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Estudo neuroquímico do núcleo pré-mamilar ventral nos animais submissos durante os encontros agonísticos sociais. / Neurochemic study of the premammillary ventralis nucleus on submissive animals during social agonistic encounters.Flavia Venetucci Gouveia 14 December 2009 (has links)
Os comportamentos agonísticos sociais dispostos por animais dominantes e subordinados podem ser notados no paradigma residente intruso. No hipotálamo há o núcleo pré-mamilar ventral (PMv) ligado a um sistema sexualmente dimórfico e relacionado a reprodução e comportamentos agonísticos. A cópula é fundamental para a modulação do comportamento de dominância e aumenta os níveis de CART (Cocaine and Amphetamine Regulated Transcript) no PMv. Animais knockout de Sintase do Óxido Nítrico (NOS) apresentam agressão acentuada. Através da hibridização in situ estudamos a expressão de CART e de NOS nos animais com experiência sexual prévia ao encontro agonístico e sem experiência sexual (naive). No grupo que copulou foi visto aumento na expressão de CART e comportamento diferente do grupo naive visto que buscam a dominância e não apresentam posturas de submissão. Este aumento não foi observado nos níveis de NOS. Sugere-se que a experiência sexual esteja relacionada ao aumento de CART no PMv e possivelmente perda do comportamento subordinado e aumento da busca da dominância. / Aggressive behavior occurs when the interests of one or more individuals conflict. Territory is one of these interests, and the resident intruder paradigm is widely used to observe the expression of social agonistic behaviors. The dominance behavior has been studied under several views and it was shown that it can be raised by the presence of the female, its olfactory clues and by the sexual behavior. In the hypothalamus there is the premammillary ventralis nucleus (PMv) connected to a sexual dimorphic system and related to reproduction and agonistic behaviors. This nucleus was suggested as being involved in the modulation of aggressive behavior, and PMvs neuropeptides can have a direct relation with the expression of those agonistic behaviors. Males exposed to females olfactory clues show an increase in the expression of CART (C Cocaine and Amphetamine Regulated Transcript) in the PMv. Nitric oxide synthase (NOS) knockout animals show increased aggression. In the present investigation, using in situ hybridization we studied the expression of the mRNA of CART and NOS on intruders exposed to the resident-intruder paradigm. Two experimental groups were examined: one with sexual experience before the agonistic encounter and other naïve. It was observed increased expression of CART in the PMv in the sexual-experienced intruder. More, these animals behaved differently from naive intruders, and did not display submissive postures and start searching for dominance. Sexual experienced intruders presented increased expression of CART, but not NOS, mRNA. Thus, suggesting that the sexual experience is related to an increase in CART expression in the PMv and possibly with the lost of submissive behavior and increased search for dominance status.
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Prospective, parallel, controlled trial of implants placed in patients diagnosed with generalized aggressive and chronic periodontitis = clinical, microbiological and immunollogical evaluations = Estudo clínico prospectivo e paralelo de implantes dentários instalados em pacientes com histórico de doença periodontal agressiva e crônica : Estudo clínico prospectivo e paralelo de implantes dentários instalados em pacientes com histórico de doença periodontal agressiva e crônica / Estudo clínico prospectivo e paralelo de implantes dentários instalados em pacientes com histórico de doença periodontal agressiva e crônica : aspectos clínicos, microbiológicos e imunológicosVale, Hugo Felipe do, 1985- 02 October 2014 (has links)
Orientador: Márcio Zaffalon Casati / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-24T15:40:58Z (GMT). No. of bitstreams: 1
