bluuebunny/crossref_metadata_2025 huggingface dataset:
Respiratory uncoupling by UCP1 and UCP2 and superoxide generation in endothelial cell mitochondria
Authors: Fink Brian D. , Reszka Krzysztof J. , Herlein Judy A. , Mathahs Mary M. , Sivitz William I.
Published: September 2004

Mitochondria represent a major source of reactive oxygen species (ROS), particularly during resting or state 4 respiration wherein ATP is not generated. One proposed role for respiratory mitochondrial uncoupling proteins (UCPs) is to decrease mitochondrial membrane potential and thereby protect cells from damage due to ROS. This work was designed to examine superoxide production during state 4 (no ATP production) and state 3 (active ATP synthesis) respiration and to determine whether uncoupling reduced the specific production of this radical species, whether this occurred in endothelial mitochondria per se, and whether this could be modulated by UCPs. Superoxide formation by isolated bovine aortic endothelial cell (BAE) mitochondria, determined using electron paramagnetic resonance spectroscopy, was approximately fourfold greater during state 4 compared with state 3 respiration. UCP1 and UCP2 overexpression both increased the proton conductance of endothelial cell mitochondria, as rigorously determined by the kinetic relationship of respiration to inner membrane potential. However, despite uncoupling, neither UCP1 nor UCP2 altered superoxide formation. Antimycin, known to increase mitochondrial superoxide, was studied as a positive control and markedly enhanced the superoxide spin adduct in our mitochondrial preparations, whereas the signal was markedly impaired by the powerful chemical uncoupler p-(trifluoromethoxyl)-phenyl-hydrazone. In summary, we show that UCPs do have uncoupling properties when expressed in BAE mitochondria but that uncoupling by UCP1 or UCP2 does not prevent acute substrate-driven endothelial cell superoxide as effluxed from mitochondria respiring in vitro.
Cd2+-induced cytochromecrelease in apoptotic proximal tubule cells: role of mitochondrial permeability transition pore and Ca2+uniporter
Authors: Lee Wing-Kee , Bork Ulrich , Gholamrezaei Fatemeh , Thévenod Frank
Published: September 2004

Cd2+induces apoptosis of kidney proximal tubule (PT) cells. Mitochondria play a pivotal role in toxic compound-induced apoptosis by releasing cytochrome c. Our objective was to investigate the mechanisms underlying Cd2+-induced cytochrome c release from mitochondria in rat PT cells. Using Hoechst 33342 or MTT assay, 10 μM Cd2+induced ∼5–10% apoptosis in PT cells at 6 and 24 h, which was associated with cytochrome c and apoptosis-inducing factor release at 24 h only. This correlated with previously described maximal intracellular Cd2+concentrations at 24 h, suggesting that elevated Cd2+may directly induce mitochondrial liberation of proapoptotic factors. Indeed, Cd2+caused swelling of energized isolated kidney cortex mitochondria (EC50∼9 μM) and cytochrome c release, which were independent of permeability transition pore (PTP) opening since PTP inhibitors cyclosporin A or bongkrekic acid had no effect. On the contrary, Cd2+inhibited swelling and cytochrome c release induced by PTP openers (PO43−or H2O2+Ca2+). The mitochondrial Ca2+uniporter (MCU) played a key role in mitochondrial damage: 1) MCU inhibitors (La3+, ruthenium red, Ru360) prevented swelling and cytochrome c release; and 2) ruthenium red attenuated Cd2+inhibition of PO43−-induced swelling. Using the Cd2+-sensitive fluorescent indicator FluoZin-1, Cd2+was also taken up by mitoplasts. The aquaporin inhibitor AgNO3abolished Cd2+-induced swelling of mitoplasts. This could be partially mediated by activation of the mitoplast-enriched water channel aquaporin-8. Thus cytosolic Cd2+concentrations exceeding a certain threshold may directly cause mitochondrial damage and apoptotic development by interacting with MCU and water channels in the inner mitochondrial membrane.
Transcriptional profiling of in vitro smooth muscle cell differentiation identifies specific patterns of gene and pathway activation
Authors: Spin Joshua M. , Nallamshetty Shriram , Tabibiazar Raymond , Ashley Euan A. , King Jennifer Y. , Chen Mary , Tsao Phillip S. , Quertermous Thomas
Published: September 2004

Mesodermal and epidermal precursor cells undergo phenotypic changes during differentiation to the smooth muscle cell (SMC) lineage that are relevant to pathophysiological processes in the adult. Molecular mechanisms that underlie lineage determination and terminal differentiation of this cell type have received much attention, but the genetic program that regulates these processes has not been fully defined. Study of SMC differentiation has been facilitated by development of the P19-derived A404 embryonal cell line, which differentiates toward this lineage in the presence of retinoic acid and allows selection for cells adopting a SMC fate through a differentiation-specific drug marker. We sought to define global alterations in gene expression by studying A404 cells during SMC differentiation with oligonucleotide microarray transcriptional profiling. Using an in situ 60-mer array platform with more than 20,000 mouse genes derived from the National Institute on Aging clone set, we identified 2,739 genes that were significantly upregulated after differentiation was completed (false-detection ratio <1). These genes encode numerous markers known to characterize differentiated SMC, as well as many unknown factors. We further characterized the sequential patterns of gene expression during the differentiation time course, particularly for known transcription factor families, providing new insights into the regulation of the differentiation process. Changes in genes associated with specific biological ontology-based pathways were evaluated, and temporal trends were identified for functional pathways. In addition to confirming the utility of the A404 model, our data provide a large-scale perspective of gene regulation during SMC differentiation.
The gene encoding mouse Muc19: cDNA, genomic organization and relationship to Smgc
Authors: Culp D.J. , Latchney L.R. , Fallon M.A. , Denny P.A. , Denny P.C. , Couwenhoven R.I. , Chuang Sally
Published: September 2004

