bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and functional proteomic analyses of osteocytes from Xenopus laevis tested under mechanical stress conditions: preliminary observations on an appropriate new animal model
Authors: Bertacchini Jessika , Benincasa Marta , Checchi Marta , Cavani Francesco , Smargiassi Alberto , Ferretti Marzia , Palumbo Carla 
Published: September 2017

AbstractHitherto, the role of the osteocyte as transducer of mechanical stimuli into biological signals is far from settled. In this study, we used an appropriate model represented by the cortex of Xenopus laevis long bone diaphysis lacking (unlike the mammalian one) of vascular structures and containing only osteocytes inside the bone matrix. These structural features allow any change of protein profile that might be observed upon different experimental conditions, such as bone adaptation to stress/mechanical loading, to be ascribed specifically to osteocytes. The study was conducted by combining ultrastructural observations and two‐dimensional electrophoresis for proteomic analysis. The osteocyte population was extracted from long bones of lower limbs of amphibian skeletons after different protocols (free and forced swimming). The experiments were performed on 210 frogs subdivided into five trials, each including free swimming frogs (controls) and frogs submitted to forced swimming (stressed). The stressed groups were obliged to swim (on movable spheres covering the bottom of a pool on a vibrating plate) continuously for 8 h, and killed 24 h later along with the control groups. Long bones free of soft tissues (periosteum, endosteum and bone marrow), as well as muscles of posterior limbs, were processed and analyzed for proteins differentially expressed or phosphorylated between the two sample groups. The comparative analysis showed that protein phosphorylation profiles differ between control and stressed groups. In particular, we found in long bones of stressed samples that both Erk1/2 and Akt are hyperphosphorylated; moreover, the different phosphorylation of putative Akt substrates (recognized by specific Akt phosphosubstrates‐antibody) in stressed vs. control samples clearly demonstrated that Akt signaling is boosted by forced swimming (leading to an increase of mechanical stress) of amphibian long bones. In parallel, we found in posterior limb muscles that the expression of heat shock protein HSP27 and HSP70 stress markers increased upon the forced swimming condition. Because the cortexes of frog long bones are characterized by the presence of only osteocytes, all our results establish the suitability of the X. laevis animal model to study the bone response to stress conditions mediated by this cell type and pave the way for further analysis of the signaling pathways involved in these signal transduction mechanisms.
How Cellphone Bans Affect Automobile Insurance Markets
Authors: Karl J. Bradley , Nyce Charles 
Published: September 2017

AbstractIn this article, we examine the effect of laws prohibiting the hand‐held use of a cellphone while driving on the automobile insurance market. Our research is motivated by prior studies that present evidence that the enactment of such laws alters drivers’ behaviors in ways that reduce the risk of automobile accidents. We posit that that, by extension, these laws should also lead to reductions in the amount of losses paid by private passenger automobile physical damage insurers. Our analysis indicates that the enactment of a ban on the hand‐held use of a cellphone while driving reduces the incurred losses and incurred loss ratios of automobile insurers by approximately 3 percent, suggesting that these bans have important economic consequences not previously documented in the literature. Additional analysis suggests that hand‐held cellphone bans eventually lead to incremental reductions in premiums, but we do not observe these reductions in premiums until a couple of years following the enactment of a ban. Our analysis of automobile insurance losses also represents a departure from most prior studies of cellphone bans and therefore contributes to the ongoing debate in the public health literature regarding the extent to which hand‐held cellphone bans have implications for traffic safety.
POROSITY AND PERMEABILITY VARIATIONS IN A TIGHT GAS SANDSTONE RESERVOIR ANALOGUE, WESTPHALIAN D, LOWER SAXONY BASIN, NW GERMANY: INFLUENCE OF DEPOSITIONAL SETTING AND DIAGENESIS
Authors: Becker I. , Wüstefeld P. , Koehrer B. , Felder M. , Hilgers C. 
Published: September 2017