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Previous issue date: 2014 / Resumo: O objetivo deste estudo foi avaliar os parâmetros clínicos, imunoenzimáticos e microbiológicos de implantes dentais de estágio único instalados em pacientes com histórico de periodontite agressiva, periodontite crônica e saúde, considerando a hipótese de nulidade de que não existe diferença entre os grupos. Foram selecionados pacientes que apresentaram histórico de periodontite agressiva generalizada (PAG) e periodontite crônica generalizada (PCG) com indicação de reabilitação protética implanto suportada. Os pacientes com necessidade de reabilitação unitária foram divididos em 3 grupos: Grupo PAG (n=13): pacientes apresentando histórico de periodontite agressiva generalizada; Grupo PCG (n=18): pacientes com histórico de PCG ; e Grupo Controle (n=14): pacientes sem histórico de periodontite. Todos os implantes foram instalados em estágio único e, após 3 meses, receberam reabilitação com próteses metalocerâmicas unitárias aparafusadas. Profundidade de sondagem, nível clínico de inserção relativo e posição da margem gengival relativo foram avaliados nos implantes no momento da instalação da prótese e 1, 3 e 6 meses após o carregamento. Avaliação radiográfica foi feita no momento 7 dias após a cirurgia, na instalação da prótese e 6 meses após o carregamento protético. Avaliação microbiológica foi realizada imediatamente após a instalação da prótese, 1, 3 e 6 meses após, por meio de PCR real time, determinando a quantidade dos microrganismos A. actinomycetemcomitans, P. gingivalis e, T. forsythia Avaliação imunológica foi realizada utilizando o sistema LUMINEX/MAGPIX® com amostras de fluido periimplantar coletado aos 15 dias após a cirurgia, imediatamente após a instalação da prótese e 6 meses após o carregamento protético, avaliando as concentrações de IL1?, IL4, IL6, IL8, IL10, TNF?, INF? e GM-CSF, além de marcadores de osteogênese e osteoclasia (OPG e RANKL). Não foram observadas diferenças entre os perfis de pacientes quanto aos parâmetros clínicos e radiográficos ao redor dos implantes em nenhum dos períodos de avaliação. No primeiro mês após a instalação das próteses verificou-se maior concentração de Aa (p<0,05) no grupo PAG. Seis meses após a instalação das próteses o grupo Controle apresentou menores concentrações de Pg (p<0,05). A avaliação dos marcadores de osteogênese/osteoclasia indicou alta concentração de OPG no grupo controle no momento da instalação da prótese. Ainda neste grupo, alta concentração de IL4 foi observada 6 meses após o carregamento dos implantes. Dentro das limitações deste estudo, pode ser concluído que 6 meses após a instalação das próteses, não há diferenças clínicas nem adicional reabsorção óssea em implantes dentários instalados em pacientes com histórico de doença periodontal / Abstract: The aim of this study was to evaluate clinical, microbiological, and immunological patterns of dental implants placed in healthy, partially edentulous, patients (HH), and those with a history of aggressive (HGAgP) or chronic periodontitis (HGCP), considering the null hypothesis that there are no difference between groups. This prospective, parallel, controlled trial enrolled 45 patients (HGAgP, n = 13; HGCP, n = 18; HH, n = 14) followed up from implant insertion until six months after implant loading. Plaque index (PI), bleeding on probing (BOP), probing depth (PD), relative clinical attachment level (rCAL), gingival margin position (rGMP), implant stability (IS), and radiographic marginal bone resorption (RMBR) around implants were evaluated. Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), and Tannerella forsythia (Tf) levels were evaluated by real-time PCR. Also, IL-1?, TNF?, IL-6, IL-8, IFN?, GM-CSF, IL-4, IL-10, RANKL, and OPG levels were evaluated with the LUMINEX/MAGPIX® platform. No inter-group differences were observed around dental implants when the clinical parameters (PI, BOP, PD, rCAL, rGMP, IS, and RMBR) (p > 0.05) were considered at any evaluation period. At the first month after implant loading, those in the HGAgP group presented a higher level of Aa (p < 0.05). Six months after implant loading, those in the HH group presented a lower level of Pg (p < 0.05). The immunologic evaluation showed higher values of OPG in those in the HH group at implant loading, and a higher IL-4 level in those in the HH group six months after implant loading. It can be concluded that, after six months of implant loading, despite some micro- and immunological differences, there are no clinical differences or additional RMBR around implants placed in patients with a history of periodontal disease / Doutorado / Periodontia / Doutor em Clínica Odontológica
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Molecular technologies in the study of periodontal diseases = Tecnologias moleculares no estudo das doenças periodontais / Tecnologias moleculares no estudo das doenças periodontaisTaiete, Tiago, 1987- 03 June 2013 (has links)
Orientador: Márcio Zaffalon Casati / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-22T14:43:32Z (GMT). No. of bitstreams: 1
