bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian Quantile Regression for Count Data with Application to Environmental Epidemiology
Authors: Lee Duncan , Neocleous Tereza
Published: July 2010

Quantile regression estimates the relationship between covariates and the τth quantile of the response distribution, rather than the mean. We present a Bayesian quantile regression model for count data and apply it in the field of environmental epidemiology, which is an area in which quantile regression is yet to be used. Our methods are applied to a new study of the relationship between long-term exposure to air pollution and respiratory hospital admissions in Scotland. We observe a decreasing relationship between pollution and the τth quantile of the response distribution, with a relative risk ranging between 1.023 and 1.070.
Simultaneous Confidence Bands in Curve Prediction Applied to Load Curves
Authors: Azaïs J. M. , Bercu S. , Fort J. C. , Lagnoux A. , Lé P.
Published: July 2010

Considering the problem of predicting the whole annual load curve of some Electricité de France customers from easily available explanatory variables, we derive simultaneous confidence bands for this prediction. The methodology that is developed, which can be applied to numerous problems, uses results on the maximum of Gaussian sequences. The paper ends with the application to Electricité de France’s problem.
Estimating a Cosmological Mass Bias Parameter with Bootstrap Bandwidth Selection
Authors: Loh Ji Meng , Jang Woncheol
Published: July 2010

We focus on selecting optimal bandwidths for non-parametric estimation of the two-point correlation function of a point pattern. We obtain these optimal bandwidths by using a bootstrap approach to select a bandwidth that minimizes the integrated squared error. The variance term is estimated by using a non-parametric spatial bootstrap, whereas the bias term is estimated with a plug-in approach using a pilot estimator of the two-point correlation function based on a parametric model. The choice of parametric model for the pilot estimator is very flexible. Depending on applications, parametric statistical point models, physical models or functional models can be used. We also explore the use of the procedure for selecting adaptive optimal bandwidths. We investigate the performance of the bandwidth selection procedure by using a simulation study. In our data example, we apply our method to a Sloan Digital Sky Survey galaxy cluster catalogue by using a pilot estimator based on the power law functional model in cosmology. The resulting non-parametric two-point correlation function estimate is then used to estimate a cosmological mass bias parameter that describes the relationship between the galaxy mass distribution and the underlying matter distribution.
Non‐invasive diagnosis and monitoring of actinic cheilitis with reflectance confocal microscopy
Authors: Ulrich M , González S , Lange‐Asschenfeldt B , Roewert‐Huber J , Sterry W , Stockfleth E , Astner S
Published: July 2010

Background  Actinic cheilitis (AC) represents the equivalent of actinic keratosis on the lip. Various treatment modalities are available and the efficacy of diclofenac in hyaluronic acid has recently been described. Reflectance confocal microscopy (RCM) is a non‐invasive imaging technique which has recently been applied for the diagnosis of actinic keratoses. Herein, we describe the applicability of RCM for the diagnosis of AC and for monitoring of treatment response of AC to diclofenac in hyaluronic acid.

Methods  Ten Caucasian patients with clinical suspicion for AC were included in this study. To obtain a non‐invasive diagnosis, RCM was performed at baseline, followed by biopsy and respective confocal‐histopathological correlation. Six patients with a histological diagnosis of AC were treated with diclofenac in hyaluronic acid, whereby monitoring was performed by RCM.

Results  Reflectance confocal microscopy was able to correctly identify 6/7 cases of AC and 3/3 cases of benign lesions. The most important RCM criteria for diagnosis of AC were cellular atypia at the stratum spinosum and granulosum with atypical honeycomb pattern. One patient with AC was misclassified as inflammatory cheilitis by RCM as it showed marked inflammatory response and lacked clear signs of cellular atypia on RCM imaging. Following topical treatment with diclofenac gel, 5/6 patients (83%) showed a good treatment response with regression of dysplasia on consecutive RCM examination.

Conclusions  Reflectance confocal microscopy is a promising tool for the non‐invasive diagnosis and monitoring of actinic cheilitis. However, marked inflammation represents a potential diagnostic pitfall. In this regard, biopsy should be performed in doubtful cases.
Psychological distress and investment in one’s appearance in patients with pemphigus
Authors: Mazzotti E , Mozzetta A , Antinone V , Alfani S , Cianchini G , Abeni D
Published: July 2010

Background  Pemphigus vulgaris is a chronic disease not currently curable. Physical involvement and the impact of chronic therapies can lead patients to changes in psychological and relational areas.

Objectives  To provide a measure of psychological distress, dysfunctional investment in one's appearance, and their relationship.

Methods  Self‐administered questionnaires (ASI, HADS) were given to 74 pemphigus inpatients.

Results  Strong associations between psychological distress and dysfunctional investment in one's appearance were observed [adjusted odds ratio (OR) = 7.36, 95% confidence intervals (CI) 1.20–45.11; OR 5.38, 95% CI 0.81–35.87, respectively, for appearance stereotyping and body‐image vulnerability], together with a perceived high disease severity (OR 6.03, 95% CI 1.90–23.46).

Conclusions  Our results are compatible with the idea that some forms of psychological distress could be in part due to one's perception of his/her own body image.
Focal dermal hypoplasia in a male patient due to mosaicism for a novel PORCN single nucleotide deletion
Authors: Vreeburg M , van Geel M , van den Heuij LGT , Steijlen PM , van Steensel MAM
Published: July 2010

Background  Focal dermal hypoplasia (FDH) is an X‐linked dominant disorder caused by nonsense mutations and deletions in the PORCN gene coding for a transmembrane endoplasmic reticulum protein required for Wingless signalling. Symptoms consist mainly of linear atrophic skin defects, skeletal deformities and, in many cases, mental retardation. Osteopathia striata is a nearly constant feature. Approximately 90% of patients are women. A few instances of father‐to‐daughter transmission and a number of sporadic male cases presumably as a result of somatic mosaicism have been recorded.

Objectives  The aim of this study was to demonstrate the presence of somatic mosaicism for PORCN mutations in a male patient.

Methods  We sequenced the PORCN gene in different tissues from a boy with symptoms of FDH.

Results  We demonstrate post‐zygotic mosaicism for a novel deletion in the PORCN gene.

Conclusions  A novel PORCN deletion, present in a post‐zygotic mosaic, causes focal dermal hyplasia in a male patient.
Efficacy and safety of itraconazole pulses vs. continuous regimen in cutaneous sporotrichosis
Authors: Song Y , Zhong S‐X , Yao L , Cai Q , Zhou J‐F , Liu Y‐Y , Huo S‐S , Li S‐S
Published: July 2010

Background  Primary observation of using itraconazole pulse regimen (commonly used for onychomycosis) in five sporotrichosis patients produced satisfactory effect, but there are no randomized controlled trials to assess this regimen and to compare with routine continuous regimen.

Objectives  The aim of this study was to compare the efficacy and safety of itraconazole pulse regimen, as a new treatment option for cutaneous sporotrichosis, with continuous regimen.

Methods  A prospective, randomized, evaluator‐blind, controlled study was performed. A total of 50 cutaneous sporotrichosis patients were divided randomly into two groups: Pulsed Rx (npulse = 25), treated with itraconazole 200 mg b.i.d. for 1 week and off for 3 weeks; Daily Rx (ncont = 25), treated with itraconazole 100 mg bid continuously. In total, 46 patients (npulse = 22, ncont = 24) were assessable at the end of the study. Cure rates at weeks 12, 24 and 48 along with the course of treatment and the rate of side effects were evaluated.

Results  In Pulsed Rx, the cure rates at weeks 12, 24 and 48 were 77.3%, 81.8%, 81.8% respectively. The mean course of treatment was 2.65 ± 0.81 pulses and the rate of side effects was 4.5%; In Daily Rx, the corresponding cure rates were 79.2%, 91.7% and 95.8% respectively. The mean course of treatment was 2.80 ± 2.33 months and the rate of side effects was 16.7%. These parameters had no significant difference between the two groups (P > 0.05).

Conclusion  The efficacy and safety of Itraconazole pulse regimen for cutaneous sporotrichosis were similar to the continuous regimen. It is an effective and safe alternative treatment for cutaneous sporotrichosis, which can also lower the cost by decreasing the number of capsules.
Reliability and cost‐effectiveness of sentinel lymph node excision under local anaesthesia versus general anaesthesia for malignant melanoma: a retrospective analysis in 300 patients with malignant melanoma AJCC Stages I and II
Authors: Stoffels I , Dissemond J , Körber A , Hillen U , Poeppel T , Schadendorf D , Klode J
Published: July 2010

Background  Sentinel lymph node excision (SLNE) for the detection of regional nodal metastases and staging of malignant melanoma has resulted in some controversies in international discussions, as it is a cost‐intensive surgical intervention with potentially significant morbidity.

Objective  The present retrospective study seeks to clarify the effectiveness and reliability of SLNE performed under tumescent local anaesthesia (TLA) and whether SLNE performed under TLA can reduce costs and morbidity. Therefore, our study is a comparison of SLNE performed under TLA and general anaesthesia (GA).

Patients  We retrospectively analysed data from 300 patients with primary malignant melanoma with a Breslow index of ≥1.0 mm.

Results  Altogether, 211 (70.3%) patients underwent SLNE under TLA and 89 (29.7%) patients underwent SLNE under GA. A total of 637 sentinel lymph nodes (SLN) were removed. In the TLA group 1.98 SLN/patient and in the GA group 2.46 SLN/patient were removed (median value). Seventy patients (23.3%) had a positive SLN. No major complications occurred. The costs for SLNE were significantly less for the SLNE in a procedures room performed under TLA (mean € 30.64) compared with SLNE in an operating room under GA (mean € 326.14, P < 0.0001).

Conclusion  In conclusion, SLNE performed under TLA is safe, reliable, and cost‐efficient and could become the new gold standard in sentinel lymph node diagnostic procedures.
How useful is the Social Communication Questionnaire in toddlers at risk of autism spectrum disorder?
Authors: Oosterling Iris , Rommelse Nanda , de Jonge Maretha , van der Gaag Rutger Jan , Swinkels Sophie , Roos Sascha , Visser Janne , Buitelaar Jan
Published: July 2010

Background:  The Social Communication Questionnaire (SCQ) is a screening instrument with established validity against the Autism Diagnostic Interview‐Revised (ADI‐R) in children aged 4 years and older. Indices of diagnostic accuracy have been shown to be strong in school‐aged samples; however, relatively little is known about the performance of the SCQ in toddlers at risk of autism spectrum disorder (ASD).

Methods:  This study replicates and extends previous research by Corsello et al. (2007) in a comparatively large (N = 208), substantially younger (20–40 months) sample of children at high risk of ASD. The usefulness of the SCQ as a second‐level screening instrument with different cut‐off scores was evaluated in relation to IQ, age, and type of ASD diagnosis. The use of the SCQ as compared to the ADI‐R was evaluated against clinical diagnosis, both alone and in combination with the ADOS.

Results:  The SCQ with different cut‐offs consistently showed an unsatisfactory balance between sensitivity and specificity in screening for ASD in high‐risk toddlers, with only a few exceptions for specific age, IQ, or diagnostic groups. Even though the SCQ and ADI‐R were highly correlated, diagnostic agreement with the best evidence clinical diagnosis was poor for both measures. The ADOS used alone consistently had the highest predictive value. For autism versus not‐autism, the combined SCQ and ADOS performed as well as the ADOS alone and notably better than the combination ADI‐R and ADOS.

Conclusions:  The SCQ is likely to result in a number of false‐positive findings, particularly in children with autism symptomatology, and the balance between sensitivity and specificity is poor. The ADOS should be considered the most valid and reliable diagnostic instrument in these very young at‐risk children.
Predicting moisture dynamics of fine understory fuels in a moist tropical rainforest system: results of a pilot study undertaken to identify proxy variables useful for rating fire danger
Authors: Ray David , Nepstad Dan , Brando Paulo
Published: July 2010

Featured paper: See Editorial p553
Low carbohydrate diet affects the oxygen uptake on‐kinetics and rating of perceived exertion in high intensity exercise
Authors: Lima‐Silva Adriano E. , Pires FláVio O. , Bertuzzi Rômulo C. M. , Lira Fábio S. , Casarini Dulce , Kiss Maria Augusta P. D. M.
Published: July 2010

The aim of this study was to determine if the carbohydrate (CHO) availability alters the rate of increase in the rating of perceived exertion (RPE) during high intensity exercise and whether this would be associated with physiological changes. Six males performed high intensity exercise after 48 h of controlled, high CHO (80%) and low CHO (10%) diets. Time to exhaustion was lower in the low compared to high CHO diet. The rate of increase in RPE was greater and the VO2 slow component was lower in the low CHO diet than in the control. There was no significant condition effect for cortisol, insulin, pH, plasma glucose, potassium, or lactate concentrations. Multiple linear regression indicated that the total amplitude of VO2 and perceived muscle strain accounted for the greatest variance in the rate of increase in RPE. These results suggest that cardiorespiratory variables and muscle strain are important afferent signals from the periphery for the RPE calculations.
Recipe development for production of a Turkish dessert, cheese halva
Authors: GÜVEN SELMA , DEMIR HÜLYA
Published: July 2010

Within the scope of this study, six different recipes were developed for the production of cheese halva. White unsalted cheeses were produced by using cow milk or sheep milk or a blend of cow and sheep milk, and each was produced with white flour or semolina. It was found that there was no significant difference among the recipes in terms of chemical properties, but there were significant differences in sensory properties. Moreover, the microbial quality of cheese halva were determined. It was found that the shelflife of cheese halva can be up to 10 days at ambient temperature and for up to 1 month when refrigerated.
Enhancement of nisin production in milk by conjugal transfer of the protease‐lactose plasmid pLP712 to the wild strain Lactococcus lactis UQ2
Authors: GARCÍA‐PARRA MARÍA D , CAMPELO ANA B , GARCÍA‐ALMENDÁREZ BLANCA E , REGALADO CARLOS , RODRÍGUEZ ANA , MARTÍNEZ BEATRIZ
Published: July 2010

Lactococcus lactis UQ2 is a wild nisin A producer isolated from a Mexican cheese that grows poorly in milk. Conjugal matings with L. lactis NCDO712 to transfer the Lac+ Prt+ plasmid pLP712 and selection with nisin and lactose yielded L. lactis NCDO712 NisA+. Naturally rifampicin resistant L. lactis UQ2Rif was isolated to provide an additional selective marker. The identity of a transconjugant L. lactis UQ2Rif Lac+ was confirmed by RAPD‐PCR fingerprinting, nisA PCR amplification, nisin production, presence of pLP712 and phospho‐β‐galactosidase activity. This strain performed well in milk and synthesised 200 IU/mL nisin, 40 times more than the original strain.
More to teamwork than knowledge, skill and attitude
Authors: Siassakos D , Draycott TJ , Crofts JF , Hunt LP , Winter C , Fox R
Published: July 2010

Please cite this paper as: Siassakos D, Draycott T, Crofts J, Hunt L, Winter C, Fox R. More to teamwork than knowledge, skill and attitude. BJOG 2010;117:1262–1269.

Objective  To assess whether team performance in simulated eclampsia is related to the knowledge, skills and attitudes of individual team members.

Design  Cross‐sectional analysis of data from the Simulation and Fire Drill Evaluation randomised controlled trial.

Setting  Six secondary and tertiary maternity units in south‐west England.

Participants  One hundred and fourteen maternity professionals in 19 teams of six members; one senior and one junior obstetrician; two senior and two junior midwives.

Methods  We validated a team performance ranking scheme with respect to magnesium administration (Magnesium Administration Rank, MAR) by expert consensus (face validity) and correlation with clinical measures (construct validity). We tested for correlation between MAR and measures of knowledge, skills and attitudes.

Main outcome measures  Correlation between team performance (MAR) and scores in validated multiple‐choice questionnaires (MCQs) (knowledge), a measure of individual manual skill to manage an obstetric emergency (skill) and scores in a widely used teamwork/safety attitude questionnaire (attitude).

Results  There was no relationship between team performance and cumulative individual MCQs, skill or teamwork/safety attitude scores.

Conclusions  The knowledge, manual skills and attitudes of the individuals comprising each team, measured by established methods, did not correlate in this study with the team’s clinical efficiency in the management of simulated eclampsia. The inference is that unidentified characteristic(s) play a crucial part in the efficiency of teams managing emergencies. Any emphasis of training programmes to promote individual knowledge, skills and attitudes alone may have to be re‐examined. This highlights a need to understand what makes a team efficient in dealing with clinical emergencies.
Effects of trimetazidine, a partial inhibitor of fatty acid oxidation, on ventricular function and survival after myocardial infarction and reperfusion in the rat
Authors: Mouquet Frederic , Rousseau Delphine , Domergue‐Dupont Valerie , Grynberg Alain , Liao Ronglih
Published: July 2010

Trimetazidine (TMZ), a partial inhibitor of fatty acid oxidation, has been effective in treating chronic angina, but its effects on the development of post‐myocardial infarction (MI) left ventricular remodeling are not defined. In this study, we tested whether chronic pre‐MI administration of TMZ would be beneficial during and after acute MI. Two‐hundred male Wistar rats were studied in four groups: sham + TMZ diet (n = 20), sham + control diet (n = 20), MI + TMZ diet (n = 80), and MI + control diet (n = 80) splitted into one short‐term and one long‐term experiments. Sham surgery consisted of a thoracotomy without coronary ligation. MI was induced by coronary occlusion followed by reperfusion. Left ventricle (LV) function and remodeling were assessed by serial echocardiography throughout a 24‐week post‐MI period. LV remodeling was also assessed by quantitative histological analysis of post‐MI scar formation at 24 weeks post‐MI. During the short‐term experiment, 10/80 rats died after MI, with no difference between groups (MI + control = 7/40, MI + TMZ = 3/40, P = 0.3). In the long‐term experiment, the deaths occurred irregularly over the 24 weeks with no difference between groups (MI + control = 16% mortality, MI + TMZ = 17%, P = 0.8). There was no difference between groups as regard to LV ejection fraction (MI + control = 36 ± 13%, MI + TMZ = 35 ± 13%, P = 0.6). In this experimental model, TMZ had no effects on the post‐MI occurrence of LV dysfunction or remodeling. Further investigations are warranted to assess whether the partial inhibition of fatty acid oxidation may limit the ability of the heart to respond to acute severe stress.
Effects of repeated maprotiline and fluoxetine treatment on gene expression of catecholamine synthesizing enzymes in adrenal medulla of unstressed and stressed rats
Authors: Spasojevic N. , Gavrilovic L. , Dronjak S.
Published: July 2010

1 Repeated maprotiline (a noradrenaline reuptake inhibitor) and fluoxetine (a serotonin reuptake inhibitor) treatment on gene expression of catecholamine biosynthetic enzymes were examined in adrenal medulla of unstressed control and chronic unpredictable mild stressed rats.

2 Maprotiline did not change gene expression of catecholamine biosynthetic enzymes in control and stressed rats.

3 Fluoxetine increased gene expression of tyrosine hydroxylase (TH) and dopamine‐β‐hydroxylase (DBH), but did not phenylethanolamine N‐methyltransferase in both unstressed and chronic unpredictable mild stressed animals.

4 In conclusion, we have demonstrated that repeated administration of fluoxetine enhanced gene transcription of TH and DBH and subsequently stimulates noradrenaline synthesis in adrenal medulla of control and stressed rats.
A Method to Calibrate the Measured Responses by MEMS Accelerometers
Authors: Badri A. , Sinha J. K. , Albarbar A.
Published: July 2010

Abstract:  Micro‐electro‐mechanical system (MEMS) accelerometers have been receiving attention because of their low cost and small size. Accurate vibration measurements of both amplitude and phase at all frequencies in the measurement frequency range are important for the reliable vibration analysis. However, it has been observed that such accelerometers show some deviation. Hence, a simple calibration method in frequency domain has been used for correcting both amplitude and phase for the measured signals by the MEMS accelerometers. The paper presents the calibration procedure and results of this study applied on two MEMS accelerometers with different technical specifications.
Smoothing Measured Displacements and Computing Strains Utilising Finite Element Method
Authors: Yoneyama S.
Published: July 2010

Abstract:  A method for smoothing measured displacements and computing strains utilising finite element and least‐squares methods is proposed. Nodal displacement values of a finite element model are determined by fitting the interpolation functions of elements to measured displacement values using the method of least‐squares. The displacements in the region where the measurement values are not obtained or unreliable are determined by solving finite element equations. Then, strains are obtained using a displacement‐strain relationship. The validity is demonstrated by applying the proposed method to the displacement distributions of a plate with a hole obtained using finite element method and those around a crack tip obtained using digital image correlation. Results show that the displacements and the strains can be determined accurately by the proposed method. Furthermore, the strains near free boundaries and strain concentration region can be computed. As strains can be evaluated easily and accurately, the proposed method can be used as one of the data processing methods for optical methods.
Guidelines for reporting experiments involving animals: the ARRIVE guidelines
Authors: McGrath JC , Drummond GB , McLachlan EM , Kilkenny C , Wainwright CL
Published: July 2010

