1,061 research outputs found

    Prediction of Sublingual Bioavailability of Buprenorphine in Newborns with Neonatal Abstinence Syndrome—a case study on physiological and developmental changes using NONMEM and SIMCYP

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    Poster presented at 2009 American College of Clinical Pharmacology conference in Orlando. April 24-28. Background: About 55 to 94% of infants born to opioid dependent mothershave neonatal abstinence syndrome (NAS). Buprenorphine (BUP) is usedclinically as an analgesic and a detoxification agent and a maintenancetreatment for opioid dependence. No data, however, has been reported about the use of sublingual administration of BUP below the age of 4 year, especially for term infants with NAS. Objectives: Characterize pharmacokinetics (PK) of BUP in newborn patients;Evaluate the developmental changes in newborns in order to assist dosingoptimization in ongoing clinical studies. Methods: In silico prediction of PK behavior and physiological development in newborn patients were evaluated using SIMCYP. Intravenous clearance was predicted through physiologically based simulation method in SIMCYP. Basedon sublingual clearance obtained from a one compartmental model developedpreviously using NONMEM, individual changes of sublingual bioavailability were evaluated with physiological development in the first one and half month during the newborn period. Results: Intrinsic clearance of BUP in newborns were incorporated into enzymekinetic data obtained from literature. Change of sublingual bioavailability fornewborns was evaluated with bioavailability-postmenstrual age profiles.Sublingual bioavailability of BUP was estimated as 8.9--56.6% in newborn patients studied during the first one and half postnatal month. Conclusion: Developmental considerations for the PK of BUP in newborns are important for the characterization of the dose-exposure relationship. We have evaluated this from “bottom-up” and “top-down” approaches with SIMCYP and NONMEM respectively and found these approaches to be complementary andvaluable for clinical trial design and routine clinical care. Presumably theywould facilitate rational decision making in pediatric drug development as well

    Senior Smiles and Wellness Program: Continuation of a hybrid Interprofessional Education [IPE] Model for Assessing Community Health

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    SCOPE (Student Community Outreach for Public Education) at University of the Pacific (UOP), Arthur A. Dugoni School of Dentistry sponsored the 26th Annual Senior Smiles Health & Wellness Fair in its clinic, located in San Francisco on April 27th, 2019. 125 San Francisco’s senior citizens with limited access to health care attended this event. As a continuation of last year’s Senior Smiles & Wellness which continued hybrid Interprofessional education (IPE) activities, SCOPE provided various health screenings to the senior attendees in partnership with Dugoni’s sister schools UOP Audiology, Pharmacy and Physical Therapy program, as well as Touro College of Pharmacy. This event was designed to be a continued effort of interdisciplinary community-outreach based learning that models UOP\u27s Dental School Helix Curriculum. This event presented a great opportunity for various health education programs to learn from each other and promote future collaborations among healthcare providers. The ultimate goal is to prepare alumni of each organization to enter the health sector with a greater understanding of the scope of practice of other health providers, allowing for better coordination and care rendered for each patient

    Cost‐effectiveness of magnetic resonance imaging and targeted fusion biopsy for early detection of prostate cancer

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144625/1/bju14151_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144625/2/bju14151.pd

    Interactive Effects of Climate Change with Nutrients, Mercury, and Freshwater Acidification on Key Taxa in the North Atlantic Landscape Conservation Cooperative Region

