text:
A bi-dimensional genome scan for prolificacy traits in pigs shows the existence of multiple epistatic QTL
José L Noguera1,
Carmen Rodríguez2,
Luis Varona1,
Anna Tomàs3,
Gloria Muñoz2,
Oscar Ramírez3,
Carmen Barragán2,
Meritxell Arqué1,
Jean P Bidanel4,
Marcel Amills3,
Cristina Ovilo2 &
Armand Sánchez3
Prolificacy is the most important trait influencing the reproductive efficiency of pig production systems. The low heritability and sex-limited expression of prolificacy have hindered to some extent the improvement of this trait through artificial selection. Moreover, the relative contributions of additive, dominant and epistatic QTL to the genetic variance of pig prolificacy remain to be defined. In this work, we have undertaken this issue by performing one-dimensional and bi-dimensional genome scans for number of piglets born alive (NBA) and total number of piglets born (TNB) in a three generation Iberian by Meishan F2 intercross.
The one-dimensional genome scan for NBA and TNB revealed the existence of two genome-wide highly significant QTL located on SSC13 (P < 0.001) and SSC17 (P < 0.01) with effects on both traits. This relative paucity of significant results contrasted very strongly with the wide array of highly significant epistatic QTL that emerged in the bi-dimensional genome-wide scan analysis. As much as 18 epistatic QTL were found for NBA (four at P < 0.01 and five at P < 0.05) and TNB (three at P < 0.01 and six at P < 0.05), respectively. These epistatic QTL were distributed in multiple genomic regions, which covered 13 of the 18 pig autosomes, and they had small individual effects that ranged between 3 to 4% of the phenotypic variance. Different patterns of interactions (a × a, a × d, d × a and d × d) were found amongst the epistatic QTL pairs identified in the current work.
The complex inheritance of prolificacy traits in pigs has been evidenced by identifying multiple additive (SSC13 and SSC17), dominant and epistatic QTL in an Iberian × Meishan F2 intercross. Our results demonstrate that a significant fraction of the phenotypic variance of swine prolificacy traits can be attributed to first-order gene-by-gene interactions emphasizing that the phenotypic effects of alleles might be strongly modulated by the genetic background where they segregate.
In the last few years, a major breakthrough in the understanding of the genetic factors that shape complex traits has been the demonstration that, in several species, a non-negligible fraction of the genetic variance is explained by epistatic interactions. The recent identification of multiple epistatic QTL controlling complex traits in mice [1–4], chickens [5, 6], and in model organisms such as yeast [7] and Drosophila melanogaster[8, 9] has been a major achievement in the understanding of the genetic nature of complex traits. In addition, the discovery that gene expression is modulated, amongst others, by a plethora of regulatory RNAs with diverse functions and properties has added a new and thick layer of complexity in the subsequent identification of the polymorphisms involved in these interactions, since many of them might reside in non-coding regions [10].
In domestic species, traits relying on reproductive physiology, such as prolificacy and fecundity, have a notable impact on the financial outcome of farming enterprises. In pigs, prolificacy is a complex trait that displays a low heritability and strong heterosis [11]. One-dimensional studies have reported the existence of several QTL affecting litter size in pigs [12–16]. However, only one of the reported QTL was significant on a genome-wide level (p < 0.05) [16], and there was a general lack of positional concordance amongst different genome scans [17]. More importantly, these QTL studies exclusively dissected the additive and dominance components of litter size, thus neglecting the analysis of epistatic interactions that, paradoxically, are expected to explain a substantial portion of genetic variation of reproductive traits [18]. In consequence, many unsolved questions concerning to the genetic architecture of pig prolificacy still remain to be answered. Which are the specific contributions of dominance and epistasis in modelling the phenotypic expression of this complex trait? If epistasis is important, which are the dimensions, geometry and intricacy of the network of interacting loci and which types of epistatic interactions are more relevant? In a cross between two inbred mice strains Peripato et al. [3] demonstrated the existence of eight interacting QTL that explain almost 49% of the phenotypic variance of litter size in this cross. These results highlighted the importance of non additive genetic variance as a fundamental component of prolificacy. Nevertheless, laboratory mice strains are usually bred in a very stable environment, where fluctuations are kept to a minimum, and they have been the subject of an intense process of genetic selection without parallel in any other mammal species. Moreover, mice belong to a different superorder (Euarchontoglires) than most of mammalian domestic species (Laurasiatheria), so it is reasonable to expect that in these two distantly related taxonomic groups the biology of reproduction can differ in many instances.
The relevance of the aforementioned questions led us to analyse the genetic architecture of prolificacy traits in pigs. In this way, we have performed an F2 intercross between two distinct European and Asian breeds, the Iberian and Meishan porcine breeds. Chinese Meishan is one of the most prolific pig breeds of the world being an excellent candidate population to perform these kinds of studies [19]. Iberian is an autochthonous Spanish breed with a very low prolificacy [20]. There is a very marked phenotypic difference for prolificacy traits between these two breeds (around 7 piglets per parity), being 14.3 the mean for the number of piglets born alive per parity of the Meishan breed [19] and 7.0 the mean for this trait of the Iberian Guadyerbas strain [20]. Interestingly, the ancestors of these breeds are assumed to have diverged at least 150,000 years before present without subsequent introgressions [21]. In consequence, it is reasonable to expect that these breeds have evolved, since then, by following independent processes of artificial selection and genetic drift, thereby establishing different adaptive epistatic genetic complexes [22]. In the current work, we have performed both a one-dimensional and a bi-dimensional genome-wide scans for prolificacy traits by employing this Iberian by Meishan F2 intercross as a genetic resource. Our main objective was to elucidate if epistasis makes a major contribution in shaping the phenotypic variability of prolificacy in pigs.
Phenotypic data recorded in the F2 sows and linkage map
A description of the data and statistics of phenotypic records of number of piglets born alive (NBA) and total number of piglets born (TNB) in the F2 population is given in Table 1. The phenotypic variance was 10.24 and 9.61 for TNB and NBA, respectively. The linkage map of the 115 markers used in the QTL analyses is shown in Table 2. Marker order and distances as well as average chromosome lengths were in general agreement with other mapping projects and the USDA genome database http://www.animalgenome.org/pig/. Markers provided coverage of the 18 autosomes, with intervals between adjacent markers that were below 20 cM whenever possible. The average marker interval was 17.6 cM (sex-averaged map distance).
Table 1 Data structure for number of piglets born alive (NBA) and total number of piglets born (TNB) in the Iberian × Meishan F2 experimental population.
Table 2 Description of the markers employed for linkage analyses
One dimensional genome scan for TNB and NBA
Results of the whole-genome scan using a single-QTL model for TNB and NBA are summarized in Table 3. Two genome-wide highly significant QTL were identified on SSC13 (P < 0.001) and SSC17 (P < 0.01) at similar positions for both traits. In SSC13, the single QTL for NBA and TNB were found at positions 50 and 55 cM, respectively (Table 3), sharing an overlapping region located between markers SW398 and SW2440. The most likely position for the QTL found on SSC17 was at 22 cM for both traits (Table 3).
Table 3 Significant single quantitative trait loci (QTL) for number of piglets born alive (NBA) and total number of piglets born (TNB)
Highly significant additive and dominance effects were detected for the SSC13 and SSC17 QTL, although the direction of these effects (Iberian vs. Meishan) depended on the chromosome under consideration. For instance, the QTL on SSC13 for NBA increased additively by 0.71 (± 0.18) piglets per copy of the Meishan allele and it had a dominance effect of 0.69 (± 0.25) piglets. Conversely, the Iberian allele was the one associated with an increase in 0.73 (± 0.19) piglets per copy for the QTL on SSC17. Moreover, this QTL on SSC17 displayed a negative dominance effect (-0.82 ± 0.29). We estimated the degree of dominance as the ratio d/a between the estimated dominance (d) and the absolute value of the additive effect (a). Values of d/a larger than unity corresponds to overdominance, while a d/a ratio between 0 and 1 represents partial dominance. In both cases (QTL on SSC13 and SSC17), the estimated d/a values were consistent with a complete dominance situation. Similar values of additive and dominance effects were obtained for the TNB QTL on SSC13 and SSC17 (Table 3), a result that is not surprising since these two traits are highly correlated. Besides, the proportion of phenotypic variance explained by these two single QTL detected on SSC13 and SSC17 ranged from 2% to 3% for both TNB and NBA.
Bi-dimensional genome scans for NBA and TNB
Identification of multiple interacting QTL for NBA and TNB
Results from the bi-dimensional genome scan for NBA are shown in Table 4. Four bi-dimensional genome-wide highly significant (P < 0.01) and five significant (P < 0.05) epistatic interactions between QTL were found. We confirmed that all the observed epistatic interactions were consistently detected across families rather than being the consequence of a single sire effect, a feature that is particularly important when the number of founder males is moderate or even small. The results obtained through the likelihood ratio test were further confirmed by using other approaches. First, a false discovery rate (FDR) was calculated based on the nominal P-values every 30 cM, with a result of 0.018 for a P-value lower than 0.001. Moreover, parametric bootstrapping confirmed the significance of the results.
Table 4 Results of a bi-dimensional genome scan for number of piglets born alive (NBA)
A graphical overview of the epistatic interactions for NBA (red arrows) is shown in Figure 1. As much as twelve of the 18 pig autosomes (1, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15 and 18) were involved in these interactions, forming a complex network with a non-radial geometry. This means that a specific region did not interact simultaneously with multiple loci, but with a very limited number of them (usually interactions were one to one). For example, the SSC12 region located at 11 cM, interacted significantly with another SSC12 region at 89 cM (Figure 1; Table 4). Similarly, two non-overlapping SSC6 QTL regions showed epistatic interactions, one of them with QTL on SSC1 and SSC7 (SSC6, 54-69 cM) and another one with SSC14 (SSC6, 1-10 cM). As shown in Figure 1, other pig chromosomes exhibiting more than one significant interacting QTL were SSC1 (at positions 76 and 153 cM respectively), and SSC7 (at positions 28 cM, and 107 cM). An interesting feature of our analysis was that the highly significant NBA QTL identified in the one-dimensional genome scan (SSC13 at 50 cM and SSC17 at 22 cM) did not show any significant epistatic interaction with other regions across the genome, meaning that its mode of action is purely additive. In contrast, a NBA QTL found on another region of SSC13 (73 cM) had significant epistatic interactions with a QTL located at position 4 cM of SSC9. Similarly, in mice, Peripato et al. [3] identified two significant QTL for litter size in a one-dimensional genome scan (chromosomes 7 and 12) that did not emerge in the bi-dimensional analysis (chromosomes 2, 4, 5, 11, 14, 15 and 18). In the light of these results and ours, we could conclude that there is a low concordance between the QTL identified in one- and bi-dimensional genome scans. This means that, in general, the additive and epistatic components of prolificacy traits encompass different sets of genes.
Network representation of the epistatic QTL interactions in thirteen pig chromosomes ( SSC ) for prolificacy traits NBA (red arrows) and TNB (black arrows).
With regard to the bi-dimensional genome-wide scan for TNB, we found three genome-wide highly significant (P < 0.01) and six significant (P < 0.05) epistatic interactions (Table 5; Figure 1). Thirteen out of the 18 pig autosomes were involved in the epistatic QTL interactions for both traits. However, the network of interacting QTL for TNB was not identical to the one reported for NBA. In this sense, only around one third of the QTL epistatic interactions detected in the current study were coincident in both traits. This was an unexpected result since NBA and TNB display a high genetic correlation (rg~ 0.9) and they are expected to share a similar genetic architecture [11]. Moreover, the number of chromosomes displaying multiple interactions was higher for TNB (SSC1, 7, 12, 13 and 14) than for NBA. Notably, four epistatic QTL on SSC7 showed significant interactions with QTL located on SSC6 (60 cM), SSC13 (77 cM) and SSC1 (79 cM and 139 cM, respectively). Other epistatic interactions involved two overlapping regions of SSC13 with one region of SSC7 and one SSC9 QTL, a feature that demonstrates the remarkable complexity and intricacy of these networks. Finally, it is worth mentioning that if we would have assumed a type 1 error α = 0.10, which corresponds to a genome-wide critical value of 25.14 for the LR test, we would have been able to detect 11 and 9 additional epistatic interactions between QTL across the genome for NBA and TNB, respectively (results not shown).
Table 5 Results of a bi-dimensional genome scan for total number of piglets born (TNB)
Partition of the phenotypic variance explained by epistatic QTL
We estimated the proportion of the phenotypic variance explained by epistatic genetic components for each TNB and NBA significant epistatic QTL pair. This contribution to the total phenotypic variance ranged from 3.26% (SSC14-SSC15) to 4.04% (SSC12-SSC12) for TNB and from 3.10% (SSC1-SSC6) to 3.62% (SSC9-SSC13) for NBA. The relative contribution of epistasis to the total phenotypic variance was estimated by adding the estimates of the partial epistatic effects of each epistatic interaction. The total phenotypic variance explained by the joint genetic effects of all epistatic QTL pairs for NBA and TNB was 37.6% and 42.4%, respectively. Nevertheless, we would like to mention that this approach might lead to an overestimation of the epistatic contribution because the models employed in our analysis are exclusive [23]. We have calculated the repeatability with a standard animal model, resulting in an estimated value of 0.27 for both TNB and NBA. This value should be considered as the limit of the total variance explained by genetic effects. This result evidences that our estimates of epistatic contributions are clearly overestimated but, in spite of this drawback, we think it is reasonable to assume that a significant proportion of the phenotypic variance of prolificacy is explained by the joint genetic effects of epistatic QTL.
Classification of epistatic effects for NBA and TNB
All four forms of epistasis (a × a, a × d, d × a and d × d) were detected among the significant epistatic pairs. In total, 9 a × a, 7 a × d, 11 d × a, and 16 d × d significant interactions were detected (Tables 4 and 5). For the SSC1-SSC6 (NBA) and SSC8-SSC14 (TNB) epistatic pairs, only one type of epistasis was significant (d × d, and a × d, respectively); whereas, the remaining pairs presented two or more types of epistasis, leading to more complex patterns of interactions. We plotted the genotypic values expected for each genotypic class (Figure 2), thus identifying 'dominance-by-dominance' and 'coadaptive' patterns of epistasis as described by Carlborg and Haley [18] and Carlborg et al. [4]. The 'dominance-by-dominance' pattern of epistasis was found in several epistatic QTL pairs and corresponded to interactions were a significant d × d effect was found. In positive d × d interactions (Figure 2a), the genotypic value of double heterozygotes I1M1-I2M2, (being I = Iberian alleles and M = Meishan alleles for loci 1 and 2) was superior to that of simple heterozygotes (I1M1-I2I2, I1M1-M2M2, I1I1-I2M2, and M1M1-I2M2); a pattern that was reversed in negative d × d interactions (Figure 2b).
Genotypic values expected for each epistatic pattern detected in the experimental F 2 Iberian × Meishan intercross. SSC: Sus Scrofa Chromosome. Genotypes are shown as II (Iberian/Iberian homozygote), IM (Iberian/Meishan heterozygote), MM (Meishan/Meishan homozygote).
According to Carlborg and Haley [18], the 'coadaptive' type of interaction occurs when positive a × a interaction effect is significant. This form of epistasis leads to enhanced performance of parental double homozygotes (I1I1-I2I2 and M1M1-M2M2) in comparison to the hybrid double homozygotes (I1I1-M2M2 or M1M1-I2I2). As an example, we found this specific pattern of epistasis in the NBA epistatic QTL pair SSC10-SSC15 (Figure 2c).
Additionally, we found another epistatic pattern where only significant a × d and/or d × a effects were present. These pairs of interacting QTL were included in a category that we named 'additive-by-dominance' epistasis because a × d and d × a interactions showed exactly the same pattern. In positive 'additive-by-dominance' interactions, one locus is overdominant, neutral, or underdominant, depending on the genotype at the second locus. Conversely, the second locus is additive, with the favoured allele being dependent on the genotype at the first locus. In negative 'additive-by-dominance' interactions, the genotypic values of homozygotes at one locus (_._I2I2 and _._M2M2) deviate from what is expectable under an additive model only when the second locus is heterozygous (I1M1-I2I2 and I1M1-M2M2, Figure 2d).
Finally, we considered as a separate category those QTL pairs that could not be classified into any of the preceding epistasis models. The main common feature of QTL pairs gathered in this group was that they all had a significant a × d or d × a epistatic term together with significant a × a and/or d × d terms, leading to 'complex' patterns of interactions (Figure 2e). These complex patterns might be explained by the existence of higher order interactions involving more than two loci or simply because small sample size for certain genotypic classes might lead to inaccurate estimates of the epistatic effects.
Identification of genome-wide significant QTL with additive and dominant effects on pig prolificacy
In the single QTL analyses, we found two genome-wide highly significant QTL located on SSC13 and SSC17 affecting NBA and TNB. So far, and to the best of our knowledge, only one study has described a genome-wide significant QTL (P < 0.05) detected at 88 cM on SSC15 for NBA [16]. In the current work, the mode of gene action strongly differed amongst QTL. For instance, the additive effect detected for the SSC13 QTL stemmed from the Meishan breed, and determined an increase of 0.71 and 0.61 piglets for NBA and TNB, respectively. This result is in agreement with the phenotypic differences observed between the purebred parental lines. Conversely, beneficial alleles for the QTL found on SSC17 appeared to derive from the Iberian breed, with increases of 0.73 and 0.68 piglets for NBA and TNB, respectively. These cryptic Iberian QTL alleles, which increase prolificacy, provide a compelling example of the complexity of the genetic architecture of these traits. In addition, significant dominance effects were also detected for the two mentioned QTL; however, the direction of the effects was complete dominance for the QTL on SSC13, and recessivity for the QTL at SSC17.
Our results confirm the existence of several previously reported suggestive QTL for litter size in pigs. De Koning et al. [13] described one suggestive QTL for TNB on SSC17 (43 cM) in an F2 cross between Meishan and commercial Dutch lines. Bidanel et al. [24] reported a QTL for ovulation rate on SSC13 with a similar location (46 cM) and effect (favourable dominant effect of the Meishan allele of 0.7 ova shed). The experiment of Bidanel et al. [24] involved an F2 cross between the same Meishan population employed in our study and a Large White population. Moreover, Cassady et al. [12] described a QTL for number of stillborn piglets on SSC13 (101 cM), although its location is relatively distant to the one reported by us (50-55 cM). Other QTL for litter traits have been described on SSC5, SSC6, SSC7, SSC8, SSC11, SSC14, SSC16 and SSC18[12–15, 25]. However, and as mentioned above, the majority of QTL reported in previous studies none reached the genome-wide significant threshold while two QTL identified in our study did. The most likely explanation for this discrepancy relies on the fact that most of previous experiments involved crosses between the Meishan breed and other standard European pig populations, such as Large White pigs, which have been shown to differ in only three to five piglets born [26]. Moreover, standard European breeds were strongly introgressed with Chinese breeds in the 18-19th centuries and, in consequence, they might not completely fulfil the assumptions and requirements of the F2 intercross design. Conversely, the Meishan and Iberian breeds are highly divergent both at the phenotypic (about 7 piglets per parity) and genetic levels. In this way, phylogenetic studies carried out with mitochondrial DNA have revealed that the Iberian breed has never been introgressed with Asian alleles [21]. Finally, the number of available reproductive records was much larger in our experiment (881 experimental data) than in previous studies (between 200 and 400 experimental data) [12–15, 25].
Phenotypic variation of prolificacy traits is affected by a complex network of epistatic QTL
The statistical evidence suggesting that epistasis might be an important component of reproductive traits in mice [3] led us to perform a bi-dimensional genome scan for NBA and TNB. This analysis allowed us to demonstrate that phenotypic variation of these traits can be strongly influenced by a complex network of interacting loci. In this sense, this is the first study that shows genome-wide significant epistatic QTL affecting prolificacy in pigs. After implementing the highly stringent Bonferroni correction for multiple testing, as much as seven QTL interactions remained significant at the 1% bi-dimensional genome-wide level, whereas 11 were significant at the 5% genome-wide level. Rather than identifying one or a few master regions interacting with multiple loci (which would have yielded a star-like geometry of interactions), we found that most chromosomal regions interacted with a single counterpart. However, almost all chromosomes in which significant epistatic QTL were found participated in more than one interaction. Five of the significant epistatic interactions detected had pleiotropic effects on both TNB and NBA traits, whereas five were only related to TNB and three to NBA. These surprising differences for two highly genetically correlated traits [27], might be interpreted in the light of the statistical values of the Likelihood ratio obtained in the contrast between models and the stringent bi-dimensional genome-wide threshold assumed. For instance, the chromosome pair SSC10-SSC15 reached an LR value of 29.41 (p < 0.05) for NBA and an LR value of 22.33 ("no significant") for TNB. Alternatively, there might be a biological meaning behind the specific differences observed in the geometry of the NBA and TNB networks, thus indicating that although similar metabolic and physiological pathways may be implicated in the regulation of both traits, other mechanisms may be operating independently.
Epistatic QTL for pig prolificacy display different types of interactions
This genetic dissection of the epistatic component of prolificacy in pigs was completed with an analysis of the types of interactions detected in the bi-dimensional genome-wide scan. All the epistatic QTL had at least one significant type of interaction (see tables 4 and 5). In total, nine pairs showed additive by additive (a × a) epistasis, which in certain circumstances can have a 'nullification effect' because epistasis might cancel out the effects of individual loci at intermediate frequencies, making difficult to detect them in a conventional one-dimensional genome scan [28]. Furthermore, seven pairs showed additive by dominance (a × d) epistasis, eleven pairs showed dominance by additive (d × a) epistasis, and sixteen pairs showed dominance by dominance (d × d) epistasis. All these forms of epistasis contribute to heterosis [29]. It has been widely supported that heterosis plays an important role in the genetic architecture of reproductive traits [11, 12].
Several patterns of interactions among genotypes were identified and classified according to Carlborg and Haley [18] and Carlborg et al. [4]. Eight pairs were classified as 'dominance-by-dominance' and two pairs as 'coadaptive' epistasis. The remaining QTL showed different patterns of epistasis from those previously described in the literature and were, therefore, grouped into two additional categories that we named 'additive-by-dominance' and 'complex' epistasis. 'dominance-by-dominance' epistasis leads to a deviated performance for the double heterozygotes compared to single heterozygotes. Among the d × d interactions found in our study, six had positive sign (Figure 2a) and two had negative sign (Figure 2b). In positive d × d interactions, the genotypic value of the double homozygotes is superior to the simple heterozygotes. Conversely, this pattern is reversed when the sign is negative. Coadaptive epistasis occurs when double homozygotes from the same parental line show enhanced performance [18]. As mentioned above, we only found two QTL pairs which displayed this form of epistasis (Figure 2c). Coadaptive epistasis is fundamental to interpret post-zygotic reproductive isolation [30–32]. In each parental population, selection may have acted leading to fixation of different alleles at the relevant loci regulating prolificacy in a way that statistical epistasis is not apparent in either population. Second-generation hybrids (F2) exhibit combination of alleles at different loci that were not present in any of the parental breeds, leading to the disruption of "co-adapted" gene pools and the appearance of new phenotypes.
The third category included two pairs where only a × d and d × a effects were significant. We called this group 'additive-by-dominance' because the a × d and d × a interactions show the same patterns but with the roles of the loci reversed (Figure 2d). Finally, we found QTL pairs which show 'complex' patterns of interactions characterised by having a significant a × d or d × a term together with significant a × a and/or d × d (Figure 2e). These interactions yielded complex patterns in which the genotypic value for a given genotype at one locus drastically changes depending on the genotype at the second locus.
In summary, the bi-dimensional genome scan of an Iberian × Meishan F2 intercross has allowed to demonstrate that the genetic architecture of pig reproduction is mostly built as a complex network of interacting genes rather than being explained by the sum of the additive effects of a yet to be defined number of loci. Individual epistatic loci have moderate effects on the phenotypic variance of prolificacy and they are distributed in multiple chromosomal locations. Moreover, they display several types of interactions that sometimes cannot be easily ascribed to well defined models, thus suggesting the existence of additional interacting loci. In the next years, the fine mapping and identification of the causal mutations that explain the segregation of epistatic QTL in pigs will be a daunting but fascinating task that will likely unveil many of the secrets that underlie the biological grounds of complex traits.
Experimental design and phenotypic data
A three-generation F2 intercross between Iberian and Meishan pig breeds was generated to map prolificacy QTL. Eighteen Meishan sows were randomly mated by artificial insemination with three Iberian boars (Guadyerbas line) to produce the F1 progeny in the INRA GEPA experimental unit (Surgères, France). This F1 offspring was purchased and transferred to NOVA GENÈTICA S. A. experimental farm (Lleida, Spain) after weaning at 22-25 days of age. At sexual maturity, eight F1 boars and 97 F1 sows were randomly selected to obtain an F2 progeny. The F1 sows produced only one litter and were slaughtered after weaning. In total, 255 F2 reproductive sows were randomly selected and mated to unrelated boars. They produced a total of 881 litters, i.e. 3.45 parities per F2 sow on average. The number of piglets born alive (NBA) and the total number of piglets born (TNB) were recorded at farrowing. Animals were managed under standard intensive conditions; in all cases, reproduction was carried out by artificial insemination. Protocols were approved by the Ethical and Animal Care Committee at IRTA.
Microsatellite and single nucleotide polymorphism genotyping
DNA was extracted from either frozen blood or tail tissue using commercial protocols (Gentra Systems, Minneapolis). Purebred grandparents, F1 breeding pigs and the 255 F2 sows were genotyped for 115 markers: 109 microsatellites and 6 single nucleotide polymorphisms (SNP). Microsatellite loci were chosen based on their ease of scoring, the absence of null alleles, their genomic location and their informativeness. Microsatellite PCR products were analyzed with the Genescan 3.7 software (Applied Biosystems, Warrington, UK) in an ABI PRISM 3100 Genetic Analyzer (Applied Biosystems). Single nucleotide polymorphisms markers in DBH, BMPR1β, PRLR and VCAM1 genes were analyzed with the SNapSHOT ddNTP primer extension multiplex kit (Applied Biosystems, Warrington, UK) [33–36]. Moreover, two polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) markers were analysed: the MC1R gene G/A283 SNP was genotyped by PCR-RFLP with NspI [37]. The PvuII estrogen receptor 1 polymorphism was genotyped following Short et al. [38]. Linkage analysis was carried out by using the 'build' option of the CRI-MAP 2.4 program [39].
NBA was considered to be the same trait across all parities and the same criterion was applied to TNB. Two statistical models were used to analyze the experimental data. The first model was a one-dimensional QTL mapping performed using a regression approach [40], based on the following mixed model:
where y ijk was the ijkthobservation for NBA or TNB, H i was the ithyear-season fixed effect, O j was the jthorder of parity fixed effect, u k was the random polygenic effect of the kthindividual, p k was the random permanent environmental effects for the kthindividual, a was the QTL additive effect, d was the dominance QTL effect and e ijkl was the random residual term; c a = pr(QQ) - pr(qq) and c d = 0.5pr(Qq) - 0.5(pr(QQ) + pr(qq)), where pr(QQ) was the probability of being homozygous of Iberian origin, pr(qq) was the probability of being homozygous of Meishan origin and pr(Qq) was the probability of being heterozygous. For computational reasons, heritability (h2) and percentage of permanent environmental effect (p2) were assumed to be known. They were obtained from the posterior mode of a previous Bayesian analysis. Estimates for h2 and p2 were 0.22 and 0.05, respectively. The analyses were performed at every centimorgan along the 2,017 cM of the 18 autosomes, by means of a likelihood ratio test (LR) comparing the models with and without the QTL effects. Nominal P-values were calculated assuming a chi-squared distribution of the LR test. Yet, nominal significance levels cannot be used directly due to the large number of tests performed. Hence, genome-wide significance levels were calculated using a Bonferroni correction and assuming independence between statistical tests every 30 cM. The genome-wide critical values of LR test for level of significance associated with type I errors α = 0.10, 0.05, 0.01 and 0.001 were 13.36, 15.13, 18.27 and 23.22, respectively.
With regard to the two-QTL analyses, two different models were employed. The first model included the effects of two non interacting QTL. The statistical mixed model was:
where a1 and a2 were the additive effects, d1 and d2 were the dominance effects for QTL 1 and 2, respectively. The coefficients ca 1, cd 1, ca 2and cd 2were calculated as before for locations 1 and 2.
The second model allowed for epistasis, i.e.:
where Ia × a, Ia × d, Id × aand Id × dwere the additive × additive, additive × dominance, dominance × additive and dominance × dominance epistatic interaction effects, respectively; ca × a, ca × d, cd × aand cd × dwere the regression coefficients calculated following Cockerham's model for epistatic interactions [41, 42], i.e.:
The two-QTL analyses were performed using a full bi-dimensional genome scan. LR-tests comparing the models with and without the epistatic interaction effects (model 3 vs model 2) were computed at 1 cM intervals along the 2,017 cM of the 18 autosomes for each of the two QTL, leading to a total of 2,069,595 regression analyses for both NBA and TNB. The values of h2 and p2 used in this analysis were identical to those considered in model 1. The statistical contrast between models for evidence of epistasis was carried out using an LR test with 4 degrees of freedom in the numerator. As before, bi-dimensional genome-wide levels of significance were calculated using a Bonferroni correction assuming statistical independence every 30 cM. The genome-wide critical values of LR test for level of significance associated with type I errors α = 0.10, 0.05, 0.01 and 0.001 were 25.14, 26.68, 30.17 and 35.06 respectively. Confidence intervals for QTL location were calculated using the Likelihood drop method [43]. Finally, we calculated the expected values of the nine genotypic classes using the Cockerham's F2-metric model [42]. In addition, statistical significance was independently assessed by using an approach based on the False Discovery Rate -FDR- [44], that was calculated based on nominal P-values every 30 cM, as well as by employing a parametric bootstrap method [45].
Brockmann GA, Kratzsch J, Haley CS, Renne U, Schwerin M, Karle S: Single QTL effects, epistasis, and pleiotropy account for two-thirds of the phenotypic F-2 variance of growth and obesity in DU6i × DBA/2 mice. Genome Research. 2000, 10: 1941-1957. 10.1101/gr.GR1499R.
Cheverud JM, Vaughn TT, Susan Pletscher L, Peripato AC, Adams ES, Erikson CF, King-Ellison KJ: Genetic architecture of adiposity in the cross of LG/J and SM/J inbred mice. Mammalian Genome. 2001, 12: 3-12. 10.1007/s003350010218.
Peripato AC, de Brito RA, Matioli SR, Pletscher LS, Vaughn T, Cheverud JM: Epistasis affecting litter size in mice. Journal of Evolutionary Biology. 2004, 3: 593-602. 10.1111/j.1420-9101.2004.00702.x.
Carlborg O, Brockmann A, Haley CS: Simultaneous mapping of epistatic QTL in DU6i × DBA/2 mice. Mammalian Genome. 2005, 16: 481-494. 10.1007/s00335-004-2425-4.
Carlborg O, Kerje S, Schütz K, Jacobsson L, Jensen P, Andersson L: A global search reveals epistatic interaction between QTL for early growth in the chicken. Genome Research. 2003, 13: 413-421. 10.1101/gr.528003.
Carlborg O, Burt D, Hocking P, Haley CS: Simultaneous mapping of epistatic QTL in chickens reveals clusters of QTL pairs with similar genetic effects on growth. Genetical Research. 2004, 83: 197-209. 10.1017/S0016672304006779.
Segre D, DeLuna A, Church GM, Kishony R: Modular epistasis in yeast metabolism. Nature Genetics. 2005, 37 (1): 77-83.
Fedorowicz GM, Fry DJ, Anholt RR, Mackay TF: Epistatic interactions between smell-impaired loci in Drosophila melanogaster. Genetics. 1998, 148: 1885-1891.
Montooth KL, Marden JH, Clark AG: Mapping determinants of variation in energy metabolism, respiration and flight in Drosophila. Genetics. 2003, 165 (2): 623-635.
Andersson L, Georges M: Domestic-animal genomics: deciphering the genetics of complex traits. Nature Review Genetics. 2004, 5: 202-212. 10.1038/nrg1294.
Rothschild MF, Bidanel JP: Biology and genetics of reproduction. The Genetics of the Pig. Edited by: Rothschild MF, Ruvinsky A. 1998, Cambridge, UK: CAB International, University Press, 313-343.
Cassady JP, Johnson RK, Pomp D, Rohrer GA, Van Vleck LD, Spiegel EK, Gilson KM: Identification of quantitative trait loci affecting reproduction in pigs. Journal of Animal Science. 2001, 79: 623-633.
De Koning DJ, Ratting AP, Harlizius B, Groenen MAM, Brascamp EW, van Arendonk JAM: Detection and characterization of quantitative trait loci for growth and reproduction traits in pigs. Livestock Production Science. 2001, 72: 185-198. 10.1016/S0301-6226(01)00226-3.
King AH, Jiang ZH, Gibson JP, Haley CS, Archibald AL: Mapping quantitative trait loci affecting female reproductive traits on porcine chromosome 8. Biology of Reproduction. 2003, 68 (6): 2172-2179. 10.1095/biolreprod.102.012955.
Tribout T, Iannuccelli T, Druet H, Gilbert J, Riquet R, Gueblez R, Mercat MJ, Bidanel JP, Milan D, le Roy P: Detection of quantitative trait loci for reproduction and production traits in Large White and French Landrace pig populations. Genetics, Selection, Evolution. 2008, 40 (1): 61-78.
Li K, Ren J, Xing Y, Zhang Z, Ma J, Guo Y, Huang L: Quantitative trait loci for litter size and prenatal loss in a White Duroc × Chinese Erhualian resource population. Animal Genetics. 2009, 40: 963-966. 10.1111/j.1365-2052.2009.01931.x.
Spötter A, Distl O: Genetic approaches to the improvement of fertility traits in the pig. Veterinary Journal. 2006, 172 (2): 234-247. 10.1016/j.tvjl.2005.11.013.
Carlborg O, Haley CS: Epistasis: too often neglected in complex trait studies?. Nature Reviews. 2004, 5: 619-625.
Bidanel JP, Caritez JC, Legault C: Estimation of crossbreeding parameters between Large White and Meishan porcine breeds. I. Reproductive performance. Genetics, Selection, Evolution. 1989, 21: 507-526. 10.1186/1297-9686-21-4-507.
Silió L, Rodriguez C, Rodrigáñez J, Toro MA: La selección de cerdos ibéricos. Porcino Ibérico: Aspectos claves. Edited by: Buxadé C, Daza A. 2001, Madrid: Mundiprensa, 125-149.
Alves E, Óvilo C, Rodríguez MC, Silió L: Mitochondrial DNA sequence variation and phylogenetic relationships among Iberian pigs and other domestic and wild pig populations. Animal Genetics. 2003, 34 (5): 319-324. 10.1046/j.1365-2052.2003.01010.x.
Fernández A, Toro MA, Rodriguez C, Silió L: Heterosis and epistasis for teat number and fluctuating asymmetry in crosses between Jiaxing and Iberian pigs. Heredity. 2004, 93 (2): 222-227. 10.1038/sj.hdy.6800498.
Beavis WD: The power and deceit of QTL experiments:lessons from comparitive QTL studies. Proceedings of the Forty-Ninth Annual Corn & Sorghum Industry Research Conference: 7-8 December 1994; Chicago. Edited by: Wilkinson DB. 1994, American Seed Trade Association, Washington DC, 250-266.
Bidanel JP, Rosendo A, Iannuccelli N, Gilbert H, Caritez JC, Billon Y, Prunier A, Milan D: Detection of quantitative trait loci for teat number and female reproductive traits in Meishan × Large White F2 pigs. Animal. 2008, 2: 813-820. 10.1017/S1751731108002097.
Holl JW, Cassady JP, Pomp D, Johnson RK: A genome scan for quantitative trait loci and imprinted regions affecting reproduction in pigs. Journal of Animal. Science. 2004, 82: 3421-3429.
Haley CS, Lee GJ, Ritchie M: Comparative reproductive-performance in Meishan and Large White pigs and their crosses. Animal Science. 1995, 60 (2): 259-267.
Canario L, Roy N, Gruand J, Bidanel JP: Genetic variation of farrowing kinetics traits and relationships with litter size and perinatal mortality in French Large White sows. Journal of Animal Science. 2006, 84: 1053-1058. 10.2527/jas.2005-775.
Routman E, Cheverud JM: Gene effects on a quantitative trait: two-locus epistatic effects measured at microsatellite markers and at estimated QTL. Evolution. 1997, 51 (5): 1654-1662. 10.2307/2411217.
Hua JP, Xing YZ, Wu WR, Xu CG, Sun XL, Yu SB, Zhang QF: Single-locus heterotic effects and dominance by dominance interactions can adequately explain the genetic basis of heterosis in an elite rice hybrid. PNAS. 2003, 100 (5): 2574-2579. 10.1073/pnas.0437907100.
Dobzhansky T: Genetics of the evolutionary process. 1937, New York: Columbia University Press
Muller HJ: Bearing of the Drosophila work on systematics. The new systematics. Edited by: Huxley J. 1940, Oxford: Clarendon, 185-268.
Muller HJ: Isolating mechanisms, evolution and temperature. Biological Symposium. 1942, 6: 71-125.
Tomàs A, Casellas J, Ramirez O, Pérez-Enciso M, Rodriguez C, Noguera JL, Sánchez A: Polymorphisms of the porcine dopamine beta-hydroxylase gene and their relation to reproduction and piglet survivability in an Iberian × Meishan F2 intercross. Animal Genetics. 2006, 37 (3): 279-282. 10.1111/j.1365-2052.2006.01457.x.
Ramirez O, Tomàs A, Casellas J, Blanch M, Noguera JL, Amills M: An Association Analysis Between a Silent C558T Polymorphism at the Pig Vascular Cell Adhesion Molecule 1 Locus and Sow Reproduction and Piglet Survivability Traits. Reproduction Domestic Animals. 2008, 43 (5): 542-546. 10.1111/j.1439-0531.2007.00949.x.
Tomàs A, Frigo E, Casellas J, Ramirez O, Ovilo C, Noguera JL, Sánchez A: An association study between polymorphisms of the porcine bone morphogenetic protein receptor type1beta(BMPR1β) and reproductive performance of Iberian × Meishan F2 sows. Animal Genetics. 2006, 37 (3): 297-298. 10.1111/j.1365-2052.2006.01456.x.
Tomàs A, Casellas J, Ramirez O, Muñoz G, Noguera JL, Sánchez A: High amino acid variation in the intracellular domain of the pig prolactin receptor (PRLR) and its relation to ovulation rate and piglet survival traits. Journal of Animal Science. 2006, 84 (8): 1991-1998. 10.2527/jas.2005-664.
Fernández A, Fabuel E, Alves E, Rodríguez C, Silió L, Ovilo C: DNA test based on coat colour genes for authentication of the raw material of meat products from Iberian pigs. Journal of the Science of Food and Agriculture. 2004, 84 (14): 1855-1860. 10.1002/jsfa.1829.
Short TH, Rothschild MF, Southwood OI, McLaren DG, de Vries A, Steen van der H, Eckardt GR, Tuggle CK, Helm J, Vaske DA, Milehan AJ, Plastow GS: Effect of the estrogen receptor locus on reproduction and production traits in four commercial pig lines. Journal of Animal Science. 1997, 75 (12): 3138-3142.
Green P, Falls K, Crooks S: Documentation of CRI-MAP. [http://linkage.rockefeller.edu/soft/crimap/]
Haley CS, Knott SA, Elsen JM: Mapping quantitative trait loci in crosses between outbreed lines using least squares. Genetics. 1994, 136: 1195-1207.
Cockerham CC: An extension of the concept of partitioning hereditary variance for analysis of covariances among relatives when epistasis is present. Genetics. 1954, 39: 859-882.
Kao C-H, Zeng Z-B: Modeling epistasis of quantitative trait loci using Cockerham's model. Genetics. 2002, 160: 1243-1261.
Lander ES, Botstein D: Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics. 1989, 121: 185-199.
Benjamini Y, Hochberg Y: Controlling the False discovery rate - a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society B. 1995, 57: 289-300.
Efron B, Tibshirani R: An Introduction to the Bootstrap. 1993, New York: Chapman & Hall
Financial support was provided by the Spanish Ministerio de Educación y Ciencia (Grant AGL2000-1229-C03). Our sincere acknowledgment to Miguel Angel Toro (INIA) for valuable discussions and useful comments. The authors are indebted to the staff of Nova Genètica, in particular to E. Ramells, F. Marquez, R. Malé, F. Rovira, for cooperating in the experimental protocol, and I. Riart (IRTA) and J. C. Caritez (INRA) for their technical support. The authors gratefully acknowledge the contributions of the INRA (France) and the CIA El Dehesón del Encinar (Spain) for providing the purebred Meishan sows and Iberian boars, respectively.
Genètica i Millora Animal, IRTA-Lleida, 25198, Lleida, Spain
José L Noguera, Luis Varona & Meritxell Arqué
Departamento de Mejora Genética Animal, SGIT-INIA, 28040, Madrid, Spain
Carmen Rodríguez, Gloria Muñoz, Carmen Barragán & Cristina Ovilo
Departament de Ciència Animal i dels Aliments, UAB, 08193, Bellaterra, Spain
Anna Tomàs, Oscar Ramírez, Marcel Amills & Armand Sánchez
UR337 Station de Génétique Quantitative et appliquée, INRA, F-78350, Jouy-en-Josas, France
Jean P Bidanel
José L Noguera
Carmen Rodríguez
Luis Varona
Anna Tomàs
Gloria Muñoz
Oscar Ramírez
Carmen Barragán
Meritxell Arqué
Marcel Amills
Cristina Ovilo
Armand Sánchez
Correspondence to José L Noguera.
JLN conceived and led the project, supervised its execution, participated in the design of the study, drafted and finalized the manuscript. CR participated in the design and coordination of the study, obtained and provided Iberian semen, performs linkage analysis, and helped to revise the manuscript. LV participated in the design of the study, developed the analysis programs, performed the statistical analysis and helped to revise the manuscript. AT has carried out part of the molecular genotyping tasks and has has been involved in drafting and revising critically the manuscript. GM performed part of the molecular genotyping tasks. OR performed part of the molecular genotyping tasks. CB has performed part of the microsatellite genotyping. MA (IRTA) participated in the experimental protocol and data collection. JPB has provided Meishan sows (INRA) to obtain F1 animals, and participated in the discussion of the results and helped to revised the manuscript. MA (UAB) has been involved in drafting the manuscript and revising it critically. CO, was responsible of DNA extraction and the selection of markers to genotype and helped to perform linkage analysis. AS participated in the design and coordination of the study and helped to draft the manuscript.
Noguera, J.L., Rodríguez, C., Varona, L. et al. A bi-dimensional genome scan for prolificacy traits in pigs shows the existence of multiple epistatic QTL. BMC Genomics 10, 636 (2009). https://doi.org/10.1186/1471-2164-10-636
Epistatic Interaction
Polymerase Chain Reaction Restriction Fragment Length Polymorphism
Prolificacy Trait
Significant Epistatic Interaction


