bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pharmacokinetics and safety of darapladib in subjects with severe renal impairment
Authors: He Magee Mindy , Shaddinger Bonnie , Collins David , Siddiqi Shabana , Soffer Joseph 
Published: May 2015

AimDarapladib is a potent and reversible orally active inhibitor of lipoprotein‐associated phospholipase A2 (Lp‐PLA2). The aim of the study was to assess the effects of severe renal impairment on the pharmacokinetics and safety/tolerability of darapladib compared with normal renal function.MethodsThis was an open label, parallel group study of darapladib following 10 day once daily 160 mg oral dosing in subjects with normal (n = 8) and severe renal impairment (estimated glomerular filtration rate <30 ml min–1 1.73 m–2, n = 8). Plasma concentrations of total and unbound darapladib as well as total darapladib metabolites were determined in samples obtained over 24 h on day 10.ResultsPlasma concentrations of total and unbound darapladib as well as all three metabolites were higher in subjects with severe renal impairment. Area under the plasma concentration vs. time curve between time zero and 24 h (AUC(0,24 h) and maximum plasma concentration (Cmax) of total darapladib in severely renally impaired subjects were 52% and 59% higher than those in the matched healthy subjects, respectively. Similar results were found with the darapladib metabolites. Darapladib was highly plasma protein bound with 0.047% and 0.034% unbound circulating in plasma in severely renally impaired and healthy subjects, respectively. Unbound plasma darapladib exposures were more than two‐fold higher in severely renally impaired subjects than in healthy controls. Adverse events (AE) were reported in 38% of healthy subjects and 75% of severely renally impaired subjects, most of which were mild or moderate in intensity.ConclusionsThe results of this study showed that darapladib exposure was increased in subjects with severe renal impairment compared with healthy controls. However, darapladib was generally well tolerated in both groups.
Hydration, fluid regulation and the eye: in health and disease
Authors: Sherwin Justin C , Kokavec Jan , Thornton Simon N 
Published: May 2015

AbstractVariation in systemic hydration status, namely chronic systemic hypohydration or dehydration, can influence the development of several chronic non‐ophthalmic diseases. Owing to the eye's high water content and unique system of fluid regulation, we hypothesized that hydration status may affect the eye in health and disease states. Therefore, we performed a systematic review of the current evidence implicating changes in hydration and their association with ocular physiology and morphological characteristics. We also reviewed relevant clinical correlations of changes in hydration and major common eye diseases. Our findings suggest that systemic hydration status broadly affects a variety of ocular pathophysiologic processes and disease states. For example, dehydration may be associated with development of dry eye syndrome, cataract, refractive changes and retinal vascular disease. On the other hand, excessive hydration is associated with some ocular diseases. Tear fluid osmolarity may be an effective marker of systemic hydration status. Recent studies implicate chronic renin‐angiotensin‐aldosterone system activation in the pathogenesis of diabetic retinopathy and glaucoma but also suggest its antagonism may be a useful therapeutic target. Our findings indicate that assessment of hydration status may be an important consideration in the management of patients with chronic eye diseases and undergoing eye surgery. Further research investigating the role of acute and chronic changes in hydration in individuals with and without ocular disease is warranted.
Clinical performance of two‐piece zirconia implants in the posterior mandible and maxilla: a prospective cohort study over 2 years
Authors: Becker Jürgen , John Gordon , Becker Kathrin , Mainusch Saskia , Diedrichs Gabriele , Schwarz Frank 
Published: May 2015

