bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural elucidation of phase I and II metabolites of bupivacaine in horse urine and fungi of the Cunninghamella species using liquid chromatography/multi‐stage mass spectrometry
Authors: Rydevik Axel , Bondesson Ulf , Hedeland Mikael 
Published: April 2012

RATIONALEBupivacaine is a local anaesthetic prohibited in equine sports. It is highly metabolized in the horse but a thorough description of its metabolite profile is lacking. An administration study should find appropriate analytical targets for doping control. Furthermore, knowledge of an in vitro system for production of metabolites would be beneficial.METHODSMarcain® (bupivacaine hydrochloride) was administered subcutaneously to a horse and urine samples were collected. In vitro metabolic systems consisting of the fungi Cunninghamella elegans and Cunninghamella blakesleeana were incubated with bupivacaine and bupivacaine‐d9. Samples were analyzed directly after dilution or cleaned up using liquid‐liquid extraction. Separation was achieved with liquid chromatography. Mass spectrometric analysis was performed using positive electrospray ionization with both a tandem quadrupole and an ion trap instrument using MSn and hydrogen/deuterium exchange.RESULTSIn horse urine, seven phase I metabolites were found: 3'‐ and 4'‐hydroxybupivacaine, N‐desbutylbupivacaine, two aliphatically hydroxylated metabolites, one N‐oxide, and dihydroxybupivacaine. Sulfated hydroxybupivacaine and glucuronides of 3'‐ and 4'‐hydroxybupivacaine and of dihydroxybupivacaine were also detected. All these metabolites were previously undescribed in the horse, except for 3'‐hydroxybupivacaine. 3'‐ and 4'‐Hydroxybupivacaine were designated as appropriate targets for doping control. Interestingly, all the equine phase I metabolites were also detected in the samples from C. elegans and C. blakesleeana.CONCLUSIONSThe qualitative aspects of the metabolism of bupivacaine in the horse have been investigated with many novel metabolites described. The fungi C. elegans and C. blakesleeana have proven to be relevant models for mammalian metabolism of bupivacaine and they may in the future be used to produce analytical reference materials. Copyright © 2012 John Wiley & Sons, Ltd.
Feature‐based Type Identification of File Fragments
Authors: Amirani Mehdi Chehel , Toorani Mohsen , Mihandoost Sara 
Published: April 2012

AbstractDigital information is packed into files when it is going to be stored on storage media. Each computer file is associated with a type. Type detection of computer data is a building block in different applications of computer forensics and security. Traditional methods were based on file extensions and metadata. The content‐based method is a newer approach with the lowest probability of being spoofed and is the only way for type detection of data packets and file fragments. In this paper, a content‐based method that deploys principle component analysis and neural networks for an automatic feature extraction is proposed. The extracted features are then applied to a classifier for the type detection. Our experiments show that the proposed method works very well for type detection of computer files when considering the whole content of a file. Its accuracy and speed is also significant for the case of file fragments, where data is captured from random starting points within files, but the accuracy differs according to the lengths of file fragments. Copyright © 2012 John Wiley & Sons, Ltd.
The enumeration of chemical space
Authors: Reymond Jean‐Louis , Ruddigkeit Lars , Blum Lorenz , van Deursen Ruud 
Published: April 2012

AbstractIn the field of medicinal chemistry, the chemical space describes the ensemble of all organic molecules to be considered when searching for new drugs (estimated >1060 molecules), as well as the property spaces in which these molecules are placed for the sake of describing them. Molecules can be enumerated computationally by the millions, which was first undertaken in the field of computer‐aided structure elucidation. Scoring the enumerated virtual libraries by virtual screening has recently become an attractive strategy to prioritize compounds for synthesis and testing. Enumeration methods include combinatorial linking of fragments, genetic algorithms based on cycles of enumeration and selection by ligand‐based or target‐based scoring functions, and exhaustive enumeration from first principles. The chemical space of molecules following simple rules of chemical stability and synthetic feasibility has been enumerated up to 13 atoms of C, N, O, Cl, S, forming the GDB‐13 database with 977 million structures. The database has been organized in a 42‐dimensional chemical space using molecular quantum numbers (MQN) as descriptors, which can be visualized by projection in two dimensions by principal component analysis, and searched within seconds using a Web browser available at www.gdb.unibe.ch. © 2012 John Wiley & Sons, Ltd.This article is categorized under:

