1,015 research outputs found

    An Empiricist’s Guide to Using Ecological Theory

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    A scientific understanding of the biological world arises when ideas about how nature works are formalized, tested, refined, and then tested again. Although the benefits of feedback between theoretical and empirical research are widely acknowledged by ecologists, this link is still not as strong as it could be in ecological research. This is in part because theory, particularly when expressed mathematically, can feel inaccessible to empiricists who may have little formal training in advanced math. To address this persistent barrier, we provide a general and accessible guide that covers the basic, step-by-step process of how to approach, understand, and use ecological theory in empirical work. We first give an overview of how and why mathematical theory is created, then outline four specific ways to use both mathematical and verbal theory to motivate empirical work, and finally present a practical tool kit for reading and understanding the mathematical aspects of ecological theory.We hope that empowering empiricists to embrace theory in their work will help move the field closer to a full integration of theoretical and empirical research

    Determining the neurotransmitter concentration profile at active synapses

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    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

    Gestational Diabetes Is Characterized by Reduced Mitochondrial Protein Expression and Altered Calcium Signaling Proteins in Skeletal Muscle

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    The rising prevalence of gestational diabetes mellitus (GDM) affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM) and obese pregnant women with normal glucose tolerance (ONGT). Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I) subunits (NDUFS3, NDUFV2) and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4) in OGDM (n = 6) vs. ONGT (n = 6). Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (−60–75%) in the OGDM (n = 8) compared with ONGT (n = 10) subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum

    Prioritising public health: a qualitative study of decision making to reduce health inequalities

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    <p>Abstract</p> <p>Background</p> <p>The public health system in England is currently facing dramatic change. Renewed attention has recently been paid to the best approaches for tackling the health inequalities which remain entrenched within British society and across the globe. In order to consider the opportunities and challenges facing the new public health system in England, we explored the current experiences of those involved in decision making to reduce health inequalities, taking cardiovascular disease (CVD) as a case study.</p> <p>Methods</p> <p>We conducted an in-depth qualitative study employing 40 semi-structured interviews and three focus group discussions. Participants were public health policy makers and planners in CVD in the UK, including: Primary Care Trust and Local Authority staff (in various roles); General Practice commissioners; public health academics; consultant cardiologists; national guideline managers; members of guideline development groups, civil servants; and CVD third sector staff.</p> <p>Results</p> <p>The short term target- and outcome-led culture of the NHS and the drive to achieve "more for less", combined with the need to address public demand for acute services often lead to investment in "downstream" public health intervention, rather than the "upstream" approaches that are most effective at reducing inequalities. Despite most public health decision makers wishing to redress this imbalance, they felt constrained due to difficulties in partnership working and the over-riding influence of other stakeholders in decision making processes. The proposed public health reforms in England present an opportunity for public health to move away from the medical paradigm of the NHS. However, they also reveal a reluctance of central government to contribute to shifting social norms.</p> <p>Conclusions</p> <p>It is vital that the effectiveness and cost effectiveness of all new and existing policies and services affecting public health are measured in terms of their impact on the social determinants of health and health inequalities. Researchers have a vital role to play in providing the complex evidence required to compare different models of prevention and service delivery. Those working in public health must develop leadership to raise the profile of health inequalities as an issue that merits attention, resources and workforce capacity; and advocate for central government to play a key role in shifting social norms.</p

