bluuebunny/crossref_metadata_2025 huggingface dataset:
The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses
Authors: DAVIS J. L. , MARSHALL J. F. , PAPICH M. G. , BLIKSLAGER A. T. , CAMPBELL N. B.
Published: June 2010

Davis, J. L., Marshall, J. F., Papich, M. G., Blikslager, A. T., Campbell, N. B. The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses. J. vet. Pharmacol. Therap.34, 12–16.

The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half‐life (t1/2k10) of 12.49 ± 1.84 h. The average maximum plasma concentration (Cmax) was 0.54 μg/mL, and was reached at 6.33 ± 3.44 h. Bioavailability was not determined because of the lack of an IV formulation. Results of in vitro COX selectivity assays showed that deracoxib was selective for COX‐2 with a COX‐1/COX‐2 ratio of 25.67 and 22.06 for the IC50 and IC80, respectively. Dosing simulations showed that concentrations above the IC80 for COX‐2 would be maintained following 2 mg/kg PO q12h, and above the IC50 following 2 mg/kg PO q24h. This study showed that deracoxib is absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.
Pharmacokinetics of ceftiofur crystalline free acid after single subcutaneous administration in lactating and nonlactating domestic goats (Capra aegagrus hircus)
Authors: DORÉ ELIZABETH , ANGELOS JOHN A. , ROWE JOAN D. , CARLSON JAN L. , WETZLICH SCOTT E. , KIEU HUNG T. , TELL LISA A.
Published: June 2010

Doré, E., Angelos, J. A., Rowe, J. D., Carlson, J. L., Wetzlich, S. E., Kieu, H. T., Tell, L. A. Pharmacokinetics of ceftiofur crystalline free acid after single subcutaneous administration in lactating and nonlactating domestic goats (Capra aegagrus hircus). J. vet. Pharmacol. Therap.34, 25–30.

Six nonlactating and six lactating adult female goats received a single subcutaneous injection of ceftiofur crystalline free acid (CCFA) at a dosage of 6.6 mg/kg. Blood samples were collected from the jugular vein before and at multiple time points after CCFA administration. Milk samples were collected twice daily. Concentrations of ceftiofur and desfuroylceftiofur‐related metabolites were measured using high‐performance liquid chromatography. Data were analyzed using compartmental and noncompartmental approaches. The pharmacokinetics of CCFA in the domestic goat was best described by a one compartment model. Mean (±SD) pharmacokinetic parameters were as follows for the nonlactating goats: area under the concentration time curve0–∞ (159 h·μg/mL ± 19), maximum observed serum concentration (2.3 μg/mL ± 1.1), time of maximal observed serum concentration (26.7 h ± 16.5) and terminal elimination half life (36.9 h; harmonic). For the lactating goats, the pharmacokinetic parameters were as follows: area under the concentration time curve0–∞ (156 h·μg/mL ± 14), maximum observed serum concentration (1.5 μg/mL ± 0.4), time of maximal observed serum concentration (46 h ± 15.9) and terminal elimination half life (37.3 h; harmonic). Ceftiofur and desfuroylceftiofur‐related metabolites were only detectable in one milk sample at 36 h following treatment. There were no significant differences in the pharmacokinetic parameter between the nonlactating and lactating goats.
The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital
Authors: MOORE S.A. , MUÑANA K.R. , PAPICH M.G. , NETTIFEE‐OSBORNE J.A.
Published: June 2010

Moore, S.A., Muñana, K.R., Papich, M.G., Nettifee‐Osborne, J.A. The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital.J. vet. Pharmacol. Therap.34, 31–34.

Levetiracetam (LEV) is a commonly used add‐on medication in dogs with refractory epilepsy. The objective of this study was to determine if the pharmacokinetics of LEV are altered by concurrent administration of phenobarbital (PB). Six healthy dogs received a single oral dose of LEV (16.7–27.8 mg/kg). Blood samples were collected at baseline and intermittently for 24 h. The study was repeated after the dogs received oral PB (2.0–3.3 mg/kg) twice daily for 21 days. Plasma LEV levels were evaluated by high pressure liquid chromatography, and data analyzed using a compartmental model. Compared with values determined when LEV was administered alone, concurrent administration of PB resulted in a decrease in LEV peak concentration (Cmax) from 32.39 ± 6.76 to 18.22 ± 8.97 (P = 0.0071), a decrease in elimination half‐life (T1/2) from 3.43 ± 0.47 to 1.73 ± 0.22 (P = 0.0005), and an increase in oral clearance from 124.93 ± 26.93 to 252.99 ± 135.43 ml/h/kg (P < 0.0001). Concurrent PB administration significantly alters the pharmacokinetics of LEV in the dog, indicating that dosage adjustments might be necessary when the drug is administered with PB.
ABC as a flexible framework to estimate demography over space and time: some cons, many pros
Authors: BERTORELLE G. , BENAZZO A. , MONA S.
Published: June 2010

