Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the Mr 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6%). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50% of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p < 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ chain (p < 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type 1 (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies. We conclude that 64K antibodies, complement-fixing islet cell antibodies and insulin autoantibodies represent sensitive serological markers in assessing high risk for a progression to Type 1 diabetes in islet cell antibody positive non-diabetic individuals

Exploring Profitable, Sustainable Livestock Businesses in an Increasingly Variable Climate

Livestock production systems will need to change in many regions of the world to meet the dual challenges of adaptation to a changing climate and reducing net greenhouse gas (GHG) emissions. The ‘Nexus project’ is exploring these options using seven case studies in eastern Australia spanning a range of production systems from semi-arid beef production in northern Australia to mixed beef and sheep production in cool temperate climates of southern Australia. Regional reference groups, made up of 4-6 local farmers and advisers, identified a series of farm systems changes that could be made to meet these challenges. Options were categorised under four themes: feedbase, animal genetics and management, management and technology, and transformational options. More options for adaptation were identified compared to options to mitigate greenhouse gas emission of sequestered carbon. Adaptation options focussed on maximising pasture production in variable climates, and having efficient and flexible animal production systems. A focus on infrastructure for water and feed storage and use was also observed. Options to reduce GHG emissions focussed on reducing feed demand and sequestering carbon in soils and trees, and limited possibilities for feed additives were noted in these pasture-based systems. Further work will explore how combinations of these options will impact production, profit and greenhouse gas emissions from these production systems in current and future climate scenarios

Dietary elimination of children with food protein induced gastrointestinal allergy – micronutrient adequacy with and without a hypoallergenic formula?

Background: The cornerstone for management of Food protein-induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake. Method: A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi-quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS). Results: One-hundred-and-five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 - 67.7]. Fifty-three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS. Conclusion: This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies

Carbon myopia: the urgent need for integrated social, economic and environmental action in the livestock sector

Livestock have long been integral to food production systems, often not by choice but by need. While our knowledge of livestock greenhouse gas emissions (GHG) mitigation has evolved, the prevailing focus has been - somewhat myopically on technology applications associated with mitigation.Here, we (1) examine the global distribution of livestock GHG emissions, (2) explore social, economic and environmental co-benefits and trade-offs associated with mitigation interventions, and (3) critique approaches for quantifying GHG emissions.This review uncovered many insights. First, while GHG emissions from ruminant livestock are greatest in low and middle-income countries (LMIC; globally, 66% of emissions are produced by Latin America and the Caribbean, East and southeast Asia, and south Asia), the majority of mitigation strategies are designed for developed countries. This serious concern is heightened by the fact that 80% of growth in global meat production over the next decade will occur in LMIC. Second, few studies concurrently assess social, economic and environmental aspects of mitigation. Of the 54 interventions reviewed, only 16 had triple-bottom line benefit with medium-high mitigation potential. Third, while efforts designed to stimulate adoption of strategies allowing both emissions reduction (ER) and carbon sequestration (CS) would achieve the greatest net emissions mitigation, CS measures have greater potential mitigation and co-benefits.The scientific community must shift attention away from the prevailing myopic lens on carbon, towards more holistic, systems-based, multi-metric approaches that carefully consider the raison d'être for livestock systems. Consequential life-cycle assessments and systems-aligned socio-economic planetary boundaries offer useful starting points that may uncover leverage points and cross-scale emergent properties. Derivation of harmonised, globally-reconciled sustainability metrics requires iterative dialogue between stakeholders at all levels. Greater emphasis on the simultaneous characterisation of multiple sustainability dimensions would help avoid situations where progress made in one area causes maladaptive outcomes in other areas

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Local flexibility in feeding behaviour and contrasting microhabitat use of an omnivore across latitudes

As the environment is getting warmer and species are redistributed, consumers can be forced to adjust their interactions with available prey, and this could have cascading effects within food webs. To better understand the capacity for foraging flexibility, our study aimed to determine the diet variability of an ectotherm omnivore inhabiting kelp forests, the sea urchin Echinus esculentus, along its entire latitudinal distribution in the northeast Atlantic. Using a combination of gut content and stable isotope analyses, we determined the diet and trophic position of sea urchins at sites in Portugal (42° N), France (49° N), southern Norway (63° N), and northern Norway (70° N), and related these results to the local abundance and distribution of putative food items. With mean estimated trophic levels ranging from 2.4 to 4.6, omnivory and diet varied substantially within and between sites but not across latitudes. Diet composition generally reflected prey availability within epiphyte or understorey assemblages, with local affinities demonstrating that the sea urchin adjusts its foraging to match the small-scale distribution of food items. A net “preference” for epiphytic food sources was found in northern Norway, where understorey food was limited compared to other regions. We conclude that diet change may occur in response to food source redistribution at multiple spatial scales (microhabitats, sites, regions). Across these scales, the way that key consumers alter their foraging in response to food availability can have important implication for food web dynamics and ecosystem functions along current and future environmental gradients

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission