ENVIRONMENTAL INFLUENCES AND EPIGENETIC MECHANISMS IN RISK FOR DEPRESSION

Genetic and environmental factors interact to influence vulnerability for internalizing psychopathology, including Major Depressive Disorder (MDD). The mechanisms that account for how environmental stress can alter biological systems are not yet well understood yet are critical to develop more accurate models of vulnerability and targeted interventions. Epigenetic influences, and more specifically, DNA methylation, may provide a mechanism by which stress could program gene expression, thereby altering key systems implicated in depression, such as frontal-limbic circuitry and its critical role in emotion regulation. This thesis investigated the role of environmental factors from infancy and throughout the lifespan affecting the serotonergic (5-HT) system in the vulnerability to and treatment of depression and anxiety and potential underlying DNA methylation processes. First, we investigated the contributions of additive genetic vs. environmental factors on an early trait phenotype for depression (negative emotionality) in infants and their stability over time in the first 2 years of life. We provided evidence of the substantial contributions of both genetic and shared environmental factors to this trait, as well as genetically- and environmentally- mediated stability and innovation. Second, we studied how childhood environmental stress is associated with peripheral DNA methylation of the serotonin transporter gene, SLC6A4, as well as long-term trajectories of internalizing behaviours. There was a relationship between childhood psychosocial adversity and SLC6A4 methylation in males, as well as between SLC6A4 methylation and internalizing trajectory in both sexes. Third, we investigated changes in emotion processing and epigenetic modification of the SLC6A4 gene in depressed adolescents before and after Mindfulness-Based Cognitive Therapy (MBCT). The alterations from pre- to post-treatment in connectivity between the ACC and other network regions and SLC6A4 methylation suggested that MBCT may work to optimize the connectivity of brain networks involved in cognitive control of emotion as well as also normalize the relationship between SLC6A4 methylation and activation patterns in frontal-limbic circuitry. Our results from these three studies strengthen the theory that environmental influences are critical in establishing early vulnerability factors for MDD, driving epigenetic processes, and altering brain processes as an individual undergoes treatment, or experiences relapse.

Risk and benefits in lifestyle sports: parkour, law and social value

This paper examines the interrelationship between law and lifestyle sports, viewed through the lens of parkour. We argue that the literature relating to legal approaches to lifestyle sport is currently underdeveloped and so seek to partially fill this lacuna. Hitherto, we argue, the law has been viewed as a largely negative presence, seen particularly in terms of the ways in which counter-cultural activities are policed and regulated, and where such activities are viewed as transgressive or undesirable. We argue that this is a somewhat unsophisticated take on how the law can operate, with law constructed as an outcome of constraints to behaviour (where the law authorises or prohibits), distinct from the legal contexts, environments and spaces in which these relationships occur. We argue that the distinctive settings in which lifestyle sports are practiced needs a more fine-grained analysis as they are settings which bear, and bring to life, laws and regulations that shape how space is to be experienced. We examine specifically the interrelationship between risk and benefit and how the law recognises issues of social utility or value, particularly within the context of lifestyle sport. We seek to move from user-centred constructions of law as an imposition, to a more nuanced position that looks at parkour at the intersections of law, space and lifestyle sport, in order to reveal how law can be used to support and extend claims to space.

Protocol: Quality of Life, Decision Making, Costs and Impact on Carers in People Managed without Dialysis - The PACKS Study

Sepsis: the LightCycler SeptiFast Test MGRADE®, SepsiTest™ and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi – a systematic review and economic evaluation

Background: Sepsis can lead to multiple organ failure and death. Timely and appropriate treatment can reduce in-hospital mortality and morbidity. Objectives: To determine the clinical effectiveness and cost-effectiveness of three tests [LightCycler SeptiFast Test MGRADE® (Roche Diagnostics, Risch-Rotkreuz, Switzerland); SepsiTest™ (Molzym Molecular Diagnostics, Bremen, Germany); and the IRIDICA BAC BSI assay (Abbott Diagnostics, Lake Forest, IL, USA)] for the rapid identification of bloodstream bacteria and fungi in patients with suspected sepsis compared with standard practice (blood culture with or without matrix-absorbed laser desorption/ionisation time-offlight mass spectrometry). Data sources: Thirteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from January 2006 to May 2015 and supplemented by hand-searching relevant articles. Review methods: A systematic review and meta-analysis of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. A decision tree was used to estimate the costs and quality-adjusted life-years (QALYs) associated with each test; all other parameters were estimated from published sources. The model was populated with evidence from the systematic review or individual studies, if this was considered more appropriate (base case 1). In a secondary analysis, estimates (based on experience and opinion) from seven clinicians regarding the benefits of earlier test results were sought (base case 2). A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Scenario analyses were used to assess uncertainty. Results: For the review of diagnostic test accuracy, 62 studies of varying methodological quality were included. A meta-analysis of 54 studies comparing SeptiFast with blood culture found that SeptiFast had an estimated summary specificity of 0.86 [95% credible interval (CrI) 0.84 to 0.89] and sensitivity of 0.65 (95% CrI 0.60 to 0.71). Four studies comparing SepsiTest with blood culture found that SepsiTest had an estimated summary specificity of 0.86 (95% CrI 0.78 to 0.92) and sensitivity of 0.48 (95% CrI 0.21 to 0.74), and four studies comparing IRIDICA with blood culture found that IRIDICA had an estimated summary specificity of 0.84 (95% CrI 0.71 to 0.92) and sensitivity of 0.81 (95% CrI 0.69 to 0.90). Owing to the deficiencies in study quality for all interventions, diagnostic accuracy data should be treated with caution. No randomised clinical trial evidence was identified that indicated that any of the tests significantly improved key patient outcomes, such as mortality or duration in an intensive care unit or hospital. Base case 1 estimated that none of the three tests provided a benefit to patients compared with standard practice and thus all tests were dominated. In contrast, in base case 2 it was estimated that all cost per QALY-gained values were below £20,000; the IRIDICA BAC BSI assay had the highest estimated incremental net benefit, but results from base case 2 should be treated with caution as these are not evidence based. Limitations: Robust data to accurately assess the clinical effectiveness and cost-effectiveness of the interventions are currently unavailable. Conclusions: The clinical effectiveness and cost-effectiveness of the interventions cannot be reliably determined with the current evidence base. Appropriate studies, which allow information from the tests to be implemented in clinical practice, are required.

U.S. Highway 20 Corridor Development Study, Report B: Improvement Alternatives, Costs and Traffic, 1992

In February the U.S. 20 Corridor Development Study's Steering Committee met to review Report A. At that meeting the Committee selected seven alternatives to be evaluated from a cost and traffic perspective. This report, Report B, presents the cost and traffic evaluation of these seven alternatives. This Report B and its cost and traffic estimates will be reviewed at the next Steering Committee meeting. At that time it is possible that, based on the traffic and cost estimates, one or more of the alternatives will be eliminated from further consideration. After that meeting the Consultant will initiate the more in-depth analyses, including the economic feasibility

What happens at the gap between knowledge and practice? Spaces of encounter and misencounter between environmental scientists and local people

Researchers studying processes of global environmental change are increasingly interested in their work having impacts that go beyond academia to influence policy and management. Recent scholarship in the conservation sciences has pointed to the existence of a research-action gap and has proposed various solutions for overcoming it. However, most of these studies have been limited to the spaces of dissemination, where the science has already been done and is then to be passed over to users of the information. Much less attention has been paid to encounters that occur between scientists and nonscientists during the practice of doing scientific research, especially in situations that include everyday roles of labor and styles of communication (i.e., fieldwork). This paper builds on theories of contact that have examined encounters and relations between different groups and cultures in diverse settings. I use quantitative and qualitative evidence from Madidi National Park, Bolivia, including an analysis of past research in the protected area, as well as interviews (N = 137) and workshops and focus groups (N = 12) with local inhabitants, scientists, and park guards. The study demonstrates the significance of currently unacknowledged or undervalued components of the research-action gap, such as power, respect, and recognition, to develop a relational and reciprocal notion of impact. I explain why, within such spaces of encounter or misencounter between scientists and local people, knowledge can be exchanged or hidden away, worldviews can be expanded or further entrenched, and scientific research can be welcomed or rejected.