The analysis of genetic variation to estimate demographic and historical parameters and to quantitatively compare alternative scenarios recently gained a powerful and flexible approach: the Approximate Bayesian Computation (ABC). The likelihood functions does not need to be theoretically specified, but posterior distributions can be approximated by simulation even assuming very complex population models including both natural and human‐induced processes. Prior information can be easily incorporated and the quality of the results can be analysed with rather limited additional effort. ABC is not a statistical analysis per se, but rather a statistical framework and any specific application is a sort of hybrid between a simulation and a data‐analysis study. Complete software packages performing the necessary steps under a set of models and for specific genetic markers are already available, but the flexibility of the method is better exploited combining different programs. Many questions relevant in ecology can be addressed using ABC, but adequate amount of time should be dedicated to decide among alternative options and to evaluate the results. In this paper we will describe and critically comment on the different steps of an ABC analysis, analyse some of the published applications of ABC and provide user guidelines.
Temporally stable genetic variability and dynamic kinship structure in a fluctuating population of the root vole Microtus oeconomus
Authors: PILOT MAŁGORZATA , DĄBROWSKI MICHAŁ J. , JANCEWICZ ELŻBIETA , SCHTICKZELLE NICOLAS , GLIWICZ JOANNA
Published: June 2010

Genetic variability, kin structure and demography of a population are mutually dependent. Population genetic theory predicts that under demographically stable conditions, neutral genetic variability reaches equilibrium between gene flow and drift. However, density fluctuations and non‐random mating, resulting e.g. from kin clustering, may lead to changes in genetic composition over time. Theoretical models also predict that changes in kin structure may affect aggression level and recruitment, leading to density fluctuations. These predictions have been rarely tested in natural populations. The aim of this study was to analyse changes in genetic variability and kin structure in a local population of the root vole (Microtus oeconomus) that underwent a fourfold change in mean density over a 6‐year period. Intensive live‐trapping resulted in sampling 88% of individuals present in the study area, as estimated from mark–recapture data. Based on 642 individual genotypes at 20 microsatellite loci, we compared genetic variability and kin structure of this population between consecutive years. We found that immigration was negatively correlated with density, while the number of kin groups was positively correlated with density. This is consistent with theoretical predictions that changes in kin structure play an important role in population fluctuations. Despite the changes in density and kin structure, there was no genetic differentiation between years. Population‐level genetic diversity measures did not significantly vary in time and remained relatively high (HE range: 0.72–0.78). These results show that a population that undergoes significant demographic and social changes may maintain high genetic variability and stable genetic composition.
Functional characterization of the SIZ/PIAS‐type SUMO E3 ligases, OsSIZ1 and OsSIZ2 in rice
Authors: PARK HYEONG CHEOL , KIM HUN , KOO SUNG CHEOL , PARK HEE JIN , CHEONG MI SUN , HONG HYEWON , BAEK DONGWON , CHUNG WOO SIK , KIM DOH HOON , BRESSAN RAY A. , LEE SANG YEOL , BOHNERT HANS J. , YUN DAE‐JIN
Published: June 2010

Sumoylation is a post‐translational regulatory process in diverse cellular processes in eukaryotes, involving conjugation/deconjugation of small ubiquitin‐like modifier (SUMO) proteins to other proteins thus modifying their function. The PIAS [protein inhibitor of activated signal transducers and activators of transcription (STAT)] and SAP (scaffold attachment factor A/B/acinus/PIAS)/MIZ (SIZ) proteins exhibit SUMO E3‐ligase activity that facilitates the conjugation of SUMO proteins to target substrates. Here, we report the isolation and molecular characterization of Oryza sativa SIZ1 (OsSIZ1) and SIZ2 (OsSIZ2), rice homologs of Arabidopsis SIZ1. The rice SIZ proteins are localized to the nucleus and showed sumoylation activities in a tobacco system. Our analysis showed increased amounts of SUMO conjugates associated with environmental stresses such as high and low temperature, NaCl and abscisic acid (ABA) in rice plants. The expression of OsSIZ1 and OsSIZ2 in siz1‐2 Arabidopsis plants partially complemented the morphological mutant phenotype and enhanced levels of SUMO conjugates under heat shock conditions. In addition, ABA‐hypersensitivity of siz1‐2 seed germination was partially suppressed by OsSIZ1 and OsSIZ2. The results suggest that rice SIZ1 and SIZ2 are able to functionally complement Arabidopsis SIZ1 in the SUMO conjugation pathway. Their effects on the Arabidopsis mutant suggest a function for these genes related to stress responses and stress adaptation.
Clinical utility of multidetector row computed tomography for diagnosing spinal dural arteriovenous fistulas undiagnosed by magnetic resonance imaging
Authors: Sakai Yoshihito , Matsuyama Yukihiro , Imagama Shiro , Ito Zenya , Wakao Norimitsu , Ishiguro Naoki
Published: June 2010

Two elderly patients with dural arteriovenous fistulas (AVF), the abnormal vessels of which were not presented on magnetic resonance imaging (MRI) are reported. Although spinal AVF was suspected from hyperintensity in the spinal cord, dilated vessels were not detected on MRI. Computed tomography (CT) angiography was performed with a 64‐detector row multidetector row CT (MDCT) system in both cases. The draining dilated vein was observed in both cases and they were interpreted as perimedullary AVF. In case 1, axial scan and the dorsal section of the coronal view demonstrated continuity of the radiculomedullary artery and intercostal artery through the spinal branch at the left Th12 level. After intravascular embolization in case 1 and surgical treatment in case 2, neurological improvement was obtained in both cases. MRI findings suggestive of dural AVF have described that intradural perimedullary tortuous low signal intensities posterior to the spinal cord, known as flow void, on T2‐weighted images is the most consistent. Recently, MDCT angiography confirmed the presence of a fistula previously suspected after MRI. There are no previous reports that describe cases of dural AVF diagnosed by MDCT angiography of which abnormal vessels were undetected by MRI images. MDCT can detect abnormal vessels which were not depicted on MRI. When dural AVF are suspected on MRI, MDCT angiography should be performed before selective angiography to diagnose. Geriatr Gerontol Int 2010; 10: 255–263.
Modulation of cortical motor outputs by the symbolic meaning of visual stimuli
Authors: Fecteau Shirley , Tormos Jose Maria , Gangitano Massimo , Théoret Hugo , Pascual‐Leone Alvaro
Published: June 2010