text:
La Farmàcia Magriñá és una botiga del Vendrell inclosa a l'Inventari del Patrimoni Arquitectònic de Catalunya.

Descripció
És un edifici compost per quatre plantes separades entre elles per motllures. La part més interessant són els baixos, millor dit la porta d'entrada a la farmàcia. Aquesta és formada per fusta i vidre, i té lletres i motius decoratius propis d'aquest tipus d'establiment. Consta, també d'una porta de fusta de quatre cossos que tanca la vidriera. A la planta principal destaca una barana de ferro que descriu unes formes còncaves-convexes. El segon pis té també un balcó i una finestra, i a la part esquerra hi ha un remat de la casa, però a la dreta encara es troba una tercera planta, rematada com el segon pis, per una cornisa sostinguda per mènsules i una barana de pedra de dibuixos geomètrics. L'interior de la farmàcia conserva encara tots els prestatges inicials, fets de fusta de Flandes, així com la decoració original.

Història
Fou construïda l'any 1899 pel Sr. Magriñá, pare de l'actual propietària. En la seva construcció van intervenir el fuster Sr. Armengol i la fusta fou importada de Flandes. Aquesta farmàcia ha tingut diferents titulars: Sr Ribes, Alsina, Miralles, Ruiz Perales, Roca Rovira. Actualment el titular és el net del Sr. Magriñá.

