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Inhaled corticosteroids are the most commonly used controller medications prescribed for asthma. Two single-nucleotide polymorphisms (SNPs), rs1876828 in CRHR1 and rs37973 in GLCCI1, have previously been associated with corticosteroid efficacy. We studied data from four existing clinical trials of asthmatics who received inhaled corticosteroids and had lung function measured by forced expiratory volume in one second (FEV1) before and after the period of such treatment. We combined the two SNPs rs37973 and rs1876828 into a predictive test of FEV1 change using a Bayesian model, which identified patients with good or poor steroid response (highest or lowest quartile, respectively) with predictive performance of 65.7% (p = 0.039 vs. random) area under the receiver-operator characteristic curve in the training population and 65.9% (p = 0.025 vs. random) in the test population. These findings show that two genetic variants can be combined into a predictive test that achieves similar accuracy and superior replicability compared with single SNP predictors.
Pharmacogenetics; Asthma; Glucocorticoids; Predictive Modeling
In order to improve therapeutic outcomes, there is a tremendous need to identify patients who are likely to respond to a given asthma treatment. Pharmacogenomic studies have explained a portion of the variability in drug response and provided an increasing list of candidate genes and SNPs. However, as phenotypic variation arises from a network of complex interactions among genetic and environmental factors, rather than individual genes or SNPs, a multidisciplinary, systems-level approach is required in order to understand the inter-relationships among these factors. Systems biology, which seeks to capture interactions between genetic factors and other variables, offers a promising approach to improved therapeutic outcomes in asthma. This aritcle will review and update progress in the pharmacogenomics of asthma and then discuss the application of systems biology approaches to asthma pharmacogenomics.
asthma; genes; GWAS; network medicine; pharmacogenomics; SNP; systems biology
Rationale: To date, most studies aimed at discovering genetic factors influencing treatment response in asthma have focused on biologic candidate genes. Genome-wide association studies (GWAS) can rapidly identify novel pharmacogenetic loci.
Objectives: To investigate if GWAS can identify novel pharmacogenetic loci in asthma.
Methods: Using phenotypic and GWAS genotype data available through the NHLBI-funded Single-nucleotide polymorphism Health association-Asthma Resource Project, we analyzed differences in FEV1 in response to inhaled corticosteroids in 418 white subjects with asthma. Of the 444,088 single nucleotide polymorphisms (SNPs) analyzed, the lowest 50 SNPs by P value were genotyped in an independent clinical trial population of 407 subjects with asthma.
Measurements and Main Results: The lowest P value for the GWAS analysis was 2.09 × 10−6. Of the 47 SNPs successfully genotyped in the replication population, three were associated under the same genetic model in the same direction, including two of the top four SNPs ranked by P value. Combined P values for these SNPs were 1.06 × 10−5 for rs3127412 and 6.13 × 10−6 for rs6456042. Although these two were not located within a gene, they were tightly correlated with three variants mapping to potentially functional regions within the T gene. After genotyping, each T gene variant was also associated with lung function response to inhaled corticosteroids in each of the trials associated with rs3127412 and rs6456042 in the initial GWAS analysis. On average, there was a twofold to threefold difference in FEV1 response for those subjects homozygous for the wild-type versus mutant alleles for each T gene SNP.
Conclusions: Genome-wide association has identified the T gene as a novel pharmacogenetic locus for inhaled corticosteroid response in asthma.
polymorphism; genome; pharmacogenomics; glucocorticoid
The response to treatment for asthma is characterized by wide interindividual variability, with a significant number of patients who have no response. We hypothesized that a genomewide association study would reveal novel pharmacogenetic determinants of the response to inhaled glucocorticoids.
We analyzed a small number of statistically powerful variants selected on the basis of a family-based screening algorithm from among 534,290 single-nucleotide polymorphisms (SNPs) to determine changes in lung function in response to inhaled glucocorticoids. A significant, replicated association was found, and we characterized its functional effects.
We identified a significant pharmacogenetic association at SNP rs37972, replicated in four independent populations totaling 935 persons (P = 0.0007), which maps to the glucocorticoid-induced transcript 1 gene (GLCCI1) and is in complete linkage disequilibrium (i.e., perfectly correlated) with rs37973. Both rs37972 and rs37973 are associated with decrements in GLCCI1 expression. In isolated cell systems, the rs37973 variant is associated with significantly decreased luciferase reporter activity. Pooled data from treatment trials indicate reduced lung function in response to inhaled glucocorticoids in subjects with the variant allele (P = 0.0007 for pooled data). Overall, the mean (± SE) increase in forced expiratory volume in 1 second in the treated subjects who were homozygous for the mutant rs37973 allele was only about one third of that seen in similarly treated subjects who were homozygous for the wild-type allele (3.2 ± 1.6% vs. 9.4 ± 1.1%), and their risk of a poor response was significantly higher (odds ratio, 2.36; 95% confidence interval, 1.27 to 4.41), with genotype accounting for about 6.6% of overall inhaled glucocorticoid response variability.
A functional GLCCI1 variant is associated with substantial decrements in the response to inhaled glucocorticoids in patients with asthma. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00000575.)
It has recently been shown that vitamin D deficiency can increase asthma development and severity and that variations in vitamin D receptor genes are associated with asthma susceptibility.
We sought to find genetic factors that might interact with vitamin D levels to affect the risk of asthma exacerbation. Methods: We conducted a genome-wide study of gene–vitamin D interaction on asthma exacerbations using population-based and family-based approaches on 403 subjects and trios from the Childhood Asthma Management Program. Twenty-three polymorphisms with significant interactions were studied in a replication analysis in 584 children from a Costa Rican cohort. Results: We identified 3 common variants in the class I MHC–restricted T cell–associated molecule gene (CRTAM) that were associated with an increased rate of asthma exacerbations based on the presence of a low circulating vitamin D level. These results were replicated in a second independent population (unadjusted combined interaction, P =.00028–.00097; combined odds ratio, 3.28–5.38). One variant, rs2272094, is a nonsynonymous coding polymorphism of CRTAM. Functional studies on cell lines confirmed the interaction of vitamin D and rs2272094 on CRTAM expression. CRTAM is highly expressed in activated human CD8+ and natural killer T cells, both of which have been implicated in asthmatic patients.
The findings highlight an important gene-environment interaction that elucidates the role of vitamin D and CD8+ and natural killer T cells in asthma exacerbation in a genome-wide gene-environment interaction study that has been replicated in an independent population. The results suggest the potential importance of maintaining adequate vitamin D levels in subsets of high-risk asthmatic patients.
Gene-environment interaction; genome-wide association study; vitamin D; asthma exacerbation
Rationale: β2-agonists, the most common treatment for asthma, have a wide interindividual variability in response, which is partially attributed to genetic factors. We previously identified single nucleotide polymorphisms in the arginase 1 (ARG1) gene, which are associated with β2-agonist bronchodilator response (BDR).
Objectives: To identify cis-acting haplotypes in the ARG1 locus that are associated with BDR in patients with asthma and regulate gene expression in vitro.
Methods: We resequenced ARG1 in 96 individuals and identified three common, 5′ haplotypes (denoted 1, 2, and 3). A haplotype-based association analysis of BDR was performed in three independent, adult asthma drug trial populations. Next, each haplotype was cloned into vectors containing a luciferase reporter gene and transfected into human airway epithelial cells (BEAS-2B) to ascertain its effect on gene expression.
Measurements and Main Results: BDR varied by haplotype in each of the three populations with asthma. Individuals with haplotype 1 were more likely to have higher BDR, compared to those with haplotypes 2 and 3, which is supported by odds ratios of 1.25 (95% confidence interval, 1.03–1.71) and 2.18 (95% confidence interval, 1.34–2.52), respectively. Luciferase expression was 50% greater in cells transfected with haplotype 1 compared to haplotypes 2 and 3.
Conclusions: The identified ARG1 haplotypes seem to alter BDR and differentially regulate gene expression with a concordance of decreased BDR and reporter activity from haplotypes 2 and 3. These findings may facilitate pharmacogenetic tests to predict individuals who may benefit from other therapeutic agents in addition to β2-agonists for optimal asthma management.
Clinical trial registered with www.clinicaltrials.gov (NCT00156819, NCT00046644, and NCT00073840).
pharmacogenetics; asthma; β2-agonist
A 900-KB inversion exists within a large region of conserved linkage disequilibrium (LD) on chromosome 17. CRHR1 is located within the inversion region and associated with inhaled corticosteroid response in asthma. We hypothesized that CRHR1 variants are in LD with the inversion, supporting a potential role for natural selection in the genetic response to corticosteroids. We genotyped 6 single nucleotide polymorphisms (SNPs) spanning chr17:40,410,565–42,372,240, including 4 SNPs defining inversion status. Similar allele frequencies and strong LD were noted between the inversion and a CRHR1 SNP previously associated with lung function response to inhaled corticosteroids. Each inversion-defining SNP was strongly associated with inhaled corticosteroid response in adult asthma (p-values 0.002–0.005). The CRHR1 response to inhaled corticosteroids may thus be explained by natural selection resulting from inversion status or by long-range LD with another gene. Additional pharmacogenetic investigations into to regions of chromosomal diversity, including copy number variation and inversions, are warranted.
CRHR1; tau haplotype; MAPT; inversion; asthma; corticosteroid; pharmacogenetics
Corticotropin - releasing hormone receptor 2 (CRHR2) participates in smooth muscle relaxation response and may influence acute airway bronchodilator response to short – acting β2 agonist treatment of asthma. We aim to assess associations between genetic variants of CRHR2 and acute bronchodilator response in asthma.
We investigated 28 single nucleotide polymorphisms in CRHR2 for associations with acute bronchodilator response to albuterol in 607 Caucasian asthmatic subjects recruited as part of the Childhood Asthma Management Program (CAMP). Replication was conducted in two Caucasian adult asthma cohorts – a cohort of 427 subjects enrolled in a completed clinical trial conducted by Sepracor Inc. (MA, USA) and a cohort of 152 subjects enrolled in the Clinical Trial of Low-Dose Theopylline and Montelukast (LODO) conducted by the American Lung Association Asthma Clinical Research Centers.
Five variants were significantly associated with acute bronchodilator response in at least one cohort (p-value ≤ 0.05). Variant rs7793837 was associated in CAMP and LODO (p-value = 0.05 and 0.03, respectively) and haplotype blocks residing at the 5’ end of CRHR2 were associated with response in all three cohorts.
We report for the first time, at the gene level, replicated associations between CRHR2 and acute bronchodilator response. While no single variant was significantly associated in all three cohorts, the findings that variants at the 5’ end of CRHR2 are associated in each of three cohorts strongly suggest that the causative variants reside in this region and its genetic effect, although present, is likely to be weak.
Asthma; genetics; corticotrophin releasing hormone receptor 2; CRHR2; bronchodilator response; polymorphism; β2 adrenergic receptor agonist
Personalized health-care promises tailored health-care solutions to individual patients based on their genetic background and/or environmental exposure history. To date, disease prediction has been based on a few environmental factors and/or single nucleotide polymorphisms (SNPs), while complex diseases are usually affected by many genetic and environmental factors with each factor contributing a small portion to the outcome. We hypothesized that the use of random forests classifiers to select SNPs would result in an improved predictive model of asthma exacerbations. We tested this hypothesis in a population of childhood asthmatics.
