339 research outputs found

    Developing a Construct-Valid Measure of Workplace Aggression

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    University of Minnesota Ph.D. dissertation. September 2019. Major: Psychology. Advisor: Paul Sackett. 1 computer file (PDF); viii, 215 pages.Conceptualizations of workplace aggression predominantly converge to suggest that intent to harm others is a necessary feature of aggression (Hershcovis et al., 2007; Jex & Bayne, 2017; Neuman & Baron, 2005). However, inspection of workplace aggression scales suggests that many items do not contain face-validity with respect to inclusion of intent to harm. In a series of four studies, this dissertation examines the effect of inclusion of intent to harm on workplace aggression’s psychometric properties, with the ultimate goal to develop a construct-valid measure of aggression. In addition to the focus on intent to harm, this research evaluates the feature of response perspective (i.e., experienced versus enacted aggression) within aggression’s measurement, as well as aggression’s nomological network and factor structure. First, a general sample of working adults is surveyed to judge the degree to which existing workplace aggression scales contain the feature of intent to harm. It is found that existing workplace aggression scales primarily do not contain sufficient levels of intent to harm, indicating a disconnect between conceptual definition and operational measurement of aggression. Second, results from another working sample suggest that inclusion of intent to harm in aggression scales has substantial implications for aggression’s occurrence rate as well as its factor structure. Specifically, prior research that does not assess intent to harm overestimates the frequency of aggression. Third, it is found that workplace aggression’s external correlations are also overestimated when failing to include intent to harm in measures of aggression. It was also found that aggression without intent is highly correlated with a related construct, counterproductive work behavior (CWB), whereas aggression measured with intent is empirically distinguished from CWB. Using data from the second and third studies, a construct-valid workplace aggression scale is devised, coined the Intentional Workplace Aggression Scale (IWAS). The IWAS displayed stronger relationships with affective constructs such as trait anger and emotional stability than the situational variables of job satisfaction and organizational justice perceptions. Additionally, workplace aggression consistently displayed three lower-order facets: verbal aggression, physical aggression, and social undermining. The fourth study represented a cross-validation effort for IWAS findings and was undertaken in a sample of Korean firefighters. Though to a smaller magnitude than in the previous study, findings surrounding the influence of intent to harm on aggression’s occurrence rate and nomological network were replicated. This study also showed moderate support for the factor structure of the IWAS. Finally, findings across multiple studies indicate that among the same individuals, workplace aggression from the victim perspective and the aggressor perspective are moderately to strongly related

    Differential Ganciclovir-Mediated Cytotoxicity and Bystander Killing in Human Colon Carcinoma Cell Lines Expressing Herpes Simplex Virus Thymidine Kinase

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    Overview summary The transfer of HSV-TK into tumor cells and the subsequent sensitization to GCV have resulted in successful antitumor effects both in vitro and in vivo for a variety of cancers. This study focuses on evaluating and comparing two colon carcinoma cell lines for their ability to metabolize GCV and transfer phosphorylated metabolites to neighboring non-HSV-TK-expressing cells (bystander effect). Here we demonstrate differences in HSV-TK expression, GCV triphosphate accumulation, and incorporation into DNA and their effect on cytotoxicity. We also provide evidence of the transfer of phosphorylated GCV to bystander cells in a cell line deficient in gap junctional intercellular communication.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63405/1/hum.1998.9.6-801.pd

    The role of DNA synthesis inhibition in the cytotoxicity of 2′,2′-difluoro-2′-deoxycytidine

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    Cytotoxicity from the anticancer drug 2′,2′-difluoro-2′-deoxycytidine (dFdCyd) has been correlated with its incorporation into DNA. However, cytotoxicity may also result from inhibition of DNA synthesis, due to either (1) dFdCyd diphosphate-mediated inhibition of ribonucleotide reductase, or (2) direct inhibition of DNA polymerases by the 5′-triphosphate of dFdCyd (dFdCTP). To elucidate the role of DNA synthesis inhibition in the cytotoxicity of dFdCyd, we compared dFdCyd to hydroxyurea (HU), a ribonucleotide reductase inhibitor, and aphidicolin, an inhibitor of DNA polymerases, in the U251 and D54 human glioblastoma cell lines.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46929/1/280_2003_Article_661.pd

    The future problem solving program international: an intervention to promote creative skills in portuguese adolescents

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    The Future Problem Solving Program International (FPSPI) is an internationally applied educational program that involves young people. Its theoretical foundation is both the Creative Problem Solving Model and the Futurist Thinking. It aims to promote creative and critical thinking through a futurist approach to problems. This study intended to analyze the effects of the program on creative skills evaluated by the Torrance Tests of Creative Thinking (Figural Version). The participants’ perceptions of the efficacy of the program were also assessed. This intervention was carried out with 131 adolescents over a period of 7 months in an extra-curricular context. The evaluation of the program takes into account periods both before and after interventions, using similar experimental and control groups. The results showed significant statistical differences for the all skills studied and very positive perceptions of the efficacy of FPSPI. Two significant gender differences in creative performance were also found. The results are described and discussed in order to promote awareness for future research concerning this program(undefined)info:eu-repo/semantics/publishedVersio