The observation of an action modulates motor cortical outputs in specific ways, in part through mediation of the mirror neuron system. Sometimes we infer a meaning to an observed action based on integration of the actual percept with memories. Here, we conducted a series of experiments in healthy adults to investigate whether such inferred meanings can also modulate motor cortical outputs in specific ways. We show that brief observation of a neutral stimulus mimicking a hand does not significantly modulate motor cortical excitability (Study 1) although, after prolonged exposure, it can lead to a relatively nonspecific modulation (Study 2). However, when such a neutral stimulus is preceded by exposure to a hand stimulus, the latter appears to serve as a prime, perhaps enabling meaning to the neutral stimulus, which then modulates motor cortical excitability in accordance with mirror neuron‐driving properties (Studies 2 and 3). Overall results suggest that a symbolic value ascribed to an otherwise neutral stimulus can modulate motor cortical outputs, revealing the influence of top‐down inputs on the mirror neuron system. These findings indicate a novel aspect of the human mirror neuron system: an otherwise neutral stimulus can acquire specific mirror neuron‐driving properties in the absence of a direct association between motor practice and perception. This significant malleability in the way that the mirror neuron system can code otherwise meaningless (i.e. arbitrarily associated) stimuli may contribute to coding communicative signals such as language. This may represent a mirror neuron system feature that is unique to humans.
Pathological stage review is indicated in primary pT1 bladder cancer
Authors: Van Rhijn Bas W.G. , Van Der Kwast Theo H. , Kakiashvili David M. , Fleshner Neil E. , Van Der Aa Madelon N.M. , Alkhateeb Sultan , Bangma Chris H. , Jewett Michael A.S. , Zlotta Alexandre R.
Published: June 2010

Study Type – Diagnosis (case series) Level of Evidence 4

OBJECTIVE

To evaluate the effect of a pathology review on the clinical outcome of patients with primary pT1 bladder cancer (BC), as the clinical course of such patients is variable.

PATIENTS AND METHODS

The slides of 164 primary (first diagnosis) pT1 bladder tumours from two university hospitals were reviewed by one pathologist for stage and grade (World Health Organization 1973 and 2004). Patients were initially managed conservatively with bacille Calmette‐Guérin (BCG). Uni‐ and multivariate analyses compared the predictive value of age, gender, hospital, carcinoma in situ (CIS), tumour‐size, reviewed grade and reviewed stage.

RESULTS

With a mean follow‐up of 6.4 years, there was disease progression in 48 (29%) patients and 26 (16%) died from BC. Associated CIS was found in 55 (34%) patients. After reviewing the slides, 24 (15%) tumours were downstaged to pTa, 134 (82%) remained pT1 and six (4%) were upstaged to ≥pT2. The grade review resulted in 74 G2, 90 G3, 37 low‐grade and 127 high‐grade lesions for the two systems used. In multivariate analyses, reviewed stage (both P < 0.001) and CIS (P = 0.017 and 0.023) had independent significance for progression and disease‐specific survival, respectively.

CONCLUSION

A stage review is indicated in pT1 BC, as almost 20% of pT1 tumours were up‐ or downstaged, and the reviewed stage predicted the patient’s prognosis. Hence, pathology review identified patients with different prognoses who might benefit from other treatment strategies than BCG. We confirmed that CIS is an unfavourable sign in pT1 bladder cancer.
DETERMINANTS OF PRIVATE INVESTMENT IN MALAYSIA: WHAT CAUSES THE POSTCRISIS SLUMPS?
Authors: ANG JAMES B.
Published: June 2010

This paper examines the determinants of private investment in Malaysia, with an emphasis on the postcrisis investment slumps. A static private investment function is derived from the neoclassical framework, with appropriate modifications to account for the structural features observed in the country. To introduce dynamics into the model, we adopt a cost minimization problem, which assumes firms optimize investment levels with respect to a quadratic loss function. The results suggest that the availability of financial resources in the economy has a significant positive impact on private investment. Macroeconomic uncertainty exerts a negative influence on the investment climate in the private sector. Both foreign direct investment and public investment are found to have a complementary effect on private investment. Consistent with the prediction of the neoclassical model, a higher level of aggregate output raises private investment, whereas the user cost of capital has the opposite impact. (JEL O16, O53)
PUBLIC VERSUS PRIVATE DELIVERY OF MUNICIPAL SOLID WASTE SERVICES: THE CASE OF NORTH CAROLINA
Authors: BAE SUHO
Published: June 2010

This paper examines the effects of different institutional arrangements and characteristics on cost savings, efficiency gains, and productivity of delivering municipal solid waste services. A cost function approach is employed, and North Carolina municipal data for three years (1997, 2001, and 2003) are used for the analysis. Empirical findings indicate that there is no significant difference in cost savings between public delivery and private contractor delivery of solid waste services, a finding similar to those of other recent studies. There are three possible reasons for this. First, the threat of competition and contracting out might have led to cost savings in the cases of public delivery. Second, there might be a lack of competition because a few large private contractors have been able to win follow‐on contracts over the years. Third, there might be substantial transaction costs arising as the result of private contracting. (JEL H40, H83, Q53)
Kripke's Account of the Rule‐Following Considerations
Authors: Guardo Andrea
Published: June 2010