We previously demonstrated expression of full-length transcripts for sublingual mucin apoprotein, Muc19, of ∼24 kb (Fallon MA, Latchney LR, Hand AR, Johar A, Denny PA, Georgel PT, Denny PC, and Culp DJ. Physiol Genomics 14: 95–106, 2003). We now describe the complete sequence and genomic organization of the apomucin encoded by 43 exons. Southern analyses indicate a central exon of ∼18 kb containing 36 tandem repeats, each encoding 163 residues rich in serine and threonine. Full-length transcripts are an estimated 22,795 bp in length that span 106 kb of genomic DNA. The transcriptional start site is 24 bp downstream of a TATA box and 42 bp upstream of the conceptual translational start codon. The putative apoprotein has an estimated mass of 693.4 kDa and contains 7,524 amino acids (80% serine, threonine, glycine, alanine, and proline). We present a model for rat Muc19 transcripts and compare the conceptually translated Muc19 proteins for mouse, rat, pig, and the 3′ end of human Muc19. Conserved among these apoproteins are a signal peptide, a large tandem repeat region, von Willebrand factor type C and D domains, a trypsin inhibitor-like Cys-rich domain, and a COOH-terminal cystine knot-like domain. Southern blot analyses indicate transcripts for Muc19 and Smgc (submandibular gland protein C) are splice variants of a larger gene, Muc19/ Smgc. Comparative Northern analyses between the major salivary glands demonstrate highly selective Muc19 expression in neonatal and adult sublingual glands, whereas Smgc is expressed in neonatal submandibular and sublingual glands. Regulation of Muc19/ Smgc gene expression is discussed with respect to alternative splicing and mucous cell cytodifferentiation.
On the economic risk capital of portfolio insurance
Authors: Hürlimann Werner
Published: September 2004

A formula for the conditional value‐at‐risk of classical portfolio insurance is derived and shown to be constant for sufficiently small loss probabilities. As illustrations, we discuss portfolio insurance for an equity market index using empirical data, and analyze the more general multivariate situation of a portfolio of risky assets.
Determination of coupled sway, roll, and yaw motions of a floating body in regular waves
Authors: Das S. N. , Das S. K.
Published: September 2004

This paper investigates the motion response of a floating body in time domain under the influence of small amplitude regular waves. The governing equations of motion describing the balance of wave‐exciting force with the inertial, damping, and restoring forces are transformed into frequency domain by applying Laplace transform technique. Assuming the floating body is initially at rest and the waves act perpendicular to the vessel of lateral symmetry, hydrodynamic coefficients were obtained in terms of integrated sectional added‐mass, damping, and restoring coefficients, derived from Frank′s close‐fit curve. A numerical experiment on a vessel of 19190 ton displaced mass was carried out for three different wave frequencies, namely, 0.56 rad/s, 0.74 rad/s, and 1.24 rad/s. The damping parameters (ςi) reveal the system stability criteria, derived from the quartic analysis, corresponding to the undamped frequencies (βi). It is observed that the sway and yaw motions become maximum for frequency 0.56 rad/s, whereas roll motion is maximum for frequency 0.74 rad/s. All three motions show harmonic behavior and attain dynamic equilibrium for time t > 100 seconds. The mathematical approach presented here will be useful to determine seaworthiness characteristics of any vessel when wave amplitudes are small and also to validate complex numerical models.
Mirror symmetry and conformal flatness in general Relativity
Authors: Gravel P. , Gauthier C.
Published: September 2004

Using symmetry arguments only, we show that every spacetime with mirror‐symmetric spatial sections is necessarily conformally flat. The general form of the Ricci tensor of such spacetimes is also determined.
Some refinements and generalizations of Carleman′s inequality
Authors: Hwang Dah-Yan
Published: September 2004

We give some refinements and generalizations of Carleman′s inequality with weaker condition for weight coefficient.
From a Liberal Occupation to an Occupation of the Welfare State
Authors: Kjølsrød Lise , Thornquist Eline
Published: September 2004