AbstractObjectivesTo assess the clinical performance of two‐piece zirconium implants over a period of up to 2 years.Material & methodsA total of 52 patients with single‐tooth gaps in the posterior mandible or maxilla received the same type of a two‐piece zirconium implant system with customized heights of the transmucosal aspect. Fibreglass abutments were cemented and restored with fixed all‐ceramic single crowns using a conventional loading protocol. The cumulative survival rate (primary outcome) was calculated according to the life table method, and Kaplan–Meier survival curves were used to estimate the survival function. Covariates (gender, implant position, implant diameter/length, oral surgeon) were tested using log‐rank tests.ResultsA total of two target implants in 2 patients were lost after a functioning time of 8 months. The cumulative survival rate was 95.8%, and the mean survival time amounted to 32.9 months. Log‐rank tests revealed a significant association for the covariate “oral surgeon” (P = 0.047). The Kaplan–Meier estimates of mechanical/technical and biological complications amounted to 2.1% and 37.5%, respectively. All implant sites revealed a marked increase of the vestibular mucosal level and gain of keratinized tissue at 24 months.ConclusionWithin the limitations of a prospective cohort study, it was concluded that this two‐piece zirconium implant/fibreglass abutment system can be successfully used in the clinical indication investigated.
The introduction of buprenorphine‐naloxone film in opioid substitution therapy in Australia: Uptake and issues arising from changing buprenorphine formulations
Authors: Larance Briony , Dietze Paul , Ali Robert , Lintzeris Nicholas , White Nancy , Jenkinson Rebecca , Degenhardt Louisa 
Published: May 2015

AbstractIntroduction and AimsBuprenorphine‐naloxone (BNX) film for opioid dependence treatment was introduced in Australia in 2011. A key difference in State policy approaches saw transfer from BNX tablets to BNX film mandated in South Australia (SA) with New South Wales (NSW) and Victoria (VIC) having less stringent policies. This study examined (i) how initiations and transfers were implemented, (ii) the profile and predictors of adverse effects as self‐reported by BNX film clients, and (iii) dosing issues.Design and MethodsSurvey of 334 buprenorphine (BPN), BNX tablet and BNX film clients and semi‐structured interviews with 39 key experts (KEs) in 2012. Comparisons are made between clients interviewed in SA versus NSW and VIC combined.ResultsAmong the 180 current BNX film clients, 23% started treatment on BNX film, 18% requested a transfer to BNX film and 59% (n = 106) reported their clinic/prescriber recommended transfer to BNX film. Among clients who were offered but refused a transfer to BNX film (n = 66), the most common reason was ‘I am happy with my current treatment and do not see a reason to change’ (53%). Some opioid substitution therapy clients and KE viewed transfers as ‘forced’ (i.e. no choice of buprenorphine formulation). Multivariable regression showed residing in SA (vs. NSW/VIC) and a shorter length of current treatment episode were associated with more BNX film‐attributed adverse effects but clinic/prescriber‐recommended transfer was not.Discussion and ConclusionsThe introduction of BNX film in Australia varied across States. A perception of restricted choice in medication may have undermined initial acceptance in SA. [Larance B, Dietze P, Ali R, Lintzeris N, White N, Jenkinson R, Degenhardt L. The introduction of BNX film in opioid substitution therapy in Australia: Uptake and issues arising from changing buprenorphine formulations. Drug Alcohol Rev 2015;34:603–610]
Gonadal failure is associated with visceral adiposity in myotonic dystrophies
Authors: Passeri Elena , Bugiardini Enrico , Sansone Valeria A. , Pizzocaro Alessandro , Fulceri Cinzia , Valaperta Rea , Borgato Stefano , Costa Elena , Bandera Francesco , Ambrosi Bruno , Meola Giovanni , Persani Luca , Corbetta Sabrina 
Published: May 2015