British Journal of Pharmacology (BJP) is pleased to publish a new set of guidelines for reporting research involving animals, simultaneously with several other journals; the ‘ARRIVE’ guidelines (Animals in Research: Reporting In Vivo Experiments). This editorial summarizes the background to the guidelines, gives our view of their significance, considers aspects of specific relevance to pharmacology, re‐states BJP's guidelines for authors on animal experiments and indicates our commitment to carrying on discussion of this important topic. We also invite feedback via the British Pharmacological Society website.
Over‐expression of mitogen‐activated protein kinase phosphatase‐2 enhances adhesion molecule expression and protects against apoptosis in human endothelial cells
Authors: Al‐Mutairi Mashael , Al‐Harthi Sameer , Cadalbert Laurence , Plevin Robin
Published: July 2010

BACKGROUND AND PURPOSE We assessed the effects of over‐expressing the dual‐specific phosphatase, mitogen‐activated protein (MAP) kinase phosphatase‐2 (MKP‐2), in human umbilical vein endothelial cells (HUVECs) on inflammatory protein expression and apoptosis, two key features of endothelial dysfunction in disease.

EXPERIMENTAL APPROACHES We infected HUVECs for 40 h with an adenoviral version of MKP‐2 (Adv.MKP‐2). Tumour necrosis factor (TNF)‐α‐stimulated phosphorylation of MAP kinase and protein expression was measured by Western blotting. Cellular apoptosis was assayed by FACS.

KEY RESULTS Infection with Adv.MKP‐2 selectively abolished TNF‐α‐mediated c‐Jun‐N‐terminal kinase (JNK) activation and had little effect upon extracellular signal‐regulated kinase or p38 MAP kinase. Adv.MKP‐2 abolished COX‐2 expression, while induction of the endothelial cell adhesion molecules, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM), two NFκB‐dependent proteins, was not affected. However, when ICAM and VCAM expression was partly reduced by blockade of the NFκB pathway, Adv.MKP‐2 was able to reverse this inhibition. This correlated with enhanced TNF‐α‐induced loss of the inhibitor of κB (IκB)α loss, a marker of NFκB activation. TNF‐α in combination with NFκB blockade also increased HUVEC apoptosis; this was significantly reversed by Adv.MKP‐2. Protein markers of cellular damage and apoptosis, H2AX phosphorylation and caspase‐3 cleavage, were also reversed by MKP‐2 over‐expression.

CONCLUSIONS AND IMPLICATIONS Over‐expression of MKP‐2 had different effects upon the expression of inflammatory proteins due to a reciprocal effect upon JNK and NFκB signalling, and also prevented TNF‐α‐mediated endothelial cell death. These properties may make Adv.MKP‐2 a potentially useful future therapy in cardiovascular diseases where endothelial dysfunction is a feature.
Participation of nuclear factor (erythroid 2‐related), factor 2 in ameliorating lithocholic acid‐induced cholestatic liver injury in mice
Authors: Tan KP , Wood GA , Yang M , Ito S
Published: July 2010

BACKGROUND AND PURPOSE Lithocholic acid (LCA), the most toxic bile acid, induces cholestatic liver injury in rodents. We previously showed that LCA activates the oxidative stress‐responsive nuclear factor (erythroid‐2 like), factor 2 (Nrf2) in cultured liver cells, triggering adaptive responses that reduce cell injury. In this study, we determined whether Nrf2 protects the liver against LCA‐induced toxicity in vivo.

EXPERIMENTAL APPROACH Nrf2 disrupted (Nrf2−/−) and wild‐type mice were treated with LCA (125 mg·kg−1 body weight) to induce liver injury. Levels of mRNA, protein and function of important Nrf2 target genes coupled with liver histology and injury biomarkers of mice were examined.

KEY RESULTS In 4 day LCA treatments, we observed a significantly higher hepatic induction of Nrf2 target, cytoprotective genes including thioredoxin reductase 1, glutamate cysteine ligase subunits, glutathione S‐transferases, haeme oxygenase‐1 and multidrug resistance‐associated proteins 3 and 4 in the wild type as compared with the Nrf2−/− mice. Moreover, basal and LCA‐induced hepatic glutathione and activities of glutathione S‐transferases and thioredoxin reductases were higher in wild‐type than in Nrf2−/− mice. This reduced production of cytoprotective genes against LCA toxicity rendered Nrf2−/− mice more susceptible to severe liver damage with the presence of multifocal liver necrosis, inflamed bile ducts and elevation of lipid peroxidation and liver injury biomarkers, such as alanine aminotransferase and alkaline phosphatase.

CONCLUSIONS AND IMPLICATIONS Nrf2 plays a crucial cytoprotective role against LCA‐induced liver injury by orchestrating adaptive responses. The pharmacological potential of targeting liver Nrf2 in the management of cholestatic liver diseases is proposed.
Curcumin prevents leptin raising glucose levels in hepatic stellate cells by blocking translocation of glucose transporter‐4 and increasing glucokinase
Authors: Tang Youcai , Chen Anping
Published: July 2010

BACKGROUND AND PURPOSE Hyperleptinemia is commonly found in obese patients, associated with non‐alcoholic steatohepatitis and hepatic fibrosis. Hepatic stellate cells (HSCs) are the most relevant effectors during hepatic fibrogenesis. We recently reported that leptin stimulated HSC activation, which was eliminated by curcumin, a phytochemical from turmeric. This study was designed to explore the underlying mechanisms, focusing on their effects on intracellular glucose in HSCs. We hypothesized that leptin stimulated HSC activation by elevating the level of intracellular glucose, which was eliminated by curcumin by inhibiting the membrane translocation of glucose transporter‐4 (GLUT4) and inducing the conversion of glucose to glucose‐6‐phosphate (G‐6‐P).

EXPERIMENTAL APPROACH Levels of intracellular glucose were measured in rat HSCs and immortalized human hepatocytes. Contents of GLUT4 in cell fractions were analysed by Western blotting analyses. Activation of signalling pathways was assessed by comparing phosphorylation levels of protein kinases.

KEY RESULTS Leptin elevated the level of intracellular glucose in cultured HSCs, which was diminished by curcumin. Curcumin suppressed the leptin‐induced membrane translocation of GLUT4 by interrupting the insulin receptor substrates/phosphatidyl inositol 3‐kinase/AKT signalling pathway. Furthermore, curcumin stimulated glucokinase activity, increasing conversion of glucose to G‐6‐P.

CONCLUSIONS AND IMPLICATIONS Curcumin prevented leptin from elevating levels of intracellular glucose in activated HSCs in vitro by inhibiting the membrane translocation of GLUT4 and stimulating glucose conversion, leading to the inhibition of HSC activation. Our results provide novel insights into mechanisms of curcumin in inhibiting leptin‐induced HSC activation.
The First Teleautomatic Low‐Voltage Prosthesis With Multiple Therapeutic Applications: A New Version of the German Artificial Sphincter System
Authors: Ruthmann Olaf , Richter Sabine , Seifert Gabriel , Karcz Wojciech , Goldschmidboing Frank , Lemke Thomas , Biancuzzi Gionvanni , Woias Peter , Schmidt Thomas , Schwarzbqch Stefan , Vodermayer Bernahard , Hopt Ulrich , Schrag Hans‐Jurgen
Published: July 2010

To date, there are no artificial sphincter prostheses for urinary or fecal incontinence that may be implemented elsewhere instead, for example, in the upper gastrointestinal tract. Conventional systems are conceptually similar but are constructed specifically for distinct applications and are manual in operation. The German Artificial Sphincter System (GASS) II is the evolution of a highly integrative, modular, telemetric sphincter prosthesis with more than one application. Redesigning and integrating multilayer actuators into the pump allows us to reduce the input voltage to −10 to +20 V (VPP = 30 V). This provides for a flow rate of 2.23 mL/min and a counterpressure stability of 260 mbar. Furthermore, multiple applications have become feasible due to our standardized connection system, therapy‐specific compression units, and application‐specific software. These innovations allow us to integrate not only severe fecal and urinary incontinence, erectile dysfunction, and therapy‐resistant reflux disease, but also morbid adiposity into the gamut of therapeutic GASS applications.
Measuring Selection Incentives in Managed Care: Evidence From the Massachusetts State Employee Insurance Program
Authors: Eggleston Karen , Bir Anupa
Published: July 2010

Abstract

Capitation gives insurers incentive to manipulate their offerings to attract the healthy and deter the sick. We calculate the incentives for such service‐specific quality distortions using managed care medical and pharmacy spending data for fiscal years 2001 and 2002 from the Massachusetts State Employee Insurance Program. Services most vulnerable to stinting are cardiac care, diabetes care, and mental health and substance abuse services. Empirically, the financial temptation to distort service quality increases nonlinearly with supply‐side cost sharing. Our empirical results highlight how selection incentives work at cross‐purposes with efforts to reward excellent chronic disease management. Initiatives coupling pay‐for‐performance with risk adjustment and mixed payment hold promise for aligning incentives with quality improvement.
Six‐ and Twelve‐Month Clinical Outcomes after Implantation of Prokinetic BMS in Patients with Acute Coronary Syndrome
Authors: BERLIN TATIANA , ROZENBAUM ELIEZER , ARBEL JOEL , REGES ORNA , EREL JACOB , SHETBOUN ISRAEL , LEIBOVITCH MORTON , MOSSERI MORRIS
Published: July 2010

Aims:
 To evaluate the Prokinetic bare metal stent implanted in patients presenting with acute coronary syndrome (ACS).

Methods:
 We retrospectively studied ACS patients who underwent percutaneous coronary intervention (PCI) with a Prokinetic stent implantation. Excluded were patients presenting with cardiogenic shock, undergoing PCI to left main coronary artery (LM), or having implantation of additional stents other than Prokinetic. Six and 12 months clinical follow‐up was obtained by phone.

Results:
 A total of 140 Prokinetic stents were implanted in 117 patients (age 64±13.0 years, 78% men). Thirty two percent of the patients had unstable angina, 36% had non ST‐elevation myocardial infarction (NSTEMI) and 33% had ST‐elevation myocardial infarction (STEMI). Forty two percent of lesions were categorized as B2 and 21% as C type. Procedural success was achieved in 99.1% of lesions. Clinical success was achieved in 97.4% of patients. Major adverse cardiac events (MACE) rate was 8.5% and 11.1% at 6 and 12 months follow‐up, respectively. The incidence of cardiac death, MI and TLR was 2.6%, 3.4% and 2.6%, respectively at 6 months, and 4.3%, 4.3%, 2.6% respectively at 12 months.

