bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venlafaxine pharmacokinetics focused on drug metabolism and potential biomarkers
Authors: Magalhães Paulo , Alves Gilberto , Llerena Adrián , Falcão Amílcar 
Published: March 2014

Abstract
Venlafaxine (VEN) is one of the safest and most effective drugs used in the treatment of selective serotonin reuptake inhibitors-resistant depression, and thereby it is nowadays one of the most commonly prescribed antidepressants. Nevertheless, patients treated with antidepressant drugs including VEN have exhibited large inter-individual variability in drug outcomes, possibly due to the influence of genetic and nongenetic factors on the drug pharmacokinetics and/or pharmacodynamics. Among them, an increased interest has emerged over the last few years on the genetic and/or phenotypic profile for drug-metabolizing cytochrome P450 isoenzymes and drug transporters such as potential predictive pharmacokinetic-based biomarkers of the variability found in drug biodisposition and antidepressant response. The integration of some of these key therapeutic biomarkers with classic therapeutic drug monitoring constitutes a promising way to individualization of VEN’s pharmacotherapy, offering to clinicians the ability to better predict and manage pharmacological treatments to maximize the drug effectiveness. Thus, this review provides an extensive discussion of the pharmacokinetics of VEN focusing in particular on metabolism issues, without forgetting the clinically relevant sources of pharmacokinetics variability (mainly the genetic sources) and aiming on the identification of phenotypic and/or genetic biomarkers for therapy optimization.
Central clearing of OTC derivatives: Bilateral vs multilateral netting
Authors: Cont Rama , Kokholm Thomas 
Published: March 2014

Abstract
We study the impact of central clearing of over-the-counter (OTC) transactions on
counterparty exposures in a market with OTC transactions across several
asset classes with heterogeneous characteristics.
The impact of
introducing a central counterparty (CCP) on expected interdealer exposure is determined by the tradeoff between multilateral netting across dealers on one hand and bilateral netting across asset classes on the other hand. We find this tradeoff to be
sensitive to assumptions on heterogeneity of asset
classes in terms of `riskyness' of the asset class as well as
correlation of exposures across asset classes.
In particular, while an analysis assuming independent,
homogeneous exposures suggests that central clearing is efficient only if one has an unrealistically high
number of participants, the opposite conclusion is reached if
differences in riskyness and correlation across asset classes are realistically taken into account.
We argue that empirically plausible specifications of model parameters lead to the conclusion that central clearing does reduce interdealer exposures: the
gain from multilateral netting in a CCP overweighs the loss of netting across asset classes in bilateral netting agreements.
When a CCP exists for interest rate derivatives, adding a CCP for credit
derivatives is shown to decrease overall exposures.
These findings are shown to be robust to the statistical assumptions of the model as well as the choice of risk measure used to quantify exposures.
Atypical Expanded-Spectrum Hemifacial Microsomia: A Case Report
Authors: Magge Keshav T. , Kim Jacqueline , Rogers Gary F. , Oh Albert K. 
Published: March 2014

Objective To present the case report of a patient with expanded hemifacial microsomia (HFM) that illustrates the complex interactions of these embryogenic factors and to review current theories and mechanism regarding the etiopathogenesis of HFM. Design and Method We present the case of an African American girl who was born at full term by cesarean section and transferred to our institution for systemic malformations. Her craniofacial findings include holoprosencephaly, cleft lip and palate, low set and posteriorly rotated ears, flat midfacial features, micrognathia, left HFM with grade 1 microtia, hypoplastic mandible, and a small preauricular pharyngeal arch remnant. Systemic anomalies included ectopic kidney, atrial-septal defect, bilateral hip dysplasia, bilateral humeroradial fusion, bilateral club feet, and bilateral low-set thumbs with the right side also being triphalangeal. Genetic evaluation did not identify a molecular diagnosis or other known syndrome. Conclusions Although vasculogenic disruption of the stapedial artery during early fetal gestation has been implicated in the etiology of HFM, the grouping and bilateral findings seen in our patient argue against this relatively simple and localized phenomenon. Instead, such diverse and widespread anomalies in the setting of expanded spectrum HFM seem to support the theory of a disorder in blastogenesis as the cause of HFM.
Relationship Between Chemokines and Dendritic Cells in Human Chronic Periodontitis
Authors: Souto Giovanna Ribeiro , Queiroz Celso Martins , Costa Fernando Oliveira , Mesquita Ricardo Alves 
Published: March 2014

Background: The purpose of this study was to evaluate the relationship between chemokines and dendritic cells (DCs) in human chronic periodontitis (CP).Methods: Gingival samples were obtained from 23 individuals with CP, and six samples of normal mucosa (NM) overlapping the third molar were used to control for the chemokine levels. Periodontal examination was conducted. Immunohistochemistry was performed for Factor XIIIa+ and cluster of differentiation (CD)1a+ immature DCs and CD83+ mature DCs. Levels of the CC chemokine ligand (CCL)2, CCL3, CCL5, CCL19, CCL20, and CXC chemokine ligand (CXCL)8 were measured in gingival tissues using enzyme‐linked immunosorbent assay. Inflammatory infiltrate, DCs, chemokines, classification of human CP, and clinical parameters were correlated and compared.Results: The expression of CCL2 and CCL20 was positively correlated with increased densities of CD1a+ DCs. CCL3 and CXCL8 were positively related to the clinical attachment level. CCL3, CCL5, CCL19, and CXCL8 levels increased in the gingival samples of patients with CP compared with NM, whereas CCL20 levels increased in advanced CP compared with mild–moderate CP.Conclusions: More CD1a+ immature DCs are related to CCL2 and CCL20. CCL3 and CXCL8 chemokines are related to a greater severity of human CP.
PCAOB Quality Control Inspection Reports and Auditor Reputation
Authors: Nagy Albert L. 
Published: March 2014

SUMMARY:
In 2002, the peer review auditor program was replaced with independent inspections of audit firms by the Public Company Accounting Oversight Board (PCAOB). The PCAOB inspections differ from the peer reviews in several key areas including the independence level of the reviewers, the nature and timing of the reviews, and the content and timing of the findings' disclosures. This study focuses on the informational value of the quality control criticisms disclosure included in Part II of the PCAOB inspection reports. After each inspection, the PCAOB issues inspection reports that include a public portion (Part I) of identified audit deficiencies, and most include a nonpublic portion (Part II) of identified quality control weaknesses. Part II of the report only becomes public if the firm fails to satisfactorily remediate the quality control deficiencies in a 12-month period. This study examines the change in audit firms' market share following the public disclosure of Part II of the inspection report. The results find that audit firms lose a significant amount of market share following the public disclosure of quality control criticisms, and suggest that such a disclosure provides a credible signal of auditor quality to audit clients.
Physical Therapists' Clinical Knowledge of Multidisciplinary Low Back Pain Treatment Guidelines
Authors: Learman Kenneth E. , Ellis Alyson R. , Goode Adam P. , Showalter Christopher , Cook Chad E. 
Published: March 2014

BackgroundNumerous clinical practice guidelines (CPGs) have been developed to assist clinicians in care options for low back pain (LBP). Knowledge of CPGs has been marginal across health-related professions.ObjectiveThe aims of this study were: (1) to measure US-based physical therapists' knowledge of care recommendations associated with multidisciplinary LBP CPGs and (2) to determine which characteristics were associated with more correct responses.DesignA cross-sectional survey was conducted.MethodsConsenting participants attending manual therapy education seminars read a clinical vignette describing a patient with LBP and were asked clinical decision-making questions regarding care, education, and potential referral. Descriptive statistics illustrating response accuracy and binary logistic regression determined adjusted associations between predictor variables and appropriate decisions.ResultsA total of 1,144 of 3,932 surveys were eligible for analysis. Correct responses were 55.9% for imaging, 54.7% for appropriate medication, 62.0% for advice to stay active, 92.7% for appropriate referral with failed care, and 16.6% for correctly answering all 4 questions. After adjustment, practicing in an outpatient facility was significantly associated with a correct decision on imaging. Female participants were more likely than male participants to correctly select proper medications, refer the patient to another health care professional when appropriate, and answer all 4 questions correctly. Participants reporting caseloads of greater than 50% of patients with LBP were more likely to select proper medications, give advice to stay active, and answer all 4 questions correctly. Participants attending more continuing education were more likely to give advice to stay active and older, and more experienced participants were more likely to appropriately refer after failed care.LimitationsThere was potential selection bias, which limits generalizability.ConclusionsThe survey identified varied understanding of CPGs when making decisions that were similar in recommendation to the CPGs. No single predictor for correct responses for LBP CPGs was found.
Multitarget, dual-electrode deep brain stimulation of the thalamus and subthalamic area for treatment of Holmes' tremor
Authors: Kobayashi Kazutaka , Katayama Yoichi , Oshima Hideki , Watanabe Mitsuru , Sumi Koichiro , Obuchi Toshiki , Fukaya Chikashi , Yamamoto Takamitsu 
Published: March 2014

Object
Holmes' tremor (HT) is generally considered to be a symptomatic tremor associated with lesions of the cerebellum, midbrain, or thalamus. Deep brain stimulation (DBS) therapy for essential tremor and parkinsonian tremor has proved quite successful. In contrast, surgical treatment outcomes for HT have often been disappointing. The use of 2 ipsilateral DBS electrodes implanted in parallel within the thalamus for severe essential tremor has been reported. Since dual-lead stimulation within a single target can cover a wider area than single-lead stimulation, it produces greater effects. On the other hand, DBS of the subthalamic area (SA) was recently reported to be effective for refractory tremor.

Methods
The authors implanted 2 DBS electrodes (one at the nucleus ventralis oralis/nucleus ventralis intermedius and the other at the SA) in 4 patients with HT. For more than 2 years after implantation, each patient's tremor was evaluated using a tremor rating scale under the following 4 conditions of stimulation: “on” for both thalamus and SA DBS; “off” for both thalamus and SA DBS; “on” for thalamus and “off” for SA DBS; and “on” for SA and “off” for thalamus DBS.

Results
The tremor in all patients was improved for more than 2 years (mean 25.8 ± 3.5 months). Stimulation with 2 electrodes exerted greater effect on the tremor than did 1-electrode stimulation. Interestingly, in all patients progressive effects were observed, and in one patient treated with DBS for 1 year, tremor did not appear even while stimulation was temporarily switched off, suggesting irreversible improvement effects.
The presence of both resting and intentional/action tremor implies combined destruction of the pallidothalamic and cerebellothalamic pathways in HT. A larger stimulation area may thus be required for HT patients. Multitarget, dual-lead stimulation permits coverage of the wide area needed to suppress the tremor without adverse effects of stimulation. Some reorganization of the neural network may be involved in the development of HT because the tremor appears several months after the primary insult. The mechanism underlying the absence of tremor while stimulation was temporarily off remains unclear, but the DBS may have normalized the abnormal neural network.

Conclusions
The authors successfully treated patients with severe HT by using dual-electrode DBS over a long period. Such DBS may offer an effective and safe treatment modality for intractable HT.
Clinical results of patients with thoracolumbar spine trauma treated according to the Thoracolumbar Injury Classification and Severity Score
Authors: Joaquim Andrei F. , Ghizoni Enrico , Tedeschi Helder , Batista Ulysses Caus , Patel Alpesh A. 
Published: March 2014

Object
The Thoracolumbar Injury Classification and Severity Score (TLICS) was developed to improve injury classification and guide surgical decision making, yet validation remains necessary. This study evaluates the neurological outcome of patients with thoracolumbar spine trauma (TLST) treated according to the TLICS.

Methods
The TLICS was prospectively applied to a consecutive series of patients treated for TLST between 2009 and 2012. Patients with a TLICS of 4 points or more were surgically treated, whereas patients with a TLICS of 3 points or fewer were conservatively managed. The primary outcome was the American Spinal Injury Association Impairment Scale (AIS).

