bluuebunny/crossref_metadata_2025 huggingface dataset:
The paradox of bardoxolone methyl: a call for every witness on the stand?
Authors: Van Laecke S. , Van Biesen W. , Vanholder R.
Published: July 2014

People with type 2 diabetes and chronic kidney disease (CKD) remain an extremely vulnerable population with increased cardiovascular morbidity, mortality and mounting societal costs. As such, any effort to improve their dismal outcome is heavily supported. Yet, most drugs fail to replicate the promising signals of early experiments in humans in large and methodologically sound trials. As a recent example, an independent data and safety committee advised the termination of a phase 3 trial due to excessive cardiovascular disease and especially heart failure in patients allocated to the antioxidant synthetic triterpenoid bardoxolone methyl versus placebo. We evaluate the reasons why this outcome in hindsight was possibly not totally unexpected and develop a mechanistic model that shows that the consistent drop in serum magnesium concentration in patients exposed to bardoxolone methyl might have contributed to the development of heart failure. As such, this trial, despite its negative outcome, might provide additional pieces of the puzzle enabling us to get a better grip on diseases that share increased inflammation and oxidative stress, such as type 2 diabetes, metabolic syndrome, heart failure and CKD.
The iterative ensemble modelling approach increases the accuracy of fish distribution models
Authors: Lauzeral Christine , Grenouillet Gaël , Brosse Sébastien
Published: July 2014

Methodological absences, i.e. when a species is not detected although it is actually present, are known to reduce the prediction accuracy of species distribution models (SDMs). To deal with this problem, we assessed whether a new iterative ensemble modelling (IEM) approach better predicts the spatial distribution of a set of 31 freshwater fish species, exhibiting a wide range of prevalence and methodological absences. Model efficiency was compared using one threshold‐independent (AUC) and three threshold‐dependent indicators of model predictive performance: the percentage of misclassified sites; the Kappa index; and the True Skill Statistic. We then reconstructed species assemblages from individual species predictions and compared observed assemblages to those predicted using EM and IEM using the Jaccard index. Compared to an EM approach, IEM improved model predictive performance for most difficult‐to‐detect species. The iterative approach outperformed EM at modelling the distribution of difficult‐to‐detect species, provided that presence data are representative of the niche of the species. At the assemblage level, the discrepancy between observed and IEM predicted assemblages was significantly lower than that between observed and EM predicted assemblages, showing that IEM can be used to predict the distribution of entire species assemblages. The IEM approach provides a way to consider difficult‐to‐detect species in species distribution models.
International Labor Mobility, Redistribution, and Domestic Political Liberalization
Authors: Bearce David H. , Laks Hutnick Jennifer
Published: July 2014

Do international labor flows influence the prospects for democratization both in the countries that export their excess workers and in the countries that import them? This paper argues that emigration should have a positive effect on political liberalization in net source countries because it decreases the amount of redistribution that would occur in a more democratic regime. Conversely, immigration should have a negative effect on political liberalization in net destination countries through the same causal channel: by increasing the amount of redistribution that would occur in a more democratic regime. South Korea and Singapore are considered as illustrative examples, and the paper provides statistical evidence to support the hypothesis that emigration (immigration) has been positively (negatively) related to future political liberalization.
Variation in mouthguard thickness due to different heating conditions during fabrication: Part 2
Authors: Takahashi Mutsumi , Koide Kaoru , Mizuhashi Fumi
Published: July 2014

The purpose of this study was to determine changes in the thickness of mouthguard sheets under different heating conditions during fabrication. Mouthguards were fabricated with polyolefin–polystyrene co‐polymer (OS) and olefin co‐polymer (OL) sheets (4.0‐mm thick) utilizing a vacuum‐forming machine under the following three conditions: (A) the sheet was moulded when it sagged 15 mm below the sheet frame (i.e. the normally used position); (B) the sheet frame was lowered to and heated at 30 mm below the top of the post and moulded when it sagged by 15 mm; and (C) the sheet frame was lowered to and heated at 50 mm below the top of the post and moulded when it sagged by 15 mm. The working model was trimmed to a height of 20 mm at the incisor and 15 mm at the first molar. Post‐moulding thickness was determined for the incisal portion (incisal edge and labial surface) and molar portion (cusp, central groove and buccal surface). Dimensions were measured, and differences in the change in thickness due to heating condition were analysed using the Kruskal–Wallis test. Under condition C, OS and OL decreased in thickness from 0.36–0.54 mm to 0.26–0.30 mm, respectively, at the incisal portion and from 0.34–0.66 mm to 0.17–0.47 mm, respectively, at the molar portion. It may be clinically useful when moulding a mouthguard to maintain the thickness of the incisal and molar portions by adjusting the height of the sheet frame.
A molecular diagnostic assay for the detection and identification of wood decay fungi of conifers
Authors: Gonthier P. , Guglielmo F. , Sillo F. , Giordano L. , Garbelotto M.
Published: July 2014