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Previous issue date: 2013 / Resumo: A periodontite agressiva é caraterizada por apresentar início precoce, rápida progressão e pobre resposta as abordagens terapêuticas quando comparado a periodontite crônica. Entretanto, os mecanismos responsáveis por essas diferenças ainda não são completamente compreendidos. Ferramentas como a genômica, proteômica ou transcriptômica podem esclarecer esses aspectos, gerando importantes informações a respeito da patogênese das doenças periodontais. Portanto, os objetivos do presente estudo foram: i) Apresentar uma revisão de literatura focada na aplicação da genômica, transcriptômica, proteômica e metabolômica no estudo das doenças periodontais. ii) Avaliar as diferenças no perfil de expressão gênica da mucosa mastigatória, sem a influência do biofilme subgengival, em indivíduos com histórico de periodontite agressiva e crônica, comparando-os entre si e também com o perfil de expressão de indivíduos sem histórico de periodontite visando à identificação de possíveis alterações constitutivas na expressão de genes que podem estar relacionadas com as diferenças entre as duas formas de periodontite. Para o primeiro objetivo, foi realizada uma revisão dos artigos que empregaram as tecnologias ômicas no estudo das doenças periodontais. Os estudos presentes na literatura indicaram que essas tecnologias podem levar a um melhor entendimento dos eventos moleculares envolvidos na patogênese das doenças periodontais. Para o segundo objetivo, foram obtidas amostras teciduais da mucosa mastigatória de 4 pacientes com histórico de periodontite crônica, 4 com periodontite agressiva generalizada e 4 indivíduos sem histórico de periodontite. As amostras foram manipuladas para a extração de RNA total, síntese de cDNA de fita dupla e a hibridização por microarranjo de DNA, avaliando a expressão de 45033 genes. Os programas R e Bioconductor foram empregados para realizar a análise de RMA (Robust-Multi-Array), calcular o valor de expressão (fold-change) e o valor de p para comparações múltiplas através do método de Benjamini-Hochberg. O enriquecimento dos dados, através de ontologia gênica e análise de via, foi realizado com o programa de bioinformática DAVID (Database for Annotation, Visualization and Integrated Discovery). Três comparações foram realizadas: comparação 1 (periodontite agressiva x indivíduos sem histórico de periodontite); comparação 2 (periodontite crônica x indivíduos sem histórico de periodontite); e comparação 3 (periodontite crônica x periodontite agressiva). A comparação entre os grupos identificou: 192 genes e 50 grupos diferencialmente expressos na comparação 1, 43 genes e 27 grupos na comparação 2 e 168 genes e 75 grupos na comparação 3. Genes com funções no sistema imune, entre os quais receptores de linfócitos natural killer, foram mais expressos em periodontite agressiva; em contraste, genes envolvidos na proliferação e diferenciação de queratinócitos, assim como genes com função em processos neurais foram menos expressos. Já os indivíduos com periodontite crônica se caracterizaram por um aumento na expressão de genes com função na resposta a estímulos externos, e uma diminuição na expressão dos genes relacionados ao sistema imune. Dentro dos limites desse estudo, pode-se concluir que existem diferenças nos perfis de expressão gênica da mucosa mastigatória de indivíduos com histórico de periodontite agressiva e crônica, quando comparadas entre si e com indivíduos sem histórico de periodontite, que podem estar associadas às diferenças em suas patogêneses / Abstract: Aggressive periodontitis is characterized by early onset, rapid progression and poor response to treatment compared to chronic periodontitis. However, mechanisms responsible for these differences are not fully understood. Tools such as genomics, proteomics and transcriptomics can clarify these aspects, producing important information about the pathogenesis of periodontal diseases. Therefore, the aims of this study were: i) Provide a literature review focused on the application of genomics, transcriptomics, proteomics, and metabolomics in the study of periodontal diseases. ii) Evaluate the gene expression profile of tissue from masticatory mucosa, without the influence of biofilm, in patients with a history of generalized aggressive and chronic periodontitis, and also with gene expression profile of individuals without periodontitis, with the aim to identify possible constitutive alterations in gene expression, which may be related to the differences between both forms of periodontitis. For the first objective, it was performed a review of articles that employed omics technologies in the study of periodontal diseases. The studies in the literature indicated that these technologies can lead to a better