Abstract: This paper argues that most of the alleged straight solutions to the sceptical paradox which Kripke (1982) ascribed to Wittgenstein can be regarded as the first horn of a dilemma whose second horn is the paradox itself. The dilemma is proved to be a by‐product of a foundationalist assumption on the notion of justification, as applied to linguistic behaviour. It is maintained that the assumption is unnecessary and that the dilemma is therefore spurious. To this end, an alternative conception of the justification of linguistic behaviour is outlined, a conception that vindicates some of the insights behind Kripke's Wittgenstein's sceptical solution of the paradox. This alternative conception is defended against two objections (both familiar from McDowell's works): (1) that it would imply that for the linguistic community there is no authority, no standard to meet and, therefore, no possibility of error and (2) that it would lead to a kind of idealism.
Specific resistances against Pseudomonas syringae effectors AvrB and AvrRpm1 have evolved differently in common bean (Phaseolus vulgaris), soybean (Glycine max), and Arabidopsis thaliana
Authors: Chen Nicolas W. G. , Sévignac Mireille , Thareau Vincent , Magdelenat Ghislaine , David Perrine , Ashfield Tom , Innes Roger W. , Geffroy Valérie
Published: June 2010

Featured paper: See Editorial p877
Some properties of Civil cheese: a type of traditional Turkish cheese
Authors: YILDIZ FILIZ , YETISEMIYEN ATILA , SENEL EBRU , DURLU‐ÖZKAYA FÜGEN , ÖZTEKIN SEBNEM , SANLI EBRU
Published: June 2010

Civil cheeses were purchased from urban vendors in the city centre of Erzurum, Turkey. The biogenic amine contents of the cheeses and their microbiological and chemical properties were determined. It was found out that biogenic amine concentrations of the samples were not exceeding the toxic doses‐values. Total aerobic mesophilic bacteria, lactic acid bacteria and Enterobacteriaceae spp. were investigated as microbial analyses in the samples while several chemical analyses were executed. Statistical analyses were carried out for the determination of the relationship between the chemical properties and the biogenic amine contents of samples, and the existence of microorganisms and biogenic amines.
The cost‐effectiveness of targeted or universal screening for vasa praevia at 18–20 weeks of gestation in Ontario
Authors: Cipriano LE , Barth WH , Zaric GS
Published: June 2010

Please cite this paper as: Cipriano L, Barth W, Zaric G. The cost‐effectiveness of targeted or universal screening for vasa praevia at 18–20 weeks of gestation in Ontario. BJOG 2010;117:1108–1118.

Objectives  To estimate the cost‐effectiveness of targeted and universal screening for vasa praevia at 18–20 weeks of gestation in singleton and twin pregnancies.

Design  Cost–utility analysis based on a decision‐analytic model comparing relevant strategies and life‐long outcomes for mother and infant(s).

Setting  Ontario, Canada.

Population  A cohort of pregnant women in 1 year.

Methods  We constructed a decision‐analytic model to estimate the lifetime incremental costs and benefits of screening for vasa praevia. Inputs were estimated from the literature. Costs were collected from the London Health Sciences Centre, the Ontario Health Insurance Program, and other sources. We used one‐way, scenario and probabilistic sensitivity analysis to determine the robustness of the results.

Main outcome measures  Incremental costs, life expectancy, quality‐adjusted life‐years (QALY) and incremental cost‐effectiveness ratio (ICER).

Results  Universal transvaginal ultrasound screening of twin pregnancies has an ICER of $5488 per QALY‐gained. Screening all singleton pregnancies with the risk factors low‐lying placentas, in vitro fertilisation (IVF) conception, accessory placental lobes, or velamentous cord insertion has an ICER of $15,764 per QALY‐gained even though identifying some of these risk factors requires routine use of colour Doppler during transabdominal examinations. Screening women with a marginal cord insertion costs an additional $27,603 per QALY‐gained. Universal transvaginal screening for vasa praevia in singleton pregnancies costs $579,164 per QALY compared with targeted screening.

Conclusions  Compared with current practice, screening all twin pregnancies for vasa praevia with transvaginal ultrasound is cost‐effective. Among the alternatives considered, the use of colour Doppler at all transabdominal ultrasound examinations of singleton pregnancies and targeted use of transvaginal ultrasound for IVF pregnancies or when the placenta has been found to be associated with one or more risk factors is cost‐effective. Universal screening of singleton pregnancies is not cost‐effective compared with targeted screening.
Monitoring healthcare quality in an obstetrics and gynaecology department using a CUSUM chart
Authors: Boulkedid R , Sibony O , Bossu‐Salvador C , Oury JF , Alberti C
Published: June 2010

Please cite this paper as: Boulkedid R, Sibony O, Bossu‐Salvador C, Oury J, Alberti C. Monitoring healthcare quality in an obstetrics and gynaecology department using a CUSUM chart. BJOG 2010;117:1225–1235.

Objective  To use cumulative sum (CUSUM) charts for the early detection of variations in quality of care in a maternity department.

Design  Retrospective analysis of prospectively collected data.

Setting  Maternity department of a teaching hospital in Paris (France).