In this study, using emergency room visits or hospitalizations as the definition of a severe asthma exacerbation, we first identified a list of top Genome Wide Association Study (GWAS) SNPs ranked by Random Forests (RF) importance score for the CAMP (Childhood Asthma Management Program) population of 127 exacerbation cases and 290 non-exacerbation controls. We predict severe asthma exacerbations using the top 10 to 320 SNPs together with age, sex, pre-bronchodilator FEV1 percentage predicted, and treatment group.
Testing in an independent set of the CAMP population shows that severe asthma exacerbations can be predicted with an Area Under the Curve (AUC) = 0.66 with 160-320 SNPs in comparison to an AUC score of 0.57 with 10 SNPs. Using the clinical traits alone yielded AUC score of 0.54, suggesting the phenotype is affected by genetic as well as environmental factors.
Our study shows that a random forests algorithm can effectively extract and use the information contained in a small number of samples. Random forests, and other machine learning tools, can be used with GWAS studies to integrate large numbers of predictors simultaneously.
Rationale: Current understanding of the molecular regulation of lung development is limited and derives mostly from animal studies.
Objectives: To define global patterns of gene expression during human lung development.
Methods: Genome-wide expression profiling was used to measure the developing lung transcriptome in RNA samples derived from 38 normal human lung tissues at 53 to 154 days post conception. Principal component analysis was used to characterize global expression variation and to identify genes and bioontologic attributes contributing to these variations. Individual gene expression patterns were verified by quantitative reverse transcriptase–polymerase chain reaction analysis.
Measurements and Main Results: Gene expression analysis identified attributes not previously associated with lung development, such as chemokine-immunologic processes. Lung characteristics attributes (e.g., surfactant function) were observed at an earlier-than-anticipated age. We defined a 3,223 gene developing lung characteristic subtranscriptome capable of describing a majority of the process. In gene expression space, the samples formed a time-contiguous trajectory with transition points correlating with histological stages and suggesting the existence of novel molecular substages. Induction of surfactant gene expression characterized a pseudoglandular “molecular phase” transition. Individual gene expression patterns were independently validated. We predicted the age of independent human lung transcriptome profiles with a median absolute error of 5 days, supporting the validity of the data and modeling approach.
Conclusions: This study extends our knowledge of key gene expression patterns and bioontologic attributes underlying early human lung developmental processes. The data also suggest the existence of molecular phases of lung development.
microarrays; surfactant; principal component analysis
Among asthmatics, bronchodilator response (BDR) to inhaled ß2- adrenergic agonists is variable, and the significance of a consistent response over time is unknown.
We assessed baseline clinical variables and determined the clinical outcomes associated with a consistently positive BDR over 4 years in children with mild-moderate persistent asthma.
In the 1,041 participants in the Childhood Asthma Management Program (CAMP), subjects with a change in FEV1 of 12% or greater (and 200mLs) after inhaled ß2 agonist at each of their yearly follow-up visits (consistent BDR) were compared with those who did not have a consistent BDR.
We identified 52 children with consistent BDR over the 4-year trial. Multivariable logistic regression modeling demonstrated that baseline pre-bronchodilator FEV1 (OR=0.71, p<0.0001), log 10 IgE level (OR=1.97, p=0.002), and lack of treatment with inhaled corticosteroids (OR=0.31, p=0.009) were associated with a consistent BDR. Individuals who had a consistent BDR had more hospital visits (p=0.007), required more prednisone bursts (p=0.0007), had increased nocturnal awakenings due to asthma (p<0.0001), and missed more days of school (p=0.03) than non-responders during the 4-year follow-up.
We have identified predictors of consistent BDR and determined that this phenotype is associated with poor clinical outcomes.
asthma; consistent bronchodilator response; outcomes
Leukotrienes are now established contributors to the inflammatory process in asthma and leukotriene modifiers are mainstays in the therapy of asthma. This review focuses on published association studies implicating the role of leukotriene pathway genes in asthma pathogenesis and treatment response, specifically focusing on those genetic variants associated with asthma affection status, the development of aspirin exacerbated respiratory disease, and pharmacogenetic response. While published studies have been limited by small sample sizes and lack of independent replication, multiple loci within multiple leukotriene pathway genes have now been associated in more than one study related to asthma or asthma treatment response. Those specific variants include two variants in ALOX5 that are both associated with response to 5-LO inhibition and to leukotriene receptor antagonists, variants in the two established cysteinyl leukotriene receptor antagonists, CYSLTR1 and CYSLTR2 that are both associated with asthma susceptibility in at least two independent populations, and a LTC4S promoter polymorphism that has been associated with asthma affection status and with asthma exacerbated respiratory disease. Desite these successes, genetic investigations into this pathway remain in their formative stages. Future studies aimed at providing a broader scope of investigation through increased sample sizes and through genome-wide approaches are needed.
Leukotrienes; SNP; asthma, 5-lipoxygenase; zileuton; montelukast; pharmacogenetics
To evaluate phenotypic and genetic variables associated with a poor long-term response to inhaled corticosteroid therapy for asthma, based independently on lung function changes or asthma exacerbations.
Materials & methods
We tested 17 phenotypic variables and polymorphisms in FCER2 and CRHR1 in 311 children (aged 5–12 years) randomized to a 4-year course of inhaled corticosteroid during the Childhood Asthma Management Program (CAMP).
Predictors of recurrent asthma exacerbations are distinct from predictors of poor lung function response. A history of prior asthma exacerbations, younger age and a higher IgE level (p < 0.05) are associated with recurrent exacerbations. By contrast, lower bronchodilator response to albuterol and the minor alleles of RS242941 in CRHR1 and T2206C in FCER2 (p < 0.05) are associated with poor lung function response. Poor lung function response does not increase the risk of exacerbations and vice versa (p = 0.72).
Genetic and phenotypic predictors of a poor long-term response to inhaled corticosteroids differ markedly depending on definition of outcome (based on exacerbations vs lung function). These findings are important in comparing outcomes of clinical trials and in designing future pharmacogenetic studies.
asthma; corticosteroid; exacerbation; lung function; pharmacogenetics
Purpose of review
Patient response to the asthma drug classes, bronchodilators, inhaled corticosteroids and leukotriene modifiers, are characterized by a large degree of heterogeneity, which is attributable in part to genetic variation. Herein, we review and update the pharmacogenetics and pharmaogenomics of common asthma drugs.
Early studies suggest that bronchodilator reversibility and asthma worsening in patients on continuous short-acting and long-acting β-agonists are related to the Gly16Arg genotype for the ADRB2. More recent studies including genome-wide association studies implicate variants in other genes contribute to bronchodilator response heterogeneity and fail to replicate asthma worsening associated with continuous β-agonist use. Genetic determinants of the safety of long-acting β-agonist require further study. Variants in CRHR1, TBX21, and FCER2 contribute to variability in response for lung function, airways responsiveness, and exacerbations in patients taking inhaled corticosteroids. Variants in ALOX5, LTA4H, LTC4S, ABCC1, CYSLTR2, and SLCO2B1 contribute to variability in response to leukotriene modifiers.
Identification of novel variants that contribute to response heterogeneity supports future studies of single nucleotide polymorphism discovery and include gene expression and genome-wide association studies. Statistical models that predict the genomics of response to asthma drugs will complement single nucleotide polymorphism discovery in moving toward personalized medicine.
asthma; genes; personalized medicine; polymorphisms; response heterogeneity
Rationale: Inhaled β-agonists are one of the most widely used classes of drugs for the treatment of asthma. However, a substantial proportion of patients with asthma do not have a favorable response to these drugs, and identifying genetic determinants of drug response may aid in tailoring treatment for individual patients.
Objectives: To screen variants in candidate genes in the steroid and β-adrenergic pathways for association with response to inhaled β-agonists.
Methods: We genotyped 844 single nucleotide polymorphisms (SNPs) in 111 candidate genes in 209 children and their parents participating in the Childhood Asthma Management Program. We screened the association of these SNPs with acute response to inhaled β-agonists (bronchodilator response [BDR]) using a novel algorithm implemented in a family-based association test that ranked SNPs in order of statistical power. Genes that had SNPs with median power in the highest quartile were then taken for replication analyses in three other asthma cohorts.
Measurements and Main Results: We identified 17 genes from the screening algorithm and genotyped 99 SNPs from these genes in a second population of patients with asthma. We then genotyped 63 SNPs from four genes with significant associations with BDR, for replication in a third and fourth population of patients with asthma. Evidence for association from the four asthma cohorts was combined, and SNPs from ARG1 were significantly associated with BDR. SNP rs2781659 survived Bonferroni correction for multiple testing (combined P value = 0.00048, adjusted P value = 0.047).
Conclusions: These findings identify ARG1 as a novel gene for acute BDR in both children and adults with asthma.
pharmacogenetics; asthma; bronchodilator agents
Rationale: Airway responsiveness is a prognostic marker for asthma symptoms in later life.
Objectives: To evaluate characteristics responsible for persistence of airway responsiveness in children with asthma.
Methods: A total of 1,041 children, initially aged 5–12 years, with mild to moderate persistent asthma enrolled in the Childhood Asthma Management Program (CAMP) were studied prospectively for 8.6 ± 1.8 years with methacholine challenges yearly.
Measurements and Main Results: Least squares geometric mean models were fit to determine effects of sex and age on airway responsiveness (provocative concentration producing 20% decrease in FEV1 [PC20]). Multiple linear regression analysis was performed to determine factors at baseline and over time, which were associated with PC20 at end of follow-up. A total of 7,748 methacholine challenges were analyzed. PC20 increased with age, with boys having greater increase after age 11 years than girls (P < 0.001). The divergence coincided with the mean age for Tanner stage 2. Postpubertal girls had greater airway responsiveness, even after adjustment for FEV1 and other potential confounders. Although multivariable regression analyses noted a variety of factors that influenced airway responsivness in both sexes, a history of hay fever (β= −0.30, P = 0.005), respiratory allergy (β= −0.32, P = 0.006), or recent inhaled corticosteroid usage (β= −0.18, P = 0.02) were associated with decrements in final log PC20 only in girls.
Conclusions: Airway responsiveness (PC20) is more severe in the postpubertal female with asthma than in males. Although there are factors associated with airway responsiveness in both males and females, sex-specific factors may contribute to new insights into asthma pathogenesis.
methacholine; PC20; FEV1; bronchoconstriction
Background. N-3 and n-6 polyunsaturated fatty acids (PUFAs) have been hypothesized to have opposing influences on neonatal immune responses that might influence the risk of allergy or asthma. However, both n-3 eicosapentaenoic acid (EPA) and n-6 arachidonic acid (AA) are required for normal fetal development.
Objective. We evaluated whether cord blood fatty acid levels were related to neonatal immune responses and whether n-3 and n-6 PUFA responses differed.
Methods. We examined the relation of cord blood plasma n-3 and n-6 PUFAs (n = 192) to antigen- and mitogen-stimulated cord blood lymphocyte proliferation (n = 191) and cytokine (IL-13 and IFN-γ; n = 167) secretion in a US birth cohort.
Results. Higher levels of n-6 linoleic acid were correlated with higher IL-13 levels in response to Bla g 2 (cockroach, P = .009) and Der f 1 (dust mite, P = .02). Higher n-3 EPA and n-6 AA levels were each correlated with reduced lymphocyte proliferation and IFN-γ levels in response to Bla g 2 and Der f 1 stimulation. Controlling for potential confounders, EPA and AA had similar independent effects on reduced allergen-stimulated IFN-γ levels. If neonates had either EPA or AA levels in the highest quartile, their Der f 1 IFN-γ levels were 90% lower (P = .0001) than those with both EPA and AA levels in the lowest 3 quartiles. Reduced AA/EPA ratio was associated with reduced allergen-stimulated IFN-γ level.