    Treatment of an Intramammary Bacterial Infection with 25-Hydroxyvitamin D3

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    Deficiency of serum levels of 25-hydroxyvitamin D3 has been correlated with increased risk of infectious diseases such as tuberculosis and influenza. A plausible reason for this association is that expression of genes encoding important antimicrobial proteins depends on concentrations of 1,25-dihydroxyvitamin D3 produced by activated immune cells at sites of infection, and that synthesis of 1,25-dihydroxyvitamin D3 is dependent on the availability of 25-hydroxyvitamin D3. Thus, increasing the availability of 25(OH)D3 for immune cell synthesis of 1,25-dihydroxyvitamin D3 at sites of infection has been hypothesized to aid in clearance of the infection. This report details the treatment of an acute intramammary infection with infusion of 25-hydroxyvitamin D3 to the site of infection. Ten lactating cows were infected with in one quarter of their mammary glands. Half of the animals were treated intramammary with 25-hydroxyvitamin D3. The 25-hydroxyvitamin D3 treated animal showed significantly lower bacterial counts in milk and showed reduced symptomatic affects of the mastitis. It is significant that treatment with 25-hydroxyvitamin D3 reduced the severity of an acute bacterial infection. This finding suggested a significant non-antibiotic complimentary role for 25-hydroxyvitamin D3 in the treatment of infections in compartments naturally low in 25-hydroxyvitamin D3 such as the mammary gland and by extension, possibly upper respiratory tract infections

    Searching for the elusive typhoid diagnostic

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    Typhoid (enteric) fever is still a common disease in many developing countries but current diagnostic tests are inadequate. Studies on pathogenesis and genomics have provided new insight into the organisms that cause enteric fever. Better understanding of the microorganisms explains, in part, why our current typhoid methodologies are limited in their diagnostic information and why developing new strategies may be a considerable challenge. Here we discuss the current position of typhoid diagnostics, highlight the need for technological improvements and suggest potential ways of advancing this area

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    The role of conversation in health care interventions: enabling sensemaking and learning

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    <p>Abstract</p> <p>Background</p> <p>Those attempting to implement changes in health care settings often find that intervention efforts do not progress as expected. Unexpected outcomes are often attributed to variation and/or error in implementation processes. We argue that some unanticipated variation in intervention outcomes arises because unexpected conversations emerge during intervention attempts. The purpose of this paper is to discuss the role of conversation in shaping interventions and to explain why conversation is important in intervention efforts in health care organizations. We draw on literature from sociolinguistics and complex adaptive systems theory to create an interpretive framework and develop our theory. We use insights from a fourteen-year program of research, including both descriptive and intervention studies undertaken to understand and assist primary care practices in making sustainable changes. We enfold these literatures and these insights to articulate a common failure of overlooking the role of conversation in intervention success, and to develop a theoretical argument for the importance of paying attention to the role of conversation in health care interventions.</p> <p>Discussion</p> <p>Conversation between organizational members plays an important role in the success of interventions aimed at improving health care delivery. Conversation can facilitate intervention success because interventions often rely on new sensemaking and learning, and these are accomplished through conversation. Conversely, conversation can block the success of an intervention by inhibiting sensemaking and learning. Furthermore, the existing relationship contexts of an organization can influence these conversational possibilities. We argue that the likelihood of intervention success will increase if the role of conversation is considered in the intervention process.</p> <p>Summary</p> <p>The generation of productive conversation should be considered as one of the foundations of intervention efforts. We suggest that intervention facilitators consider the following actions as strategies for reducing the barriers that conversation can present and for using conversation to leverage improvement change: evaluate existing conversation and relationship systems, look for and leverage unexpected conversation, create time and space where conversation can unfold, use conversation to help people manage uncertainty, use conversation to help reorganize relationships, and build social interaction competence.</p

    Explicit expressions for the estimation of the elastic constants of lamellar bone as a function of the volumetric mineral content using a multi-scale approach

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    [EN] In this work, explicit expressions to estimate all the transversely isotropic elastic constants of lamellar bone as a function of the volumetric bone mineral density (BMD) are provided. The methodology presented is based on the direct homogenization procedure using the finite element method, the continuum approach based on the Hill bounds, the least-square method and the mean field technique. Firstly, a detailed description of the volumetric content of the different components of bone is provided. The parameters defined in this step are related to the volumetric BMD considering that bone mineralization process occurs at the smallest scale length of the bone tissue. Then, a thorough description provides the details of the numerical models and the assumptions adopted to estimate the elastic behaviour of the forward scale lengths. The results highlight the noticeable influence of the BMD on the elastic modulus of lamellar bone. Power law regressions fit the Young's moduli, shear stiffness moduli and Poisson ratios. In addition, the explicit expressions obtained are applied to the estimation of the elastic constants of cortical bone. At this scale length, a representative unit cell of cortical bone is analysed including the fibril orientation pattern given by Wagermaier et al. (Biointerphases 1:1-5, 2006) and the BMD distributions observed by Granke et al. (PLoS One 8:e58043, 2012) for the osteon. Results confirm that fibril orientation arrangement governs the anisotropic behaviour of cortical bone instead of the BMD distribution. The novel explicit expressions obtained in this work can be used for improving the accuracy of bone fracture risk assessment.The authors acknowledge the Ministerio de Economia y Competitividad for the financial support received through the project DPI2013-46641-R and to the Generalitat Valenciana for Programme PROMETEO 2016/007. The authors declare that they have no conflict of interestVercher Martínez, A.; Giner Maravilla, E.; Belda, R.; Aigoun, A.; Fuenmayor Fernández, F. (2018). Explicit expressions for the estimation of the elastic constants of lamellar bone as a function of the volumetric mineral content using a multi-scale approach. Biomechanics and Modeling in Mechanobiology. 17(2):449-464. https://doi.org/10.1007/s10237-017-0971-xS449464172Akiva U, Wagner HD, Weiner S (1998) Modelling the three-dimensional elastic constants of parallel-fibred and lamellar bone. J Mater Sci 33:1497–1509Ascenzi A, Bonucci E (1967) The tensile properties of single osteons. Ana Rec 158:375–386Barbour KE, Zmuda JM, Strotmeyer ES, Horwitz MJ, Boudreau R, Evans RW, Ensrud K, Petit MA, Gordon CL, Cauley JA (2013) Correlates of trabecular and cortical volumetric bone mineral density of the radius and tibia older men: the osteoporotic fractures in men study. J Bone Miner Res 25(5):1017–1028Bar-On B, Wagner HD (2013) Structural motifs and elastic properties of hierarchical biological tissues—a review. J Struct Biol 183:149–164Cowin SC (2000) How is a tissue built? J Biomech Eng 122:553–569Cowin SC (2001) Bone mechanics handbook, 2nd edn. CRC Press, Boca RatonCurrey JD (1986) Power law models for the mechanical properties of cancellous bone. Eng Med 15(3):153–154Currey JD (1988) The effect of porosity and mineral content on the Young’s modulus of elasticity of compact bone. J Biomech 21:131–139Daszkiewicz K, Maquer G, Zysset PK (2017) The effective elastic properties of human trabecular bone may be approximated using micro-finite element analyses of embedded volume elements. Biomech Model Mechanobiol 16:731–742Faingold A, Sidney RC, Wagner HD (2012) Nanoindentation of osteonal bone lamellae. J Mech Biomech Materials 9:198–206Fratzl P, Fratzl-Zelman N, Klaushofer K, Vogl G, Koller K (1991) Nucleation and growth of mineral crystals in bone studied by small-angle X-ray scattering. Calcif Tissue Int 48:407–413Fritsch A, Hellmich C (2007) ’Universal’ microstructural patterns in cortical