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Showing papers by "York University published in 1995"


Journal ArticleDOI
Joseph E. LeDoux1
TL;DR: The Neural Basis of Fear, Volitional Control of Emotion, and Psychopathological Issues are reviewed.
Abstract: CONTENTS INTRODUCTION ......... ........ .... .... .... .... 209 NEURAL BASIS OF EMOTION ..... . . .. ... . . ..... . . . . . .. . . . . . . .. . . . . . . . . . ... . . . . . . .. . . . . . . 210 Neural Basis of Fear ........ 210 Neural Pathways Mediating Fear Conditioning .... 211 Cellular Mechanisms Involved in Fear Conditioning , 216 Extinction of Conditioned Fear 219 Conditioned Fear and Instrumental Action (Coping) 220 Fear Conditioning; Conclusions . . . ... 221 Relation of the Neural Basis of Fear to Other Emotions . . 222 IMPLICATIONS OF THE NEURAL BASIS OF FEAR FOR UNDERSTANDING EMOTION 223 Cognitive-Emotional Interactions . . . . . 223 Conscious versus Unconscious Processes in Emotion ........ ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... 227 Volitional Control of Emotion ..... .... .... .... .... .... .... .... .... 227 Psychopathological Issues . . . . ... . . . . . . .... . . . . . . ... . . . . . . . .... . . . . . . .... .... .... .... 228 CONCLUSIONS .... . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... .... .... 230

1,664 citations


Journal ArticleDOI
TL;DR: In this paper, the authors examine the use of what they call internal territorialization in establishing control over natural resources and the people who use them and examine the emergence of territoriality in state power in Thailand.
Abstract: Weber and many other theorists have defined the state as a political organization that claims and upholds a monopoly on the legitimate use of physical force in a given territory.1 Writers who draw on this Weberian approach have devoted considerable theoretical attention to political organization, legitimacy, and physical coercion in the making of modern states. Until recently, however, the meaning of territory as a key practical aspect of state control has been relatively neglected by many theorists of the sources of state power. Territorial sovereignty defines people's political identities as citizens and forms the basis on which states claim authority over people and the resources within those boundaries.2 More important for our purposes here, modern states have increasingly turned to territorial strategies to control what people can do inside national boundaries. In this article, we aim to outline the emergence of territoriality in state power in Thailand, formerly called Siam. In particular, we examine the use of what we call internal territorialization in establishing control over natural resources and the people who use them.

707 citations


Journal ArticleDOI
TL;DR: Both dorsal and ventral regions of mPFC are involved in the fear system, but each modulates different aspects of fear responsivity.
Abstract: The emotional reactivity of rats with lesions of the dorsal portion of medial prefrontal cortex (mPFC) was examined using a classical fear conditioning paradigm. Conditioned fear behavior (freezing responses) was measured during both the acquisition and extinction phases of the task. Lesions enhanced fear reactivity to both the conditioned stimlulus (CS) and contextual stimuli during both phases, suggesting that dorsal mPFC lesions produce a general increase in fear reactivity in response to fear conditioning. M. A. Morgan, L. M. Romanski, and J. E. LeDoux (1993) found that lesions just ventral to the present lesions had no effect during acquisition of the same task and prolonged the fear response to the CS (but not the context) during extinction. Thus, both dorsal and ventral regions of mPFC are involved in the fear system, but each modulates different aspects of fear responsivity.

705 citations


Journal ArticleDOI
TL;DR: The authors explored the relationship between perceived efficacy, depth of processing, and message framing for various health-related issues, such as sexually transmitted disease, and found that perceived efficacy was correlated with the depth and breadth of message framing.
Abstract: The authors explore the relationship between perceived efficacy, depth of processing, and message framing. They conduct two experiments on varying health-related issues: sexually transmitted diseas...

512 citations


Journal ArticleDOI
TL;DR: In this article, a critical study of learning to teach is presented, focusing on the relation between the discourses that render ethnography intelligible and the ethnographic report, and the role of poststructural theories in the production of ethnographic narratives.
Abstract: This article engages current poststructural debates over ethnographic representation. It questions three types of ethnographic authority: the authority of empiricism, the authority of language, and the authority of reading. In performing a form of self‐speculative critique, the author moves behind the scenes of her own ethnography, Practice Makes Practice: A Critical Study of Learning to Teach, to consider the problem of what poststructural theories “do” to ethnographic writing. Two related themes are elaborated in relation to how poststructural debates fashioned interpretive efforts: conceptual issues in the poststructural study of teaching and theoretical issues in the production of ethnographic narratives. Can there be an educational ethnography that exceeds the constraints of humanism? What if the ethnographer began not just to question the discourse of others but to engage the relation between the discourses that render ethnography intelligible and the ethnographic report?

