The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis

Summary: Expression of the initiator methionine tRNA (tRNAi Met) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi Met expression levels influence tumor progression. We have found that tRNAi Met expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi Met in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi Met contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi Met gene (2+tRNAi Met mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi Met mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi Met mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi Met significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi Metoverexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl- 3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi Met-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi Met mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi Met levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis

Working with families affected by mental distress: stakeholders' perceptions of mental health nurses educational needs

Family and informal caregivers provide a substantial amount of care and support to people who experience mental health problems. The aim of this study was to explore mental health nurses’, students’ and service users’ perceptions of the knowledge, skills and attitudes that are required by mental health nurses to work with families and carers using a qualitative methodology. Three themes emerged from the data: Knowledge of the family and how mental distress affects the family; Working with the family – support and education and Valuing the role of the family. The three themes demonstrate the complexity of preparing mental health nurses to work with families and carers and the paper offers recommendations about how this might be achieved

Which dressing do donor site wounds need?: study protocol for a randomized controlled trial

Donor site wounds after split-skin grafting are rather 'standard' wounds. At present, lots of dressings and topical agents for donor site wounds are commercially available. This causes large variation in the local care of these wounds, while the optimum 'standard' dressing for local wound care is unclear. This protocol describes a trial in which we investigate the effectiveness of various treatment options for these donor site wounds. A 14-center, six-armed randomized clinical trial is being carried out in the Netherlands. An a-priori power analysis and an anticipated dropout rate of 15% indicates that 50 patients per group are necessary, totaling 300 patients, to be able to detect a 25% quicker mean time to complete wound healing. Randomization has been computerized to ensure allocation concealment. Adult patients who need a split-skin grafting operation for any reason, leaving a donor site wound of at least 10 cm2 are included and receive one of the following dressings: hydrocolloid, alginate, film, hydrofiber, silicone dressing, or paraffin gauze. No combinations of products from other intervention groups in this trial are allowed. Optimum application and changes of these dressings are pursued according to the protocol as supplied by the dressing manufacturers. Primary outcomes are days to complete wound healing and pain (using a Visual Analogue Scale). Secondary outcomes are adverse effects, scarring, patient satisfaction, and costs. Outcome assessors unaware of the treatment allocation will assess whether or not an outcome has occurred. Results will be analyzed according to the intention to treat principle. The first patient was randomized October 1, 2009. This study will provide comprehensive data on the effectiveness of different treatment options for donor site wounds. The dressing(s) that will prevail in effectiveness, satisfaction and costs will be promoted among clinicians dealing with such patients. Thus, we aim to contribute a well-designed trial, relevant to all clinicians involved in the care for donor site wounds, which will help enhance uniformity and quality of care for these patients. http://www.trialregister.nl, NTR1849. Date registered: June 9, 200

Development of an occupational advice intervention for patients undergoing lower limb arthroplasty (the OPAL study)

Background: There are an increasing number of patients of working age undergoing hip and knee replacements. Currently there is variation in the advice and support given about sickness absence, recovery to usual activities and return to work after these procedures. Earlier, sustainable, return to work improves the health of patients and benefits their employers and society. An intervention that encourages and supports early recovery to usual activities, including work, has the potential to reduce the health and socioeconomic burden of hip and knee replacements. Methods/design: A two-phase research programme delivered over 27 months will be used to develop and subsequently test the feasibility of an occupational advice intervention to facilitate return to work and usual activities in patients undergoing lower limb arthroplasty. The 2 phases will incorporate a six-stage intervention mapping process: Phase 1: Intervention mapping stages 1–3: 1 Needs assessment (including rapid evidence synthesis, prospective cohort analysis and structured stakeholder interviews) 2 Identification of intended outcomes and performance objectives 3 Selection of theory-based methods and practical strategies Phase 2: Intervention mapping stages 4–6: 4 Development of components and materials for the occupational advice intervention using a modified Delphi process 5 Adoption and implementation of the intervention 6 Evaluation and feasibility testing The study will be undertaken in four National Health Service (NHS) hospitals in the United Kingdom and two Higher Education Institution. Discussion: OPAL (Occupational advice for Patients undergoing Arthroplasty of the Lower limb) aims to develop an occupational advice intervention to support early recovery to usual activities including work, which is tailored to the requirements of patients undergoing hip and knee replacements. The developed intervention will then be assessed with a specific focus on evaluating its feasibility as a potential trial intervention to improve speed of recovery to usual activities including work