Conclusion. Increased levels of fetal n-3 EPA and n-6 AA might have similar effects on attenuation of cord blood lymphocyte proliferation and IFN-γ secretion.
Clinical implications. The implications of these findings for
Asthma; child; cord blood; cytokine; fatty acids; lymphocyte proliferation; AA: Arachidonic acid; BMI: Body mass index; CBMC: Cord blood mononuclear cell; CI: Confidence interval; DHA: Docosohexaenoic acid; EPA: Eicosapentaenoic acid; FA: Fatty acid; LA: Linoleic acid; NICU: Neonatal intensive care unit; OVA: Ovalbumin; PG: Prostaglandin; PUFA: Polyunsaturated fatty acid; SI: Stimulation index
Maternal and perinatal environmental exposures, as well as inherited factors, may influence neonatal immune responses.
To determine relations of maternal and perinatal exposures to antigen-specific cord blood lymphoproliferative responses.
In 427 newborns from a Boston pregnancy/birth cohort, lymphoproliferative responses in cord blood mononuclear cells to stimulation with cockroach (Bla g 2), house dust mite (Der f 1), ovalbumin, and mitogen phytohemagglutinin were measured as stimulation index (SI). We used the Wilcoxon rank sum and χ2 tests to evaluate predictors of ovalbumin SI as a continuous ranked or dichotomous outcome. We used t test and Spearman correlation for univariate testing and linear regression to evaluate predictors of natural log-transformed Bla g 2, Der f 1, and phytohemagglutinin SI. Logistic multivariate regression was applied to evaluate predictors of Bla g 2, Der f 1, and phytohemagglutinin SI dichotomized at 2 or at the median for phytohemagglutinin.
Maternal smoking during pregnancy, inadequate or excessive maternal weight gain during pregnancy, neonate black race/ethnicity (compared with white), and Apgar score less than 8 were each independently associated with increased cord blood mononuclear cell proliferative responses to stimulation with Bla g 2 and/or Der f 1. Maternal history of asthma was associated only with increased lymphoproliferative response to ovalbumin stimulation.
Distinct fetal and perinatal exposures and black race/ethnicity may be associated with increased cord blood lymphoproliferative responses. The implications of these findings for future development of allergy or asthma are, as yet, unknown.
Little is known about the relation between cytokine profile at birth and acute lower respiratory illnesses in the first year of life. The purpose of this work was to examine the relation between cytokine secretions by cord blood mononuclear cells and acute lower respiratory illness in a birth cohort of 297 children.
Cord blood mononuclear cells were isolated, and secretion of interferon-γ, interleukin-13, interleukin-10, and tumor necrosis factor-α at baseline and in response to allergens (Blatella germanica 2 and Dermatophagoides farinae 1) and mitogen (phytohemagglutinin) were quantified using enzyme-linked immunosorbent assay. Acute lower respiratory illness was defined as a parental report of a diagnosis of bronchiolitis, pneumonia, bronchitis, and/or croup by a health care professional in the first year of life. Differences in the levels of cord blood cytokines between children with and without acute lower respiratory illness were examined using 2-sample Wilcoxon tests. Logistic regression models were used to examine the relation between various categories of cord blood cytokines and acute lower respiratory illness.
Median levels of interferon-γ secreted by cord blood mononuclear cells in response to Blatella germanica 2 and Dermatophagoides farinae 1 were higher among children without acute lower respiratory illness as compared with children with acute lower respiratory illness. After adjustment for other covariates, the odds of acute lower respiratory illness was reduced among children in the top category (at or more than the median of detectable values) of interferon-γ level, significantly so in response to Blatella germanica 2.
In a cohort of children from the general population, we found that upregulated interferon-γ secretion at birth is associated with reduced risk of acute lower respiratory illness in the first year of life.
lower respiratory illnesses; cytokines; neonates; IFN-γ
Low intakes of dietary antioxidants may contribute to increases in asthma and allergy.
We investigated the association of maternal total intakes (foods + supplements) of 10 antioxidant nutrients during pregnancy with wheezing and eczema in 2-y-old children.
Subjects were 1290 mother-child pairs in an ongoing cohort study. Maternal dietary and supplement intakes were assessed by using a validated food-frequency questionnaire administered in the first and second trimesters. Antioxidant nutrient intakes were calculated, and the mean for each nutrient was considered to be the exposure during pregnancy. The outcomes of interest were any wheezing by the child during either the first or second year of life, recurrent wheezing in both years, and eczema in either the first or second year.
No association was observed between maternal total intake of any antioxidant nutrient and eczema. In multivariate logistic regression models, the highest quartile compared with the lowest quartile of maternal total intakes of vitamin E [odds ratio (OR): 0.70; 95% CI: 0.48, 1.03] and zinc (OR: 0.59; 95% CI: 0.41, 0.88) was inversely associated with any wheezing at 2 y of age (P for trend = 0.06 and 0.01 over quartiles of intake for vitamin E and zinc, respectively). Similar results were obtained for recurrent wheezing at 2 y of age with vitamin E (OR: 0.49; 95% CI: 0.27, 0.90) and zinc (OR: 0.49; 95% CI: 0.27, 0.87) (P for trend = 0.05 and 0.06 over quartiles of intake for vitamin E and zinc, respectively).
Our results suggest that higher maternal total intakes of antioxidants during pregnancy may decrease the risks for wheezing illnesses in early childhood.
Asthma; diet; antioxidants; eczema; childhood wheezing
Rationale: Interpatient variability in montelukast response may be related to variation in leukotriene pathway candidate genes.
Objective: To determine associations between polymorphisms in leukotriene pathway candidate genes with outcomes in patients with asthma receiving montelukast for 6 mo who participated in a clinical trial.
Methods: Polymorphisms were typed using Sequenom matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass array spectrometry and published methods; haplotypes were imputed using single nucleotide polymorphism–expectation maximization (SNP-EM). Analysis of variance and logistic regression models were used to test for changes in outcomes by genotype. In addition, χ2 and likelihood ratio tests were used to test for differences between groups. Case-control comparisons were analyzed using the SNP-EM Omnibus likelihood ratio test.
Measurements: Outcomes were asthma exacerbation rate and changes in FEV1 compared with baseline.
Results: DNA was collected from 252 participants: 69% were white, 26% were African American. Twenty-eight SNPs in the ALOX5, LTA4H, LTC4S, MRP1, and cysLT1R genes, and an ALOX5 repeat polymorphism were successfully typed. There were racial disparities in allele frequencies in 17 SNPs and in the repeat polymorphism. Association analyses were performed in 61 whites. Associations were found between genotypes of SNPs in the ALOX5 (rs2115819) and MRP1 (rs119774) genes and changes in FEV1 (p < 0.05), and between two SNPs in LTC4S (rs730012) and in LTA4H (rs2660845) genes for exacerbation rates. Mutant ALOX5 repeat polymorphism was associated with decreased exacerbation rates. There was strong linkage disequilibrium between ALOX5 SNPs. Associations between ALOX5 haplotypes and risk of exacerbations were found.
Conclusions: Genetic variation in leukotriene pathway candidate genes contributes to variability in montelukast response.
antiinflammatory; montelukast; pharmacodynamic; pharmacogenetic
Identifying genetic determinants for lung function is important in providing insight into the pathophysiology of asthma. Signal transducer and activator of transcription 3 is a transcription factor latent in the cytoplasm; the gene (STAT3) is activated by a wide range of cytokines, and may play a role in lung development and asthma pathogenesis.
We genotyped six single nucleotide polymorphisms (SNPs) in the STAT3 gene in a cohort of 401 Caucasian adult asthmatics. The associations between each SNP and forced expiratory volume in 1 second (FEV1), as a percent of predicted, at the baseline exam were tested using multiple linear regression models. Longitudinal analyses involving repeated measures of FEV1 were conducted with mixed linear models. Haplotype analyses were conducted using imputed haplotypes. We completed a second association study by genotyping the same six polymorphisms in a cohort of 652 Caucasian children with asthma.
We found that three polymorphisms were significantly associated with baseline FEV1: homozygotes for the minor alleles of each polymorphism had lower FEV1 than homozygotes for the major alleles. Moreover, these associations persisted when we performed an analysis on repeated measures of FEV1 over 8 weeks. A haplotypic analysis based on the six polymorphisms indicated that two haplotypes were associated with baseline FEV1. Among the childhood asthmatics, one polymorphism was associated with both baseline FEV1 and the repeated measures of FEV1 over 4 years.
Our results indicate that genetic variants in STAT3, independent of asthma treatment, are determinants of FEV1 in both adults and children with asthma, and suggest that STAT3 may participate in inflammatory pathways that have an impact on level of lung function.
The hygiene hypothesis states that childhood asthma develops as a result of decreased exposure to infectious agents during infancy and early childhood. This results in the persistence of the neonatal T helper lymphocyte 2 immunophenotype, thereby predisposing the child to atopic disease. While multiple studies support the hygiene hypothesis in asthma ontogeny, the evidence remains inconclusive; multiple other environmental exposures in early childhood also alter predisposition to asthma. Moreover, the current paradigm for asthma development extends far beyond simple childhood environmental exposures to include fetal development, genetic predisposition, and interactions of the developmental state and genetics with the environment.
asthma; child; fetal programming; gene by environment; infection
A pro-asthmatic culture milieu and β2-agonist (isoproterenol) were previously shown to regulate the expression of select transcription factors (TFs) within human airway epithelial and smooth muscle cells. This study tests 1116 single nucleotide polymorphisms (SNPs) across 98 of these TF genes for association with bronchodilator response (BDR) in asthma patients. Genotyping was conducted using the Illumina HumanHap550v3 Beadchip in 403 non-Hispanic White asthmatic children and their parents. SNPs were evaluated for association with BDR using family and population-based analyses. Forty-two SNPs providing p values < 0.1 in both analyses were then genotyped in three adult asthma trials. One SNP 5’ of the thyroid hormone receptor beta gene was associated with BDR in the childhood population and two adult populations (p value = 0.0012). This investigation identified a novel locus for inter-individual variability in BDR and represents a translation of a cellular drug-response study to potential personalization of clinical asthma management.
Bronchodilator response; transcription factor; association; thyroid hormone receptor β; asthma; pharmacogenetics
Airway hyperresponsiveness (AHR), a primary characteristic of asthma, involves increased airway smooth muscle contractility in response to certain exposures. We sought to determine whether common genetic variants were associated with AHR severity.
A genome-wide association study (GWAS) of AHR, quantified as the natural log of the dosage of methacholine causing a 20% drop in FEV1, was performed with 994 non-Hispanic white asthmatic subjects from three drug clinical trials: CAMP, CARE, and ACRN. Genotyping was performed on Affymetrix 6.0 arrays, and imputed data based on HapMap Phase 2, was used to measure the association of SNPs with AHR using a linear regression model. Replication of primary findings was attempted in 650 white subjects from DAG, and 3,354 white subjects from LHS. Evidence that the top SNPs were eQTL of their respective genes was sought using expression data available for 419 white CAMP subjects.
The top primary GWAS associations were in rs848788 (P-value 7.2E-07) and rs6731443 (P-value 2.5E-06), located within the ITGB5 and AGFG1 genes, respectively. The AGFG1 result replicated at a nominally significant level in one independent population (LHS P-value 0.012), and the SNP had a nominally significant unadjusted P-value (0.0067) for being an eQTL of AGFG1.
Based on current knowledge of ITGB5 and AGFG1, our results suggest that variants within these genes may be involved in modulating AHR. Future functional studies are required to confirm that our associations represent true biologically significant findings.
Asthma; Airway hyperresponsiveness; Genome-wide association study; ITGB5; AGFG1

