Search

Objectives: We linked databases to improve identification of American Indians/Alaska Natives (AI/ANs) in determining prostate cancer death and incidence rates., Methods: We linked prostate cancer mortality and incidence data with Indian Health Service (IHS) patient records; analyses focused on residents of IHS Contract Health Service Delivery Area (CHSDA) counties. We calculated age-adjusted incidence and death rates for AI/AN and White men for 1999 to 2009; men of Hispanic origin were excluded., Results: Prostate cancer death rates were higher for AI/AN men than for White men. Death rates declined for White men (-3.0% per year) but not for AI/AN men. AI/AN men had lower prostate cancer incidence rates than White men. Incidence rates declined among Whites (-2.2% per year) and AI/ANs (-1.9% per year)., Conclusions: AI/AN men had higher prostate cancer death rates and lower prostate cancer incidence rates than White men. Disparities in accessing health care could contribute to mortality differences, and incidence differences could be related to lower prostate-specific antigen testing rates among AI/AN men.

Background: Pediatric melanoma rates are increasing nationally. Our purpose was to determine the incidence of melanoma in New Mexico's (NM's) American Indian, Hispanic, and non-Hispanic white children., Methods: A retrospective review (1981 to 2009) of the NM Tumor Registry was conducted. Melanomas diagnosed in children <19 years of age were identified. Average annual age-adjusted incidence rates per million were calculated., Results: Sixty-four cases were identified. Rates per million were 7.4 for non-Hispanic whites, 2.1 for Hispanics, and 3.3 for American Indians. Fifty-nine percent were women. Fifty-five (86%) cases were localized, 6 (9%) were regional, and 1 (3%) case was metastatic. Majority of cases (49/64; 77%) occurred in children >14 years of age. American Indians presented with thicker melanomas as compared to whites and Hispanics., Conclusions: Incidence rates for pediatric melanoma in NM are highest for non-Hispanic whites. Distant metastasis is uncommon. Melanoma in children is rare, but practitioners must be aware of its occurrence for prompt diagnosis and treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The purpose of this study was to examine individual differences in eye-movement behavior. Six metrics (Fixation Rate, Duration, and Size; Saccade Amplitude; Micro-Saccade Rate and Amplitude) were used to measure individuals' eye-movement behavior profiles (EmBP). We replicate previous research (Andrews & Coppola, 1999; Castelhano & Henderson, 2008) by finding consistent individual differences in fixation duration and saccade amplitude across tasks, and present new findings of stable idiosyncrasies in measures of fixational eye-movement (Fixation Size, Micro-Saccade Rate and Amplitude). Moreover, we observed consistent inter-metric correlations across tasks (e.g., individuals that exhibited relatively high Fixation Rates also presented relative low Micro-Saccade Rates and relatively high Micro-Saccade Amplitudes). Factor Analysis linked the six EmBP metrics together with a single factor, which we speculate might be related to the operational effectiveness of the attentional system, given that individual factor scores were correlated with scores on a self-report measure of attentional function. Normal subjects with relatively high scores on this attention-deficit measure exhibited relatively frequent fixations of short duration and large spatial extent, and relatively infrequent micro-saccades of large amplitude. This EmBP is similar to a general pattern of eye-movement behavior observed with ADHD individuals - difficulty controlling eye movements, maintaining fixation, and inhibiting intrusive saccades. Results of this study indicate that normal individuals exhibit idiosyncratic EmBPs that are quite stable across tasks and are related to attentional ability., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Mouse lemurs are non-human primate models of cerebral aging and neurodegeneration. Much smaller than other primates, they recapitulate numerous features of human brain aging, including progressive cerebral atrophy and correlation between regional atrophy and cognitive impairments. Characterization of brain atrophy in mouse lemurs has been done by MRI measures of regional CSF volume and by MRI measures of regional atrophy. Here, we further characterize mouse lemur brain aging using ex vivo MR microscopy (31 µm in-plane resolution). First, we performed a non-biased, direct volumetric quantification of dentate gyrus and extended Ammon's horn. We show that both dentate gyrus and Ammon's horn undergo an age-related reorganization leading to a growth of the dentate gyrus and an atrophy of the Ammon's horn, even in the absence of global hippocampal atrophy. Second, on these first MR microscopic images of the mouse lemur brain, we depicted cortical and hippocampal hypointense spots. We demonstrated that their incidence increases with aging and that they correspond either to amyloid deposits or to cerebral microhemorrhages.

