Expanding Alaska–Canada Rail Brooks, Colin; Kourous-Harrigan, Helen; Billmire, Mike ...
Transportation research record,
01/2011, Letnik:
2261, Številka:
1
Journal Article
Recenzirano
Recent changes in global markets have raised the value of mineral resources in northwestern Canada and Alaska. The development of these resources depends on the economics of rail infrastructure ...expansion. Transportation decision makers need revenue and cost assessments to plan investment in rail infrastructure. A tool based on a geographic information system was developed for mineral resource evaluation and visualization. The tool incorporated expert-augmented mineral resource data for more than 22,000 occurrences in the region. The tool included the proposed Alaska–Canada Rail Link, which would connect Alaska rail to the lower 48 states. Users selected locations of known mineral occurrences near actual or proposed rail routes and used statistical mineral deposit models to estimate resource sizes and extractable value over time by combining current or user-entered commodity prices with multimodal revenue freight volumes and optimally routed transportation costs. The tool translated the revenue scenario into likely carbon dioxide emissions according to the transport of mineral concentrates to regional and international destinations. Users could select and visualize multimodal transportation networks to understand and minimize mobile-source carbon emissions as part of their scenarios. Statistical estimates of mine capital expenditure and operating costs were also calculated according to type. The tool calculated the gross metal value of a mineral occurrence with statistical deposit models. This index was linked to the positive regional economic impact associated with the developed resource in terms of jobs, taxes and royalties, and resupply. This information helped decision makers close the loop on infrastructure investment assessments.
To assess the role of resistance mutations in subjects experiencing virological failure on zidovudine (ZDV) and lamivudine (3TC) combined with a protease inhibitor (PI) to those failing on ZDV/3TC ...alone.
Samples were obtained from previously antiretroviral therapy-naive subjects enrolled into two studies, AVANTI 2 and AVANTI 3. Subjects were randomized to receive either: ZDV/3TC or ZDV/3TC plus indinavir (IDV) for 52 weeks (AVANTI 2), and ZDV/3TC or ZDV/3TC and nelfinavir (NFV) for 28 weeks (AVANTI 3). Emergence of viral resistance mutations was monitored by population sequencing and phenotypic resistance was determined by the recombinant virus assay.
Genotypic data were obtained for subjects with plasma HIV-1 RNA > 400 copies/ml. In AVANTI 2, ZDV mutations were detected in 27% of ZDV/3TC-treated patients at week 52, but were absent in subjects treated with ZDV/3TC/IDV. No subjects from either arm of AVANTI 3 developed ZDV resistance mutations at week 28. The M184V mutation developed in most ZDV/3TC-treated subjects from both studies. The presence of M184V was, however, associated with significantly lower plasma viral RNA levels when compared with values obtained before initiation of treatment. There was a high frequency (4 of 11) of the protease L10F substitution in ZDV/3TC/IDV-treated patients that was associated with virological failure but did not result in phenotypic resistance to any of the PIs tested.
ZDV mutations were not detected in ZDV/3TC/PI-treated patients and they developed slowly in those treated with ZDV/3TC. Few protease mutations known to confer phenotypic PI resistance developed in the ZDV/3TC/PI arms of either study. The low prevalence of ZDV and PI mutations is encouraging regarding the future treatment options of these patients.
The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear.
To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa ...supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes.
Multicenter, parallel-group, double-blind, randomized controlled trial.
Academic movement disorders clinics at 22 sites in the United States and Canada.
Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001.
Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability.
Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events.
Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval CI, 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups.
Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.
The QT interval BEDNAR, Martin M; HARRIGAN, Edmund P; ANZIANO, Richard J ...
Progress in cardiovascular diseases,
2001 Mar-Apr, Letnik:
43, Številka:
5
Journal Article
Recenzirano
The effects of disease states and therapeutic drugs on the QT interval have been extensively studied in an attempt to understand the relationship between QT and the risk of torsade de pointes and ...sudden cardiac death. Differences in heart rate correction methods, electrocardiogram lead placement, and other internal (eg, genetic, physiologic) and external (eg, food, time of day) factors have confounded the interpretation of this relationship. A comprehensive review of the epidemiologic literature suggests that the corrected QT interval (QTc) is an important but imprecise marker of cardiovascular disease. The association between QTc prolongation and mortality has been identified in patients with cardiac disease but is unclear in patients without cardiac disease. Drug-related prolongation of QTc can clearly increase the risk of torsade de pointes, but this arrhythmia is rarely associated with a QTc of less than 500 ms. It also appears that noncardiac drugs that are associated with QTc prolongation are not identical in their proarrhythmic capacities and that increased exposure via clinically significant drug interactions is a major contributor to the liability of noncardiac drug-induced arrhythmia. Recognition of the aforementioned variables in conjunction with careful QTc measurements assists in establishing a more precise benefit-risk ratio for a specific drug therapy or for arrhythmia risk associated with various pathophysiologic or genetic states.
PDF