409 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigated the existence and automaticity of a mental association between the concepts of power and sex, and its consequences for sexual harassment tendencies using a subliminal priming paradigm.
Abstract: One characteristic of men who sexually harass is that they are not aware that their actions are inappropriate or a misuse of their power (L. F. Fitzgerald, 1993a). We investigated the existence and automaticity of a mental association between the concepts of power and sex, and its consequences for sexual harassment tendencies. Using a subliminal priming paradigm, Experiment 1 demonstrated an automatic link between power and sex, and only for men high in the likelihood to sexually harass or aggress. In Experiment 2, male participants were unobtrusively primed with either power-related or neutral stimuli. For men likely to sexually aggress, but not other participants, attraction ratings of a female confederate were significantly higher in the power priming than the neutral priming condition.

401 citations


Journal ArticleDOI
TL;DR: In this article, it is argued that the development trajectory of Japan will be replicated in a succession of sectors and countries, but this approach fails to capture the complexities of the contemporary regionalization of industrial production.
Abstract: Product cycle theory as expressed in the analogy of flying geese has become a widely accepted way of conceptualizing industrial diffusion across East Asia. As the product cycle is repeated for increasingly sophisticated products, so, it is argued, the development trajectory of Japan will be replicated in a succession of sectors and countries. This approach fails, however, to capture the complexities of the contemporary regionalization of industrial production. East Asian industrial production should not be seen as a tightly coupled process in which the rise of national economies parallels successive product cycles. Rather than Japan's development trajectory being replicated in country after country, industrial diffusion has been characterized by shifting hierarchical networks of production and partial diffusion into diverse politicoeconomic contexts at differing historical junctures. It has also resulted in a triangulation of the region's trade patterns that has generated large imbalances in trade both within the region and between the region and the United States.

374 citations


Journal ArticleDOI
TL;DR: A review of the state and direction of biosphere-atmosphere model development and an assessment of the data needs of the models can be found in this article, where a prioritized list of data sets required to meet this need is discussed.

318 citations


Journal ArticleDOI
TL;DR: In this paper, the authors used video cameras and remote microphones to observe peer interactions of aggressive and nonaggressive children on the school playground and found that the effectiveness of this methodology is illustrated with results from their studies of children on school playgrounds.
Abstract: This article describes a methodology that is uniquely suited to study peer interactions, particularly those of aggressive children. To date, researchers have used laboratory and naturalistic observations to investigate children's aggressive interactions. To overcome difficulties such as the constraints of laboratory situations and reactivity to proximal observations, video cameras and wireless microphones were used in a study of the peer relations of aggressive and nonaggressive children. Details about the equipment and procedures are provided, along with logistical and ethical considerations. Remote audiovisual observations provide a unique opportunity to observe children's interactions that generally occur beyond adults' view. The primary strength of this observational methodology is its external validity. Children being observed are completely mobile on the school playground and are able to choose the activities and partners for their play. The effectiveness of this methodology is illustrated with results from our studies of children on school playgrounds. Researchers have identified peer relations as an important mechanism in the development of adaptive and maladaptive behaviors (e.g., Hartup, 1983; Parker & Asher, 1987). In the case of aggressive children, peer interactions are presumed to exacerbate behavior problems and propel these children along the trajectory to an antisocial lifestyle (Cairns, Cairns, Neckerman, Gest, & Gariepy, 1988; Patterson, DeBaryshe, & Ramsey, 1989). The study of aggressive children's peer relations has taken many forms: self-reports, peer reports, and adult reports; laboratory paradigms; and naturalistic observations. At present, there are gaps and inconsistencies in our understanding of the peer relations of aggressive children because of methodological issues such as the lack of agreement between raters (Loeber, Green, Lahey, & Stouthamer-Loeber, 1989), the constraints of laboratory situations, and the difficulty of naturalistic observations with school-age children (Asher & Hymel, 1981). To overcome some of these methodological difficulties, we used video cameras and remote microphones to observe peer interactions of aggressive and nonaggressive children on the school playground. In this article, we discuss observational methodologies commonly used in the study of children's aggressive behavior, review the strengths and weaknesses of each methodology, describe our alternative observational strategy, and illustrate its effectiveness in addressing the challenge of naturalistic observations of aggressive children on the school playground. Even

