Driver Opinions of Simulator-Based Commercial Driver Training

Simulator-based training provides the opportunity to train drivers in a potentially lower cost and safer environment than traditional, behind-the-wheel, training methods. Thus, many motor carriers have begun adopting simulators for use during in-house driver training. This report presents the result of focus groups with drivers who experienced truck simulator-based training at two large motor carriers. In general, drivers at both carriers had positive opinions of simulatorbased training. Most suggestions to improve the program were directed towards modification of how the program was implemented and/or creating a more realistic simulation of the driving environment

In Vitro , Ex Vivo , and In Vivo Activities of Diamidines against Trypanosoma congolense and Trypanosoma vivax

ABSTRACT African animal trypanosomosis (AAT) is caused by the tsetse fly-transmitted protozoans Trypanosoma congolense and T. vivax and leads to huge agricultural losses throughout sub-Saharan Africa. Three drugs are available to treat nagana in cattle (diminazene diaceturate, homidium chloride, and isometamidium chloride). With increasing reports of drug-resistant populations, new molecules should be investigated as potential candidates to combat nagana. Dicationic compounds have been demonstrated to have excellent efficacy against different kinetoplastid parasites. This study therefore evaluated the activities of 37 diamidines, using in vitro and ex vivo drug sensitivity assays. The 50% inhibitory concentrations obtained ranged from 0.007 to 0.562 μg/ml for T. congolense and from 0.019 to 0.607 μg/ml for T. vivax . On the basis of these promising results, 33 of these diamidines were further examined using in vivo mouse models of infection. Minimal curative doses of 1.25 mg/kg of body weight for both T. congolense - and T. vivax -infected mice were seen when the diamidines were administered intraperitoneally (i.p.) over 4 consecutive days. From these observations, 15 of these 33 diamidines were then further tested in vivo , using a single bolus dose for administration. The total cure of mice infected with T. congolense and T. vivax was seen with single i.p. doses of 5 and 2.5 mg/kg, respectively. This study identified a selection of diamidines which could be considered lead compounds for the treatment of nagana

Reconceptualising and Reconstructing Consumer Involvement: Modeling Involvement in a Nomological Network of Relevant Constructs

The research reported herein concerns a specific stream of research within the general domain of consumer behaviour. The dissertation attempts to reconceptualise the construct of involvement and develop an instrument to measure consumers involvement. Largely, the significance of this dissertation rests in the development and presentation of a comprehensive model for the conceptualisation and analysis of involvement and key individual variables that act as antecedents to involvement and consequences of it. The study focuses on the philosophical and practical questions of involvement's content, nature and the direction and strength of its relationship with theoretically important constructs. It fundamentally asks the question: how should the construct of involvement be conceptualised and operationalised, and what is the relationship between involvement and self-image product-image congruency, consumer values, product knowledge/expertise, consumer confidence and consumption consequences. The methodology is based on the development and administration of a survey questionnaire. A mail survey was sent to a random sample of 900 students at an Australian University. The primary analytic procedure for the study was structural equation modeling using the computer program AMOS. The results of the research indicate significant support for the theoretical propositions developed in this study. The theoretical formulations of product involvement, purchase decision involvement, communications involvement and consumption involvement were strongly supported. Further, the introduction of consumer involvement as a second-order factor for the four forms of involvement proved significant. Nomological validity between involvement, values systems, product knowledge, consumer confidence, consumption consequences and self-image product-image congruency was established. A number of theoretical and managerial implications for marketers are identified and discussed

The diamidine DB75 targets the nucleus of Plasmodium falciparum

Abstract Background DB289, [2,5-bis(4-amidinophenyl)furan bis-O-methylamidoxime], is a broad spectrum anti-parasitic compound which has been shown to be effective against malaria in recent clinical trials. DB75, [2,5-bis(4-amidinophenyl)furan], is the active metabolite of this drug. The objective of this study was to determine the mechanism of action of DB75 in Plasmodium falciparum. Methods Live parasites were observed by confocal microscopy after treatment with organelle specific dyes and DB75, an inherently fluorescent compound. Parasites were exposed to DB75 and assessed for growth and morphological changes over time using blood smears and light microscopy. Also, to determine if DB75 affects gene transcription, real time PCR was used to monitor transcript levels over time for six developmentally expressed genes, including trophozoite antigen R45-like (PFD1175w), lactate dehydrogenase (PF13_0141), DNA primase (PFI0530c), isocitrate dehydrogenase (PF13_0242), merozoite surface protein-1 (PFI1475w), and merozoite surface protein-7 (PF13_0197). Results The results show that DB75 localizes in the parasite nucleus but not in other organelles. Once rings are exposed, parasites mature to the trophozoite stage and stall. No stage-dependent or gene-specific inhibition of transcription was seen. However, DB75 delayed peak transcription of trophozoite-stage genes. Conclusion Taken together, DB75 appears to concentrate in the nucleus and delay parasite maturation

The Mitochondrion Is a Site of Trypanocidal Action of the Aromatic Diamidine DB75 in Bloodstream Forms of Trypanosoma brucei