Ten taxon‐specific primers were designed to amplify the Internal Transcribed Spacer of the rRNA operon of several important decay fungi of coniferous wood, including Armillaria spp., Echinodontium spp., Fomitopsis pinicola, Fuscoporia torulosa, Heterobasidion annosum sensu lato (s.l.), Onnia spp., Phaeolus schweinitzii, Phellinus weirii s.l., Pholiota spp. and Porodaedalea spp. Primers designed in this study and in a previous one for the identification of Laetiporus sulphureus and Stereum spp. were combined in two multiplex PCRs, which were tested for efficiency and specificity, and detected at least 1 pg of fungal target DNA. Target DNA at concentrations of 10−1 pg or lower can be detected with this assay using SYBR® Green Real‐Time PCR. Validation assays performed on 129 naturally infected wood samples or fruiting bodies confirmed the reliability of the multiplex PCR‐based diagnostic method. This method represents a simple and rapid diagnostic tool for the detection of a number of destructive wood decay fungi of conifer wood.
Rituximab, Gemcitabine, Cisplatin and Methylprednisolone (R‐GEM‐P) is an effective regimen in relapsed diffuse large B‐cell lymphoma
Authors: Barton Sarah , Hawkes Eliza A. , Cunningham David , Peckitt Clare , Chua Sue , Wotherspoon Andrew , Attygalle Ayoma , Horwich Alan , Potter Mike , Ethell Mark , Dearden Claire , Gleeson Mary , Chau Ian
Published: July 2014

Background

Patients with relapsed diffuse large B‐cell lymphoma (DLBCL) have a poor prognosis. Gemcitabine, methylprednisolone, cisplatin +/− rituximab (GEM‐P+/−R) is a salvage regimen with limited overlap in toxicity with first‐line therapy and short duration of inpatient delivery.

Methods

We assessed the efficacy and safety of GEM‐P+/−R in a retrospective single‐centre analysis including patients meeting criteria of ≥18 yr of age, histologically proven DLBCL, treated between 2001 and 2011 in second‐line with gemcitabine 1000 mg/m2 day 1, 8 and 15, methylprednisolone 1000 mg day 1–5, cisplatin 100 mg/m2 day 15 (replaced with carboplatin AUC5 if contraindication/toxicity) +/− rituximab 375 mg/m2 day 1 and 15, every 28 d.

Results

Forty‐five patients aged 25–74 received a median of three cycles of GEM‐P+/−R; 64% received rituximab. In 44 evaluable patients receiving GEM‐P+/−R, overall response rate (ORR) was 48%; in 28 evaluable patients treated with rituximab + GEM‐P (R‐GEM‐P), ORR was 61%. With median follow‐up of 50.5 months (95% CI: 28.3–72.7), 3‐yr overall survival (OS) from start of GEM‐P+/−R was 31.4% (95% CI: 16.5–46.3); in patients treated with R‐GEM‐P, 3‐yr OS was 49.1% (95% CI: 28.7–69.5). Predominant grade ≥ 3 toxicities were haematological; thrombocytopenia 69%, neutropenia 60% and febrile neutropenia 7%.

Conclusion

R‐GEM‐P is a deliverable regimen with useful activity in second‐line treatment of DLBCL. Our data suggest that rituximab should be given concurrently.
Derangement of the T‐cell repertoire in patients with B‐cell non‐Hodgkin's lymphoma
Authors: Fozza Claudio , Corda Giovanna , Virdis Patrizia , Contini Salvatore , Barraqueddu Francesca , Galleu Antonio , Isoni Antonella , Cossu Antonella , Dore Fausto , Careddu Maria G. , Bonfigli Silvana , Giannico Barbara , Longinotti Maurizio
Published: July 2014

Although a number of studies suggest that different immune pathways may play a role in the pathogenesis of non‐Hodgkin's lymphomas (NHL), the shape of the T‐cell compartment has been only superficially explored in these patients. In our study, we analyzed the peripheral T‐cell receptor (TCR) repertoire and the distribution of different T‐cell subsets – including regulatory T cells (Treg) – in 30 patients with NHL, by combining flow cytometry and spectratyping. We first demonstrated by flow cytometry an increased frequency of expanded T‐cell subpopulations expressing the same TCR beta variable (BV) subfamilies in CD8+ cells from NHL patients when compared with healthy controls, beside a higher frequency of Treg. Moreover, NHL patients were characterized by a higher percentage of BVs showing a skewed CDR3 profile both in CD4+ and CD8+ cells when analyzed by spectratyping. Our data suggest that the T‐cell branch of the immune system of patients with B‐cell NHL is deeply deranged, as witnessed by the increased degree of activation and skewing of their TCR repertoire along with the higher frequency of Treg.
Collapsin response‐mediator protein 5 (CRMP5) phosphorylation at threonine 516 regulates neurite outgrowth inhibition
Authors: Brot Sébastien , Smaoune Hinda , Youssef‐Issa Mina , Malleval Céline , Benetollo Claire , Besançon Roger , Auger Carole , Moradi‐Améli Mahnaz , Honnorat Jérôme
Published: July 2014

