of Utah and the members of the Utah Senate and the Utah House of Representatives: 1) to support the goal of career and college ready outcomes for Utah students; 2) to resist the demands calling to 'remove Utah from the Common Core' based on erroneous information; and 3) to collaborate with the State Board of Education in supporting teachers, parents and students during the transition to these new Utah Core Standards," the resolution states.
The Utah State Board of Education voted Friday to adopt a set of new education standards in reading and mathematics.
The second resolution establishes the State School Board's position on the storing and sharing of personal student information and urges lawmakers to "pass and/or revise such laws as are necessary to strongly secure and protect the sensitive personal data of students and teachers." The resolution is a response to concerns by some critics of the Common Core that participation in the standards would lead to Utah student information being stored in a national database.
Crandall said part of the confusion around the Common Core stems from a misunderstanding of what the standards are. He said the Utah Core Standards are a series of benchmarks students in a particular grade are expected to reach and do not dictate the curriculum of an individual school district, school or classroom.
For example, a mathematics standard may call for students in a certain grade to be able to multiply and divide fractions, which would be reflected in end-of-level testing, but the day-to-day classroom content would be up to local control.
"How the individual districts implement that and what specific readings they have (students) do, what books they have and what they include in their curriculum are completely up to the local school districts and charter schools," Crandall said. "Ultimately what it comes down to is we want students to be career and college ready."
Full transition to the new Utah Core Standards is scheduled to be completed for the 2014-15 academic year. Crandall said each school district is taking their own steps to adopt the standards, but generally the efforts are progressing well statewide.
"For the most part, there's pretty broad support from the districts themselves and from the charter schools," he said.


Our practice is centered on traditional chiropractic principles straight from the 100 year old tradition of B.J. Palmer, a philosophically and scientifically-driven doctor. We believe that our duty is to share with our patients how a balanced nervous system is the major key to vibrant health. Dr. Roger offers public health talks every Wednesday (6:00pm-7:00pm) for new patients in order to help you better understand the importance of a balanced nervous system.
Traditional based chiropractic care can benefit all human beings regardless of whether or not they have aches and pains in the back. It helps to maintain the integrity of the spine's alignment which is an important factor in maintaining a properly functioning nervous system and ultimately a healthier body.
It is empowering both to the patient and the doctors to understand that the body has an incredible ability to heal itself when nerve interference is removed. The human brain, through the spinal cord and nerves, controls everything in the body. Imagine what a better functioning nervous system can do for you and your family physically, chemically and emotionally.
People know they can turn to a chiropractor for back pain relief, but they are just now beginning to realize the possibilities of chiropractic. We believe strongly in the benefits of chiropractic in achieving optimum health without the use of drugs or surgery.
We made the decision to sell our two very successful chiropractic practices in the Phoenix, AZ area and make the move to Ormond Beach, so we could be close to our family. We want our children (Boston 12, Dayva 10, and Max 3) to grow up with the benefits of a large family support group.
We are committed to bringing the community better health and a better way of life by teaching and practicing the true principles of chiropractic wellness care. Our goal is to have a wellness-based practice filled with members from the community that are eager to improve their overall expression of health through regular chiropractic care. We look forward to seeing your family at our practice to start enjoying a healthier spine and a healthier body.


The Aachen Computer Graphics Library (we are not very creative with names) is intended to simplify prototyping and development of (OpenGL) graphics applications. It proved a platform independent way for loading OpenGL function pointers, wrappers for OpenGL objects, helper classes (e.g. a camera class) and functions for loading some simple mesh and texture formats. It is not a full rendering engine. Basic knowledge of OpenGL 3.2 or later or OpenGl ES 3.0 is required to understand the basic concepts. In addition to the library, some examples are provided.


text:
Q: как удалить повторяющиеся значения в массиве чтобы остались только не повторяющиеся Есть массив
Array
(
 [0] => 1
 [1] => 2
 [2] => 2
)

как удалить из него повторяющиеся значения? Чтобы результат был
Array
(
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array_unique оставляет одну двойку, которая не нужна


Welcome to the Recurrent Events weekly news update for retro pop culture headlines, links, videos, and more! Christmas is only a couple weeks away so be prepared for more holiday articles and links from RD80s and our friends. A little reminder that coming this Thursday Dec 15 we'll be featuring a new article and Memory Jogger Podcast as a part of an '80s Christmas collaboration. We'll be telling you about out Top 3 Gifts we received as kids in the '80s (a few more in the podcast) along with 80s Reboot Overdrive, Return to the 80s, Weegie Midget, and Killer Kitsch.
I also wanted to invite all my fellow bloggers to enter the Retrodaze Christmas Article contest between now and December 20. Top prize is a $750 Amazon gift card! Lee and Linz over at Pop Rewind will be judging the contest and have all the details. I've submitted my article and will share on social media when it goes live. It's all about Christmas 1985 and my first camera which was a present that year.
The new Ducktales series is coming next summer! The Disney television animation news YouTube channel debuted the following teaser this week and says the 1st season will consist of 21 half-hour episodes and two one-hour specials. As long as they keep the theme song (which sounds like they will), I'm on board for checking it out!
Here are your Recurrent Events links for Dec 10, 2016!


