Biomedical subjects

Neal O Jeffries

Publications and source records attributed to Neal O Jeffries.

6 recordsLinked to original sources

PubMed2006

Multiple comparisons distortions of parameter estimates.

In experiments involving many variables, investigators typically use multiple comparisons procedures to determine differences that are unlikely to be the result of chance. However, investigators rarely consider how the magnitude of the greatest observed effect sizes may have been subject to bias resulting from multiple testing. These questions of bias become important to the extent investigators focus on the magnitude of the observed effects. As an example, such bias can lead to problems in attempting to validate results, if a biased effect size is used to power a follow-up study. An associated important consequence is that confidence intervals constructed using standard distributions may be badly biased. A bootstrap approach is used to estimate and adjust for the bias in the effect sizes of those variables showing strongest differences. This bias is not always present; some principles showing what factors may lead to greater bias are given and a proof of the convergence of the bootstrap distribution is provided.

Bias↗

PubMed2004

Performance of a genetic algorithm for mass spectrometry proteomics.

BACKGROUND: Recently, mass spectrometry data have been mined using a genetic algorithm to produce discriminatory models that distinguish healthy individuals from those with cancer. This algorithm is the basis for claims of 100% sensitivity and specificity in two related publicly available datasets. To date, no detailed attempts have been made to explore the properties of this genetic algorithm within proteomic applications. Here the algorithm's performance on these datasets is evaluated relative to other methods. RESULTS: In reproducing the method, some modifications of the algorithm as it is described are necessary to get good performance. After modification, a cross-validation approach to model selection is used. The overall classification accuracy is comparable though not superior to other approaches considered. Also, some aspects of the process rely upon random sampling and thus for a fixed dataset the algorithm can produce many different models. This raises questions about how to choose among competing models. How this choice is made is important for interpreting sensitivity and specificity results as merely choosing the model with lowest test set error rate leads to overestimates of model performance. CONCLUSIONS: The algorithm needs to be modified to reduce variability and care must be taken in how to choose among competing models. Results derived from this algorithm must be accompanied by a full description of model selection procedures to give confidence that the reported accuracy is not overstated.

Algorithms↗

PubMed2003

Corpus callosum development in childhood-onset schizophrenia.

OBJECTIVE: Corpus callosum (CC) size and interhemispheric communication differences have been reported between patients with schizophrenia and normal controls. Childhood-onset schizophrenia (COS) is a severe form of the disorder that is continuous with later-onset disorder. Corpus callosal area was examined for COS at initial scan and prospectively through adolescence, and related to other developmental abnormalities for this group. METHOD: A total of 113 anatomic brain MRI scans were obtained from 55 COS (22 female) and 110 scans from 56 age- and gender-matched healthy volunteers (22 female), across ages 8-24. Baseline and prospective rescans were obtained at approximately 2-year intervals. The midsagittal areas for total corpus callosum and seven subregions were calculated using an automated system. Cross-sectional and longitudinal data were combined using mixed model regression analysis to compare developmental changes for the two groups. RESULTS: No diagnostic differences were seen at time of initial scan. Longitudinally, and in contrast to healthy volunteers, patients with schizophrenia showed a significant difference in developmental trajectory for the area of the splenium, both before (p=0.012) and after (p=0.05) adjustment for total cerebral volume. The area of the splenium becomes significantly smaller in COS, starting at about age 22. CONCLUSION: Patients with schizophrenia showed a significant difference in developmental trajectory for the splenial area, which seems to decline for COS. If replicated, this may reflect anticipated late occipital and extrastriate changes in brain regions.

Adolescent↗

PubMed2003

Progressive loss of cerebellar volume in childhood-onset schizophrenia.