and trabecular, extracellular and extravascular bone materials: micromechanics-based prediction of anisotropic elasticity. J Theo Biol 24:597–620Grampp S, Genant HK, Mathur A, Lang P, Jergas M, Takada M, Glüer CC, Lu Y, Chavez M (1997) Comparisons of noninvasive bone mineral measurements in assessing age-related loss, fracture discrimination and diagnostic classification. J Bone Miner Res 12:697–711Grant CA, Langton C, Schuetz MA, Epari DR (2011) Determination of the material properties of ovine cortical bone. Poster No. 2226, 57th Orthopaedic Research Society (ORS) Annual meeting, Long Beach, CaliforniaGranke M, Gourrier A, Rupin F, Raum K, Peyrin F, Burghammer M, Saïd A, Laugier P (2012) Microfibril orientation dominates the microelastic properties of human bone tissue at the lamellar length scale. PLoS One 8:e58043Gurtin ME (1972) The linear theory of elasticity. Handbuch del Physik VIa 2:1–296Hamed E, Jasiuk I (2012) Elastic modeling of bone at nanostructural level. Mat Sci Eng R73:27–49Hernández CJ, Beaupré GS, Keller TS, Carter DR (2001a) The influence of bone volume fraction and ash fraction on bone strength and modulus. Bone 29:74–78Hill R (1952) The elastic behaviour of a crystalline aggregate. Proc Phys Soc Sec A 65:349–354Hodge AJ, Petruska JA (1963) Recent studies with the electron microscope on ordered aggregates of the tropocollagen macromolecule. In: Ramachandran GN (ed) Aspects of protein structure. Academic Press, New York, pp 289–300Jäger I, Fratzl P (2000) Mineralized collagen: a mechanical model with a staggered arrangement of mineral particles. Biophys J 78:1737–1746Kuhn JL, Goldstein SA, Choi K, London M, Feldkamp LA, Matthews LS (1989) Comparison of the trabecular and cortical tissue moduli from human iliac crests. J Orthop Res 7:876–884Landis WJ, Song MJ, Leith A, McEwen L, McEwen BF (1993) Mineral and organic matrix interaction in normally calcifying tendon visualized in three dimensions by high-voltage electron microscopic tomography and graphic image reconstruction. J Struct Biol 110:39–54Lees S, Heeley JD, Cleary PF (1979) A study of some properties of a sample of bovine cortical bone using ultrasound. Calcif Tissue Int 29:107–117Lekhnitskii SG (1963) Theory of elasticity of anisotropic elastic body. Holden-Day, San Francisco, pp 1–73Lempriere BM (1968) Poisson’s ratio in orthotropic materials. Am Inst Aeronaut Astronaut J J6:2226–2227Liu Y, Kim YK, Dai L, Li N, Khan SO, Pashley DH, Tay FR (2011) Hierarchical and non-hierarchical mineralization of collagen. Biomater 32:1291–1300Majumdar S, Kothari M, Augat P, Newitt DC, Link TM, Lin JC, Lang T, Lu Y, Genant HK (1998) High-resolution magnetic resonance imaging: three-dimensional trabecular bone architecture and biomechanical properties. Bone 22(5):445–454Martínez-Reina J, Domínguez J, García-Aznar JM (2011) Effect of porosity and mineral content on the elastic constants of cortical bone: a multiscale approach. Biomech Model Mechanobiol 10:309–322Nobakhti S, Limbert G, Thurner PJ (2014) Cement lines and interlamellar areas in compact bone as strain amplifiers—Contributors to elasticity, fracture toughness and mechanotransduction. J Mech Behav Biomed Mater 29:235–251Orgel JPRO, Irving TC, Miller A, Wess TJ (2006) Microfibrillar structure of type I collagen in situ. PNAS USA 103:9001–9005Reisinger AG, Pahr DH, Zysset PK (2010) Sensitivity analysis and parametric study of elastic properties of unidirectional mineralized bone fibril-array using mean field methods. Biomech Model Mechanobiol 9:499–510Reisinger AG, Pahr DH, Zysset PK (2011) Elastic anisotropy of bone lamellae as a function of fibril orientation pattern. Biomech Model Mechanobiol 10:67–77Rho JY, Kuhn-Spearing L, Zioupos P (1998) Mechanical properties and the hierarchical structure of bone. Med Eng Phys 20:92–102Robinson RA, Rochester MD (1952) An electron-microscopic study of the crystalline inorganic component of bone and its relationship to the organic matrix. J Bone Joint Surg 34–a:389–435Roque WL, Arcaro