268 research outputs found

    A fuzzy-based evaluation of financial risks in build-own-operate-transfer water supply projects

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    The build–own–operate–transfer (BOOT) scheme is widely used for the provision of new bulk water supply. However, this scheme is complex and carries significant financial risks because of the characteristics of the water sector and the involvement of public-private stakeholders with new and extended responsibilities, large private capital, and long contract duration. Drawing on the Nungua Seawater Desalination Plant (NSDP) in Ghana, this study seeks to identify and assess the critical financial risks associated with BOOT water supply projects and evaluate the financial risk level of the NSDP project. The risks and their relative criticality on the NSDP project are investigated by using a questionnaire survey method. The questionnaire was formulated with a set of 18 risks derived from extant literature and project documentation. Perceived critical financial risks affecting the NSDP project were assessed by a team of experts who had direct involvement in the project. A fuzzy synthetic evaluation suggests that the project is financially risky and that all the risks are critical to the project. Bankruptcy of consortium members, unfavorable economy of the host country, uncertainty in tariff adjustment of water products, rate of return restrictions, and availability problem of private capital are the five most highly-ranked risks. The fuzzy technique is used to represent and model experiential knowledge of the survey participants and to address the fuzziness of their expert judgments. The study’s results facilitate prioritization of risks and a comprehensive risk management program during the lifecycle of the case project and future projects. The fuzzy technique is suitable for early phases of BOOT projects to prioritize the risks that require a detailed analysis and to predict the risk level of a project

    Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.

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    A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology.This is the final version of the article. It first appeared from The Company of Biologists via http://dx.doi.org/10.1242/dev.12385

    The diacylglycerol kinase α/Atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness

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    Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells

    One Problem, Many Solutions: Simple Statistical Approaches Help Unravel the Complexity of the Immune System in an Ecological Context

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    The immune system is a complex collection of interrelated and overlapping solutions to the problem of disease. To deal with this complexity, researchers have devised multiple ways to measure immune function and to analyze the resulting data. In this way both organisms and researchers employ many tactics to solve a complex problem. One challenge facing ecological immunologists is the question of how these many dimensions of immune function can be synthesized to facilitate meaningful interpretations and conclusions. We tackle this challenge by employing and comparing several statistical methods, which we used to test assumptions about how multiple aspects of immune function are related at different organizational levels. We analyzed three distinct datasets that characterized 1) species, 2) subspecies, and 3) among- and within-individual level differences in the relationships among multiple immune indices. Specifically, we used common principal components analysis (CPCA) and two simpler approaches, pair-wise correlations and correlation circles. We also provide a simple example of how these techniques could be used to analyze data from multiple studies. Our findings lead to several general conclusions. First, relationships among indices of immune function may be consistent among some organizational groups (e.g. months over the annual cycle) but not others (e.g. species); therefore any assumption of consistency requires testing before further analyses. Second, simple statistical techniques used in conjunction with more complex multivariate methods give a clearer and more robust picture of immune function than using complex statistics alone. Moreover, these simpler approaches have potential for analyzing comparable data from multiple studies, especially as the field of ecological immunology moves towards greater methodological standardization

    Maternal risk factors for abnormal placental growth: The national collaborative perinatal project

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    <p>Abstract</p> <p>Background</p> <p>Previous studies of maternal risk factors for abnormal placental growth have focused on placental weight and placental ratio as measures of placental growth. We sought to identify maternal risk factors for placental weight and two neglected dimensions of placental growth: placental thickness and chorionic plate area.</p> <p>Methods</p> <p>We conducted an analysis of 24,135 mother-placenta pairs enrolled in the National Collaborative Perinatal Project, a prospective cohort study of pregnancy and child health. We defined growth restriction as < 10<sup>th </sup>percentile and hypertrophy as > 90<sup>th </sup>percentile for three placental growth dimensions: placental weight, placental thickness and chorionic plate area. We constructed parallel multinomial logistic regression analyses to identify (a) predictors of restricted growth (vs. normal) and (b) predictors of hypertrophic growth (vs. normal).</p> <p>Results</p> <p>Black race was associated with an increased likelihood of growth restriction for placental weight, thickness and chorionic plate area, but was associated with a reduced likelihood of hypertrophy for these three placental growth dimensions. We observed an increased likelihood of growth restriction for placental weight and chorionic plate area among mothers with hypertensive disease at 24 weeks or beyond. Anemia was associated with a reduced likelihood of growth restriction for placental weight and chorionic plate area. Pre-pregnancy BMI and pregnancy weight gain were associated with a reduced likelihood of growth restriction and an increased likelihood of hypertrophy for all three dimensions of placental growth.</p> <p>Conclusion</p> <p>Maternal risk factors are either associated with placental growth restriction or placental hypertrophy not both. Our findings suggest that the placenta may have compensatory responses to certain maternal risk factors suggesting different underlying biological mechanisms.</p

