bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaling factors for the in vitro–in vivo extrapolation (IV–IVE) of renal drug and xenobiotic glucuronidation clearance
Authors: Knights Kathleen M. , Spencer Shane M. , Fallon John K. , Chau Nuy , Smith Philip C. , Miners John O. 
Published: January 2016

AimTo determine the scaling factors required for inclusion of renal drug glucuronidation clearance in the prediction of total clearance via glucuronidation (CLUGT).MethodsMicrosomal protein per gram of kidney (MPPGK) was determined for human ‘mixed’ kidney (n = 5) microsomes (MKM). The glucuronidation activities of deferiprone (DEF), propofol (PRO) and zidovudine (AZT) by MKM and paired cortical (KCM) and medullary (KMM) microsomes were measured, along with the UGT 1A6, 1A9 and 2B7 protein contents of each enzyme source. Unbound intrinsic clearances (CLint,u,UGT) for PRO and morphine (MOR; 3‐ and 6‐) glucuronidation by MKM, human liver microsomes (HLM) and recombinant UGT1A9 and 2B7 were additionally determined. Data were scaled using in vitro–in vivo extrapolation (IV–IVE) approaches to assess the influence of renal CLint,u,UGT on the prediction accuracy of the calculated CLUGT values of PRO and MOR.ResultsMPPGK was 9.3 ± 2.0 mg g−1 (mean ± SD). The respective rates of DEF (UGT1A6), PRO (UGT1A9) and AZT (UGT2B7) glucuronidation by KCM were 1.4‐, 5.2‐ and 10.5‐fold higher than those for KMM. UGT 1A6, 1A9 and 2B7 were the only enzymes expressed in kidney. Consistent with the activity data, the abundance of each of these enzymes was greater in KCM than in KMM. The abundance of UGT1A9 in MKM (61.3 pmol mg−1) was 2.7 fold higher than that reported for HLM.ConclusionsScaled renal PRO glucuronidation CLint,u,UGT was double that of liver. Renal CLint,u,UGT should be accounted for in the IV–IVE of UGT1A9 and considered for UGT1A6 and 2B7 substrates.
Utility of Pilot Studies for Predicting Ratios and Intrasubject Variability in High‐Variability Drugs
Authors: Moreno Isabel , Ochoa Dolores , Román Manuel , Cabaleiro Teresa , Abad‐Santos Francisco 
Published: January 2016

AbstractPilot studies can be used to identify adequate test formulations for pivotal bioequivalence trials. The objective of this study was to evaluate the usefulness of pilot studies in predicting ratios and the intrasubject coefficient of variation (CVw) for pivotal studies of high‐variability drugs. Seven cross‐over and replicate bioequivalence trials were selected. A hundred simulations of pilot studies were performed for different sample sizes and designs. The pharmacokinetic data of the selected formulations were analysed using WinNonLin based on an analysis of variance (anova). The CVw was estimated using the formula recommended by the European Medicines Agency based on the mean square of the anova. We calculated the predictivity index ± 10% and ± 20% of the real value. The predictivity index of ± 20% in the 2 × 2 design with 12 volunteers was 100% for AUC0–t ratio, 87% for Cmax ratio, 50% for the CVw of AUC0–t and 52% for the CVw of Cmax. The results of the 4 × 4 design with 8 volunteers were similar to those of the 2 × 2 design with 12 volunteers. These results were worse for the predictivity index of ± 10% in both designs. Pilot studies do not seem useful for predicting sample size. However, they were very good for predicting the AUC0–t ratio and good for predicting the Cmax ratio. The most adequate design for pilot studies seems to be the 2 × 2 design with at least 12 volunteers.
Pediatric Chiropractic Care: The Subluxation Question And Referral Risk
Authors: Homola Samuel 
Published: January 2016