Population  Data from 20 519 women and 21 448 infants were collected between January 2000 and December 2007.

Methods  CUSUM charts were used to monitor the rate of 19 pre‐selected quality indicators over 3 years (2005–2007), against standards developed by department obstetrician gynaecologists. Periods with adverse event rates that did not meet the standards were identified.

Main outcome measures  Quality indicator rates.

Results  Indicators fell into three groups based on the number of periods with unacceptable rates: less than one per year [e.g. the rate of intensive care unit (ICU) admission of mothers and rate of third‐ or fourth‐degree perineal tears]; one every 2–12 months on average (e.g. blood transfusion and sulprostone use in the overall population of women); and at least one per month (insufficient availability of epidural analgesia).

Conclusion  CUSUM charts for a broad range of quality indicators can be used to monitor the quality of care in an obstetrics department. A prospective study investigating the ability of CUSUM‐based monitoring to improve maternal and neonatal outcomes would be of interest.
The role of lymph node resection in ovarian cancer: analysis of the surveillance, epidemiology, and end results (SEER) database
Authors: Rouzier R , Bergzoll C , Brun J‐L , Dubernard G , Selle F , Uzan S , Pomel C , Daraï E
Published: June 2010

Please cite this paper as: Rouzier R, Bergzoll C, Brun J, Dubernard G, Selle F, Uzan S, Pomel C, Daraï E. The role of lymph node resection in ovarian cancer: analysis of the surveillance, epidemiology, and end results (SEER) database. BJOG 2010;117:1451–1458.

Objective  The therapeutic role of lymphadenectomy on the survival in patients with ovarian cancer is controversial. The aim of this study was to evaluate the survival impact of lymphadenectomy, depending on the disease stage and extent of the surgery.

Design  The surveillance, epidemiology, and end results (SEER) registry provided ovarian cancer data from 17 registries.

Setting  Surveillance, Epidemiology, and End Results database.

Population  The study population comprised 49 783 patients.

Methods  Survival was studied according to the number of lymph nodes removed, with stratifications on disease stage and extent of surgery.

Main outcome measure  The 5‐year cause‐specific survival rate.

Results  The median follow up for patients alive at the last follow‐up visit was 39 months. The five‐year cause‐specific survival rates were 37, 62, and 71% for the groups in which no lymph nodes were examined, in which between one and nine nodes were examined, and in which ten or more nodes were examined, respectively (P < 0.001). Avoiding lymphadenectomy was deleterious in all stages of the disease. It was maximal for International Federation of Gynecology and Obstetrics (FIGO) stage‐II patients, but there was no significant interaction between stage and extent of lymphadenectomy. The cause‐specific survival was found to significantly increase when more nodes were resected, even if the surgical procedure consisted of debulking surgery or a pelvic exenteration.

Conclusion  Our study suggests a beneficial effect of lymphadenectomy in epithelial ovarian tumours, regardless of the stage of disease and extent of surgery. However, potential biases inherent to this retrospective methodology, such as staging migration, defining the extent of residual disease, and the possibility that thorough lymphadenectomy may reflect the quality of cytoreductive surgery, preclude any formal conclusions on the therapeutic role of lymphadenectomy.
Depressive symptoms in adulthood and intrauterine exposure to pre‐eclampsia: the Helsinki Birth Cohort Study
Authors: Tuovinen S , Räikkönen K , Kajantie E , Pesonen A–K , Heinonen K , Osmond C , Barker DJP , Eriksson JG
Published: June 2010

Please cite this paper as: Tuovinen S, Räikkönen K, Kajantie E, Pesonen A, Heinonen K, Osmond C, Barker D, Eriksson J. Depressive symptoms in adulthood and intrauterine exposure to pre‐eclampsia: the Helsinki Birth Cohort Study. BJOG 2010;117:1236–1242.

Objective  We studied whether pre‐eclampsia predicts depressive symptoms in offspring.

Design  Retrospective longitudinal cohort study.

Setting  Participants in the Helsinki Birth Cohort 1934–44 Study.

Population  We classed 788 women and men born at term after a normotensive, hypertensive or pre‐eclamptic pregnancy, by using the mother’s blood pressure and urinary protein measurements, at maternity clinics and birth hospitals.

Methods  Linear and logistic regression analyses. We made adjustments for the mother’s age and body mass index (BMI) at delivery, the participant’s body size at birth/length of gestation, sex and childhood socio‐economic status, age and educational attainment at testing.

Main outcome measures  Beck depression inventory (BDI) scores completed twice, at the ages of 60 and 63 years.

Result  Participants born after a primiparous pregnancy complicated by pre‐eclampsia had over 30% (P < 0.04) higher depressive symptom scores in adulthood compared with those born after a primiparous normotensive pregnancy. We found no evidence of the association between pre‐eclampsia and depression among participants born after multiparous pregnancies. Gestational hypertension and depressive symptoms were not significantly associated. The models adjusting for mother’s age and BMI at delivery, the participant’s body size at birth/length of gestation, sex, childhood socio‐economic status, age and educational attainment at testing did not change the results.