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    The North Atlantic Landscape Conservation Cooperative LCC (NA LCC) is a public-private partnership that provides information to support conservation decisions that may be affected by global climate change (GCC) and other threats. The NA LCC region extends from southeast Virginia to the Canadian Maritime Provinces. Within this region, the US National Climate Assessment documented increases in air temperature, total precipitation, frequency of heavy precipitation events, and rising sea level, and predicted more drastic changes. Here, we synthesize literature on the effects of GCC interacting with selected contaminant, nutrient, and environmental processes to adversely affect natural resources within this region. Using a case study approach, we focused on 3 stressors with sufficient NA LCC region-specific information for an informed discussion. We describe GCC interactions with a contaminant (Hg) and 2 complex environmental phenomena-freshwater acidification and eutrophication. We also prepared taxa case studies on GCC- and GCC-contaminant/nutrient/process effects on amphibians and freshwater mussels. Several avian species of high conservation concern have blood Hg concentrations that have been associated with reduced nesting success. Freshwater acidification has adversely affected terrestrial and aquatic ecosystems in the Adirondacks and other areas of the region that are slowly recovering due to decreased emissions of N and sulfur oxides. Eutrophication in many estuaries within the region is projected to increase from greater storm runoff and less denitrification in riparian wetlands. Estuarine hypoxia may be exacerbated by increased stratification. Elevated water temperature favors algal species that produce harmful algal blooms (HABs). In several of the region\u27s estuaries, HABs have been associated with bird die-offs. In the NA LCC region, amphibian populations appear to be declining. Some species may be adversely affected by GCC through higher temperatures and more frequent droughts. GCC may affect freshwater mussel populations via altered stream temperatures and increased sediment loading during heavy storms. Freshwater mussels are sensitive to un-ionized ammonia that more toxic at higher temperatures. We recommend studying the interactive effects of GCC on generation and bioavailability of methylmercury and how GCC-driven shifts in bird species distributions will affect avian exposure to methylmercury. Research is needed on how decreases in acid deposition concurrent with GCC will alter the structure and function of sensitive watersheds and surface waters. Studies are needed to determine how GCC will affect HABs and avian disease, and how more severe and extensive hypoxia will affect fish and shellfish populations. Regarding amphibians, we suggest research on 1) thermal tolerance and moisture requirements of species of concern, 2) effects of multiple stressors (temperature, desiccation, contaminants, nutrients), and 3) approaches to mitigate impacts of increased temperature and seasonal drought. We recommend studies to assess which mussel species and populations are vulnerable and which are resilient to rising stream temperatures, hydrological shifts, and ionic pollutants, all of which are influenced by GCC

    Interactive Effects of Climate Change with Nutrients, Mercury, and Freshwater Acidification on Key Taxa in the North Atlantic Landscape Conservation Cooperative Region

    Get PDF
    The North Atlantic Landscape Conservation Cooperative LCC (NA LCC) is a public–private partnership that provides information to support conservation decisions that may be affected by global climate change (GCC) and other threats. The NA LCC region extends from southeast Virginia to the Canadian Maritime Provinces. Within this region, the US National Climate Assessment documented increases in air temperature, total precipitation, frequency of heavy precipitation events, and rising sea level, and predicted more drastic changes. Here, we synthesize literature on the effects of GCC interacting with selected contaminant, nutrient, and environmental processes to adversely affect natural resources within this region. Using a case study approach, we focused on 3 stressors with sufficient NA LCC regionspecific information for an informed discussion. We describe GCC interactions with a contaminant (Hg) and 2 complex environmental phenomena—freshwater acidification and eutrophication. We also prepared taxa case studies on GCCand GCC-contaminant/nutrient/process effects on amphibians and freshwater mussels. Several avian species of high conservation concern have blood Hg concentrations that have been associated with reduced nesting success. Freshwater acidification has adversely affected terrestrial and aquatic ecosystems in the Adirondacks and other areas of the region that are slowly recovering due to decreased emissions of N and sulfur oxides. Eutrophication in many estuaries within the region is projected to increase from greater storm runoff and less denitrification in riparian wetlands. Estuarine hypoxia may be exacerbated by increased stratification. Elevated water temperature favors algal species that produce harmful algal blooms (HABs). In several of the region\u27s estuaries, HABs have been associated with bird die-offs. In the NA LCC region, amphibian populations appear to be declining. Some species may be adversely affected by GCC through higher temperatures and more frequent droughts. GCC may affect freshwater mussel populations via altered stream temperatures and increased sediment loading during heavy storms. Freshwater mussels are sensitive to un-ionized ammonia that more toxic at higher temperatures. We recommend studying the interactive effects of GCC on generation and bioavailability of methylmercury and how GCC-driven shifts in bird species distributions will affect avian exposure to methylmercury. Research is needed on how decreases in acid deposition concurrent with GCC will alter the structure and function of sensitive watersheds and surface waters. Studies are needed to determine how GCC will affect HABs and avian disease, and how more severe and extensive hypoxia will affect fish and shellfish populations. Regarding amphibians, we suggest research on 1) thermal tolerance and moisture requirements of species of concern, 2) effects of multiple stressors (temperature, desiccation, contaminants, nutrients), and 3) approaches to mitigate impacts of increased temperature and seasonal drought. We recommend studies to assess which mussel species and populations are vulnerable and which are resilient to rising stream temperatures, hydrological shifts, and ionic pollutants, all of which are influenced by GCC

    Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel: Lack of prediction by the erythromycin breath test