Understanding the spatial variability of reservoir properties in tight gas sandstones can significantly reduce uncertainties in reservoir characterization. This study focuses on two outcrops of Upper Carboniferous (Westphalian D) fluvial sandstones in the southern part of the Lower Saxony Basin, NW Germany, which are analogues for tight, gas‐producing reservoir rocks at fields in the north of the basin. Large‐scale differences in reservoir quality occur between the two outcrops which are separated by a distance of approximately 15 km and by 600 m of stratigraphy. Smaller‐scale heterogeneities in the form of channel geometries occur within individual fluvial cycles, as evidenced in a 30 m (high) by 150 m (long) porosity‐permeability profile at one of the outcrops studied.In the Woitzel quarry, lower Westphalian D deposits consist of fining‐upwards cycles of channel and bar sandstones with intercalated floodplain sediments and coal seams. In abandoned quarries at the Hüggel location, upper Westphalian D strata are composed of grey and red coloured sandstones which suggest deposition in a fluvial – alluvial plain environment under increasingly arid conditions.Reservoir quality is higher in the upper Westphalian D sandstones at Hüggel (permeability: up to 1 mD; mean porosity: 19%) than in the lower Westphalian D sandstones at Woitzel (permeability: <0.1 mD; mean porosity: 15%). Due to the high degree of compaction of the upper and lower Westphalian D deposits (intergranular volumes of 21.9% and 19.4% respectively) and the high proportions of pseudomatrix, porosity in these sandstones is mainly secondary with up to 80% microporosity. Reservoir quality is in general higher in the upper Westphalian D sandstones where kaolinite is present. In contrast, intense illitization has degraded the reservoir quality of the lower Westphalian D sandstones.A positive correlation between permeability and grain size is exhibited by the kaolinite‐bearing upper Westphalian D sandstones. No such correlation is evident in the illite‐bearing lower Westphalian D sandstones, unless samples with permeabilities of <0.01 mD are excluded from the correlation. However, such a low permeability cut‐off is not related to sorting, grain size or authigenic quartz cementation.At a small scale, permeability varies laterally by two orders of magnitude from 0.001 mD to 0.1 mD in a single, approximately 3 m thick tight sandstone bed over a distance of 150 m. Repeated, centimetre‐scaled fining‐upwards grading and bed‐internal erosion contribute to lateral variations in reservoir flow characteristics.Integrated studies of the depositional environment, diagenesis and sedimentary geometries of the deposited units are a key to the understanding of heterogeneities in tight fluvial sandstones and thus to the successful development of Upper Carboniferous reservoirs in the Lower Saxony Basin and elsewhere.
Training Vouchers and Labour Market Outcomes in Chile
Authors: Novella Rafael , Rucci Graciana , Vazquez Claudia , Kaplan David S. 
Published: September 2017

AbstractThis paper evaluates the impact of a training voucher programme in Chile, called Bono Trabajador Activo, on two labour market outcomes: monthly earnings and employment probabilities. Using detailed administrative datasets of the National Employment Service and the unemployment insurance system, we combine matching and difference‐in‐difference estimators to measure these effects up to five years after the application to the programme. Our main results indicate that the voucher has an overall positive impact on earnings, on the order of 3.2 per cent, and a small negative impact on formal employment. We find that the programme particularly improves earnings for less educated workers.
Speciation below ground: Tempo and mode of diversification in a radiation of endogean ground beetles
Authors: Andújar Carmelo , Pérez‐González Sergio , Arribas Paula , Zaballos Juan P. , Vogler Alfried P. , Ribera Ignacio 
Published: September 2017

