The impact of Scotland‟s economy on the environment : a note on input-output and ecological footprint analysis

Several recent papers examining the impact of the Scottish and Jersey economy on the environment have criticised the Ecological Footprint (EF) method and have suggested the use of input-output (IO) analysis instead (McGregor et al., 2004a; McGregor et al., 2004b; Ferguson et al., 2004; Allan et al., 2004). It is argued that “IO can be used to provide a coherent and practical alternative method to the Ecological Footprint of locating the responsibility and source of resource use and waste/pollution” (Allan et al., 2004) and several aspects of the EF methodology are criticised specifically. In this paper we reply to these critiques and discuss the scope and limitations of both the NCLAS as well as the Ecological Footprint. We argue that EF and IO are complementary methods that can be combined in a meaningful way. We suggest a way forward that helps to improve the scientific understanding of key sustainable development issues

Genetic basis for personalized medicine in asthma

There is heterogeneity in patient responses to current asthma medications. Significant progress has been made identifying genetic polymorphisms that influence the efficacy and potential for adverse effects to asthma drugs, including; β2-adrenergic receptor agonists, corticosteroids and leukotriene modifiers. Pharmacogenetics holds great promise to maximise clinical outcomes and minimize adverse effects. Asthma is heterogeneous with respect to clinical presentation and inflammatory mechanisms underlying the disease, which is likely to contribute to variable results in clinical trials targeting specific inflammatory mediators. Genome-wide association studies have begun to identify genes underlying asthma (e.g., IL1RL1), which represent future therapeutic targets. In this article, we review and update the pharmacogenetics of current asthma therapies and discuss the genetics underlying selected Phase II and future targets

Landscape-Level Wolf Space Use is Correlated With Prey Abundance, Ease of Mobility and the Distribution of Prey Habitat

Predator space use influences ecosystem dynamics, and a fundamental goal assumed for a foraging predator is to maximize encounter rate with prey. This can be achieved by disproportionately utilizing areas of high prey density or, where prey are mobile and therefore spatially unpredictable, utilizing patches of their prey\u27s preferred resources. A third, potentially complementary strategy is to increase mobility by using linear features like roads and/or frozen waterways. Here, we used novel population-level predator utilization distributions (termed localized density distributions ) in a single-predator (Wolf), two-prey (moose and caribou) system to evaluate these space-use hypotheses. The study was conducted in contrasting sections of a large boreal forest area in northern Ontario, Canada, with a spatial gradient of human disturbances and predator and prey densities. Our results indicated that wolves consistently used forest stands preferred by moose, their main prey species in this part of Ontario. Direct use of prey-rich areas was also significant but restricted to where there was a high local density of moose, whereas use of linear features was pronounced where local moose density was lower. These behaviors suggest that Wolf foraging decisions, while consistently influenced by spatially anchored patches of prey forage resources, were also determined by local ecological conditions, specifically prey density. Wolves appeared to utilize prey-rich areas when regional preferred prey density exceeded a threshold that made this profitable, whereas they disproportionately used linear features that promoted mobility when low prey density made directly tracking prey distribution unprofitable

Impact of a (poly)phenol-rich extract from the brown algae Ascophyllum nodosum on DNA damage and antioxidant activity in an overweight or obese population: a randomized controlled trial

Background Epidemiologic evidence suggests that a diet rich in (poly)phenols has beneficial effects on many chronic diseases. Brown seaweed is a rich source of (poly)phenols. Objective The aim of this study was to investigate the bioavailability and effect of a brown seaweed (Ascophyllum nodosum) (poly)phenol extract on DNA damage, oxidative stress, and inflammation in vivo. Design A randomized, double-blind, placebo-controlled crossover trial was conducted in 80 participants aged 30–65 y with a body mass index (in kg/m2) ≥25. The participants consumed either a 400-mg capsule containing 100 mg seaweed (poly)phenol and 300 mg maltodextrin or a 400-mg maltodextrin placebo control capsule daily for an 8-wk period. Bioactivity was assessed with a panel of blood-based markers including lymphocyte DNA damage, plasma oxidant capacity, C-reactive protein (CRP), and inflammatory cytokines. To explore the bioavailability of seaweed phenolics, an untargeted metabolomics analysis of urine and plasma samples after seaweed consumption was determined by ultra-high-performance liquid chromatography–high-resolution mass spectrometry. Results Consumption of the seaweed (poly)phenols resulted in a modest decrease in DNA damage but only in a subset of the total population who were obese. There were no significant changes in CRP, antioxidant status, or inflammatory cytokines. We identified phlorotannin metabolites that are considered potential biomarkers of seaweed consumption including pyrogallol/phloroglucinol-sulfate, hydroxytrifurahol A-glucuronide, dioxinodehydroeckol-glucuronide, diphlorethol sulfates, C-O-C dimer of phloroglucinol sulfate, and C-O-C dimer of phloroglucinol. Conclusions To the best of our knowledge, this work represents the first comprehensive study investigating the bioactivity and bioavailability of seaweed (poly)phenolics in human participants. We identified several potential biomarkers of seaweed consumption. Intriguingly, the modest improvements in DNA damage were observed only in the obese subset of the total population. The subgroup analysis should be considered exploratory because it was not preplanned; therefore, it was not powered adequately. Elucidation of the biology underpinning this observation will require participant stratification according to weight in future studies. This trial was registered at clinicaltrials.gov as NCT02295878

Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data

<p>Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.</p> <p>Methods: The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.</p> <p>Results: The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.</p> <p>Conclusion: This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.</p&gt

