bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydroxyethyl starch: A review of pharmacokinetics, pharmacodynamics, current products, and potential clinical risks, benefits, and use
Authors: Glover Polly A. , Rudloff Elke , Kirby Rebecca 
Published: August 2014

AbstractObjectiveTo review and summarize the pharmacokinetics and pharmacodynamics of hydroxyethyl starch (HES), as well as reported risks and benefits of HES infusion, and to provide administration and monitoring recommendations for HES use in dogs and cats.Data SourcesVeterinary and human peer‐reviewed medical literature, including scientific reviews, clinical and laboratory research articles, and authors’ clinical experience.SummaryHES solutions are the most frequently used synthetic colloid plasma volume expanders in human and veterinary medicine. The majority of research in human medicine has focused on the adverse effects of HES infusion, with emphasis on acute kidney injury and coagulation derangements. The studies often differ in or fail to report factors, such as the type, amount, interval, and concentration of HES administered; the patient population studied; or concurrent fluids administered. Currently, there is no definitive clinical evidence that the reported adverse effects of HES use in human medicine occur in veterinary species. There is little information available on HES administration techniques or simultaneous administration of additional fluids in human and veterinary medicine. The rationale for HES use in small animals has been largely extrapolated from human medical studies and guidelines. A controlled approach to intravenous fluid resuscitation using crystalloid and HES volumes titrated to reach desired resuscitation end point parameters is outlined for small animal practitioners.ConclusionThe extrapolation of data from human studies directly to small animals should be done with the knowledge that there may be species variations and different pharmacokinetics with different HES solutions. Veterinary reports indicate that bolus and continuous rate infusions of 6% hetastarch solutions at moderate doses are well tolerated in feline and canine subjects. Further research in domesticated species is necessary to better define and expand the knowledge regarding use of HES solutions in small animal medicine.
AFFECTED BY NATURE: A HERMENEUTICAL TRANSFORMATION OF ENVIRONMENTAL ETHICS
Authors: Van den Noortgaete Francis , De Tavernier Johan 
Published: August 2014

AbstractThe value‐action gap poses a considerable challenge to normative environmental ethics. Because of the wide array of empirical research results that have become available in the fields of environmental psychology, education, and anthropology, ethicists are at present able to take into account insights on what effectively motivates proenvironmental behavior. The emotional aspect apparently forms a key element within a transformational process that leads to an internalization of nature within one's identity structure. We compare these findings with studies on environmental activists, which appear to a significantly lesser degree hampered by the value‐action gap, thereby attempting to understand what provides them with the drive to act more consistently on their moral attitudes. Hermeneutics is found to play a crucial role in the processes that lead to lasting and consistent motivation toward proenvironmental behavior. An empirically informed hermeneutical approach could therefore provide a promising impetus for contemporary environmental ethics.
ENTHEOGENS IN A RELIGIOUS CONTEXT: THE CASE OF THE SANTO DAIME RELIGIOUS TRADITION
Authors: Barnard G. William 
Published: August 2014

AbstractThis essay first draws upon the work of William James and others to propose a nonphysicalistic understanding of the relationship between the brain and consciousness in order to articulate a philosophical perspective that can understand entheogenic visionary/mystical experiences as something other than hallucinations. It then focuses on the Santo Daime tradition, a religious movement that began in Brazil in the early part of the twentieth century, to provide an example of the personal and social ramifications of taking an entheogen (ayahuasca) within a disciplined religious context. The essay claims that the Santo Daime is one example of a contemporary mystery school; gives a brief history of the development of this religion; discusses the key theological assumptions of this movement; investigates the important role played by visionary/mystical experiences within this religion; underscores the centrality of healing and spiritual transformation for members of this tradition; and ends with an examination of the crucial significance of spiritual discipline within this entheogenically based religion.
BY ITS FRUITS? MYSTICAL AND VISIONARY STATES OF CONSCIOUSNESS OCCASIONED BY ENTHEOGENS
Authors: Hummel Leonard 
Published: August 2014

AbstractA new era has emerged in research on entheogens largely due to clinical trials conducted at Johns Hopkins University and similar studies sponsored by the Council for Spiritual Practices. In these notes and queries, I reflect on implications of these developments for psychological studies of religion and on what this research may mean for Christian churches in the United States. I conclude that the aims and methods of this research fit well within Jamesian efforts of contemporary psychology of religion to assess religious practices by their fruits for life. Furthermore, some communitarian religious concerns that religious experiences occasioned by entheogens pose risks to the integrity of religious community are shown to be largely unfounded. However, it is suggested that certain risks for religious life posed by all investigations/interventions by knowledge experts—in particular, the colonization of the religious life world and the commodification of its practices—also attend these developments for Christian churches. Additionally, risks of individual harm in the use of entheogens appear to be significant and, therefore, warrant earnest ethical study.
RELIGION IS EASY, BUT SCIENCE IS HARD … UNDERSTANDING McCAULEY'S THESIS
Authors: Van Slyke James A. 
Published: August 2014

AbstractRobert N. McCauley's new book Why Religion Is Natural and Science Is Not (2011) presents a new paradigm for investigating the relationship between science and religion by exploring the cognitive foundations of religious belief and scientific knowledge. McCauley's contention is that many of the differences and disagreements regarding religion and science are the product of distinct features of human cognition that process these two domains of knowledge very differently. McCauley's thesis provides valuable insights into this relationship while not necessarily leading to a dismissive view of theology or religious belief. His paradigm allows the research lens to focus on cognitive differences in processing scientific versus religious information and the important role of automatic, unconscious, and intuitive cognitive processes in understanding both the natural and supernatural worlds.
ON McCAULEY'S WHY RELIGION IS NATURAL AND SCIENCE IS NOT: SOME FURTHER OBSERVATIONS
Authors: Peterson Gregory R. 
Published: August 2014

AbstractRobert McCauley's Why Religion Is Natural and Science Is Not provides a summary interpretive statement of the standard model in cognitive science of religion, what I have previously called the HADD + ToM + Cultural Epidemiology model, along with a more general argument comparing religious cognition to scientific thinking and a novel framework for understanding both in terms of the concept of the maturationally natural. I here follow up on some observations made in a previous paper, developing them in light of McCauley's own response to my previous arguments.
THE IMAGO DEI AS THE MIND OF JESUS CHRIST
Authors: Carter Christopher 
Published: August 2014

AbstractIn this essay I examine David Clough's interpretation of the imago Dei and his use of “creaturely” language in his book On Animals: Volume 1, Systematic Theology. Contrary to Clough, I argue that the imago Dei should be interpreted as being uniquely human. Using a neuroscientific approach, I elaborate on my claim that while Jesus is the image of God perfected, the imago Dei is best understood as having the mind of Christ. In regards to language, I make the case that using terms such as “creature” when referring to nonhuman animals is problematic in that it can serve to alienate human beings from their capacity to image God. In addition I argue that “creaturely” language raises concerns for the African American community given Western Christianity's history as it relates to their valuation of black bodies and human enslavement.
THE PARTICULARITY OF ANIMALS AND OF JESUS CHRIST
Authors: Adam Margaret B. 
Published: August 2014

AbstractClough's theological account of animals critiques the familiar negative identification of animals as not‐human. Instead, Clough highlights both the distinctive particularity of each animal as created by God and the shared fleshly creatureliness of human and nonhuman animals. He encourages Christians to recognize Jesus Christ as God enfleshed more than divinely human, and consequently to care for nonhuman animals as those who share with human animals in the redemption of all flesh. This move risks downplaying the possibilities for creaturely specific forms of redemption; limiting the cosmic efficacy of salvation in Christ; and losing the particularity of Christ's divine and human natures. Another, possibly less risky, direction to take Clough's insights about creatureliness and well‐formed theological ethics might attend to the perverse ways that humans assess the worthiness of human and nonhuman animals by substituting particularities of use and abuse for the particularities of creation and salvation.
TOWARD A WEAK ANTHROPOCENTRISM
Authors: Webb Stephen H. 
Published: August 2014