    Invasion and Persistence of Infectious Agents in Fragmented Host Populations

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    One of the important questions in understanding infectious diseases and their prevention and control is how infectious agents can invade and become endemic in a host population. A ubiquitous feature of natural populations is that they are spatially fragmented, resulting in relatively homogeneous local populations inhabiting patches connected by the migration of hosts. Such fragmented population structures are studied extensively with metapopulation models. Being able to define and calculate an indicator for the success of invasion and persistence of an infectious agent is essential for obtaining general qualitative insights into infection dynamics, for the comparison of prevention and control scenarios, and for quantitative insights into specific systems. For homogeneous populations, the basic reproduction ratio plays this role. For metapopulations, defining such an ‘invasion indicator’ is not straightforward. Some indicators have been defined for specific situations, e.g., the household reproduction number . However, these existing indicators often fail to account for host demography and especially host migration. Here we show how to calculate a more broadly applicable indicator for the invasion and persistence of infectious agents in a host metapopulation of equally connected patches, for a wide range of possible epidemiological models. A strong feature of our method is that it explicitly accounts for host demography and host migration. Using a simple compartmental system as an example, we illustrate how can be calculated and expressed in terms of the key determinants of epidemiological dynamics

    Isospin symmetry in B(E2) values: Coulomb excitation study of Mg-21

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    The TzT_z~=~32-\frac{3}{2} nucleus 21{}^{21}Mg has been studied by Coulomb excitation on 196{}^{196}Pt and 110{}^{110}Pd targets. A 205.6(1)-keV γ\gamma-ray transition resulting from the Coulomb excitation of the 52+\frac{5}{2}^+ ground state to the first excited 12+\frac{1}{2}^+ state in 21{}^{21}Mg was observed for the first time. Coulomb excitation cross-section measurements with both targets and a measurement of the half-life of the 12+\frac{1}{2}^+ state yield an adopted value of B(E2;52+12+)B(E2;\frac{5}{2}^+\rightarrow\frac{1}{2}^+)~=~13.3(4)~W.u. A new excited state at 1672(1)~keV with tentative 92+\frac{9}{2}^+ assignment was also identified in 21{}^{21}Mg. This work demonstrates large difference of the B(E2;52+12+)B(E2;\frac{5}{2}^+\rightarrow\frac{1}{2}^+) values between TT~=~32\frac{3}{2}, AA~=~21 mirror nuclei. The difference is investigated in the shell-model framework employing both isospin conserving and breaking USD interactions and using modern \textsl{ab initio} nuclear structure calculations, which have recently become applicable in the sdsd shell.Comment: 8 pages, 6 figures, submitted to Phys. Rev. C, Rapid Communicatio

    Differential response effects of data collection mode in a cancer screening study of unmarried women ages 40–75 years: A randomized trial

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    <p>Abstract</p> <p>Background</p> <p>Little is known about the impact of data collection method on self-reported cancer screening behaviours, particularly among hard-to-reach populations. The purpose of this study is to examine the effects of data collection mode on response to indicators of cancer screenings by unmarried middle-aged and older women.</p> <p>Methods</p> <p>Three survey methods were evaluated for collecting data about mammography and Papanicolaou (hereafter, Pap) testing among heterosexual and sexual minority (e.g., lesbian and bisexual) women. Women ages 40–75 were recruited from June 2003 – June 2005 in Rhode Island. They were randomly assigned to receive: Self-Administered Mailed Questionnaire [SAMQ; N = 202], Computer-Assisted Telephone Interview [CATI; N = 200], or Computer-Assisted Self-Interview [CASI; N = 197]. Logistic regression models were computed to assess survey mode differences for 13 self-reported items related to cancer screenings, adjusting for age, education, income, race, marital status, partner gender, and recruitment source.</p> <p>Results</p> <p>Compared to women assigned to CATI, women assigned to SAMQ were less likely to report two or more years between most recent mammograms (CATI = 23.2% vs. SAMQ = 17.7%; AOR = 0.5, 95% CI = 0.3 – 0.8) and women assigned to CASI were slightly less likely to report being overdue for mammography (CATI = 16.5% vs. CASI = 11.8%; AOR = 0.5, 95% CI = 0.3 – 1.0) and Pap testing (CATI = 14.9% vs. CASI = 10.0%; AOR = 0.5, 95% CI = 0.2 – 1.0). There were no other consistent mode effects.</p> <p>Conclusion</p> <p>Among participants in this sample, mode of data collection had little effect on the reporting of mammography and Pap testing behaviours. Other measures such as efficiency and cost-effectiveness of the mode should also be considered when determining the most appropriate form of data collection for use in monitoring indicators of cancer detection and control.</p

    Are the affluent prepared to pay for the planet? Explaining willingness to pay for public and quasi-private environmental goods in Switzerland

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    A large number of ‘environmental justice’ studies show that wealthier people are less affected by environmental burdens and also consume more resources than poorer people. Given this double inequity, we ask, to what extent are affluent people prepared to pay to protect the environment? The analyses are couched within the compensation/affluence hypothesis, which states that wealthier persons are able to spend more for environmental protection than their poorer counterparts. Further, we take into account various competing economic, psychological and sociological determinants of individuals’ willingness to pay (WTP) for both public environmental goods (e.g., general environmental protection) and quasi-private environmental goods (e.g., CO2-neutral cars). Such a comprehensive approach contrasts with most other studies in this field that focus on a limited number of determinants and goods. Multivariate analyses are based on a general population survey in Switzerland (N = 3,369). Although income has a positive and significant effect on WTP supporting the compensation hypothesis, determinants such as generalized interpersonal trust that is assumed to be positively associated with civic engagement and environmental concern prove to be equally important. Moreover, we demonstrate for the first time that time preferences can considerably influence survey-based WTP for environmental goods; since investments in the environment typically pay off in the distant future, persons with a high subjective discount rate are less likely to commit
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