understanding of molecular events involved in the pathogenesis of periodontal diseases. For the second objective, masticatory mucosa tissue samples were obtained from 4 patients with a history of chronic periodontitis, 4 with generalized aggressive periodontitis, and 4 from subjects without history of periodontitis. Tissue samples were processed for total RNA extraction, double-strand cDNA synthesis for subsequent hybridization reaction on microarrays, which assessed the expression of 45033 genes. R and Bioconductor softwares used to perform the RMA analysis (Robust Multi-Array), calculate the value of expression (fold-change) and the p-value for multiple comparisons through Benjamini-Hochberg method. Enrichment analysis, through gene ontology (GO) and pathway analysis, was performed with DAVID (Database for Annotation, Visualization and Integrated Discovery). Three comparisons were performed: comparison 1 (aggressive periodontitis x healthy subjects); comparison 2 (chronic periodontitis x healthy subjects); and comparison 3 (chronic periodontitis x aggressive periodontitis). Comparisons analysis found 192 genes and 50 groups differentially expressed in comparison 1, 43 genes and 27 groups in comparison 2, and 168 genes and 75 groups in comparison 3. Genes with function in the immune system, including natural killer cells receptors, were higher expressed in aggressive periodontitis; in contrast, genes involved in proliferation and differentiation of keratinocytes, as well as genes with function in neural process were lower expressed. Chronic periodontitis subjects were characterized by increased expression of genes related to response to external stimuli, and a decrease in the expression of genes related to the immune system. Within the limits of this study, it can be concluded that there are differences in the gene expression profile of masticatory mucosa of patients with a history of chonic and aggressive periodontitis, when compared among them and with healthy group, which may be associated with differences in their pathogenesis / Mestrado / Periodontia / Mestre em Clínica Odontológica
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The Effect of male-male competition and its Underlying Regulatory Mechanisms on the Electric Signal of the Gymnotiform fish <em>Brachyhypopomus gauderio</em>Salazar, Vielka Lineth 30 October 2009 (has links)
Sexually-selected communication signals can be used by competing males to settle contests without incurring the costs of fighting. The ability to dynamically regulate the signal in a context-dependent manner can further minimize the costs of male aggressive interactions. Such is the case in the gymnotiform fish Brachyhypopomus gauderio, which, by coupling its electric organ discharge (EOD) waveform to endocrine systems with circadian, seasonal, and behavioral drivers, can regulate its signal to derive the greatest reproductive benefit. My dissertation research examined the functional role of the EOD plasticity observed in male B. gauderio and the physiological mechanisms that regulate the enhanced male EOD. To evaluate whether social competition drives the EOD changes observed during male-male interactions, I manipulated the number of males in breeding groups to create conditions that exemplified low and high competition and measured their EOD and steroid hormone levels. My results showed that social competition drives the enhancement of the EOD amplitude of male B. gauderio. In addition, changes in the EOD of males due to changes in their social environment were paralleled by changes in the levels of androgens and cortisol. I also examined the relationship between body size asymmetry, EOD waveform parameters, and aggressive physical behaviors during male-male interactions in B. gauderio, in order to understand more fully the role of EOD waveforms as reliable signals. While body size was the best determinant of dominance in male B. gauderio, EOD amplitude reliably predicted body condition, a composite of length and weight, for fish in good body condition. To further characterize the mechanisms underlying the relationship between male-male interactions and EOD plasticity, I identified the expression of the serotonin receptor 1A, a key player in the regulation of aggressive behavior, in the brains of B. gauderio. I also identified putative regulatory regions in this receptor in B. gauderio and other teleost fish, highlighting the presence of additional plasticity. In conclusion, male-male competition seems to be a strong selective driver in the evolution of the male EOD plasticity in B. gauderio via the regulatory control of steroid hormones and the serotonergic system.
