329 research outputs found

    Reflection on the Theology of Joseph Ratzinger (Pope Benedict XVI)

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    This essay looks at ways in which the theology of Joseph Ratzinger, now Pope Benedict XVI, shows affinities with Reformation theological thought. Following a brief look at the background to my own interest in Ratzinger, I present some important features of his theology, shedding light on it particularly through drawing attention to those theological figures in the Christian tradition, Augustine and Bonaventure, who have influenced him the most. A brief treatment is then offered of how these theological forefathers are reflected in his work and, following this, Reformation “flavours” shown to have been present in his writings are traced, briefly, through examining three areas of his thought: ethics, his theology of political life, and ecumenism. The purpose of the article is to indicate, in an incipient way for an audience largely of the Reformed tradition, that Ratzinger is not as distant from their theological concerns as might easily be imagined

    The Politics of Service Delivery Reform

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    This article identifies the leaders, the supporters and the resisters of public service reform. It adopts a principal–agent framework, comparing reality with an ‘ideal’ situation in which citizens are the principals over political policy-makers as their agents, and policy-makers are the principals over public service officials as their agents. Reform in most developing countries is complicated by an additional set of external actors — international financial institutions and donors. In practice, international agencies and core government officials usually act as the ‘principals’ in the determination of reforms. The analysis identifies the interests involved in reform, indicating how the balance between them is affected by institutional and sectoral factors. Organizational reforms, particularly in the social sectors, present greater difficulties than first generation economic policy reforms

    The Use of Transport Time Scales as Indicators of Pollution Persistence in a Macro-Tidal Setting

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    An understanding of water exchange processes is essential for assessing water quality management issues in coastal bays. This paper evaluates the impact of water exchange processes on pollution persistence in a macro-tidal semi-closed coastal bay through two transport time scales (TTS), namely residence time and exposure time. The numerical model was calibrated against field-measured data for various tidal conditions. Simulated current speeds and directions were shown to agree well with the field data. By considering different release scenarios of a conservative tracer by the refinement of an integrated hydrodynamic and solute transport model (the EFDC), the two TTS were used for interpreting the water exchange processes in a semi-closed system, and for describing the effects of advective and dispersive processes on the transport and fate of pollutants. The results indicate that the magnitudes of river inflows to the bay, tidal ranges, and tracer release times significantly influence the residence and exposure times. Return coefficients were shown to be variable, confirming the different effects of returning water for the different conditions that were studied. For the tested river flow magnitudes and tide conditions, the exposure times were generally higher than the residence times, but particularly so for neap tide conditions. The results, therefore, highlight the risks associated with pollutants leaving a specified domain on an outgoing tide but re-entering on subsequent incoming tides. The spatial distributions of the exposure and residence times across the model domain confirmed that for the case of Dublin Bay, river inputs have a potentially greater impact on water quality on the northern side of the bay

    Perspectives on weak interactions in complex materials at different length scales

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    Nanocomposite materials consist of nanometer-sized quantum objects such as atoms, molecules, voids or nanoparticles embedded in a host material. These quantum objects can be exploited as a super-structure, which can be designed to create material properties targeted for specific applications. For electromagnetism, such targeted properties include field enhancements around the bandgap of a semiconductor used for solar cells, directional decay in topological insulators, high kinetic inductance in superconducting circuits, and many more. Despite very different application areas, all of these properties are united by the common aim of exploiting collective interaction effects between quantum objects. The literature on the topic spreads over very many different disciplines and scientific communities. In this review, we present a cross-disciplinary overview of different approaches for the creation, analysis and theoretical description of nanocomposites with applications related to electromagnetic properties

    Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series

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    <p>Abstract</p> <p>Introduction</p> <p>The use of methadone as an analgesic is on the increase, but it is widely recognized that the goal of predictable and reproducible dosing is confounded by considerable variability in methadone pharmacokinetics, and unpredictable side effects that include sedation, respiratory depression and cardiac arrhythmias. The mechanisms underlying these unpredictable effects are frequently unclear. Here, to the best of our knowledge we present the first report of an association between accidental methadone overexposure and increased plasma protein binding, a new potential mechanism for drug interactions with methadone.</p> <p>Case presentation</p> <p>We describe here the cases of two patients who experienced markedly different responses to the same dose of methadone during co-administration of letrozole. Both patients were post-menopausal Caucasian women who were among healthy volunteers participating in a clinical trial. Under the trial protocol both patients received 6 mg of intravenous methadone before and then after taking letrozole for seven days. One woman (aged 59) experienced symptoms consistent with opiate overexposure after the second dose of methadone that were reversed by naloxone, while the other (aged 49) did not. To understand the etiology of this event, we measured methadone pharmacokinetics in both patients. In our affected patient only, a fourfold to eightfold increase in methadone plasma concentrations after letrozole treatment was observed. Detailed pharmacokinetic analysis indicated no change in metabolism or renal elimination in our patient, but the percentage of unbound methadone in the plasma decreased 3.7-fold. As a result, the volume of distribution of methadone decreased approximately fourfold. The increased plasma binding in our affected patient was consistent with observed increases in plasma protein concentrations.</p> <p>Conclusions</p> <p>The marked increase in the total plasma methadone concentration observed in our patient, and the enhanced pharmacodynamic effect, appear primarily due to a reduced volume of distribution. The extent of plasma methadone binding may help to explain the unpredictability of its pharmacokinetics. Changes in volume of distribution due to plasma binding may represent important causes of clinically meaningful drug interactions.</p

    New/emerging psychoactive substances and associated psychopathological consequences

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    Submitted 24 November 2018, Revised 18 June 2019, Accepted 26 June 2019, Published online 22 July 2019BackgroundThe present paper provides an updated review of both the large number of new/novel/emerging psychoactive substances (NPS) and their associated psychopathological consequences. Focus was here given on identification of those NPS being commented in specialised online sources and the related short-/long-term psychopathological and medical ill-health effects.MethodsNPS have been identified through an innovative crawling/navigating software, called the 'NPS.FinderÂź', created in order to facilitate the process of early recognition of NPS online. A range of information regarding NPS, including chemical and street names; chemical formula; three-dimensional image and anecdotally reported clinical/psychoactive effects, were here made available.ResultsUsing the 'NPS.FinderÂź' approach, a few thousand NPS were here preliminarily identified, a number which is about 4-fold higher than those figures suggested by European and international drug agencies. NPS most commonly associated with the onset of psychopathological consequences included here synthetic cannabinoids/cannabimimetics; new synthetic opioids; ketamine-like dissociatives; novel stimulants; novel psychedelics and several prescription and over-the-counter medicines.ConclusionsThe ever-increasing changes in terms of recreational psychotropics' availability represent a relatively new challenge for psychiatry, as the pharmacodynamics and pharmacokinetics of many NPS have not been thoroughly understood. Health/mental health professionals should be informed about the range of NPS; their intake modalities; their psychoactive sought-after effects; the idiosyncratic psychotropics' combinations and finally, their medical and psychopathological risks.Peer reviewe

    FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

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    Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours
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