bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative pharmacogenetic analysis of risk polymorphisms in Caucasian and Vietnamese children with acute lymphoblastic leukemia: prediction of therapeutic outcome?
Authors: Vu Hoang Phuong Thu , Ambroise Jérôme , Dekairelle Anne‐France , Durant Jean‐François , Butoescu Valentina , Dang Chi Vu Luan , Huynh Nghia , Nguyen Tan Binh , Robert Annie , Vermylen Christiane , Gala Jean‐Luc 
Published: August 2014

AimsAcute lymphoblastic leukemia (ALL) is the most common of all paediatric cancers. Aside from predisposing to ALL, polymorphisms could also be associated with poor outcome. Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and/or thiopurine metabolic pathways, i.e. cyclin D1 (CCND1‐G870A), γ‐glutamyl hydrolase (GGH‐C452T), methylenetetrahydrofolate reductase (MTHFR‐C677T and MTHFR‐A1298C), thymidylate synthase promoter (TYMS‐TSER), thiopurine methyltransferase (TPMT*3A and TPMT*3C) and inosine triphosphate pyrophosphatase (ITPA‐C94A), in Caucasian (n = 94, age < 20) and Vietnamese (n = 141, age < 16 years) childhood ALL and (b) to assess the impact of a multilocus genetic risk score (MGRS) on relapse‐free survival (RFS) using a Cox proportional‐hazards regression model.ResultsThe prevalence of MTHFR‐677TT genotype was significantly higher in Caucasians (P = 0.008), in contrast to the prevalence of TYMS‐TSER*3R/3R and ITPA‐94AA/AC genotypes which were significantly higher in Vietnamese (P < 0.001 and P = 0.02, respectively). Compared with children with a low MGRS (≤3), those with a high MGRS (≥4) were 2.06 (95% CI = 1.01, 4.22; P = 0.04) times more likely to relapse. Adding MGRS into a multivariate Cox regression model with race/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC from 0.682 to 0.709 at 24 months).ConclusionIncluding MGRS into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatric ALL. Whether variants on other genes associated with folate metabolism can substantially improve the predictive value of current MGRS is not known but deserves further evaluation.
Model‐based evaluation of drug‐induced QTc prolongation for compounds in early development
Authors: Dubois Vincent F. S. , Yu Huixin , Danhof Meindert , Della Pasqua Oscar ,   Cardiovascular Safety Project Team and TI Pharma PKPD Platform
Published: August 2014

AimsSignificant differences between dogs and humans have been observed in the concentration–QTc effect relationship of compounds with known pro‐arrhythmic properties. These findings suggest that interspecies differences must be considered when evaluating drug effects. The aim of this study was to evaluate the performance of a model‐based approach to assess the risk of QTc prolongation for three investigational compounds (NCE01, NCE02 and NCE03).MethodsPharmacokinetic and pharmacodynamic data from experiments in conscious dogs and healthy subjects were included in this analysis. Pharmacokinetic modelling and deconvolution methods were applied to derive drug concentrations at the time of each QT measurement. An integrated pharmacokinetic–pharmacodynamic (PKPD) model was then used to describe QT prolongation. A threshold of ≥10 ms was used to characterize the probability of QTc prolongation.ResultsThe PKPD relationships of all three compounds were successfully described in both species. A strong effect was observed after administration of NCE01 to dogs and humans, with a slope of 0.0061 and 0.0662 ms nm−1, respectively, and maximal probability of QTc prolongation ≥10 ms at peak concentration. For NCE02 and NCE03, QTc‐shortening and borderline QT effects were observed both in dogs and humans, as described by negative or very shallow slopes (NCE02, −0.00098 and −0.01 ms nm−1; NCE03, 0.00064 and −0.0002 ms nm−1).ConclusionsWhilst NEC01 shows clear pro‐arrhythmic effects, the liability for QT/QTc prolongation for NCE02 and NCE03 can be deemed low at the expected therapeutic exposure. Moreover, our results show the advantages of an integrated PKPD approach as the basis for translating pro‐arrhythmic effects from dogs to humans.
Terminology and quantification of environmental heterogeneity in species‐richness research
Authors: Stein Anke , Kreft Holger 
Published: August 2014