domain: literature


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With spaciousness creates perfect conditions for relaxation. Very convenient and comfortable, additionally equipped with a sofa. Room available on request, with separate beds TWIN or DBL bed type. Also suitable for 3 persons.
In this standard, we have rooms with bath or shower.
The price includes breakfast, internet access, coffee and -tea service.
Room size: 25 m2
Within: till 26.04 and from 01.09.15
Within: 27.04 till 31.08.15

domain: travel


text:
Almost Medicinal: Clarus is Key Component of Patient Care
Does a Glassboard a day keep the doctor away? Clarus Glassboards are quickly becoming an essential part of the patient care process in healthcare facilities all over North America.
How important is patient-practitioner communication? In an overnight stay, with daily communication essential for such things as instructions, treatment approach, next time to take medicine, general reminders and of course, cheerful motivation, the bond between patient and medical professionals is paramount for success.
H-C-A-H-P-S. To some it might read like an eye-chart. But to doctors and nurses, this stands for ‘Hospital Consumer Assessment of Healthcare Providers and Systems’. And it’s defined as ‘a survey instrument and data collection methodology for measuring patients’ perceptions of their hospital experience’.
The surveys are delivered to patients upon discharge. And HCAHPS scores are publicly reported based on four consecutive quarters of data. Because solid scores are important for reimbursement and market share, hospital administrators must seek effective ways to uplift their service. While medical decision making and procedure is the first deliverable for a successful recovery, the experience is a close second.
Becker’s Hospital Review lists strategies to boost HCAHPS scores, and the number one strategy for improving this critical measure of effectiveness is to ‘Communicate clearly and often.’
But in reading their expert suggestions, it’s clear that Clarus Glassboards’ Healthboard product is a critical solution – and highly effective at helping achieve these goals.
Becker points out that the surveys ask patients if they received information in writing about symptoms. And how well staff described their treatment. Communication is clearly paramount for a great patient experience, not to mention high HCAHPS scores.
But chief among suggestions, is Becker’s call for nurses and physicians to use multiple modes of communication. The sentiment is reinforced in the article by Elizabeth Chabner Thompson, MD, MPH who said “To reinforce important information to patients, staff should both write instructions and repeat them verbally, giving patients time to respond with questions.”
Becker’s points out that patients’ rooms can consider whiteboards a solution, as in South Nassau Communities Hospital in Oceanside, New York – of course whiteboards are a staple of many such rooms nationwide.
But given the imperative to communicate well, to inspire and heal, and to make 100% sure that patients feel you are investing in the communication facet of their experience, Glassboards are the better solution for medical facilities.
As Clarus’ Healthboard product line takes the market by storm, instantly adding communication prowess to any facility, practitioners appreciate them for a few simple, but logical reasons.
- Glass is not porous, like whiteboard plastic, and Clarus glass is even less porous. Quite simply, cheap whiteboards harbor bacteria, Glassboards don’t. Do practitioners always wash their hands before using boards? Glassboards have the antimicrobial resistance to wipe clean and sanitize. Because the surface is glass, literally any cleaner will do. This is critical for healthcare facilities that have millions of nuanced ways they have to clean and care for products. Clarus Glassboards are the opposite of high maintenance.
- Glassboards do not ghost or stain, leaving no chance for patient confidentiality to be compromised with leftover marker or smudge. Ask any nurse out there, unfortunately they know this pain all-to-well.
- The adhesion strength of Clarus Glassboards is rated to withstand 6500lbs of sheer force, meaning in a busy hospital, you can rest assured they’re at no risk of injuring patients. Can other glassboards say the same?
- Glassboards last forever. A Recent study by MarketScale demonstrated that whiteboards last only 4-6 years in a commercial setting – that could be even less in a busy hospital with daily, sometimes hourly use.
- Glassboards are inspiring. The candy paint colors are healing alone. And practitioners can frame their ideas and communications in an almost artful way, down to the smiley face.
HCAHPS is an important measurement. It is truly remarkable how critical the patient experience is to overall success during a hospital stay. Informed and inspired patients are motivated patients. And while healing and recovering in a room full of unfamiliar machines, technology and people, the written cheer on beautiful glass is a reminder for patients that their nurses and physicians care, that life is most of all beautiful and they have a friend in the process.

domain: health


Adidas Originals Classic Adibreak Tracksuit Bottom – Orange
• Regular fit
• Drawcord on elastic waist
• 100% recycled polyester tricot
• Side zip pockets
This classic Adidas Originals Adibreak Orange Tracksuit bottom has been around since time immemorial. This tracksuit bottoms snap buttons and 3-Stripes along the leg. It is made with Primegreen, a series of high-performance recycled materials.
Only logged in customers who have purchased this product may leave a review.