K, Alberich-Bayarri A (2013) Mechanical competence of bone: a new parameter to grade trabecular bone fragility from tortuosity and elasticity. IEEE Trans Bio Eng 60:1363–1370Rubin MA, Jasiuk I, Taylor J, Rubin J, Ganey T, Apkarian RP (2003) TEM analysis of the nanostructure of normal and osteoporotic human trabecular bone. Bone 33:270–282Sasaki N, Tagami A, Goto T, Taniguchi M, Nakata M, Hikichi K (2002) Atomic force microscopic studies on the structure of bovine femoral cortical bone at the collagen fibril-mineral level. J Mater Sci Mater Med 13(3):333–337Schaffler MB, Burr DB (1988) Stiffness of compact bone: effects of porosity and density. J Biomech 21:13–16Silver FH, Landis WJ (2011) Deposition of apatite in mineralizing vertebrate extracellular matrices: a model of possible nucleation sites on type I collagen. Connect Tissue Res 52:242–254Tommasini SM, Nasser P, Hu B, Jepsen KJ (2008) Biological co-adaptation of morphological and composition traits contributes to mechanical functionality and skeletal fragility. J Bone Miner Res 23:236–246Ulrich D, Rietbergen B, Weinans H, Rüegsegger P (1998) Finite element analysis of trabecular bone structure: a comparison of image-based meshing techniques. J Biomech 31:1187–1192Ulrich D, Rietbergen B, Laib A, Rüegsegger P (1999) The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone. Bone 25:55–60Vercher A, Giner E, Arango C, Tarancón JE, Fuenmayor FJ (2014) Homogenized stiffness matrices for mineralized collagen fibrils and lamellar bone using unit cell finite element models. Biomech Model Mechanobiol 13:437–449Vercher-Martínez A, Giner E, Arango C, Fuenmayor FJ (2015) Influence of the mineral staggering on the elastic properties of the mineralized collagen fibril in lamellar bone. J Mech Behav Biomed Mater 42:243–256Wagermaier W, Gupta HS, Gourrier A, Burghammer M, Roschger P, Fratzl P (2006) Spiral twisting of fiber orientation inside bone lamellae. Biointerphases 1:1–5Weiner S, Traub W (1986) Organization of hydroxiapatite within collagen fibrils. FEBS Lett 206:262–266Weiner S, Wagner HD (1998) The material bone: structure-mechanical function relations. Annu Rev Mater Sci 28:271–298Yang L, Palermo L, Black DM, Eastell R (2014) Prediction of incident hip fracture with the estimated femoral strength by finite element analysis of DXA scans in the study of osteoporotic fractures. JBMR 29:2594–2600Yuan YJ, Cowin SC (2008a) The estimated elastic constants for a single bone osteonal lamella. Biomech Model Mechanobiol 7:1–11Yu W, Glüer CC, Grampp S, Jergas M, Fuerst T, Wu CY, Lu Y, Fan B, Genant HK (1995) Spinal bone mineral assessment in postmenopausal women: a comparison between dual X-ray absorptiometry and quantitative computed tomography. Osteoporos Int 5:433–439Yang L, Palermo L, Black DM, Eastell R (2014) Prediction of incident hip fracture with the estimated femoral strength by finite element analysis of DXS Scans in the study of osteoporotic fractures. J Bone Miner Res 29(12):2594–2600Yuan F, Stock SR, Haeffner DR, Almer JD, Dunand DC, Brinson LC (2011) A new model to simulate the elastic properties of mineralized collagen fibril. Biomech Model Mechanobiol 10:147–16

    PathogenFinder - Distinguishing Friend from Foe Using Bacterial Whole Genome Sequence Data.

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    Although the majority of bacteria are harmless or even beneficial to their host, others are highly virulent and can cause serious diseases, and even death. Due to the constantly decreasing cost of high-throughput sequencing there are now many completely sequenced genomes available from both human pathogenic and innocuous strains. The data can be used to identify gene families that correlate with pathogenicity and to develop tools to predict the pathogenicity of newly sequenced strains, investigations that previously were mainly done by means of more expensive and time consuming experimental approaches. We describe PathogenFinde
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