Feasibility of Multi-site Clinical Structural Neuroimaging Studies of Aging Using Legacy Data

The application of advances in biomedical computing to medical imaging research is enabling scientists to conduct quantitative clinical imaging studies using data collected across multiple sites to test new hypotheses on larger cohorts, increasing the power to detect subtle effects. Given that many research groups have valuable existing (legacy) data, one goal of the Morphometry Biomedical Informatics Research Network (BIRN) Testbed is to assess the feasibility of pooled analyses of legacy structural neuroimaging data in normal aging and Alzheimer’s disease. The present study examined whether such data could be meaningfully reanalyzed as a larger combined data set by using rigorous data curation, image analysis, and statistical modeling methods; in this case, to test the hypothesis that hippocampal volume decreases with age and to investigate findings of hippocampal asymmetry. This report describes our work with legacy T1-weighted magnetic resonance (MR) and demographic data related to normal aging that have been shared through the BIRN by three research sites. Results suggest that, in the present application, legacy MR data from multiple sites can be pooled to investigate questions of scientific interest. In particular, statistical analyses suggested that a mixed-effects model employing site as a random effect best fits the data, accounting for site-specific effects while taking advantage of expected comparability of age-related effects. In the combined sample from three sites, significant age-related decline of hippocampal volume and right-dominant hippocampal asymmetry were detected in healthy elderly controls. These expected findings support the feasibility of combining legacy data to investigate novel scientific questions. Brad Dickerson and Randy L. Gollub contributed equally.     

Lumbar drainage for subarachnoid hemorrhage: technical considerations and safety analysis

Introduction  

Recent and on going clinical research trials may indicate that the incidence of vasospasm is less in patients treated with lumbar drains following SAH than with patients treated with external ventricular drainage (EVD) alone. These studies have sparked interest in the more aggressive use of LDs in patients with aneurysmal SAH but some clinicians have been concerned about safety.     

Managing childhood fever and pain--the comfort loop

Parents can transmit their anxiety to their child, and just as children can pick up on parental anxiety, they can also respond to a parent's ability to stay calm in stressful situations. Therefore, when treating children, it is important to address parental anxiety and to improve their understanding of their child's ailment. Parental understanding and management of both pain and fever - common occurrences in childhood - is of utmost importance, not just in terms of children's health and welfare, but also in terms of reducing the economic burden of unnecessary visits to paediatric emergency departments. Allaying parental anxiety reduces the child's anxiety and creates a positive feedback loop, which ultimately affects both the child and parentIn this review, the integral role of parental perception of the child's condition and the efficacy of treatment in the management of childhood fever and pain will be discussed.     

Cerebral proton magnetic resonance spectroscopy in children with diabetic ketoacidosis

BACKGROUND AND PURPOSE: Subclinical cerebral edema occurs in many, if not most, children with diabetic ketoacidosis (DKA) and may be an indicator of subtle brain injury. Brain ratios of N-acetylaspartate (NAA) to creatine (Cr), measured by proton MR spectroscopy, decrease with neuronal injury or dysfunction. We hypothesized that brain NAA/Cr ratios may be decreased in children in DKA, indicating subtle neuronal injury. MATERIALS AND METHODS: Twenty-nine children with DKA underwent cerebral proton MR spectroscopy during DKA treatment (2-12 hours after initiating therapy) and after recovery from the episode (72 hours or more after the initiation of therapy). We measured peak heights of NAA, Cr, and choline (Cho) in 3 locations within the brain: the occipital gray matter, the basal ganglia, and periaqueductal gray matter. These regions were identified in previous studies as areas at greater risk for neurologic injury in DKA-related cerebral edema. We calculated the ratios of NAA/Cr and Cho/Cr and compared these ratios during the acute illness and recovery periods. RESULTS: In the basal ganglia, the ratio of NAA/Cr was significantly lower during DKA treatment compared with that after recovery (1.68 +/- 0.24 versus 1.86 +/- 0.28, P<.005). There was a trend toward lower NAA/Cr ratios during DKA treatment in the periaqueductal gray matter (1.66 +/- 0.38 versus 1.91 +/- 0.50, P=.06) and the occipital gray matter (1.97 +/- 0.28 versus 2.13 +/- 0.18, P=.08). In contrast, there were no significant changes in Cho/Cr ratios in any region. CONCLUSIONS: NAA/Cr ratios are decreased in children during DKA and improve after recovery. This finding suggests that during DKA neuronal function or viability or both are compromised and improve after treatment and recovery.     