Referències

Patrimoni monumental del Vendrell
Edificis del Vendrell
Farmàcies de Catalunya

redpajama_set_name: RedPajamaWikipedia


text:
package com.ebay.epd.dockerrunner;

import com.github.dockerjava.api.DockerClient;
import com.github.dockerjava.api.NotModifiedException;
import com.github.dockerjava.api.command.InspectContainerResponse;
import com.github.dockerjava.api.command.StartContainerCmd;
import com.github.dockerjava.api.model.*;
import com.google.common.base.Function;
import com.google.common.collect.Iterables;
import com.google.common.collect.Lists;
import org.apache.commons.io.IOUtils;

import java.io.BufferedReader;
import java.io.IOException;
import java.io.InputStream;
import java.io.InputStreamReader;
import java.util.HashMap;
import java.util.List;
import java.util.Map;
import java.util.UUID;

public class Container {
    private final DockerClient client;
    private final String imageName;
    private final Iterable<Link> links;
    private final String host;
    private Option<String> cpuset;
    private Option<Memory> memory;
    private List<Env> envs;
    private StartedContainer startedContainer;
    private Option<String> dns;
    private List<DockerRunner.VolumeMapping> volumeMappings;
    private List<Integer> additionalPorts;
    private final BlockUntil noBlock = new BlockUntil() {
        @Override
        public boolean conditionMet(DockerContext context) {
            return true;
        }
    };
    private String id;

    public Container(DockerClient client, String imageName, Iterable<Link> links, String host, Option<String> cpuset, Option<Memory> memory, List<Env> envs, Option<String> dns, List<DockerRunner.VolumeMapping> volumeMappings, List<Integer> additionalPorts) {
        this.client = client;
        this.imageName = imageName;
        this.links = links;
        this.host = host;
        this.cpuset = cpuset;
        this.memory = memory;
        this.envs = envs;
        this.dns = dns;
        this.volumeMappings = volumeMappings;
        this.additionalPorts = additionalPorts;
    }

    public StartedContainer start() {
        return start(noBlock, 0);
    }

    public StartedContainer start(BlockUntil blockUntil, int secondsTimeout) {
        if (startedContainer == null) {
            pullIfRequired();
            List<String> envStrs = Lists.transform(envs, new Function<Env, String>() {
                @Override
                public String apply(Env input) {
                    return String.format("%s=%s", input.key, input.value);
                }
            });
            List<Bind> volumes = Lists.transform(volumeMappings, new Function<DockerRunner.VolumeMapping, Bind>() {
                @Override
                public Bind apply(DockerRunner.VolumeMapping input) {
                    return new Bind(input.hostPath, new Volume(input.containerPath));
                }
            });
            List<ExposedPort> exposePorts = Lists.transform(additionalPorts, new Function<Integer, ExposedPort>() {
                @Override
                public ExposedPort apply(Integer input) {
                    return new ExposedPort(input);
                }
            });
            id = client
                  .createContainerCmd(imageName)
                  .withEnv(envStrs.toArray(new String[]{}))
                  .withExposedPorts(exposePorts.toArray(new ExposedPort[]{}))
                  .exec()
                  .getId();
            final StartContainerCmd startContainerCmd = client
                                                         .startContainerCmd(id).withBinds()
                                                         .withPublishAllPorts(true)
                                                         .withLinks(containerLinks())
                                                         .withBinds(volumes.toArray(new Bind[]{}));

            dns.doIfPresent(new Option.OptionalCommand<String>() {
                @Override
                public void apply(String dns) {
                    startContainerCmd.withDns(dns);
                }
            });
            try {
                UUID correlationId = UUID.randomUUID();
                System.out.println(String.format("DockerRunner %s, starting container for image %s at time %s", correlationId, imageName, System.currentTimeMillis()));
                startContainerCmd.exec();
                InspectContainerResponse inspectContainerResponse = client.inspectContainerCmd(id).exec();
                for (Ports.Binding[] bindings : inspectContainerResponse.getNetworkSettings().getPorts().getBindings().values()) {
                    for (Ports.Binding binding : bindings) {
                        System.out.println(String.format("DockerRunner %s, started container for image %s at time %s with port binding %s", correlationId, imageName, System.currentTimeMillis(), binding.getHostPort()));
                    }
                }
            } catch (NotModifiedException e) {
                //swallow... this is fine!
            }
            Map<String, StartedContainer> linkedContainers = new HashMap<>();
            for (Link link : links) {
                linkedContainers.put(link.alias, link.container);
            }
            startedContainer = new StartedContainer(client, id, linkedContainers);
        }
        waitFor(blockUntil, System.currentTimeMillis() + secondsTimeout * 1000);
        return startedContainer;
    }

    private com.github.dockerjava.api.model.Link[] containerLinks() {
        Iterable<com.github.dockerjava.api.model.Link> contLinkIterable = Iterables.transform(links, new Function<Link, com.github.dockerjava.api.model.Link>() {
            @Override
            public com.github.dockerjava.api.model.Link apply(Link input) {
                return new com.github.dockerjava.api.model.Link(input.container.name(), input.alias);
            }
        });

        int linkCount = Iterables.size(contLinkIterable);
        com.github.dockerjava.api.model.Link[] contLinks = new com.github.dockerjava.api.model.Link[linkCount];
        int i = 0;
        for (com.github.dockerjava.api.model.Link link : contLinkIterable) {
            contLinks[i++] = link;
        }
        return contLinks;
    }

    private void pullIfRequired() {
        String nameWithTag;
        if (imageName.contains(":")) {
            nameWithTag = imageName;
        } else {
            nameWithTag = imageName + ":latest";
        }
        List<Image> images = client.listImagesCmd().exec();
        for (Image image : images) {
            for (String name : image.getRepoTags()) {
                if (name.equals(nameWithTag)) {
                    return;
                }
            }
        }
        InputStream pullLog = client.pullImageCmd(imageName).exec();
        BufferedReader reader = new BufferedReader(new InputStreamReader(pullLog));
        String line = null;
        try {
            while ((line = reader.readLine()) != null) {
                System.out.println(line);
            }
        } catch (IOException e) {
            throw new RuntimeException(e);
        }
    }

    private void waitFor(BlockUntil blockUntil, long timeToStop) {
        DockerContext context = new DockerContext(host, startedContainer);
        while (true) {
            try {
                if (blockUntil.conditionMet(context)) {
                    return;
                }
            } catch (Exception e) {
                //Exception is equivalent to false... carry on.
            }
            if (System.currentTimeMillis() > timeToStop) {
                String logMessage;
                try {
                    logMessage = IOUtils.toString(client.logContainerCmd(id).withStdErr().withStdOut().exec());
                } catch (IOException e) {
                    logMessage = "An error occurred trying to pull the logs from the docker container.";
                }
                for (StartedContainer linkedContainer : startedContainer.linkedContainers()) {
                    linkedContainer.stop();
                }
                startedContainer.stop();
                System.out.println(logMessage);
                throw new ContainerStartupTimeoutException(logMessage);
            }
            try {
                Thread.sleep(100);
            } catch (InterruptedException e) {
                //Do we need to worry about this?
            }
        }
    }

    void stopIfStarted() {
        if (startedContainer != null) {
            startedContainer.stop();
        }
    }