Monitoring consumptive resource use in South African national parks

Monitoring is an essential component of measuring the performance of protected areas. This requirement led to the development of a biodiversity monitoring system for South African National Parks (SANParks). The system comprises of ten major programmes, each focusing on a core area of conservation biodiversity monitoring, with resource use being one of the focal areas. With the growing appreciation of the importance of natural resources for the socio-economic well-being of communities and other stakeholders, sustainable resource use is an important component of the management of natural areas and national parks. To gauge sustainability, a sound monitoring and research programme that fits within the context of the SANParks’ adaptive management approach towards social-ecological system management is required. The purpose of this article was to define the context and scope in which consumptive resource use takes place within SANParks and to outline the criteria necessary for developing a sound monitoring programme to assess the sustainability of such use. The monitoring programme is structured in view of the fact that sustainable resource use is achievable only where all dimensions of sustainability (social, economic and ecological) are considered simultaneously. In terms of the social and economic dimensions of sustainability, the programme provides for assessing stakeholder needs, trends in resource use and the social and economic impacts of resource use. Monitoring that relates to the ecological dimension of sustainability of biological resource use deals with the rate of turnover and population dynamics of target species, as well as harvest impact. In terms of abiotic (non-renewable) resources, monitoring deals with sound management practices to minimise impact on the environment, and to optimise benefits through responsible use. Conservation implications: The resource use monitoring programme is intended to ensure that monitoring relating to the harvesting of natural resources from national parks is scientifically sound and conducted in a structured way, towards meeting the objective of sustainable use and compliance with national legislation. The article illustrates how SANParks meets its obligation to monitor biodiversity conservation while at the same time meeting the needs for the consumptive use of resources

Climate-smart agriculture global research agenda: Scientific basis for action

Background: Climate-smart agriculture (CSA) addresses the challenge of meeting the growing demand for food, fibre and fuel, despite the changing climate and fewer opportunities for agricultural expansion on additional lands. CSA focuses on contributing to economic development, poverty reduction and food security; maintaining and enhancing the productivity and resilience of natural and agricultural ecosystem functions, thus building natural capital; and reducing trade-offs involved in meeting these goals. Current gaps in knowledge, work within CSA, and agendas for interdisciplinary research and science-based actions identified at the 2013 Global Science Conference on Climate-Smart Agriculture (Davis, CA, USA) are described here within three themes: (1) farm and food systems, (2) landscape and regional issues and (3) institutional and policy aspects. The first two themes comprise crop physiology and genetics, mitigation and adaptation for livestock and agriculture, barriers to adoption of CSA practices, climate risk management and energy and biofuels (theme 1); and modelling adaptation and uncertainty, achieving multifunctionality, food and fishery systems, forest biodiversity and ecosystem services, rural migration from climate change and metrics (theme 2). Theme 3 comprises designing research that bridges disciplines, integrating stakeholder input to directly link science, action and governance. Outcomes: In addition to interdisciplinary research among these themes, imperatives include developing (1) models that include adaptation and transformation at either the farm or landscape level; (2) capacity approaches to examine multifunctional solutions for agronomic, ecological and socioeconomic challenges; (3) scenarios that are validated by direct evidence and metrics to support behaviours that foster resilience and natural capital; (4) reductions in the risk that can present formidable barriers for farmers during adoption of new technology and practices; and (5) an understanding of how climate affects the rural labour force, land tenure and cultural integrity, and thus the stability of food production. Effective work in CSA will involve stakeholders, address governance issues, examine uncertainties, incorporate social benefits with technological change, and establish climate finance within a green development framework. Here, the socioecological approach is intended to reduce development controversies associated with CSA and to identify technologies, policies and approaches leading to sustainable food production and consumption patterns in a changing climate