    Affinity of the antiviral enantiomers of oxathiolane cytosine nucleosides for human 2'-deoxycytidine kinase

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    The two enantiomers of 2',3'-dideoxy-3'-thiacytidine (BCH-189) and their 5-fluoro analogs (FTC) were found to be good substrates for human 2'-deoxycytidine kinase with Km values in the 5.7 to 42.1 [mu]M range. The affinity of the (-)-enantiomers was greater than that of the (+)-compounds. These results may explain the greater in vitro antiviral potency against human immunodeficiency virus and hepatitis B virus of the (-)-enantiomers when compared to their (+)-counterparts. The (+)- and (-)-enantiomers of FTC and BCH-189 are the first nucleoside analogs for which we have observed lower apparent kinetic constants for this enzyme in the presence of ATP compared to UTP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30848/1/0000510.pd

    Inhibition of fludarabine metabolism by arabinosylcytosine during therapy

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    The active 5′-triphosphate of arabinosyl-2-fluoroadenine (F-ara-ATP) increases the anabolism of arabinosylcytosine (ara-C), whereas ara-C 5′-triphosphate inhibits the phosphorylation of arabinosyl-2-fluoroadenine (F-ara-A) in human leukemia cells in vitro. These interactions have a potential impact on drug scheduling. Clinical trials of relapsed leukemia in which fludarabine (F-ara-A 5′-monophosphate) and ara-C were given in sequence provided the opportunity to evaluate the effects of ara-C infusion on two sequelae: the pharmacokinetics of F-ara-A in plasma and that of F-ara-ATP in leukemia cells. First, F-ara-A pharmacokinetics were altered by ara-C infusion. This was visualized as a transient increase in F-ara-A plasma levels during the ara-C infusion that was given 4 h after fludarabine. The perturbation in F-ara-A plasma levels was dependent on the dose of ara-C. Second, peak F-ara-ATP concentrations were lower in leukemia cells of patients who received ara-C in addition to fludarabine as compared with those who received fludarabine alone. The terminal half-life of F-ara-A in plasma and the half-life of intracellular F-ara-ATP were reduced after the ara-C infusion in a concentration-dependent manner. Studies using purified deoxycytidine kinase support the conclusion that the increase in plasma levels of F-ara-A is in part the result of an effective competition by ara-C for phosphorylation by this enzyme, leading to a perturbation of the pharmacokinetics of intracellular F-ara-ATP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46924/1/280_2004_Article_BF00685547.pd

    Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study

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    The safety and efficacy of gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with resected pancreatic cancer was determined. Patients with resected adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice-weekly (40 mg m−2) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy in 5½ weeks). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg m−2) weekly for two cycles. Each cycle consisted of 3 weeks of treatment followed by 1 week without treatment. Forty-seven patients were entered, 46 of whom are included in this analysis. Characteristics: median age 61 years (range 35–79); 24 females (58%); 73% stage T3/T4; and 70% lymph node positive. Grade III/IV gastrointestinal or haematologic toxicities were infrequent. The median survival was 18.3 months, while the median time to disease recurrence was 10.3 months. Twenty-four percent of patients were alive at 3 years. Only six of 34 patients with progression experienced local regional relapse as a component of the first site of failure. These results confirm the feasibility of delivering adjuvant concurrent gemcitabine and radiation to the upper abdomen. This strategy produced good local regional tumour control

    On the development of gemcitabine-based chemoradiotherapy regimens in pancreatic cancer

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    The use of chemotherapy with concurrent radiation therapy remains a standard treatment option for patients with unresectable or resected adenocarcinoma of the pancreas. This treatment strategy is based in large part on data from serial Gastrointestinal Tumor Study Group trials that have included 5-fluorouracil. Unfortunately, the majority of patients continue to succumb to the disease process. Recently, there has been a resurgence in clinical trials utilizing gemcitabine as a single agent, in combination chemotherapy regimens, and with concurrent radiation therapy. Use with concurrent radiation therapy is based in part on laboratory studies investigating mechanisms of radiosensitization and strategies that might increase the therapeutic index. In the current review, the authors summarize the preclinical data that support the use of gemcitabine as a radiosensitizing agent and the clinical trials that have been conducted to date. Issues regarding the use of gemcitabine in concurrent radiotherapy regimens need to be viewed in the context of both local and distant disease control, given the radiosensitizing and systemic activity of this agent. Cancer 2002;95:933–40. © 2002 American Cancer Society. DOI 10.1002/cncr.10754Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34363/1/10754_ftp.pd
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