Conclusion  Pre‐eclampsia is associated with later depressive symptoms in individuals born at term and after a primiparous pregnancy. These findings are compatible with the adverse fetal ‘programming’ by a suboptimal prenatal environment.
Dopamine inhibition of glycine release in the rat trigeminal nucleus pars caudalis: possible involvement of trace amine receptors
Authors: Choi In‐Sun , Cho Jin‐Hwa , Jang Il‐Sung
Published: June 2010

J. Neurochem.(2010)114, 1639–1650.

Dopamine (DA)‐induced pre‐synaptic inhibition of glycinergic transmission was studied from substantia gelatinosa (SG) neurons of the trigeminal nucleus pars caudalis using a conventional whole‐cell patch clamp technique. The action potential‐dependent glycinergic inhibitory post‐synaptic currents (IPSCs) were recorded from SG neurons in the presence of 3 mM kynurenic acid and 10 μM 6‐imino‐3‐(4‐methoxyphenyl)‐1(6H)‐pyridazinebutanoic acid HBr (SR95531). In these conditions, bath applied DA (100 μM) reduced the amplitude of glycinergic IPSCs and increased the paired‐pulse ratio, suggesting that DA acts pre‐synaptically to reduce the probability of glycine release. However, the inhibitory action of DA on glycinergic IPSCs was not blocked by SCH23390 (10 μM) and spiperone (1 μM), selective D1‐ and D2‐like receptor antagonists, respectively. In addition, either SKF38393 (100 μM), a selective D1‐like receptor agonist, or quinpirole (100 μM), a selective D2‐like receptor agonist, had no pre‐synaptic effect on glycinergic IPSCs. The results suggest that both D1‐ and D2‐like receptors are not involved in the DA‐induced decrease in glycinergic IPSCs. On the other hand, tyramine (100 μM), one of representative trace amines, reduced the amplitude of glycinergic IPSCs and increased the paired‐pulse ratio, suggesting that tyramine acts pre‐synaptically to reduce the probability of glycine release. Considering that DA can activate trace amine (TA) receptors and that TA receptors are exclusively expressed on the trigeminal nucleus pars caudalis, DA might act on putative pre‐synaptic TA receptors, rather than classical DA receptors, to inhibit glycinergic transmission onto SG neurons of the trigeminal nucleus pars caudalis.
t‐SNARE cluster organization and dynamics in chromaffin cells
Authors: López‐Font Inmaculada , Torregrosa‐Hetland Cristina J. , Villanueva José , Gutiérrez Luis M.
Published: June 2010

J. Neurochem. (2010) 114, 1550–1556.

Adrenomedullary chromaffin cells represent an excellent model to study the molecular events linked to exocytosis, because they use the same type of SNAREs for vesicle docking and fusion as neurons. In these cells, both in the intact tissue and in isolated cells in culture, syntaxin‐1 and SNAP‐25 are present in the plasmalemma unevenly distributed in patches, even when exogenous t‐SNAREs are expressed. In fact, the expression of SNAP‐25 fused to green fluorescent protein has been useful to study the movement of these clusters by total internal reflection fluorescent microscopy. These microdomains move little in the plasma membrane plane but they undertake relatively large displacements of 100 nm in the axis perpendicular to the membrane. Movement in either axis is dependent on molecular interactions within the t‐SNARE complex and indeed, clusters formed by recombinant SNAP‐25 Δ9, the product of Botulinum neurotoxin A cleavage, undergo larger displacement. Interestingly, altering the movement of t‐SNARE clusters also influences the mobility of the chromaffin vesicles associated with these t‐SNAREs. Furthermore, highly mobile vesicles associated with the clusters formed by SNAP‐25 Δ9 present a low probability of exocytosis and also slower fusion kinetics. Finally, we discuss some of the factors that could influence the movement of t‐SNARE clusters and how these dynamics may influence the mobility and the fusion properties of the vesicles in the vicinity of active sites.
Cross‐Correlation and Differential Technique Combination to Determine Displacement Fields
Authors: Sousa A. M. R. , Xavier J. , Vaz M. , Morais J. J. L. , Filipe V. M. J.
Published: June 2010

Abstract:  This study presents a method to measure the displacement fields on the surface of planar objects with sub‐pixel resolution, by combining image correlation with a differential technique. First, a coarse approximation of the pixel level displacement is obtained by cross‐correlation (CC). Two consecutive images, taken before and after the application of a given deformation, are recursively split in sub‐images, and the CC coefficient is used as the similarity measure. Secondly, a fine approximation is performed to assess the sub‐pixel displacements by means of an optical flow method based on a differential technique. To validate the effectiveness and robustness of the proposed method, several numerical tests were carried out on computer‐generated images. Moreover, real images from a static test were also processed for estimating the displacement resolution. The results were compared with those obtained by a commercial digital image correlation code. Both methods showed similar and reliable results according to the proposed tests.
Experimental Study of the Creep Behaviour of the Cold‐Drawn 304L Stainless Steel
Authors: Vakili‐Tahami F. , Daei‐Sorkhabi A. H. , Biglari F. R.
Published: June 2010

Abstract:  In this article, the material and physical parameters for the creep constitutive equations of cold‐drawn 304L stainless steel have been determined using experimental data. Austenitic stainless steel 304L is used mostly in power generation and petrochemical industries because of its high‐temperature creep resistance even at above yield stresses. Test samples have been obtained from cold‐drawn bars, and the material conforms to ASTM A276‐05a specifications. The creep behaviour and properties have been examined for this material by conducting uni‐axial creep tests. Constant temperature and constant load uni‐axial creep tests have been carried out at three temperatures of 680,700 and 720 °C, subjected to constant loads which produce below and above yield initial stresses of 200, 250, 320, 340 and 360 MPa. The experimental data have been used to obtain the creep constitutive parameters using numerical optimisation techniques. In addition, the temperature and stress dependency of the creep properties for this alloy have been investigated using Larson–Miller and Monkman–Grant parameters.
Study of Shear Ultrasonic Waves Propagating in Materials under Static Uniaxial Loadings
Authors: Si‐chaib M. O. , Djelouah H. , Nour A.
Published: June 2010