Results
A total of 65 patients were treated. In 37 patients, the TLICS was 3 points or fewer and the patients were treated nonsurgically (Group 1). The remaining 28 patients with a TLICS of 4 or more points underwent surgical treatment (Group 2). In Group 1, 28 patients underwent some follow-up at the authors' institution; all of these patients were neurologically intact with compression or burst fractures (TLICS of 1 or 2 points; median 2). The average age in this group was 44.5 years, and follow-up ranged from 1 to 36 months (mean 6.7 months, median 3 months). Two patients (both with a TLICS of 2 points) underwent late surgery for axial back pain and mild focal kyphosis, without significant clinical improvement. In Group 2, follow-up ranged from 1 to 18 months (mean 4.4 months, median 3 months) and the TLICS ranged from 4 to 10 points (median 7 points). In this group, preoperatively, 9 (32%) patients had AIS Grade E injuries, 6 (21%) had AIS Grade C, 1 (4%) had AIS Grade B, and 12 (43%) had AIS Grade A injuries. At the final follow-up, the AIS grade was E in 11 patients (39%), D in 5 (18%), and A in 12 (43%). No patient had neurological worsening during the follow-up.

Conclusions
The TLICS can be used to guide treatment that is safe with regard to the neurological status of patients treated for TLST.
L'institution de la famille
Authors: Broda Philippe 
Published: March 2014

Cet article examine la position de Commons et Veblen sur une institution spécifique, la famille. Commons adhère au modèle conventionnel, dans lequel l’homme est responsable des moyens de subsistance et la femme, de la dimension affective. Il accepte donc l’inégalité entre les hommes et les femmes. L’évolution historique laisse simplement espérer une relation davantage fondée sur la persuasion que sur la coercition. De son côté, Veblen soutient la cause féministe. Il considère que la femme doit s’émanciper et travailler. La maintenir à l’intérieur du foyer permet au contraire l’instauration de rapports de domination qui s’expriment à travers la consommation « ostentatoire » et le loisir « par délégation ».
The Immunology of Food Allergy
Authors: Johnston Laura K. , Chien Karen B. , Bryce Paul J. 
Published: March 2014

Abstract
Food allergies represent an increasingly prevalent human health problem, and therapeutic options remain limited, with avoidance being mainstay, despite its adverse effects on quality of life. A better understanding of the key immunological mechanisms involved in such responses likely will be vital for development of new therapies. This review outlines the current understanding of how the immune system is thought to contribute to prevention or development of food allergies. Drawing from animal studies, as well as clinical data when available, the importance of oral tolerance in sustaining immunological nonresponsiveness to food Ags, our current understanding of why oral tolerance may fail and sensitization may occur, and the knowledge of pathways that may lead to anaphylaxis and food allergy–associated responses are addressed.
Preparation and Characterization of Light‐Cured Dental Resin without Methacrylate Monomers Derived from Bisphenol A
Authors: Yu Biao , Liu Dongliang , Liu Fang , He Jingwei 
Published: March 2014

ABSTRACTWith the growing attention on health, dentistry‐used methacrylate monomers like 2.2‐bis[p‐(2'‐hydroxy‐3'‐methacryl‐oxypropoxy)phenylene]propane (Bis‐GMA), which are derived from bisphenol A (BPA), have been doubted because of the estrogenic effect of BPA. In this research, new BPA‐free dental resin systems urethane dimethacrylate monomer/1,6‐bis(2'‐methacryloyoxy‐ethoxycarbonyl‐amino)‐2,4,4‐trimethylhexane/triethyleneglycol dimethacrylate (UDMTA/UDMA/TEGDMA) were prepared with the aim to replace the commonly used Bis‐GMA/TEGDMA dental resin system. Physicochemical properties such as double bond conversion, volumetric shrinkage, water sorption and solubility, flexural strength, and modulus of new resin systems were studied. The results showed that the new BPA‐free dental resins had comparable or better physicochemical properties when compared with Bis‐GMA/TEGDMA dental resin except for their water sorption that was higher than that of Bis‐GMA/TEGDMA dental resin. Therefore, the BPA‐free UDMTA/UDMA/TEGDMA resin system has potential to be used as a resin matrix of dental materials, but much more studies need to be undertaken in future.
Closing Aubry Sets I
Authors: Figalli A. , Rifford L. 
Published: March 2014