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domain: pet


text:
Chicago firefighter contract upgrades ambulances
The five-year deal gives Chicago medics and firefighters an 11 percent raise plus back pay
By Fran Spielman
CHICAGO — Chicago will get a dramatic upgrade in ambulance care — and firefighters will get $32 million in back pay — under a five-year contract approved Wednesday that opens the door to even higher pay raises.
The agreement ratified by the City Council guarantees 4,645 firefighters, paramedics and emergency medical technicians an 11 percent pay raise over five years, but ends free health care for those who retire between the ages of 55 and 65. After Dec. 31, those retirees will be forced to contribute 2 percent of their annuities toward the cost of their health insurance until they're eligible for Medicare.
All 15 of Chicago’s basic-life-support ambulances will be converted to advanced-life-support, giving Chicago 75 ambulances capable of administering the most sophisticated level of care.

domain: news


If you (or your kids) grew up playing The Oregon Trail, a game that pitted a band of settlers against the dangers of nature as they journeyed from Missouri to Oregon, Mental Floss has the fascinating story of the game, which was conceived as a way to teach history. Though it was popularized on the Apple ][, the original game was actually played on a teletype, where students would have to type “bang” quickly and accurately to hunt game. follow link
Mac OS X Zip Expanding Utility
Firefox (and possibly other applications) may ask you what you want to do with .zip archives that you download from the Internet. If you want to expand them with Mac OS X (rather than StuffIt Expander), you may be unsure of which application actually does the job. You're looking for Archive Utility (in Leopard and later) or BOMArchiveHelper (in Tiger). In either case, the application is stored in Hard Drive/System/Library/Core Services/. Don't move it from there, though, or you'll confuse matters.
- ExtraBITS for 5 August 2013 (05 Aug 13)
The Story of The Oregon Trail


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Red Bull driver Max Verstappen of the Netherlands reacts following the Singapore Formula One Grand Prix at the Marina Bay circuit, Singapore, Sunday, Sept. 17, 2023. Photo: AP
The Dutchman finished fifth under the Marina Bay lights after starting 11th on the grid, meaning he will not be able to clinch his third straight world title at Suzuka.
But Verstappen, who has won 12 of the 15 races so far this season, can move to the cusp of retaining his crown while his Red Bull team can seal the constructors' championship.
The 25-year-old told reporters after struggling with Singapore's street circuit, where overtaking is all but impossible, that "this track is so different to Suzuka and it doesn't relate".
"We have learned a bit from today and have a few ideas with what we got wrong," he said after Carlos Sainz triumphed for Ferrari to ruin Red Bull's perfect record this season.
"I cannot go into details but I feel good about Suzuka."
Verstappen certainly enjoyed his last visit to Japan, beating Ferrari's Charles Leclerc to clinch last season's championship there.
The Dutchman won a chaotic race shortened by rain and then saw nearest rival Leclerc relegated to third by a five-second penalty, handing Verstappen the title.
Verstappen was only informed he had clinched the championship midway through the post-race TV interview, and even the driver himself was not sure if he had secured the title.
With Verstappen a whopping 151 points clear of Red Bull teammate and nearest challenger Sergio Perez in the current campaign, he could be crowned champion again as early as next month's Qatar Grand Prix.
This year's race in Japan has been shifted two weeks earlier in the Formula One calendar and the forecast is for dry conditions.
That should give Verstappen the chance to cut loose on Suzuka's sweeping bends and dramatic elevation changes.
He could barely contain his excitement last year as the race returned after a three-year absence because of the coronavirus pandemic.
"Nothing feels like here in Suzuka because of just the old-school nature -- the gravel and the grass," he said.
"You know you have to really build up your confidence and really build up to the limit."
Perez finished eighth in Singapore in a rare weekend to forget for Red Bull, whose hopes of sweeping every race in 2023 came to an end.
The last time neither Verstappen nor Perez stood on the top step of the podium was in Brazil in November 2022.
Instead it was Ferrari's Sainz who took the honours in Singapore, ahead of McLaren's Lando Norris and Mercedes' Lewis Hamilton.
Hamilton's teammate George Russell was pushing hard for the victory until he crashed on the final lap.
After the drama and unpredictability of Singapore, the Red Bulls will start as heavy favourites to restore normal order on Suzuka's high-speed circuit.
Red Bull lead nearest challengers Mercedes by 308 points in the constructors' championship and will clinch the title this weekend with a one-two finish with the fastest lap.
Like with Verstappen, it is only a matter of time.
"I'm expecting Red Bull to be dominant again for the next few weekends," conceded Norris.
"We're getting there, we're making progress and that's the best thing that we can do at this time."
(For more sports news and updates, follow Ahram Online Sports on Twitter at @AO_Sports and on Facebook at AhramOnlineSports.)


Overview of Textiles at OLA
Textiles at OLA is an exciting subject which mixes practical learning with modern technology, whilst encouraging all pupils to build confidence and learn independently. The use of technology is fully embedded in the Textiles curriculum and pupils regularly use iPads, the vinyl cutter and Adobe Photoshop/Illustrator to extend their learning.
Textiles is part of the core curriculum followed by all pupils in Years 7 and 8, where it is taught for half a year alongside other areas of Design and Technology. In Year 9 pupils can opt to continue their Textiles education and the GCSE course begins in Year 10. At OLA we also offer an A Level in this subject.
The Textiles room has benefited from much improvement and investment over the past few years. We have recently purchased a class set of brand new Bernina sewing machines which all pupils are taught to use independently at the start of Year 7. In addition to new sewing machines we have also acquired 4 new pattern cutting tables, giving the pupils room to work effectively in a studio style environment. The classroom also benefits from a trolley of iPads which are used across all year groups, alongside the dedicated CAD suite (shared with the Food and Nutrition department) where all the computers have the full Adobe Creative Cloud software installed.
Years 7 to 9 Textiles Curriculum
In Year 7 pupils have the opportunity to create a 'Pugglie' which is an ugly monster that is produced using sustainable fabrics and components. They are taught a range of machine and hand sewing techniques, and encouraged to use them to enhance their 'Pugglie' design ideas.
Year 8 pupils look at commercial fabric printing techniques. Using Graffiti as a source of inspiration they will use the iPads to create a repeat pattern which will then be outsourced to a professional printing company to sublimate their design on to fabric. The fabric produced is used to make a pair of drawstring pyjama shorts and pupils add a pocket and/or decoration to an existing T shirt to complement their product.
In Year 9 pupils will investigate batch production and Biomimicry. Taking inspiration from nature, they will learn a range of new techniques and processes. These skills will be documented in a beautifully presented sketch book that they will be able to use for reference in years to come. Towards the end of the module pupils will work in teams to produce a range of cushions that will 'Mimic Nature' in some way. They will learn how products are produced in industry and contribute to several aspects of all of the products being made by the group.
The work in Years 7 to 9 is assessed in line with the GCSE marking criteria. Practical work is assessed at the end of the project and folder work and homework assignments are regularly assessed throughout the term. The combination of practical work, and all written based work accounts for 60% of the final mark, while an end of rotation examination accounts for the other 40%.
Pupils are required to bring in fabric from home to recycle in Year 7. Pupils in Year 8 are invoiced a small fee for the fabric they produce when making their pyjamas shorts. In addition, they are asked to bring in a plain white T Shirt or vest top from home to embellish to complete their pyjamas. Pupils in Year 9 generally source fabric from the textiles cupboard for their cushion project. From time to time they may need to purchase additional materials as required.
Trips for Textiles in Years 7 to 9
There may be the opportunity for pupils to take part in a combined Textiles/Design and Technology trip in the Trinity Term of Year 7 and/or Year 8. This will be charged at cost. Year 9 pupils are often invited to attend the GCSE Textiles trip.
Co-curricular Textiles Activities in Years 7 to 9
Ms Gable offers sock club for Years 7 and 8 on a weekly basis. Pupils build upon skills taught in lessons to create animals and creatures out of new socks.
Textiles Curriculum for Years 10 and 11
This curriculum is undergoing change at present meaning that a different specification is being used in each year. Pupils will be expected to provide their own fabric for all projects during Years 10 and 11. In addition to fabrics, pupils may be asked to purchase extra components of sample fabrics for their development work.
AQA Fashion and Textiles: Technical Award Specification code 3720
This new and exciting Technical Award qualification in Fashion and Textiles has been developed for young learners who want to study textiles in a practical way. It replaces the out-going GCSE in Textiles Technology. Technical Awards will be equivalent to a GCSE qualification. They will be considered as equal to a GCSE in fulfilling the entry requirements for post 16 study. Please note that this specification has not yet been accredited and so some details may change before September 2017.
Pupils will develop a range of skills and knowledge including:-
1. A greater understanding of the fashion industry and design related areas
2. Working with fashion design briefs
3. Learning basic pattern cutting skills
4. Researching about relevant fashion designers and textiles artists
5. Learning an exciting range of garment construction techniques
6. Developing fabric and surface decoration techniques
7. Learning the basics of fashion drawing and interpreting your designs and ideas on paper
8. Being given the opportunity to design and make a range of textile products and samples
Unit 1: Skills Demonstration - Internally Assessed (30%)
Pupils have the chance to carry out a number of bite-sized projects to demonstrate their competency in the core skills outlined in the specification. Practical evidence of 12 core skills will be recorded in a portfolio. One of the skills assessed will be teamwork.
Unit 2: Extended Making Project - Internally Assessed (30%)
For this unit, pupils will undertake an Extended Making Project that showcases the skills they have developed in unit 1. Pupils will develop skills in planning and development, making, testing and evaluation and communication. The Extending Making Project will respond to a brief set by the Awarding Body.
Unit 3: External Assessment (written examination – 40%)
Pupils will study the fundamentals of the fashion and textiles industry and the industrial and commercial processes that exist within it. They will learn about materials and their properties and also about possible careers within the industry.
AQA Textiles Technology Specification Code 4570
Textiles Technology develops a wide range of skills and knowledge and is a good area of study for those interested in any aspect of the subject. Areas covered include choice and use of fabrics, design, creative textiles, use and care of equipment, fibres and fabrics, technical textiles, computer aided design (CAD) and manufacturing (CAM), and ethical trading and sustainability. Alongside creative and technical skills pupils will develop: problem solving, investigative skills and decision making expertise.
The controlled assessments cover a wide range of topics designed to encourage individuals to develop their particular strengths and interests within Textiles. Areas of study on offer include interior design, the influence of other cultures, recycled fashion, fashion trends, Fairtrade textiles, Techno textiles, textiles for children and fashion influenced by another culture. There are approximately twelve design briefs to choose from.
Examination: 2 hours (40% of the final grade)
Controlled Assessment: (60% of the final grade)
Trips for Textiles in Years 10 and 11
Each year there is a combined GCSE and A Level day trip to a Fashion or Textiles related establishment. Previous trips have visited the Clothes Show Live in Birmingham, The Victoria and Albert Museum and the Design Museum in London.
Co-curricular Textiles Activities in Years 10 and 11
Mrs Sharkey offers Adobe Photoshop/Adobe Illustrator club every week to help pupils build their computer aided design skills.
Sixth Form Textiles Curriculum
Please click here for full details on Sixth Form Textiles.