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Closeness and Conflict in Children’s Friendships: Relations with Friendship Stability, Adjustment and Sociometric StatusParker, Richard J. January 2011 (has links)
Not many children report relationships with friends that are both close and conflictual. There is a paucity of research examining the trajectory of children's relationship closeness and conflict together over time. This is unfortunate because contentious relationships are related to cardiovascular problems, at least in young adults and because the trajectories of these two aspects of children's relationship quality over time is not understood. Therefore, two longitudinal data sets with younger (mean age 7.5 years at Time 1; four data points over 2 years) and older (mean age 9.9 years at Time 1; two data points over 1 year) children were studied. In both cohorts, measures of friendship quality and peer nominations of liking/disliking as well as overt and relational (older cohort) aggression were completed. Children who reported relationships high in both closeness and conflict were generally satisfied with their friendships; they were not more likely to end their friendships than were children who reported different levels of closeness and conflict (younger cohort). Both boys' and girls' relationship closeness increased over time according to growth curve analyses. The relationships of girls who remained in the same friendship, and who therefore provided ratings on the same friend at each time point, tended to increase in closeness at a different rate over time than the relationships of girls who provided ratings on different friends (younger cohort). Children who reported relationships high in closeness and in conflict were not more aggressive over time than were children who reported different levels of relationship closeness and conflict. However, girls' closeness and overt aggression tracked each other (increased) over time (younger cohort). Girls who reported low social support and negative interactions in their friendships increased the most in overt aggression over time (older cohort). Aggressive and nonaggressive children generally reported similar friendship quality (both cohorts), but the friendship closeness of chronically aggressive boys decreased over time (younger cohort). There were negligible friendship quality differences amongst the sociometric groups. The discussion centers on friendship quality changes in children's continuing friendships, the potential dire effects of turbulent friendships and the friendships of aggressive as well as controversial children.
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Patient and disease precursors and clinical predictors of prolonged cytopenias in patients with aggressive B-cell non-Hodgkin's lymphoma treated with chimeric antigen receptor T-cell therapySaucier, Anna 29 November 2020 (has links)
INTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapy is a new treatment for hematologic malignancies including aggressive B-cell non-Hodgkin’s lymphoma (NHL). Although it has provided an effective treatment option for patients who have few options, CAR T-cell therapy does have many associated toxicities. Prolonged cytopenias are one of the lesser understood toxicities that can affect upwards of 40% of patients.
METHODS: In this retrospective study, we reviewed 106 patients who received commercial CAR T-cell therapy between November 2017 and September 2019. Prolonged cytopenias were defined as having absolute neutrophil count (ANC) <1000/mm3, platelets (PLT) <50,000/mm3, and/or hemoglobin (Hgb) <10 g/dL at least once after 30 days post-CAR T-cell infusion. Furthermore, if only one incidence of cytopenia was recorded 30 days post infusion, we required that the patient had to have received either a transfusion or granulocyte-colony stimulating factor (GCSF) after the date of the recorded cytopenic value to be considered a part of the cytopenic cohort.
RESULTS: 22 patients met the criteria of having prolonged cytopenias. 64% of the cytopenic cohort had >1 type of prolonged cytopenias. Anemia was the most prevalent affecting 72% of cytopenic patients. The length of time from diagnosis of aggressive B-cell NHL to date of CAR T-cell infusion was found to be positively correlated with an increased risk of developing prolonged cytopenias following CAR T-cell therapy. Additional risk factors associated with an increased risk of delayed cytopenias by univariate analysis included neutropenia on the day of infusion (day 0), a high C-reactive protein (CRP) before lymphodepletion and on day 0, day 0 PLT count, and Hgb before lymphodepletion and on day 0. On multivariate analysis, only high CRP before lymphodepletion was associated with an increased risk of prolonged cytopenias while high ferritin and PLT values on day 0 were associated with not developing prolonged cytopenias. There was no statistical difference between the cytopenic and non-cytopenic cohorts in rates of progression free survival (PFS) and overall survival (OS). Also, no difference was seen in rates or severity of other toxicities between cohorts. 41% of the cytopenic cohort experienced infectious complications post-infusion with one patient dying from their infectious complications. However, there was no association with incidence of infection and prolonged cytopenias when compared to the incidence of infection in the non-cytopenic cohort.