Purpose: SEER (Surveillance, Epidemiology and End Results) is the leading source of population level data on prostate cancer, including the positive surgical margin incidence at radical prostatectomy. Recently studies showed wide ranges in positive surgical margin rates among individual registries, which we hypothesized was the result of coding inaccuracies. Thus, we systematically audited SEER prostate cancer data., Materials and Methods: The New Mexico Tumor Registry, a SEER core registry, was queried for incident prostate cancer cases in 2007 that met certain criteria, including 1) adenocarcinoma histology, 2) malignant behavior and 3) radical prostatectomy as the first course of therapy. Pathological stage codes were audited by examining original radical prostatectomy pathology reports in accordance with SEER coding guidelines. The incidence and sites of positive surgical margins were critically analyzed., Results: Of the 305 cases that met all study inclusion criteria with complete source documents available 92 (30%) were coded incorrectly. The most common error was failure to properly account for surgical margin status (46 of 92 cases or 50%). The incidence of positive surgical margins in organ confined disease cases was 13% by SEER coding rules but 28% by a more clinical definition of positive surgical margins (p<0.001). In organ confined cases positive surgical margins occurred principally at the apex but in nonorgan confined cases most were multifocal., Conclusions: In this SEER registry 30% of radical prostatectomy cases in 2007 were coded inaccurately. SEER coding guidelines result in underestimating the positive surgical margin incidence. Clinicians and investigators should recognize the limitations of tumor registry data on positive surgical margins., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Expeditions organized by commercial companies are becoming increasingly popular. Charity expeditions take inexperienced participants on trips all over the world, with participants being sponsored to raise funds for charitable causes. The incidence of illness or injury while participating in charity expeditions is unknown. The objective of this study is to report the incidence and severity of illness and injuries occurring on worldwide charity expeditions., Methods: Retrospective, observational study reviewing expedition medical reports from 232 expeditions organized by a single commercial expedition company for a 5-year period (January 1, 2004 through December 31, 2008)., Results: Complete expedition medical reports were available for 210 (91%) trips, involving 4077 participants over 1524 expedition days. Expeditions reported a total of 1564 incidents over 42482 participant-days in the field, including days spent traveling to the expedition site. In 1465 (94%) cases "minor" injury or illness was recorded, 79 (5%) "moderate," and 20 (1%) "major" in severity. No deaths were reported. Gastrointestinal upset was the commonest reported minor condition and severe acute mountain sickness the commonest major condition. Overall, the incidence per 1000 participant-days of minor illness or injury was 34.48, moderate illness or injury 1.86, and major illness or injury 0.47., Conclusion: The risk of sustaining major injury or illness on an overseas charity expedition is low. The consequences of becoming injured or unwell in a remote environment can be serious, and appropriate medical care is required., (Copyright © 2010 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Background: Dexmedetomidine has been increasingly used as an adjunct to opioid-propofol total intravenous anesthesia (TIVA). The authors tested the hypothesis and found that clinically relevant blood levels of dexmedetomidine do not produce significant attenuation of the amplitude of transcranial electric motor-evoked potentials either independently or by interaction with propofol in a dose-dependent manner., Methods: The authors planned to recruit 72 patients with idiopathic scoliosis who had posterior spine fusion surgery during propofol and remifentanil TIVA with dexmedetomidine as an adjunct. However, the authors terminated the study after enrolling 44 patients because of change in surgical technique. Before administering dexmedetomidine, baseline transcranial electric motor-evoked potentials were acquired during TIVA with remifentanil and propofol. Patients were randomized to varying targeted blood levels of dexmedetomidine (0.4, 0.6, and 0.8 ng/ml) and propofol (2.5, 3.75, and 5 microg/ml) using a factorial design. The primary outcome variable was amplitude of transcranial electric motor-evoked potential. The secondary outcome was amplitude of cortical somatosensory-evoked potentials., Results: Of the 44 recruited patients, 40 completed the study, and their data were analyzed. The administration of dexmedetomidine in increasing doses as an adjunct to propofol-based TIVA caused a clinically and statistically significant attenuation of amplitudes of transcranial electric motor-evoked potentials., Conclusion: The authors conclude that under the stimulation conditions used, dexmedetomidine as an anesthetic adjunct to propofol-based TIVA at clinically relevant target plasma concentrations (0.6-0.8 ng/ml) can significantly attenuate the amplitude of transcranial electric motor-evoked potentials.