AbstractDispersal is a critical factor determining the spatial scale of speciation, which is constrained by the ecological characteristics and distribution of a species’ habitat and the intrinsic traits of species. Endogean taxa are strongly affected by the unique qualities of the below‐ground environment and its effect on dispersal, and contrasting reports indicate either high dispersal capabilities favoured by small body size and mediated by passive mechanisms, or low dispersal due to restricted movement and confinement inside the soil. We studied a species‐rich endogean ground beetle lineage, Typhlocharina, including three genera and more than 60 species, as a model for the evolutionary biology of dispersal and speciation in the deep soil. A time‐calibrated molecular phylogeny generated from >400 individuals was used to delimit candidate species, to study the accumulation of lineages through space and time by species–area–age relationships and to determine the geographical structure of the diversification using the relationship between phylogenetic and geographic distances across the phylogeny. Our results indicated a small spatial scale of speciation in Typhlocharina and low dispersal capacity combined with sporadic long distance, presumably passive dispersal events that fuelled the speciation process. Analysis of lineage growth within Typhlocharina revealed a richness plateau correlated with the range of distribution of lineages, suggesting a long‐term species richness equilibrium mediated by density dependence through limits of habitat availability. The interplay of area‐ and age‐dependent processes ruling the lineage diversification in Typhlocharina may serve as a general model for the evolution of high species diversity in endogean mesofauna.
Prospective evaluation of the SeptiFAST multiplex real‐time PCR assay for surveillance and diagnosis of infections in haematological patients after allogeneic stem cell transplantation compared to routine microbiological assays and an in‐house real‐time PCR method
Authors: Elges Sandra , Arnold Renate , Liesenfeld Oliver , Kofla Grzegorz , Mikolajewska Agata , Schwartz Stefan , Uharek Lutz , Ruhnke Markus 
Published: September 2017

SummaryWe prospectively evaluated a multiplex real‐time PCR assay (SeptiFast, SF) in a cohort of patients undergoing allo‐BMT in comparison to an in‐house PCR method (IH‐PCR). Overall 847 blood samples (mean 8 samples/patient) from 104 patients with haematological malignancies were analysed. The majority of patients had acute leukaemia (62%) with a mean age of 52 years (54% female). Pathogens could be detected in 91 of 847 (11%) samples by SF compared to 38 of 205 (18.5%) samples by BC, and 57 of 847 (6.7%) samples by IH‐PCR. Coagulase‐negative staphylococci (n=41 in SF, n=29 in BC) were the most frequently detected bacteria followed by Escherichia coli (n=9 in SF, n=6 in BC). Candida albicans (n=17 in SF, n=0 in BC, n=24 in IH‐PCR) was the most frequently detected fungal pathogen. SF gave positive results in 5% of samples during surveillance vs in 26% of samples during fever episodes. Overall, the majority of blood samples gave negative results in both PCR methods resulting in 93% overall agreement resulting in a negative predictive value of 0.96 (95% CI: 0.95‐0.97), and a positive predictive value of 0.10 (95% CI: −0.01 to 0.21). SeptiFast appeared to be superior over BC and the IH‐PCR method.
Chronic kidney disease and vitamin D metabolism in human bone marrow–derived MSCs
Authors: Zhou Shuanhu , Glowacki Julie 
Published: September 2017

AbstractVitamin D that is synthesized in the skin or is ingested undergoes sequential steps of metabolic activation via a cascade of cytochrome P450 enzymatic hydroxylations in the liver and kidney to produce 1α,25‐dihydroxyvitamin D (1α,25(OH)2D). There are many tissues that are able to synthesize 1α,25(OH)2D, but the biological significance of extrarenal hydroxylases is unresolved. Human marrow‐derived mesenchymal stem cells (marrow stromal cells, hMSCs) give rise to osteoblasts, and their differentiation is stimulated by 1α,25(OH)2D. In addition to being targets of 1α,25(OH)2D, hMSCs can synthesize it; on the basis of those observations, we further examined the local autocrine/paracrine role of vitamin D metabolism in osteoblast differentiation. Research with hMSCs from well‐characterized subjects provides an innovative opportunity to evaluate the effects of clinical attributes on the regulation of hMSCs. Like the renal 1α‐hydroxylase, the enzyme in hMSCs is constitutively decreased with age and chronic kidney disease (CKD); both are regulated by PTH1‐34, insulin‐like growth factor 1, calcium, 1α,25(OH)2D, 25(OH)D, and fibroblast growth factor 23. CKD is associated with impaired renal biosynthesis of 1α,25(OH)2D, low bone mass, and increased fracture risk. Studies with hMSCs from CKD patients or aged subjects indicate that circulating 25(OH)D may have an important role in osteoblast differentiation on vitamin D metabolism and action in hMSCs.
Erosive pustular dermatosis of the scalp after aplasia cutis congenita in a 9‐year‐old patient: A 5‐year follow‐up
Authors: Fertig Raymond , Maddy Austin , Cadore de Farias Débora , Simão Corrêa Filho Sandro , Rigatti Marcelo , Tosti Antonella 
Published: September 2017