299 citations





Journal ArticleDOI
TL;DR: It is concluded that there seems to be, in fact, real psychological effects associated with the golden section, but that they are relatively sensitive to careless methodological practices.
Abstract: Since at least the time of the Ancient Greeks, scholars have argued about whether the golden section-a number approximately equal to 0618-holds the key to the secret of beauty Empirical investigations of the aesthetic properties of the golden section date back to the very origins of scientific psychology itself, the first duties being conducted by Fechner in the 1860s In this paper historical and contemporary issues are reviewed with regard to the alleged aesthetic properties of the golden section In the introductory section the most important mathematical occurrences of the golden section are described As well, brief reference is made to research on natural occurrences of the golden section, and to ancient and medieval knowledge and application of the golden section, primarily in art and architecture Two major sections then discuss and critically examine empirical studies of the putative aesthetic properties of the golden section dating from the mid-19th century up to the 1950s, and the empirical work of the last three decades, respectively It is concluded that there seems to be, in fact, real psychological effects associated with the golden section, but that they are relatively sensitive to careless methodological practices

Journal ArticleDOI
TL;DR: The authors compared the cognitive processing of 12 anglophone second-year French undergraduate students who were prompted to write an argumentative text in both L1 (English) and L2 (French).
Abstract: This study compared the cognitive processing of 12 anglophone second-year French undergraduate students who were prompted to write an argumentative text in both L1 (English) and L2 (French). The students' speaking aloud protocols and textual drafts provided the basis of collected data. In the first part of the study, the writers' planning, evaluation, and revision strategies were (a) analyzed in terms of the pragmatic., textual, and linguistic manifestations of these processes and (b) compared for differences in processing behaviors between their L1 and L2 writing. In the second part, we measured linguistic processing occurrences to analyze their effect on more global processing behaviors at the pragmatic and textual levels. The linguistic constraints imposed by the writers' knowledge of the second language (French) point toward some significant differences in discourse level processing between L1 and L2 writing behaviors. However, the results reveal that the state of the writers' strategic knowledge and capacity for meaningful multiple-level discourse processing explains the constraining effects of linguistic processing on L2 written discourse production.

Journal ArticleDOI
TL;DR: In this article, the authors report the results of an ex post study of the effects of leveraged buyouts (LBOs) upon the goals, strategy, structure, and performance of firms.
Abstract: This article reports the results of an ex post study of the effects of leveraged buyouts (LBOs) upon the goals, strategy, structure, and performance of firms. Our study was designed to test argumen...

Journal ArticleDOI
TL;DR: Using a combined idiographic and nomothetic experimental paradigm, two studies examined the role of chronic accessibility of significant-other representations in transference and found that greater false-positive memory in the significant- other condition, relative to control, even in the absence of priming.
Abstract: Research has shown that the activation and application of a significant-other representation to a new person, or transference, occurs in everyday social perception (S. M. Andersen & A. Baum, 1994; S. M. Andersen & S. W. Cole, 1990). Using a combined idiographic and nomothetic experimental paradigm, two studies examined the role of chronic accessibility of significant-other representations in transference. After learning about 4 fictional people, 1 of whom resembled a significant other, participants' recognition memory was assessed. Both studies showed greater false-positive memory in the significant-other condition, relative to control, even in the absence of priming. Study 2 showed that although the effect was greater when the significant-other representation was concretely applicable to the target information, it occurred even when no such applicability was present. Results implicate the chronic accessibility of significant-other representations in transference.

Book ChapterDOI
01 Mar 1995
TL;DR: In particular, there has been a tendency to perpetuate the rigid conceptual separation of the 'economic' and 'political' which has served capitalist ideology so well ever since the classical economists discovered the 'economy' in the abstract and began emptying capitalism of its social and political content as discussed by the authors.
Abstract: The original intention of historical materialism was to provide a theoretical foundation for interpreting the world in order to change it. This was not an empty slogan. It had a very precise meaning. It meant that Marxism sought a particular kind of knowledge, uniquely capable of illuminating the principles of historical movement and, at least implicitly, the points at which political action could most effectively intervene. This is not to say that the object of Marxist theory was to discover a ‘scientific’ programme or technique of political action. Instead, the purpose was to provide a mode of analysis especially well equipped to explore the terrain on which political action must take place. Marxism since Marx has often lost sight of his theoretical project and its quintessentially political character. In particular, there has been a tendency to perpetuate the rigid conceptual separation of the ‘economic’ and the ‘political’ which has served capitalist ideology so well ever since the classical economists discovered the ‘economy’ in the abstract and began emptying capitalism of its social and political content. These conceptual devices do reflect, if only in a distorting mirror, a historical reality specific to capitalism, a real differentiation of the ‘economy’; and it may be possible to reformulate them so that they illuminate more than they obscure, by reexamining the historical conditions that made such conceptions possible and plausible. The purpose of this reexamination would not be to explain away the ‘fragmentation ’ of social life in capitalism, but to understand exactly what it is in the historical nature of capitalism that appears as a differentiation of ‘spheres’, especially the ‘economic’ and the ‘political’.