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I’m currently reading Clayton Christensen’s How Will You Measure Your Life. Before hitting Add to Cart on Amazon I spent a few minutes searching the web for things he’s written and for things written about him. I came away with several quotes and ideas. The guy is something else. From Forbes:
I’m an optimistic person. But for the first time in my life, with all my problems, I focused more and more on me–and it was depressing, literally. Sometimes I just wanted to quit trying to learn and speak and write again and just go into my basement and build furniture. I learned an important lesson from this. I learned that focusing on my own problems does not bring happiness. God didn’t say, “Okay. For those with problems it’s okay to focus on yourself. And for those who don’t have problems, I want you to focus on helping others.” Even in dire times God does not exempt me from his commandment to focus my life on others, because it transforms hardship to joy.
Another article ends with this powerful quote:
The person I decide to be has to be robust enough that it doesn’t matter what happens in my life… Life will happen to me. But I don’t want what happens in life to determine who Clay Christensen becomes.


With 12 months to go before Porsche’s 918 Spyder hits the road, the development car has already exceeded Porsche’s goal of lapping the Nürburgring Nordschleife in less than seven minutes and 30 seconds.
In fact, earlier this week a Porsche 918 Spyder prototype turned in a single-lap best time of just 7min 14 seconds for the 12.9 mile circuit.
“By turning in a fabulous time of 07:14 minutes, the 918 Spyder prototype has already fully confirmed the viability of its future concept after just a few months on the road”, said Dr. Frank Walliser, project leader for the 918 Spyder.
Although Porsche didn’t confirm who was driving the prototype 918 Spyder, the tracking shots show rally legend and Porsche ambassador, Walter Röhrl at the wheel. It was Rohrl who set the 7min 28.71 second lap time for its predecessor, the Carrera GT, which was achieved back in 2004.
The prototype with over 784bhp was wearing production Michelin road tyres as well as the optional “Weissach” package, which integrates a series of modifications that boost driving performance.
The Weissach package is rumoured to include, enhancements to the 918’s four-wheel steering, upgraded carbon ceramic brakes, and numerous weight-saving measures that turn the cabin of the 918 Spyder into that of a pseudo race car.
Porsche will offer the package with the option of two exterior liveries – Martini Racing Design and Salzburg Racing Design. In addition to these two historic designs, other film packages in solid colours with carbon contrast elements will also be available.
Other colours offered for the standard 918 Spyder include; solid colours – White, Black, Racing Yellow and Guards Red. Metallic colours – Rhodium Silver, Basalt Black, Sapphire Blue, Dark Blue, Meteor Grey and GT Silver.
Two premium quality ‘Special’ colours are also available – Liquid Metal Silver and Liquid Metal Chrome Blue – which are uniquely applied directly to the carbon-fibre reinforced plastic.
The 918 Spyder is powered by a mid-mounted 4.6-litre petrol engine, producing 572bhp and ‘two’ electric motors adding a further 212bhp to deliver a total of 784bhp. Peak torque is quoted at 627lb-ft (850Nm), more than 44% greater than the Carrera GT.
The combustion engine drives the rear wheels, while each electric motor is used to power either front or rear axle respectively.


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The 26th edition of the Astra Film Festival digs deep into history
- Films about Stalin, Gorbachev and the Romanian Revolution will be in the spotlight at the impending documentary festival
With 126 films in the selection this year (see the news), the Astra Film Festival (14-20 October, Sibiu) is ready for a deep reflection on the past: an important part of the selection focuses on relevant historical moments, including the Romanian Revolution of 1989, as well as present-day issues that make us look at the past in a different light.
Sergei Loznitsa, who received the festival’s top award in 2014 for Maidan [+see also:
film profile], returns to Astra with his newest feature, State Funeral [+see also:
film profile]. The film will open the festival on 14 October and will also be competing in the Central and Eastern European competition, one of the four official competitions at this edition.
The 30th anniversary of the fall of communism in Europe and the Romanian Revolution of 1989 will be acknowledged through two thematic sidebars at Astra. Europe 30: Inbetweening looks at these three decades as a period of time between two walls. One is the Berlin Wall and its fall in November 1989, while the other is represented by the walls built in Europe in order to stop the influx of migrants. Among the films being shown in this sidebar are Jürgen Böttcher's 1989 classic The Wall and Nikolaus Geyrhalter's The Border Fence [+see also:
film profile] (Austria).
The festival will also turn its gaze closer to home with the Videograms-Romania 1989 strand. The star of the show is Andrei Ujică and Harun Farocki’s Videograms of a Revolution (1992), which uses footage from those days in order to show the chaos and the euphoria of the revolution. Dobrivoie Kerpenisan’s Rebels with a Cause starts from the pictures taken by the director during the revolution and revisits the protagonists of those images in the present day, an occasion to question both that period in December 1989 and the three decades that followed.
Did you enjoy reading this article? Please subscribe to our newsletter to receive more stories like this directly in your inbox.

domain: artistic


THE NEWSPAPER THAT SUPPORTS AN INDEPENDENT SCOTLAND ‘The headlines that caught my eye’ £60M spent on Westminster ’Vanity Project’ as benefits are cut, exclusive SNP MP says; Use of big sums on buildings is ’abhorrent’ as Tories slash the incomes of the poorest people in the U.K As thousands of households are seeing their income [...]
Understanding the difference Photo Credit: Ahmed Akacha I’ve been asked in the past why I support refugees but not so much migrants? It’s not that I don’t support migrants, it’s the different reasons as to why one wants to flee their country. Migrants have a choice, while they may want to travel and live in [...]
War of Nations The British Government is not without complicity when it comes to being influenced by the American Government, America has never been great, nor will they be, they are equal to any other country. The British and American Government need to understand just how hated they are around the world and that’s never [...]
Meghan & Harry In The News Again via Thomas Markle News So, again more news regarding Thomas Markle trending on Twitter this morning and this one via ‘The Daily Express’ Quote: Thomas Markle to ‘bare his soul’ in bombshell interview on Meghan and Harry TONIGHT. I do wonder if what people say; ‘A deflection from [...]
Commission of Investigation Report With thanks to Tony Donlan for the opening day of the Big House Oct 6 2019 Introduction Sean Ross mother & baby home opened in 1931 and closed its doors in 1969. During that time almost 6,500 woman were admitted and around 6,079 children were born or admitted to the home. [...]
http://www.facebook.com/112083440587536/posts/116203826842164/ My new book, also advertised on my other fb & website SOFA TALK MEDIA Please feel free to follow me for updates on my Documentary filming begins April 2021 stay up to date with future Podcasts and contact me if you are interested in podcasts on belindaconnissofficial.org B.


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We use only the finest quality materials in our bead and pearl bracelets
. Our bracelets include hand-fired ceramic beads, faceted acrylics, exotic woods, polished precious stones, dyed jade, czech glass, sterling-silver, and much more. And for convenience, our bracelets are strung on a stretchy Powercord which allows the bracelet to easily slide on and off the wearer’s wrist.
Chunky bead bracelets are perfect for effortlessly spicing up an outfit while also adding a touch of personality and pizzaz. Throw on a chunky bracelet
with a pair of jeans and a t-shirt for a jazzed-up casual look. Or pair an elegant pearl bracelet
with that little black dress for an evening out on the town. The key to wearing chunky jewelry
is not to over-accessorize. You want to create a bold look without looking gaudy. So if you are pairing your chunky bracelet with rings
, earrings, or a necklace
, be sure to choose minimalistic styles.