Given a Tonelli Hamiltonian H:T*M → ℝ of class Ck, with k ≥ 2, we prove the following results: (1) Assume there exist a recurrent point of the projected Aubry set and a critical viscosity subsolution u such that u is a C1 critical solution in an open neighborhood of the positive orbit of . Suppose further that u is “C2 at ”. Then there exists a Ck potential V : M → ℝ, small in C2‐topology, for which the Aubry set of the new Hamiltonian H + V is either an equilibrium point or a periodic orbit. (2) If M is two dimensional, (1) holds replacing “C1 critical solution + C2 at ” by “CM3 critical subsolution”.These results can be considered as a first step through the attempt of proving the Mañé's conjecture in C2‐topology. In a second paper [27], we will generalize (2) to arbitrary dimension. Moreover, such an extension will need the introduction of some new techniques, which will allow us to prove in [27] the Mañé's density conjecture in C1‐topology. Our proofs are based on a combination of techniques coming from finite‐dimensional control theory and Hamilton‐Jacobi theory, together with some of the ideas that were used to prove C1‐closing lemmas for dynamical systems.© 2014 Wiley Periodicals, Inc.
Genetic diversity of a successful colonizer: isolated populations of Metrioptera roeselii regain variation at an unusually rapid rate
Authors: Kaňuch Peter , Berggren Åsa , Cassel‐Lundhagen Anna 
Published: March 2014

AbstractNewly founded isolated populations need to overcome detrimental effects of low genetic diversity. The establishment success of a population may therefore depend on various mechanisms such as assortative mating, purging of deleterious alleles, creation of new mutations and/or repeated inflow of new genotypes to reduce the effects of inbreeding and further loss of genetic variation. We compared the level of genetic variation in introduced populations of an insect species (Metrioptera roeselii) far beyond its natural distribution with levels found in their respective founder populations and coupled the data with timing since establishment. This allowed us to analyze if the introduced populations showed signs of temporal changes in genetic variation and have made it possible to evaluate underlying mechanisms. For this, we used neutral genetic markers, seven microsatellite loci and a 676–bp‐long sequence of the mtDNA COI gene. All tested indices (allelic richness, unbiased expected heterozygosity, effective size, haplotype diversity, and nucleotide diversity) except inbreeding coefficient had significantly higher values in populations within the founding populations inside the continuous area of the species distribution compared with the introduced populations. A logarithmic model showed a significant correlation of both allelic richness and unbiased expected heterozygosity with age of the isolated populations. Considering the species' inferred colonization history and likely introduction pathways, we suggest that multiple introductions are the main mechanism behind the temporal pattern observed. However, we argue that influences of assortative mating, directional selection, and effects of an exceptional high intrapopulation mutation rate may have impacts. The ability to regain genetic diversity at this level may be one of the main reasons why M. roeselii successfully continue to colonize northern Europe.
Crater lake cichlids individually specialize along the benthic–limnetic axis
Authors: Kusche Henrik , Recknagel Hans , Elmer Kathryn Rebecca , Meyer Axel 
Published: March 2014

AbstractA common pattern of adaptive diversification in freshwater fishes is the repeated evolution of elongated open water (limnetic) species and high‐bodied shore (benthic) species from generalist ancestors. Studies on phenotype‐diet correlations have suggested that population‐wide individual specialization occurs at an early evolutionary and ecological stage of divergence and niche partitioning. This variable restricted niche use across individuals can provide the raw material for earliest stages of sympatric divergence. We investigated variation in morphology and diet as well as their correlations along the benthic‐limnetic axis in an extremely young Midas cichlid species,Amphilophus tolteca,endemic to the Nicaraguan crater lakeAsososcaManagua. We found thatA. toltecavaried continuously in ecologically relevant traits such as body shape and lower pharyngeal jaw morphology. The correlation of these phenotypes with niche suggested that individuals are specialized along the benthic‐limnetic axis. No genetic differentiation within the crater lake was detected based on genotypes from 13 microsatellite loci. Overall, we found that individual specialization in this young crater lake species encompasses the limnetic‐ as well as the benthic macro‐habitat. Yet there is no evidence for any diversification within the species, making this a candidate system for studying what might be the early stages preceding sympatric divergence.