Conclusions:
 Clinical outcomes at 6 and 12 months after Prokinetic stent implantation are excellent and may be attributable to its unique combination of composition, design and coating. (J Interven Cardiol 2010;23:377–381)
Left Atrial Dysfunction in Patients with Patent Foramen Ovale and Atrial Septal Aneurysm Scheduled for Transcathter Closure May Play a Role in Aura Genesis
Authors: RIGATELLI GIANLUCA , DELL’AVVOCATA FABIO , CARDAIOLI PAOLO , RONCO FEDERICO , GIORDAN MASSIMO , BRAGGION GABRIELE , AGGIO SILVIO , CHINAGLIA MAURO , CHENG JACK P. , NANJUNDAPPA ARAVINDA
Published: July 2010

Background:
 It has been suggested that a left atrial (LA) dysfunction induced by large shunt and large atrial septal aneurysm (ASA) may act as a concurrent mechanism of arterial embolism in patients with patent foramen ovale (PFO) and prior stroke. We aimed to evaluate the potential contribution of this mechanism as trigger of migraine in patients with PFO.

Methods:
 From January 2007 to September 2009, we prospectively enrolled subjects with migraine who underwent percutaneous PFO closure. Echocardiographic parameter of LA dysfunction was evaluated: pre‐ and postoperative values were compared to values of different sex and heart rate matched populations: 30 healthy patients, 21 migraine patients without PFO (MwoPFO), and a group of 25 PFO patients without migraine (PFOwoM). The Migraine Disability Assessment Score (MIDAS) was used to assess the incidence and severity of migraine.

Results:
 Forty‐five patients (38 females, mean age 38 ± 6.7 years, mean MIDAS 35.8 ± 4.7, and 28 patients with migraine with aura) fulfilled the inclusion criteria. After successful percutaneous closure (mean follow‐up of 18.2 ± 4.8 months), PFO closure remained complete in 95%; 35 of 45 patients reported resolution or amelioration of migraine (mean MIDAS score 12.3 ± 8.8, P < 0.03). All patients with aura reported aura resolution. Preclosure values demonstrated significantly greater LA dysfunction, when compared with healthy and MwoPFO groups. Among patients in the study group, only patients with migraine with aura showed LA dysfunction comparable to PFOwoM patients.

Conclusion:
 This study suggests that LA dysfunction probably does not contribute to migraine itself but may play a role in the genesis of aura symptoms. (J Interven Cardiol 2010;23:370–376)
Predictor of Stent Thrombosis in Patients Treated with Turbostratic Carbon‐Coated Stent Implantation for Acute Myocardial Infarction
Authors: MIGLIORINI ANGELA , VALENTI RENATO , MOSCHI GUIA , PARODI GUIDO , CERISANO GIAMPAOLO , BUONAMICI PIERGIOVANNI , CARRABBA NAZARIO , ANTONIUCCI DAVID
Published: July 2010

Background:
 Stent thrombosis is a major complication after percutaneous coronary intervention (PCI) for ST‐segment elevation acute myocardial infarction (AMI) and is associated with reinfarction and increased risk of death.

Methods:
 Patients treated with the turbostratic carbon‐coated stent (CID, Saluggia, Italy) for AMI were identified from a prospective primary PCI database. Primary end‐point was stent thrombosis within 6 months. Forward stepwise Cox proportional hazards analysis was used to identify independent predictors of stent thrombosis.

Results:
 Between 2001 and 2008, 746 patients underwent turbostratic carbon‐coated stent implantation for AMI. Patients had a mean age of 65 ± 12 years, 9% had cardiogenic shock on admission, 48% had multivessel coronary disease, 78% had baseline target vessel TIMI grade 0–1. Multiple stent implantation was performed in 26% of patients. The majority of patients (78%) received abciximab treatment and a postprocedural TIMI grade 3 flow was achieved in 98% patients. Definite stent thrombosis occurred in 10 patients (1.3%), while three patients (0.4%) had possible stent thrombosis. No probable stent thrombosis occurred. There were no procedural stent thromboses. In patients who received abciximab stent thrombosis the rate was 1%, while it was 4.3% in patients not receiving abciximab treatment. After adjusting for all clinical, angiographic, and procedural variables, abciximab treatment (HR 0.17; 95% CI 0.05–0.56, P = 0.003) and major bleedings (HR 14.2; 85% CI 2.79–72.44, P = 0.001) were the only two predictors related to stent thrombosis.

Conclusions:
 Patients with AMI treated with turbostratic carbon‐coated stent implantation and abciximab treatment have a low incidence of stent thrombosis. Abciximab treatment along with major bleeding complications are the only predictors related to stent thrombosis. (J Interven Cardiol 2010;23:554–559)
The Role of Explanation in Discovery and Generalization: Evidence From Category Learning
Authors: Williams Joseph J. , Lombrozo Tania
Published: July 2010

Research in education and cognitive development suggests that explaining plays a key role in learning and generalization: When learners provide explanations—even to themselves—they learn more effectively and generalize more readily to novel situations. This paper proposes and tests a subsumptive constraints account of this effect. Motivated by philosophical theories of explanation, this account predicts that explaining guides learners to interpret what they are learning in terms of unifying patterns or regularities, which promotes the discovery of broad generalizations. Three experiments provide evidence for the subsumptive constraints account: prompting participants to explain while learning artificial categories promotes the induction of a broad generalization underlying category membership, relative to describing items (Exp. 1), thinking aloud (Exp. 2), or free study (Exp. 3). Although explaining facilitates discovery, Experiment 1 finds that description is more beneficial for learning item details. Experiment 2 additionally suggests that explaining anomalous observations may play a special role in belief revision. The findings provide insight into explanation’s role in discovery and generalization.
Bootstrapping the Mind: Analogical Processes and Symbol Systems
Authors: Gentner Dedre
Published: July 2010