    public static class Env {
        private final String key;
        private final String value;

        public Env(String key, String value) {
            this.key = key;
            this.value = value;
        }
    }

    public static class ContainerException extends RuntimeException {
        public ContainerException(Exception e) {
            super(e);
        }
    }

    public static class ContainerStartupTimeoutException extends RuntimeException {

        private final String logMessage;

        public ContainerStartupTimeoutException(String logMessage) {
            this.logMessage = logMessage;
        }

        public String containerLog() {
            return logMessage;
        }
    }

}

redpajama_set_name: RedPajamaGithub


We need a system that recognizes the important contribution of immigrants to U.S. culture, politics, and, in particular, the economy.
Cutting aid to Guatemala, Honduras, and El Salvador would be counter-productive to U.S. interests, but maybe that's what President Trump wants.
Latin America is facing its worst refugee crisis in its history. Will it repeat the EU's mistakes regarding Syrian refugees?
Host countries should come to terms with the possibility that many displaced Venezuelans aren't going anywhere anytime soon. Long-term economic and social integration should be the strategy.
Over the years I've talked with hundreds of immigrants, and across all these conversations, one common thread stands out: migrants are risk takers.
The thousands of brave souls currently leaving Nicaragua are not doing so because they want to. Whether due to political persecution or out of economic necessity, they are fleeing for their lives.
The act, introduced by three prominent voices for Latin America in Congress, demands State reunify the 2,342 migrant children separated from their parents. It also addresses the root causes of the flow.
The humanitarian crisis in Venezuela has led to a growing diaspora of displaced Venezuelans throughout the region. At home, the Maduro regime denies and minimizes the phenomenon.
Though not without precedent, the decision to send troops to the border comes as attempted crossings reach an historic low. The decision is pure politics, if not ugly, populist racism.
Climate change is driving an increasing number of Latin Americans northwards toward Mexico and to the United States.


As part of London Craft Week 2018, Milliners Rachel Trevor Morgan, Edwina Ibbotson and Noel Stewart curated an exhibition to highlight the excellence of the craft of British milliners. In a first for the industry 'Unveiled – the Craft of Millinery' was held at the Art Workers Guild in Queens Square and sought to reveal the workings of the best hat makers in the country.
Each milliner/hat was chosen to highlight a different a skill, material or design approach and each designer was asked to provide materials, tools and work in progress to reveal some of the inner workings of their craft. A large proportion of the exhibits were created exclusively for the exhibition including Karen Henriksen who focused on the unique ability of felt to be stitched invisibly to other materials and House Of Flora created a waved hairstyle shaped hat showing exactly how felt can be shaped unlike any other material. Stephen Jones gave us a fabric covered top hat inspired by the cotton reels of most milliners childhood and Philip Treacy showed how to clip and shape a feather like only he can. With special creations from up and coming milliners Jo Miller and Harvy Santos this exhibition was a landmark for the best milliners in the UK right now.
The week also included a program of ticketed millinery related talks and demonstrations. These we very well received and attended, milliners generously donated their time to get involved. Demonstrations included felt blocking with Edwina Ibbotson, rolling sinamay with Bridget Bailey. Talks included a fascinating Q&A with Jane Smith, doyenne of theatrical millinery, New practices in Millinery with Noel Stewart chatting to with Paul Stafford and Jo Miller, and Hilary Alexander interviewed Rachel Trevor Morgan. There was also a curators' talk on Friday evening.
Thursday evening was the Private View which was well attended by over 100 people and generously supported by the the Livery who provided Cava for the evening.
All profits raised from the week (approx. £900) are going to the Master Charitable fund.
Many thanks must go to all involved. Special thanks to Carol Denford for organizing the films and her help throughout the week. Hilary Alexander and Piers Atkinson for their input with the PR. Special thanks to all at The ArtWorkers' Guild, especially the guild steward Elspeth Dennision. The Guild generously provided the space and nothing was too much trouble!


Snapchat today said that it was rolling out a self-service ad-buying tool, confirming a Digiday report of a few weeks ago.
The move comes at a time when marketers are seeking a third scalable option outside of Google and Facebook, and pushing back against transparency issues with those platforms. Agencies predicted the move will encourage marketers to spend more on Snapchat and make it more competitive with Facebook.
"Snap had to make a self-serve platform available to both large and small businesses in order to compete with Facebook," Bold Worldwide CEO Brian Cristiano said.
Cristiano said the ability to target custom audiences is the most appealing part of the platform.
Snap also rolled out a new Snapchat Mobile Dashboard that lets marketers track campaigns from their phones, and a Business Manager site for configuring roles and permissions of various marketing team members.


text:
Campus, community celebrate Pride Month
June 1, 2022 By Nate Moll
Pride Month celebrations include pride parades, picnics, parties, workshops, symposia and concerts. They attract millions of participants around the world. Photo illustration by Nate Moll
In June 1969, the Stonewall Uprising in Manhattan led by queer and trans people against police harassment was a catalyst for the Gay Rights Movement in the United States.
Today Pride Month has grown and evolved to become a time for celebration, education, visibility and liberation for the spectrum of people who make up the LGBTQ+ community. Throughout June, the campus and the Madison community have a series of events to celebrate the self-affirmation, dignity, equality and visibility of the diverse group of people who make up the lesbian, gay, bisexual, transgender, gender-nonconforming, queer-plus community.
Below you can find a listing of campus events and resources. (Note: Off-campus and community events are unaffiliated with UW–Madison, but are listed as a courtesy.)
Celebrate Pride Month on campus:
Come enjoy the Pride Fest Show from 7 to 9 p.m. June 17. The free, live, music event will take place at Memorial Union Terrace.
Join the Pride Picnic on the Hill on from 12:30 to 2 p.m. Thursday, June 23. Join the Gender & Sexuality Campus Center for a community gathering on Bascom Hill, the site of the 1990 ROTC protests. BYOBlanket. Everyone welcome. RSVP for accommodations and by Monday, June 20 for provided lunch at go.wisc.edu/PridePicnic.
The Pride Month Watch Party will feature LGBTQ+ series and movies on Fridays, June 3, 10, 17 and 24. Each watch party will begin at 1 p.m. and will be screened with captions.
Find community through the Gender and Sexuality Campus Center (GSCC). And, if you need support, connect with a peer mentor or professional staff in the GSCC office in the Red Gym, or make an appointment Monday – Friday from 9 a.m. – 5 p.m. Look out for GSCC watch parties during June. Each LGBTQ+ focused series or movie will begin at 1 p.m. Heartstopper: Fridays (6/3, 10, 17, 24); Noah's Arc: Wednesdays and Thursdays (6/8-6/22); Saving Face: Wednesday 6/29; The Incredibly True Adventure of Two Girls in Love: Thursday 6/30
Take in the Pride flags flying at Memorial Union, Union South, and the Wisconsin State Capitol. And visit Recreation and Wellbeing at night to see rainbow lights shine up the track. More details to come.
Pronouns matter. And so do Names. Learn how to choose Pronouns in Use on Canvas, along with your Name in Use in the MyUW application, and why it matters. We want to honor and use the pronouns and names our community members use.
Join University Health Services (UHS) virtual LGBTQIA+ Let's Talk group sessions for easy access to informal and confidential support every Tuesday from 2-4 p.m. Or attend group counseling support: Students who identify as bisexual, gay, lesbian, queer, questioning, transgender, or any other personally meaningful term are all welcome to join the LGBTQ Support & Empowerment group that meets Fridays from 10:30 a.m. – 12 p.m. Students who identity as transgender, gender non-conforming, genderqueer, and any other personally meaningful term can find community through the Transgender and Gender Non-Conforming Support and Empowerment Group that meets on Wednesdays from 1-2:30 p.m.
Download the Wisconsin Union's Pride wallpapers for your phone and laptop. Get your Terrace Pride t-shirt and stickers! Or pick up a button at the Memorial Union Terrace while supplies last.
Explore  GSCC's helpful list of campus resources and trainings for building healthy relationships, acting in solidarity, and more.
Use your Wiscard to check out books and DVDs about LGBTQIA+ identity, life, and health from the UW–Madison Libraries.
Join student organizations working to support the LGBTQIA+ community on campus.
June 2–4: PrideFest Milwaukee. One of the largest and longest-running LGBTQ+ festivals in the country, PrideFest Milwaukee returns to Henry Maier Festival Park this June 2 to 4 after a two-year hiatus due to the COVID-19 pandemic. This year's festival will feature music, comedy, children's programming, a history exhibit, plus new stages and food vendor buildings, an expanded health and wellness area, and more.
June 4: Trek Pride Ride x Forward Madison FC. Trek and Forward Madison FC are encouraging fans and cyclists around the Madison Area to grab their bikes and ride together to celebrate love, diversity and the powerful history of the LGBTQ+ community with the nationwide Trek Pride Ride on June 4 at Breese Stevens Field.
June 4: Chip-In Fore the Community Golf Outing. The Outreach LGBTQ Community Center will host a golfing event at Door Creek Golf Course in an effort to fight LGBTQ homelessness in Madison.
June 5: Milwaukee Pride Parade. The Milwaukee Pride Parade returns on June 5th after a two-year hiatus. The 2022 theme, "Pride is…", invites every attendee to fill in the blank with what pride means to them. The parade was founded in 2004 with the mission to provide a family-fun oriented celebration of LGBT Pride for the citizens of South East Wisconsin and Milwaukee.
June 11: Forward Madison FC Pride Night. Celebrate inclusivity in the Madison community on Saturday, June 11 during Pride Night at Breese Stevens Field and join the Flock as the Flamingos take on Greenville Triumph SC.
June 15: Madison Queer Meditation Group. The Madison LGBTQ+ Meditation Group aspires to be a welcoming and inclusive space for all meditation practitioners and aspiring meditators who self-identify as LGBTQ+. Members of the group represent students from various Buddhist and non-Buddhist traditions that come together bimonthly to create a refuge of mutual respect and understanding.
June 17: Madison Mallards Pride Night. Join the LGBTQ+ community, friends, family and community to celebrate Pride Night on June 17 at the Duck Pond baseball stadium in Warner Park as the Madison Mallards face the Wisconsin Rapids Rafters.
June 23: OPEN Annual Dinner. The Out Professional Engagement Network (OPEN) will host its 12th annual dinner at the Monona Terrace from 5 – 9 p.m. The 2022 theme, "Redefine Professional — Come as You Are" is focused on embracing individuality and empowering people from all career paths.
June 24: Live on Queen Street: Drag & Dance Block Part. Madison's free, outdoor concert series, Live on King Street, is throwing a drag and dance block party on Friday, June 24.
June 24-26: CapitalQ Theatre Festival. A fresh, new spin on the perennial favorite, "Queer Shorts," this festival will take over both stages at the Bartell Theatre. It will be a weekend filled with original short plays, staged readings of brand new works and one-act plays submitted from across the country.
June 30-July 3: National Women's Music Festival. The National Women's Music Festival is a four-day musical and cultural extravaganza that incorporates all facets of women's lives. It's a jam-packed long weekend where choices for things to do range from workshops, concerts, comedy, theatre presentations, a marketplace, newly released films and videos, a live auction, spirituality series, writer's series and more.
June 30: Punk Pride Night. Celebrate Punk Pride Night at Crucible Madison on Thursday, June 30 featuring multiple bands.
August 21: Magic Pride Festival. OutReach LGBTQ+ Community Center is hosting its 4th annual Magic Pride Festival on Sunday, Aug. 21, at Warner Park. The festival will include a stage show with local LGBTQ+ performers, large vendor area, games and activities for youth and families, food and beverages, and more.
Social media: Badger Pride social media graphics are available for download.

