bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of specific adenylyl cyclase isoforms by lithium and carbamazepine, but not valproate, may be related to their antidepressant effect
Authors: Mann Liad , Heldman Eliahu , Bersudsky Yuly , Vatner Stephen F , Ishikawa Yoshihiro , Almog Orna , Belmaker Robert H , Agam Galila
Published: November 2009

Objectives: Lithium, valproate, and carbamazepine decrease stimulated brain cyclic‐AMP (cAMP) levels. Adenylyl cyclase (AC), of which there are nine membrane‐bound isoforms (AC1‐AC9), catalyzes the formation of cAMP. We have recently demonstrated preferential inhibition of AC5 by lithium. We now sought to determine whether carbamazepine and valproate also preferentially inhibit specific AC isoforms or decrease cAMP levels via different mechanisms.

Methods: COS7 cells were transfected with one of AC1‐AC9, with or without D1‐dopamine receptors. Carbamazepine’s and valproate’s effect on forskolin‐ or D1 agonist‐stimulated ACs was studied. The effect of Mg2+on lithium’s inhibition was studied in membrane‐enriched fraction from COS7 cells co‐expressing AC5 and D1 receptors. AC5 knockout mice were tested for a behavioral phenotype similar to that of lithium treatment.

Results: Carbamazepine preferentially inhibited forskolin‐stimulated AC5 and AC1 and all D1 agonist‐stimulated ACs, with AC5 and AC7 being the most sensitive. When compared to 1 or 3 mM Mg2+, 10 mM Mg2+reduced lithium‐induced AC5 inhibition by 70%.In silicomodeling suggests that among AC isoforms carbamazepine preferentially affects AC1 and AC5 by interacting with the catechol‐estrogen site. Valproate did not affect any forskolin‐ or D1 receptor‐stimulated AC. AC5 knockout mice responded similarly to antidepressant‐ or lithium‐treated wild‐types in the forced‐swim test but not in the amphetamine‐induced hyperactivity mania model.

Conclusions: Lithium and carbamazepine preferentially inhibit AC5, albeit via different mechanisms. Lithium competes with Mg2+, which is essential for AC activity; carbamazepine competes for AC’s catechol‐estrogen site. Antidepressant‐like behavior of AC5 knockout mice in the forced‐swim test supports the notion that AC5 inhibition is involved in the antidepressant effect of lithium and carbamazepine. The effect of lithium and carbamazepine to lower cAMP formation in AC5‐rich dopaminergic brain regions suggests that D1‐dopamine receptors in these regions are involved in the antidepressant effect of mood stabilizers.
Suicidal ideation and depressive symptoms among bipolar patients as predictors of the health and well‐being of caregivers
Authors: Chessick Cheryl A , Perlick Deborah A , Miklowitz David J , Dickinson L Miriam , Allen Michael H , Morris Chad D , Gonzalez Jodi M , Marangell Lauren B , Cosgrove Victoria , Ostacher Michael ,   the STED‐BD Family Experience Collaborative Study Group
Published: November 2009

Objectives:  Few studies have addressed the physical and mental health effects of caring for a family member with bipolar disorder. This study examined whether caregivers’ health is associated with changes in suicidal ideation and depressive symptoms among bipolar patients observed over one year.

Methods:  Patients (N = 500) participating in the Systematic Treatment Enhancement Program for Bipolar Disorder and their primary caregivers (N = 500, including 188 parental and 182 spousal caregivers) were evaluated for up to one year as part of a naturalistic observational study. Caregivers’ perceptions of their own physical health were evaluated using the general health scale from the Medical Outcomes Study 36‐item Short‐Form Health Survey. Caregivers’ depression was evaluated using the Center for Epidemiological Studies of Depression Scale.

Results:  Caregivers of patients who had increasing suicidal ideation over time reported worsening health over time compared to caregivers of patients whose suicidal ideation decreased or stayed the same. Caregivers of patients who had more suicidal ideation and depressive symptoms reported more depressed mood over a one‐year reporting period than caregivers of patients with less suicidal ideation or depression. The pattern of findings was consistent across parent caregivers and spousal caregivers.

Conclusions:  Caregivers, rightly concerned about patients becoming suicidal or depressed, may try to care for the patient at the expense of their own health and well‐being. Treatments that focus on the health of caregivers must be developed and tested.
Penile Extramedullary Plasmacytoma in a Dog
Authors: Kim Min‐Su , Kim Dong Hoo , Choi Ul Soo
Published: November 2009

Contents

Penile tumours are rare in dogs. Reported herein is a case of a penile extramedullary plasmacytoma (EMP) in a 5‐year‐old male cocker spaniel that was brought to a local hospital for an evaluation of a penile mass. The mass was approximately 1.3 cm in diameter at the time of presentation. In fine needle aspiration and histopathological examinations, the neoplastic cells showed eccentric round nuclei, a moderate amount of basophilic cytoplasm, and a peri‐nuclear clear zone, consistent with plasma cell morphology. There was nuclear pleomorphism with mononuclear giant cells and occasional bi‐nucleation. Round cells on the periphery of the mass demonstrated plasmacytic differentiation. Immunohistochemically, the neoplastic cells stained positive for MUM1 and light lambda chain. Based on the cytological and pathological observations, a diagnosis of penile EMP was established.
Factors influencing death at home in terminally ill cancer patients
Authors: Nakamura Shunsuke , Kuzuya Masafumi , Funaki Yoshimasa , Matsui Wataru , Ishiguro Naoki
Published: November 2009

Aim:  The purpose of this study is to investigate factors affecting terminally ill cancer patients dying at home.

