249 research outputs found

    Improving Hurricane Power Outage Prediction Models Through the Inclusion of Local Environmental Factors

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    Tropical cyclones can significantly damage the electrical power system, so an accurate spatiotemporal forecast of outages prior to landfall can help utilities to optimize the power restoration process. The purpose of this article is to enhance the predictive accuracy of the Spatially Generalized Hurricane Outage Prediction Model (SGHOPM) developed by Guikema et al. (2014). In this version of the SGHOPM, we introduce a new two‐step prediction procedure and increase the number of predictor variables. The first model step predicts whether or not outages will occur in each location and the second step predicts the number of outages. The SGHOPM environmental variables of Guikema et al. (2014) were limited to the wind characteristics (speed and duration of strong winds) of the tropical cyclones. This version of the model adds elevation, land cover, soil, precipitation, and vegetation characteristics in each location. Our results demonstrate that the use of a new two‐step outage prediction model and the inclusion of these additional environmental variables increase the overall accuracy of the SGHOPM by approximately 17%.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147200/1/risa12728_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147200/2/risa12728.pd

    Model of Yield Response of Corn to Plant Population and Absorption of Solar Energy

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    Biomass yield of agronomic crops is influenced by a number of factors, including crop species, soil type, applied nutrients, water availability, and plant population. This article is focused on dependence of biomass yield (Mg ha−1 and g plant−1) on plant population (plants m−2). Analysis includes data from the literature for three independent studies with the warm-season annual corn (Zea mays L.) grown in the United States. Data are analyzed with a simple exponential mathematical model which contains two parameters, viz. Ym (Mg ha−1) for maximum yield at high plant population and c (m2 plant−1) for the population response coefficient. This analysis leads to a new parameter called characteristic plant population, xc = 1/c (plants m−2). The model is shown to describe the data rather well for the three field studies. In one study measurements were made of solar radiation at different positions in the plant canopy. The coefficient of absorption of solar energy was assumed to be the same as c and provided a physical basis for the exponential model. The three studies showed no definitive peak in yield with plant population, but generally exhibited asymptotic approach to maximum yield with increased plant population. Values of xc were very similar for the three field studies with the same crop species

    A framework for developing an evidence-based, comprehensive tobacco control program

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    BACKGROUND: Tobacco control is an area where the translation of evidence into policy would seem to be straightforward, given the wealth of epidemiological, behavioural and other types of research available. Yet, even here challenges exist. These include information overload, concealment of key (industry-funded) evidence, contextualization, assessment of population impact, and the changing nature of the threat. METHODS: In the context of Israel's health targeting initiative, Healthy Israel 2020, we describe the steps taken to develop a comprehensive tobacco control strategy. We elaborate on the following: a) scientific issues influencing the choice of tobacco control strategies; b) organization of existing evidence of effectiveness of interventions into a manageable form, and c) consideration of relevant philosophical and political issues. We propose a framework for developing a plan and illustrate this process with a case study in Israel. RESULTS: Broad consensus exists regarding the effectiveness of most interventions, but current recommendations differ in the emphasis they place on different strategies. Scientific challenges include integration of complex and sometimes conflicting information from authoritative sources, and lack of estimates of population impact of interventions. Philosophical and political challenges include the use of evidence-based versus innovative policymaking, the importance of individual versus governmental responsibility, and whether and how interventions should be prioritized.The proposed framework includes: 1) compilation of a list of potential interventions 2) modification of that list based on local needs and political constraints; 3) streamlining the list by categorizing interventions into broad groupings of related interventions; together these groupings form the basis of a comprehensive plan; and 4) refinement of the plan by comparing it to existing comprehensive plans. CONCLUSIONS: Development of a comprehensive tobacco control plan is a complex endeavour, involving crucial decisions regarding intervention components. "Off the shelf" plans, which need to be adapted to local settings, are available from a variety of sources, and a multitude of individual recommendations are available. The proposed framework for adapting existing approaches to the local social and political climate may assist others planning for smoke-free societies. Additionally, this experience has implications for development of evidence-based health plans addressing other risk factors