Learning from one another: evaluating the impact of horizontal knowledge exchange for environmental management and governance

There is increasing advocacy for inclusive community-based approaches to environmental management, and growing evidence that involving communities improves the sustainability of social-ecological systems. Most community-based approaches rely on partnerships and knowledge exchange between communities, civil society organizations, and professionals such as practitioners and/or scientists. However, few models have actively integrated more horizontal knowledge exchange from community to community. We reflect on the transferability of community owned solutions between indigenous communities by exploring challenges and achievements of community peer-to-peer knowledge exchange as a way of empowering communities to face up to local environmental and social challenges. Using participatory visual methods, indigenous communities of the North Rupununi (Guyana) identified and documented their community owned solutions through films and photostories. Indigenous researchers from this community then shared their solutions with six other communities that faced similar challenges within Guyana, Suriname, Venezuela, Colombia, French Guiana, and Brazil. They were supported by in-country civil society organizations and academics. We analyzed the impact of the knowledge exchange through interviews, field reports, and observations. Our results show that indigenous community members were significantly more receptive to solutions emerging from, and communicated by, other indigenous peoples, and that this approach was a significant motivating force for galvanizing communities to make changes in their community. We identified a range of enabling factors, such as building capacity for a shared conceptual and technical understanding, that strengthens the exchange between communities and contributes to a lasting impact. With national and international policy-makers mobilizing significant financial resources for biodiversity conservation and climate change mitigation, we argue that the promotion of community owned solutions through community peer-to-peer exchange may deliver more long-lasting, socially and ecologically integrated, and investment-effective strategies compared to top-down, expert led, and/or foreign-led initiatives.

WikiRate.org - Leveraging collective awareness to understand companies' environmental, social and governance performance

Abstract. WikiRate is a Collective Awareness Platform for Sustainability and Social Innovation (CAPS) project with the aim of \crowdsourcing better companies" through analysis of their Environmental Social and Governance (ESG) performance. Research to inform the design of the platform involved surveying the current corporate ESG information landscape, and identifying ways in which an open approach and peer production ethos could be e ffectively mobilised to improve this landscape's fertility. The key requirement identi ed is for an open public repository of data tracking companies' ESG performance. Corporate Social Responsibility reporting is conducted in public, but there are barriers to accessing the information in a standardised analysable format. Analyses of and ratings built upon this data can exert power over companies' behaviour in certain circumstances, but the public at large have no access to the data or the most infuential ratings that utilise it. WikiRate aims to build an open repository for this data along with tools for analysis, to increase public demand for the data, allow a broader range of stakeholders to participate in its interpretation, and in turn drive companies to behave in a more ethical manner. This paper describes the quantitative Metrics system that has been designed to meet those objectives and some early examples of its use.

Survey of veterinery drug residues, environmental contaminants and mycotoxins of cultured shirmp in Iran

Economical achievement of optimal growth in developing countries may lead to sustainable poverty reduction. Agricultural activities play an important role in economy and human being welfare, which leads to establishment of food security and quality. Aquaculture products in developing countries share 51.4 percent of total agricultural production and 241 percent in developed countries. Therefore undoubtedly food production by means of quality and quantity has to be increased .The history of shrimp production goes back to 500 years ago. Today 50 countries of the world produce shrimp. In Islamic Republic of Iran shrimp production started since 1992 in the coastal region of Persian Gulf. The shrimp culture farms can be classified in to 4 different categories; extensive, semi-extensive, intensive and super intensive. Global ecological maintenance is one of the major concerns of authorities Human manipulation of nature is the most destructive activity. Industrial sewage leakage in to the rivers and water sources is a big issue that causes reduction in the aquatic population. Heavy metals have an inhibitory effect in the production and growth of sea life. Human intake of food treated with anti-microbial cause's allergy, hypersensitivity and develops microbial resistance. Organochlorine compounds contamination may found in hepatopancreatic tissue of aquatic products, Arsenic may transfer to man via plant and animal product contamination.

