bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cost‐effectiveness of dapagliflozin versus sulfonylurea as an add‐on to metformin in the treatment of Type 2 diabetes mellitus
Authors: Charokopou M. , McEwan P. , Lister S. , Callan L. , Bergenheim K. , Tolley K. , Postema R. , Townsend R. , Roudaut M. 
Published: March 2015

AbstractAimsTo assess the cost‐effectiveness of dapagliflozin, a sodium–glucose co‐transporter–2 (SGLT–2) inhibitor, compared with a sulfonylurea, when added to metformin for treatment of UK people with Type 2 diabetes mellitus inadequately controlled on metformin alone.MethodsClinical inputs sourced from a head‐to‐head randomized controlled trial (RCT) informed the Cardiff diabetes decision model. Risk equations developed from the United Kingdom Prospective Diabetes Study (UKPDS) were used in conjunction with the clinical inputs to predict disease progression and the incidence of micro‐ and macrovascular complications over a lifetime horizon. Cost and utility data were generated to present the incremental cost‐effectiveness ratio (ICER) for both treatment arms, and sensitivity and scenario analyses were conducted to assess the impact of uncertainty on the final model results.ResultsThe dapagliflozin treatment arm was associated with a mean incremental benefit of 0.467 quality‐adjusted life years (QALYs) [95% confidence interval (CI): 0.420; 0.665], with an incremental cost of £1246 (95% CI: £613; £1637). This resulted in an ICER point estimate of £2671 per QALY gained. Incremental costs were shown to be insensitive to parameter variation, with only treatment‐related weight change having a significant impact on the incremental QALYs. Probabilistic sensitivity analysis determined that dapagliflozin had a 100% probability of being cost‐effective at a willingness‐to‐pay threshold of £20 000 per QALY.ConclusionsDapagliflozin in combination with metformin was shown to be a cost‐effective treatment option compared with sulfonylurea from a UK healthcare perspective for people with Type 2 diabetes mellitus who are inadequately controlled on metformin monotherapy.
How sampling influences the statistical power to detect changes in abundance: an application to river restoration
Authors: Vaudor Lise , Lamouroux Nicolas , Olivier Jean‐Michel , Forcellini Maxence 
Published: March 2015

Summary

Assessing how populations respond to ecological restoration is particularly difficult because their abundance results from many sources of variation. In addition, abundance estimates depend on sampling efforts that are limited by financial or practical constraints.

We used local abundance counts from the Rhône river restoration monitoring programme to quantify how sampling strategies and population characteristics influenced statistical power for detecting restoration effects.

We first fitted observed changes in abundance of 13 fish taxa and 35 invertebrate taxa collected in microhabitats of four restored reaches of the Rhône river over 15 years, using a generalised linear mixed model. The model accounted for a restoration effect, random temporal variation between field surveys and spatial variation within surveys (i.e. microhabitat variation in abundance was assumed to follow a negative binomial distribution). We then used numerical simulations to calculate the statistical power (i.e. the probability of detecting a true change) and the type I error (the probability of detecting a non‐existent change) associated with various hypotheses of restoration effect size, mean abundance and temporal and spatial variation.

Model fits revealed that accounting for temporal variation is needed to reduce type I error associated with the effect of restoration. Significant abundance changes were observed for 27 of 104 (26%) of the taxa‐reach combinations.

When assuming temporal variation and population characteristics typical of our data sets, power simulations showed that the probability of detecting a moderate change (50–200%) in abundance was <38% in all tests. The average probability of detecting large changes (500–1000%) was 61%. In these conditions, power was increased by low spatial variation and high sampling effort. Large numbers of surveys (e.g. 16 instead of 4) increased the power by 20 points if surveys were balanced before and after restoration.

Because our simulations covered a wide variety of population characteristics and sampling strategies, they can be used a priori to determine which sampling strategy is best adapted for detecting restoration effects from repeated abundance counts.
The ecological restoration of large rivers needs science‐based, predictive tools meeting public expectations: an overview of the Rhône project
Authors: Lamouroux Nicolas , Gore James A. , Lepori Fabio , Statzner Bernhard 
Published: March 2015

Summary

Effective environmental management needs models that reliably predict quantitative ecological changes as a function of restoration effort (e.g. cost) and meet expectations of stakeholders. Principal threats to large rivers are linked to human‐caused modifications of discharge and morphology of channels and floodplains. However, comprehensive large‐scale tests of the reliability of models predicting ecological consequences of restoring these elements are still lacking.

Following a governmental decision, water managers, local authorities and the ‘Compagnie Nationale du Rhône’ financed a scientific programme to develop, test and subsequently use predictive models to assess the restoration (particularly minimum flow increases and reconnections of floodplain channels with the main channel) of eight regulated reaches of the French Rhône River. This approach was fostered by (i) the existence of local initiatives aimed at the ecological improvement of the Rhône; (ii) a history of interactions based on trust among stakeholders; and (iii) knowledge provided by a large interdisciplinary research group that studied the Rhône for two decades before the programme started in 1998.

This Special Issue synthesises the insights gained over recent decades of research during which four river reaches (total length 47 km) were restored since 1999. It contains 11 articles including this overview. One article relates physical habitats in the floodplain to river hydrology and morphology; five articles test predictive models linking changes in habitat conditions to changes in taxa abundance, community metrics and biological traits of macroinvertebrates and fish; and four articles address the effects of restoration in larger contexts (long‐term community trends, optimisation of sampling strategies, social processes and bioindication).

We describe the Rhône restoration project, explain the conceptual framework used to predict the effects of restoration on river biota and describe the contents of the Special Issue, the main results and their implications.

The Rhône restoration led to more lotic and diverse aquatic communities and renewed social links with the river. When reliable pre‐restoration data are available, simple habitat models can be used to predict quantitative ecological changes as a function of restoration effort. The project illustrates the need to describe changes in hydraulic conditions in studies of physical river restoration and shows the effort required for a powerful assessment of restoration effects.
Optical Evaluation of In Situ Crack Propagation by Using Mechanoluminescence of SrAl2O4:Eu2+, Dy3+
Authors: Timilsina Suman , Lee Kwang Ho , Kwon Yong Nam , Kim Ji Sik 
Published: March 2015

New theoretical solutions involving conventional crack propagation from static to dynamic fracture in terms of mechanoluminescence (ML) and the experimental techniques to trace the in situ crack and its instantaneous stress intensity factor (SIF) have been suggested in SrAl2O4:Eu2+, Dy3+ (SAO). The direct optical method to determine the moving crack tip on behalf of ML was verified by indirect crack mouth opening displacement (CMOD). The mode I SIF calculated from the instantaneous cumulative ML fringes showed proper agreement with the SIFs and acquired from conventional ASTM E‐399 measurements under quasidynamic condition. The magnitude and shape of the theoretically predicted crack tip stress field was in accordance with the experimental in situ ML evidence while determining the quasidynamic SIF from the cumulative ML intensity. Therefore, the use of ML technology could be one of the possible substitutive and substantial alternatives for structural health monitoring systems due to its simplicity but effectiveness in detecting arrested or propagating crack tips and in assessing the instantaneous structural integrity by means of the ML fracture parameters.
Hypercoagulability in Dogs with Blastomycosis
Authors: McMichael M.A. , O'Brien M. , Smith S.A. 
Published: March 2015

BackgroundBlastomycosis is a potentially fatal fungal disease that most commonly affects humans and dogs. The organism causes systemic inflammation and has a predilection for the lungs. The inflammation might lead to a hypercoagulable state with microemboli in the pulmonary circulation which could contribute to inadequate oxygen exchange in infected dogs.Hypothesis/ObjectivesDogs with blastomycosis will be hypercoagulable compared with healthy case‐matched controls.AnimalsClient‐owned dogs with a diagnosis of blastomycosis (n = 23) and healthy case‐matched controls (n = 23).MethodsProspective case‐controlled study of client‐owned dogs presented to a veterinary teaching hospital with clinical signs compatible with blastomycosis. Complete blood counts, fibrinogen,PT,aPTT, thromboelastometry (TE), thrombin antithrombin complexes (TAT), and thrombin generation were evaluated.ResultsCases had a leukocytosis compared with controls [mean (SD) 16.6 (7.6) × 103/μL versus 8.2 (1.8) × 103/μL,P < .001], hyperfibrinogenemia [median 784 mg/dL, range 329–1,443 versus median 178 mg/dL, range 82–257,P < .001], and increasedTATconcentrations [mean (SD) 9.0 (5.7) μg/L versus 2.0 (2.8) μg/L,P < .001]. As compared to controls, cases were also hypercoagulable as evaluated by thromboelastometry and had increased in vitro thrombin generation on calibrated automated thrombography.Conclusions and Clinical ImportanceHypercoagulability occurs in dogs with systemic blastomycosis. Additional studies are needed to explore a possible contribution of thrombogenicity to the clinical manifestations of systemic blastomycosis.
Quantitative Physicochemical Analysis of Acid‐Base Balance and Clinical Utility of Anion Gap and Strong Ion Gap in 806 Neonatal Calves with Diarrhea
Authors: Trefz F.M. , Constable P.D. , Lorenz I. 
Published: March 2015