Abstract:  Non‐destructive evaluation of applied loadings level in mechanical components and structures constitutes a versatile tool to predict the behaviour of their materials in engineering industries and check services. Ultrasonic non‐destructive techniques stand advantageously to allow predictions and diagnosis where other measurement methods are difficult or not possible. For analysing the effects of static uniaxial loads, the present work relates to the modification of waveforms of ultrasonic shear waves propagating in statically loaded materials. To predict the behaviour of waveforms of shear ultrasonic waves propagating in media under stress, an analytical method is proposed. The simulated waveforms are reconstructed by using parameters from an experimental signal measured on specimens free of any loading. Assuming the hypothesis of progressive ultrasonic plane waves and taking into account the elastic deformation and the stressed ultrasonic velocity, the time of flight calculation allowed the simulation of shear waveforms for each applied stress. To validate this method, some ultrasonic measurements have been carried out. A linearly polarised shear wave transducer is used for probing C35 steel and 2017A (AU4G) alloy samples of known macroscopic properties. Simulated and measured ultrasonic waveforms are partially in good agreement, in particular for the extra delay effect induced under compressive and tensile elastic loads.
AE Monitoring and Numerical Simulation of a Two‐span Model Masonry Arch Bridge Subjected to Pier Scour
Authors: Invernizzi S. , Lacidogna G. , Manuello A. , Carpinteri A.
Published: June 2010

Abstract:  A scaled model of a two‐span masonry arch bridge has been built to investigate the effect of the central pile settlement because of riverbank erosion. The bridge geometry and the structural details, included the masonry bricks and mortar joints, are realized in the scale 1 : 2. The model bridge has been equipped with different Non‐Destructive Testing (NDT) instruments, including accelerometers, displacement transducers LVTD, strain gages, optic fibres strain sensors and Acoustic Emissions (AE) transducers. The model bridge has been subjected to incremental settlement of the pile, which was sustained on a mobile support. The exact mechanism and temporal evolution of the pier scour has been investigated numerically and experimentally by mean of a hydraulic model. In this article, a detailed description of AE data and damage localization is provided. During the first stage of the settlement, the AE counting has been recorded. Based on the interpretation of the AE rate, it is possible to monitor the criticality of the ongoing process. In addition, thanks to the AE equipment, it has been possible to localize the main damaged zones. The statistical properties AE time series have been analysed using an estimation of the b‐value of the Gutenberg‐Richter (GR) law permitting to determine the damage level reached in the model. The damage evolution has been also interpreted numerically with the aid of a finite element programme able to predict the nucleation and propagation of fracture. In this way, some criteria for the monitoring and interpretation of full‐scale structure cracking are provided for the assessment in presence of riverbank erosion phenomena.
Virtual Fields Method on Planar Tension Tests for Hyperelastic Materials Characterisation
Authors: Palmieri G. , Sasso M. , Chiappini G. , Amodio D.
Published: June 2010

Abstract:  New methods are emerging in the material characterisation field with the aim of exploiting innovative full‐field strain measurement techniques. Besides experimental issues, also numerical procedures for inverse problems should adapt to a new philosophy: the large amount of data referred to local strains should be used in an appropriate way to obtain as much benefits as possible. In this context, an experimental and numerical procedure for the characterisation of hyperelastic materials is proposed. Planar tension tests have been performed on flat rubber specimens of different geometries. Strain maps obtained by means of a 2D Digital Image Correlation system are used to implement the virtual fields method, to estimate material dependent parameters of two of the most known hyperelastic constitutive laws: Ogden and 2nd order Mooney‐Rivlin models. Numerical results and comparisons with experimental data are shown, analysing also aspects concerning implementation of the numerical procedures and computational efficiency of the algorithms.
A Remarkable Increase in Total Homocysteine Concentrations in the CSF of Migraine Patients With Aura
Authors: Isobe Chiaki , Terayama Yasuo
Published: June 2010

(Headache 2010;50:1561‐1569)

Objective.— To investigate whether total and free homocysteine (HC) levels are increased in the cerebrospinal fluid (CSF) of patients with migraine headache compared with normal control populations.

Methods.— The concentrations of free and total HC in the CSF of migraine without aura (MOA) and migraine with aura (MWA) patients were determined.

Results.— The concentration of free HC did not differ significantly from normal controls, but the total HC concentration was significantly higher in MOA and MWA patients (41% increase in MOA, P < .001 and 376% increase in MWA, P < .0001) in the mean of the confidence interval of each groups compared with normal controls).

Conclusions.— These findings suggest that an increase of total HC concentration in the brain is commonly seen in migraine patient and is particularly pronounced in MWA sufferers. We speculate that total HC not only contribute to the development of atherosclerotic conditions, including cardiocerebrovascular diseases, but also reflects an epiphenomenon.
Orthostatic Headaches in the Syndrome of the Trephined: Resolution Following Cranioplasty
Authors: Mokri Bahram
Published: June 2010

Objective.—To draw attention to the syndrome of the trephined as a potential cause for orthostatic headaches without cerebrospinal fluid (CSF) leak.