domain: design


Dakota Alert 2500 Series IR2500 Indoor Motion Sensor
The IR-2500 is a passive infrared detector capable of monitoring an area up to 100° wide. With the integral mask, the detection area can be narrowed down to 20° or anywhere in between. With the swivel mount, the IR-2500 sensor can be adjusted right to left up to 80° and up and down up to 50°. With three different sensitivity settings, the IR-2500 can detect a person up to 12 feet, 25 feet or 40 feet away. The IR-2500 is powered by one 9 volt battery (not included) and is designed for indoor or light duty outdoor applications under an eave or other protected location and will send a wireless signal up to a ½ mile* back to the DCR-2500 receiver.
*Actual range will depend on the local terrain.
The Dakota 2500 series is not compatible with the new 4000 series
IR-2500 Dakota Alert Indoor Motion Sensor - Specifications
- Size: 3/75" x 2.75' x 2.5"
- Frequency: 434 MHz
- 256 Code Combinations
- Battery required: 9-volt alkaline(not included)
- Wireless Range: 2500'*
- Detection Range: 12', 25' or 40'
- Detection Angle: 20 to 100 degrees
- Swivel Angel: 80 degrees right to left, 50 degrees up and down
IR-2500 Dakota Alert Indoor Motion Sensor - Included
- 1 - IR-2500 Indoor Motion Sensor
IR-2500 Dakota Alert Indoor Motion Sensor - Support
ReviewsI bought 2 receivers and 4 motion sensors. Even though the motion sensors indicate INDOOR I use them outdoors under porches/eves. I called the company and they indicated it was ok. I selected this model because it is white and not gray like the outdoor models. The two receivers are needed and both placed in different bedrooms. The description could be improved. It only has 4 alert sounds. One is like a whistle which I selected for the carport. The others are melody or a ding dong sound. You should look at the documentation to see how to see what the sounds are and how to select the sounds. It works as intended but it does pickup small animals like a cat. But the sensors come with shields that can be configured to limit the sensor view. I have not done this yet but will if that cat continues to come around. I own the wireless doorbell from Dakota and initially thought the motion sensors/receiver would work similar to that - meaning it would have numerous sound selections available on the receiver for each sensor for each zone and the receiver would control the sound for each sensor. The sensor controls the zone and sound.Carlie
Excellent unitMy first unit was defective and was replaced immediately. I am using it to cover a carport in conjunction with a driveway alert and the combination works great. Each sensor is on a different chime so I know where I am getting an alarm. Have not received any false alarms.
Leave a Review
DetailsCurrent Stock:SKU: IR2500Width: 5.50Height: 3.75Depth: 2.75


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- This event has passed.
Crooner’s: Claudia Schmidt with Bryan Nichols & Dean Magraw-Buy Tickets Here!
September 10, 2018 @ 7:30 pm - 9:30 pm
Impact Services invites you to join us for a special evening of music at Crooner’s Dunsmore Room benefiting our new Voices of Impact – A Dementia-Friendly Choir.
Claudia Schmidt with Bryan Nichols & Dean Magraw will provide an evening of folk, blues and jazz music throughout the evening.
Purchase your Tickets here for $15.
September 10 at 7:30
Crooner’s – Dunsmore Room
6161 Highway 65 NE Mpls, MN 55432
Tickets are $15.00


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New Orleans has long acknowledged that activities on the streets represent a vibrant form of living art that spans both visual and performance. With a population including many natives of New Orleans, St. Tammany Parish is the logical place for an organization to spring up with roots in the marching club traditions that have long been a part of the city. Now in its 11th year, The Divine Protectors of Endangered Pleasures continue to take to the streets of New Orleans on the Friday before Mardi Gras in a riotous display of brilliant color and saucy attitudes as they strut to the sounds of the brass band that accompanies them on their route through the French Quarter.
Arriving early on the day of the event, 200 women travel from the north shore and other parts of Louisiana, as well as other states, to participate in a luncheon and balcony fling as a prelude to the annual promenade. Adding random glitter and glitz to the delight of slow-moving tourists who venture out before 9 a.m. in the Quarter, small groups of Divas head to Arnaud’s Restaurant on the morning of Diva Day. En route, they often put on spontaneous displays of early morning merriment, a signal of delights to come during the remainder of the day. In fact, these Diva sightings are an opportunity to really appreciate the elaborately beaded bustiers before the huge crowds and the sheer numbers in the marching group become a fantastic blur of sights and sounds.
For all the emphasis on pleasure and frivolity, the cultural significance of the organization’s original design and execution of beaded corsets lies in the collaborative nature of what was traditionally considered “women’s work.”
The promenade each year spoofs as well as salutes the efforts of women in times gone by whose role in the household included sewing and mending and often clothing their families. Even wealthy women were taught these skills, though perhaps for more decorative rather than functional purposes. The clearest example exists as an ongoing activity in the months leading up to Diva Day. Groups of women gather to share ideas for themes and designs as well as consult on process and execution. When the beading starts, one becomes aware of the relationship between beading and quilting circles as groups gather to socialize as they work.
Each summer, a collection of ensembles from Diva Day are displayed on the north shore. For the past two years, this showcase event has taken place at St. Tammany Art Association. This year, a new partnership has evolved between the organizations expanding the outreach of the event to include a philanthropic endeavor beneficial to both.
A selected group of hand-decorated contemporary corsets from past Diva Day Promenades will be on display along with the original costumes worn for Diva Day 2012. These one-of-a-kind contemporary corsets from the private collections of the Divine Protectors of Endangered Pleasures were inspired by themes from literature, history, music, folk narratives, film and popular culture. They are offered in silent auction with proceeds benefitting the Louisiana Breast Cancer Task Force, a cause supported by the DIVA’S, and the St. Tammany Art Association, providing arts and education to St. Tammany Parish for over 50 years.
An opening reception will be held on Saturday from 6-8:30 p.m. in the Art House, 320 North Columbia St., Covington. Silent bidding for one-of-a kind bustiers will begin during the reception and continue through Aug. 31, the evening of Covington’s Final Friday Block Party, when the winning bids will be announced. Don’t miss this opportunity to support two great causes and to add a beaded bustier to your collection. The corsets may be functional and many adjust to various body sizes because of the lace closure. They are, however, more often displayed as eclectic art objects either on decorative dress forms, tables, pedestals, and even suspended. All are certain to be interesting topics of conversation and a reminder of the creativity and perseverance of all women.
For more information, contact the St. Tammany Art Association at 892.8650.

domain: hobby


2011 Louisiana Laws
TITLE 39 — Public finance
RS 39:52.1 — Change in expenditure limit
§52.1. Change in expenditure limit
A change to the expenditure limit shall be made pursuant to a concurrent resolution adopted by a favorable vote of two-thirds of the elected members of each house directing the commissioner of administration to change the expenditure limit to a designated amount for a specified fiscal year.
Acts 1997, No. 1149, §1, eff. June 1, 1997.


Your 4-day local weather forecast
Guyra rally against the forced amalgamation.
The 109th Guyra Show has wrapped up for another year.
David Bearup thinks the main street refurb money could be better spent.
Health minister announces changes to improve supply and access to medicinal cannabis in Australia.
Local Dean Mulligan is putting on a massive bull riding event.
Optimum soil health workshop in Guyra.
The Guyra Library celebrates 70 years.


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Online mobile sexting without signups
In forums and on message boards, questions like, “Anyone wanna Kik? Unlike sending regular text messages, though, Kik uses either data or Wifi, which is something to consider if you’re on the verge of going over your data limits.
However, users with SMS messaging limits might find that a plus because it means that you can get an unlimited number of messages per month.
For purposes of this article, "sexting" is the practice of sending nude or semi-nude pictures by cell phone or other electronic media; it is a sexual text ('sext') message.
Sexting is a recent phenomenon, fueled by widespread availability of affordable mobile phones with picture-taking and sending capabilities.
Also, Kik messages are stored only on the device, so the company doesn’t have access to them.
NSPCC chief executive Peter Wanless said: “Sharing nude selfies can put young people at risk of bullying by peers or being targeted by adult sex offenders, so it’s vital that parents talk to their children and that young people feel empowered to say no to sexting requests.“We realize that talking about sexting can be an embarrassing or awkward conversation for both parents and children.“And although most parents said they would seek help if an indecent image of their child had been shared on the internet, half of them weren’t confident about getting the right support.”The trend for sharing explicit images among youngsters has emerged as a challenging issue for authorities following the explosion in smartphone ownership, with warnings that it can leave teenagers vulnerable to exploitation or blackmail.
In 2015, it was disclosed that child protection officers were probing one case involving the practise every day, while figures obtained by showed hundreds of under-18s have been investigated for sexting.
Kik has become such a popular sexting platform that the word is now virtually synonymous with sexting.
Just search #kikme on Twitter and you’ll find a hodgepodge of cleavage, masturbation vids and tweets like, “Feeling horny and selling nudes” — all followed by a Kik username.
But, if you want to improve your sext life, there are some apps out there that can help you step up your thumb game.


All-American Rejects and Gomez will also turn their shows ‘Red’
She will play charity show tomorrow (May 1)
Jaunt will kick off in San Francisco on May 21
No explanation given for new title
But Santi White doesn't mind getting negative MySpace comments
Granted, ‘Say Aha’ loses out considerably in the amazingness stakes simply by virtue of not being ‘LES Artistes’. But who said this was a...
Low Vs Diamond draw a huge hometown crowd
Santi White will support The Streets in London
As streams of ticker-tape blanket KOKO in silver, a gold lamé-jacketed chanteuse in brilliantly tasteless shades cuts some serious rug below, immersed in the...
From Kanye to Casablancas, it seems there isn’t anyone who doesn’t want to work with Santi White. Ever since she came on to the...