The collapsin response‐mediator proteins (CRMPs) are multifunctional proteins highly expressed during brain development but down‐regulated in the adult brain. They are involved in axon guidance and neurite outgrowth signalling. Among these, the intensively studied CRMP2 has been identified as an important actor in axon outgrowth, this activity being correlated with the reorganisation of cytoskeletal proteins via the phosphorylation state of CRMP2. Another member, CRMP5, restricts the growth‐promotional effects of CRMP2 by inhibiting dendrite outgrowth at early developmental stages. This inhibition occurs when CRMP5 binds to tubulin and the microtubule‐associated protein MAP2, but the role of CRMP5 phosphorylation is still unknown. Here, we have studied the role of CRMP5 phosphorylation by mutational analysis. Using non‐phosphorylatable truncated constructs of CRMP5 we have demonstrated that, among the four previously identified CRMP5 phosphorylation sites (T509, T514, T516 and S534), only the phosphorylation at T516 residue was needed for neurite outgrowth inhibition in PC12 cells and in cultured C57BL/6J mouse hippocampal neurons. Indeed, the expression of the CRMP5 non‐phosphorylated form induced a loss of function of CRMP5 and the mutant mimicking the phosphorylated form induced the growth inhibition function seen in wildtype CRMP5. The T516 phosphorylation was achieved by the glycogen synthase kinase‐3β (GSK‐3β), which can phosphorylate the wildtype protein but not the non‐phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin‐binding property of CRMP5. Therefore, CRMP5‐induced growth inhibition is dependent on T516 phosphorylation through the GSK‐3β pathway. The findings provide new insights into the mechanisms underlying neurite outgrowth.
The Ephrin receptor EphA4 restricts axonal sprouting and enhances branching in the injured mouse optic nerve
Authors: Joly Sandrine , Jordi Noémie , Schwab Martin E. , Pernet Vincent
Published: July 2014

The lack of axonal regeneration in the adult central nervous system is in part attributable to the presence of inhibitory molecules present in the environment of injured axons such as the myelin‐associated proteins Nogo‐A and MAG and the repulsive guidance molecules Ephrins, Netrins and Semaphorins. In the present study, we hypothesized that EphA4 and one of its potential binding partners EphrinA3 may participate in the inhibition of adult axon regeneration in the model of adult mouse optic nerve injury. Axonal regeneration was analysed in three dimensions after tissue clearing of EphA4 knockout (KO), EphrinA3 KO and wild‐type (WT) optic nerves. By immunohistochemistry, EphA4 was highly expressed in Müller glia endfeet in the retina and in astrocytes in the retina and the optic nerve, while EphrinA3 was present in retinal ganglion cells and oligodendrocytes. Optic nerve crush did not cause expression changes. Significantly more axons grew in the crushed optic nerve of EphA4 KO mice than in WT or EphrinA3 KO animals. Single axon analysis revealed that EphA4 KO axons were less prone to form aberrant branching than axons in the other mouse groups. The expression of growth‐associated proteins Sprr1a and Gap‐43 did not vary between EphA4 KO and WT retinae. However, glial fibrillary acidic protein‐expressing astrocytes were withdrawn from the perilesional area in EphA4 KO, suggesting that gliosis down‐regulation may locally contribute to improve axonal growth at the injury site. In summary, our three‐dimensional analysis of injured mouse optic nerves reveals beneficial effects of EphA4 ablation on the intensity and the pattern of optic nerve axon regeneration.
Top‐down inputs from the olfactory cortex in the postprandial period promote elimination of granule cells in the olfactory bulb
Authors: Komano‐Inoue Sayaka , Manabe Hiroyuki , Ota Mizuho , Kusumoto‐Yoshida Ikue , Yokoyama Takeshi K. , Mori Kensaku , Yamaguchi Masahiro
Published: July 2014

Elimination of granule cells (GCs) in the olfactory bulb (OB) is not a continual event but is promoted during a short time window in the postprandial period, typically with postprandial sleep. However, the neuronal mechanisms for the enhanced GC elimination during the postprandial period are not understood. Here, we addressed the question of whether top‐down inputs of centrifugal axons from the olfactory cortex (OC) during the postprandial period are involved in the enhanced GC elimination in the OB. Electrical stimulation of centrifugal axons from the OC of anesthetized mice increased GC apoptosis. Furthermore, pharmacological suppression of top‐down inputs from the OC to the OB during the postprandial period of freely behaving mice by γ‐aminobutyric acid (GABA)A receptor agonist injection in the OC significantly decreased GC apoptosis. Remarkable apoptotic GC elimination in the sensory‐deprived OB was also suppressed by pharmacological blockade of top‐down inputs. These results indicate that top‐down inputs from the OC to the OB during the postprandial period are the crucial signal promoting GC elimination, and suggest that the life and death decision of GCs in the OB is determined by the interplay between bottom‐up sensory inputs from the external world and top‐down inputs from the OC.
New distribution record of the invasive bronze bug Thaumastocoris peregrinus Carpintero and Dellapé (Heteroptera, Thaumastocoridae) in Italy
Authors: Suma P. , Nucifora S. , Bella S.
Published: July 2014

The presence of the bronze bug Thaumastocoris peregrinus Carpintero and Dellapé (Heteroptera; Thaumastocoridae), a serious invasive pest of Eucalyptus (Myrtaceae) plantations, was recently reported for the first time in Europe in the Italian region of Latium. This study provides information on its occurrence in Sicily from Eucalyptus camaldulensis Dehnh.
Costs of antibiotic resistance – separating trait effects and selective effects
Authors: Hall Alex R. , Angst Daniel C. , Schiessl Konstanze T. , Ackermann Martin
Published: July 2014

Antibiotic resistance can impair bacterial growth or competitive ability in the absence of antibiotics, frequently referred to as a ‘cost’ of resistance. Theory and experiments emphasize the importance of such effects for the distribution of resistance in pathogenic populations. However, recent work shows that costs of resistance are highly variable depending on environmental factors such as nutrient supply and population structure, as well as genetic factors including the mechanism of resistance and genetic background. Here, we suggest that such variation can be better understood by distinguishing between the effects of resistance mechanisms on individual traits such as growth rate or yield (‘trait effects’) and effects on genotype frequencies over time (‘selective effects’). We first give a brief overview of the biological basis of costs of resistance and how trait effects may translate to selective effects in different environmental conditions. We then review empirical evidence of genetic and environmental variation of both types of effects and how such variation may be understood by combining molecular microbiological information with concepts from evolution and ecology. Ultimately, disentangling different types of costs may permit the identification of interventions that maximize the cost of resistance and therefore accelerate its decline.
Linking Northeast Pacific recruitment synchrony to environmental variability
Authors: Stachura Megan M. , Essington Timothy E. , Mantua Nathan J. , Hollowed Anne B. , Haltuch Melissa A. , Spencer Paul D. , Branch Trevor A. , Doyle Miriam J.
Published: July 2014