Human African trypanosomiasis (HAT) is a fatal tropical disease caused by infection with protozoans of the species Trypanosoma brucei gambiense and T. b. rhodesiense. An oral prodrug, DB289, is a promising new therapy undergoing phase III clinical trials for early-stage HAT. DB289 is metabolically converted to the active trypanocidal diamidine DB75 [2,5-bis(4-amidinophenyl)furan]. We previously determined that DB75 inhibits yeast mitochondrial function (C. A. Lanteri, B. L. Trumpower, R. R. Tidwell, and S. R. Meshnick, Antimicrob. Agent Chemother. 48:3968-3974, 2004). The purpose of this study was to investigate if DB75 targets the mitochondrion of T. b. brucei bloodstream forms. DB75 rapidly accumulates within the mitochondria of living trypanosomes, as indicated by the fluorescent colocalization of DB75 with a mitochondrion-specific dye. Fluorescence-activated cell sorting analysis of rhodamine 123-stained living trypanosomes shows that DB75 and other trypanocidal diamidines (pentamidine and diminazene) collapse the mitochondrial membrane potential. DB75 inhibits ATP hydrolysis within T. brucei mitochondria and appears to inhibit the oligomycin-sensitive F1F0-ATPase and perhaps other ATPases. DB75 is most likely not an inhibitor of electron transport within trypanosome mitochondria, since DB75 fails to inhibit mitochondrial respiration when glycerol-3-phosphate is used as the respiratory substrate. However, DB75 inhibits whole-cell respiration (50% inhibitory concentration, 20 μM) at drug concentrations and incubation durations that also result in the dissipation of the mitochondrial membrane potential. Taken together, these findings suggest that the mitochondrion is a target of the trypanocidal action of DB75

Pentamidine congeners 1: Synthesis of Cis- and Trans-butamidine analogues as anti-Pneumocystis carinii pneumonia agents.

Butamidine analogues possessing unsaturation in the ether bridge between the bisamidinophenyl or bisimidazolinophenyl functionalities have been synthesized as semirigid congeners of pentamidine. These compounds demonstrated good anti-P. carinii pueumonia activity in a rat model of the disease

In Vitro and In Vivo Evaluation of 28DAP010, a Novel Diamidine for Treatment of Second-Stage African Sleeping Sickness

This is the published version.African sleeping sickness is a neglected tropical disease transmitted by tsetse flies. New and better drugs are still needed especially for its second stage, which is fatal if untreated. 28DAP010, a dipyridylbenzene analogue of DB829, is the second simple diamidine found to cure mice with central nervous system infections by a parenteral route of administration. 28DAP010 showed efficacy similar to that of DB829 in dose-response studies in mouse models of first- and second-stage African sleeping sickness. The in vitro time to kill, determined by microcalorimetry, and the parasite clearance time in mice were shorter for 28DAP010 than for DB829. No cross-resistance was observed between 28DAP010 and pentamidine on the tested Trypanosoma brucei gambiense isolates from melarsoprol-refractory patients. 28DAP010 is the second promising preclinical candidate among the diamidines for the treatment of second-stage African sleeping sickness

Efficacy of DB289 in Thai Patients with Plasmodium vivax or Acute, Uncomplicated Plasmodium falciparum Infections

BackgroundDB289 is the orally active prodrug of the diamidine DB75, which was developed for the treatment of human African trypanosomiasis MethodsWe tested the safety and efficacy of DB289 for the treatment of Plasmodium vivax and acute, uncomplicated P. falciparum infections in an open-label pilot study at the Hospital for Tropical Diseases in Bangkok. Nine patients with P. vivax infections and 23 patients with P. falciparum infections were admitted and treated with 100 mg of DB289 given orally twice a day for 5 days and were followed for 28 days. Patients with P. vivax infections were also treated with primaquine on days 10-23 ResultsAll patients cleared parasites by day 7, with a mean±SD clearance time of 43±41 h. One patient with a P. vivax infection had a recurrence of parasitemia on day 9. Of the 23 patients with P. falciparum infections, 3 had recurrences of parasitemia caused by P. vivax and 2 had recurrences of parasitemia caused by P. falciparum. In only 1 of 2 recurrences of parasitemia caused by P. falciparum were the parasites genotypically distinct from the infecting parasites the patient had at enrollment, which means there was a 96% cure rate ConclusionsDB289 is a promising new antimalarial compound that could become an important component of new antimalarial combination

Efficacy, safety, and dose of Pafuramidine, a new oral drug for treatment of first stage sleeping sickness, in a phase 2a clinical study and phase 2b randomized clinical studies

Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.; The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.; Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3

An Anti-American Ban On Critique: A Critical Policy Commentary

We are a group of educational leaders who are doctoral candidates and faculty members in the Educational Leadership for Social Justice EdD program at California State University, East Bay. Our work centers around 1) creating shared knowledge about inequities and how they are reproduced by institutional systems, such as education, and 2) finding ways to address these systemic issues to create a more equal, healthy society. This work is informed by multiple critical perspectives, such as critical pedagogy (Freire, 1970; hooks, 1994), critical race theory (Ladson-Billings & Tate, 1995), and Black feminisms (Collins, 2002; Crenshaw, 1989). These perspectives, while varying somewhat, offer a common thread guided by the understanding that the world operates via power relations that privilege some groups while subordinating others; but these relationships, and the oppressions that result, are masked by the dominant culture’s insistence on painting reality with a brush of neutrality and a failure to engage with our history in a way that helps us understand and act on its repercussions on humanity