AbstractErosive pustular dermatosis of the scalp (EPDS) is a rare inflammatory skin disease that occurs mainly in elderly adults with a history of trauma to the scalp, but a few cases of EPDS in children have been reported. We report a rare case of EPDS after aplasia cutis congenita in a child.
A Family of Goodness‐of‐Fit Tests for Copulas Based on Characteristic Functions
Authors: Bahraoui Tarik , Bouezmarni Taoufik , Quessy Jean‐François 
Published: September 2017

AbstractA general class of rank statistics based on the characteristic function is introduced for testing goodness‐of‐fit hypotheses about the copula of a continuous random vector. These statistics are defined as L2 weighted functional distances between a nonparametric estimator and a semi‐parametric estimator of the characteristic function associated with a copula. It is shown that these statistics behave asymptotically as degenerate V‐statistics of order four and that the limit distributions have representations in terms of weighted sums of independent chi‐square variables. The consistency of the tests against general alternatives is established and an asymptotically valid parametric bootstrap is suggested for the computation of the critical values of the tests. The behaviour of the new tests in small and moderate sample sizes is investigated with the help of simulations and compared with a competing test based on the empirical copula. Finally, the methodology is illustrated on a five‐dimensional data set.
English in a post‐Brexit European Union
Authors: MODIANO MARKO 
Published: September 2017

ABSTRACTThis article speculates about the possible effects of the Brexit process on the status and functions of English in the European Union (EU). One issue here is whether Brexit will result in the weakening of the status of English within the Union, or whether this process will, ironically, strengthen the power of English as the principal working language of the EU, as well as the primary L2 among Europeans. One possibility here is that the exit of Britain from the Union will clear the sociolinguistic space for the emergence of an authentic European English, used by members of the EU as a ‘second language’ or (even) a quasi‐Outer Circle English, serving the needs of the European Union as the common link language for administration and cooperation between member states.
Cerebrovascular response to the cold pressor test – the critical role of carbon dioxide
Authors: Tymko Michael M. , Kerstens Thijs P. , Wildfong Kevin W. , Ainslie Philip N. 
Published: September 2017

New Findings
What is the central question of this study?
What is the role of carbon dioxide in the cerebral blood flow (CBF) response to the cold pressor test (CPT)?

What is the main finding and its importance?
The CBF response was elevated during the isocapnic (controlled CO2) CPT in the middle cerebral artery and the internal carotid artery compared with the poikilocapnic (uncontrolled CO2) CPT, owing to ventilation‐associated reductions in end‐tidal CO2. Furthermore, the common carotid artery vasodilated to a greater extent during the isocapnic compared with the poikilocapnic CPT, whereas the internal carotid artery vasoconstricted during both CPTs. Our data highlight the importance of CO2 control when investigating the CBF response to the CPT.