We investigated the hypothesis that synchronous recruitment is due to a shared susceptibility to environmental processes using stock–recruitment residuals for 52 marine fish stocks within three Northeast Pacific large marine ecosystems: the Eastern Bering Sea and Aleutian Islands, Gulf of Alaska, and California Current. There was moderate coherence in exceptionally strong and weak year‐classes and correlations across stocks. Based on evidence of synchrony from these analyses, we used Bayesian hierarchical models to relate recruitment to environmental covariates for groups of stocks that may be similarly influenced by environmental processes based on their life histories. There were consistent relationships among stocks to the covariates, especially within the Gulf of Alaska and California Current. The best Gulf of Alaska model included Northeast Pacific sea surface height as a predictor of recruitment, and was particularly strong for stocks dependent on cross‐shelf transport during the larval phase for recruitment. In the California Current the best‐fit model included San Francisco coastal sea level height as a predictor, with higher recruitment for many stocks corresponding to anomalously high sea level the year before spawning and low sea level the year of spawning. The best Eastern Bering Sea and Aleutian Islands model included several environmental variables as covariates and there was some consistent response across stocks to these variables. Future research may be able to utilize these across‐stock environmental influences, in conjunction with an understanding of ecological processes important across early life history stages, to improve identification of environmental drivers of recruitment.
Diazepam improves aspects of social behaviour and neuron activation in NMDA receptor‐deficient mice
Authors: Mielnik C. A. , Horsfall W. , Ramsey A. J.
Published: July 2014

NR1 knockdown (NR1KD) mice are genetically modified to express low levels of the NR1 subunit of N‐methyl‐d‐aspartate (NMDA) receptors, and show deficits in affiliative social behaviour. In this study, we determined which brain regions were selectively activated in response to social stimulation and asked whether differences in neuronal activation could be observed in mice with reduced sociability. Furthermore, we aimed to determine whether brain activation patterns correlated with the amelioration of social deficits through pharmacological intervention. The cingulate cortex, lateral septal nuclei, hypothalamus, thalamus and amygdala showed an increase in c‐Fos immunoreactivity that was selective for exposure to social stimuli. NR1KD mice displayed a reduction in social behaviour and a reduction in c‐Fos immunoreactivity in the cingulate cortex and septal nuclei. Acute clozapine did not significantly alter sociability; however, diazepam treatment did increase sociability and neuronal activation in the lateral septal region. This study has identified the lateral septal region as a neural substrate of social behaviour and the GABA system as a potential therapeutic target for social dysfunction.
A global assessment of forest surface albedo and its relationships with climate and atmospheric nitrogen deposition
Authors: Leonardi Stefano , Magnani Federico , Nolè Angelo , Van Noije Twan , Borghetti Marco
Published: July 2014

We present a global assessment of the relationships between the short‐wave surface albedo of forests, derived from theMODISsatellite instrument product at 0.5° spatial resolution, with simulated atmospheric nitrogen deposition rates (Ndep), and climatic variables (mean annual temperatureTmand total annual precipitationP), compiled at the same spatial resolution. The analysis was performed on the following five forest plant functional types (PFTs): evergreen needle‐leaf forests (ENF); evergreen broad‐leaf forests (EBF); deciduous needle‐leaf forests (DNF); deciduous broad‐leaf forests (DBF); and mixed‐forests (MF). Generalized additive models (GAMs) were applied in the exploratory analysis to assess the functional nature of short‐wave surface albedo relations to environmental variables. The analysis showed evident correlations of albedo with environmental predictors when data were pooled acrossPFTs:TmandNdepdisplayed a positive relationship with forest albedo, while a negative relationship was detected withP. These correlations are primarily due to surface albedo differences between conifer and broad‐leaf species, and different species geographical distributions. However, the analysis performed within individualPFTs, strengthened by attempts to select ‘pure’ pixels in terms of species composition, showed significant correlations with annual precipitation and nitrogen deposition, pointing toward the potential effect of environmental variables on forest surface albedo at the ecosystem level. Overall, our global assessment emphasizes the importance of elucidating the ecological mechanisms that link environmental conditions and forest canopy properties for an improved parameterization of surface albedo in climate models.
Cognitive Value and Numerical Accuracy in Geocomputation: Choosing a Method to Compute the Log‐Jacobian Term
Authors: Smirnov Oleg A.
Published: July 2014

This article addresses the importance of cognitive value, numerical accuracy, and technical feasibility for geospatial models and methods. Researchers pursue large spatial data in an analysis to improve the statistical efficiency of parameter estimates and the cognitive value of the results. The critical requirement for this strategy is the availability of numerically accurate computational methods, without which parameter estimates lose their cognitive value. This article illustrates the relationship between cognitive value and numerical accuracy by establishing properties of popular polynomial schemes for approximating the log‐Jacobian term in spatial autoregressive models. It shows that numerical inaccuracies might be more misleading than is commonly assumed.