Material:  Ninety‐two terminally ill cancer patients who were receiving home medical care services and died between April 2005 and December 2006 were included in the study. The data included patients' and caregivers' demographic characteristics, disease‐related information, place of death, and status of home care support. To identify the factors predicting the place of death, multivariate logistic regression analyses were performed.

Results:  Patients of families who had no preference regarding the place of death or a preference for death at home were more likely to die at home (vs preference for hospital death, odds ratio = 5.87, 95% confidence interval = 1.02–36.53; odds ratio = 90.35, 95% confidence interval = 8.15–1001.51, respectively) after adjusting for potential confounders. Meanwhile, if the patient's family preferred that the patient not die at home, the patient's place of death was not at his/her home irrespective of his/her preference.

Conclusion:  The results suggested the stronger involvement of families' preferences regarding the patients' place of death over patients' own preferences. Therefore, factors affecting families' preferences need to be clarified for the dissemination of death at home for terminally ill cancer patients.
Hypertrophic cardiomyopathy in the elderly
Authors: Kubo Toru , Kitaoka Hiroaki , Okawa Makoto , Nishinaga Masanori , Doi Yoshinori L
Published: November 2009

Hypertrophic cardiomyopathy (HCM) is a relatively common genetic cardiac disorder with heterogeneous morphological, functional and clinical features. Although the risk of sudden death and incapacitating symptoms in young patients has been focused upon, the disease has been found with increasing frequency in elderly patients. However, there have been few studies on clinical features of HCM in the elderly. We established a cardiomyopathy registration study in Kochi Prefecture, which is one of the most aged communities in Japan, to provide detailed descriptions of the clinical features of HCM in a community‐based patient cohort. The unselected regional HCM population consisted largely of elderly patients (70% of the study cohort being ≥60 years of age at registration), although HCM has been regarded largely as a disease of the young. Cardiac hypertrophy that becomes clinically apparent late in life can be a genetic disorder, and mutations in the cardiac myosin‐binding protein C gene are the most common cause of late‐onset or elderly HCM. In the morphological features, sarcomere gene defects seem to have a predilection for a crescent‐shaped left ventricular cavity with reversed septal curvature even in elderly patients, although an ovoid left ventricular shape was frequently seen in elderly patients in previous clinical studies on morphological characteristics of HCM. In middle‐aged or elderly patients with HCM, heart failure and embolic events, which were strongly associated with atrial fibrillation, were very important. It is important to manage HCM patients from the standpoint of longitudinal evolution in order to prevent those clinical complications.
Dietary supplementation of n‐3 PUFA reduces weight gain and improves postprandial lipaemia and the associated inflammatory response in the obese JCR:LA‐cp rat
Authors: Hassanali Z. , Ametaj B. N. , Field C. J. , Proctor S. D. , Vine D. F.
Published: November 2009

Background: Postprandial dyslipidaemia occurs in obesity and insulin resistance (IR), and is associated with an increased risk of developing cardiovascular disease. We have recently established that the JCR:LA‐cp rodent model develops postprandial dyslipidaemia concomitant with complications of the metabolic syndrome. Dietary n‐3 polyunsaturated fatty acids (n‐3 PUFAs) are proposed to modulate plasma lipids, serum hormone levels, lipoprotein metabolism and the inflammatory state; however, results remain inconsistent during conditions of IR.

Aim: To assess the acute metabolic and inflammatory effects of dietary fish oil supplementation on existing postprandial dyslipidaemia in the JCR:LA‐cp model.

Methods: JCR:LA‐cp rats (14 weeks of age) were fed either a control, isocaloric, lipid balanced diet (15% w/w total fat, 1.0% cholesterol, P:S ratio 0.4), a lipid balanced diet with 5% n‐3 PUFA [fish oil derived eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] or a lipid balanced diet with 10% n‐3 PUFA for 3 weeks. Fasting plasma lipid, cytokine levels, postprandial chylomicron (apoB48) metabolism and the postprandial inflammatory response [haptoglobin and lipopolysaccharide binding protein (LBP)] were assessed following a standardized ‘oral fat challenge’.

Results: n‐3 PUFA treatment resulted in a significant improvement (i.e. decrease) in the postprandial response for triglyceride (45%) (p < 0.05), apoB48 (45%) (p < 0.03) and LBP (33%) (p < 0.05) compared to controls (measured as area under the clearance curve). In contrast, we observed a significant elevation in postprandial haptoglobin (165%) (p < 0.001) in obese rats supplemented with 10% n‐3 PUFA. Treatment with 5% n‐3 PUFA in the JCR:LA‐cp obese animals resulted in a complementary decrease in total body weight gain (6%) (p < 0.001) and an increase (i.e. improvement) in adiponectin (33%) (p < 0.05) compared to controls, without a concomitant reduction in food intake.

Conclusion: Acute dietary n‐3 PUFA dietary supplementation can improve fasting as well as postprandial lipid metabolism and components of the associated inflammatory response in the JCR:LA‐cp rat. Further, moderate dose n‐3 PUFA supplementation may reduce corresponding body weight during conditions of hypercholesterolaemia and/or modulate inflammation associated with obesity and the metabolic syndrome.
A randomized, treat‐to‐target trial comparing insulin lispro protamine suspension and insulin detemir in insulin‐naive patients with Type 2 diabetes
Authors: Fogelfeld L. , Dharmalingam M. , Robling K. , Jones C. , Swanson D. , Jacober S.
Published: November 2009

Diabet. Med. 27, 181–188 (2010)

Aims  Insulin lispro protamine suspension (ILPS) and insulin detemir were compared in insulin‐naive patients with Type 2 diabetes poorly controlled by oral glucose‐lowering agents (OGLAs) to demonstrate non‐inferior overall glycaemic control.

Methods  This was a 24‐week, multinational, open‐label, parallel‐group, treat‐to‐target trial. Adults taking two or more OGLAs were randomized to ILPS (n = 223) or detemir (n = 219) once daily at bedtime. Doses were titrated to target fasting blood glucose (FBG) 5.0–7.2 mmol/l. A pre‐breakfast dose was added up to week 8 per prespecified criteria. The primary objective was comparison of glycated haemoglobin (HbA1c) change from baseline (non‐inferiority margin 0.4%).

Results  At end‐point, HbA1c decreased from 8.8 ± 0.7% in both groups to 7.3 ± 0.9% (ILPS) and 7.5 ± 1.1% (detemir). Least‐squares mean difference (95% confidence interval) for HbA1c [−0.21% (−0.39, −0.03)] and glycaemic variability [0.10 mmol/l (−0.02, 0.23)] demonstrated non‐inferiority. End‐point mean FBG was 7.0 vs. 6.9 mmol/l (P = 0.85), and percentages of patients achieving H < 7.0% were 34.9% vs. 31.2% for ILPS vs. detemir. More ILPS patients used twice‐daily dosing (59% vs. 49%). Mean daily insulin dose was 0.39 vs. 0.46 U/kg (P = 0.005) and weight gain was 1.88 vs. 0.36 kg (P < 0.001) for ILPS vs. detemir. Overall hypoglycaemia (episodes?patient‐1?year‐1) (24.2 ± 33.0 vs. 16.2 ± 26.1, P = 0.001) and nocturnal (6.3 ± 12.1 vs. 3.8 ± 13.2, P < 0.001) rates were higher for ILPS.

Conclusions  At end‐point, ILPS was non‐inferior to detemir in HbA1c change from baseline. Patients using ILPS achieved lower end‐point HbA1c with lower insulin doses but greater hypoglycaemia and weight gain.
INCENTIVES AND SOCIAL NORMS: A MOTIVATION‐BASED ECONOMIC ANALYSIS OF SOCIAL NORMS
Authors: Festré Agnès
Published: November 2009

Abstract It is now commonplace to regard social norms as a subject of growing interest in the economic literature (e.g. game theoretical approaches based on ‘other‐regarding’ individual preferences, the analysis of the impact of rewards or punishment on individuals’ behaviour through experimental economics as well as field experiments, the revival of the institutionalist tradition spurred on by the influential work of Douglas North and followed by many others and the growing influence of neuroeconomics). In this paper, we focus on the relationship between incentives and social norms and survey the literature that could constitute the foundations of a motivation‐based economic analysis of social norms. Our main findings are that (1) the interaction between incentives and social norms is far from obvious since taking social norms into account involves the introduction of supplementary motives, in addition to self‐interest, into the economic analytical framework; (2) the analysis of the interaction between incentives and social norms resists an approach exclusively in terms of crowding‐in and ‐out effects because it is sensitive to whether it concerns behaviours driven by honour or by social stigma; (3) as a result, it is difficult to precisely evaluate the policy implication of the interactions between incentives and social norms.
“The Old Vexed Question:” Divergent Attitudes and Practices in the Sacred Music of Early Ballarat
Authors: DOGGETT ANNE
Published: November 2009

When gold was discovered at Ballarat in 1851, the peaceful pastoral community was transformed into a rough mining camp. People from all parts of the world came in search of wealth, bringing with them a diversity of cultural and spiritual affiliations. As the musical life of the various denominational groups developed according to specific doctrinal principles and local influences, strong opinions were expressed in the community regarding the place of music in worship. This article looks at the developments in sacred music during the two decades that saw Ballarat transformed into a major city. The strong differences in discourse and practice that were evident between and within particular religious groups form a background for reflecting upon contemporary perceptions of the function of music in worship.
“Moral Panic” or Pejorative Labelling? Rethinking the Mazengarb Inquiry into Underage Sex in the Hutt Valley in 1954
Authors: GUY LAURIE
Published: November 2009

This article re‐examines the interpretation of widespread concern over significant underage sex in the Hutt Valley, Wellington, which resulted in a government inquiry in 1954. It challenges the typical “moral panic” interpretive lens concerning the inquiry, arguing that the term obscures more than it reveals. The term focuses on reaction to the Hutt Valley affair but fails to address sufficiently the causative question of why such concern existed in the first place. The “moral panic” framing of the Hutt Valley incidents has failed to give adequate recognize that the developments were early indicators of increasing societal shifts that threatened long‐held public views on sexuality; that manifest, societal, sexuality values changes in the next two decades showed that concerned people of 1954 were right within the framework of their worldview to have such concern; and that the so‐called “moral panic” concern of 1954 already existed prior to the Hutt Valley disclosures.
Nonrecurring Accounting Transactions and Stock Option Grants
Authors: Zhang Wei , Cahan Steven F.
Published: November 2009

Abstract:  We examine the effect of nonrecurring accounting transactions on stock option grants for a sample of US companies. After controlling for both the economic and corporate governance‐related determinants of option grants, we find that the aggregate value of stock option grants is more positively related to nonrecurring gains than to nonrecurring losses. We also examine whether the asymmetric treatment of nonrecurring gains and losses arises because (1) information contained in the nonrecurring transactions is related to firms’ long‐term prospects, (2) weak corporate governance fails to curb more favorable executive pay arrangements, (3) executives possess superior bargaining power in the labor marketplace, and (4) firms have significant growth opportunities. While we find no support for the first explanation and some support for the third, we find more consistent support for the growth explanation and two factors related to the corporate governance explanation: director‐executive duality and the frequency of board meetings.
National and Office‐Specific Measures of Auditor Industry Expertise and Effects on Audit Quality
Authors: REICHELT KENNETH J. , WANG DECHUN
Published: November 2009

Our paper examines whether audit quality is higher for industry audit specialists at the national and city‐office levels using the framework developed in Ferguson et al. [2003] and Francis et al. [2005]. We find that auditors who are both national and city‐specific industry specialists have clients with the lowest abnormal accruals, suggesting that joint national and city‐specific industry specialists have the highest audit quality. In addition, we find some evidence that abnormal accruals of firms audited by city‐industry specialists alone (without also being national specific industry specialists) are lower than those audited by nonindustry specialists. Using alternative measures of audit quality, we find that when the auditor is both a national and a city‐specific industry specialist, its clients are less likely to meet or beat analysts' earnings forecasts by one penny per share and more likely to be issued a going‐concern audit opinion. Together these results provide consistent evidence that audit quality is higher when the auditor is both a national and city‐specific industry specialist, suggesting that auditors' national positive network synergies and the individual auditors' deep industry knowledge at the office level are jointly important factors in delivering higher audit quality.
Rosiglitazone via upregulation of Akt/eNOS pathways attenuates dysfunction of endothelial progenitor cells, induced by advanced glycation end products
Authors: Liang Chun , Ren Yusheng , Tan Hongbin , He Zhiqing , Jiang Qijun , Wu Jianxiang , Zhen Yi , Fan Min , Wu Zonggui
Published: November 2009

Background and purpose:  Advanced glycation end products (AGEs) and endothelial progenitor cells (EPCs) play key roles in pathogenesis of diabetes‐related vascular complications. AGEs can induce dysfunction in EPCs. The peroxisome proliferator‐activated receptor‐gamma (PPARγ) agonists are widely used in the treatment of type 2 diabetes, and it remains unknown if they could attenuate EPC dysfunction induced by AGEs.

Experimental approach:  EPCs isolated from healthy adults were cultured with various concentrations of AGEs (0, 50, 100 and 200 mg·L−1) with or without rosiglitazone (10 nM), antibody for the receptors for AGE‐human serum albumin (anti‐receptor for advanced glycation end products (RAGE); 50 µg·mL−1), phosphatidylinositol‐3‐kinase (PI3K) inhibitor (LY294002, 5 µM), nitric oxide (NO) synthase inhibitor (L‐NG‐nitro‐arginine methyl ester (L‐NAME), 100 µM) or sodium nitroprusside (SNP, 25 µM). Proliferation, apoptosis, cell adhesion, migration and NO production in EPCs were assessed, and expressions of endothelial NO synthase (eNOS) and Akt were determined.

Key results:  Number, proliferation/migration capacities, eNOS and Akt phosphorylation as well as NO synthesized by EPCs were increased by rosiglitazone and reduced by AGEs. AGEs promoted while rosiglitazone reduced EPC apoptosis. The AGE‐induced effects were significantly ameliorated by pre‐incubation with rosiglitazone, RAGE antibody and SNP. The beneficial effects of rosiglitazone could be blocked by pretreatment with L‐NAME and LY294002.

Conclusions and implications:  The PPARγ agonist rosiglitazone increased EPC function and attenuated EPC dysfunction induced by AGEs via upregulating the Akt‐eNOS signal pathways of EPCs.
Hydrogen peroxide affects contractile activity and anti‐oxidant enzymes in rat uterus
Authors: Appiah I , Milovanovic S , Radojicic R , Nikolic‐Kokic A , Orescanin‐Dusic Z , Slavic M , Trbojevic S , Skrbic R , Spasic MB , Blagojevic D
Published: November 2009

Background and purpose:  The effects of hydrogen peroxide (H2O2) on uterine smooth muscle are not well studied. We have investigated the effect and the mechanism of action of exogenous hydrogen peroxide on rat uteri contractile activity [spontaneous and calcium ion (Ca2+)‐induced] and the effect of such treatment on anti‐oxidative enzyme activities.

Experimental approach:  Uteri were isolated from virgin Wistar rats and suspended in an organ bath. Uteri were allowed to contract spontaneously or in the presence of Ca2+ (6 mM) and treated with H2O2 (2 µM–3 mM) over 2 h. Anti‐oxidative enzyme activities (manganese superoxide dismutase‐MnSOD, copper‐zinc superoxide dismutase‐CuZnSOD, catalase‐CAT, glutathione peroxidase‐GSHPx and glutathione reductase‐GR) in H2O2‐treated uteri were compared with those in uteri immediately frozen after isolation or undergoing spontaneous or Ca2+‐induced contractions, without treatment with H2O2. The effect of inhibitors (propranolol, methylene blue, L‐NAME, tetraethylamonium, glibenclamide and 4‐aminopyridine) on H2O2‐mediated relaxation was explored.

Key results:  H2O2 caused concentration‐dependent relaxation of both spontaneous and Ca2+‐induced uterine contractions. After H2O2 treatment, GSHPx and MnSOD activities were increased, while CuZnSOD and GR (In Ca2+‐induced rat uteri) were decreased. Nω‐nitro‐L‐arginine methyl ester antagonized the effect of H2O2 on Ca2+‐induced contractions. H2O2‐induced relaxation was not affected by propranolol, potentiated by methylene blue and antagonized by tetraethylamonium, 4‐aminopyridine and glibenclamide, with the last compound being the least effective.

Conclusions and implications:  H2O2 induced dose‐dependent relaxation of isolated rat uteri mainly via changes in voltage‐dependent potassium channels. Decreasing generation of reactive oxygen species by stimulation of anti‐oxidative pathways may lead to new approaches to the management of dysfunctional uteri.
[6S]‐5‐methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild‐type 677C→T polymorphism of methylenetetrahydrofolate reductase
Authors: Prinz‐Langenohl R , Brämswig S , Tobolski O , Smulders YM , Smith DEC , Finglas PM , Pietrzik K
Published: November 2009

Background and purpose:  5,10‐Methylenetetrahydrofolate reductase (MTHFR) is responsible for the synthesis of 5‐methyltetrahydrofolate (5‐MTHF). The 677C→T mutation of MTHFR reduces the activity of this enzyme. The aim of this study was, first, to compare pharmacokinetic parameters of [6S]‐5‐MTHF and folic acid (FA) in women with the homozygous (TT) and wild‐type (CC) 677C→T mutation, and second, to explore genotype differences. The metabolism of [6S]‐5‐MTHF and FA was evaluated by measuring plasma folate derivatives.

Experimental approach:  Healthy females (TT, n= 16; CC, n= 8) received a single oral dose of FA (400 µg) and [6S]‐5‐MTHF (416 µg) in a randomized crossover design. Plasma folate was measured up to 8 h after supplementation. Concentration‐time‐profile [area under the curve of the plasma folate concentration vs. time (AUC)], maximum concentration (Cmax) and time‐to‐reach‐maximum (tmax) were calculated.

Key results:  AUC and Cmax were significantly higher, and tmax significantly shorter for [6S]‐5‐MTHF compared with FA in both genotypes. A significant difference between the genotypes was observed for tmax after FA only (P < 0.05). Plasma folate consisted essentially of 5‐MTHF irrespective of the folate form given. Unmetabolized FA in plasma occurs regularly following FA supplementation, but rarely with [6S]‐5‐MTHF.

Conclusions and implications:  These data suggest that [6S]‐5‐MTHF increases plasma folate more effectively than FA irrespective of the 677C→T mutation of the MTHFR. This natural form of folate could be an alternative to FA supplementation or fortification.
Comparison of the antiepileptogenic effects of an early long‐term treatment with ethosuximide or levetiracetam in a genetic animal model of absence epilepsy
Authors: Russo Emilio , Citraro Rita , Scicchitano Francesca , De Fazio Salvatore , Di Paola Eugenio D. , Constanti Andrew , De Sarro Giovambattista
Published: November 2009

Purpose: Epilepsy is a heterogeneous syndrome characterized by recurrent, spontaneous seizures; continuous medication is, therefore, necessary, even after the seizures have long been suppressed with antiepileptic drug (AED) treatments. The most disturbing issue is the inability of AEDs to provide a persistent cure, because these compounds generally suppress the occurrence of epileptic seizures without necessarily having antiepileptogenic properties. The aim of our experiments was to determine, in the WAG/Rij model of absence epilepsy, if early long‐term treatment with some established antiabsence drugs might prevent thedevelopmentof seizures, and whether such an effect could be sustained.

Methods: WAG/Rij rats were treated for ∼3.5 months (starting at 1.5 months of age, before seizure onset) with either ethosuximide (ETH; drug of choice for absence epilepsy) or levetiracetam (LEV; a broad‐spectrum AED with antiabsence and antiepileptogenic properties).

Results: We have demonstrated that both drugs are able to reduce the development of absence seizures, exhibiting antiepileptogenic effects in this specific animal model.

Discussion: These findings suggest that absence epilepsy in this strain of rats very likely follows an epileptogenic process during life and that early therapeutic intervention is possible, thereby opening a new area of research for absence epilepsy and AED treatment strategies.
Meta‐analysis of the association between cysticercosis and epilepsy in Africa
Authors: Quet Fabrice , Guerchet Maëlenn , Pion Sebastien D. S. , Ngoungou Edgard B. , Nicoletti Alessandra , Preux Pierre‐Marie
Published: November 2009

Purpose:  The association between cysticercosis and epilepsy has been widely studied in Latin America and Asia and has proven to be one of the main causes of epilepsy. Despite high prevalences of both diseases in Africa, their association remains unclear. In this article we quantified the strength of the association between epilepsy and cysticercosis in Africa and we proposed some guidelines for future studies.

Methods:  We performed a systematic review of literature on cysticercosis (considered as exposure) and epilepsy (considered as the disease) and collected data from both cross‐sectional and case–control studies. A common odds ratio was estimated using a random‐effects meta‐analysis model of aggregate published data.

Results:  Among 21 retrieved documents, 11 studies located in 8 African countries were included in the meta‐analysis. Odds ratio of developing epilepsy when presenting cysticercosis (defined as Taenia solium seropositivity) ranged from 1.3–6.1. Overall, association between cysticercosis and epilepsy was found significant with a common odds ratio of 3.4 [95% confidence interval (CI) 2.7–4.3; p < 0.001].

Discussion:  The variability of the association found between the studies could be due to differences in study design or in pathogenesis of cysticercosis. Further studies should overcome identified problems by following some guidelines to improve epidemiologic and clinical assessment of the association. Better understanding of the relation between cysticercosis and epilepsy is a key issue in improving prevention of epilepsy in Africa.
Dravet syndrome and deep brain stimulation: Seizure control after 10 years of treatment
Authors: Andrade Danielle M. , Hamani Clement , Lozano Andres M. , Wennberg Richard A.
Published: November 2009

Dravet syndrome is a genetically determined severe epilepsy associated with cognitive decline and ataxia. The many types of seizures seen in these patients are typically pharmacoresistant. Here we describe two adults with Dravet syndrome who were treated with thalamic deep brain stimulation (DBS) and followed for 10 years. One patient with partial onset seizures received DBS at age 19 and showed a marked improvement in seizure control after DBS insertion and stimulation. The other patient with generalized onset seizures received DBS at age 34 and did not show any immediate benefit. No side effects or changes in cognition were observed in either of the patients. This is the first report of (short‐ and) long‐term results in Dravet patients treated with thalamic DBS. We speculate that the results of DBS for epilepsy in patients with Dravet syndrome may be related to age at initiation of DBS treatment and seizure type.
Prevention, Adaptation, and Threat Denial: Flooding Experiences in the Netherlands
Authors: Zaalberg Ruud , Midden Cees , Meijnders Anneloes , McCalley Teddy
Published: November 2009

Delta areas such as the Netherlands are more and more at risk of future flooding due to global climate change. Motivating residents living in flood‐prone areas to effectively cope with local floods may lead to minimization of material losses and loss of life. The aim of this research was to investigate whether the extent to which residents had been exposed to flooding in the past was a key factor in motivating residents to effectively cope with future flooding. We also focused on the psychological variables that mediated this relationship. We conducted a survey (N = 516) among flood victims and nonvictims. We assessed subjective experiences due to past flooding, affective and cognitive appraisals, and coping responses. Results show that victims reported stronger emotions (negative and positive), and the receipt of more social support due to past flooding than did nonvictims. Moreover, victims worry more about future flooding, perceive themselves as more vulnerable to future flooding, perceive the consequences of future flooding as more severe, and have stronger intentions to take adaptive actions in the future than nonvictims. Structural equation modeling reveals that the latter effect was fully mediated by specific experiences and appraisals. Insights into factors and processes that have the potential to motivate residents to effectively cope with future floods may prove helpful in developing interventions to inform residents how to act effectively in case of an imminent flood.
Alveolar bone dimensional changes of post‐extraction sockets in humans: a systematic review
Authors: Van der Weijden Fridus , Dell'Acqua Federico , Slot Dagmar Else
Published: November 2009

Objective:To review the literature to assess the amount of change in height and width of the residual ridge after tooth extraction.

Material and Methods:MEDLINE‐PubMed and the Cochrane Central register of controlled trials (CENTRAL) were searched through up to March 2009. Appropriate studies which data reported concerning the dimensional changes in alveolar height and width after tooth extraction were included. Approximal height change, mid‐buccal change, mid‐crestal change, mid‐lingual change, Alveolar width change and socket fill were selected as outcome variables. Mean values and if available standard deviations were extracted. Weighted mean changes were calculated.

Results:Independent screening of the titles and abstracts of 1244 MEDLINE‐PubMed and 106 Cochrane papers resulted in 12 publications that met the eligibility criteria. The reduction in width of the alveolar ridges was 3.87 mm. The mean clinical mid‐buccal height loss was 1.67 mm. The mean crestal height change as assessed on the radiographs was 1.53 mm. Socket fill in height as measured relative to the original socket floor was on an average 2.57 mm.

Conclusion:During the post‐extraction healing period, the weighted mean changes as based on the data derived from the individual selected studies show the clinical loss in width to be greater than the loss in height, assessed both clinically as well as radiographically.
Early healing of implants placed into fresh extraction sockets: an experimental study in the beagle dog. III:soft tissue findings
Authors: Vignoletti Fabio , De Sanctis Massimo , Berglundh Tord , Abrahamsson Ingemar , Sanz Mariano
Published: November 2009

Aim:To describe histologically the early phases of soft tissue healing to implants placed into fresh extraction sockets.

Materials and Methods:In 16 beagle dogs, 64 3.25‐mm‐wide cylindrical screw implants were inserted into the distal sockets of the third and fourth lower premolars using a one‐stage trans‐mucosal healing protocol. Biopsies were then taken at 1, 2, 4 and 8 weeks and prepared for histological examination.

Results:One‐week specimens showed a junctional epithelium and an underlying loose connective tissue rich in inflammatory cells. At 2 weeks, signs of epithelial proliferation and a more organized connective tissue were observed. At 4 and 8 weeks, inflammation was absent; the epithelium appeared mature and in close contact with the surface of the healing abutment or the implant. The connective tissue was dense in an area close to the implant surface and the fibres were aligned parallel to the implant surface. The soft tissue dimensions at 8 weeks were approximately 5 mm, including about 3–3.5 mm of epithelium and 1–1.5 mm of connective tissue.

Conclusion:Soft tissue healing to implants placed in fresh extraction sockets may result in a longer epithelial interface than implants placed in a healed ridge.
Inhibition of procarcinogen‐bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin
Authors: Chang Thomas K. H. , Chen Jie , Yang Guixiang , Yeung Eugene Y. H.
Published: November 2009

Abstract: Administration of melatonin to rodents decreases the incidence of tumorigenesis initiated by benzo[a]pyrene or 7,12‐dimethylbenz[a]anthracene, which requires bioactivation by cytochrome P450 enzymes, such as CYP1A1, CYP1A2 and CYP1B1, to produce carcinogenic metabolites. The present study tested the hypothesis that melatonin is a modulator of human CYP1 catalytic activity and gene expression. As a comparison, we also investigated the effect of melatonin on the catalytic activity of CYP2A6, which is also a procarcinogen‐bioactivating enzyme. Melatonin (3–300 μm) decreased 7‐ethoxyresorufinO‐dealkylation catalyzed by human hepatic microsomes and recombinant CYP1A1, CYP1A2 and CYP1B1, whereas it did not affect coumarin 7‐hydroxylation catalyzed by hepatic microsomes or recombinant CYP2A6. Melatonin inhibited CYP1 enzymes by mixed inhibition, with apparentKivalues (mean ± S.E.M.) of 59 ± 1 (CYP1A1), 12 ± 1 (CYP1A2), 14 ± 2 (CYP1B1) and 46 ± 8 μm(hepatic microsomes). Additional experiments indicated that melatonin decreased benzo[a]pyrene hydroxylation catalyzed by hepatic microsomes and CYP1A2 but not by CYP1A1 or CYP1B1. Treatment of MCF‐10A human mammary epithelial cells with melatonin (up to 300 μm) did not affect basal or benzo[a]pyrene‐inducible CYP1A1 or CYP1B1 gene expression. Consistent with this finding, melatonin did not influence reporter activity in aryl hydrocarbon receptor‐dependent pGudluc6.1‐transfected MCF‐10A cells treated with or without benzo[a]pyrene, as assessed in an in vitro cell‐based luciferase reporter gene assay. Overall, melatonin is an in vitro inhibitor of human CYP1 catalytic activity, and it may be useful to develop potent analogues of melatonin as potential cancer chemopreventive agents that block CYP1‐mediated chemical carcinogenesis.
Gendered observations and experiences in executive women's work
Authors: Murray Peter A. , Syed Jawad
Published: November 2009

This article explores gendered observations and experiences of executive women on the basis of common world views or lenses through which gender differences are interpreted and understood. Three types of lenses are identified from both the literature and the data: monocultural, statistical and structural. The discussion explores the relationships and ties between each lens noting the overlapping characteristics. A qualitative study is used to index the various themes and the coping strategies employed by executive women in Australia based on specific work experiences in leadership and gender relations. The study adds to existing gender theory by highlighting how gendered lenses can be used to explore gender hierarchies and inequality regimes which lie at the centre of executive women's work.
The Pearls and Perils of Identifying Potential
Authors: Silzer Rob , Church Allan H.
Published: November 2009

Organizations today are increasingly focused on talent as a strategic asset and a competitive advantage for achieving business success. As a result, most major organizations have recognized the need for and outlined a formal process to identify and assess high-potential talent. There is, however, little agreement within or between organizations on the definition and components of the concept of potential. The existing definitions and models of potential are often narrowly focused on only a few select factors and give little attention to the broad spectrum of potential talent in an organization. This article introduces a new integrated model of potential that incorporates previous literature and current assessment practice regarding high potentials, provides a coherent structure of potential, and is reflective of a variety of different talent pools. The model provides a useful method for answering the key question—Potential for what? Three key components of potential are described by the model: (a) foundational dimensions, (b) growth dimensions, and (c) career dimensions. Implications for assisting organizations in more effectively managing their high potential talent for strategic business objectives are discussed.
Piston Ring Lubrication—Part 1: The Historical Development of Piston Ring Technology
Authors: Economou P. N. , Dowson D. , Baker A. J. S.
Published: November 2009

The history of the piston seal may be traced far beyond the Industrial Revolution, for the problems inherent in sealing a moving piston within a cylinder were well known to the early Greek and Roman engineers. Substantial progress in piston sealing technology was not made, however, until the 17th and 18th centuries, and it was the advent of the steam engine that was to spawn the many and elaborate piston packings of the reciprocating engine. The invention of the modern piston ring is generally attributed to John Ramsbottom, who announced his self-tensioning device in the mid-19th Century. In some respects, the piston ring used in current engineering practice is superficially the same as the Ramsbottom ring, but it is important to note that many of the features of piston rings in reciprocating machinery emerged in the steam rather than in the internal combustion engine age. In this paper, we trace the history of the piston ring from the early civilizations to the present day and establish the current state of technology of piston rings in the light of their varied history. It is widely recognized that a substantial proportion of the power loss within a reciprocating engine is attributable to piston-ring-liner interactions, and there is a pressing need for a better understanding of the sealing and lubrication process in order to minimize these losses. Much of the progress in piston ring technology is attributable to materials, but important and recent developments in the field of lubrication analysis have enhanced our understanding of piston ring operation. It is now possible to identify the role of geometrical features of the rings in determining important operating characteristics of a ring pack such as sealing, lubrication and lubricant transport and there are indications that novel design features will further enhance piston ring performance in the future. In addition to providing the historical background to piston ring development, this paper will also serve to introduce some of the basic concepts of piston ring operation developed in recent years which form the basis for the analysis presented in detail in Parts II and III.
Experimental Investigations Into the Behavior of Elastohydrodynamic Lubricating Films
Authors: Shawki G. S. A. , Mokhtar M. O. A. , Abdel-Ghany A. A.
Published: November 2009

This paper presents the results of experimental investigations conducted on a disk machine specially designed and constructed to determine film behavior under elastohydrodynamic lubrication conditions. Oil film thickness is measured by a novel electronic technique utilizing a capacitive transducer. Besides film geometry, measurements include temperature distribution and frictional traction in the film, all taken under pure sliding conditions. Recordings of full contact profile confirm by way of example the development of a critical reduction in film thickness towards the exit end of the Hertzian zone, this being accompanied by a critical increase in contact temperature. Further work on the subject is proceeding.
Development of Foil Journal Bearings for High Load Capacity and High Speed Whirl Stability
Authors: Heshmat H. , Shapiro W. , Gray S.
Published: November 2009

This paper describes the development of two types of air-lubricated foil journal bearings, designed for separate purposes; stability and load capacity. The first was a three-pad configuration, with each pad forming a wedge whose convergence increases with operating speed (of 120,000 rpm max.). The net result is a highly stable bearing at high operating speed. The second was a single pad journal bearing (43.7 mm diameter × 34.9 mm long) that produced a load capacity of 352 KPa (51 psi) at an operating speed of 68,000 rpm.
Operating Characteristics of Journal Bearings in Turbulent Inertial Flow
Authors: Constantinescu V. N. , Galetuse S.
Published: November 2009

A numerical method for solving the lubrication equations including an iterative procedure to account for the inertial effects is outlined, together with appropriate boundary conditions for film rupture. Data concerning the operating characteristics of full journal bearings are provided, function of length/diameter ratio, clearance ratio, Reynolds number, and eccentricity ratio. As compared to other existing numerical procedures, the present method has the main advantage that it can be easily implemented to any existing program for calculating the operating characteristics of a bearing in laminar and turbulent flow. Moreover, it was found that the first iteration gives sufficiently accurate results, so that convergence problems related to the iteration procedure (which may appear when the product between the Reynolds number and the clearance ratio is very large) does not alter its practical utility.
The Influence of Fluid Inertia in Unsteady Lubrication Films
Authors: Sestieri A. , Piva R.
Published: November 2009

The influence of the inertial forces in steady and unsteady lubrication films has been analyzed by means of an accurate computational model of the complete set of Navier Stokes equations for incompressible flows. A coordinate transformation accounts for the geometrical shape of the film boundary and its variation in time, reducing the numerical integration to a rectangular constant domain in the transformed plane. A dimensional analysis of the equations, both in steady and unsteady conditions, is performed to deduce the most significant nondimensional variables and parameters to be considered for a proper evaluation of the inertial effects. The applications are restricted to two-dimensional fields and simple boundary conditions to test the simulation capabilities of the computational model, by comparison with analytical solutions available in literature. Several geometrical and kinematic conditions are discussed and the effect of the convective and time dependent inertial terms is quantitatively evaluated.
Pressure Distributions in a Superlaminar Journal Bearing
Authors: Roberts J. B. , Hinton R. E.
Published: November 2009

The main features of a comprehensive set of pressure measurements, obtained from a short, plain journal bearing, are presented. The pressure field in the lubricant film was measured in both the circumferential and axial directions over a Reynolds number range of 40–50,000. In cases where the film is noncavitating the pressure distributions are separated into viscous and inertial components. The inertial components are found to agree fairly well with an approximate short bearing theory. Axially averaged, total pressure distributions are compared with the predictions of a simple, empirical theory based on measured friction factors and incorporating inertial effects.
Effect of Preset on the Performance of Finite Journal Bearings Supporting Rigid and Flexible Rotors
Authors: Singh A. , Gupta B. K.
Published: November 2009

A large number of cylindrical bearings are manufactured in two halves and assembled in such a way that there exists a possibility that the center may get displaced along the parting line. Very little published data are available on the effect of this displacement on the performance of journal bearings. This paper is directed toward the theoretical study of the static and dynamic behavior of the finite displaced lobe or “offset” bearings where the displacement or “preset” is either accidental due to the faulty manufacture or intentional to improve the performance. It has been found that the static dynamic properties of journal bearings are greatly influenced by preset. Data on load capacity, dynamic coefficients and stability are presented in this paper for several values of preset, L/D ratio and shaft flexibility. Offset bearings are found to be much more stable in comparison to conventional cylindrical journal bearings, specially for low loads.
Frequency-Domain Estimation of Linearized Oil-Film Coefficients
Authors: Burrows C. R. , Sahinkaya M. N.
Published: November 2009

A frequency domain algorithm for estimating linearized oil-film bearing coefficients is developed and evaluated under controlled conditions. Its ability to produce meaningful coefficient estimates from noisy data is examined, and a confidence bound is provided for the estimates. Results obtained from both simulated and experimental data show that the technique is more efficient than the time-domain algorithm described in earlier work. A comparison of experimentally estimated and theoretically derived coefficients for a squeeze-film bearing suggests that closed-form expressions for the velocity coefficient obtained by assuming a 180 deg oil-film are valid for a wider range of eccentricity ratios than have been previously demonstrated.
The Pivoted, Spherical Cap Slider Bearing
Authors: Lund J. W.
Published: November 2009

In hydraulic pumps of the positive displacement type, the shoes which guide the piston motion may be designed as pivoted slider bearings. One such design, where the bearing geometry is that of a spherical cap, is analyzed and results are presented for the load carrying capacity and the friction.