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    The CYP3A subfamily of cytochromes P450 metabolize many medications and environmental contaminants. CYP3A4 and, in 25% of patients, CYP3A5 seem to be the major CYP3A genes expressed in adult liver. Hepatic levels of CYP3A4 can be estimated by the erythromycin breath test and vary at least 10-fold among patients. CYP3A4 has also been shown to be present in small bowel where it is responsible for significant "first-pass" metabolism of orally administered substrates. However, it is not known whether there is significant interindividual variability in the intestinal expression of CYP3A4, or whether the liver and intestinal catalytic activities of CYP3A4 correlate within an individual. It is also not known whether CYP3A5 is expressed in the small intestine. To address these questions, we administered the erythromycin breath test to 20 patients and obtained biopsies from their small bowel. There was a 6-fold variation in CYP3A catalytic activity (midazolam hydroxylation), an 11-fold variation in CYP3A4 protein content, and an 8-fold variation in CYP3A4 mRNA content in intestinal biopsies. There was an excellent correlation between intestinal CYP3A4 protein level and catalytic activity (r = 0.86; p = 0.0001); however, neither parameter significantly correlated with hepatic CYP3A4 activity as measured by the erythromycin breath test result (r = 0.27; p = 0.24 and r = 0.33; p = 0.15, respectively). We also found that CYP3A5 protein was readily detectable in biopsies from 14 (70%) of the patients, indicating that CYP3A5 is commonly expressed in human small intestine

    Contextual-value approach to the generalized measurement of observables

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    We present a detailed motivation for and definition of the contextual values of an observable, which were introduced by Dressel et al. [Phys. Rev. Lett. 104 240401 (2010)]. The theory of contextual values extends the well-established theory of generalized state measurements by bridging the gap between partial state collapse and the observables that represent physically relevant information about the system. To emphasize the general utility of the concept, we first construct the full theory of contextual values within an operational formulation of classical probability theory, paying special attention to observable construction, detector coupling, generalized measurement, and measurement disturbance. We then extend the results to quantum probability theory built as a superstructure on the classical theory, pointing out both the classical correspondences to and the full quantum generalizations of both L\"uder's rule and the Aharonov-Bergmann-Lebowitz rule in the process. We find in both cases that the contextual values of a system observable form a generalized spectrum that is associated with the independent outcomes of a partially correlated and generally ambiguous detector; the eigenvalues are a special case when the detector is perfectly correlated and unambiguous. To illustrate the approach, we apply the technique to both a classical example of marble color detection and a quantum example of polarization detection. For the quantum example we detail two devices: Fresnel reflection from a glass coverslip, and continuous beam displacement from a calcite crystal. We also analyze the three-box paradox to demonstrate that no negative probabilities are necessary in its analysis. Finally, we provide a derivation of the quantum weak value as a limit point of a pre- and postselected conditioned average and provide sufficient conditions for the derivation to hold.Comment: 36 pages, 5 figures, published versio

    Major flaws in conflict prevention policies towards Africa : the conceptual deficits of international actors’ approaches and how to overcome them

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    Current thinking on African conflicts suffers from misinterpretations oversimplification, lack of focus, lack of conceptual clarity, state-centrism and lack of vision). The paper analyses a variety of the dominant explanations of major international actors and donors, showing how these frequently do not distinguish with sufficient clarity between the ‘root causes’ of a conflict, its aggravating factors and its triggers. Specifically, a correct assessment of conflict prolonging (or sustaining) factors is of vital importance in Africa’s lingering confrontations. Broader approaches (e.g. “structural stability”) offer a better analytical framework than familiar one-dimensional explanations. Moreover, for explaining and dealing with violent conflicts a shift of attention from the nation-state towards the local and sub-regional level is needed.Aktuelle Analysen afrikanischer Gewaltkonflikte sind hĂ€ufig voller Fehlinterpretationen (Mangel an Differenzierung, Genauigkeit und konzeptioneller Klarheit, Staatszentriertheit, fehlende mittelfristige Zielvorstellungen). Breitere AnsĂ€tze (z. B. das Modell der Strukturellen StabilitĂ€t) könnten die Grundlage fĂŒr bessere Analyseraster und Politiken sein als eindimensionale ErklĂ€rungen. hĂ€ufig differenzieren ErklĂ€rungsansĂ€tze nicht mit ausreichender Klarheit zwischen Ursachen, verschĂ€rfenden und auslösenden Faktoren. Insbesondere die richtige Einordnung konfliktverlĂ€ngernder Faktoren ist in den jahrzehntelangen gewaltsamen Auseinandersetzungen in Afrika von zentraler Bedeutung. Das Diskussionspapier stellt die große Variationsbreite dominanter ErklĂ€rungsmuster der wichtigsten internationalen Geber und Akteure gegenĂŒber und fordert einen Perspektivenwechsel zum Einbezug der lokalen und der subregionalen Ebene fĂŒr die ErklĂ€rung und Bearbeitung gewaltsamer Konflikte
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