Book ChapterDOI
19 Aug 1995
TL;DR: A novel approach to high-level agent programming based on a highly developed logical theory of action, which includes a solution to the frame problem, allows agents to have incomplete knowledge of their environment, and handles perceptual actions.
Abstract: This paper describes a novel approach to high-level agent programming based on a highly developed logical theory of action. The user provides a specification of the agents' basic actions (preconditions and effects) as well as of relevant aspects of the environment, in an extended version of the situation calculus. He can then specify behaviors for the agents in terms of these actions in a programming language where one can refer to conditions in effect in the environment. When an implementation of the basic actions is provided, the programs can be executed in a real environment; otherwise, a simulated execution is still possible. The interpreter automatically maintains the world model required to execute programs based on the specification. The theoretical framework includes a solution to the frame problem, allows agents to have incomplete knowledge of their environment, and handles perceptual actions. The theory can also be used to prove programs correct. A simple meeting scheduling application is used to present the approach. Ongoing work on implementing the approach and handling outstanding problems is also described.

Journal ArticleDOI
TL;DR: The results indicate that these two marine diatoms have the capacity to accumulate inorganic carbon in the light as a consequence, in part, of the active uptake of bicarbonate.
Abstract: Some physiological characteristics of photosynthetic inorganic carbon uptake have been examined in the marine diatoms Phaeodactylum tricornutum and Cyclotella sp. Both species demonstrated a high affinity for inorganic carbon in photosynthesis at pH7.5, having K 1/2 (CO 2 ) in the range 1.0 to 4.0 mmol m -3 and O 2- and temperature-insensitive CO 2 compensation concentrations in the range 10.8 to 17.6 cm 3 m -3 . Intracellular accumulation of inorganic carbon was found to occur in the light ; at an external pH of 7.5 the concentration in P. tricornutum was twice, and that in Cyclotella 3.5 times, the concentration in the suspending medium. Carbonic anhydrase (CA) was detected in intact Cyclotella cells but not in P. tricornutum, although internal CA was detected in both species. The rates of photosynthesis at pH 8.0 of P. tricornutum cells and Cyclotella cells treated with 0.1 mol m -3 acetazolamide, a CA inhibitor, were 1.5- to 5-fold the rate of CO 2 supply, indicating that both species have the capacity to take up HCO 3 - as a source of substrate for photosynthesis. No Na + dependence for HCO 3 - could be detected in either species. These results indicate that these two marine diatoms have the capacity to accumulate inorganic carbon in the light as a consequence, in part, of the active uptake of bicarbonate.


Journal ArticleDOI
Kevin T. Reilly1
TL;DR: This paper examined the establishment size-wage effect and showed that when a dummy variable on computer access in the establishment is introduced as a regressor, the establishment's size variable is an insignificant regressor.
Abstract: This paper examines the issue of the establishment size-wage effect. It analyzes a cross-section for the year 1979, with information on 607 individuals and the 60 private sector establishments where they work. It discusses four theories of the establishment size-wage effect and uses empirical proxies to test them. It shows that when a dummy variable on computer access in the establishment is introduced as a regressor, the establishment size variable is an insignificant regressor. This result and other evidence supports the contention that the establishment size coefficient captures the effect of unobserved human capital accumulation.

Journal ArticleDOI
TL;DR: Topical application of T4N5 liposomes after UV irradiation had no effect on UV-induced skin edema and only partially protected against sunburn cell formation and local suppression of contact hypersensitivity, although its ability to protect against alterations in dendritic immune cells was comparable to that of the sunscreens.

Journal Article
TL;DR: This paper developed the School-Age Temperament Inventory (SATI) as a parental report of children ages 8-11 years, based on previous studies of temperament in children, four empirically derived dimensions were proposed: task persistence, negative reactivity, approach/withdrawal and energy.
Abstract: The purpose of this study was to develop the School-Age Temperament Inventory (SATI) as a parental report of children ages 8-11 years. Based on previous studies of temperament in children, four empirically derived dimensions were proposed: task persistence, negative reactivity, approach/withdrawal, and energy. Parent informants included 435 mothers and 228 of their spouses. Principal factor analysis with varimax rotation supported, in general, the empirically derived dimensions. The validity and reliability of the SATI was then evaluated. Cronbach's alphas were .85 to.90. Correlations between maternal and paternal reports were.51 to.68. Test-retest reliability was.80 to.89. The impact of gender and age was minimal. Convergent validity was evaluated by comparing the SATI with another temperament questionnaire designed for preschool children. Although continued development is recommended, the SATI appears to have adequate validity and reliability for use in research and structured parenting programs.

Journal ArticleDOI
TL;DR: In this article, the carbon kinetic isotope effect in the reaction between Cl and CH4 (KIECl) has been measured using tunable diode laser absorption spectroscopy to determine 13CH4/12CH4 ratios.
Abstract: The carbon kinetic isotope effect in the reaction between Cl and CH4 (KIECl) has been measured using tunable diode laser absorption spectroscopy to determine 13CH4/12CH4 ratios. Cl atoms were generated by the irradition of Cl2 in static mixtures of Cl2/CH4/N2 or Cl2/CH4/N2/O2. Both methods resulted in a (KIECl) of 1.066±0.002 at 297 K. The KIECl displayed a slight temperature dependence, increasing to 1.075±0.005 at 223 K. This result suggests a significant influence of the title reaction on the stratospheric CH4 isotopic composition and may help to resolve discrepancies between measurements of stratospheric 13CH4/12CH4 profiles and laboratory measurements of KIEOH.

Journal ArticleDOI
TL;DR: The authors explored ways in which the wholesale transfer of assumptions from LI literacy can sometimes complicate the process of acquiring L2 literacy and suggested that teachers need to reach a fuller understanding of their unconscious assumptions about literacy if they are to help L2 learners.
Abstract: This paper explores ways in which the wholesale transfer of assumptions from LI literacy can sometimes complicate the process of acquiring L2 literacy. Using the methods of narrative inquiry, I describe my attempts to reach a deeper understanding of L2 literacy via an autobiographical study of Chinese literacy acquisition. The article describes the ways in which my prior English language literacy experiences affected my progress in the L2 and outlines the very complex set of unconscious assumptions about literacy which were held by my Chinese tutor and myself. Some of the key areas in which my tutor and I held different assumptions about literacy included: the qualities of self which literacy skills display; the value of analytic approaches to learning literacy versus holistic ones; the relationship between form and content; and the signs of a good learner. The article also touches on the emotional impact of this experience and suggests that teachers need to reach a fuller understanding of their unconscious assumptions about literacy if they are to help L2 literacy learners.

Journal ArticleDOI
TL;DR: The authors found that players endorsing traditional masculine behavior were more likely to engage in violence than players who held weaker masculine beliefs, and moderate support was found for the predicted relationship between higher masculinity and increased violence, particularly at the preprofessional Junior A level.
Abstract: Qualitative research on the relationship between masculinity and hockey violence has suggested that players endorsing traditional masculine behavior were more likely to engage in violence than players who held weaker masculine beliefs. Data were collected from white, middle class players on five Toronto hockey teams representing two different age groups (14.3 and 17.7 years respectively) and skill levels (Bantam and Junior A). Moderate support was found for the predicted relationship between higher masculinity and increased violence, particularly at the preprofessional Junior A level. Subscales of the Brannon Masculinity Scale, applied to a sport situation, were seen to be a valid measure of gender typing. Increased levels of violence (especially fist fights), more than playing or skating skills were seen to lead to greater perception of competence by both teammates and coaches.

Journal ArticleDOI
TL;DR: Findings were that 1 in 4 women in the sample was physically assaulted by a male intimate, 1 in 2 women reported being raped or experiencing an attempted rape, and nearly half of the respondents reported experiencing some kind of sexual abuse before reaching 16 years of age.
Abstract: This article is a summary of the methods and quantitative prevalence findings from a community-based study of sexual violence in women's lives. The research was based on in-depth face-to-face interviews with 420 women who comprised a random sample of women living in the city of Toronto, Canada's largest urban center. The study generated findings on the prevalence and effects of various forms of sexual abuse and violence in women's lives, including an exploration of the links between these forms of violence over the course of women's lifetimes. Sexual abuse in childhood (including incest), sexual assault, sexual harassment, and physical assault in intimate relationships were documented, as was revictimization and the increased vulnerability for sexual assault and violence experienced by many women sexually abused in childhood. Among the findings were that 1 in 4 women in the sample was physically assaulted by a male intimate, 1 in 2 women reported being raped or experiencing an attempted rape, and nearly h...