En este artículo se aborda la importancia del valor cognitivo, la precisión numérica, y la viabilidad técnica de los modelos y métodos geoespaciales. Los investigadores interesados en análisis espacial tienden a preferir el uso de bases de datos de gran tamaño con el fin de mejorar la eficiencia estadística de sus estimaciones de parámetros y el valor cognitivo de los resultados. El requisito crítico para esta estrategia es la disponibilidad de métodos computacionales numéricamente precisos, sin los cuales las estimaciones de parámetros pierden su valor cognitivo. En este artículo se ilustra la relación entre el valor cognitivo y precisión numérica mediante la determinante jacobiano tipo log en modelos espaciales autorregresivos (spatial autorregresive models‐SAR). El estudio demuestra que las imprecisiones numéricas pueden ser más engañosas de lo que se asume comúnmente.

本文描述了地理空间模型和方法中认知价值、数值精度、技术可行性的重要性。研究者一般倾向于通过追求大规模空间数据，来提升参数估计的统计有效性和结果的认知价值。这一策略的关键是有实用的精确数值计算方法，否则参数估计将失去其认知价值。本文通过建立普遍使用的多项式方案来逼近空间自回归（SAR）模型中的Log‐Jacobian，从而说明认知价值和数值精度间的关系。结果表明数值不确定性可能比通常假设的误导性更大。
Long‐chain alcohols did not improve predictions of the composition of tall fescue and red clover mixtures over n‐alkanes alone
Authors: Vargas Jurado N. , Tanner A. E. , Blevins S. R. , McNair H. M. , Mayes R. W. , Lewis R. M.
Published: July 2014

Feed intake and diet choice affect production efficiency in livestock. Plant waxes, in particular n‐alkanes, have been used as markers to predict intake and diet preferences. Still, when n‐alkane profiles of plants within mixed swards are similar, they alone may not produce reliable predictions. Including long‐chain alcohols (LCOHs) may help. In this study, the reliability of predicting forage mixtures was assessed using n‐alkanes and LCOH separately and in combination. Reliability was characterized as the regression of observed on predicted fescue proportion in forage mixtures and the Kulczyński similarity index. Two technicians performed extractions of n‐alkanes and LCOHs of pure red clover and ‘Fawn’ tall fescue, and nine mixtures of them. The concentrations of n‐alkanes C27, C29, C31 and C33 and alcohols C26‐OH, C28‐OH and C30‐OH were compared among forage mixtures and between technicians. Technicians were consistent in their measures of n‐alkanes (P > 0·12), but differed in their measures of C26‐OH and C28‐OH (P < 0·002). Longer‐chained compounds were more consistently quantified. Forage delineations were not improved by C26‐OH. With n‐alkanes alone, estimated and actual fescue proportions closely agreed. Including LCOH offered no improvement. Despite variation in measured concentrations between technicians, fescue and red clover mixtures were reliably predicted using n‐alkanes alone.
Sedgwick and his trilobite
Authors: McNamara Ken
Published: July 2014

Standing on guard at the entrance to the Palaeozoic section of the University of Cambridge's Sedgwick Museum is a bronze statue of the man after whom the museum was named—the 7th Woodwardian Professor, the Reverend Adam Sedgwick. In one hand he holds his trusty geological hammer, in the other is a rock. Sedgwick, the man who unraveled many of the mysteries of the early Palaeozoic rocks of Wales, looks as if he has just cracked a piece of rock off an outcrop. Yet, rather incongruously, he is swathed in his academic gown—our man is clearly both the consummate field geologist and the academic.
The Upper Oligocene of Antigua: the volcanic to limestone transition in a limestone Caribbee
Authors: Donovan Stephen K. , Jackson Trevor A. , Harper David A.T. , Portell Roger W. , Renema Willem
Published: July 2014

Antigua is a small island at the northern end of the Lesser Antilles chain. Its geology is largely limited to the Upper Oligocene and it records with unusual fidelity the transition from island arc volcanism to quiescence and limestone deposition. Despite the apparent limitation of a rock record confined to a short stratigraphical interval, Antigua has a geodiversity that ranges from thick andesites through silicified logs and freshwater snails in cherts to limestones that include both shallow and deeper water facies, and fine karstic features.
Uncertainty Analysis of a Groundwater Flow Model in East‐Central Florida
Authors: Sepúlveda Nicasio , Doherty John
Published: July 2014

A groundwater flow model for east‐central Florida has been developed to help water‐resource managers assess the impact of increased groundwater withdrawals from the Floridan aquifer system on heads and spring flows originating from the Upper Floridan Aquifer. The model provides a probabilistic description of predictions of interest to water‐resource managers, given the uncertainty associated with system heterogeneity, the large number of input parameters, and a nonunique groundwater flow solution. The uncertainty associated with these predictions can then be considered in decisions with which the model has been designed to assist. The “Null Space Monte Carlo” method is a stochastic probabilistic approach used to generate a suite of several hundred parameter field realizations, each maintaining the model in a calibrated state, and each considered to be hydrogeologically plausible. The results presented herein indicate that the model's capacity to predict changes in heads or spring flows that originate from increased groundwater withdrawals is considerably greater than its capacity to predict the absolute magnitudes of heads or spring flows. Furthermore, the capacity of the model to make predictions that are similar in location and in type to those in the calibration dataset exceeds its capacity to make predictions of different types at different locations. The quantification of these outcomes allows defensible use of the modeling process in support of future water‐resources decisions. The model allows the decision‐making process to recognize the uncertainties, and the spatial or temporal variability of uncertainties that are associated with predictions of future system behavior in a complex hydrogeological context.
Parameter Estimation for Groundwater Models under Uncertain Irrigation Data
Authors: Demissie Yonas , Valocchi Albert , Cai Ximing , Brozovic Nicholas , Senay Gabriel , Gebremichael Mekonnen
Published: July 2014