    Central Role of Pyrophosphate in Acellular Cementum Formation

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    Background: Inorganic pyrophosphate (PPi) is a physiologic inhibitor of hydroxyapatite mineral precipitation involved in regulating mineralized tissue development and pathologic calcification. Local levels of PPi are controlled by antagonistic functions of factors that decrease PPi and promote mineralization (tissue-nonspecific alkaline phosphatase, Alpl/TNAP), and those that increase local PPi and restrict mineralization (progressive ankylosis protein, ANK; ectonucleotide pyrophosphatase phosphodiesterase-1, NPP1). The cementum enveloping the tooth root is essential for tooth function by providing attachment to the surrounding bone via the nonmineralized periodontal ligament. At present, the developmental regulation of cementum remains poorly understood, hampering efforts for regeneration. To elucidate the role of PPi in cementum formation, we analyzed root development in knock-out ((-/-)) mice featuring PPi dysregulation. Results: Excess PPi in the Alpl(-/-) mouse inhibited cementum formation, causing root detachment consistent with premature tooth loss in the human condition hypophosphatasia, though cementoblast phenotype was unperturbed. Deficient PPi in both Ank and Enpp1(-/-) mice significantly increased cementum apposition and overall thickness more than 12-fold vs. controls, while dentin and cellular cementum were unaltered. Though PPi regulators are widely expressed, cementoblasts selectively expressed greater ANK and NPP1 along the root surface, and dramatically increased ANK or NPP1 in models of reduced PPi output, in compensatory fashion. In vitro mechanistic studies confirmed that under low PPi mineralizing conditions, cementoblasts increased Ank (5-fold) and Enpp1 (20-fold), while increasing PPi inhibited mineralization and associated increases in Ank and Enpp1 mRNA. Conclusions: Results from these studies demonstrate a novel developmental regulation of acellular cementum, wherein cementoblasts tune cementogenesis by modulating local levels of PPi, directing and regulating mineral apposition. These findings underscore developmental differences in acellular versus cellular cementum, and suggest new approaches for cementum regeneration

    National health policy-makers’ views on the clarity and utility of Countdown to 2015 country profiles and reports: findings from two exploratory qualitative studies

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    Background: The use of sets of indicators to assess progress has become commonplace in the global health arena. Exploratory research has suggested that indicators used for global monitoring purposes can play a role in national policy-making, however, the mechanisms through which this occurs are poorly understood. This article reports findings from two qualitative studies that aimed to explore national policy-makers’ interpretation and use of indicators from country profiles and reports developed by Countdown to 2015. Methods: An initial study aimed at exploring comprehension of Countdown data was conducted at the 2010 joint Women Deliver/Countdown conference. A second study was conducted at the 64th World Health Assembly in 2011, specifically targeting national policy-makers. Semi-structured interviews were carried out with 29 and 22 participants, respectively, at each event. Participants were asked about their understanding of specific graphs and indicators used or proposed for use in Countdown country profiles, and their perception of how such data can inform national policy-making. Responses were categorised using a framework analysis. Results: Respondents in both studies acknowledged the importance of the profiles for tracking progress on key health indicators in and across countries, noting that they could be used to highlight changes in coverage, possible directions for future policy, for lobbying finance ministers to increase resources for health, and to stimulate competition between neighbouring or socioeconomically similar countries. However, some respondents raised questions about discrepancies between global estimates and data produced by national governments, and some struggled to understand the profile graphs shown in the absence of explanatory text. Some respondents reported that use of Countdown data in national policy-making was constrained by limited awareness of the initiative, insufficient detail in the country profiles to inform policy, and the absence of indicators felt to be more appropriate to their own country contexts. Conclusions: The two studies emphasise the need for country consultations to ensure that national policy-makers understand how to interpret and use tools like the Countdown profile for planning purposes. They make clear the value of qualitative research for refining tools used to promote accountability, and the need for country level Countdown-like processes

    Gene therapy: the end of the rainbow?

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    The increased understanding of the molecular basis of oral cancer has led to expectations that correction of the genetic defects will lead to improved treatments. Nevertheless, the first clinical trials for gene therapy of oral cancer occurred 20 years ago, and routine treatment is still not available. The major difficulty is that genes are usually delivered by virus vectors whose effects are weak and temporary. Viruses that replicate would be better, and the field includes many approaches in that direction. If any of these are effective in patients, then gene therapy will become available in the next few years. Without significant advances, however, the treatment of oral cancer by gene therapy will remain as remote as the legendary pot of gold at the end of the rainbow

    What can global health institutions do to help strengthen health systems in low income countries?

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    Weaknesses in health systems contribute to a failure to improve health outcomes in developing countries, despite increased official development assistance. Changes in the demands on health systems, as well as their scope to respond, mean that the situation is likely to become more problematic in the future. Diverse global initiatives seek to strengthen health systems, but progress will require better coordination between them, use of strategies based on the best available evidence obtained especially from evaluation of large scale programs, and improved global aid architecture that supports these processes. This paper sets out the case for global leadership to support health systems investments and help ensure the synergies between vertical and horizontal programs that are essential for effective functioning of health systems. At national level, it is essential to increase capacity to manage and deliver services, situate interventions firmly within national strategies, ensure effective implementation, and co-ordinate external support with local resources. Health systems performance should be monitored, with clear lines of accountability, and reforms should build on evidence of what works in what circumstances

    Integrin-Specific Mechanoresponses to Compression and Extension Probed by Cylindrical Flat-Ended AFM Tips in Lung Cells