redpajama_set_name: RedPajamaCommonCrawl


text:
Supreme Court re-confirms EPA responsibility to regulate carbon dioxide
The court's opinion holds that a 2007 Supreme Court decision "made plain that emissions of carbon dioxide qualify as air pollution subject to regulation under" the Clean Air Act
Washington, D.C., June 21, 2011 — The U. S. Supreme Court in American Electric Power v. Connecticut underscored the U.S. Environmental Protection Agency's congressionally mandated responsibility to address global warming pollution from power plants and other major pollution sources.
The court's opinion holds that a 2007 Supreme Court decision "made plain that emissions of carbon dioxide qualify as air pollution subject to regulation under" the Clean Air Act, and that the act "'speaks directly' to emissions of carbon dioxide from the defendants' plants." Power plant smokestacks are the single largest source of carbon pollution in our nation, responsible for nearly 40 percent of all U.S. emissions.
"The most important thing about this decision is that it buttresses the foundation for EPA to do its job," said Environmental Defense Fund President Fred Krupp. "The Supreme Court strongly underscored EPA's responsibility under the law to address climate pollution that threatens the health and well-being of our nation."
The high court ruled in American Electric Power Co. v. Connecticut that common law nuisance claims brought by the states of California, Connecticut, Iowa, New York, Rhode Island and Vermont to abate the extensive pollution discharged by the nation's five largest emitting power companies (AEP, Southern Co., Xcel Energy, Cinergy and TVA) are displaced by EPA's responsibility under the Clean Air Act to address global warming pollution that endangers human health and welfare.
The court describes the EPA's development of greenhouse gas New Source Performance Standards for new and existing power plants, a major source of global warming pollution, under the nation's Clean Air Act and its commitment to complete action by May 2012.
EPA evaluates risk from electric power facilities, proposes no additional federal requirements
Emerald Transformer increases Lexington investment, expands service territory
Electric utility residential customer satisfaction increases in 2019, J.D. Power finds
Distribution transformer inspections
Effective safety training
N.C. regulators approve Duke Energy's innovative microgrid project in Madison County
Hubbell Lenoir City and BURNDY® combine to create integrated C&I sales force
Artificial intelligence improves power transmission, researchers say
Cooper Tire launches new SEVERE series tire for construction trucks
MSTS collaborates with GM Fleet to launch parts discount program
Tuffy Security Products expands security console insert product line
Vehicles & Accessories: Snow Plow Headlight
City of Toledo implements formal heavy equipment training with CM Labs Vortex Simulators
East Penn Launches New Li-Ion Product


Tundra 5 7 Oil Change. welcome to my blog here I will show you a little more what you are looking for Tundra 5 7 Oil Change below there are some photos and a little about Tundra 5 7 Oil Change that you can see and read, hopefully in accordance with what you are looking for.
#removing 08 tundra oil filter.#tundra oil filter location.#2014 toyota tundra oil change.#2010 tundra oil filter location.#2012 tundra oil filter location.#07 toyota tundra oil change.#2008 toyota tundra oil change.#2011 tundra oil filter.#tundra wheels.#differential fluid change.#oil change light.#2008 tundra oil filter removal.#2013 tundra oil filter location.#2012 tundra oil change.#2000 toyota tundra oil filter location.#2011 toyota tundra oil filter change.#2013 tundra oil change.#toyota tundra recommended oil.#2010 toyota tundra oil change.#toyota tundra oil filter change.#rear differential oil.#tundra 5.7 oil filter location.#toyota 4runner oil change.#2011 toyota tundra oil change.#tundra engine.#2003 toyota tundra oil change.#toyota tundra oil change tool.#tundra oil filter wrench.#tundra 5.7 oil filter change.#toyota tundra oil change.


text:
Darren Fletcher makes exciting prediction for James Garner at Manchester United
Darren Fletcher believes Ole Gunnar Solskjaer will hand James Garner plenty of chances at Manchester United
Josh ChalliesSports Content Writer
James Garner in action for Manchester United against Leeds United. (Image: (Photo by Will Russell/Getty Images))
Former Manchester United midfielder Darren Fletcher has predicted that James Garner will become a regular fixture in Ole Gunnar Solskjaer's side by the end of the season.
United have had an indifferent start to the 2019/20 campaign, losing to West Ham last weekend and requiring penalties to defeat Rochdale in the Carabao Cup.
That has raised the pressure ahead of a big week for Solskjaer and his side, who tackle Arsenal on Monday evening before switching their attention to the Europa League clash with AZ Alkmaar and next weekend's trip to Newcastle.
In the first few weeks of the campaign, Solskjaer has turned to some of the younger contingent at United - including summer signings Aaron Wan-Bissaka and Daniel James.
Victor Lindelof's agent makes Manchester United Barcelona transfer claim
Andy Cole's advice for Manchester United strikers Marcus Rashford and Mason Greenwood
Many are calling for more academy graduates to be handed the chance though, with Mason Greenwood, Angel Gomes and Garner among those most likely to benefit if Solskjaer turns to youth.
While big things are expected of Greenwood this season, Fletcher has told fans to watch out for Garner and believes he could be seen regularly over the course of the campaign.
"I think the history of the club says they demand and they want young players in the team and they support that," he told BBC Radio 5 Live.
"It does give your more time when you give youngsters a chance because people see it as refreshing and see it as building for the future.
Manchester United told 'not even Liverpool boss Jurgen Klopp' could solve their problems
"I think that they are more than ready to play, it's just that, can you have too many at once?
"People talk about the leaders and who is going to help them, which is an important side, so it's a difficult one but I'm sure as the season goes on you're going to see more of James Garner because he's top class.
"I'm surprised he's not featured so far but by the end of the season I'm sure that people will know who he is without a doubt, if you don't by now."
Ole Gunnar Solskjaer
Victor Lindelof


This policy aims to ensure all participants, officials and spectators are protected from the harmful effects of the sun throughout the year, and that we provide a sporting environment that supports sun safety awareness and practices.
Consider all sun protection measures when planning outdoor events and/or training.
Hold training sessions and competitions at venues that provide adequate shade.
Encourage participants, officials and spectators to use the shade available, and encourage people to bring their own umbrellas and shade tents.
Ensure that officials and participants are provided with or encouraged to wear sun-safe hats that protect the face, neck and ears. Recommended sun-safe hats include legionnaire, board-brimmed and bucket hats. Baseball caps do not provide adequate sun protection and are not recommended.
Encourage members who do not bring hats to play in an area protected from the sun or enforce a 'no hat, play in the shade' rule for junior members.
Ensure that officials and participants are provided with or encouraged to wear sun-safe clothing that covers as much skin as possible, including shirts/tops with longer sleeves and a collar, and long shorts or pants.
Incorporate clothing that is cool, loose fitting and made of densely woven fabric into the club uniform. Any fabric with an ultraviolet protection factor (UPF) rating above 15 provides good protection against UV radiation, but UPF50+ is recommended (AS/NZS 4399:1996).
Sunscreen is available that is at least SPF 30+, broad-spectrum and water-resistant and participants, coaches, officials and spectators are encouraged to use it appropriately.
Ensure that sunscreen is applied at least 20 minutes before going outdoors, and is reapplied every 2 hours when outdoors, or after getting wet or perspiring.
Encourage officials and participants to wear close-fitting, wrap-around sunglasses that cover as much of the eye area as possible and comply with Australian Standard AS/NZS 1067:2003 (Sunglasses: Category 2, 3 or 4).
Regularly promote sun protection information to officials, participants and spectators through briefings or training sessions, newsletters, notice boards, online communications, enrolment and announcements at sporting events.
Encourage all officials, coaches, trainers and adult members of the club to act as positive role models for younger members in all aspects of sun safe behaviour, including using a combination of sun protection measures.
Regularly monitor and review the effectiveness of the Sun Protection Policy to ensure it remains relevant and current.


Welcome to the Laguna Beach real estate and homes for sale real estate and mortgage glossary for Laguna Niguel, Dana Point, San Juan Capistrano, Aliso Viejo, Laguna Beach, Newport Beach and Orange County, CA areas. Understanding real estate terminology can be of great assistance in buying or selling a home, commercial property, or investment property. In order to help you understand words commonly used in a real estate transaction, I have prepared a list of real estate terms you should become familiar with. Thanks again and be sure to contact me for any of your Laguna Niguel real estate needs or real estate needs for Dana Point, San Juan Capistrano, Aliso Viejo, Laguna Beach, Newport Beach here in Orange County, CA.
If you are looking for Laguna Beach real estate and homes for sale or real estate and homes for sale in Laguna Niguel, Dana Point, San Juan Capistrano, Aliso Viejo, Laguna Beach, Newport Beach or any nearby Orange County, CA area, I am here to help. Please use this simple real estate request form that will help you when you are looking for a home for sale in Laguna Niguel, Dana Point, San Juan Capistrano, Aliso Viejo, Laguna Beach, or Newport Beach. Whether you are buying or selling Laguna Niguel or Laguna Beach real estate and homes, you have come to the right place. Please note all of your information will be kept strictly confidential and will only be used to provide you with outstanding real estate services.