Validity of the Actical accelerometer step-count function

PURPOSE: To assess the validity of the new Actical accelerometer step count function. METHODS: Actical step counts were compared according to two criterion standards. 1) Eight Acticals were assessed using a mechanical shaker table under six different testing conditions. 2) Thirty-eight volunteers (aged 9-59 yr) wore eight Acticals and eight Actigraphs during treadmill walking (50 and 83 m.min(-1)) and running (133 m.min(-1)) for 6 min at each speed. Steps were counted during the second and fourth minutes of each speed by a trained observer. RESULTS: The correlation between Actical step counts and the mechanical shaker step counts was excellent (r = 1.0). Compared with visually counted steps, both the Actical and Actigraph step counts were significantly different at 50 m.min(-1); however, no significant differences were evident at 83 and 133 m.min(-1). The criterion-related validity correlations (r) for the Actical and Actigraph, respectively, were 0.73 and 0.52 at the slow walk condition and 0.99 and 0.99 at the normal walk and run conditions. CONCLUSION: The new step count function of the Actical accelerometer provides valid estimates of step counts at 83 and 133 m.min(-1) on a range of healthy participants.     

Age and gender differences in youth physical activity: does physical maturity matter?

PURPOSE: To investigate whether observed gender differences in objectively measured physical activity (PA) in children (8-13 yr) are confounded by physical maturity differences. METHODS: Four hundred and one children (194 boys and 207 girls) volunteered for this study. An Actigraph accelerometer was used to obtain seven consecutive days of minute-by-minute PA data for each participant. Minutes of moderate to vigorous PA per day (MVPA), continuous minutes of MVPA per day (CMVPA), and minutes of vigorous PA per day (VPA) were derived from the accelerometer data. Age at peak height velocity (APHV), an indicator of somatic maturity, was predicted in all individuals. Gender differences in the PA variables were analyzed using a two-way (gender x age) ANOVA. RESULTS: Levels of PA decreased with increasing chronological age in both genders (P < 0.05). When aligned on chronological age, boys had a higher MVPA at 10-13 yr, a higher CMVPA at 9-12 yr, and a higher VPA at 9-13 yr (P < 0.05). When aligned on biological age, PA declined with increasing maturity (P < 0.05); however, gender differences between biological age groups disappeared. CONCLUSION: The observed age-related decline in adolescent boys and girls PA is antithetical to public health goals; as such, it is an important area of research. To fully understand gender disparities in PA, consideration must be given to the confounding effects of physical maturity.     

Knee cartilage morphologic characteristics and muscle status of professional weight lifters and sprinters: a magnetic resonance imaging study

BACKGROUND: Whereas muscle and bone mass have been shown to strongly depend on mechanical stimulation (loading history), this relationship has not been established for articular cartilage. HYPOTHESIS: Subjects with high muscle strength display thicker knee cartilage and larger joint surface areas than nonathletic volunteers, and knee cartilage morphologic characteristics correlate more strongly with muscle force than with muscle cross-sectional areas. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Fourteen young, healthy adult professional athletes (7 weight lifters and 7 bobsled sprinters) were examined and compared with 14 adult nonathletic volunteers who had never performed strength training. Muscle moments were measured with a dynamometer and muscle cross-sectional areas and knee cartilage morphologic characteristics with magnetic resonance imaging. RESULTS: Weight lifters and sprinters displayed significantly (P < .001) larger extensor muscle moments and cross-sectional areas. They showed significantly greater (P < .01) patellar cartilage thickness than nonathletic volunteers (+14% [95% confidence interval, 6% to 22%] and +17% [95% confidence interval, 9% to 26%], respectively) but no significant differences in the cartilage thickness of the other knee joint cartilage plates or joint surface areas. Muscle moments did not correlate more strongly with knee cartilage volume or thickness than muscle cross-sectional areas of the thigh. CONCLUSIONS: Direct measurements of muscle forces do not predict cartilage thickness more accurately than muscle cross-sectional areas. These findings suggest that cartilage thickness has much less ability, if any, to adapt to mechanical loading than muscle. Large cohorts of athletes will need to be studied to detect potentially significant differences in cartilage versus nonathletic controls.     

Keyhole limpet hemocyanin: an effective adjunct against melanoma in vivo

BACKGROUND: We have previously demonstrated the potent in vitro antiproliferative effects of keyhole limpet hemocyanin (KLH) against melanoma. Our prior studies directed us to hypothesize that KLH would be effective in vivo against melanoma, alone and in combination with conventional immunotherapy. METHODS: Mice were inoculated with 2 x 10(7) HTB68 cells and randomized to 6 groups. Treatment groups consisted of control, KLH 200 microg, alpha interferon (AIFN) 1000 IU, interleukin-2 (IL-2) 5000 IU, KLH + AIFN, and KLH + IL-2. RESULTS: KLH + IL-2 exhibited the greatest reduction in tumor volume (30%) as compared to control (P = .014), followed by KLH + AIFN (28%, P = .031). Singly treated animals had less tumor inhibition: IL-2 (30%, P = .022), KLH (18%, not significant), and AIFN (16%, not significant). CONCLUSIONS: KLH augments the effects of AIFN, one of the standard immunotherapeutic agents against melanoma in vivo. Further in vivo and early clinical studies into the effects of KLH as both a single and combined agent are warranted.