Computer and Information Science > Chemoinformatics
Cerebrospinal fluid amyloid-β 2-42 is decreased in Alzheimer’s, but not in frontotemporal dementia
Authors: Bibl Mirko , Gallus Marion , Welge Volker , Esselmann Hermann , Wolf Stefanie , Rüther Eckart , Wiltfang Jens 
Published: April 2012

Abstract
Alzheimer’s dementia (AD) and frontotemporal dementias (FTD) are common and their clinical differential diagnosis may be complicated by overlapping symptoms, which is why biomarkers may have an important role to play. Cerebrospinal fluids (CSF) Aβ2-42 and 1-42 have been shown to be similarly decreased in AD, but 1-42 did not display sufficient specificity for exclusion of other dementias from AD. The objective of the present study was to clarify the diagnostic value of Aβ2-42 peptides for the differential diagnosis of AD from FTD. For this purpose, 20 non-demented disease controls (NDC), 22 patients with AD and 17 with FTD were comparatively analysed by a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol with subsequent Aβ-SDS-PAGE/immunoblot, allowing the quantification of peptides 1-38ox, 2-40 and 2-42 along with Aβ 1-37, 1-38, 1-39, 1-40, 1-40ox and 1-42. CSF Aβ1-42 was decreased in AD as compared to NDC, but not to FTD. In a subgroup of the patients analyzed, the decrease of Abeta2-42 in AD was evident as compared to both NDC and FTD. Aβ1-38 was decreased in FTD as compared to NDC and AD. For differentiating AD from FTD, Aβ1-42 demonstrated sufficient diagnostic accuracies only when combined with Aβ1-38. Aβ2-42 yielded diagnostic accuracies of over 85 % as a single marker. These accuracy figures could be improved by combining Aβ2-42 to Aβ1-38. Aβ2-42 seems to be a promising biomarker for differentiating AD from other degenerative dementias, such as FTD.
Cell surface associated glycohydrolases in normal and Gaucher disease fibroblasts
Authors: Aureli Massimo , Bassi Rosaria , Loberto Nicoletta , Regis Stefano , Prinetti Alessandro , Chigorno Vanna , Aerts Johannes M. , Boot Rolf G. , Filocamo Mirella , Sonnino Sandro 
Published: April 2012

AbstractGaucher disease (GD) is the most common lysosomal disorder and is caused by an inherited autosomal recessive deficiency in β‐glucocerebrosidase. This enzyme, like other glycohydrolases involved in glycosphingolipid (GSL) metabolism, is present in both plasma membrane (PM) and intracellular fractions. We analyzed the activities of CBE‐sensitive β‐glucosidase (GBA1) and AMP‐DNM‐sensitive β‐glucosidase (GBA2) in total cell lysates and PM of human fibroblast cell lines from control (normal) subjects and from patients with GD clinical types 1, 2, and 3. GBA1 activities in both total lysate and PM of GD fibroblasts were low, and their relative percentages were similar to those of control cells. In contrast, GBA2 activities were higher in GD cells than in control cells, and the degree of increase differed among the three GD types. The increase of GBA2 enzyme activity was correlated with increased expression of GBA2 protein as evaluated by QRT‐PCR. Activities of β‐galactosidase and β‐hexosaminidase in PM were significantly higher for GD cells than for control cells and also showed significant differences among the three GD types, suggesting the occurrence of cross‐talk among the enzymes involved in GSL metabolism. Our findings indicate that the profiles of glycohydrolase activities in PM may provide a valuable tool to refine the classification of GD into distinct clinical types.
Pathology supported genetic testing and treatment of cardiovascular disease in middle age for prevention of Alzheimer’s disease
Authors: Kotze Maritha J. , van Rensburg Susan J. 
Published: April 2012