The Texas & Pacific purchased five 4-8-2s (road numbers 900 through 904) from the American Locomotive Company in 1925. These "Mountains" were designated as Class M-1 and had 27 x 30 cylinders, 73" drivers, a 210 psi boiler pressure, a tractive effort of 52,500 lbs and weighed 360,500 pounds.
In 1928, another five 4-8-2s were delivered. This time, they came from the Baldwin Locomotive Works and were designated as Class M-2 and assigned road numbers 905 through 909. These locomotives were very similar to the Class M-1s except for an increase in total weight. Later, the boiler pressure of these last five oil burners was raised to 225 psi, which increased the tractive effort to 57,300 pounds.
There are no surviving T&P "Mountains".
Five built in 1926 by Alco and described in Railway Age Gazette. Data from T&P 1 - 1950ca Locomotive Diagrams supplied in May 2005 by Allen Stanley from his extensive Rail Data Exchange. Works numbers were 66444-66448 in November 1925.
Firebox had combustion chamber and two Nicholson Thermic Syphons of 70 sq ft total heating surface, boiler fitted with Elesco feedwater heater. The Baldwin engines of 1928 had some slight differences; see Locobase 8511.
Al1 ten 4-8-2s handled the long-haul passenger trains such as the Sunshine Special, the Texan, and the Southerner.
Data from T&P 1 - 1950ca Locomotive Diagrams supplied in May 2005 by Allen Stanley from his extensive Rail Data Exchange. (Thanks to John B Price for his 9 June 2016 email correcting the feedwater information.) See also DeGolyer, Volume 80, pp. 664+. Works numbers were 60551-60555 in July 1928.
The first five Mountains procured for passenger service by the T & P came from Schenectady in 1926 (See Locobase 229). The current entry describes the later five that arrived three years later. Like the M-1s, the M-2s had fireboxes whose heating surface area included 119 sq ft (11.05 sq m) in the combustion chamber and two Nicholson Thermic Syphons adding 70 sq ft (6.5 sq m).
The Walschaert valve gear operated 14" (356 mm) piston valves with 8" (203 mm) travel. Unlike the M-1s, which had Elescos, the M-2 boiler was fitted with the Coffin C-80 feedwater heater. The differences between the two classes were admittedly small: a slight increase in grate area and, consequently, in firebox heating surface and a more substantial reduction in superheater area.
Al1 ten 4-8-2s handled the long-haul passenger trains such as the Sunshine Special, the Texan, and the Southerner. The T & P was an early adopter of an all-diesel motive-power roster and the last steam run of any sort came in 1951.


When working with a large set of routes, roughly exceeding 30,000 route table entries, TNSR may require additional memory to be allocated for the VPP dataplane Forwarding Information Bases (FIB). Smaller routing tables do not require special configuration.
The format of the size is <number>[KMG], for example: 512M or 1G for 512 Megabytes or 1 Gigabyte, respectively.


but every person is a special kind of artist."
Art, Design, & Craft are qualities with which we can approach any personal task or profession. Your Art & Craft evolves as you ask yourself the deeper questions regarding what you do and how you do it. Perhaps you paint or write. Perhaps you fix cars or manage people. No matter what kind of "artist" you are, you are drawn to that sense of flow and connection in your work. Few things beat the feeling that something new has happened because you were there to welcome it.
The creative life is much like a hike into the woods. You get off the grid and out of the city where you can enjoy the wild beauty of nature, stretch your legs and feel yourself coming back into life. However, getting off the beaten path also means that you can get lonely, get wet, get hungry, and get turned around. Joy and trouble go together. Whether you are just beginning to think about how your life could be more creative or are deep into your craft, this search is central to meaning and happiness in your life. At the same time it can throw you up against every kind of practical trouble, philosophical enigma, and personal block.
I have walked this unmarked path for decades. I offer companionship, advice, and new challenges to professional and amateur artists - and to anyone who wants to make their life or their job more creative and real.


text:
Antonio Orsini (n. Nàpols, 1843) fou un compositor i pianista italià.

Estudià el piano amb Antonio Coop, i després d'haver-se donat a conèixer com a concertista en la seva vila nadiua, es presenta als públics de Roma, París i Londres. De retorn a la seva pàtria a causa del servei militar, guanyà per concurs el càrrec de director de banda d'un regiment d'infanteria.

A Nàpols publicà:
 Fughe per 4 voci.
 Norme per apprendere la composizione musicale ed il contrappunto.
 Schema di un indirizzo all' arte del canto.

A més, se li deu, l'òpera Benvenuto Cellini, que no tingué èxit.

Bibliografia
 Enciclopèdia Espasa Volum núm. 40, pàg. 690 (ISBN 84-239-4540-5)
 Treballs per o sobre Antonio Orsini en biblioteques (catàleg WorldCat)

Compositors d'òpera italians
Napolitans

redpajama_set_name: RedPajamaWikipedia