Lobbying by Trade Associations on EU Climate Policy

Climate change has been recognised as one of the greatest challenges of the 21st Century. Its impacts, and they way that we choose to deal with them will profoundly affect how business and society operates. This report focuses on European Union (EU) climate policy – the governance structures, rules and regulations that have been put in place at the EU level to attempt to mitigate and adapt to the impacts of climate change. Specifically, it focuses on how trade associations representing industrial sectors or broader business interest have lobbied on EU climate policy, and the impact that they have had on the policymaking process. The report then goes on to discuss whether the impacts of this lobbying align with the stated policies of the companies that are members of these trade associations.

Acute hypoxia reduces plasma myostatin independent of hypoxic dose

Background: Muscle atrophy is seen ~ 25 % of patients with cardiopulmonary disorders, such as chronic obstructive pulmonary disorder and chronic heart failure. Multiple hypotheses exist for this loss, including inactivity, inflammation, malnutrition and hypoxia. Healthy individuals exposed to chronic hypobaric hypoxia also show wasting, suggesting hypoxia alone is sufficient to induce atrophy. Myostatin regulates muscle mass and may underlie hypoxic-induced atrophy. Our previous work suggests a decrease in plasma myostatin and increase in muscle myostatin following 10 hours of exposure to 12 % O2. Aims: To establish the effect of hypoxic dose on plasma myostatin concentration. Concentration of plasma myostatin following two doses of normobaric hypoxia (10.7 % and 12.3 % O2) in a randomised, single-blinded crossover design (n = 8 lowlanders, n = 1 Sherpa), with plasma collected pre (0 hours), post (2 hours) and 2 hours following (4 hours) exposure. Results: An effect of time was noted, plasma myostatin decreased at 4 hours but not 2 hours relative to 0 hours (p = 0.01; 0 hours = 3.26 [0.408] ng.mL-1, 2 hours = 3.33, [0.426] ng.mL-1, 4 hours = 2.92, [0.342] ng.mL-1). No difference in plasma myostatin response was seen between hypoxic conditions (10.7 % vs. 12.3 % O2). Myostatin reduction in the Sherpa case study was similar to the lowlander cohort. Conclusions: Decreased myostatin peptide expression suggests hypoxia in isolation is sufficient to challenge muscle homeostasis, independent of confounding factors seen in chronic cardiopulmonary disorders, in a manner consistent with our previous work. Decreased myostatin peptide may represent flux towards peripheral muscle, or a reduction to protect muscle mass. Chronic adaption to hypoxia does not appear to protect against this response, however larger cohorts are needed to confirm this. Future work will examine tissue changes in parallel with systemic effects.

Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity.

The limited ability of common variants to account for the genetic contribution to complex disease has prompted searches for rare variants of large effect, to partly explain the 'missing heritability'. Analyses of genome-wide genotyping data have identified genomic structural variants (GSVs) as a source of such rare causal variants. Recent studies have reported multiple GSV loci associated with risk of obesity. We attempted to replicate these associations by similar analysis of two familial-obesity case-control cohorts and a population cohort, and detected GSVs at 11 out of 18 loci, at frequencies similar to those previously reported. Based on their reported frequencies and effect sizes (OR≥25), we had sufficient statistical power to detect the large majority (80%) of genuine associations at these loci. However, only one obesity association was replicated. Deletion of a 220 kb region on chromosome 16p11.2 has a carrier population frequency of 2×10(-4) (95% confidence interval [9.6×10(-5)-3.1×10(-4)]); accounts overall for 0.5% [0.19%-0.82%] of severe childhood obesity cases (P = 3.8×10(-10); odds ratio = 25.0 [9.9-60.6]); and results in a mean body mass index (BMI) increase of 5.8 kg.m(-2) [1.8-10.3] in adults from the general population. We also attempted replication using BMI as a quantitative trait in our population cohort; associations with BMI at or near nominal significance were detected at two further loci near KIF2B and within FOXP2, but these did not survive correction for multiple testing. These findings emphasise several issues of importance when conducting rare GSV association, including the need for careful cohort selection and replication strategy, accurate GSV identification, and appropriate correction for multiple testing and/or control of false discovery rate. Moreover, they highlight the potential difficulty in replicating rare CNV associations across different populations. Nevertheless, we show that such studies are potentially valuable for the identification of variants making an appreciable contribution to complex disease.

Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study.

We sought to provide a contemporary picture of the presentation, etiology, and outcome of infective endocarditis (IE) in a large patient cohort from multiple locations worldwide. Prospective cohort study of 2781 adults with definite IE who were admitted to 58 hospitals in 25 countries from June 1, 2000, through September 1, 2005. The median age of the cohort was 57.9 (interquartile range, 43.2-71.8) years, and 72.1% had native valve IE. Most patients (77.0%) presented early in the disease (<30 days) with few of the classic clinical hallmarks of IE. Recent health care exposure was found in one-quarter of patients. Staphylococcus aureus was the most common pathogen (31.2%). The mitral (41.1%) and aortic (37.6%) valves were infected most commonly. The following complications were common: stroke (16.9%), embolization other than stroke (22.6%), heart failure (32.3%), and intracardiac abscess (14.4%). Surgical therapy was common (48.2%), and in-hospital mortality remained high (17.7%). Prosthetic valve involvement (odds ratio, 1.47; 95% confidence interval, 1.13-1.90), increasing age (1.30; 1.17-1.46 per 10-year interval), pulmonary edema (1.79; 1.39-2.30), S aureus infection (1.54; 1.14-2.08), coagulase-negative staphylococcal infection (1.50; 1.07-2.10), mitral valve vegetation (1.34; 1.06-1.68), and paravalvular complications (2.25; 1.64-3.09) were associated with an increased risk of in-hospital death, whereas viridans streptococcal infection (0.52; 0.33-0.81) and surgery (0.61; 0.44-0.83) were associated with a decreased risk. In the early 21st century, IE is more often an acute disease, characterized by a high rate of S aureus infection. Mortality remains relatively high.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Variants in MTNR1B influence fasting glucose levels.