AbstractBackgroundHypogonadism occurs in myotonic dystrophies type 1 (MD1) and type 2 (MD2). Sertoli and Leydig cell secretions, including insulin‐like peptide‐3 (INSL3), anti‐Müllerian hormone (AMH) and inhibin B, were evaluated in male patients with MD.DesignAcademic settings. Forty‐four male patients with MD [31 MD1, 13 MD2, aged 59 (50–64) years, median (interquartile range)], age‐, sex‐ and BMI‐matched non‐MD hypogonadal patients (n = 14) and healthy controls (n = 32). Serum FSH, LH, inhibin B, AMH, testosterone (T) and INSL3 were measured; fat and muscle masses were evaluated by DEXA.ResultsOvert primary hypogonadism occurred in 29% of patients with MD1 and 46% of patients with MD2. Considering subclinical forms, the prevalence increased to 69% of MD1 and 100% of MD2. A half of patients with MD experienced symptoms. INSL3 levels were unaffected in most patients with MD. By contrast, AMH and inhibin B were reduced in most patients with MD and unrelated to age. Patients with MD showed increased body and visceral fat. Free T levels were negatively predicted by fat mass, and AMH and FSH levels were negatively correlated with waist/hip ratio and fat mass. AMH, inhibin B and FSH levels positively correlated with muscle strength and muscle mass.ConclusionsAMH and inhibin B secretion failures are common in male patients with MD and are more severe than Leydig cell hormones impairment. AMH and inhibin B measurements might provide clinical utility in evaluating fertility in patients with MD. Serum T, AMH and inhibin B productions are negatively influenced by increased fat mass, while AMH and inhibin B might be markers of muscle impairment.
Molecular diagnostics of myeloproliferative neoplasms
Authors: Langabeer Stephen E. , Andrikovics Hajnalka , Asp Julia , Bellosillo Beatriz , Carillo Serge , Haslam Karl , Kjaer Lasse , Lippert Eric , Mansier Olivier , Oppliger Leibundgut Elisabeth , Percy Melanie J. , Porret Naomi , Palmqvist Lars , Schwarz Jiri , McMullin Mary F. , Schnittger Susanne , Pallisgaard Niels , Hermouet Sylvie ,   the MPN&MPNr‐EuroNet
Published: May 2015

AbstractSince the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN‐specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. Whilst many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN‐associated mutations are considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN‐associated mutations, and it therefore appears likely that emerging technologies such as next‐generation sequencing and digital PCR will in the future play an increasing role in the molecular diagnosis of MPN.
Low efficiency IDO2 enzymes are conserved in lower vertebrates, whereas higher efficiency IDO1 enzymes are dispensable
Authors: Yuasa Hajime J. , Mizuno Keiko , Ball Helen J. 
Published: May 2015

Indoleamine 2,3‐dioxygenase (IDO) is a Trp‐degrading enzyme that catalyzes the first step in the kynurenine pathway. Two IDO genes, IDO1 and IDO2, are found in vertebrates and the timing of the gene duplication giving rise to the genes has been controversial. In the present study, we report that several fishes and two turtles also have both IDO1 and IDO2. This represents definitive evidence for the gene duplication occurring before the divergence of vertebrates, with IDO1 having been lost in a number of lower vertebrate lineages. IDO2 enzymes have a relatively low affinity for l‐Trp; however, Anolis carolinensis (lizard) IDO2 has an affinity for l‐Trp comparable to mammalian IDO1 enzymes. We identified a Ser residue located in the distal heme pocket of IDO1 (distal‐Ser) (corresponding to Ser167 of human IDO1) that is conserved in all IDO1 enzymes and the lizard IDO2. This residue is conserved as Thr (distal‐Thr) in other IDO2 enzymes. Biochemical analyses, using IDO variants with either Ser or Thr substitutions, suggest that the distal‐Ser change was crucial for the improvement in affinity for l‐Trp in ancient IDO1. The ancestral IDO1 likely had a ‘moderate’ enzymatic efficiency for l‐Trp, clearly higher than IDO2 but lower than mammalian IDO1. The distal‐Ser of lizard IDO2 bestows a high affinity for l‐Trp, however, this unique IDO2 has a low enzymatic efficiency because of its very low catalytic velocity. Thus, low efficiency IDO2 enzymes have been conserved throughout vertebrate evolution, whereas higher efficiency IDO1 enzymes are dispensable in many lower vertebrate lineages.
Elevated atmospheric [CO2] stimulates sugar accumulation and cellulose degradation rates of rice straw
Authors: Zhu Chunwu , Xu Xi , Wang Dan , Zhu Jianguo , Liu Gang , Seneweera Saman 
Published: May 2015