This article demonstrates how Norwegian physiotherapy has developed as part of the state apparatus over the past decades. From the state's point of view, the methods and skills of physiotherapy are deemed valuable because they are designed to encourage people to take an active part in constructing and reconstructing their own health. From the physiotherapists' point of view, the state is an attractive ally in their seemingly endless struggle to escape from the shadow of medicine. The occupation was drawn into the public domain and given a wider mandate as part of a bio-political strategy. In return, it has experienced growth, gained nationwide representation, and obtained greater autonomy vis-à-vis the law. The case illustrates the larger issues of how modern welfare states expand and contribute to the regulation of complex societies.
Researching Race Relations
Authors: Lyon E. Stina
Published: September 2004

This paper explores the research methodology of Gunnar Myrdal's study of race relations in the United States, An American Dilemma: The Negro Problem and Modern Democracy (1944). It gives an overview of the methodological framework it presents for the study of racism and its consequences. The interpretative paradigm that underpinned this forcefully anti-racist synthesis of a large amount of empirical evidence is discussed, and three core elements of the normative theoretical framework are highlighted: the role of human rights values in theory and practice, the concept of `social environmentalism' and the principle of `cumulative causation'. Examples are then given of quantitative and qualitative evidence in support of the overall arguments about racism and its consequences. The paper concludes by noting that Myrdal's explicit value perspective, coupled with detailed empirical attention to the causal institutional effects of racism as a belief system, is a research tradition worthy of continued attention.
Trends in the Outsourcing of Domestic Work and Childcare in the Netherlands
Authors: de Ruijter Esther
Published: September 2004

Changes in the composition of households-especially the growing number of dual earners and singles-are often assumed to be associated with an increase in domestic outsourcing. In this article, trends in the outsourcing of household tasks (employing a domestic help and eating out) and the use of child daycare are analyzed with Dutch data (TBO 1980-2000, AVO 1983-1999). As it turns out, the observed increase over the past few decades in the outsourcing of household tasks can be explained by compositional changes. The supply of outsourcing services has not always grown accordingly. Trends in outsourcing are more than the total sum of individual demand factors. An example is the use of domestic help, which shows a net decrease. Our findings suggest that own domestic production has become more efficient, which has led to a reduction in the demand for outsourcing. The increase in the use of daycare for children can be explained as a general behavioral change, indicative of a shift in societal values concerning childcare. Parents are more inclined to hire childcare, irrespective of their personal characteristics. No systematic evidence was found for micro-level behavioral changes in outsourcing.
Understanding Shareholder Activism: Which Corporations are Targeted?
Authors: Rehbein Kathleen , Waddock Sandra , Graves Samuel B.
Published: September 2004

This study provides preliminary empirical evidence that shareholder activists target companies because of their size as well as specific stakeholder-related practices. The data show that shareholder activists target companies with shareholder resolutions demanding changes in corporate behaviors for companies producing problematic products and where environmental concerns exist. Furthermore, companies in specific industries are targeted based on poor employee and community-related practices. Activists, that is, are selective in their targeting of companies, choosing the most visible (largest) companies and those whose practices raise specific issues of interest to society.
Stakeholder Pressure, Organizational Size, and the Allocation of Departmental Responsibility for the Management of Corporate Charitable Giving
Authors: Brammer Stephen , Millington Andrew
Published: September 2004

Based on new survey evidence, this article analyzes the allocation of departmental responsibility for the management of corporate charitable giving within a sample of large U.K. companies. Several qualitatively different forms of management are identified, and a model of the determinants of the choice among these forms is estimated. The findings indicate that the allocation of internal responsibility for the management of corporate giving is significantly influenced by the extent and type of managerially perceived stakeholder pressures, organizational size, and industry characteristics. The evidence indicates that, given the firm is sufficiently large to delegate the management of its charitable contributions, the choice over the location of control is largely a function of the nature of the prevailing forms of stakeholder pressure experienced by the organization.
The Relationship between Perceptions of Corporate Citizenship and Organizational Commitment
Authors: Peterson Dane K.
Published: September 2004

The results of a survey of business professionals verified a relationship between perceptions of corporate citizenship and organizational commitment. More important, the results demonstrated that the relationship between corporate citizenship and organizational commitment was stronger among employees who believe highly in the importance of the social responsibility of businesses. The results also indicated that the ethical measure of corporate citizenship was a stronger predictor of organization commitment than the economic, legal, and discretionary measures. Last, the results revealed that the discretionary measure was more strongly associated with organizational commitment among female employees.
Varieties of Capitalism in an Internationalized World
Authors: Thatcher Mark
Published: September 2004

This article examines how internationalization affects domestic decisions about the reform of market institutions. A developing literature argues that nations maintain different “varieties of capitalism” in the face of economic globalization because of diverse domestic settings. However, in an internationalized world, powerful forces for change applying across border scan affect decision making within domestic arenas. The article therefore analyzes how three factors (transnational technological and economic developments, overseas reforms, and European regulation) affected institutional reform in a selected case study of telecommunications regulation in Britain, France, Germany, and Italy between the 1960s and 2002. The author argues that when different forms of internationalization are strong and combined, they can overwhelm institutional inertia and the effects of different national settings to result in rapid change and cross-national convergence in market institutions. Hence different varieties of capitalism may endure only when international pressures are low and/or for limited periods of time.
Democracy and Human Capital Formation
Authors: Brown David S. , Hunter Wendy
Published: September 2004