Practical challenges in moving to Open Access: a focus on research funders and universities

At the Berlin7 conference in Paris on 3 December 2009 Knowledge Exchange provided a workshop on the practical challenges to be addressed in moving to Open Access. Presentations where provided by John Houghton and Alma Swan discussing the outcomes of studies on the costs and benefits of Open Access for institutions and the society as a whole. These were followed by presentations by two funding agencies on the results of financing publication costs both at an institutional and national level in Germany. Also the results of the Springer deal in the Netherlands where presented. The third section was focused on the results of implementing mandates both by funding bodies and institutions.

Estimating production costs and profitability of strawberry genotypes in southeast Queensland using plant traits

In Queensland the subtropical strawberry (Fragaria ×ananassa) breeding program aims to combine traits into new genotypes that increase production efficiency. The contribution of individual plant traits to cost and income under subtropical Queensland conditions has been investigated. The study adapted knowledge of traits and the production and marketing system to assess the economic impact (gross margin) of new cultivars on the system, with the overall goal of improving the profitability of the industry through the release of new strawberry cultivars. Genotypes varied widely in their effect on gross margin, from 48% above to 10% below the base value. The advantage of a new genotype was also affected by the proportion of total area allocated to the new genotype. The largest difference in gross margin between that at optimum allocation (8% increase in gross margin) and an all of industry allocation (20% decrease in gross margin) of area to the genotype was 28%. While in other cases the all of industry allocation was also the optimum allocation, with one genotype giving a 48% benefit in gross margin.

Influence of environmental variability and age on the body condition of small pelagic fish in the Gulf of Lions

Endogenous and environmental variables are fundamental in explaining variations in fish condition. Based on more than 20 yr of fish weight and length data, relative condition indices were computed for anchovy and sardine caught in the Gulf of Lions. Classification and regression trees (CART) were used to identify endogenous factors affecting fish condition, and to group years of similar condition. Both species showed a similar annual cycle with condition being minimal in February and maximal in July. CART identified 3 groups of years where the fish populations generally showed poor, average and good condition and within which condition differed between age classes but not according to sex. In particular, during the period of poor condition (mostly recent years), sardines older than 1 yr appeared to be more strongly affected than younger individuals. Time-series were analyzed using generalized linear models (GLMs) to examine the effects of oceanographic abiotic (temperature, Western Mediterranean Oscillation [WeMO] and Rhone outflow) and biotic (chlorophyll a and 6 plankton classes) factors on fish condition. The selected models explained 48 and 35% of the variance of anchovy and sardine condition, respectively. Sardine condition was negatively related to temperature but positively related to the WeMO and mesozooplankton and diatom concentrations. A positive effect of mesozooplankton and Rhone runoff on anchovy condition was detected. The importance of increasing temperatures and reduced water mixing in the NW Mediterranean Sea, affecting planktonic productivity and thus fish condition by bottom-up control processes, was highlighted by these results. Changes in plankton quality, quantity and phenology could lead to insufficient or inadequate food supply for both species.

Impact of parenteral nutrition standardization on costs and quality in adult patients

Background: Parenteral nutrition (PN) is a costly therapy that can also be associated with serious complications. Therefore, efforts are focusing on reducing rate of complications, and costs related to PN. Objective: The aim was to analyze the effect of the implementation of PN standardization on costs and quality criteria. Secondary aim was to assess the use of individualized PN based on patient's clinical condition. Methods: We compare the use of PN before and after the implementation of PN standardization. Demographic, clinical and PN characteristics were collected. Costs analysis was performed to study the costs associated to the two different periods. Quality criteria included were: 1) PN administration; 2) nutrition assessment (energy intake between 20-35 kcal/kg/day; protein contribution according to nitrogen balance); 3) safety and complications (hyperglycemia, hypertriglyceridemia, hepatic complications, catheter-related infection); 4) global efficacy (as serum albumin increase). Chi-square test was used to compare percentages; logistic regression analysis was performed to evaluate the use of customized PN. Results: 296 patients were included with a total of 3,167 PN compounded. During the first period standardized PN use was 47.5% vs 85.7% within the second period (p < 0.05). No differences were found in the quality criteria tested. Use of individualized PN was related to critical care patients, hypertriglyceridemia, renal damage, and long-term PN. Mean costs of the PN decreased a 19.5%. Annual costs savings would be € 86,700. Conclusions: The use of customized or standard PN has shown to be efficient and flexible to specific demands; however customized PN was significantly more expensive.