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels

The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease aggressiveness. We aimed to identify novel genetic and biomolecular mechanisms regulating scuPAR levels. Elevated serum scuPAR levels were identified in asthma (n=514) and chronic obstructive pulmonary disease (COPD; n=219) cohorts when compared to controls (n=96). In these cohorts, a genome-wide association study of serum scuPAR levels identified a human plasma kallikrein gene (KLKB1) promoter polymorphism (rs4253238) associated with serum scuPAR levels in a control/asthma population (P=1.17×10−7), which was also observed in a COPD population (combined P=5.04×10−12). Using a fluorescent assay, we demonstrated that serum KLKB1 enzymatic activity was driven by rs4253238 and is inverse to scuPAR levels. Biochemical analysis identified that KLKB1 cleaves scuPAR and negates scuPAR's effects on primary human bronchial epithelial cells (HBECs) in vitro. Chymotrypsin was used as a proproteolytic control, while basal HBECs were used as a control to define scuPAR-driven effects. In summary, we reveal a novel post-translational regulatory mechanism for scuPAR using a hypothesis-free approach with implications for multiple human diseases

The role of ALOX5AP, LTA4H and LTB4R polymorphisms in determining baseline lung function and COPD susceptibility in UK smokers

<p>Abstract</p> <p>Background</p> <p>We have previously shown evidence that polymorphisms within genes controlling leukotriene B₄(LTB₄) production (<it>ALOX5AP </it>and <it>LTA4H</it>) are associated with asthma susceptibility in children. Evidence also suggests a potential role of LTB₄in COPD disease mechanisms including recruitment of neutrophils to the lung. The aim of the current study was to see if these SNPs and those spanning the receptor genes for LTB₄(<it>LTB4R1 </it>and <it>LTB4R2</it>) influence baseline lung function and COPD susceptibility/severity in smokers.</p> <p>Methods</p> <p>Eight <it>ALOX5AP</it>, six <it>LTA4H </it>and six <it>LTB4R </it>single nucleotide polymorphisms (SNPs) were genotyped in a UK Smoking Cohort (n = 992). Association with baseline lung function (FEV₁and FEV₁/FVC ratio) was determined by linear regression. Logistic regression was used to compare smoking controls (n = 176) with spirometry-defined COPD cases (n = 599) and to more severe COPD cases (GOLD stage 3 and 4, n = 389).</p> <p>Results</p> <p>No association with <it>ALOX5AP</it>, <it>LTA4H </it>or <it>LTB4R </it>survived correction for multiple testing. However, we showed modest association with <it>LTA4H </it>rs1978331C (intron 11) with increased FEV₁(p = 0.029) and with increased FEV₁/FVC ratio (p = 0.020).</p> <p>Conclusions</p> <p>These data suggest that polymorphisms spanning <it>ALOX5AP</it>, <it>LTA4H </it>and the <it>LTB4R </it>locus are not major determinants of baseline lung function in smokers, but provide tentative evidence for <it>LTA4H </it>rs1978331C (intron 11) in determining baseline FEV₁and FEV₁/FVC ratio in Caucasian Smokers in addition to our previously identified role in asthma susceptibility.</p

The Canadian Bandaging Trial: Evidence-informed leg ulcer care and the effectiveness of two compression technologies

Background: Objective: To determine the relative effectiveness of evidence-informed practice using two high compression systems: four-layer (4LB) and short-stretch bandaging (SSB) in community care of venous leg ulcers. Design and Setting: Pragmatic, multi-centre, parallel-group, open-label, randomized controlled trial conducted in 10 centres. Cognitively intact adults (≥18 years) referred for community care (home or clinic) with a venous ulceration measuring ≥0.7cm and present for ≥1 week, with an ankle brachial pressure index (ABPI) ≥0.8, without medication-controlled Diabetes Mellitus or a previous failure to improve with either system, were eligible to participate.Methods: Consenting individuals were randomly allocated (computer-generated blocked randomization schedule) to receive either 4LB or SSB following an evidence-informed protocol. Primary endpoint: time-to- healing of the reference ulcer. Secondary outcomes: recurrence rates, health-related quality of life (HRQL), pain, and expenditures.Results: 424 individuals were randomized (4LB n = 215; SSB n = 209) and followed until their reference ulcer was healed (or maximum 30 months). An intent-to-treat analysis was conducted on all participants. Median time to ulcer healing in the 4LB group was 62 days [95% confidence interval (CI) 51 to 73], compared with 77 days (95% CI 63 to 91) in the SSB group. The unadjusted Kaplan-Meier curves revealed the difference in the distribution of cumulative healing times was not significantly different between group (log rank χ2 = 0.001, P = 0.98) nor ulcers recurrence (4LB, 10.1%; SSB, 13.3%; p = 0.345). Multivariable Cox Proportional Hazard Modeling also showed no significant between-bandage differences in healing time after controlling for significant covariates (p = 0.77). At 3-months post-baseline there were no differences in pain (no pain: 4LB, 22.7%; SSB, 26.7%; p = 0.335), or HRQL (SF-12 Mental Component Score: 4LB, 55.1; SSB, 55.8; p = 0.615; SF-12 Physical Component Score: 4LB, 39.0; SSB, 39.6; p = 0.675). The most common adverse events experienced by both groups included infection, skin breakdown and ulcer deterioration.Conclusions: The Canadian Bandaging Trial revealed that in the practice context of trained RNs using an evidence-informed protocol, the choice of bandage system (4LB and SSB) does not materially affect healing times, recurrence rates, HRQL, or pain. From a community practice perspective, this is positive news for patient-centred care allowing individual/family and practitioner choice in selecting compression technologies based on circumstances and context.Trial registration: clinicaltrials.gov Identifier: NCT00202267