Abstract
Chronic, multi-factorial conditions caused by a complex interaction between genetic and environmental risk factors frequently share common disease mechanisms, as evidenced by an overlap between genetic risk factors for cardiovascular disease (CVD) and Alzheimer’s disease (AD). Single nucleotide polymorphisms (SNPs) in several genes including ApoE, MTHFR, HFE and FTO are known to increase the risk of both conditions. The E4 allele of the ApoE polymorphism is the most extensively studied risk factor for AD and increases the risk of coronary heart disease by approximately 40 %. It furthermore displays differential therapeutic responses with use of cholesterol-lowering statins and acetylcholinesterase inhibitors, which may also be due to variation in the CYP2D6 gene in some patients. Disease expression may be triggered by gene-environment interaction causing conversion of minor metabolic abnormalities into major brain disease due to cumulative risk. A growing body of evidence supports the assessment and treatment of CVD risk factors in midlife as a preventable cause of cognitive decline, morbidity and mortality in old age. In this review, the concept of pathology supported genetic testing (PSGT) for CVD is described in this context. PSGT combines DNA testing with biochemical measurements to determine gene expression and to monitor response to treatment. The aim is to diagnose treatable disease subtypes of complex disorders, facilitate prevention of cumulative risk and formulate intervention strategies guided from the genetic background. CVD provides a model to address the lifestyle link in most chronic diseases with a genetic component. Similar preventative measures would apply for optimisation of heart and brain health.
Screws versus hooks: Implant cost and deformity correction in adolescent idiopathic scoliosis
Authors: Jaquith Bradley P. , Chase Adam , Flinn Phillip , Sawyer Jeffrey R. , Warner William C. , Freeman Barney L. , Kelly Derek M. 
Published: April 2012

Objective To compare the costs of two spinal implants—hook and hybrid constructs and pedicle screw constructs—in posterior spinal fusion for adolescent idiopathic scoliosis (AIS) as they relate to intraoperative deformity correction. Study design and method This retrospective study examined 50 patients with AIS who were treated with posterior spinal fusion using segmental hook-hybrid constructs (23) or pedicle screws (27). Radiographic parameters measured on immediate preoperative and initial standing postoperative scoliosis films were the coronal Cobb angles of the upper thoracic, middle thoracic, lumbar, and instrumented curves; global coronal and sagittal balance; thoracic kyphosis; lumbar lordosis; and type and number of implants used. Current implant cost data were obtained from three major spinal implant manufacturers to determine the total cost of the constructs, cost per degree of correction, cost per level fused, and cost per degree of correction of the major curve. Results After surgery, the average percentage of correction for the middle thoracic curve or major curve was 57 % in the hook-hybrid group compared to 73 % in the pedicle screw group ( P < 0.001). The average amount of correction of the major curve was 31.1° in the hook-hybrid group compared to 42.7° in the pedicle screw group ( P < 0.001). The average number of fused levels was 10.7 in the hook-hybrid group compared to 12.2 in the pedicle screw group ( P < 0.001). The average number of implants was 14.8 in the hook-hybrid group compared to 23.3 in the pedicle screw group ( P < 0.001). The average total cost of implants was $11,248 in the hook-hybrid group compared to $22,826 in the pedicle screw group ( P < 0.001), and the average cost per fused level was $1,058 in the hook-hybrid group compared to $1,878 in the pedicle screw group ( P < 0.001). The average cost per degree of correction of the major curve was $415 in the hook-hybrid group compared to $559 in the pedicle screw group ( P = 0.0014). The global coronal balance, global sagittal balance, thoracic kyphosis, and lumbar lordosis did not differ significantly between the two groups. Conclusion Pedicle screw instrumentation was shown to be more expensive overall, per fused level, and per degree of correction. Also, more implants were used and more levels were fused in the pedicle screw group than in the hook-hybrid group. Pedicle screws showed a statistically significantly greater percentage of correction of the major curve. Physicians must evaluate each patient individually and determine if the increased percentage of correction warrants the increased cost for pedicle screw constructs.
Survival hydrodynamics
Authors: Triantafyllou M. S. 
Published: April 2012

AbstractFish escaping from predators exhibit amazing acceleration. The hydrodynamic mechanisms employed to power this acceleration are highlighted in the paper by Gazzola, van Rees & Koumoutsakos (J. Fluid Mech., this issue, vol. 698, 2012, pp. 5–17), showing that the fish bends its entire body and caudal fin, in order to entrap and then accelerate as large a mass of water as possible. It is also shown that hydrodynamic optimization drives the fast-start kinematics.
Sources of Gains in Corporate Mergers: Refined Tests from a Neglected Industry
Authors: Becher David A. , Mulherin J. Harold , Walkling Ralph A. 
Published: April 2012