Human cognition is striking in its brilliance and its adaptability. How do we get that way? How do we move from the nearly helpless state of infants to the cognitive proficiency that characterizes adults? In this paper I argue, first, that analogical ability is the key factor in our prodigious capacity, and, second, that possession of a symbol system is crucial to the full expression of analogical ability.
Gender Stereotypes: An Explanation to the Underrepresentation of Women in Emergency Medicine
Authors: Pelaccia Thierry , Delplanq Hervé , Triby Emmanuel , Bartier Jean‐Claude , Leman Cécile , Hadef Hysham , Pottecher Thierry , Dupeyron Jean‐Pierre
Published: July 2010

ACADEMIC EMERGENCY MEDICINE 2010; 17:775–779 © 2010 by the Society for Academic Emergency Medicine

Objectives:  Women are underrepresented in emergency medicine (EM) residency programs in comparison with many other specialties. The reasons for this are unclear. One hypothesis is that negative gender stereotypes about EM careers might exist among female medical students. In the field of education, negative gender stereotypes are known to lead to career avoidance, because they tend to decrease self‐efficacy perception. The aims of this study were to assess the prevalence of negative gender stereotypes about EM practice among medical students and to measure the effects of these stereotypes on females’ self‐efficacy perception toward EM learning.

Methods:  A survey was conducted of the 255 third‐year medical students from three medical schools who attended a mandatory EM academic program in France. They completed an anonymous questionnaire exploring their gender stereotypes about EM practice and their self‐efficacy perception toward EM learning.

Results:  Gender stereotypes are common among medical students, especially in women. Self‐efficacy perception is negatively correlated to female students’ belief that EM careers are better suited for men (p < 0.05).

Conclusions:  Negative gender stereotypes among female medical students may lead to EM career avoidance, because of the decrease in their self‐efficacy perception toward EM learning.
Knowledge of Treatment Group Does Not Bias Assessment of Time to Seizure in an Animal Model of Cocaine Poisoning
Authors: Heard Kennon J. , Krier Shay , Cleveland Nathan R.
Published: July 2010

ACADEMIC EMERGENCY MEDICINE 2010; 17:E75–E77 © 2010 by the Society for Academic Emergency Medicine

Objectives:  Blinded outcome assessment decreases bias in human clinical trials. The necessity of blinded outcome assessment on animal studies is unknown. The authors determined the effect of knowledge of treatment group on assessment of time to seizure in an animal model of cocaine poisoning.

Methods:  Four subjects observed 20 animal experiments where all animals were administered a high dose of cocaine and placebo. For each experiment, two of the observers were told the animal had been treated with placebo and two were told the animal had been treated with a medication expected to delay the onset of seizures. Each observer recorded the time from cocaine administration to onset of seizure. The median time to seizure was compared between observers told the animal received placebo and those told the animal received active treatment.

Results:  Seizures were reported by all subjects in 12 animals and by no subjects in five animals, and there was disagreement in three animals. The reported median time to seizure was similar for observers told that the animals were treated with placebo and those told they were treated with study medication.

Conclusions:  It is feasible to determine whether unblinded assessments are biased in an animal study. Knowledge of treatment group did not bias the assessment of time to seizure in this animal model.
Emergency Department Tachypnea Predicts Transfer to a Higher Level of Care in the First 24 hours After ED Admission
Authors: Farley Heather , Zubrow Marc T. , Gies Jonna , Kolm Paul , Mascioli Susan , Mahoney Donna D. , Weintraub William S.
Published: July 2010

ACADEMIC EMERGENCY MEDICINE 2010; 17:718–722 © 2010 by the Society for Academic Emergency Medicine

Objectives:  The authors hypothesized that vital sign abnormalities detected in the emergency department (ED) can be used to forecast clinical deterioration occurring within 24 hours of hospital admission.

Methods:  This was a retrospective case‐control study performed after implementation of a hospitalwide rapid response team (RRT) system. Inclusion criteria for study patients consisted of age ≥ 18 years, admission to the general floor though the ED, and RRT activation and subsequent transfer to a higher level of care in the first 24 hours. Control patients were ≥18 years, were admitted to the floor though the ED, never required RRT or transfer to a higher level of care, and were matched to cases by risk of mortality. Multilevel logistic regression was used to model the odds of an adverse outcome as a function of race and sex, respiratory rate (RR), heart rate (HR), and systolic (sBP) and diastolic blood pressure (dBP) at time of transfer from the ED.

Results:  A total of 74 cases and 246 controls were used. RR (odds ratio [OR] = 2.79 per 10‐point change, 95% confidence interval [CI] = 1.41 to 5.51) and to a lesser extent dBP (OR = 0.81, 95% CI = 0.67 to 0.97) contributed significantly to the odds of intensive care unit (ICU) or intermediate care transfer within 24 hours of admission; HR (OR = 1.15, 95% CI = 0.98 to 1.37) did not.

Conclusions:  Emergency department RR preceding floor transfer appears to have a significant relationship to the need for ICU or intermediate care transfer in the first 24 hours of hospital admission.