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Impact of Calif. prison ruling
Poor care cited in ruling to release Calif. inmates
Severe prison overcrowding is a violation of inmates’ constitutional rights, a 5-4 majority of the U.S. Supreme Court has ruled.
California has one of the largest and most troubled prison systems in the nation, and now must cut its inmate population by about 32,000 prisoners within the next two years, the court ruled last week in an opinion citing inadequate medical and mental health care for the incarcerated.
The ruling sends a message to states that they must deal with overtaxed prisons because severe overcrowding can lead to deficiencies in healthcare, said Rebekah Evenson, attorney with the not-for-profit Prison Law Office at San Quentin, Calif., which argued the case before the court. However, Evenson said California is an outlier.
“The reality on the ground is that the California prison system is vastly more overcrowded than any other state except perhaps Alabama,” Evenson said, adding that Alabama is a much smaller state. “We’re out of the ballpark.”
The high court’s decision backed what lower courts have been saying for decades: California prisoners are receiving woefully inadequate healthcare, and curtailing overcrowding is necessary to improve the
A Supreme Court ruling last week cited inadequate medical and mental health care for prison inmates.

domain: sociology


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On the latest episode of his podcast, Jerry Lawler revealed that he's re-signed with WWE.
Lawler noted on Monday's episode of "Dinner with the King" that he's signed a two-year contract with WWE. Lawler said his deal with WWE comes up on January 10 every year, and he texted Kevin Dunn a reminder about it on January 8. Lawler said he was offered a two-year deal with a raise the next day.
Lawler also said he's going to be on commentary for this year's men's Royal Rumble match. Lawler said it sounds like it will be him, Michael Cole, and JBL calling the match. Chase Field in Phoenix, Arizona is hosting the pay-per-view on January 27.
With this Monday's Raw taking place at the FedExForum in Memphis, Tennessee, Lawler made a brief appearance on the episode. He was shown coming out of Vince McMahon's office during a backstage segment where wrestlers were waiting outside the door to meet with McMahon about wanting to challenge for Brock Lesnar's Universal Championship at the Royal Rumble. The segment ended with Lawler looking bewildered as No Way Jose's conga line went by him.

domain: entertainment


Social media is one of the most cost-effective and dynamic tools for small businesses to use to market and advertise their products and services. Once the realm of college students, social media users now cover a wide spectrum of ages, geographical locations, and socio-economic backgrounds. Social media is now all but a necessity for any business that has an online presence; the ability it offers to reach a vast audience at a small cost is simply unparalleled.
The Organic Nature of Effective Social Media Marketing
Effective Small Business Social Media campaigns create a communal environment in which followers and the business interact in a friendly and unassuming manner. Modern marketing techniques have shifted to a more natural or “organic” approach to reaching consumers; the days of inundating people with repetitive messages and information are over. Social media gives small businesses the ability to interact with customers in an engaging manner through the use of informative and entertaining text, images, and videos.
The Value Mobile User Friendly Social Media
Industry experts estimate that the majority of internet access will eventually be done via smart phones, tablets, and other mobile devices. Following this trend, mobile device users are increasingly using mobile web applications to stay connected with social media throughout their daily activities. Small businesses that keep an eye towards maintaining a mobile friendly social media presence are likely to reach larger audiences and reap the best possible marketing and advertising results.
High Potential Pay Per Click Social Media Advertising
While social media marketing doesn’t necessarily require any spending, the pay per click (PPC) advertising opportunities offered by social media sites can be highly effective. The immense amount of personal information that users provide on social media gives the sites the ability to target the intended market with pin point accuracy. Instead of utilizing the “throw out a wide net” PPC approach of the past, social media PPC ads are placed to attract the users that are most likely to click through or “like” the advertisement. When properly designed and managed, social media PPCs will help small businesses develop a bigger following in a relatively short period of time.
Real Time Monitoring of Customer Reaction
The ability to monitor and learn from conversations between customers or current clients is one of the most valuable benefits provided by social media. The ideal communal and organic social media environment encourages discussions and comments regarding a business’s products and services, giving the business a consistent overview of their target consumers’ needs. This allows businesses to analyze any customer complaints, compliments, requests, and monitor satisfaction levels of current clients.
The Value of Professional Social Media Management Services
Small businesses that want to get the most out of their social media use often team up with outside services to develop the most effective social media presence possible. Outside social media development services start by creating campaigns that are custom tailored to each client from the ground up. Once a business’s “page” or site is custom built, the service will typically manage the campaign to ensure that all content and updates will attract and continually engage with the target market. Working with these services is a team project, allowing the business to manage their social media in tandem with outside help to ensure continued results. Business related social media is an increasingly competitive environment; professional assistance is one of the best ways to stay ahead of the curve.
Social media continues to play a vital role in business branding, advertising, customer interaction, and all around marketing. Small businesses now have the opportunity to compete against larger competitors without breaking the bank, as well have the opportunity to develop quality relationship with target customers and further build on relationships with current clients. With some social media sites attracting over a billion active users, this is a tool that no business should go without.


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They say good things come in threes, but we're overachievers! We just had to give you a whole list,
so check out all these ideas for gift inspiration. Our Gift Gurus are constantly scouting out products,
and there's nothing they like more than sharing their new finds with you. Enjoy the show and share your favorites on Pinterest or Facebook! --
For your favorite little goblin, a personalized treat bag to fill with all those goodies (Maximum 12 characters; all lowercase.) The keepsake felt bag has cute appliques, whipstitch trim and can be used for years. 11" x 14". Imported. Please allow 2 weeks for personalization.
A Personal Creations Exclusive! Perfect for both boys and ghouls, these whimsical treat baskets are sure to get noticed on Halloween! Each one has charming 3-dimensional accents and an oversized reflective face that makes it easy for other trick-or-treaters to see your little one. Please specify Jack-o-Lantern, Witch, Bat, Cat, Spider, Frankenstein, Vampire or Skull design. We personalize it with
A Personal Creations Exclusive! Fiendishly fun trick-or-treat bags feature exciting glow-in-the dark designs. Choose Mustache, Pumpkin, Witches Shoes, or Cat. We personalize each one with any name, up to 10 characters. (When personalizing Mustache design, please note that the apostrophe S will always appear.) Our black cotton canvas tote bag measures 14 L x 13 W. Machine washable.


When the new Toyota [TM] Mirai goes on sale in 2015, those who have access to a hydrogen fueling station will be able to purchase it for roughly $57,500, less than the price of Tesla’s [TSLA] Model S. Both qualify as “zero emission” vehicles; however, when accelerating onto the highway, their similarities begin to diverge. The 85 kWh Model S has the equivalent of 362 horsepower. The Mirai? 153.
Several electric vehicle models have approximately the same horsepower as the new Mirai, but are much lower priced. The Nissan [NSANY] Leaf with 107 HP sells for approximately $29,000, the Ford [F] Focus with 123 HP for about $30,000, and the Chevrolet [GM] Volt with 149 HP for around $34,000. Consequently, the Mirai and other fuel cell vehicles will be in a difficult competitive position at their proposed prices.
Indeed, the correlation between horsepower and price points is quite strong, with fuel cell vehicles standing out as negative outliers. Given the current relationship (shown below), if the Mirai’s horsepower were to double to over 300 HP, its cost would be prohibitive, doubling its price point to approximately $115,000- well above models offered by Tesla.
Fuel cell vehicles promise to eliminate “range anxiety,” the fear of being stranded before reaching a fueling station. The Toyota Mirai’s range will be 300 miles per tank of hydrogen and, though drivers may have to travel a distance to find a station, refueling will take fewer than five minutes. As shown below, while most EV models of similar horsepower are limited to 50-100 miles, Tesla is closer to 285 miles in range per recharge. Estimated to be priced at approximately $35,000, Tesla’s 2017 Model III is designed to deliver a similar price per mile of range as the Mirai.
Given the variables of range, horsepower, and price, the Mirai stands out only in range. Unfortunately, without a massive build-out of fuel cell infrastructure, range will not matter. Tesla’s Supercharger stations now stretch along both coasts and across the country. Given the weak link in fuel cell infrastructure, Tesla’s performance advantage will be more important to most American car buyers. In fact, given its range disadvantage in the luxury/premium space and its price disadvantage in the mass market, the Mirai will struggle to find a “future.”
UPDATE November 18, 2014: This post has been updated by ARK Thematic Analyst David Conway from its original form published on September 2, 2014 by ARK Thematic Analyst Intern Andrew Margrave.


China's Sinosteel Signs Contract For Mill At Bolivia Iron-Ore Mine
31 March 2016
Bolivia's government and state-owned Chinese company Sinosteel signed a contract Wednesday for the construction of a steel mill at the massive El Mutun iron-ore mine, a project that will involve an investment outlay of $422 million.
Bolivian President Evo Morales attended the signing ceremony in Puerto Suarez, a town on the Andean nation's border with Brazil where the mine is located.
The contract marks Bolivia's third attempt in the past 10 years to set up a steel-making facility to process the output from El Mutun. Previous efforts involving Brazilian company EBX and India's Jindal failed.
Morales said in his speech that Sinosteel must build the mill in 30 months and then remain in the country for a year to provide operational assistance to Bolivian technicians, who also are to receive training at Chinese universities.
The plant will have the capacity to process 650,000 tons of raw mineral reserve annually to obtain 250,000 tons of sponge iron and 150,000 tons of construction steel, Morales said.
Of the sponge iron that is produced, roughly 86,000 tons will be exported, the government said.
A Chinese loan will cover 85 percent of the $422 million cost of the steel mill, while the Bolivian government will provide the remaining 15 percent.
Morales' administration is aiming to achieve local production of high-quality construction steel, which would compete in the domestic market with imports from Argentina, Brazil and Peru.
The domestic construction steel market is valued at an estimated $380 million annually, according to the press.
Morales recalled the two previous failed attempts to produce steel at El Mutun, noting that EBX's project was unviable because that company wanted to use vegetable carbon instead of natural gas for a proposed foundry and that Jindal had "failed to comply" with its investment obligations. EFE
Source : foxnews.com


Clew Bay Folk Club Westival Special
Matt Molloy’s Yard Bar
Sat 26th Oct, 2.30pm
Clew Bay Folk Club was set up five years ago by local musicians Tim Rogers and Tony Reidy. Tired of playing in noisy pubs, Tim and Tony wanted to create a platform for people to play where the emphasis is on the music rather than boozy socialising. “We gather monthly and share songs and verse around an agreed theme. It’s lively and informal ... everyone is welcome and everyone shows respect and support for one another,” Tim Rogers explains.
The club’s motto? ‘Not a gig. Not a session. A space to play and to listen.' Essentially, it’s an open mic with the people of Westport. And sure, you never know who might show up!


'Helena Nomad' Mini Cheetah Print Dress
This is the 'Helena Nomad' Mini Cheetah Print Dress by our friends at Auguste The Label! Kinda wild (that’s up to you, really), our Nomad Helena Mini is an ode to easy dressing with its faultless fit, blouson sleeves and your favourite: leopard print.
- Designer: Auguste The Label
- Fabric: 50% Cotton, 50% Viscose
- Colour: Beige
- Wash: Cold Hand Wash