Genetic diversity and connectivity of southern right whales (Eubalaena australis) found in the Brazil and Chile-Peru wintering grounds and the South Georgia (Islas Georgias del Sur) feeding ground

As species recover from exploitation, continued assessments of connectivity and population structure are warranted to provide information for conservation and management. This is particularly true in species with high dispersal capacity, such as migratory whales, where patterns of connectivity could change rapidly. Here we build on a previous long-term, large-scale collaboration on southern right whales (Eubalaena australis) to combine new (nnew) and published (npub) mitochondrial (mtDNA) and microsatellite genetic data from all major wintering grounds and, uniquely, the South Georgia (Islas Georgias del Sur: SG) feeding grounds. Specifically, we include data from Argentina (npub mtDNA/microsatellite=208/46), Brazil (nnew mtDNA/microsatellite=50/50), South Africa (nnew mtDNA/microsatellite=66/77, npub mtDNA/microsatellite=350/47), Chile-Peru (nnew mtDNA/microsatellite=1/1), the Indo-Pacific (npub mtDNA/microsatellite=769/126), and SG (npub mtDNA/microsatellite=8/0, nnew mtDNA/microsatellite=3/11) to investigate the position of previously unstudied habitats in the migratory network: Brazil, SG and Chile-Peru. These new genetic data show connectivity between Brazil and Argentina, exemplified by weak genetic differentiation and the movement of one genetically identified individual between the South American grounds. The single sample from Chile-Peru had a mtDNA haplotype previously only observed in the Indo-Pacific and had a nuclear genotype that appeared admixed between the Indo-Pacific and South Atlantic, based on genetic clustering and assignment algorithms. The SG samples were clearly South Atlantic, and were more similar to the South American than the South African wintering grounds. This study highlights how international collaborations are critical to provide context for emerging or recovering regions, like the SG feeding ground, as well as those that remain critically endangered, such as Chile-Peru

A Functional Role for Modality-Specific Perceptual Systems in Conceptual Representations

Theories of embodied cognition suggest that conceptual processing relies on the same neural resources that are utilized for perception and action. Evidence for these perceptual simulations comes from neuroimaging and behavioural research, such as demonstrations of somatotopic motor cortex activations following the presentation of action-related words, or facilitation of grasp responses following presentation of object names. However, the interpretation of such effects has been called into question by suggestions that neural activation in modality-specific sensorimotor regions may be epiphenomenal, and merely the result of spreading activations from “disembodied”, abstracted, symbolic representations. Here, we present two studies that focus on the perceptual modalities of touch and proprioception. We show that in a timed object-comparison task, concurrent tactile or proprioceptive stimulation to the hands facilitates conceptual processing relative to control stimulation. This facilitation occurs only for small, manipulable objects, where tactile and proprioceptive information form part of the multimodal perceptual experience of interacting with such objects, but facilitation is not observed for large, nonmanipulable objects where such perceptual information is uninformative. Importantly, these facilitation effects are independent of motor and action planning, and indicate that modality-specific perceptual information plays a functionally constitutive role in our mental representations of objects, which supports embodied assumptions that concepts are grounded in the same neural systems that govern perception and action

Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested case-control study of 1,072 cases of lymphoid malignancies and 1,072 individually matched controls from the European Prospective Investigation into Cancer and Nutrition. Odds ratios (ORs) and confidence intervals (CIs) for lymphoma were calculated using conditional logistic regression. IGF-I concentration was not associated with overall lymphoma risk (multivariable-adjusted OR for highest versus lowest third = 0.77 [95% CI = 0.57-1.03], ptrend  = 0.06). There was no statistical evidence of heterogeneity in this association with IGF-I by sex, age at blood collection, time between blood collection and diagnosis, age at diagnosis, or body mass index (pheterogeneity for all  ≥ 0.05). There were no associations between IGF-I concentration and risk for specific BCL subtypes, T-cell lymphoma or Hodgkin lymphoma, although number of cases were small. In this European population, IGF-I concentration was not associated with risk of overall lymphoma. This study provides the first prospective evidence on circulating IGF-I concentrations and risk of lymphoma. Further prospective data are required to examine associations of IGF-I concentrations with lymphoma subtypes.The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A11692, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)