People like to talk about "one medicine" a lot. It refers to the concept that we're all animals, and that human and veterinary medicine should be one big happy family of healthcare providers that maintain the health of the entire family, human and non-human. I get a bit jaded talking about one medicine because there's a lot of talk but it's hard to get a lot of action. One problem is that while some people in both human and veterinary medicine are strong supporters of the one medicine concept, it doesn't always filter down to the ground level.
A study in the latest edition of the Journal of the American Veterinary Medical Association (Hill et al. 2012) presents some concerning but not surprising information about "Tennessee veterinarian and physician attitudes, knowledge and practices regarding zoonoses prevention among animal owners with HIV infection or AIDS."
The study consisted of a survey sent to 454 vets and 1737 physicians in Tennessee. Response was pretty poor (a common problem with surveys), with only 43% of vets and 15% of physicians completing it. You have to wonder why the physician rate was so low. One potential issue is that the topic is not even on the radar of most physicians so they didn't bother to respond. If that's the case, then the people who responded could be more interested than average, potentially biasing the results (meaning that the problems described below are actually underestimated).
73% of veterinarians, but only 50% of MDs, said that veterinarians should always or almost always be involved in advising clients with HIV/AIDS about zoonotic disease risks.
Considering a large percentage of physicians don't initiate the discussion and don't get any additional education in zoonotic diseases (see below), I'm not sure what the other 50% of physicians think should be happening in terms of zoonotic disease counseling.
58% of veterinarians had zoonotic disease educational materials available in their clinics compared to only 3.5% of MDs.
Not surprising at all. Actually, the fact that some MDs have info in their offices is a bit of a surprise.
Only 5% of MDs had any continuing education (CE) on zoonotic diseases in the past three years, compared to 29% of veterinarians.
Pretty pathetic numbers all around. Veterinarians probably have easier access to this kind of CE since zoonotic disease topics are commonly presented at veterinary conferences, although attendance tends to be limited (as evidenced here). It would be nice to know why almost no MDs have had CE on zoonotic diseases. Is it lack of interest? Is it lack of availability? These are two completely different issues that can be addressed differently.
Almost 70% of veterinarians reported regularly talking to pet owners about the risk of zoonotic diseases in people with compromised immune systems.
One problem here is knowing with whom to have the talk. Asking people their medical history isn't (logically) part of the normal pet examination process, and while it's good information to have, veterinarians aren't going to cross that line and routinely ask those types of questions. That raises the question about how to initiate the discussion, and a crucial factor is having pet owners who are willing to bring up the subject. For that to happen, they need to realize that it's relevant, that the veterinarian knows something about the topic and can help, and that all information will be treated confidentially. Therefore, client education is key.
51% of physicians said they never see zoonotic infections in HIV/AIDS patients, while 44% said they almost never see them.
In part, that's a testament to the effectiveness of highly active anti-retroviral therapy (HAART), which has had a tremendous impact on management of patients with HIV. However, it also may be an indication that MDs don't recognize some infections as zoonotic. Certainly, a patient with Salmonella would (hopefully) result in some thought about zoonotic transmission, but there are a range of other pathogens where the zoonotic risks are less clear or less well known. When you consider that 71% of MDs never or almost never ask HIV/AIDS patients about pet ownership and animal contact, you can see how discussion and consideration of zoonoses might be poor.
Only 26% of veterinarians and 33% of MDs were able to correctly identify zoonotic pathogens of greatest concern to people with HIV/AIDS.
Pretty concerning numbers (especially among MDs, who do the diagnosing).
100% of MDs never or rarely contacted vets about zoonoses, and 97% of veterinarians never or rarely contacted physicians.
For all the talk about one medicine, this shows how far we have to go.
We need to do a better job of actually practicing one medicine. Veterinarians and MDs need to communicate. Both groups need to realize that they play a role in zoonotic disease prevention, and that the other group has an important role as well. Zoonotic diseases is a niche field in human and veterinary medicine but that doesn't mean they should be ignored. While serious zoonotic diseases are uncommon, they occur, and the failure to actually practice one medicine means that some people are at higher risk than they should be, and infections that occur may not always be identified and managed optimally.
Last year before my son began radiation and chemotherapy for brain cancer I made a point of asking his doctors if it was okay for him to be around our big, hairy collie, or if I needed to keep the dog isolated from him. They said the dog didn't need to be kept isolated but not to let the dog "slobber" all over him.
Sometime during the period when my son was undergoing his chemotherapy, the dog developed a skin infection that required weeks of daily antibiotics to clear up. At that time I asked our veterinarian if the dog's infection was transmissible to people, especially to people with cancer who are undergoing chemotherapy. He said that this infection was NOT transmissible to people, not even in my son's circumstances.
Everything turned out fine, but my point is, it is important for all of us to ASK our doctors, both physician and veterinarian, and to be proactive when it comes to our and our animal's health and welfare.


text:
Pandora to test interactive voice ads later this year
Radio ads broadcast a message to listeners, but Pandora's new voice ads will allow listeners to respond by speaking aloud — either to get more information about the product being advertised, or to skip the ad if it's not of interest. The company confirmed it has an agreement to test interactive voice ads where listeners engage by speaking back to the ad. The test will be powered by the San Francisco-based adtech company, Instreamatic, and will launch into beta sometime later this year.
Unlike web and mobile ads — which can be measured through things like impressions and clicks — traditional audio ads aren't clickable. That means advertisers don't know for sure how many people who heard the ad later went to seek out more information, or make a purchase.
Interactive voice ads could change that. And they arrive at a time when consumers have grown comfortable interacting with voice assistants, including those on smart speakers like the Amazon Echo, as well as on smartphones, as with Siri on iPhone.
Instead of simply airing an advertiser's message, an interactive voice ad could ask the listener if they want to learn more about the product. For example, an ad about a new smartphone could include a verbal call-to-action inviting listeners to learn about its features. The listener would respond out loud to the ad to get more information. Of they could respond negatively to skip the ad.
In addition, Instreamatic claims its voice ads platform is powered by AI technologies that allow customers to say more than just "yes" or "no" when interacting with an advertisement. Using technology like machine learning and natural language understanding, the ads understand user intent — and this ability improves the more customers engage with them.
For Pandora, the idea is that its advertisers could target listeners at times they aren't typically able to respond — like when they're out running, at the gym, driving or cooking, for example. They aren't then able to click or tap on ads, or otherwise engage with the advertiser content.
While Instreamatic made an announcement about its deal with Pandora for interactive voice ads, it's not the only way Pandora is targeting this market.
"Pandora is deeply investing in voice advertising and is driving the market forward by facilitating an ecosystem," said Eric Picard, Pandora VP, Ad Product Management.
"Pandora is building a comprehensive voice solution across our consumer-facing offerings with advertising services on top of it to enable our own 'first party' offering as well as 'third-party vendors' such as Instreamatic and AdsWizz to plug in. Our expectation is that the buy-side — advertisers and agencies — are going to want to do 'build-once-buy-everywhere' solutions for voice ads just like they have for other markets, and Instreamatic is the first company focused on supporting buy-side voice ads across publishers," he explained.
Instreamatic launched five years ago as a digital audio ad network, but has grown its suite of tools to now include voice-activated ads. The company has made other deals for this format, including with free music platform Audiomack; one of Russia's largest radio groups, Gazprom-Media Radio; and European radio company Global's DAX, which will allow advertisers to insert ads with verbal prompts into streaming apps like TuneIn and AccuRadio.
Pandora, however, is a notable customer win — and one that could prove out the viability of voice-activated ads on a sizable user base.
Currently, Pandora has an agreement to test the format with Instreamatic and plans to support other third-party vendors like AdsWizz, also sometime later this year. Picard says he's not aware of any scaled solutions for interactive voice ads beyond these two companies at this time.
That means publishers will need to either provide their own voice solution or rely on these vendors if they want to participate.
Pandora isn't sharing further details about its voice-enabled ads strategy, but will likely go more in-depth when the tests launch in order to fill in the blanks for potential advertisers.
"The age of voice has arrived, yet there's remained a stark need for meaningful consumer engagement – and measurable metrics – in the audio ad space," said Stas Tushinskiy, CEO, Instreamatic.ai, in a statement. "We believe Instreamatic provides the ideal ad platform to serve this marketplace. We're excited to be engaged with Pandora to bring this AI-enabled technology to its listeners and advertisers, and prepared to scale these new experiences very quickly once deployed."


We a small family business. We have been doing house decorations, renovations for 22 years. In our work we aim to do professional job in the quickest possible time. Our satisfied customers prove that we are reliable and provide high standard services.
Joe & his team were great. They painted the whole house & their attention to detail is fab. They transformed my house with their painting skills & the quality of work was exceptional. I would never appoint anybody else. I highly recommend them for the quality of work & peace of mind. They also did some extra work for free. You are in safe hands with Joe & his great team. Thank you guys for doing a lovely job & making my house feel as a home. Very very highly recommended.
I wish I could give a rating of higher than 5*. Excellent work - attention to detail was incredible and the guys worked very hard. They arrived on time every day, cleaned up before they left and did a perfect job. I will happily be asking them to do the rest of the house as and when we need it done.
Great job all round. Friendly and helpful. Professional finish. Would definitely recommend.
We let Joe and his team come in and paint our living room, kitchen, bathroom, stairs and hallway while we were away on holiday. When we arrived back, it was like walking into someone else's house! The quality of work was top notch, fantastic colour pay off with clean lines, and he even fixed up some damage and imperfections that we had on the walls. Joe was tidy, trustworthy with reasonable prices. We just told him what paint we wanted, and he went and got it for us. Thanks for a fantastic job Joe!
We hired Joe and his team to decorate two rooms in our house, and the service received was fantastic throughout. From the prompt and fair quote to the quick start, and then during the actual work we couldn't fault either Joe or any of his friendly and professional team. All workers arrived on time each day, and worked really hard all day. They even went the extra mile and worked over a Saturday and Sunday in order to complete the job in time. Thanks Joe for a great job - we know who we'll call next time!
We had Joe, Mark and the team to redecorate our lounge, dining room, kitchen and hallway/stairs. Removed the woodchip wallpaper, re-plastered walls and ceilings, painted, new skirting boards and flooring. We are very very pleased with the results. The team were on time, allowed us to change start times to suit work and they worked very hard. The job was completed in two weeks and final invoice was inline with quote. We will be having them back to do bedrooms!
I found this family company to be hardworking, and reliable but more than that they did a really good job. I would highly recommend to those looking for high quality work ( for me it was painting , decorating, and laying new flooring). At the end of each day they clean up and leave the working area tidy. They were always helpful and polite and I will look forward to them returning to do other work on my home.