The success of modeling groundwater is strongly influenced by the accuracy of the model parameters that are used to characterize the subsurface system. However, the presence of uncertainty and possibly bias in groundwater model source/sink terms may lead to biased estimates of model parameters and model predictions when the standard regression‐based inverse modeling techniques are used. This study first quantifies the levels of bias in groundwater model parameters and predictions due to the presence of errors in irrigation data. Then, a new inverse modeling technique called input uncertainty weighted least‐squares (IUWLS) is presented for unbiased estimation of the parameters when pumping and other source/sink data are uncertain. The approach uses the concept of generalized least‐squares method with the weight of the objective function depending on the level of pumping uncertainty and iteratively adjusted during the parameter optimization process. We have conducted both analytical and numerical experiments, using irrigation pumping data from the Republican River Basin in Nebraska, to evaluate the performance of ordinary least‐squares (OLS) and IUWLS calibration methods under different levels of uncertainty of irrigation data and calibration conditions. The result from the OLS method shows the presence of statistically significant (p < 0.05) bias in estimated parameters and model predictions that persist despite calibrating the models to different calibration data and sample sizes. However, by directly accounting for the irrigation pumping uncertainties during the calibration procedures, the proposed IUWLS is able to minimize the bias effectively without adding significant computational burden to the calibration processes.
Tubulin β‐III: a novel immunohistochemical marker for intrahepatic peripheral cholangiocarcinoma
Authors: Zen Yoh , Britton David , Mitra Vikram , Pike Ian , Sarker Debashis , Itoh Tomoo , Heaton Nigel , Quaglia Alberto
Published: July 2014

Aims

Our recent proteomic study identified tubulin β‐III (TUBB3) as a potential tissue marker for intrahepatic cholangiocarcinomas (CCs). This validation study was conducted to see whether or not TUBB3 can serve as a novel immunohistochemical marker for peripheral CCs, using a large cohort (n = 197) covering various liver tumours and premalignant conditions.

Methods and results

Immunostaining using a monoclonal antibody demonstrated TUBB3 expression in 14/28 cases of peripheral CCs (50%), while its expression was significantly less common in perihilar CCs (6/40, 15%) (P = 0.002). No significant difference was identified in clinicopathological features between TUBB3‐positive and ‐negative cases. TUBB3 expression was entirely negative in hepatocellular carcinomas, biliary premalignant lesions (i.e., biliary intraepithelial neoplasias, intraductal papillary neoplasms), peribiliary gland hamartomas (bile duct adenomas), and non‐neoplastic biliary epithelium. TUBB3 expression was only focally noted in 2/12 cases of mixed hepatocellular and cholangiocarcinomas (<10% of cancer cells). Compared with other biliary (CK7 and CK19) and malignant markers (p53 and MUC1), TUBB3 was less sensitive but more specific for peripheral CCs. TUBB3 was also expressed in 40% of metastatic colorectal or breast cancers.

Conclusions

This study revealed that TUBB3 is a moderately sensitive and highly specific tissue marker for discriminating peripheral CCs from other primary liver tumours.
Stratified mucin‐producing intraepithelial lesion (SMILE): report of a case series with associated pathological findings
Authors: Boyle David P , McCluggage W Glenn
Published: July 2014

Aims

Stratified mucin‐producing intraepithelial lesion (SMILE) is an uncommon premalignant cervical lesion showing morphological overlap with cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS)/cervical glandular intraepithelial neoplasia. Given the limited literature on SMILE, we aimed to document its frequency and assess the associated pathology in a large series of cases.

Methods and results

Over a 6‐year period, we documented all cases of SMILE and the associated findings. SMILE was diagnosed in 69 specimens from 60 patients (50 loop excisions and 19 punch biopsy specimens), constituting 0.6% of cervical specimens. Overall, SMILE coexisted with high‐grade CIN in 93% of cases, AIS in 42%, and a carcinoma in 10%. When SMILE was diagnosed on a cervical punch biopsy, there was high‐grade CIN in the follow‐up loop in most cases. SMILE was consistently diffusely p16‐positive and IMP3‐negative.

Conclusions

Given the morphological overlap and significant association with high‐grade CIN and AIS, we believe that SMILE is best regarded as a form of high‐grade reserve cell dysplasia, probably arising from reserve or stem cells with the capacity for multidirectional differentiation. We recommend that management of SMILE should be as for AIS.
Dental hygienists' perception of preparation and use for ultrasonic instrumentation
Authors: Asadoorian J , Botbyl D , Goulding MJ
Published: July 2014

Objectives

Ultrasonic scaling technology has evolved dramatically providing greater clinical utility subgingivally including instrumentation of light deposits and biofilm disruption. It is unknown whether dental hygiene curriculum has kept pace with the progression and reflects current applications. The first part of this two‐part study aimed to determine new dental hygiene graduates' use and perceptions of preparedness in ultrasonic instrumentation. Part 2 investigates ultrasonic curriculum from the programme director perspective and will be reported on in a subsequent paper.

Method

Part 1 of the study surveys recently graduated Canadian dental hygienists about their use and perceptions of preparedness with ultrasonic instruments through an electronic questionnaire developed for this study.