AbstractOur work provides refined tests of the source of merger gains in a neglected industry: utilities. Utilities offer fertile ground for analysis of traditional theories: synergy, collusion, hubris, and anticipation. Utility mergers create wealth for the combined firm, consistent with both the synergy and collusion hypotheses. To distinguish between these hypotheses, we study rival stock returns across dimensions related to collusion: deregulation, geography, and horizontal and withdrawn deals. We also find that the impact of mergers on consumer prices is consistent with synergy rather than collusion. Analysis of industry rivals that become targets also rejects collusion and is consistent with anticipation.
Earthquake spectra and near‐source attenuation in the Cascadia subduction zone
Authors: Gomberg J. , Creager K. , Sweet J. , Vidale J. , Ghosh A. , Hotovec A. 
Published: April 2012

Models of seismic source displacement spectra are flat from zero to some corner frequency, fc, regardless of source type. At higher frequencies spectral models decay as f−1 for slow events and as f−2 for fast earthquakes. We show that at least in Cascadia, wave propagation effects likely control spectral decay rates above ∼2 Hz. We use seismograms from multiple small‐aperture arrays to estimate the spectral decay rates of near‐source spectra of 37 small ‘events’ and find strong correlation between source location and decay rate. The decay rates (1) vary overall by an amount in excess of that inferred to distinguish slow sources from fast earthquakes, (2) are indistinguishable for sources separated by a few tens of km or less, and (3) separate into two populations that correlate with propagation through and outside a low‐velocity zone imaged tomographically. We find that some events repeat, as is characteristic of low‐frequency earthquakes (LFEs), but have spectra similar to those of non‐repeating earthquakes. We also find no correlation between spectral decay rates and rates of ambient tremor activity. These results suggest that earthquakes near the plate boundary, at least in Cascadia, do not distinctly separate into ‘slow’ and ‘fast’ classes, and correctly accounting for propagation effects is necessary to characterize sources.
Site Choice among Minnesota Walleye Anglers: The Influence of Resource Conditions, Regulations and Catch Orientation on Lake Preference
Authors: Carlin Caroline , Schroeder Susan A. , Fulton David C. 
Published: April 2012

Abstract
Understanding angler site choice preferences is important in the management of recreational fisheries to forecast angling demand and effort. This study investigated lake choice by recreational anglers fishing for walleye Sander vitreus in Minnesota and examined how choices were influenced by lake characteristics, angler demographics, and angler catch orientation. We collected data through a stated choice preference experiment using a survey administered to a sample of Minnesota resident (n = 1096) and nonresident (n = 535) anglers. Multinomial probit choice models were used to estimate preferences in lake choice. Lake characteristics included walleye abundance, walleye size, bag limit, slot limit, and distance from primary residence. Models included (1) lake characteristics only, (2) lake characteristics and angler demographics, and (3) lake characteristics with angler demographics and catch orientation factors. The coefficients of lake attributes had expected signs with greater preference for higher walleye abundance, larger walleye, bigger bag limits, absence of slot limits, and less driving time from home (P &lt; 0.001 for all lake characteristics in the first model). Lake choice was influenced by the interaction of lake characteristics with age (negative with abundance of fish, P &lt; 0.100; positive with distance from home, P &lt; 0.001), metropolitan and out-of-state residency (positive with distance from home, P &lt; 0.001), and strength of preference for walleye (positive with distance, P &lt; 0.01). A stronger orientation to keep walleye was positively related to increased bag limits (P &lt; 0.001) and negatively related to slot limits (P &lt; 0.01). Study results have clear implications for managers—bag limits, relative to other lake characteristics, had a large influence on anglers’ lake choice for walleye fishing. Because of a stronger catch orientation among walleye anglers, low bag limits reduce lake preference. The results clarify the trade-offs that anglers make when selecting a place to fish for walleye and demonstrate how different management scenarios might influence angler participation.
Received July 20, 2011; accepted January 4, 2012
Meta‐analysis of randomized controlled trials evaluating left ventricular vs. biventricular pacing in heart failure: effect on all‐cause mortality and hospitalizations
Authors: Boriani Giuseppe , Gardini Beatrice , Diemberger Igor , Reggiani Maria Letizia Bacchi , Biffi Mauro , Martignani Cristian , Ziacchi Matteo , Valzania Cinzia , Gasparini Maurizio , Padeletti Luigi , Branzi Angelo 
Published: April 2012