AbstractRice straw can serve as potential material for bioenergy production. However, the quantitative effects of increasing atmospheric carbon dioxide concentration [CO2] on rice straw quality and the resulting consequences for bioenergy utilization are largely unknown. In this study, two rice varieties, WYJ and LY, that have been shown previously to have a weak and strong stimulatory response to rising [CO2], respectively, were grown with and without additional CO2 at China free‐air carbon dioxide enrichment (FACE) platform. Qualitative and quantitative measurements in response to [CO2] included straw biomass (including leaf, sheath, and stem), the concentration of nonstructural and structural carbohydrates, the syringyl‐to‐guaiacyl (S/G) ratio of lignin, glucose and xylose release from structural carbohydrate, total sugar release by enzymatic saccharification, and sugar yield and the ratio of cellulose and hemicellulose degradation. Elevated [CO2] significantly increased straw biomass and nonstructural carbohydrate contents while enhancing the degraded ratio of structural carbohydrates as indicated by the decreased lignin content and increased S/G ratio. Overall, total sugar yield (g m−2) in rice straw significantly increased by 27.1 and 57% for WYJ and LY at elevated [CO2], respectively. These findings, while preliminary, suggest that rice straw quality and potential biofuel utilization may improve as a function of rising [CO2].
Towards a glacial‐sensitive model of island biogeography
Authors: Fernández‐Palacios José María , Rijsdijk Kenneth F. , Norder Sietze J. , Otto Rüdiger , de Nascimento Lea , Fernández‐Lugo Silvia , Tjørve Even , Whittaker Robert J. 
Published: May 2015

AbstractAlthough the role that Pleistocene glacial cycles have played in shaping the present biota of oceanic islands world‐wide has long been recognized, their geographical, biogeographical and ecological implications have not yet been fully incorporated within existing biogeographical models. Here we summarize the different types of impacts that glacial cycles may have had on oceanic islands, including cyclic changes in climate, shifts in marine currents and wind regimes and, especially, cycles of sea level change. The latter have affected geographical parameters such as island area, isolation and elevation. They have also influenced the configurations of archipelagos via island fusion and fission, and cycles of seamount emergence and submergence. We hypothesize that these sea level cycles have had significant impacts on the biogeographical processes shaping oceanic island biotas, influencing the rates and patterns of immigration and extinction and hence species richness. Here we provide a first step toward the development of a glacial‐sensitive model of island biogeography, representing the tentative temporal evolution of those biogeographical parameters during the last glacial cycle. From this reasoning we attempt to derive predictions regarding the imprint of sea level cycles on genetic, demographic or biogeographical patterns within remote island biotas.
Resident Perceptions of New Urban Tourism: A Neglected Geography of Prejudice
Authors: Dirksmeier Peter , Helbrecht Ilse 
Published: May 2015

AbstractResearch on urban tourism has focused on the search for alternative, authentic, lively, and mundane urban neighbourhoods by visitors. This so‐called new urban tourism is characterised by the increasing quest by tourists for contact with mundane life in ordinary residential quarters. The intrusion of new urban tourism into day‐to‐day life also affects residents' perceptions of visitors, which are prone to become stereotypes and prejudices rather than just perceptions. The paper offers a review of the urban residents' perceptions research literature through the lens of the new urban tourism phenomenon, aligning it with wider geographies of prejudices. Consequently, the paper argues that an understanding of residents' attitudes towards the new urban tourism phenomenon offers a framework through which geographies of prejudices subtly at work in these resident/visitors encounters can be more deeply researched.
Assembling Political Parties
Authors: Page Sam , Dittmer Jason 
Published: May 2015

AbstractThis paper argues for political geographers to reengage with party politics. We review the treatment of political parties in political geography and beyond, finding fault with the purported divide between society and political parties. In contrast, we argue that political parties are necessarily embroiled and enmeshed in and of society, and that assemblage and affect provide potentially vibrant ways to reengage with their importance and meaning. Assemblage theory foregrounds embodied and affective aspects of voters as well as the multiple temporalities that come together to create the election as an event. In order to ground this theoretical argument, we investigate the potentials of an election campaign flyer, as well as suggesting other avenues of study.
Animating the Sacred, Sentient and Spiritual in Post‐Humanist and Material Geographies
Authors: Gergan Mabel Denzin 
Published: May 2015