This article examines the relationship between democratic representation and spending on education in Latin America. The authors assess the impact that democracy has on the distribution of resources between different levels of schooling and on total spending on education. Specifically, they test whether democratic governments allocate a greater share of resources to primary education, the level that benefits the largest segment of the electorate and that is most critical for human capital formation in developing countries. Using time-series cross-sectional analysis, the authors find that democracies devote a higher percentage of their educational resources to primary education and that they maintain higher absolute spending levels on education in the aggregate, thereby enhancing the prospects of human capital formation.
The Democratic Peace and a Sequential, Reciprocal, Causal Arrow Hypothesis
Authors: Rasler Karen , Thompson William R.
Published: September 2004

One of the democratic peace puzzles is the question of whether and to what extent the democracy → peace relationship underestimates the possibility that peace precedes democracy: the reversed causal arrow hypothesis. From a war making–state making perspective, democratization needs to be viewed as a partial function of external threat and domestic power concentration. All three variables are found to be interrelated as predicted and related in turn to the external conflict behavior of major powers from 1816 to 1992. These monadic findings, however, do not appear to negate the dyadic relationship between democratization and selectively reduced conflict behavior. In sum, there is substantial support for the reversed causal arrow hypothesis, but it does not render the regime type → conflict behavior relationships spurious. Rather, it enriches the understanding of the context in which democratization has emerged to have some effect on international politics.
Explaining Voter Turnout in Latin America, 1980 to 2000
Authors: Fornos Carolina A. , Power Timothy J. , Garand James C.
Published: September 2004

Previous cross-national research on voter turnout has focused attention primarily on Western industrial democracies, with relatively little attention paid to turnout in developing countries. In this article, the authors extend the research program on comparative voter turnout to presidential and legislative elections held in Latin American countries from 1980 to 2000. Building on previous research, the authors estimate a series of models that represent the effects of institutional, socioeconomic, and political variables in shaping turnout. The findings suggest that turnout in Latin American countries is influenced primarily by institutional variables (such as unicameralism, compulsoryvoting, and concurrent legislative and executive elections) and political variables (i.e., founding elections and political freedoms). Surprisingly, the authors find that socioeconomic variables, which are found to have strong effects on turnout in Western democracies, are unrelated to turnout in Latin American countries.
Democratization, State Formation, and Civil War in Finland and Ireland
Authors: Kissane Bill
Published: September 2004

In both Finland and Ireland, democracy was the product of long-term processes of development, and the question is why the presence of democratic norms and institutions did not prevent their civil wars. Arguably both systems were destabilized by the delay between the first democratic elections and the achievement of legislative independence, when crises over who should inherit the empires’ legislative power became interlinked with the absence of coercive institutions.
The Baltic Sea Subregion after Dual Enlargement
Authors: Hubel Helmut
Published: September 2004

It is argued in this article that the enlargement processes of the two major institutions of the West significantly affect the ‘externalities’ of the Baltic Sea area, and that this area should therefore be understood as a European subregion rather than as a distinct region. Whereas the extent of institutional adaptations of the European Union and NATO since the end of the East-West conflict is impressive, both enlargements are also creating new problems. In the case of the EU, its homogeneity and the functioning of its institutions promise to be stretched to their very limits, particularly given the tendencies towards ‘opting out’ of the aquis in several EU member states of the Baltic Sea area. Concerning NATO, the author recognizes the irony that the new members hoped to join the ‘old alliance’, while in reality this has already undergone transformation from a defence body to an institution dealing primarily with out-of-area problems. For both the enlarged EU and NATO the ‘partnership’ with Russia is more a modus vivendi than a clear perspective for the future and there is a need for further adapations on both sides.
Russia in the Baltic Sea Region
Authors: Morozov Viatcheslav
Published: September 2004

Relations between Russia and the Baltic States — the weakest link in the Baltic Rim — have significantly improved since 2000. One of the explanations for this improvement is the fact that in contemporary Russian political discourse national identity is desecuritized. The role of the Baltic states has radically changed: they are no longer considered as an embodiment of the ‘false’, anti-Russian Europe. However, despite the desecuritization of national identity, security as the model of structuring and governing the ‘external’ world still dominates political discourse. The preponderance of the war against terrorism as discursive articulation, as well as the modernist nature of President Putin’s political project, leads to the marginalization of the Baltic Sea area on the political agenda. Some new departures in Russia’s policy as regards the Baltic Sea area are possible, however, once Russia has gone through its election campaign, and the enlargements of NATO and the EU are complete.
Of Struggles and Whistles: Mamelodi’s Black Youth Culture
Authors: Zegeye Abebe
Published: September 2004

Youth of African descent in South Africa who have greater cultural exposure develop a healthier self-image and greater capacity for civic participation than those with less cultural exposure. Research among black youth in Mamelodi shows the need for more investigation in the following fields: comparing youthful and adult black responses; class-differentiated black responses; gender-related black responses; pre-and post-apartheid black responses and relevant black and white youthful responses; the effects of poverty on the development of South African youth identities; government expenditure on social reconstruction and global financial demands; cultural deprivation among the youth of South Africa; the meaning of education to the youth in South Africa; the failure of education among the youth of South Africa, including continuing inequality in education; youthful perceptions of job prospects; the internal dynamics of youth optimism regarding the future; the degree and dynamics of the political awareness of the youth and youth’s role in building a more cohesive nation in South Africa.
Living in ‘Jan Bom’: Making and Imagining Lives after Apartheid in a Council Housing Scheme in Johannesburg
Authors: Du Plessis Irma
Published: September 2004

Since the end of formal apartheid, former council housing schemes for racially designated groups are being remodelled and reconfigured. These communities, still home to the poor, are burdened by their past and challenged by their present circumstances. This article attempts to locate discourses on transition and identity in the context of Jan Hofmeyr, a former ‘poor white’ council housing scheme in Johannesburg. Drawing on the methods of life histories, documentary review and semi-structured in-depth interviews, it asks how, against the background of the formal end to apartheid and the liberalization of the South African economy, and inserted into the changing landscape of the post-colonial city, do residents make and understand their lives in material and symbolic ways. The article approaches notions of identity within the frame of discourse, practice and performance.
The Mute Always Speak: On Women’s Silences at the Truth and Reconciliation Commission
Authors: Motsemme Nthabiseng
Published: September 2004

In expanding our conceptual tools to understand the workings of silences we reveal the invisible but agentic work of the imagination to reconfigure our social worlds. When we reject dominant western oppositional hierarchies of silence and speech, and instead adopt frameworks where words, silence, dreams, gestures, tears all exist interdependently and within the same interpretive field, we find that the muted are always speaking. The article interrogates these ideas by discussing the institutional and symbolic features of the Truth and Reconciliation Commission, within which women’s recollections were framed. It identifies the limits of verbal language and proposes that we reinterpret silence as language by outlining why and how. The article locates ways of reading these silences present in TRC testi-monies through a discussion of the following themes: silence as resistance and courage; silence as illusion of stability; and silence as a site for coping and the reconstitution of self.
Crystallization Behavior of Polyamide-6 Microcellular Nanocomposites
Authors: Yuan Mingjun , Turng Lih-Sheng , Gong Shaoqin , Winardi Andreas , Caulfield Daniel
Published: September 2004

The crystallization behaviors of polyamide-6 (PA-6) and its nanocomposites undergoing the microcellular injection molding process are studied using Transmission Electron Microscopy (TEM), X-ray Diffractometer (XRD), Polarized Optical Microscopy (POM), and Differential Scanning Calorimetry (DSC). The relationships among the morphology, the mechanical property of the molded parts, and the crystallization behavior are investigated. With the addition of nanoclays in microcellular injection molded parts, the growth of the γ-form crystal is suppressed and the formation of γ-form crystals is promoted. Both nanoclay and dissolved gas have a big influence on PA-6 crystalline structures. The existence of nanoclay increases the initial crystallization rate. But with extra addition of nanoclays in the polymer matrix, the increase of crystallization rate is reduced. Microcellular injection molded nanocomposites with proper amount of nanoclays possess the maximum crystallization activation energy and produce a finer and denser microcell structure which leads to better mechanical properties.
Torsion Properties of Cylindrical Polymer Foams
Authors: Rodrigue Denis , Pelletier Yan , Gosselin Ryan
Published: September 2004

Solid-state viscoelastic shear moduli (G0 and G00) of cylindrical polymer foams are measured as a function of frequency. Extruded samples are produced via a cylindrical die to obtain foams of various morphologies. To perform the shear measurements, a modification of the torsion rectangular setup on an ARES rheometer is made. The setup, calibration, and test conditions are presented. The data are discussed and compared to simple models taken from the literature.
Porous Polystyrene Foam Produced at Supercritical Conditions
Authors: Wong Chang-Ming , Liang Wen-Chung , Ying Chih-Hung , Hung Ming-Lang
Published: September 2004

This work examines four polystyrene (PS) resins and PS resins with fillers. The materials are processed into sheets and then the sheets are foamed at various supercritical conditions. The morphology of the foam is studied and a large porous PS foam is also developed for a vacuum insulation panel.
Pharmacokinetics of Frovatriptan in Adolescent Migraineurs
Authors: Elkind Arthur H. , Wade Andrew , Ishkanian Gary
Published: September 2004