In addition to increasing sympathetic nervous activity, blood pressure and cerebral blood flow (CBF), the cold pressor test (CPT) stimulates pain receptors, which may increase ventilation above metabolic demand; this response is likely to reduce the partial pressure of end‐tidal carbon dioxide () and will attenuate elevations in CBF. Our hypotheses were as follows: (i) the CPT will elicit hyperventilation, effectively lowering ; (ii) the CBF response will be elevated during an isocapnic (controlled ) compared with a poikilocapnic CPT (uncontrolled ); and (iii) in response to the CPT, the common carotid artery (CCA) will vasodilate, while the internal carotid artery (ICA) will remain unchanged to help regulate CBF. Using a new, randomized experimental design, we measured the cerebrovascular response in the middle cerebral artery (MCA), CCA and internal carotid artery (ICA), during an isocapnic and poikilocapnic CPT in 15 participants. Blood pressure and cardiac output (finger photoplethysmography), heart rate (ECG), MCA mean velocity (transcranial Doppler ultrasound) and CCA and ICA CBF (Duplex ultrasound) were recorded during both CPT trials. Our findings were as follows: (i) ventilation increased, which reduced (−5.3 ± 6.4 mmHg) during the poikilocapnic compared with the isocapnic CPT; (ii) the CBF response was elevated during the isocapnic compared with the poikilocapnic CPT in the MCA and ICA, but not in the CCA; and (iii) the CCA dilated to a greater extent during the isocapnic compared with the poikilocapnic CPT, and the ICA vasoconstricted during both trials. Our data emphasize the importance of control in the CBF response to the CPT and in the differential vasomotor regulation between the CCA and ICA.
Exposure-Response Relationships for Isavuconazole in Patients with Invasive Aspergillosis and Other Filamentous Fungi
Authors: Desai Amit V. , Kovanda Laura L. , Hope William W. , Andes David , Mouton Johan W. , Kowalski Donna L. , Townsend Robert W. , Mujais Salim , Bonate Peter L. 
Published: September 2017

ABSTRACT

Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and infections by other filamentous fungi from the SECURE clinical trial. Two hundred thirty-one patients who received the clinical dosing regimen and had exposure parameters were included in the analysis. The primary drug exposure parameters included were predicted trough steady-state plasma concentrations, predicted trough concentrations after 7 and 14 days of drug administration, and area under the curve estimated at steady state (AUCss). The exposure parameters were analyzed against efficacy endpoints that included all-cause mortality through day 42 in the intent-to-treat (ITT) and modified ITT populations, data review committee (DRC)-adjudicated overall response at end of treatment (EOT), and DRC-adjudicated clinical response at EOT. The safety endpoints analyzed were elevated or abnormal alanine aminotransferase, increased aspartate aminotransferase, and a combination of the two. The endpoints were analyzed using logistic regression models. No statistically significant relationship (
P
> 0.05) was found between isavuconazole exposure and either efficacy or safety endpoints. The lack of association between exposure and efficacy indicates that the isavuconazole exposures achieved by clinical dosing were appropriate for treating the infecting organisms in the SECURE study and that increases in alanine or aspartate aminotransferase were not related to increase in exposures. Without a clear relationship, there is no current clinical evidence for recommending routine therapeutic drug monitoring for isavuconazole.
Emergence of Echinocandin Resistance Due to a Point Mutation in the
fks1
Gene of Aspergillus fumigatus in a Patient with Chronic Pulmonary Aspergillosis
Authors: Jiménez-Ortigosa Cristina , Moore Caroline , Denning David W. , Perlin David S. 
Published: September 2017

ABSTRACT

We have identified the first case of an
fks1
hot spot 1 point mutation causing echinocandin resistance in a clinical
Aspergillus fumigatus
isolate recovered from a chronic pulmonary aspergillosis patient with an aspergilloma who first failed azole and polyene therapy and subsequently failed micafungin treatment.
A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity
Authors: Finch Natalie A. , Zasowski Evan J. , Murray Kyle P. , Mynatt Ryan P. , Zhao Jing J. , Yost Raymond , Pogue Jason M. , Rybak Michael J. 
Published: September 2017

ABSTRACT

Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC
24
) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC
24
values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC
24
and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80;
P
= 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78;
P
= 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure.