Monitoring the impacts of trade agreements on food environments

The liberalization of international trade and foreign direct investment through multilateral, regional and bilateral agreements has had profound implications for the structure and nature of food systems, and therefore, for the availability, nutritional quality, accessibility, price and promotion of foods in different locations. Public health attention has only relatively recently turned to the links between trade and investment agreements, diets and health, and there is currently no systematic monitoring of this area. This paper reviews the available evidence on the links between trade agreements, food environments and diets from an obesity and non-communicable disease (NCD) perspective. Based on the key issues identified through the review, the paper outlines an approach for monitoring the potential impact of trade agreements on food environments and obesity/NCD risks. The proposed monitoring approach encompasses a set of guiding principles, recommended procedures for data collection and analysis, and quantifiable ‘minimal’, ‘expanded’ and ‘optimal’ measurement indicators to be tailored to national priorities, capacity and resources. Formal risk assessment processes of existing and evolving trade and investment agreements, which focus on their impacts on food environments will help inform the development of healthy trade policy, strengthen domestic nutrition and health policy space and ultimately protect population nutrition.The following organizations provided funding support for the travel of participants to Italy for this meeting and the preparation of background research papers: The Rockefeller Foundation, International Obesity Taskforce (IOTF), University of Auckland, Deakin University, The George Institute, University of Sydney, Queensland University of Technology, University of Oxford, University of Pennsylvania Perelman School of Medicine, World Cancer Research Fund International, University of Toronto, and The Australian National University. The Faculty of Health at Deakin University kindly supported the costs for open access availability of this paper, and the Australian National Health and Medical Research Council Centre for Research Excellence in Obesity Policy and Food Systems (APP1041020) supported the coordination and finalizing of INFORMAS manuscripts

Copper Chaperone for Cu/Zn Superoxide Dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc

BACKGROUND: Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status. METHODS: Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status. RESULTS: Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4). CONCLUSION: Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn

Gene Expression Patterns of Oxidative Phosphorylation Complex I Subunits Are Organized in Clusters

After the radiation of eukaryotes, the NUO operon, controlling the transcription of the NADH dehydrogenase complex of the oxidative phosphorylation system (OXPHOS complex I), was broken down and genes encoding this protein complex were dispersed across the nuclear genome. Seven genes, however, were retained in the genome of the mitochondrion, the ancient symbiote of eukaryotes. This division, in combination with the three-fold increase in subunit number from bacteria (N = ∼14) to man (N = 45), renders the transcription regulation of OXPHOS complex I a challenge. Recently bioinformatics analysis of the promoter regions of all OXPHOS genes in mammals supported patterns of co-regulation, suggesting that natural selection favored a mechanism facilitating the transcriptional regulatory control of genes encoding subunits of these large protein complexes. Here, using real time PCR of mitochondrial (mtDNA)- and nuclear DNA (nDNA)-encoded transcripts in a panel of 13 different human tissues, we show that the expression pattern of OXPHOS complex I genes is regulated in several clusters. Firstly, all mtDNA-encoded complex I subunits (N = 7) share a similar expression pattern, distinct from all tested nDNA-encoded subunits (N = 10). Secondly, two sub-clusters of nDNA-encoded transcripts with significantly different expression patterns were observed. Thirdly, the expression patterns of two nDNA-encoded genes, NDUFA4 and NDUFA5, notably diverged from the rest of the nDNA-encoded subunits, suggesting a certain degree of tissue specificity. Finally, the expression pattern of the mtDNA-encoded ND4L gene diverged from the rest of the tested mtDNA-encoded transcripts that are regulated by the same promoter, consistent with post-transcriptional regulation. These findings suggest, for the first time, that the regulation of complex I subunits expression in humans is complex rather than reflecting global co-regulation

Index-Free De Novo Assembly and Deconvolution of Mixed Mitochondrial Genomes

Second-generation sequencing technology has allowed a very large increase in sequencing throughput. In order to make use of this high throughput, we have developed a pipeline for sequencing and de novo assembly of multiple mitochondrial genomes without the costs of indexing. Simulation studies on a mixture of diverse animal mitochondrial genomes showed that mitochondrial genomes could be reassembled from a high coverage of short (35 nt) reads, such as those generated by a second-generation Illumina Genome Analyzer. We then assessed this experimentally with long-range polymerase chain reaction products from mitochondria of a human, a rat, a bird, a frog, an insect, and a mollusc. Comparison with reference genomes was used for deconvolution of the assembled contigs rather than for mapping of sequence reads. As proof of concept, we report the complete mollusc mitochondrial genome of an olive shell (Amalda northlandica). It has a very unusual putative control region, which contains a structure that would probably only be detectable by next-generation sequencing. The general approach has considerable potential, especially when combined with indexed sequencing of different groups of genomes

Synthesis and electrical properties of fullerene-based molecular junctions on silicon substrate

We report the synthesis and the electrical properties of fullerene-based molecular junctions on silicon substrate in which the highly \pi-conjugated molecule C60 (\pi quantum well) is isolated from the electrodes by alkyl chains (\sigma tunnel barriers). Initially, the Si/SiO2/\sigmaC60 architecture was prepared either by sequential synthesis (3 different routes) or by direct grafting of the presynthesized C60-\sigma-Si(OEt)3 molecule. We described the chemical synthesis of these routes and the physico-chemical properties of the molecular monolayers. Then, the second \sigma tunnel barrier was added on the Si/SiO2/\sigma C60 junction by applying a hanging mercury drop electrode thiolated with an alkanethiol monolayer. We compared the electronic transport properties of the Si/SiO2/\sigma C60//Hg and Si/SiO2/\sigma C60//\sigmaHg molecular junctions, and we demonstrated by transition voltage spectroscopy that the fullerene LUMO - metal Fermi energy offset can be tailored from ~ 0.2 eV to ~ 1 eV by changing the length of the alkyl chain between the C60 core and the Hg metal electrode (i. e. from direct C60//Hg contact to 14 carbon atoms tunnel barrier).Comment: Single pdf file including: main text, figures, tables and supporting information

Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis

A previous systematic review reported that topical NSAIDs were effective in relieving pain in chronic conditions like osteoarthritis and tendinitis. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. Studies were identified by searching electronic databases, and writing to manufacturers. We identified randomised, double blind trials comparing topical NSAID with either placebo or another active treatment, in adults with chronic pain. The primary outcome was a reduction in pain of approximately 50% at two weeks, and secondary outcomes were local and systemic adverse events and adverse event-related withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative harm and number-needed-to-harm (NNH) were calculated, and the effects of trial quality, validity and size, outcome reported, and condition treated, were examined by sensitivity analyses. Twelve new trials were added to 13 trials from a previous review. Fourteen double blind placebo-controlled trials had information from almost 1,500 patients. Topical NSAID was significantly better than placebo with relative benefit 1.9 (95% confidence interval 1.7 to 2.2), NNT 4.6 (95% confidence interval 3.8 to 5.9). Results were not affected by trial quality, validity or size, outcome reported, or condition treated. Three trials with 764 patients comparing a topical with an oral NSAID found no difference in efficacy. Local adverse events (6%), systemic adverse events (3%), or the numbers withdrawing due to an adverse event were the same for topical NSAID and placebo. Topical NSAIDs were effective and safe in treating chronic musculoskeletal conditions for two weeks. Larger and longer trials are necessary to fully elucidate the place of topical NSAIDs in clinical practice

Meta-analysis: Neither quick nor easy

BACKGROUND: Meta-analysis is often considered to be a simple way to summarize the existing literature. In this paper we describe how a meta-analysis resembles a conventional study, requiring a written protocol with design elements that parallel those of a record review. METHODS: The paper provides a structure for creating a meta-analysis protocol. Some guidelines for measurement of the quality of papers are given. A brief overview of statistical considerations is included. Four papers are reviewed as examples. The examples generally followed the guidelines we specify in reporting the studies and results, but in some of the papers there was insufficient information on the meta-analysis process. CONCLUSIONS: Meta-analysis can be a very useful method to summarize data across many studies, but it requires careful thought, planning and implementation

Attributable mortality to radon exposure in Galicia, Spain. Is it necessary to act in the face of this health problem?

<p>Abstract</p> <p>Background</p> <p>Radon is the second risk factor for lung cancer after tobacco consumption and therefore it is necessary to know the burden of disease due to its exposure. The objective of this study is to estimate radon-attributable lung cancer mortality in Galicia, a high emission area located at the Northwest Spain.</p> <p>Methods</p> <p>A prevalence-based attribution method was applied. Prevalence of tobacco use and radon exposure were obtained from a previously published study of the same area. Attributable mortality was calculated for each of six possible risk categories, based on radon exposure and smoking status. Two scenarios were used, with 37 Bq/m³and 148 Bq/m³as the respective radon exposure thresholds. As the observed mortality we used lung cancer mortality for 2001 from the Galician mortality registry.</p> <p>Results</p> <p>Mortality exclusively attributable to radon exposure ranged from 3% to 5% for both exposure thresholds, respectively. Attributable mortality to combined exposure to radon and smoking stood at around 22% for exposures above 148 Bq/m³. Applying the United States Environmental Protection Agency (EPA) action level, radon has a role in 25% of all lung cancers.</p> <p>Conclusions</p> <p>Although the estimates have been derived from a study with a relatively limited sample size, these results highlight the importance of radon exposure as a cause of lung cancer and its effect in terms of disease burden. Radon mitigation activities in the study area must therefore be enforced.</p

Topical NSAIDs for acute pain: a meta-analysis

BACKGROUND: A previous systematic review reported that topical NSAIDs were effective in relieving pain in acute conditions like sprains and strains, with differences between individual drugs for efficacy. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. METHODS: Studies were identified by searching electronic databases and writing to manufacturers. We selected randomised double blind trials comparing topical NSAID with either placebo or another active treatment in adults with acute pain, and extracted dichotomous information approximating to a 50% reduction in pain at one week, together with details of adverse events and withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative risk and number-needed-to-harm (NNH) were calculated, with sensitivity analyses where appropriate to investigate differences between individual drugs and aspects of trial design. RESULTS: Twenty-six double blind placebo controlled trials had information from 2,853 patients for evaluation of efficacy. Topical NSAID was significantly better than placebo in 19 of the 26 trials, with a pooled relative benefit of 1.6 (95% confidence interval 1.4 to 1.7), and NNT of 3.8 (95% confidence interval 3.4 to 4.4) compared with placebo for the outcome of half pain relief at seven days. Results were not affected by outcome reported, or condition treated, but smaller trials yielded a larger estimate of efficacy. Indirect comparisons of individual topical NSAIDs showed that ketoprofen was significantly better than all other topical NSAIDs, while indomethacin was barely distinguished from placebo. Three trials, with 433 patients, compared topical with oral NSAID (two trials compared the same drug, one compared different drugs) and found no difference in efficacy. Local adverse events, systemic adverse events, or withdrawals due to an adverse event were rare, and no different between topical NSAID and placebo. CONCLUSIONS: Topical NSAIDs were effective and safe in treating acute painful conditions for one week

Are decision trees a feasible knowledge representation to guide extraction of critical information from randomized controlled trial reports?

<p>Abstract</p> <p>Background</p> <p>This paper proposes the use of decision trees as the basis for automatically extracting information from published randomized controlled trial (RCT) reports. An exploratory analysis of RCT abstracts is undertaken to investigate the feasibility of using decision trees as a semantic structure. Quality-of-paper measures are also examined.</p> <p>Methods</p> <p>A subset of 455 abstracts (randomly selected from a set of 7620 retrieved from Medline from 1998 – 2006) are examined for the quality of RCT reporting, the identifiability of RCTs from abstracts, and the completeness and complexity of RCT abstracts with respect to key decision tree elements. Abstracts were manually assigned to 6 sub-groups distinguishing whether they were primary RCTs versus other design types. For primary RCT studies, we analyzed and annotated the reporting of intervention comparison, population assignment and outcome values. To measure completeness, the frequencies by which complete intervention, population and outcome information are reported in abstracts were measured. A qualitative examination of the reporting language was conducted.</p> <p>Results</p> <p>Decision tree elements are manually identifiable in the majority of primary RCT abstracts. 73.8% of a random subset was primary studies with a single population assigned to two or more interventions. 68% of these primary RCT abstracts were structured. 63% contained pharmaceutical interventions. 84% reported the total number of study subjects. In a subset of 21 abstracts examined, 71% reported numerical outcome values.</p> <p>Conclusion</p> <p>The manual identifiability of decision tree elements in the abstract suggests that decision trees could be a suitable construct to guide machine summarisation of RCTs. The presence of decision tree elements could also act as an indicator for RCT report quality in terms of completeness and uniformity.</p