BackgroundAcid‐base abnormalities in neonatal diarrheic calves can be assessed by using the Henderson‐Hasselbalch equation or the simplified strong ion approach which use the anion gap (AG) or the strong ion gap (SIG) to quantify the concentration of unmeasured strong anions such asd‐lactate.Hypothesis/ObjectivesTo determine and compare the clinical utility ofAGandSIGin quantifying the unmeasured strong anion charge in neonatal diarrheic calves, and to examine the associations between biochemical findings and acid‐base variables by using the simplified strong ion approach. We hypothesized that theSIGprovides a more accurate prediction of unmeasured strong anions than theAG.AnimalsEight hundred and six neonatal diarrheic calves admitted to a veterinary teaching hospital.MethodsRetrospective study utilizing clinicopathologic findings extracted from medical records.ResultsHyperphosphatemia was an important predictor of venous bloodpH. Serum inorganic phosphorus and plasmad‐lactate concentrations accounted for 58% of the variation in venous bloodpHand 77% of the variation inAGandSIG. Plasmad‐ and total lactate concentrations were slightly better correlated withSIG(rs = −0.69; −0.78) than toAG(rs = 0.63; 0.74).Conclusions and Clinical ImportanceStrong ion gap is slightly better at quantifying the unmeasured strong anion concentration in neonatal diarrheic calves thanAG. Phosphorus concentrations should be included as part of the calculation ofAtotwhen applying the simplified strong ion approach to acid‐base balance to critically ill animals with hyperphosphatemia.
Polo‐like kinase 3 is associated with improved overall survival in cholangiocarcinoma
Authors: Juntermanns Benjamin , Sydor Svenja , Kaiser Gernot M. , Jaradat Derar , Mertens Joachim C. , Sotiropoulos Georgios C. , Swoboda Sandra , Neuhaus Jan P. , Meng Wei , Mathé Zoltan , Baba Hideo A. , Canbay Ali , Paul Andreas , Fingas Christian D. 
Published: March 2015

AbstractBackground & AimsCholangiocarcinomas (CCA) paradoxically express the death ligand TRAIL and thus, are dependent on effective survival signals to circumvent apoptosis. Hedgehog signalling exerts major survival signals in CCA by regulating serine/threonine kinase polo‐like kinase (PLK)2. We here aimed to examine the role of PLK1/2/3 expression for CCA tumour biology.MethodsWe employed CCA samples from 73 patients and human HUCCT–1/Mz–CHA1/KMCH‐1 CCA cells. Immunohistochemistry for PLK1/2/3 was performed using tissue microarrays from representative tumour areas.ResultsPLK1/2/3‐immunoreactive cancer cells were present in most of the CCA samples. However, only PLK1 and especially PLK3 were expressed in higher amounts within CCA cells as compared to normal liver. Given that fibroblast growth factor (FGF) can induce PLK3 expression and also is present in CCA, we examined the effect of FGF on PLK3 in vitro. Indeed, rhFGF rapidly increased PLK3 mRNA expression all three CCA cell lines giving an explanation for the abundant PLK3 presence in the tissue samples. Clinicopathologically, PLK3 expression was associated with decreased tumour cell migration and lymph/blood vessel infiltration whereas higher levels of PLK1 were correlated with larger tumour sizes. Moreover, strong PLK3 expression was associated with prolonged overall survival.ConclusionsThe results suggest that PLK3 predominantly is expressed in CCA cells and that high PLK3 expression correlates with prolonged overall survival. These observations might have implications for prognosis prediction of human CCA as well as the potential therapeutic use of polo‐like kinase inhibitors (i.e., PLK1/2 specifity).
Habitat fragmentation in coastal southern California disrupts genetic connectivity in the cactus wren (Campylorhynchus brunneicapillus)
Authors: Barr Kelly R. , Kus Barbara E. , Preston Kristine L. , Howell Scarlett , Perkins Emily , Vandergast Amy G. 
Published: March 2015