AbstractChiropractors commonly treat children for a variety of ailments by manipulating the spine to correct a ‘vertebral subluxation’ or a ‘vertebral subluxation complex’ alleged to be a cause of disease. Such treatment might begin soon after a child is born. Both major American chiropractic associations – the International Chiropractic Association and the American Chiropractic Association – support chiropractic care for children, which includes subluxation correction as a treatment or preventive measure. I do not know of any credible evidence to support chiropractic subluxation theory. Any attempt to manipulate the immature, cartilaginous spine of a neonate or a small child to correct a putative chiropractic subluxation should be regarded as dangerous and unnecessary. Referral of a child to a chiropractor for such treatment should not be considered lest a bad outcome harms the child or leads to a charge of negligence or malpractice.
Alternative Medicine and the Ethics Of Commerce
Authors: Macdonald Chris , Gavura Scott 
Published: January 2016

AbstractIs it ethical to market complementary and alternative medicines? Complementary and alternative medicines (CAM) are medical products and services outside the mainstream of medical practice. But they are not just medicines (or supposed medicines) offered and provided for the prevention and treatment of illness. They are also products and services – things offered for sale in the marketplace. Most discussion of the ethics of CAM has focused on bioethical issues – issues having to do with therapeutic value, and the relationship between patients and those purveyors of CAM. This article aims instead to consider CAM from the perspective of commercial ethics. That is, we consider the ethics not of prescribing or administering CAM (activities most closely associated with health professionals) but the ethics of selling CAM.
Moral Legitimacy: The Struggle Of Homeopathy in the NHS
Authors: Crawford Louise 
Published: January 2016

AbstractThis article deploys a well‐established theoretical model from the accountability literature to the domain of bioethics. Specifically, homeopathy is identified as a controversial industry and the strategic action of advocates to secure moral legitimacy and attract public funding is explored. The Glasgow Homeopathic Hospital (GHH) is used as the location to examine legitimizing strategies, from gaining legitimacy as a National Health Service (NHS) hospital in 1948, followed by maintaining and repairing legitimacy in response to government enquires in 2000 and 2010. An analysis of legitimizing strategies leads to the conclusion that advocates have been unsuccessful in maintaining and repairing moral legitimacy for homeopathy, thus threatening continued public funding for this unscientific medical modality. This is an encouraging development towards open and transparent NHS accountability for targeting limited public resources in pursuit of maximizing society's health and well‐being. Policy implications and areas for future research are suggested.
Who returns home? Study on placement outcomes of Flemish foster children
Authors: Vanderfaeillie Johan , Van Holen Frank , De Maeyer Skrallan , Belenger Laurence , Gypen Laura 
Published: January 2016

AbstractUntil recently, Flemish family foster care was a temporary measure with as its most important goal, the reunification of the foster child with the birth parents. To date, nothing is known on the number of reunifications, nor has any study been undertaken into the factors (child, parent, foster parent and foster care process) associated with reunification. Case files of 127 foster children who exited foster care in 2007 were analysed. Dependent variables were type of foster care placement outcome (reunification, successful placement without reunification or breakdown) and place of residence after placement ending (with birth parents, extended family, foster family, residential care or living independently). After placement ending, only 40% of foster children went living with their parents, including foster children who were reunified (26%) and foster children who moved to their parents after a placement breakdown (14%). Characteristics of the foster children, and in particular absence of problem behaviour, were associated mainly with a return home. This may indicate that too much attention is paid to the functioning of the foster child and too little to improving the competencies of the parents and the (future) home environment.
A Taxonomy and Survey of Dynamic Graph Visualization
Authors: Beck Fabian , Burch Michael , Diehl Stephan , Weiskopf Daniel 
Published: January 2016

AbstractDynamic graph visualization focuses on the challenge of representing the evolution of relationships between entities in readable, scalable and effective diagrams. This work surveys the growing number of approaches in this discipline. We derive a hierarchical taxonomy of techniques by systematically categorizing and tagging publications. While static graph visualizations are often divided into node‐link and matrix representations, we identify the representation of time as the major distinguishing feature for dynamic graph visualizations: either graphs are represented as animated diagrams or as static charts based on a timeline. Evaluations of animated approaches focus on dynamic stability for preserving the viewer's mental map or, in general, compare animated diagrams to timeline‐based ones. A bibliographic analysis provides insights into the organization and development of the field and its community. Finally, we identify and discuss challenges for future research. We also provide feedback from experts, collected with a questionnaire, which gives a broad perspective of these challenges and the current state of the field.
Effects of payments for ecosystem services on wildlife habitat recovery
Authors: Tuanmu Mao‐Ning , Viña Andrés , Yang Wu , Chen Xiaodong , Shortridge Ashton M. , Liu Jianguo 
Published: January 2016

AbstractConflicts between local people's livelihoods and conservation have led to many unsuccessful conservation efforts and have stimulated debates on policies that might simultaneously promote sustainable management of protected areas and improve the living conditions of local people. Many government‐sponsored payments‐for‐ecosystem‐services (PES) schemes have been implemented around the world. However, few empirical assessments of their effectiveness have been conducted, and even fewer assessments have directly measured their effects on ecosystem services. We conducted an empirical and spatially explicit assessment of the conservation effectiveness of one of the world's largest PES programs through the use of a long‐term empirical data set, a satellite‐based habitat model, and spatial autoregressive analyses on direct measures of change in an ecosystem service (i.e., the provision of wildlife species habitat). Giant panda (Ailuropoda melanoleuca) habitat improved in Wolong Nature Reserve of China after the implementation of the Natural Forest Conservation Program. The improvement was more pronounced in areas monitored by local residents than those monitored by the local government, but only when a higher payment was provided. Our results suggest that the effectiveness of a PES program depends on who receives the payment and on whether the payment provides sufficient incentives. As engagement of local residents has not been incorporated in many conservation strategies elsewhere in China or around the world, our results also suggest that using an incentive‐based strategy as a complement to command‐and‐control, community‐ and norm‐based strategies may help achieve greater conservation effectiveness and provide a potential solution for the park versus people conflict.
Sorbitan sesquioleate; a rare cause of contact allergy in consecutively patch tested dermatitis patients
Authors: Bennike Niels Højsager , Johansen Jeanne Duus 
Published: January 2016

SummaryBackgroundSorbitan sesquioleate (SSO) has been added to fragrance mix I (FM I) as an emulsifier since the 1990s. Being a contact allergen itself, SSO has the potential to cause false‐positive reactions to FM I. Recent results obtained with selected FM I‐positive patients have shown that 5% have concomitant positive reactions to SSO.ObjectivesTo investigate the 5‐year prevalence of contact allergy to SSO and evaluate the importance of SSO allergy when patch test results for FM I are interpreted.MethodsThis was a retrospective database study of consecutively patch tested eczema patients (n = 4 6 3 7) from 2010 to 2014. All patients were tested with our baseline series including FM I and SSO 20% in pet.ResultsSensitization to SSO was identified in 9 (0.2%) patients. The proportion of FM I‐positive patients with concomitant positive reactions to SSO was 1.4%.ConclusionsSSO is a rare cause of contact allergy, with a 5‐year prevalence of 0.2% in consecutively tested patients. Contact allergy to the emulsifier does not play a major role when the overall frequency of contact allergy to FM I is evaluated. However, to correctly diagnose individual patients, concomitant patch testing with FM I and SSO is encouraged.
Regional variation in climate change winners and losers highlights the rapid loss of cold‐dwelling species
Authors: Tayleur Catherine M. , Devictor Vincent , Gaüzère Pierre , Jonzén Niclas , Smith Henrik G. , Lindström Åke 
Published: January 2016