AbstractMaterialist and post‐humanist scholarship within the discipline has opened up exciting philosophical and theoretical possibilities with which to understand both human and nonhuman worlds. Yet, recent scholarship has been critical of the modern secular tendencies within this approach especially in its lack of engagement with sacred, sentient, and spiritual accounts and experiences. This review draws on perspectives from literary fiction, the subfields of indigenous and religious geographies and disciplines like anthropology, religious studies, and post‐colonial studies to highlight these absences and spaces for meaningful engagement.
Geographical Approaches to Understanding Urban Decline: From Evolutionary Theory to Political Economy…and Back?
Authors: Weaver Russell , Holtkamp Chris 
Published: May 2015

AbstractThis article surveys selected theories of urban growth and decline, from an American shrinking cities perspective, on the backdrop of three key themes. First, urban change is context‐dependent. Second, urban (de)growth processes are multiscalar. And third, growth and shrinkage are not part of a dichotomy but are different realizations of similar underlying processes. Because the relationships between globalization and regional‐ and city‐level urban restructuring tendencies are relatively established in the shrinking cities literature, the present article focuses primarily onsublocaltheoretical approaches. This is intended to uncover insights about the mechanisms and bottom‐up constraints that influence the direction of urban change. The review leads to a proposed framework for understanding how urban neighborhoods (do not) respond to internal or external pressures to change. Notably, the framework is partially derived from efforts that seek to re‐ground the study of urban change in evolutionary theory, which in some ways represents a theoretical turn back toward the earliest (ecological) school of thought on urban decline. However, while earlier evolutionary approaches were acontextual and deterministic, the proposed framework emphasizes that analyzing urban change demands attention to multiple spatial scales and location‐specific features, particularly the distribution of social capital within a city.
Seeds, Agricultural Systems and Socio‐natures: Towards an Actor–Network Theory Informed Political Ecology of Agriculture
Authors: Watts Natasha , Scales Ivan R. 
Published: May 2015

AbstractAgriculture has recently been the subject of considerable research and policy attention. Events such as the 2008 ‘world food price crisis’ and concerns over the future of global food security have led to calls for a ‘New Green Revolution’, with an emphasis on boosting yields through new transgenic crop varieties. However, critics have raised concerns over the growing role of global agribusiness and transnational capital in agriculture, as well as the potential social and ecological impacts of new technologies. An analysis of emerging agricultural trends thus demands a framework that is able to negotiate the complex multi‐scalar interplay between environmental, technological, scientific, political and economic factors. In this paper, we focus on the potential contribution of a synthesis between political ecology and Actor–Network Theory to our understanding of agricultural networks. We review the literature with a view to teasing out key insights and sketching out future research priorities. We focus on questions surrounding power and agency, the political ecology of scale and the role of situated knowledges and practices.
A Review of Volunteered Geographic Information for Disaster Management
Authors: Haworth Billy , Bruce Eleanor 
Published: May 2015

AbstractThe immediacy of locational information requirements and importance of data currency for natural disaster events highlights the value of volunteered geographic information (VGI) in all stages of disaster management, including prevention, preparation, response, and recovery. The practice of private citizens generating online geospatial data presents new opportunities for the creation and dissemination of disaster‐related geographic data from a dense network of intelligent observers. VGI technologies enable rapid sharing of diverse geographic information for disaster management at a fraction of the resource costs associated with traditional data collection and dissemination, but they also present new challenges. These include a lack of data quality assurance and issues surrounding data management, liability, security, and the digital divide. There is a growing need for researchers to explore and understand the implications of these data and data practices for disaster management. In this article, we review the current state of knowledge in this emerging field and present recommendations for future research. Significantly, we note further research is warranted in the pre‐event phases of disaster management, where VGI may present an opportunity to connect and engage individuals in disaster preparation and strengthen community resilience to potential disaster events. Our investigation of VGI for disaster management provides broader insight into key challenges and impacts of VGI on geospatial data practices and the wider field of geographical science.