To measure the association between use of estrogenic botanical supplements and serum sex hormones in postmenopausal breast cancer survivors, a total 502 postmenopausal women were queried 2-3 years after breast cancer diagnosis about their use of botanical supplements, and supplements were categorized according to their estrogenic properties. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin. Adjusted means of the serum hormones were calculated by use of estrogenic supplements. Women reporting use of any estrogenic botanical supplement had significantly lower levels of estrone (20.8 vs. 23.6 pg/ml), estradiol (12.8 vs. 14.7 pg/ml), free estradiol (0.29 vs. 0.35 pg/ml), and DHEAS (47.7 vs. 56.2 microg/dl) compared to women reporting no use. Data from this cross-sectional study suggest the use of estrogenic botanical supplements may be associated with sex hormone concentrations in breast cancer survivors. Considering the high use of these supplements among breast cancer patients, further research is needed to clarify the relative estrogenicity/antiestrogenicity of these compounds and their relation with prognosis.

Objective: To measure the association between alcohol intake and 11 hormones and peptides in postmenopausal breast cancer survivors and to evaluate whether this association differs by tamoxifen use., Methods: Self-reported alcohol intake was assessed via food frequency questionnaire on average 30 months post-breast cancer diagnosis in 490 postmenopausal women from three western states. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, C-peptide, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3. Adjusted means of these hormones and peptides were calculated for categories of alcohol intake, overall and stratified by tamoxifen use., Results: The association between alcohol intake and serum hormone and peptide levels differed by tamoxifen use. We found statistically significant inverse associations between alcohol intake and both leptin and SHBG values but only among tamoxifen users. In women not using tamoxifen, we found a positive association between alcohol intake and DHEAS but no association in tamoxifen users., Conclusion: Tamoxifen may modify the association between alcohol intake and serum hormones and peptides. The significant associations found for DHEAS and SHBG are in a direction considered unfavorable for breast cancer prognosis. Postmenopausal breast cancer survivors may benefit from decreasing their alcohol intake.

Background: Adults with X-linked adrenoleukodystrophy (X-ALD) remain at risk for progressive neurological deterioration. Phenotypes vary in their pathology, ranging from axonal degeneration to inflammatory demyelination. The severity of symptoms is poorly explained by conventional imaging., Objective: To test the hypothesis that neurochemistry in normal-appearing brains differs in adult phenotypes of X-ALD and that neurochemical changes correlate with the severity of symptoms., Patients and Methods: Using a 7-Tesla scanner, we performed structural and proton magnetic resonance spectroscopic imaging in 13 adult patients with X-ALD: 4 patients with adult cerebral ALD, 5 patients with adrenomyeloneuropathy (AMN), and 4 female heterozygotes. Nine healthy controls were included., Results: Among adult X-ALD phenotypes, the myo-inositol to creatine ratio was 46% higher and the choline to creatine ratio was 21% higher in normal-appearing white matter of those with adult cerebral ALD compared with those with AMN (P < .05). Both N-acetylaspartate to creatine (P = .03) and glutamate to creatine (P = .04) ratios were lower in AMN patients than in controls. There were no significant differences between patients with AMN and female heterozygotes. In the cortex, patients with adult cerebral ALD had lower N-acetylaspartate to creatine ratios compared with female heterozygotes and controls (P = .02). The global myo-inositol to creatine ratio demonstrated a significant association with Expanded Disability Status Scale score (Spearman rho = 0.66, P = .04)., Conclusions: Seven-Tesla proton magnetic resonance spectroscopic imaging reveals differences in the neurochemistry of adult cerebral ALD but cannot distinguish AMN patients from female heterozygotes. Myo-inositol to creatine ratio correlates with the severity of the symptoms and may be a meaningful biomarker in adult X-ALD.