AbstractIn his work on the moral status of nonhuman animals, David Clough rejects the theory of anthropocentrism while accepting its practical importance. He thus leaves theology in a dilemma: reflection on animals should not support the very concept that practical approaches to animals require. An alternative is a “weak anthropocentrism” along the line of Gianni Vattimo's “weak ontology.” A weak anthropocentrism is better suited to a Neoplatonic theory of participation, not the traditional framework of creation out of nothing, and it also can give new meaning to the idea of imago Dei and a Christocentric affirmation of nonhuman value.
THE CHANGING CULTURAL CONTEXT OF THE INSTITUTE ON RELIGION IN AN AGE OF SCIENCE AND ZYGON
Authors: Peters Karl E. 
Published: August 2014

AbstractSince Zygon: Journal of Religion and Science was founded 49 years ago and since one of its co‐publishers, the Institute on Religion in an Age of Science (IRAS), was founded 60 years ago, there have been significant developments in their various cultural contexts—in science, in religion, in culture, in academia, and in the science and religion dialogue. This article is a personal remembrance and reflection that compares the context of IRAS in 1954 when it was first organized with the context of IRAS and Zygon today. It considers the contemporary niche of IRAS in relation to the developments that have occurred over the past 60 years.
RALPH BURHOE: RECONSIDERING THE MAN AND HIS VISION OF YOKING RELIGION AND SCIENCE
Authors: Hefner Philip 
Published: August 2014

AbstractRalph Wendell Burhoe was a leading figure in relating religion and science in the second half of the twentieth century. His autodidactic style and character as a public intellectual resulted in a vision that is comprehensive in its concern for the salvation of society. He does not fit easily into academic frameworks, even though he has been influential upon scholars who work in academia. This article discusses some conundrums posed by his work. There are also brief presentations of the concerns that motivated Burhoe, his style of work, and the content of his vision.
3D/3D registration of coronary CTA and biplane XA reconstructions for improved image guidance
Authors: Dibildox Gerardo , Baka Nora , Punt Mark , Aben Jean‐Paul , Schultz Carl , Niessen Wiro , van Walsum Theo 
Published: August 2014

Purpose:The authors aim to improve image guidance during percutaneous coronary interventions of chronic total occlusions (CTO) by providing information obtained from computed tomography angiography (CTA) to the cardiac interventionist. To this end, the authors investigate a method to register a 3D CTA model to biplane reconstructions.Methods:The authors developed a method for registering preoperative coronary CTA with intraoperative biplane x‐ray angiography (XA) images via 3D models of the coronary arteries. The models are extracted from the CTA and biplane XA images, and are temporally aligned based on CTA reconstruction phase and XA ECG signals. Rigid spatial alignment is achieved with a robust probabilistic point set registration approach using Gaussian mixture models (GMMs). This approach is extended by including orientation in the Gaussian mixtures and by weighting bifurcation points. The method is evaluated on retrospectively acquired coronary CTA datasets of 23 CTO patients for which biplane XA images are available.Results:The Gaussian mixture model approach achieved a median registration accuracy of 1.7 mm. The extended GMM approach including orientation was not significantly different (P > 0.1) but did improve robustness with regards to the initialization of the 3D models.Conclusions:The authors demonstrated that the GMM approach can effectively be applied to register CTA to biplane XA images for the purpose of improving image guidance in percutaneous coronary interventions.
Clinical and
In Vitro
Resistance to GS-9669, a Thumb Site II Nonnucleoside Inhibitor of the Hepatitis C Virus NS5B Polymerase
Authors: Dvory-Sobol Hadas , Voitenleitner Christian , Mabery Eric , Skurnac Taylor , Lawitz Eric J. , McHutchison John , Svarovskaia Evguenia S. , Delaney William , Miller Michael D. , Mo Hongmei 
Published: August 2014

ABSTRACT

Treatment with GS-9669, a novel nonnucleoside inhibitor (site II) of hepatitis C virus (HCV) nonstructural 5B (NS5B) polymerase, resulted in significant antiviral activity in HCV genotype (GT) 1 patients dosed at 50 and 500 mg once daily (QD) and at 50, 100, and 500 mg twice daily (BID) for 3 days. This report characterizes the virologic resistance to GS-9669
in vitro
and in GT1 HCV-infected patients from a phase I clinical study. An
in vitro
resistance selection study with GS-9669 revealed substitutions at several NS5B residues that conferred resistance. The M423 variants were selected at low drug concentrations (5× the 50% effective concentration [EC
50
]), and the L419, R422, and I482 variants were selected at higher drug concentrations (20× the EC
50
). During the phase I clinical study, substitutions at NS5B residues 419, 422, and 486 were the predominant changes associated with GS-9669 monotherapy. Substitutions at position 423 were observed only in GT1a patients in the low-dose groups (50 and 100 mg BID). Interestingly, four HCV patients had substitutions at position 423 at baseline. Consistent with the low resistance level at this position, three patients with M423I or M423V at baseline achieved >2-log
10
reductions of HCV RNA when treated with 100 mg BID or with 500 mg QD or BID of GS-9669. The fourth patient, who had the M423V substitution at baseline, had a 4.4-log
10
reduction of HCV RNA with 500 mg BID of GS-9669. Phenotypic analyses demonstrated that the viral isolates with multiple GS-9669 resistance-associated variants have reduced susceptibility to GS-9669 and lomibuvir (VX-222) but are not cross-resistant to other classes of HCV inhibitors. (This study has been registered at
ClinicalTrials.gov
under registration no. NCT01431898.)
Development of a Population Pharmacokinetic Model Characterizing the Tissue Distribution of Azithromycin in Healthy Subjects
Authors: Zheng Songmao , Matzneller Peter , Zeitlinger Markus , Schmidt Stephan 
Published: August 2014

ABSTRACTRecent clinical trials indicate that the use of azithromycin is associated with the emergence of macrolide resistance. The objective of our study was to simultaneously characterize free target site concentrations and correlate them with the MIC90s of clinically relevant pathogens. Azithromycin (500 mg once daily [QD]) was administered orally to 6 healthy male volunteers for 3 days. The free concentrations in the interstitial space fluid (ISF) of muscle and subcutaneous fat tissue as well as the total concentrations in plasma and polymorphonuclear leukocytes (PMLs) were determined on days 1, 3, 5, and 10. All concentrations were modeled simultaneously in NONMEM 7.2 using a tissue distribution model that accounts for nonlinear protein binding and ionization state at physiological pH. The model performance and parameter estimates were evaluated via goodness-of-fit plots and nonparametric bootstrap analysis. The model we developed described the concentrations at all sampling sites reasonably well and showed that the overall pharmacokinetics of azithromycin is driven by the release of the drug from acidic cell/tissue compartments. The model-predicted unionized azithromycin (AZM) concentrations in the cytosol of PMLs (6.0 ± 1.2 ng/ml) were comparable to the measured ISF concentrations in the muscle (8.7 ± 2.9 ng/ml) and subcutis (4.1 ± 2.4 ng/ml) on day 10, whereas the total PML concentrations were >1,000-fold higher (14,217 ± 2,810 ng/ml). The total plasma and free ISF concentrations were insufficient to exceed the MIC90s of the skin pathogens at all times. Our results indicate that the slow release of azithromycin from low pH tissue/cell compartments is responsible for the long terminal half-life of the drug and thus the extended period of time during which free concentrations reside at subinhibitory concentrations.
Lack of Clinically Significant Pharmacokinetic Interaction between the Thrombopoietin Receptor Agonist Eltrombopag and Hepatitis C Virus Protease Inhibitors Boceprevir and Telaprevir
Authors: Wire Mary Beth , Fang Lei , Hussaini Azra , Kleha Joseph F. , Theodore Dickens 
Published: August 2014

ABSTRACT

Eltrombopag is an orally bioavailable thrombopoietin receptor agonist approved for the treatment of thrombocytopenia associated with chronic immune (idiopathic) thrombocytopenic purpura and chronic hepatitis C virus (HCV) infection. This study evaluated the potential drug-drug interactions between eltrombopag and the HCV protease inhibitors boceprevir and telaprevir. In this open-label, 3-period, single-sequence, and crossover study, 56 healthy adult subjects were randomized 1:1 to cohort 1 (boceprevir) or 2 (telaprevir). The dosing was as follows: period 1, single 200-mg dose of eltrombopag; period 2, 800 mg boceprevir or 750 mg telaprevir every 8 hours (q8h) for 10 days; and period 3, single 200-mg dose of eltrombopag with either 800 mg boceprevir or 750 mg telaprevir q8h (3 doses). All doses were administered with food, and eltrombopag was administered specifically with low-calcium food. There was a 3-day washout between periods 1 and 2 and no washout between periods 2 and 3. Serial pharmacokinetic samples were collected for 72 h in periods 1 and 3 and for 8 h in period 2. The coadministration of eltrombopag increased the rate of boceprevir absorption, resulting in a 20% increase in the maximum concentration in plasma (
C
max
), a 1-h-earlier time to
C
max
(
T
max
) for boceprevir, a 32% decrease in the concentration at the end of the dosing interval (
C
τ
), and no change in the area under the concentration-time curve over the dosing interval (AUC
0-τ
). The coadministration of eltrombopag did not alter telaprevir pharmacokinetics, and the coadministration of boceprevir or telaprevir did not alter eltrombopag pharmacokinetics. Dysgeusia, headache, and somnolence occurred in ≥2 subjects. One subject withdrew because of nausea, headache, dizziness, sinus pressure, and vomiting. There were no severe or serious adverse events. Dose adjustment is not required when eltrombopag is coadministered with boceprevir or telaprevir given the lack of clinically significant pharmacokinetic interaction.
The 6-Aminoquinolone WC5 Inhibits Different Functions of the Immediate-Early 2 (IE2) Protein of Human Cytomegalovirus That Are Essential for Viral Replication
Authors: Mercorelli Beatrice , Luganini Anna , Muratore Giulia , Massari Serena , Terlizzi Maria Elena , Tabarrini Oriana , Gribaudo Giorgio , Palù Giorgio , Loregian Arianna 
Published: August 2014

ABSTRACT

The human cytomegalovirus (HCMV) immediate-early 2 (IE2) protein is a multifunctional factor essential for viral replication. IE2 modulates both viral and host gene expression, deregulates cell cycle progression, acts as an immunomodulator, and antagonizes cellular antiviral responses. Based on these facts, IE2 has been proposed as an important target for the development of innovative antiviral approaches. We previously identified the 6-aminoquinolone WC5 as a promising inhibitor of HCMV replication, and here, we report the dissection of its mechanism of action against the viral IE2 protein. Using glutathione
S
-transferase (GST) pulldown assays, mutagenesis, cell-based assays, and electrophoretic mobility shift assays, we demonstrated that WC5 does not interfere with IE2 dimerization, its interaction with TATA-binding protein (TBP), and the expression of a set of cellular genes that are stimulated by IE2. On the contrary, WC5 targets the regulatory activity exerted by IE2 on different responsive viral promoters. Indeed, WC5 blocked the IE2-dependent negative regulation of the major immediate-early promoter by preventing IE2 binding to the
crs
element. Moreover, WC5 reduced the IE2-dependent transactivation of a series of indicator constructs driven by different portions of the early
UL54
gene promoter, and it also inhibited the transactivation of the murine CMV early
E1
promoter by the IE3 protein, the murine cytomegalovirus (MCMV) IE2 homolog. In conclusion, our results indicate that the overall anti-HCMV activity of WC5 depends on its ability to specifically interfere with the IE2-dependent regulation of viral promoters. Importantly, our results suggest that this mechanism is conserved in murine CMV, thus paving the way for further preclinical evaluation in an animal model.