Search

Background and purposeLesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions.Materials and methodsMR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites.ResultsThe proposed count and the criterion standard count were highly correlated (r = 0.97, P < .001) and not significantly different (t59 = -.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated (t58 = -2.73, P < .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale (r = 0.35, P < .01) than lesion load (r = 0.10, P = .44) or lesion count (r = -.12, P = .36) alone.ConclusionsThis study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone.

Background and purposeMR imaging can be used to measure structural changes in the brains of individuals with multiple sclerosis and is essential for diagnosis, longitudinal monitoring, and therapy evaluation. The North American Imaging in Multiple Sclerosis Cooperative steering committee developed a uniform high-resolution 3T MR imaging protocol relevant to the quantification of cerebral lesions and atrophy and implemented it at 7 sites across the United States. To assess intersite variability in scan data, we imaged a volunteer with relapsing-remitting MS with a scan-rescan at each site.Materials and methodsAll imaging was acquired on Siemens scanners (4 Skyra, 2 Tim Trio, and 1 Verio). Expert segmentations were manually obtained for T1-hypointense and T2 (FLAIR) hyperintense lesions. Several automated lesion-detection and whole-brain, cortical, and deep gray matter volumetric pipelines were applied. Statistical analyses were conducted to assess variability across sites, as well as systematic biases in the volumetric measurements that were site-related.ResultsSystematic biases due to site differences in expert-traced lesion measurements were significant (P < .01 for both T1 and T2 lesion volumes), with site explaining >90% of the variation (range, 13.0-16.4 mL in T1 and 15.9-20.1 mL in T2) in lesion volumes. Site also explained >80% of the variation in most automated volumetric measurements. Output measures clustered according to scanner models, with similar results from the Skyra versus the other 2 units.ConclusionsEven in multicenter studies with consistent scanner field strength and manufacturer after protocol harmonization, systematic differences can lead to severe biases in volumetric analyses.

Reported are the results of a randomized trial of a single dose of mefloquine (15 mg/kg or 25 mg/kg body weight) for the treatment of uncomplicated multidrug-resistant falciparum malaria. Of the 110 adult patients enrolled in the study 57 were randomly assigned to the 15 mg/kg group and 53 to the 25 mg/kg group. The baseline characteristics of the patients did not differ significantly in the two groups, except that those in the 15 mg/kg group had lower haemoglobin levels. Adverse effects following treatment were commoner in the 25 mg/kg group, but not significantly so. Seven patients (6%) did not complete the 42-day follow-up. The parasitological failure rates in the 15 and 25 mg/kg groups were, respectively, 50% (28/56) and 43% (23/53) on day 28, and 62% (33/53) and 56% (28/50) on day 42. Treatment failures were not correlated with the serum mefloquine concentrations on day 2, and 13 out of 19 patients with serum mefloquine concentrations >2000 [micro]g/l on day 2 showed an R response during the follow-up. The mean ratio between the concentrations of the (SR)-(-) and (RS)-(+) enantiomers of mefloquine on day 2 was 3.37, indicating that there are differences in their pharmacokinetics. Re-treatment of patients who showed an R response with seven days of quinine (30 mg.[kg.sup.-1].[day.sup.-1])+ tetracycline (25 mg.[kg.sup.-1].[day.sup.-1]) was successful in 93% of the cases., Introduction Mefloquine has been used since 1984 to treat uncomplicated falciparum malaria in Thailand. To delay the development of mefloquine resistance in Plasmodium falciparum strains, mefloquine was at first given [...]

The improvement of grain mold resistance in sorghum [Sorghum bicolor (L.) Moench] has been difficult, presumably because of the complex inheritance of the trait. The objective of this study was to determine the inheritance of grain mold resistance by generation means analysis. The [F.sub.1], [F.sub.2], and backcross generations of a cross between `Sureno' (a dual-purpose food grain and forage variety, resistant to grain mold) and `RTx430' (a widely adapted inbred line, highly susceptible to grain mold) were evaluated in eight different field environments. Significant differences in grain mold incidence between the generations evaluated in this study were observed in all environments. Combined analysis detected a significant generation five-environment interaction indicating that the genotypes reacted differently to each environment. Generation means analysis of transformed grain mold scores detected additive effects in all eight environments, and dominance effects were detected in seven of eight environments. Epistatic effects were detected in only two of eight environments, but combined analysis indicated that higher order interactions were important when evaluated across environment. Broad-sense heritability estimates ranged from 0.46 to 0.82, while narrow-sense heritability estimates ranged from 0.39 to 0.59. At least four to 10 genes were estimated to contribute to grain mold resistance. The results of this study indicate that selection in specific environments is useful for enhancing resistance to mold in these environments, but it may not be as effective in providing grain mold resistance across a wide range of environments., IN MANY REGIONS OF THE WORLD where sorghum is produced, grain mold is a serious disease that reduces grain quality and utilization. The term grain mold is used to describe [...]