Background.—Orthostatic headaches typically result from CSF leaks but sometimes may occur in conditions without any evidence of CSF leakage.

Methods.—A 37‐year‐old right‐handed woman became comatose after a motor vehicle accident with cerebral contusions and massive left cerebral edema. A large frontoparietal craniectomy was carried out. In 5 months, she made good neurologic recovery. Freeze‐preserved bone flap was placed back. In several weeks she was functionally near normal. Two years later, she began to complain of orthostatic headache and gradually additional manifestations appeared including progressive gait unsteadiness, imprecise speech, cognitive difficulties, and an increasing left hemiparesis along with progressive sinking of the skull defect and shift of the midline and ventricular distortion. She underwent removal of resorptive sinking bone flap and construction of an acrylic cranioplasty.

Results.—At 6‐month follow‐up, there was complete resolution of the orthostatic headaches, remarkable neurologic improvement along with resolution of midline shift and ventricular distortion.

Conclusion.—The syndrome of the trephined is yet another cause of orthostatic headaches without CSF leak.
Familial form of typical childhood absence epilepsy in a consanguineous context
Authors: Abouda Hanen , Hizem Yosr , Gargouri Amina , Depienne Christel , Bouteiller Delphine , Riant Florence , Tournier‐Lasserve Elisabeth , Gourfinkel‐An Isabelle , LeGuern Eric , Gouider Riadh
Published: June 2010

Causative genes for childhood absence epilepsy (CAE) are unknown partly because families are small or phenotypically heterogeneous. In five consanguineous Tunisian families with at least two sibs with CAE, 14 patients fulfilled the diagnostic criteria for CAE (Epilepsia 1989;30:389–399). Linkage analyses or direct sequencing excluded CACNG2, CACNA1A, CACNB4, and CACNA2D2, orthologs of genes responsible for autosomal recessive (AR) absence seizures in mice. These families will help identify (a) gene(s) responsible for CAE.
Historical control monotherapy design in the treatment of epilepsy
Authors: French Jacqueline A. , Wang Steven , Warnock Bob , Temkin Nancy
Published: June 2010

Purpose: Monotherapy approvals have been difficult to obtain from the U.S. Food and Drug Administration (FDA), and have almost all been achieved using a trial design entitled “withdrawal to monotherapy” in treatment‐resistant patients, which employs a so‐called “pseudo‐placebo” as a comparator arm. The authors submitted a white paper to the FDA advocating use of a virtual placebo historical control as an alternative to pseudo‐placebo. Such an approach reduces patient risk that would result from exposure to pseudo‐placebo. In this article, we present the data submitted to the FDA to justify a historical control.

Methods: We analyzed individual patient data from eight previously completed withdrawal to monotherapy studies, which we determined had similar design. All studies employed percent meeting predetermined exit criteria (denoting worsening of seizure control) as the outcome measure. Kaplan‐Meier estimates of the percent exiting were calculated at 112 days.

Results: The percent meeting exit criteria were uniformly high, ranging from 74.9–95.9%. The eight studies appear to meet the criteria set forth for use of historical control. The estimate of the combined percent exit based on the noniterative mixed‐effects model is 85.1%, with a lower bound of the 95% prediction interval of 65.3%, and 72.2% for an 80% prediction interval.

Conclusion: There is justification for proposing that these data can serve as a historical control for future monotherapy studies, obviating the need for a placebo/pseudo‐placebo arm in trials intended to demonstrate the efficacy of approved drugs as monotherapy in treatment‐resistant patients.
The effects of cryopreservation on red blood cell rheologic properties
Authors: Henkelman Sandra , Lagerberg Johan W.M. , Graaff Reindert , Rakhorst Gerhard , Van Oeveren Willem
Published: June 2010

BACKGROUND: In transfusion medicine, frozen red blood cells (RBCs) are an alternative for liquid‐stored RBCs. Little is known about the rheologic properties (i.e., aggregability and deformability) of thawed RBCs. In this study the rheologic properties of high‐glycerol frozen RBCs and postthaw stored in saline‐adenine‐glucose‐mannitol medium were compared to those of conventionally liquid‐stored and fresh RBCs.

STUDY DESIGN AND METHODS: Fresh RBCs were obtained from healthy volunteers. Leukoreduced liquid‐stored and thawed deglycerolized RBC units were obtained from the Sanquin Blood Bank. RBCs were tested for aggregability (aggregation index [AI]), deformability (elongation index [EI]), and various hematologic variables.

RESULTS: The AI of thawed RBCs was reduced, compared to fresh and liquid‐stored RBCs (p < 0.05). The EI of stored RBCs was significantly enhanced over a shear stress range of 2.0 to 50 Pa compared to fresh RBCs (p < 0.05). No significant differences in EI between thawed and 21‐ or 35‐day liquid‐stored RBCs were observed. The osmotic fragility, hemolysis, mean cell volume, and mean cell hemoglobin concentration of thawed RBCs were markedly altered, compared to fresh and liquid‐stored RBCs (p < 0.05). The adenosine triphosphate (ATP) content of thawed RBCs was similar to 3‐ or 21‐day liquid‐stored and fresh RBCs.

CONCLUSIONS: Thawed RBCs are more fragile than conventionally liquid‐stored and fresh RBC. The freeze‐thaw‐wash process, however, did not adversely affect the aggregability and deformability or the ATP content of thawed RBCs. Based on the rheologic properties, cryopreserved RBCs are a valuable alternative to liquid‐stored RBCs.