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    Cells from lung and other tissues are subjected to forces of opposing directions that are largely transmitted through integrin-mediated adhesions. How cells respond to force bidirectionality remains ill defined. To address this question, we nanofabricated flat-ended cylindrical Atomic Force Microscopy (AFM) tips with ∼1 µm2 cross-section area. Tips were uncoated or coated with either integrin-specific (RGD) or non-specific (RGE/BSA) molecules, brought into contact with lung epithelial cells or fibroblasts for 30 s to form focal adhesion precursors, and used to probe cell resistance to deformation in compression and extension. We found that cell resistance to compression was globally higher than to extension regardless of the tip coating. In contrast, both tip-cell adhesion strength and resistance to compression and extension were the highest when probed at integrin-specific adhesions. These integrin-specific mechanoresponses required an intact actin cytoskeleton, and were dependent on tyrosine phosphatases and Ca2+ signaling. Cell asymmetric mechanoresponse to compression and extension remained after 5 minutes of tip-cell adhesion, revealing that asymmetric resistance to force directionality is an intrinsic property of lung cells, as in most soft tissues. Our findings provide new insights on how lung cells probe the mechanochemical properties of the microenvironment, an important process for migration, repair and tissue homeostasis

    Impaired Adult Neurogenesis in the Dentate Gyrus of a Triple Transgenic Mouse Model of Alzheimer's Disease

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    It has become generally accepted that new neurones are added and integrated mainly in two areas of the mammalian CNS, the subventricular zone and the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus, which is of central importance in learning and memory. The newly generated cells display neuronal morphology, are able to generate action potentials and receive functional synaptic inputs, i.e. their properties are similar to those found in mature neurones. Alzheimer's disease (AD) is the primary and widespread cause of dementia and is an age-related, progressive and irreversible neurodegenerative disease that deteriorates cognitive functions. Here, we have used male and female triple transgenic mice (3xTg-AD) harbouring three mutant genes (β-amyloid precursor protein, presenilin-1 and tau) and their respective non-transgenic (non-Tg) controls at 2, 3, 4, 6, 9 and 12 months of age to establish the link between AD and neurogenesis. Using immunohistochemistry we determined the area density of proliferating cells within the SGZ of the DG, measured by the presence of phosphorylated Histone H3 (HH3), and their possible co-localisation with GFAP to exclude a glial phenotype. Less than 1% of the HH3 labeled cells co-localised with GFAP. Both non-Tg and 3xTg-AD showed an age-dependent decrease in neurogenesis. However, male 3xTg-AD mice demonstrated a further reduction in the production of new neurones from 9 months of age (73% decrease) and a complete depletion at 12 months, when compared to controls. In addition, female 3xTg-AD mice showed an earlier but equivalent decrease in neurogenesis at 4 months (reduction of 63%) with an almost inexistent rate at 12 months (88% decrease) compared to controls. This reduction in neurogenesis was directly associated with the presence of β-amyloid plaques and an increase in the number of β-amyloid containing neurones in the hippocampus; which in the case of 3xgTg females was directly correlated. These results suggest that 3xTg-AD mice have an impaired ability to generate new neurones in the DG of the hippocampus, the severity of which increases with age and might be directly associated with the known cognitive impairment observed from 6 months of age onwards . The earlier reduction of neurogenesis in females, from 4 months, is in agreement with the higher prevalence of AD in women than in men. Thus it is conceivable to speculate that a recovery in neurogenesis rates in AD could help to rescue cognitive impairment

    Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii

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    During infection with the intracellular parasite Toxoplasma gondii, the presentation of parasite-derived antigens to CD4+ and CD8+ T cells is essential for long-term resistance to this pathogen. Fundamental questions remain regarding the roles of phagocytosis and active invasion in the events that lead to the processing and presentation of parasite antigens. To understand the most proximal events in this process, an attenuated non-replicating strain of T. gondii (the cpsII strain) was combined with a cytometry-based approach to distinguish active invasion from phagocytic uptake. In vivo studies revealed that T. gondii disproportionately infected dendritic cells and macrophages, and that infected dendritic cells and macrophages displayed an activated phenotype characterized by enhanced levels of CD86 compared to cells that had phagocytosed the parasite, thus suggesting a role for these cells in priming naïve T cells. Indeed, dendritic cells were required for optimal CD4+ and CD8+ T cell responses, and the phagocytosis of heat-killed or invasion-blocked parasites was not sufficient to induce T cell responses. Rather, the selective transfer of cpsII-infected dendritic cells or macrophages (but not those that had phagocytosed the parasite) to naïve mice potently induced CD4+ and CD8+ T cell responses, and conferred protection against challenge with virulent T. gondii. Collectively, these results point toward a critical role for actively infected host cells in initiating T. gondii-specific CD4+ and CD8+ T cell responses
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