CONCLUSIONS: A longer time from diagnosis of aggressive B-cell NHL to time of CAR T-cell infusion was associated with prolonged cytopenias while the number of lines of prior chemotherapy and rate of prior high dose chemotherapy with an autologous stem cell transplant (HD-ASCT) were not associated. It would be valuable to confirm this association and why it is associated since the other two factors were not. We lacked bone marrow biopsies before CAR T-cell infusion and did not have bone marrow biopsies for many patients after CAR T-cell infusion. It would be beneficial to collect data regarding bone marrow biopsies from these time points to highlight any changes that could be related to CAR T-cell therapy. Cytogenetic information of individual patient’s diseases would be worth analyzing to help determine if there are biological factors associated with prolonged cytopenias in response to CAR T-cell therapy. Additional studies should investigate the laboratory values we found to have associations with either cohort to help identify possible predictive values providers could use to identify patients at higher risk of having prolonged cytopenias. There is also a need to see if specific prior chemotherapy regimens increase a patient’s risk of having prolonged cytopenias. Overall, since prolonged cytopenias after CAR T-cell infusions have not been heavily investigated, further investigation is needed to better understand the predictive factors and identify possible mechanisms of prolonged cytopenias seen in CAR T-cell patients.
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Agresivní obchodní praktiky v hospodářské soutěži / Aggressive business practices in competitionSchwetzová, Tereza January 2020 (has links)
Thesis title: Aggressive business practices in competition This thesis deals with an analysis of aggressive business practices within competition, focusing on aggressive business practices in relation to other competitors, i.e. B2B relations. The thesis is divided into four chapters with an unnumbered introduction and conclusion. The most crucial part of the thesis can be found in the second and third chapter. The first chapter introduces reader to the issue of unfair competition. In particular, the chapter deals with the analysis of the general clause, as the key provision within the private law framework of unfair competition. Above mentioned is the reason of a brief historical development of this provision being also included in this chapter. Furthermore, the chapter considers the adaptation of unfair competition among the European Union. The second chapter deals with the analysis of the factual phenomena of aggressive business practices, namely denigration (section 2984), unlawful comparative advertising (section 2980) and breach of trade secrets (section 2985), considering the newly adopted directive on the protection of undisclosed know-how and business information (trade secrets). The chapter also incorporates relevant case law. Third chapter deals with aggressive business practices...
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Relationship satisfaction as a protective factor against aggressive tendencies in military related couples with posttraumatic stress disorder symptomsMcDermott, Elizabeth Anne 25 August 2021 (has links)
No description available.
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Differing Types of Cellular Phone Conversations and Dangerous DrivingDula, Chris S., Martin, Benjamin A., Fox, Russell T., Leonard, Robin L. 01 January 2011 (has links)
This study sought to investigate the relationship between cell phone conversation type and dangerous driving behaviors. It was hypothesized that more emotional phone conversations engaged in while driving would produce greater frequencies of dangerous driving behaviors in a simulated environment than more mundane conversation or no phone conversation at all. Participants were semi-randomly assigned to one of three conditions: (1) no call, (2) mundane call, and, (3) emotional call. While driving in a simulated environment, participants in the experimental groups received a phone call from a research confederate who either engaged them in innocuous conversation (mundane call) or arguing the opposite position of a deeply held belief of the participant (emotional call). Participants in the no call and mundane call groups differed significantly only on percent time spent speeding and center line crossings, though the mundane call group consistently engaged in more of all dangerous driving behaviors than did the no call participants. Participants in the emotional call group engaged in significantly more dangerous driving behaviors than participants in both the no call and mundane call groups, with the exception of traffic light infractions, where there were no significant group differences. Though there is need for replication, the authors concluded that whereas talking on a cell phone while driving is risky to begin with, having emotionally intense conversations is considerably more dangerous.
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A Social-Cognitive Model of Driver Aggression: Taking Situations and Individual Differences Into AccountDula, Chris S., Geller, E. Scott, Chumney, Frances L. 01 December 2011 (has links)
Aggressive driving is a phenomenon that has taken on tremendous significance in society. While the issue has been studied from perspectives of several disciplines, relatively few comprehensive empirical investigations have been conducted. This may be due, at least in part, to a scarcity of comprehensive theoretical works in the field, from which methodical research hypotheses could be derived. This paper reviews major extant theories of general aggression to offer a rationale for choosing a particular framework to apply to the topic of aggressive driving. The social-cognitive model of aggressive driving is recommended, as it takes into account wide-ranging cognitive, situational, and dispositional factors. Implications for future research are also considered.
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