OBJECTIVE: Childhood-onset schizophrenia is a severe and unremitting form of the disorder. Prospective brain magnetic resonance imaging (MRI) studies have found progressive loss of total cerebral volume during adolescence, primarily attributable to accelerated loss of cortical gray matter. Because there is evidence of cerebellar involvement in schizophrenia, the authors examined cerebellar volume and its relation to cortical gray matter development during adolescence in patients with childhood-onset schizophrenia and healthy comparison subjects. METHOD: Total cerebellar volume was algorithmically calculated for 108 anatomical brain MRI scans from 50 patients (20 of whom were female) and 101 scans from 50 age- and gender-matched healthy volunteers (20 of whom were female). The age range of the patients and comparison subjects was 8 to 24. Midsagittal vermal area and posterior-inferior vermal lobe volume were measured by hand. Prospective rescans were obtained at approximately 2-year intervals. Cross-sectional and longitudinal data were combined in mixed model regressions to compare developmental changes for the groups. RESULTS: In contrast to healthy volunteers, patients with schizophrenia showed a progressive loss of cerebellar volume during adolescence. Cerebellar and cerebral volume decreases were significantly correlated in childhood-onset schizophrenia. CONCLUSIONS: Childhood-onset schizophrenia is associated with significant progressive loss of cerebellar volume during adolescence, consistent with previously reported decreases in total cerebral and cortical gray matter. At least in these patients with severe early-onset schizophrenia, the loss appears secondary to a generalized process.

Adolescent↗

PubMed2003

Progressive brain volume loss during adolescence in childhood-onset schizophrenia.

OBJECTIVE: Previous reports have documented a striking progressive reduction in cortical gray matter volume during adolescence in patients with childhood-onset schizophrenia. This study examined the rate of loss in cortical gray matter volume in relation to age and clinical status in adolescent patients over a follow-up period of 2-6 years. METHOD: A total of 131 brain magnetic resonance imaging scans were acquired for 60 subjects with childhood-onset schizophrenia (mean age=14.5 years, SD=2.5), and 140 scans were acquired for 64 matched healthy comparison subjects. One or more follow-up scans were acquired at approximately 2-year intervals for 39 subjects with childhood-onset schizophrenia and 43 healthy subjects. Developmental trajectories for total and regional brain volumes were examined in relation to age by using polynomial growth models and data from all available scans. The rate of gray matter reduction in patients with childhood-onset schizophrenia was examined in relation to developmental and clinical measures by using stepwise regression. RESULTS: Rates of brain volume reduction were significantly higher for patients with childhood-onset schizophrenia than for healthy comparison subjects. In childhood-onset schizophrenia, the rate of gray matter reduction was related to premorbid impairment and baseline severity of clinical symptoms but not to gender, ethnicity, or age at onset of the disorder. Unexpectedly, greater clinical improvement was significantly related to a higher rate of gray matter reduction. Longitudinal trajectories suggested that the rate of cortical loss plateaus during adolescence. CONCLUSIONS: Striking loss of cerebral gray matter is seen through adolescence in patients with childhood-onset schizophrenia. The rate of reduction was related to premorbid impairment and baseline symptom severity, but it may also be in part a plastic response to illness.

Adolescent↗

PubMed2002

Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.

CONTEXT: Various anatomic brain abnormalities have been reported for attention-deficit/hyperactivity disorder (ADHD), with varying methods, small samples, cross-sectional designs, and without accounting for stimulant drug exposure. OBJECTIVE: To compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated male and female patients with ADHD and healthy controls. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, Md, of 152 children and adolescents with ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images. MAIN OUTCOME MEASURES: Using completely automated methods, initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of the brain were compared in patients and controls. RESULTS: On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in smaller total cerebral volumes (-3.2%, adjusted F(1,280) = 8.30, P =.004) and in significantly smaller cerebellar volumes (-3.5%, adjusted F(1,280) = 12.29, P =.001). Compared with controls, previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes (overall F(2,288) = 6.65; all pairwise comparisons Bonferroni corrected, -5.8%; P =.002) and cerebellar volumes (-6.2%, F( 2,288) = 8.97, P<.001). Unmedicated children with ADHD also exhibited strikingly smaller total white matter volumes (F(2,288) = 11.65) compared with controls (-10.7%, P<.001) and with medicated children with ADHD (-8.9%, P<.001). Volumetric abnormalities persisted with age in total and regional cerebral measures (P =.002) and in the cerebellum (P =.003). Caudate nucleus volumes were initially abnormal for patients with ADHD (P =.05), but diagnostic differences disappeared as caudate volumes decreased for patients and controls during adolescence. Results were comparable for male and female patients on all measures. Frontal and temporal gray matter, caudate, and cerebellar volumes correlated significantly with parent- and clinician-rated severity measures within the ADHD sample (Pearson coefficients between -0.16 and -0.26; all P values were <.05). CONCLUSIONS: Developmental trajectories for all structures, except caudate, remain roughly parallel for patients and controls during childhood and adolescence, suggesting that genetic and/or early environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.

Adolescent↗