AimRandomized controlled trials (RCTs) showed that biventricular (BiV) pacing reduces heart failure (HF) hospitalizations and mortality in patients with New York Heart Association (NYHA) class III–IV HF, left ventricular (LV) dysfunction, and wide QRS. We performed a systematic review and meta‐analysis of the RCTs comparing LV‐only vs. biventricular (BiV) pacing in candidates for cardiac resynchronization therapy (CRT).Methods and resultsThe systematic review selected five RCTs (out of 1888 analysed reports) with a cumulative number of 372 patients randomized to BiV pacing and 258 to LV‐only pacing. The meta‐analysis shows that BiV pacing is not superior to LV‐only pacing and that these two pacing modalities do not differ with regard to death or heart transplantation [LV‐only vs. BiV pacing odds ratio (OR) 1.24, 95% confidence interval (CI) 0.57–2.70 with the fixed effect model, OR 1.25, 95% CI 0.48–3.24 with the random effect model]. Specific data on hospitalizations were available only in two RCTs with a cumulative number of 127 patients randomized to BiV and 123 to LV‐only pacing. The meta‐analysis shows that BiV pacing is not superior to LV‐only pacing and that these two pacing modalities do not differ with regard to this outcome (LV‐only vs. BiV pacing OR 0.86, 95% CI 0.49–1.50 with the fixed effect model, OR 0.86, 95% CI 0.49–1.50 with the random effect model).ConclusionsBiventricular pacing is not superior to LV‐only pacing, and these two pacing modalities appear to achieve similar efficacy in candidates for CRT for moderate to severe HF, in terms of all‐cause mortality and hospitalizations during follow‐up.
Double jeopardy: the influence of excessive daytime sleepiness and impaired cognition on health‐related quality of life in adults with heart failure
Authors: Riegel Barbara , Ratcliffe Sarah J. , Weintraub William S. , Sayers Steven L. , Goldberg Lee R. , Potashnik Sheryl , Weaver Terri E. , Pressler Susan J. 
Published: April 2012

AimsTo determine how excessive daytime sleepiness (EDS) and impaired cognition contribute to health‐related quality of life (HRQL) in heart failure (HF).Methods and resultsAdults with chronic HF were enrolled into a prospective cohort study. Data were obtained from 280 subjects enrolled from three sites in the northeastern USA; 242 completed the 6‐month study. At baseline, cohorts with and without EDS were identified using the Epworth Sleepiness Scale. Each EDS group was further subdivided into those with and without impaired cognition using a battery of five neuropsychological tests. Two disease‐specific measures, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Functional Outcomes of Sleep Questionnaire (FOSQ), were used to measure HRQL. General linear modelling of square‐transformed variables was used to test the hypothesis that cohort membership was a significant predictor of HRQL. At 6 months the remaining sample was 62.5 [standard deviation (SD) 12] years old, mostly male (63%), white (65%), and functionally compromised [72% New York Heart Association (NYHA) class III/IV]. The cohort with both EDS and impaired cognition had the lowest KCCQ overall summary score (60.5 ± 22.5) compared with the cohort without EDS or impaired cognition (74.6 ± 17.4, P ≤ 0.001). A similar effect was seen on the FOSQ (16.0 ± 2.8 vs. 18.5 ± 2.2, P < 0.001).ConclusionImpaired cognition alone did not explain poor HRQL, but the addition of EDS poses a significant risk for poor HRQL. Interventions designed to influence EDS may improve HRQL in this population.
The Role of Application Assistance and Information in College Decisions: Results from the H&R Block Fafsa Experiment*
Authors: Bettinger Eric P. , Long Bridget Terry , Oreopoulos Philip , Sanbonmatsu Lisa 
Published: April 2012

Abstract
Growing concerns about low awareness and take-up rates for government support programs like college financial aid have spurred calls to simplify the application process and enhance visibility. We present results from a randomized field experiment in which low-income individuals receiving tax preparation help were also offered immediate assistance and a streamlined process to complete the Free Application for Federal Student Aid (FAFSA) for themselves or their children. Treated participants were also provided with aid estimates that were compared against tuition cost amounts for nearby colleges. The combined assistance and information treatment substantially increased FAFSA submissions and ultimately the likelihood of college attendance, persistence, and aid receipt. In particular, high school seniors whose parents received the treatment were 8 percentage points more likely to have completed two years of college, going from 28% to 36%, during the first three years following the experiment. Families who received aid information but no assistance with the FAFSA did not experience improved outcomes. The findings suggest many other opportunities for using personal assistance to increase participation in programs that require filling out forms to become eligible.