Results

Participants reported using ultrasonics about half of their instrumentation time predominantly with magnetostrictive technology. Use focussed on heavier deposits with straight, slim inserts. Subjects were generally satisfied with ultrasonic education and felt reasonably well prepared in using ultrasonics. Higher levels of perceived preparedness were most associated with graduates from the 3‐year diploma programme, whereas graduates from 18‐month programmes were associated with greater levels of confidence in using ultrasonics. Confidence with ultrasonics did not have an effect on subsequent use – mostly all participants increased use once in practice. An earlier introduction and more practice time in school were both associated with increased feelings of preparation and confidence.

Conclusions

New dental hygiene graduates perceive greater preparedness, confidence and use of ultrasonic instrumentation within a more traditional paradigm. In addition, the results indicate a potential incorrect and/or inappropriate application of current technology.
‘Fresh variants and formulations frozen’: Structural features of commercial signs in Oman
Authors: Buckingham Louisa
Published: July 2014

This study analyses structural features of English on commercial signs on shop frontages throughout Oman. The study identifies frequently used structural features which appear to be undergoing a process of nativization (Schneider 2003) within the context of this text type. These include word class flexibility, the extensive use of the gerund at the end of noun phrases and the use of multiple verbs to itemize discrete activities. In some cases, features appear to serve the functions of economizing, or heightening the prominence or degree of explicitness of content; in other cases, structural features revealed the influence of Arabic. Limited evidence was also found for features previously identified in other lingua franca contexts such as the genitive structure with inanimate nouns and plural uncountable nouns.
Prospective evaluation of automatized PF4/heparin immunoassays HemosIL HIT‐ab (PF4‐H) for the diagnosis of heparin‐induced thrombocytopenia
Authors: Jourdy Y. , Nougier C. , Rugeri L. , Bordet J. C. , Sobas F. , Negrier C.
Published: July 2014

Introduction

Recently, rapid immunoassays have been developed to allow the detection of antibodies anti‐PF4/heparin. In this prospective study, we evaluated the performances of a automatized immunoassay (HemosIL HIT‐Ab) in comparison with an ELISA (Zymutest HIA IgG) used for the diagnosis of heparin‐induced thrombocytopenia (HIT) in association with the 4T's score.

Methods

According to the 4T's score, samples with score ≤3 had no further analysis. Two immunological assays Zymutest HIA IgG and HemosIL HIT‐Ab were performed in samples with score ≥4. In patients with at least one positive immunological assay or two negative immunological assays but with high‐pretest probability (4T's score ≥6), HIT was screened by one functional assay using washed platelets.

Results

The sensitivities of both assays were excellent and comparable (100%). The specificity was 92.3% for ELISA and 91.2% for HemosIL HIT‐Ab. The analysis of the operating characteristics showed that both assays have almost identical ROCs (AUROC, 0.9951 and 0.9853, respectively, for ELISA and HemosIL HIT‐Ab) and the calculating of the κ coefficient revealed a good agreement (0.67).

Conclusion

Performance characteristics of the HemosIL HIT‐Ab are comparable to the Zymutest HIA IgG. The HemosIL HIT‐Ab can be used in association with the 4T's score to rule out HIT.
Performance comparisons in major uro‐oncological surgeries between the USA and Japan
Authors: Sugihara Toru , Yasunaga Hideo , Horiguchi Hiromasa , Fushimi Kiyohide , Dalton Jarrod E , Schold Jesse , Kattan Michael W , Homma Yukio
Published: July 2014

Objectives

To elucidate the differences in clinical practice between the USA and Japan in major types of uro‐oncological surgery by a head‐to‐head comparison of national databases in the two countries.

Methods

We compared variations in surgical modality, length of stay, total charges, caseload centralization, transfusion incidence, and in‐hospital mortality between the two countries for four major types of uro‐oncological surgery (radical prostatectomy, radical cystectomy, nephrectomy and nephroureterectomy) in 2011. Additionally, the chronological changes in surgical modalities were investigated for 2009–11. The national estimates were based on data from the Japanese Diagnosis Procedure Combination database and the US National Inpatient Sample.

Results

For radical prostatectomy, radical cystectomy, nephrectomy and nephroureterectomy, minimally‐invasive surgery accounted for 24.2% versus 70.2%, 0% versus 14.0%, 50.7% versus 30.7% and 50.2% versus 30.5%, respectively, in Japan versus the USA in 2011. Although minimally‐invasive surgery has become increasingly frequent in both countries, the major procedures were robot‐assisted surgery in the USA and laparoscopic surgery in Japan. The USA was generally characterized by a slightly younger age at operation, far higher hospital volume, a shorter length of stay, higher charges and less use of transfusion than Japan.

Conclusions

The findings suggest substantial differences between the USA and Japan regarding clinical practices in uro‐oncological surgery. Standing at the beginning of robotic surgery era in Japan, the precise recognition of these differences will aid a proper understanding of clinical practices.
Nationwide survey of urogenital tuberculosis in Japan
Authors: Nakane Keita , Yasuda Mitsuru , Deguchi Takashi , Takahashi Satoshi , Tanaka Kazushi , Hayami Hiroshi , Hamasuna Ryoichi , Yamamoto Shingo , Arakawa Soichi , Matsumoto Tetsuro
Published: July 2014

Objectives

To determine current epidemiology and treatment patterns of urogenital tuberculosis in Japan.