Frovatriptan is a selective 5‐HT1B/1D receptor agonist available for acute treatment of migraine in adults (18 years and older). The objective of this study was to determine key pharmacokinetic parameters of frovatriptan in adolescent migraineurs after a single 2.5‐mg oral dose and to compare these results with those from an earlier study completed in adults. Subjects were stratified by age (12–14 and 15–17 years) and gender, and serial blood and urine samples were collected over 48 hours. A total of 25 subjects (13 male, 12 female) completed the study. Pharmacokinetic profiles for adolescent subjects were similar to those observed in adults. The median tmax ranged from 2 (male subjects) to 3 (female subjects) hours. The AUC0–24h and Cmax were slightly lower in adolescent subjects as compared with adults. As seen in adults, AUC0–24h and Cmax values were approximately 2‐fold higher in females than in their male counterparts (AUC mean range 40.5–59.8 ng•h/mL vs 21.2–23.5 ng•h/mL and Cmax mean range 4.02–6.14 vs ng•h/mL 2.52–2.99 ng/mL, in female and male adolescent subjects, respectively). Elimination was biphasic, with an approximate terminal elimination half‐life (t1/2) between 12.2 and 25.5 hours. Renal clearance was similar in adolescents and adults, being somewhat higher in female than male subjects. Frovatriptan was well tolerated with no serious or treatment‐related adverse effects. In addition, there were no clinically significant changes in safety parameters. Overall, the pharmacokinetic profile of frovatriptan in adolescents (12–17 years) is similar to that seen in adults, and dosing adjustments are unlikely to be needed.
The Effects of Modifying In Vivo Cytochrome P450 3A (CYP3A) Activity on Etoricoxib Pharmacokinetics and of Etoricoxib Administration on CYP3A Activity
Authors: Agrawal Nancy G. B. , Matthews Catherine Z. , Mazenko Ralph S. , Woolf Eric J. , Porras Arturo G. , Chen Xun , Miller Jutta L. , Michiels Nicole , Wehling Martin , Schultz Armin , Gottlieb Alice B. , Kraft Walter K. , Greenberg Howard E. , Waldman Scott A. , Curtis Sean P. , Gottesdiener Keith M.
Published: September 2004

To investigate the influence of modifying in vivo cytochrome P450 3A (CYP3A) activity on the pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase‐2, and of etoricoxib administration on CYP3A activity, a 3‐part, randomized, crossover study was conducted in 3 panels of healthy volunteers. In part I, 8 subjects were administered a single dose of 60 mg etoricoxib alone and following daily doses of 400 mg ketoconazole, a known strong inhibitor of CYP3A. In part II, 8 different subjects were administered a single dose of 60 mg etoricoxib alone and following daily doses of 600 mg rifampin, a known strong inducer of CYP3A. In parts I and II, plasma samples were collected following each etoricoxib dose and analyzed for etoricoxib. In part III, 8 different subjects were administered 120 mg etoricoxib or placebo once daily for 11 days, and the erythromycin breath test was administered on day 11 of each period. Coadministration of etoricoxib with daily doses of ketoconazole resulted in an average 43% increase in etoricoxib AUC; based on previous studies, this increase would not be expected to have any clinically meaningful effect. In contrast, coadministration of etoricoxib with daily doses of rifampin had a potentially clinically important effect on etoricoxib pharmacokinetics (average 65% decrease in etoricoxib AUC). Etoricoxib had no effect on hepatic CYP3A activity, as assessed by the erythromycin breath test.
Pharmacodynamics and Pharmacokinetics of Oral Levosimendan and Its Metabolites in Patients With Severe Congestive Heart Failure: A Dosing Interval Study
Authors: Põder Pentti , Eha Jaan , Sundberg Stig , Antila Saila , Heinpalu Marika , Loogna Imbrit , Planken Ülle , Rantanen Satu , Lehtonen Lasse
Published: September 2004

The objective of this study was to explore the pharmacodynamics and pharmacokinetics of oral levosimendan in patients with severe congestive heart failure. This was a randomized, parallel‐group, double‐blind, placebo‐controlled trial. Oral levosimendan 2 to 8 mg daily or placebo was administered to 25 patients with New York Heart Association class III–IV congestive heart failure for 4 weeks. Pharmacodynamic variables consisted of heart rate‐corrected electromechanical systole, heart rate, and systolic and diastolic blood pressure. The pharmacokinetics of levosimendan and its metabolites, OR‐1855 and OR‐1896, was assessed. The 4‐ to 8‐mg daily doses of oral levosimendan showed moderate inotropic effects. Blood pressure remained unchanged with all doses. A moderate increase in heart rate was observed except with the 2‐mg dose. Pharmacokinetic parameters of the metabolites increased linearly with the dose (P .002 for Cmax and AUC0–8h for both treatment groups). It was concluded that oral levosimendan has inotropic and chronotropic effects in patients with severe congestive heart failure. Plasma concentrations of its metabolites increase dose dependently.
Dermal Absorption of Camphor, Menthol, and Methyl Salicylate in Humans
Authors: Martin Debra , Valdez Jennifer , Boren James , Mayersohn Michael
Published: September 2004

Camphor, menthol, and methyl salicylate occur in numerous over‐the‐counter products. Although extensively used, there have been no estimates of human exposure following administration via dermal application. Furthermore, there is little information about the pharmacokinetics of those compounds. The authors report the plasma concentrations of the intact compounds as a function of dose following dermal patch application. Three groups of 8 subjects (4 male, 4 female) applied a different number of commercial patches (2, 4, or 8) to the skin for 8 hours. Plasma samples were assayed using sensitive and selective gas‐chromatographic methods. For the 8‐patch group, the average maximum plasma concentrations (Cmax ± SD) were 41.0 ± 5.8 ng/mL, 31.9 ± 8.8 ng/mL, and 29.5 ± 10.5 ng/mL for camphor, menthol, and methyl salicylate, respectively. The corresponding values for the 4‐patch group were 26.8 ± 7.2 ng/mL, 19.0 ± 5.4 ng/mL, and 16.8 ± 6.8 ng/mL. The harmonic mean terminal half‐lives were 5.6 ± 1.3 hours, 4.7 ± 1.6 hours, and 3.0 ± 1.2 hours for camphor, menthol, and methyl salicylate, respectively. The 2‐patch group had measurable but low plasma concentrations of each compound. Low‐dose dermal application for an extended time results in low plasma concentrations of all 3 compounds. Four and 8 patches, when applied for 8 hours, gave measurable and nearly proportional plasma concentrations. Although unable to determine the absolute dermal bioavailability of these compounds, there appears to be relatively low systemic exposure to these potentially toxic compounds, even when an unrealistically large number of patches are applied for an unusually long time.
Could the WHO Model List of Essential Medicines Do More for the Safe and Appropriate Use of Injections?
Authors: Logez Sophie M. D. , Hutin Yvan J. F. , Holloway Kathleen , Gray Robin , Hogerzeil Hans V.
Published: September 2004

A national drug policy addressing the safe and appropriate use of injections is an important element to prevent overuse and unsafe use of injections. Because the World Health Organization World Health Organization Model List of Essential Medicines is a keystone of national drug policies, the authors examined the way it addresses injection practices. They reviewed the 11th World Health Organization Model List of Essential Medicines to collect information on (1) injectable medicines, (2) diluents, and (3) the recommendations regarding the procurement of injection devices. Of 306 active ingredients on the list, 135 (44%) are mentioned in injectable form. Of these, 41 (30%) need diluents for reconstitution. The list does not mention the need to procure appropriate diluents, injection devices, and safety boxes in quantities that match the quantities of injectable medicines. In addition, the list provides limited information that can be used to forecast the needs of injection devices to administer the injectable medicines that are included in the list. Future revisions of the World Health Organization Model List of Essential Medicines should attempt to reduce the number of injectable formulations on the basis of evidence. In addition, the list should specify that when injectable medicines are being supplied, diluents, single‐use syringes, and safety boxes should be supplied. The volume of syringes needed for administration should be specified for each injectable medication on the list to facilitate the forecasting of the needs of injection devices.
Stability of Modus Operandi in Sexual Offending
Authors: Sjöstedt Gabrielle , Långström Niklas , Sturidsson Knut , Grann Martin
Published: September 2004

Little is known about the stability of modus operandi (MO) in sexual offending. The authors studied a cohort of all sexual offenders released from prison into the Swedish community during the years from 1993 to 1997 ( N = 1,303) and analyzed sexual reoffenders’ MO in terms of victim choice, offense nature, and severity, comparing prior offenses with those registered during an average 6-year follow-up. Stability in MO, explored with Cohen’s Kappa and Odds Ratios (ORs) as measures of agreement across registered sexual offenses, was high, specifically with respect to victim choice. Results are discussed in relation to sexual deviance and opportunity structure. The authors argue that assessment and management of sexual recidivism risk might benefit from information on offense MO. Furthermore, the results could inform police investigative strategies, such as linking multiple offenses committed by an unidentified offender.
Exploring Prison Adjustment among Female Inmates
Authors: Warren Janet I. , Hurt Susan , Loper Ann Booker , Chauhan Preeti
Published: September 2004

This article explores the factor structure and concurrent validity of the Prison Adjustment Questionnaire with a cohort of 777 maximum-security female inmates. Results suggest a two-factor solution of a Distress factor and a Conflict factor, both of which demonstrate good concurrent validity using the Brief Symptom Inventory (BSI) Global Severity Score, institutional misconduct, security level, and self-report violence. Regression analyses indicate scores on the Distress factor were predicted by the BSI Anxiety Scale, having children, not being of minority status, and prior incarceration. Scores on the Conflict factor were predicted by BSI Hostility, BSI Phobic Anxiety, presence of a personality disorder, being married, being the victim of threats and physical assaults, time served, and being incarcerated for a violent crime.
The Assessment of Social Functioning in Individuals with Mental Retardation
Authors: Bielecki Joanne , Swender Stephen L.
Published: September 2004

Social skills deficits and excesses are a defining aspect of mental retardation (MR). Research indicates that there is an established relationship between social skills and maladaptive behaviors. A number of studies demonstrate that the social competence of individuals with MR and comorbid psychopathology can be enhanced with social skills training. However, to design an effective training package, an accurate assessment of adaptive and social functioning must first be conducted. Unique problems arise when assessing social skills in individuals with severe and profound MR(i.e., individuals often have limited verbal repertoires). Thus, a clinician must often rely on observable behavior and caregiver report rather than self-report. The three most common methods for assessing social skills are behavioral observations, role-playing, and checklists. These assessment strategies will be discussed, as well as suggestions for future research.
Preference Assessment Procedures for Individuals with Developmental Disabilities
Authors: Hagopian Louis P. , Long Ethan S. , Rush Karena S.
Published: September 2004