Journal ArticleDOI
TL;DR: The complete structure for the core oligosaccharide region of the water-insoluble low-M(r) lipopolysaccharide of Campylobacter jejuni serotype O:3 from phenol/water extraction of bacterial cells was assigned through studies on derivatives of the liberated oligosACcharide.
Abstract: The complete structure for the core oligosaccharide region of the water-insoluble low-M(r) lipopolysaccharide of Campylobacter jejuni serotype O:3 from phenol/water extraction of bacterial cells was assigned through studies on derivatives of the liberated oligosaccharide. Structure determinations were performed using 1H-NMR and 31P-NMR spectroscopies, methylation analysis supported by fast-atom-bombardment mass spectrometry, and Smith degradation experiments. It was concluded that the complete chains in the core oligosaccharide had the following structure in which a proportion of the terminal residues were phosphorylated: [formula: see text] From a similar series of experiments, it was concluded that an associated polysaccharide, which was isolated from the water phase of the phenol/water extracts, had the following repeating unit in which a proportion of the previously unknown L-glycero-D-ido-heptose (L-alpha-D-ido-Hep) residues were present as 3-hydroxypropanoyl esters, and were not covalently linked to the lipopolysaccharide: [formula see: text]

Journal ArticleDOI
TL;DR: Vibrating the agonist increases antagonist coactivity, but does not alter the rate at which coactivation increases during fatigue, which supports the idea that agonist coactivation is controlled by a central mechanism.
Abstract: 1. Biceps femoris antagonist coactivation increases during progressive fatigue. Our purpose was to determine if the mechanism that increases coactivation during fatigue is susceptible to vibration. Vibration drives alpha-motoneurons via the Ia loop, producing force without descending motor drive, and thus uncoupling antagonist and agonist activation. Evidence that vibration increases coactivation disproportionately from its 'common drive' would suggest the possibility that some of the effects of fatigue are mediated through a segmental reflex loop. 2. Ten male subjects performed repeated maximal voluntary isometric contractions (MVCs) of the knee extensors of one leg. Paired submaximal test contractions (50% of MVC), without visual feedback, were performed when MVC reached 85, 70 and then 50% of its initial value. Vibration was applied to the patellar tendon during one test contraction in each pair. 3. Vibration reduced test contraction force below control values. However, coactivation increased at the same rate in both conditions. Biceps femoris coactivation was greater during vibration, but did not change during fatigue in either condition. 4. Our observations suggest that agonist-antagonist muscle pairs are controlled as a single motor unit pool by a common central drive. Vibrating the agonist increases antagonist coactivity, but does not alter the rate at which coactivation increases during fatigue. This supports the idea that agonist coactivation is controlled by a central mechanism.

Journal ArticleDOI
TL;DR: Trovafloxacin (CP-99,219) is a new fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and was well tolerated at doses of 300 mg or below.
Abstract: Trovafloxacin (CP-99,219) is a new fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. The pharmacokinetics and safety of trovafloxacin were characterised in healthy male volunteers after administration of single oral doses of 30, 100, 300, 600 and 1000 mg. trovafloxacin was rapidly absorbed and serum concentrations reached a maximum approximately 1 h after dosing. The corresponding mean Cmax values (mean +/- SD) were 0.3 +/- 0.0, 1.5 +/- 0.5, 4.4 +/- 1.1, 6.6 +/- 1.4 and 10.1 +/- 0.5 mg/L. Terminal-phase half-life was independent of dose, with an overall mean of 9.9 +/- 2.5 h. Generally, Cmax and AUC0-infinity increased linearly with dose. Less than 10% of the administered dose was recovered unchanged in urine. Over the dosing range, trovafloxacin renal clearance was fairly constant, averaging 0.67 +/- 0.36 L/h. Trovafloxacin binding to serum proteins was moderate (70%). Trovafloxacin was well tolerated at doses of 300 mg or below. There were no significant changes in the clinical chemistry or haematology parameters evaluated over the entire dosing range.