Adaptation of environmental data to national and sectorial context: application for reinforcing steel sold on the French market

Purpose: Environmental data for steel products are generally proposed at a continental or a global scale. The question we are tackling here is: does the fact that steel as a global market necessarily reduces the need for national data? Methods: In this study, the environmental impact of reinforcing steel sold in France is evaluated. To do so, a specific environmental inventory is adapted from Ecoinvent database. CML method is used for impact calculation and both methods "recycled content” as well as "end of life recycling approach” are tested. Results and discussion: This study shows that there is a specificity of reinforcing steel products sold in France compared to European value. It is due to the fact that reinforcing steel is mainly made with recycled steel as the market growth for construction product in France is limited allowing a very high recycled content. This result is not sensitive neither to the allocation method used for recycling (cut-off approach or system expansion) nor to transport distance and electricity country mix used. Conclusions: The result of this study can be used with confidence in every construction site work located on the French territory. Furthermore, the present study advocates for an adaptation of global database to local context defined by a specific industrial sector and a geographic region even for product such as steel that may be considered as a first approximation as a global produc

Association of Killer Cell Immunoglobulin-Like Receptor Genes with Hodgkin's Lymphoma in a Familial Study

BACKGROUND: Epstein-Barr virus (EBV) is the major environmental factor associated with Hodgkin's lymphoma (HL), a common lymphoma in young adults. Natural killer (NK) cells are key actors of the innate immune response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs), which are expressed in variable numbers on NK cells. Various viral and virus-related malignant disorders have been associated with the presence/absence of certain KIR genes in case/control studies. We investigated the role of the KIR cluster in HL in a family-based association study. METHODOLOGY: We included 90 families with 90 HL index cases (age 16–35 years) and 255 first-degree relatives (parents and siblings). We developed a procedure for reconstructing full genotypic information (number of gene copies) at each KIR locus from the standard KIR gene content. Out of the 90 collected families, 84 were informative and suitable for further analysis. An association study was then carried out with specific family-based analysis methods on these 84 families. PRINCIPAL FINDINGS: Five KIR genes in strong linkage disequilibrium were found significantly associated with HL. Refined haplotype analysis showed that the association was supported by a dominant protective effect of KIR3DS1 and/or KIR2DS1, both of which are activating receptors. The odds ratios for developing HL in subjects with at least one copy of KIR3DS1 or KIR2DS1 with respect to subjects with neither of these genes were 0.44[95% confidence interval 0.23–0.85] and 0.42[0.21–0.85], respectively. No significant association was found in a tentative replication case/control study of 68 HL cases (age 18–71 years). In the familial study, the protective effect of KIR3DS1/KIR2DS1 tended to be stronger in HL patients with detectable EBV in blood or tumour cells. CONCLUSIONS: This work defines a template for family-based association studies based on full genotypic information for the KIR cluster, and provides the first evidence that activating KIRs can have a protective role in HL

Results of the family-based association study between <i>KIR</i> genes and Hodgkin's lymphoma using a dominant model

a<p>informative families are those with at least one heterozygous (+,−) parent for the corresponding KIR gene.</p>b<p>computed using the FBAT software.</p>c<p>computed by conditional logistic regression.</p>d<p>association results for allelic forms of the same KIR locus are provided for the first variant of the pair.</p>e<p>deleted form</p>f<p>wild type</p

Phenotypic distribution of KIRs in Hodgkin's lymphoma cases.

<p>The proportion (percentages) of present <i>KIR</i> genes, as determined by <i>KIR</i> gene content analysis are presented for the index HL cases (n = 90). Eleven <i>KIR</i> genes are presented in the figure. Two pairs of <i>KIR</i> genes are allelic: <i>KIR3DL1/3DS1,</i> and <i>KIR2DL2/2DL3</i>.</p

Summary of the genotypic reconstruction results for the nine variable <i>KIR</i> genes in 322 subjects. The procedure of reconstruction is detailed in figure 3.

a<p>estimated from all the reconstructed genotypes after the 2^nd step.</p>b<p>excluded after the second step of reconstruction.</p

Effect of <i>KIR3DS1</i> and <i>KIR2DS1</i> stratified on HL patients characteristics

a<p>computed by conditional logistic regression</p>b<p>computed by the FBAT software under a dominant model</p>c<p>at least one present allele. Only two HL patients are <i>Bw4I80</i> homozygotes.</p>d<p>missing in 11 cases</p>e<p>missing in 1 case</p>f<p>PBMCs corresponds to peripheral blood mononuclear cells</p

Genotypic reconstruction.

<p><i>KIR</i> gene content analysis provides only binary phenotyping results for each KIR (absent or present), rather than complete genotypic information. Thus, for genotype analysis (i.e. the number of copies of each <i>KIR</i> gene), genotypic reconstruction in two successive steps was required. The first step combined the results of <i>KIR</i> gene content analysis, knowledge of allelic forms of <i>KIRs</i>, the additional allele typing carried out for three <i>KIR</i> genes, and the analysis of intra-familial segregation. <i>KIR</i> gene content made it possible to determine genotype unambiguously only in individuals with a negative phenotypic result. For example, an individual with a negative <i>KIR2DS2</i> phenotype has no copy of the gene, and its genotype can be deduced and denoted <i>KIR2DS2</i>(−,−). Conversely, an individual with a positive phenotype for <i>KIR2DS2</i> may have either one copy of the gene, denoted <i>KIR2DS2</i>(+,−), or two copies of the gene, denoted <i>KIR2DS2</i>(+,+). Two of the nine variable <i>KIR</i> genes have known allelic forms: <i>KIR2DL2/2DL3</i> and <i>KIR3DS1/3DL1</i>. We defined as (+,+) the <i>KIR3DS1/3DL1</i> genotype of subjects homozygous for the presence of <i>KIR3DS1</i> (phenotype <i>KIR3DS1</i>+, <i>KIR3DL1</i>−) and as (−,−) the genotype of subjects homozygous for the absence of <i>KIR3DS1</i> (phenotype <i>KIR3DS1</i>−, <i>KIR3DL1+</i>). An individual with the <i>KIR3DS1</i>+, <i>KIR3DL1</i>+ phenotype has one copy of each gene and is therefore heterozygous at the locus, with genotype <i>KIR3DS1/3DL1</i>(+,−). The genotypes of <i>KIR2DL2/2DL3</i> followed the same principle. Additional <i>KIR</i> allele typing was especially useful for the analysis of familial gene segregation<i>.</i> In particular, for <i>KIR2DS4,</i> it made it possible to distinguish between the two common forms, <i>2DS4wt</i> and <i>2DS4del</i> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000406#pone-0000406-g001" target="_blank">Figure 1</a>). The second step of the reconstruction was based on the <i>KIR</i> haplotype determination of individuals in each family. We first estimated the pairwise linkage disequilibrium (LD) pattern between <i>KIR</i> genes in our families, using the genotypic information obtained from the first step of reconstruction (see statistical analysis). Perfect and complete LD between pairs of <i>KIRs</i> made it possible to infer certain genotypes. For the few remaining unsolved <i>KIR</i> genotypes, haplotypic reconstruction was based on previously described haplotypes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000406#pone.0000406-Hsu1" target="_blank">[26]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000406#pone.0000406-Uhrberg1" target="_blank">[33]</a>.</p