Significant advancements have been made in the development of procedures to systematically identify preferred stimuli that may function as reinforcers for persons with developmental disabilities. Indirect assessment procedures include care provider and client interviews, whereas direct assessment procedures involve systematically exposing participants to stimuli while recording their responses. These types of direct assessment procedures can be categorized as either approach-based or engagement-based. Approach-based procedures involve recording the individuals’ approach responses to stimuli presented singly or concurrently with other stimuli, whereas engagement-based procedures involve recording duration of engagement with stimuli. Although the predictive validity of indirect preference assessment procedures has yet to be established, using them in combination with direct measures of preferencemaybe most efficacious for identifying potential reinforcers. Recent research on preference assessment procedures used with persons with developmental disabilities is reviewed and the variables that one might consider prior to selecting which procedure to use in a given situation are discussed.
Assessment of Seizures and Related Symptomatology in Persons with Mental Retardation
Authors: Mayville Erik A. , Matson Johnny L.
Published: September 2004

Seizures can be debilitating across a number of physical, social, occupational, and personal variables. Given the deficits in all of these areas frequently present in persons with mental retardation, effective assessment and subsequent treatment of seizures is a primary goal for individuals with both mental retardation and epilepsy. To thoroughly address the behavioral domains related to seizures in persons with mental retardation and epilepsy, areas of assessment should include seizure behavior, triggering stimuli, reinforcing consequences, and antiepileptic medication side effects. Assessment of these areas in this population often deviates from methods typically used with persons of normal intelligence. Specifically, direct behavioral observation and third-party report with structured interviews are the most viable and accessible means of assessment, and efforts to establish reliable and valid protocols have been successful in some areas. This article reviews this assessment methodology and discusses the extant issues in establishing and proliferating such approaches.
Optimizing Balanced Incomplete Block Designs for Educational Assessments
Authors: van der Linden Wim J. , Veldkamp Bernard P. , Carlson James E.
Published: September 2004

A popular design in large-scale educational assessments as well as any other type of survey is the balanced incomplete block design. The design is based on an item pool split into a set of blocks of items that are assigned to sets of “assessment booklets.” This article shows how the problem of calculating an optimal balanced incomplete block design can be formulated as a problem in combinatorial optimization. Several examples of structural and practical requirements for balanced incomplete block designs are shown to be linear constraints on the optimization problem. In addition, a variety of possible objective functions to optimize the design is discussed. The technique is demonstrated using the 1996 Grade 8 Mathematics National Assessment of Educational Progress (NAEP) as a case study.
Mokken Scale Analysis Using Hierarchical Clustering Procedures
Authors: van Abswoude Alexandra A. H. , Vermunt Jeroen K. , Hemker Bas T. , van der Ark L. Andries
Published: September 2004

Mokken scale analysis (MSA) can be used to assess and build unidimensional scales from an item pool that is sensitive to multiple dimensions. These scales satisfy a set of scaling conditions, one of which follows from the model of monotone homogeneity. An important drawback of the MSA program is that the sequential item selection and scale construction procedure may not find the dominant underlying dimensionality of the responses to a set of items. The authors investigated alternative hierarchical item selection procedures and compared the performance of four hierarchical methods and the sequential clustering method in the MSA context. The results showed that hierarchical clustering methods can improve the search process of the dominant dimensionality of a data matrix. In particular, the complete linkage and scale linkage methods were promising in finding the dimensionality of the item response data from a set of items.
Implementation and Measurement Efficiency of Multidimensional Computerized Adaptive Testing
Authors: Wang Wen-Chung , Chen Po-Hsi
Published: September 2004

Multidimensional adaptive testing (MAT) procedures are proposed for the measurement of several latent traits by a single examination. Bayesian latent trait estimation and adaptive item selection are derived. Simulations were conducted to compare the measurement efficiency of MAT with those of unidimensional adaptive testing and random administration. The results showed that the higher the correlation between latent traits, the more latent traits there were, and the more scoring levels there were in the items, the more efficient MAT was than the other two procedures. For tests containing multidimensional items, only MAT is applicable, whereas unidimensional adaptive testing is not. Issues in implementing MAT are discussed.
Using Set Covering with Item Sampling to Analyze the Infeasibility of Linear Programming Test Assembly Models
Authors: Huitzing Hiddo A.
Published: September 2004

This article shows how set covering with item sampling (SCIS) methods can be used in the analysis and preanalysis of linear programming models for test assembly (LPTA). LPTA models can construct tests, fulfilling a set of constraints set by the test assembler. Sometimes, no solution to the LPTA model exists. The model is then said to be infeasible. Causes of infeasibility can be difficult to find. A method is proposed that constitutes a helpful tool for test assemblers to detect infeasibility before hand and, in the case of infeasibility, give insight into its causes. This method is based on SCIS. Although SCIS can help to detect feasibility or infeasibility, its power lies in pinpointing causes of infeasibility such as irreducible infeasible sets of constraints. Methods to resolve infeasibility are also given, minimizing the model deviations. A simulation study is presented, offering a guide to test assemblers to analyze and solve infeasibility.