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

Blood pressure loci identified with a gene-centric array.

Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.

New gene functions in megakaryopoiesis and platelet formation.

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Características del subsistema demersal durante el crucero de evaluación del recurso merluza (Cr. BIC SNP-1, 9505-06)

Describe la composición por especies de las capturas obtenidas durante la etapa de evaluación del crucero BIC SNP-1 9505-06, entre el 10 de mayo al 13 de junio de 1995, comprendiendo desde Huarmey hasta Puerto Pizarro. Se capturaron 80 especies entre peces (64), crustáceos (10), moluscos (4), equinodermos (1). La mayor diversidad de especies se encontró al norte de los 6°S (subáreas A, B, C, D); se destaca una disminución hacia el sur de este paralelo.

Estructura especiológica de los subsistemas dermesal costero y pelagial costero. Prospección E/E Huamanga 9611-12

Se analiza la composición especiológica y distribución de las capturas obtenidas en la Prospección Pesquera Costera efectuada entre Punta Malpelo (03°30,32 'S; 80°33,36 'W), sur de Puerto Pizarro, y bahía Grande (11°12,46 'S; 77°43,20 'W), al norte de Huacho. Se capturaron 115 especies: 86 peces, 17 crustáceos, 6 moluscos, 3 equinodermos, un cnidario, un sálpido y un poliqueto. Los recursos demersales, con lances de arrastre de fondo, efectuados entre las Puntas Malpelo y Malabrigo (07°43,05 'S, 79°38,75 'W), tuvieron la mayor diversidad (113 especies) y la mayor captura (11 639,4 kg de pesca) destacando por sus volúmenes, tres especies que representaron el 74% de la pesca de arrastre: la merluza (Merluccius gayi peruanus con 6.508,1 kg) seguida del falso volador (Prionotus stephanophrys con 1.603,85 kg) y la anchoveta blanca (Anchoa nasus con 499,85 kg). Los recursos pelágicos se capturaron en menor volumen (581,2 kg), y dos especies constituyeron el 95,3% del total: la anchoveta (Engraulis ringens con 251,95 kg) y el bagre con faja (Galeichthys peruvianus con 301,7 kg).

Características de la estructura especiológica del subsistema demersal durante el invierno de 1996

La fauna acompañante en la pesca de arrastre de la merluza, varía en su composición especiológica, distribución batimétrica, latitudinal y estacional de acuerdo a las condiciones de medio marino. Para el invierno de 1996, se analiza la ocurrencia de la fauna marina de aguas tropicales y templadas, entre Punta Capones y el Puerto de Chimbote durante el Crucero de Evaluación de la Merluza BIC SNP-1 9607-08, empleando una red de fondo tipo Granton 400/127. Se capturaron 69 especies: 56 peces, 4 crustáceos, 5 moluscos, un equinodermo, un cnidario y un cordado. La mayor riqueza íctica se encontró al norte del paralelo 6°S. La captura total en el área estudiada fue de 20.021,43 kg de peces (99%) y 211,24 kg (1%) de invertebrados. La merluza Merluccius gayi peruanus, destaca por su abundancia y frecuencia, se capturaron 18.501,52 kg (91,4% del volumen total). Entre los elasmobranquios, destaca la "raya águila" Myliobatis chilensis y dentro de los teleósteos (peces óseos), los Pisciformes con 19 spp., siendo la familia Sciaenidae la mejor representada con 7 especies.

Estructura especiológica del subsistema costero. E/P San Jacinto I 9512-9601

Se presenta la composición especiológica, el análisis comunitario y distribución de las capturas, obtenidas durante la prospección pesquera EP San Jacinto 9512-9601, desde Puerto Pizarro (03°29,0S) hasta Ilo (17°38.4S). Los arrastres de fondo mostraron que entre Puerto Pizarro y Salaverry se encuentra la mayor diversidad de especies (95), constituyendo los peces (58) el 93% (3,391 kg); destacan la "merluza" Merluccius gayi peruanus (1.311,1 Kg), el "falso volador" Prionotus stephanophrys (626,1 kg), la "cabrilla" Paralabrax humeralis (316,4 kg) y la "lorna" Sciaena deliciosa (247,3 kg). La mayor riqueza (33 especies) y el mayor índice de diversidad se obtuvo en la subárea B (04°-05°S), pero la mayor captura (2.295,2 kg) correspondió a la subárea C (05°-06° S). Los arrastres de media agua, se realizaron desde la desembocadura del río Piura hasta Ilo. El "camaroncito rojo" Pleuroncodes monodon alcanzó el 94% (1.089 kg) de la captura total, pero su distribución abarcó desde los 12° S hasta Ilo con las mayores capturas en las subáreas J (12°.13° S y L(14°-15° S) con 351 y 700 kg respectivamente. Los peces sólo representaron el 6% (46 kg) del volumen total de captura.

Estudio biológico pesquero del perico en Huacho durante el mes de diciembre 1997 y enero 1998

Presenta información que permite mejorar el conocimiento de la biología y pesquería del recurso perico en la zona de Huacho. Presenta datos básicos que contribuye al ordenamiento pesquero del recurso.