Methods

A questionnaire was sent to the urological departments of 1203 Japanese hospitals. Clinical data was reviewed retrospectively; no time range was specified.

Results

Of the 1203 hospitals, 399 returned questionnaires with information about 355 urogenital tuberculosis patients. Of the 399, 153 institutions reported at least one patient, and 201 patients were identified between 2000 and 2007. Infections were located in the kidneys (n = 242), ureter (n = 96), bladder (n = 100), epididymis or testes (n = 81) and prostate (n = 9).

Conclusions

Urogenital tuberculosis is rare in Japan, but patients do exist, and we should not ignore them.
Chronic kidney disease and perioperative outcomes in urological oncological surgery
Authors: Schmid Marianne , Ravi Praful , Abd‐El‐Barr Abd‐El‐Rahman M , Klap Julia , Sammon Jesse D , Chang Steven L , Menon Mani , Kibel Adam S , Fisch Margit , Trinh Quoc‐Dien
Published: July 2014

Objectives

To evaluate baseline renal dysfunction among patients undergoing urological oncological surgery and its impact on early postoperative outcomes.

Methods

Between 2005 and 2011, patients who underwent minimally‐invasive or open radical prostatectomy, partial nephrectomy and radical nephrectomy, or open radical cystectomy, respectively, were identified in the National Surgical Quality Improvement Program dataset. Preoperative kidney function was assessed using estimated glomerular filtration rate and staged according to National Kidney Foundation definitions. Multivariable logistic regression was used to model the association between preoperative renal function and the risk of 30‐day mortality and major complications. Furthermore the impact of chronic kidney disease on operation time and length of hospital stay was assessed.

Results

Overall, 13 168 patients underwent radical prostatectomy (65.4%), partial nephrectomy (10.7%) and radical nephrectomy (16.1%) and radical cystectomy (7.8%), respectively; 50.1% of evaluable patients had reduced kidney function (chronic kidney disease II), and a further 12.6, 0.7 and 0.9% were respectively classified into chronic kidney disease stages III, IV, and V. Chronic kidney disease was an independent predictor of 30‐day major postoperative complications (chronic kidney disease III: odds ratio 1.61, P < 0.001; chronic kidney disease IV: odds ratio 2.24, P = 0.01), of transfusions (chronic kidney disease III: odds ratio 2.14, P < 0001), of prolonged length of stay (chronic kidney disease III: odds ratio 2.61, P < 0.001; chronic kidney disease IV: odds ratio 3.37, P < 0.001; and chronic kidney disease V: odds ratio 1.68; P = 0.03) and of 30‐day mortality (chronic kidney disease III: odds ratio 4.15, P = 0.01; chronic kidney disease IV: odds ratio 10.10, P = 0.003; and chronic kidney disease V: odds ratio 17.07, P < 0.001) compared with patients with no kidney disease.

Conclusions

Renal dysfunction might be underrecognized in patients undergoing urological cancer surgery. Chronic kidney disease stages III, IV and V are independent predictors for poor 30‐day postoperative outcomes.
Decreased urinary nerve growth factor reflects prostatic volume reduction and relief of outlet obstruction in patients with benign prostatic enlargement treated with dutasteride
Authors: Wada Naoki , Matsumoto Seiji , Kita Masafumi , Hashizume Kazumi , Kakizaki Hidehiro
Published: July 2014

Objectives

To examine urinary nerve growth factor before and after dutasteride treatment, and to analyze correlations between clinical parameters and change of urinary nerve growth factor in patients with benign prostatic enlargement.

Methods

We prospectively studied 30 patients with benign prostatic enlargement who had not been satisfied with α‐adrenergic antagonist monotherapy for more than 3 months. Before and 24 weeks after dutasteride add‐on treatment, we assessed International Prostate Symptom Score, prostatic volume, filling cystometry and pressure‐flow study. Urinary nerve growth factor was measured by enzyme‐linked immunosorbent assay, and normalized to the urinary creatinine (nerve growth factor/creatinine) before and 24 weeks after dutasteride add‐on treatment.

Results

In baseline characteristics before dutasteride, there was no significant correlation between urinary nerve growth factor/creatinine and any clinical parameters including age, International Prostate Symptom Score, prostatic volume, presence of detrusor overactivity, detrusor pressure at maximum flow rate, bladder outlet obstruction index or bladder contractility index. Dutasteride significantly reduced prostatic volume (from 68 ± 31 mL to 49 ± 28 mL) and improved International Prostate Symptom Score (from 17.2 ± 8.7 to 13.1 ± 6.8), storage (from 8.0 ± 4.3 to 6.0 ± 2.9) and voiding symptom subscore of International Prostate Symptom Score (from 9.3 ± 5.7 to 7.1 ± 4.5). In urodynamic study, detrusor pressure at maximum flow rate (from 77 ± 32 cmH2O to 59 ± 24 cmH2O) and bladder outlet obstruction index (from 62 ± 32 to 42 ± 27) were significantly decreased after dutasteride treatment. Urinary nerve growth factor/creatinine was significantly decreased after dutasteride from 2.61 ± 2.50 to 1.64 ± 1.68. The change of urinary nerve growth factor/creatinine significantly correlated only with the change of prostatic volume (r = 0.38) and bladder outlet obstruction index (r = 0.36).

Conclusions

Urinary nerve growth factor decreases in association with reduction of prostatic volume and relief of bladder outlet obstruction. Urinary nerve growth factor might be useful as a biomarker to monitor the improvement of bladder outlet obstruction in patients with benign prostatic enlargement.