AbstractAchieving long‐term persistence of species in urbanized landscapes requires characterizing population genetic structure to understand and manage the effects of anthropogenic disturbance on connectivity. Urbanization over the past century in coastal southern California has caused both precipitous loss of coastal sage scrub habitat and declines in populations of the cactus wren (Campylorhynchus brunneicapillus). Using 22 microsatellite loci, we found that remnant cactus wren aggregations in coastal southern California comprised 20 populations based on strict exact tests for population differentiation, and 12 genetic clusters with hierarchical Bayesian clustering analyses. Genetic structure patterns largely mirrored underlying habitat availability, with cluster and population boundaries coinciding with fragmentation caused primarily by urbanization. Using a habitat model we developed, we detected stronger associations between habitat‐based distances and genetic distances than Euclidean geographic distance. Within populations, we detected a positive association between available local habitat and allelic richness and a negative association with relatedness. Isolation‐by‐distance patterns varied over the study area, which we attribute to temporal differences in anthropogenic landscape development. We also found that genetic bottleneck signals were associated with wildfire frequency. These results indicate that habitat fragmentation and alterations have reduced genetic connectivity and diversity of cactus wren populations in coastal southern California. Management efforts focused on improving connectivity among remaining populations may help to ensure population persistence.
The Ibāḍī Approach to the Methodology of Qur'anic Exegesis
Authors: Albayrak İsmail , al‐Shueili Sulayman 
Published: March 2015

AbstractIn recent times, research on the Ibāḍī tradition by both Muslim and non‐Muslim scholars has increased, but has not yet shed light on the wider significance of this tradition. While the primary focus of researchers has been on the Ibāḍī tradition as a school of thought, its important contribution to various Islamic disciplines is still neglected. For this reason, there is a serious need for a comprehensive study of the Ibāḍī works on Islam, especially as new manuscripts are continually being discovered. When we look at Ibāḍī Islamic literature in general and compare Ibāḍī jurisprudence and theology, we realise that the poorest and most unexplored field of study consists of the Ibāḍī works on exegesis (tafsīr). The once inaccessible and insufficient amount of Ibāḍī sources and materials may have accounted for this lack of interest; however, today, materials related to Ibāḍī exegesis and understanding are becoming available. In this article, we focus on the methodology of Qur'anic exegesis with reference to commentators from the Ibāḍī tradition. As far as we know, this paper is a first in this field of research, and will discuss the primary features of the Ibāḍī method, its similarities to and differences from other exegetical approaches, and its original contributions.
Neonatal sepsis in a rapidly growing, tertiary neonatal intensive care unit: Trends over 18 years
Authors: Heo Ju Sun , Shin Seung Han , Jung Young Hwa , Kim Ee‐Kyung , Choi Eun Hwa , Kim Han‐Suk , Lee Hoan Jong , Choi Jung‐Hwan 
Published: March 2015

AbstractBackgroundWe investigated changes in the admission patterns of neonatal intensive care units and the epidemiology of neonatal sepsis following the rapid expansion and improvements in neonatal intensive care.MethodsData on the admission of neonates with culture‐proven sepsis between 1996 and 2013 (period I, 1996–2005; period II, 2006–2013) were collected retrospectively.ResultsThe admission of extremely low‐birthweight (ELBW) infants increased between periods I and II (11.1 vs 28.7 infants per 1000 live births, P < 0.001). The survival rate of the ELBW infants improved (57.5 vs 80.1%, P < 0.001), and duration of hospital stay increased (median, 64 vs 80 days, P = 0.001). The incidence of sepsis among all infants and ELBW infants increased (all infants, 5.9 vs 12.7 cases per 1000 live births; ELBW infants, 189.5 vs 290.1 cases per 1000 live births). In ELBW infants, the incidence of sepsis caused by coagulase‐negative Staphylococcus (CONS), significantly increased during period II (8.8 vs 25.4%, P = 0.039). On multivariate analysis, central vascular catheters and prolonged hospitalization were independently associated with increased sepsis rate, particularly CONS in ELBW infants.ConclusionsThe inborn admission rate for ELBW infants has increased significantly and is accompanied by improved survival and longer hospital stay. The incidence of neonatal sepsis, particularly in ELBW infants, has also increased, and CONS has emerged as a major pathogen. Central vascular catheters and prolonged hospitalization could be independent risk factors for the increased sepsis rate, particularly sepsis due to CONS.
Supernatants from stored red blood cell (RBC) units, but not RBC‐derived microvesicles, suppress monocyte function in vitro
Authors: Muszynski Jennifer A. , Bale Justin , Nateri Jyotsna , Nicol Kathleen , Wang Yijie , Wright Valerie , Marsh Clay B. , Gavrilin Mikhail A. , Sarkar Anasuya , Wewers Mark D. , Hall Mark W. 
Published: March 2015

BACKGROUNDWe have previously shown that critically ill children transfused with red blood cells (RBCs) of longer storage durations have more suppressed monocyte function after transfusion compared to children transfused with fresher RBCs and that older stored RBCs directly suppress monocyte function in vitro, through unknown mechanisms. We hypothesized that RBC‐derived microvesicles (MVs) were responsible for monocyte suppression.STUDY DESIGN AND METHODSTo determine the role of stored RBC unit–derived MVs, we cocultured monocytes with supernatants, isolated MVs, or supernatants that had been depleted of MVs from prestorage leukoreduced RBCs that had been stored for either 7 or 30 days. Isolated MVs were characterized by electron microscopy and flow cytometry. Monocyte function after coculture experiments was measured by cytokine production after stimulation with lipopolysaccharide (LPS).RESULTSMonocyte function was suppressed after exposure to supernatants from 30‐day RBC units compared to monocytes cultured in medium alone (LPS‐induced tumor necrosis factor‐α production, 17,611 ± 3,426 vs. 37,486 ± 5,598 pg/mL; p = 0.02). Monocyte function was not suppressed after exposure to MV fractions. RBC supernatants that had been depleted of MVs remained immunosuppressive. Treating RBC supernatants with heat followed by RNase (to degrade protein‐bound RNA) prevented RBC supernatant–induced monocyte suppression.CONCLUSIONOur findings implicate soluble mediators of stored RBC‐induced monocyte suppression outside of MV fractions and suggest that extracellular protein‐bound RNAs (such as microRNA) may play a role in transfusion‐related immunomodulation.
Fiber‐optic detector for real time dosimetry of a micro‐planar x‐ray beam
Authors: Belley Matthew D. , Stanton Ian N. , Hadsell Mike , Ger Rachel , Langloss Brian W. , Lu Jianping , Zhou Otto , Chang Sha X. , Therien Michael J. , Yoshizumi Terry T. 
Published: March 2015

Purpose:Here, the authors describe a dosimetry measurement technique for microbeam radiation therapy using a nanoparticle‐terminated fiber‐optic dosimeter (nano‐FOD).Methods:The nano‐FOD was placed in the center of a 2 cm diameter mouse phantom to measure the deep tissue dose and lateral beam profile of a planar x‐ray microbeam.Results:The continuous dose rate at the x‐ray microbeam peak measured with the nano‐FOD was 1.91 ± 0.06 cGy s−1, a value 2.7% higher than that determined via radiochromic film measurements (1.86 ± 0.15 cGy s−1). The nano‐FOD‐determined lateral beam full‐width half max value of 420 μm exceeded that measured using radiochromic film (320 μm). Due to the 8° angle of the collimated microbeam and resulting volumetric effects within the scintillator, the profile measurements reported here are estimated to achieve a resolution of ∼0.1 mm; however, for a beam angle of 0°, the theoretical resolution would approach the thickness of the scintillator (∼0.01 mm).Conclusions:This work provides proof‐of‐concept data and demonstrates that the novel nano‐FOD device can be used to perform real‐time dosimetry in microbeam radiation therapy to measure the continuous dose rate at the x‐ray microbeam peak as well as the lateral beam shape.