AbstractAimsClimate change is known to drive both the reshuffling of whole assemblages and range shifts of individual species. Less is known about how local colonizations and extinctions of individual species contribute to changes at the community level. Our aim was to estimate the contribution of individual species to a change in community composition attributed to climate change and to relate these species‐specific contributions to species’ commonness, climatic niche characteristics and life history traits most likely to influence species sensitivity to climate change.LocationSweden.MethodsFocussing on birds, we analysed changes from 1998 to 2012 in the Community Temperature Index (CTI), a measure of the average climatic niche of a community. Using a jackknife approach we assessed the contribution of individual species to the temporal trend in CTI in four different regions across Sweden, controlling for habitat distribution. We further tested whether species contribution was related to population trends and rarity to identify species most vulnerable to climate change.ResultsCommunity Temperature Index had increased over time with the greatest gains occurring in the north of the country, reflecting the larger temperature increases in this area. Changes in the regional CTI were driven both by warm‐dwelling species colonizing new sites and by extirpations of cold‐dwelling species. Furthermore, the community changes were influenced by both rare and common species. At the same time, the distribution changes of a large number of species were seemingly unaffected by climate change.Main conclusionsBoth range expansion and contractions contributed to the relative increase of warm‐dwelling species in Swedish bird communities. We successfully identified the climatic impacts on some of Sweden's rarest species, including cold‐dwelling species in the mountainous north. Our approach may be an efficient tool to use when characterizing the impacts of climate change on species and communities.
New findings about the spatial and temporal use of the Eastern Atlantic Ocean by large juvenile loggerhead turtles
Authors: Varo‐Cruz Nuria , Bermejo Juan A. , Calabuig Pascual , Cejudo Daniel , Godley Brendan J. , López‐Jurado Luis F. , Pikesley Stephen K. , Witt Matthew J. , Hawkes Lucy A. 
Published: January 2016

AbstractAimsEffective conservation of threatened or endangered species requires a robust understanding of their spatio‐temporal distribution. Although a huge amount is known about the movements of Atlantic adult sea turtles, much less is known about juvenile turtles, and much of the life history model is therefore inferred. We set out to describe the spatio‐temporal distribution of juvenile loggerheads turtles found around the Canary Islands.LocationEastern North Atlantic Ocean.MethodsBetween 1999 and 2012, we satellite‐tracked 24 healthy large juvenile loggerhead turtles (mean straight carapace length = 47.4 cm, range = 34.6–54.5 cm) captured in the waters around the Canary Islands. We describe their regional distribution, identify high‐use areas and create a model for habitat suitability using minimum convex polygons, density rasters and ensemble ecological niche modelling, integrated with physical and biological environmental data.ResultsTurtles used a huge oceanic area (2.5 million km2) with particularly high usage around the Canary Islands, Spain, Portugal, Morocco and Western Sahara. In spring and summer, turtles generally moved further north towards the Iberian Peninsula. Ecological niche modelling identified sea surface temperature as the most important contributory variable to the habitat models. We also recorded three juvenile turtles making westward migrations away from the eastern Atlantic Ocean, presumably back towards their original natal beaches near sexual maturity.Main conclusionsThe results of the present study provide insight into a significant knowledge gap on the spatio‐temporal distribution of large juvenile loggerhead turtles in the eastern Atlantic Ocean. The data highlight that turtles occupy a vast open oceanic area, which hampers the ability of static conservation approaches to afford effective protection. However, ensemble ecological niche modelling highlights key suitable habitat for juvenile loggerhead turtles, which could be used in dynamic conservation protection.
Beyond the Sterility of a Distinct African Bioethics: Addressing the Conceptual Bioethics Lag in Africa
Authors: Ssebunnya Gerald M. 
Published: January 2016

AbstractIn the current debate on the future of bioethics in Africa, several authors have argued for a distinct communitarian African bioethics that can counter the dominancy of Western atomistic principlism in contemporary bioethics. In this article I examine this rather contentious argument and evaluate its validity and viability. Firstly, I trace the contextual origins of contemporary bioethics and highlight the rise and dominance of principlism. I particularly note that principlism was premised on a content‐thin notion of the common morality that is in need of enrichment. I also contend that bioethics is essentially two‐dimensional, being both conceptual and empirical, and indicate the lag in Africa with regard to conceptual bioethics. I then appeal for authentic engagement by 1) African health care professionals, 2) African health care training institutions, 3) Africa's bioethics development partners, and 4) African bioethicists and philosophers, towards addressing this critical lag. I underline the need to maintain the essential universality of bioethics as a discipline. I particularly argue against the pursuit of a distinct African bioethics, as it appears to be rooted in sterile African ethno‐philosophy. Rather, African bioethicists and philosophers would do well to elucidate the universalisability of insights from traditional African thought, for the benefit of bioethics as a whole. Thus we must engage beyond the sterility of a distinct African bioethics ‐ authentically reflecting on the essentially universal contemporary bioethical concerns ‐ to effectively articulate a viable trajectory for bioethics in Africa.
Identification of Factors that Predict whether the Right Parasternal View Is Required for Accurate Evaluation of Aortic Stenosis Severity
Authors: Cho Eun Jeong , Kim Sung‐Mok , Park Sung‐Ji , Lee Sang‐Chol , Park Seung Woo 
Published: January 2016

BackgroundTo accurately assess aortic stenosis (AS) severity, multiple windows should be used to best align the Doppler beam with the flow direction of the stenotic jet. To evaluate: (1) the frequency at which the highest peak AV velocity is found in the right parasternal window (RPW), (2) the extent of correlation between aortic root angulation and the location of the highest peak AV jet velocity, and (3) which patients would benefit most from RPW‐based assessment of AS severity.MethodsWe evaluated AS velocity in the apical window (AW) and RPW by continuous‐wave Doppler (CWD) in 263 patients with more than moderate AS. If the AV was inaccessible by the left parasternal long‐axis view, the aortoseptal angle was measured by echocardiography and a sagittal view of a computed tomography (CT).ResultsPatients were divided into two groups, the RPW group and the AW group. Significant differences were observed between the two groups regarding the sinus of Valsalva diameter, the aortoseptal angle as measured by echocardiography, and the type of valve. The aortoseptal angle as measured by echocardiography was larger in the AW group compared with the RPW group. Aortoseptal angle (P < 0.001) and valve type (P = 0.036) were independent predictors that the highest AV Vmax would be obtained from the RPW.ConclusionsThe right parasternal window must be evaluated to achieve the most accurate assessment of AS severity, especially in patients with an aortoseptal angle <119° in the parasternal long‐axis view as measured by echocardiography.
The contribution of inner and outer retinal photoreceptors to infra‐slow oscillations in the rat olivary pretectal nucleus
Authors: Orlowska‐Feuer Patrycja , Allen Annette E. , Storchi Riccardo , Szkudlarek Hanna J. , Lewandowski Marian H. 
Published: January 2016

AbstractA subpopulation of olivary pretectal nucleus (OPN) neurons discharges action potentials in an oscillatory manner, with a period of approximately two minutes. This ‘infra‐slow’ oscillatory activity depends on synaptic excitation originating in the retina. Signals from rod‐cone photoreceptors reach theOPNvia the axons of either classic retinal ganglion cells or intrinsically photosensitive retinal ganglion cells (ipRGCs), which use melanopsin for photon capturing. Although both cell types convey light information, their physiological functions differ considerably. The aim of the present study was to disentangle how rod‐cone and melanopsin photoresponses contribute to generation of oscillatory activity. Pharmacological manipulations of specific phototransduction cascades were used whilst recording extracellular single‐unit activity in theOPNof anaesthetized rats. The results show that under photopic conditions (bright light), ipRGCs play a major role in driving infra‐slow oscillations, as blocking melanopsin phototransmission abolishes or transiently disturbs oscillatory firing of theOPNneurons. On the other hand, blocking rod‐cone phototransmission does not change firing patterns in photopic conditions. However, under mesopic conditions (moderate light), when melanopsin phototransmission is absent, blocking rod‐cone signalling causes disturbances or even the disappearance of oscillations implying that classic photoreceptors are of greater importance under moderate light. Evidence is provided that all photoreceptors are required for the generation of oscillations in theOPN, although their roles in driving the rhythm are determined by the lighting conditions, consistent with their relative sensitivities. The results further suggest that maintained retinal activity is crucial to observe infra‐slow oscillatory activity in theOPN.