ABSTRACTSpatial environmental heterogeneity (EH) is an important driver of species diversity, and its influence on species richness has been analysed for numerous taxa, in diverse ecological settings, and over a large range of spatial scales. The variety and ambiguity of concepts and terminology, however, have hampered comparisons among studies. Based on a systematic literature survey of 192 studies including 1148 data points, we provide an overview of terms and measures related to EH, and the mechanisms that relate EH to species richness of plants and animals in terrestrial systems. We identify 165 different measures used to quantify EH, referred to by more than 350 measure names. We classify these measures according to their calculation method and subject area, finding that most studies have analysed heterogeneity in land cover, topography, and vegetation, whereas comparatively few studies have focused on climatic or soil EH. Overall, elevation range emerged as the most frequent measure in our dataset. We find that there is no consensus in the literature about terms (such as ‘habitat diversity’ or ‘habitat complexity’), their meanings and associated quantification methods. More than 100 different terms have been used to denote EH, with largely imprecise delimitations. We reveal trends in use of terms and quantification with respect to spatial scales, study taxa, and locations. Finally, we discuss mechanisms involved in EH–richness relationships, differentiating between effects on species coexistence, persistence, and diversification. This review aims at guiding researchers in their selection of heterogeneity measures. At the same time, it shows the need for precise terminology and avoidance of ambiguous synonyms to enhance understanding and foster among‐study comparisons and synthesis.
Effects of adenoid/tonsillectomy on inflammatory response in snoring children with witnessed apnoea
Authors: Mutlu M. , Vuralkan E. , Yardim Akaydin S. , Akin I. , Miser E. 
Published: August 2014

ObjectiveThe aim of this study was to investigate the clinical significance of preoperative serum C‐reactive protein (CRP), interleukin‐6 (IL‐6), fetuin‐A, cystatin C, adiponectin and tumour necrosis factor‐alpha (TNF‐α) levels in children with adenoid/tonsillar hypertrophy and compare these results with postoperative values.Study designProspective clinical trial.SettingSingle tertiary care centre.ParticipantsThirty‐five children (14 boys and 21 girls) participated in this study.Main outcome measuresThe operations were performed with the indication of sleep‐disordered breathing (SDB). Blood samples were taken preoperatively and at 6 months postoperatively to determine the changes in serum high‐sensitivity CRP (hs‐CRP), IL‐6, fetuin‐A, cystatin C, adiponectin and TNF‐α levels. Pre‐ and postoperative values of body weights and heights of the participants were recorded preoperatively and at postoperative 6 months.ResultsPatients underwent adenoidectomy (n = 21) or adenotonsillectomy (n = 21). The mean age at surgery was 8.74 ± 3.33 years (range 3–16 years). Mean serum levels of parameters measured preoperatively and at postoperative 6 months. The observed differences between pre‐ and postoperative values were statistically significant (P < 0.05), excluding cystatin C levels (P > 0.05).ConclusionHigh levels of IL‐6, hs‐CRP and TNF‐α and low levels of fetuin‐A in serum might have a clinical significance in patients with sleep‐disordered breathing. Levels of cytokines in children with sleep‐disordered breathing because of adenotonsillar disease decreased after surgical treatment. The risks of development of cardiovascular disease are decreased in association with lower levels of cytokines, which are also closely associated with many disease states.
Understanding the sources and effects of abandoned, lost, and discarded fishing gear on marine turtles in northern Australia
Authors: Wilcox Chris , Heathcote Grace , Goldberg Jennifer , Gunn Riki , Peel David , Hardesty Britta Denise 
Published: August 2014

AbstractGlobally, 6.4 million tons of fishing gear are lost in the oceans annually. This gear (i.e., ghost nets), whether accidently lost, abandoned, or deliberately discarded, threatens marine wildlife as it drifts with prevailing currents and continues to entangle marine organisms indiscriminately. Northern Australia has some of the highest densities of ghost nets in the world, with up to 3 tons washing ashore per kilometer of shoreline annually. This region supports globally significant populations of internationally threatened marine fauna, including 6 of the 7 extant marine turtles. We examined the threat ghost nets pose to marine turtles and assessed whether nets associated with particular fisheries are linked with turtle entanglement by analyzing the capture rates of turtles and potential source fisheries from nearly 9000 nets found on Australia's northern coast. Nets with relatively larger mesh and smaller twine sizes (e.g., pelagic drift nets) had the highest probability of entanglement for marine turtles. Net size was important; larger nets appeared to attract turtles, which further increased their catch rates. Our results point to issues with trawl and drift‐net fisheries, the former due to the large number of nets and fragments found and the latter due to the very high catch rates resulting from the net design. Catch rates for fine‐mesh gill nets can reach as high as 4 turtles/100 m of net length. We estimated that the total number of turtles caught by the 8690 ghost nets we sampled was between 4866 and 14,600, assuming nets drift for 1 year. Ghost nets continue to accumulate on Australia's northern shore due to both legal and illegal fishing; over 13,000 nets have been removed since 2005. This is an important and ongoing transboundary threat to biodiversity in the region that requires attention from the countries surrounding the Arafura and Timor Seas.Entender las Fuentes y Efectos de Equipo de Pesca Abandonado, Perdido y Desechado sobre las Tortugas Marinas del Atlántico Norte
Accounting for enforcement costs in the spatial allocation of marine zones
Authors: Davis Katrina , Kragt Marit , Gelcich Stefan , Schilizzi Steven , Pannell David 
Published: August 2014

AbstractMarine fish stocks are in many cases extracted above sustainable levels, but they may be protected through restricted‐use zoning systems. The effectiveness of these systems typically depends on support from coastal fishing communities. High management costs including those of enforcement may, however, deter fishers from supporting marine management. We incorporated enforcement costs into a spatial optimization model that identified how conservation targets can be met while maximizing fishers’ revenue. Our model identified the optimal allocation of the study area among different zones: no‐take, territorial user rights for fisheries (TURFs), or open access. The analysis demonstrated that enforcing no‐take and TURF zones incurs a cost, but results in higher species abundance by preventing poaching and overfishing. We analyzed how different enforcement scenarios affected fishers’ revenue. Fisher revenue was approximately 50% higher when territorial user rights were enforced than when they were not. The model preferentially allocated area to the enforced‐TURF zone over other zones, demonstrating that the financial benefits of enforcement (derived from higher species abundance) exceeded the costs. These findings were robust to increases in enforcement costs but sensitive to changes in species’ market price. We also found that revenue under the existing zoning regime in the study area was 13–30% lower than under an optimal solution. Our results highlight the importance of accounting for both the benefits and costs of enforcement in marine conservation, particularly when incurred by fishers.Justificación de los Costos de Aplicación en la Asignación Espacial de Zonas Marinas
The challenge of implementing the European network of protected areas Natura 2000
Authors: Kati Vassiliki , Hovardas Tasos , Dieterich Martin , Ibisch Pierre L. , Mihok Barbara , Selva Nuria 
Published: August 2014

AbstractEstablished under the European Union (EU) Birds and Habitats Directives, Natura 2000 is one of the largest international networks of protected areas. With the spatial designation of sites by the EU member states almost finalized, the biggest challenge still lying ahead is the appropriate management of the sites. To evaluate the cross‐scale functioning of Natura 2000 implementation, we analyzed 242 questionnaires completed by conservation scientists involved in the implementation of Natura 2000 in 24 EU member states. Respondents identified 7 key drivers of the quality of Natura 2000 implementation. Ordered in decreasing evaluation score, these drivers included: network design, use of external resources, legal frame, scientific input, procedural frame, social input, and national or local policy. Overall, conservation scientists were moderately satisfied with the implementation of Natura 2000. Tree modeling revealed that poor application of results of environmental impact assessments (EIA) was considered a major constraint. The main strengths of the network included the substantial increase of scientific knowledge of the sites, the contribution of nongovernmental organizations, the adequate network design in terms of area and representativeness, and the adequacy of the EU legal frame. The main weaknesses of Natura 2000 were the lack of political will from local and national governments toward effective implementation; the negative attitude of local stakeholders; the lack of background knowledge of local stakeholders, which prevented well‐informed policy decisions; and the understaffing of Natura 2000 management authorities. Top suggestions to improve Natura 2000 implementation were increase public awareness, provide environmental education to local communities, involve high‐quality conservation experts, strengthen quality control of EIA studies, and establish a specific Natura 2000 fund.El Reto de Implementar la Red Europea de Áreas Protegidas Natura 2000
Interactive Activation and Mutual Constraint Satisfaction in Perception and Cognition
Authors: McClelland James L. , Mirman Daniel , Bolger Donald J. , Khaitan Pranav 
Published: August 2014

AbstractIn a seminal 1977 article, Rumelhart argued that perception required the simultaneous use of multiple sources of information, allowing perceivers to optimally interpret sensory information at many levels of representation in real time as information arrives. Building on Rumelhart's arguments, we present the Interactive Activation hypothesis—the idea that the mechanism used in perception and comprehension to achieve these feats exploits an interactive activation process implemented through the bidirectional propagation of activation among simple processing units. We then examine the interactive activation model of letter and word perception and the TRACE model of speech perception, as early attempts to explore this hypothesis, and review the experimental evidence relevant to their assumptions and predictions. We consider how well these models address the computational challenge posed by the problem of perception, and we consider how consistent they are with evidence from behavioral experiments. We examine empirical and theoretical controversies surrounding the idea of interactive processing, including a controversy that swirls around the relationship between interactive computation and optimal Bayesian inference. Some of the implementation details of early versions of interactive activation models caused deviation from optimality and from aspects of human performance data. More recent versions of these models, however, overcome these deficiencies. Among these is a model called the multinomial interactive activation model, which explicitly links interactive activation and Bayesian computations. We also review evidence from neurophysiological and neuroimaging studies supporting the view that interactive processing is a characteristic of the perceptual processing machinery in the brain. In sum, we argue that a computational analysis, as well as behavioral and neuroscience evidence, all support the Interactive Activation hypothesis. The evidence suggests that contemporary versions of models based on the idea of interactive activation continue to provide a basis for efforts to achieve a fuller understanding of the process of perception.
Chitosan as a biocontrol agent against the pinewood nematode (Bursaphelenchus xylophilus)
Authors: Nunes da Silva M. , Cardoso A. R. , Ferreira D. , Brito M. , Pintado M. E. , Vasconcelos M. W. 
Published: August 2014

SummaryThe pine wilt disease (PWD) is caused by Bursaphelenchus xylophilus and poses great environmental and economic challenges. Thus, the development of sustainable techniques for the control of this epidemic disease is of major importance. This work aimed at evaluating if the application of different molecular weight (MW) chitosans as a soil amendment could be used to control the PWD in maritime pine (Pinus pinaster, very susceptible to the disease) and stone pine (Pinus pinea, less susceptible). At the end of the experimental period (24 days after inoculation), P. pinaster and P. pinea untreated plants presented ca. 3825 ± 100 and 70 ± 47 nematodes, respectively. In P. pinaster, the high‐MW chitosan prompted the most drastic results, inducing a 21.9‐fold reduction in nematodes numbers, whereas in P. pinea, the most effective was the low MW chitosan, which reduced nematodes numbers up to 7‐fold, compared with untreated plants. P. pinea seems to be highly resistant to the disease, presenting nematode numbers up to 54.6‐fold lower than P. pinaster and less severe chlorophyll loss (ca. 2‐fold).
Supporting dementia patients and their caregivers in daily life challenges: review of physical, cognitive and psychosocial intervention studies
Authors: Nehen H. ‐G. , Hermann D. M. 
Published: August 2014

Background and purposeDementia is associated with multiple daily life challenges that have a major impact for health outcome, affecting both the patients and their caregivers. In this review, the efficacy of physical, cognitive and psychosocial interventions in the treatment of dementia patients is evaluated, and how caregiver education and support may contribute to patient care is analysed.Results and conclusionsDue to the complex nature of cognitive and psychosocial interventions, their efficacy depends strongly on local settings. Thus, active components of these interventions are not always obvious, even in controlled randomized trials. Successful patient management includes (i) the safekeeping of basic support, (ii) the provision of a stable external milieu that is adjusted to the patients' cognitive resources and (iii) the provision of multimodal therapeutic concepts that are closely adapted to the practical needs of the patients and caregivers.
Hindlimb lameness associated with proximal suspensory desmopathy and injury of the accessory ligament of the suspensory ligament in five horses
Authors: Dyson S. 
Published: August 2014

SummaryThe accessory ligament of the hindlimb suspensory ligament arises from the plantar aspect of the calcaneus and fourth tarsal bones and blends with the suspensory ligament in the proximal aspect of the metatarsus. The accessory ligament of the suspensory ligament of both hindlimbs of 12 mature horses, with no history of hindlimb lameness, was assessed ultrasonographically. The ligament comprised linear parallel echoes which were consistently shorter than those of the lateral digital flexor tendon; the dorsal and plantar borders were parallel. Lameness associated with injury of the accessory ligament of the suspensory ligament was identified in 6 of 8 lame hindlimbs of 5 horses, unilaterally in 4 horses and bilaterally in one horse. In all horses there was concurrent proximal suspensory desmopathy. There was localised oedematous swelling on the distal medial aspect of the chestnut extending distally in 2 horses. Lameness was best identified when the horses were ridden. Perineural analgesia of the deep branch of the lateral plantar nerve abolished lameness in 3 horses but perineural analgesia of the tibial nerve was required to abolish lameness in the hindlimb with injury of the accessory ligament of the suspensory ligament in 2 horses. Injury of the accessory ligament of the suspensory ligament was characterised by marked decrease in echogenicity of the ligament and loss of parallel alignment of the linear echoes, which were shorter than normal in longitudinal images.
Review of the biology and control of Oxyuris equi
Authors: Reinemeyer C. R. , Nielsen M. K. 
Published: August 2014

SummaryOxyuris equi is a well‐known equine parasite that has evolved over time from an easily controlled, minor nuisance into an increasingly prevalent pest that may frustrate even the most intensive management efforts. This paper reviews essential features of the biology, epidemiology, pathology, diagnosis and control of Oxyuris infections, and describes the current status of recent biological adaptations.
Diagnosis and treatment of biaxial keratomas in the left fore foot of a 15‐year‐oldClydesdale mare
Authors: Rowland A. L. , Goodrich L. R. , Bass L. D. , Aldrich E. D. , Edmondson E. F. , Mueller L. W. 
Published: August 2014

SummaryA 15‐year‐oldClydesdale mare presented for further diagnostics and treatment of waxing and waning lameness and recurrent subsolar abscesses. Radiographs and computed tomography revealed biaxial masses extending from the hoof capsule, causing bone resorption of the distal phalanx. Surgery was performed to remove the masses and post operative care included regional limb perfusions, systemic antibiotics and therapeutic shoeing. Histopathology was consistent with the diagnosis of keratoma for each of the masses; this is the first case of confirmed biaxial keratomas. Two months after surgery the horse is sound at the walk and is expected to return to full function within the next year.