Background: Gallbladder cancer (GBC) is rare; however, it disproportionately affects the American Indian and Alaska Natives (AI/AN) population. The purpose of the study was to characterize GBC among AI/AN in the US population., Methods: Cases of GBC diagnosed between 1999 and 2004 and collected by state-based cancer registries were included. Registry records were linked with Indian Health Service (IHS) administration records to decrease race misclassification of AI/AN. GBC rates and/or percent distributions for AI/AN and non-Hispanic whites (NHW) were calculated by sex, IHS region, age, and stage for all US counties and IHS Contract Health Service Delivery Area (CHSDA) counties, in which approximately 56% of US AI/AN individuals reside., Results: In CHSDA counties, the GBC incidence rate among AI/AN was 3.3 per 100,000, which was significantly higher than that among NHW (P < .05). Rates varied widely among IHS regions and ranged from 1.5 in the East to 5.5 in Alaska. Rates were higher among AI/AN females than males in all regions, except the Northern Plains. Higher percentages of GBC were diagnosed among AI/AN aged <65 years compared with NHW. GBC was most often diagnosed at the regional stage among AI/AN, whereas GBC was most often diagnosed at regional or distant stages among NHW., Conclusions: To the authors' knowledge to date, this is the most comprehensive study of GBC incidence among AI/AN in the US. The accurate characterization of GBC in this population could help inform the development of interventions aimed at reducing morbidity and mortality from this disease.

It is shown that biological networks with serial regulation (each node regulated by at most one other node) are constrained to direct functionality, in which the sign of the effect of an environmental input on a target species depends only on the direct path from the input to the target, even when there is a feedback loop allowing for multiple interaction pathways. Using a stochastic model for a set of small transcriptional regulatory networks that have been studied experimentally, it is further found that all networks can achieve all functions permitted by this constraint under reasonable settings of biochemical parameters. This underscores the functional versatility of the networks.

Purpose: Long-term follow-up studies sometimes rely on retrospective identification of the cohort to be followed. Few such studies have been conducted, however, that rely on very old source records, perhaps because of concern that identification and location of a cohort based on very old records would not be feasible., Methods: The Hanford Thyroid Disease Study (HTDS), conducted in the 1990s, identified 5199 cohort members using Washington state birth records from 1940-1946. The limited information contained therein was used to trace cohort members to the present day, nearly 50 years later., Results: We found the best strategy to locate individuals efficiently is to use a combination of methods and resources in a phased approach, beginning with readily available and easy-to-use sources of information before employing more time-intensive strategies that are costly and rely on information that is difficult to obtain. Motor vehicle licensing records and directories were the most useful individual sources of information. Using this approach, the HTDS successfully located 94% of the 5199 cohort members identified., Conclusions: It is feasible to successfully trace and locate a very high proportion of individuals identified from very old records that contain little information.

Background: The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate annually to provide updated information on cancer occurrence and trends in the U.S. The 2007 report features a comprehensive compilation of cancer information for American Indians and Alaska Natives (AI/AN)., Methods: Cancer incidence data were available for up to 82% of the U.S. population. Cancer deaths were available for the entire U.S. population. Long-term (1975 through 2004) and fixed-interval (1995 through 2004) incidence and mortality trends were evaluated by annual percent change using regression analyses (2-sided P < .05). Cancer screening, risk factors, socioeconomic characteristics, incidence data, and stage were compiled for non-Hispanic whites (NHW) and AI/AN across 6 regions of the U.S., Results: Overall cancer death rates decreased by 2.1% per year from 2002 through 2004, nearly twice the annual decrease of 1.1% per year from 1993 through 2002. Among men and women, death rates declined for most cancers. Among women, lung cancer incidence rates no longer were increasing and death rates, although they still were increasing slightly, were increasing at a much slower rate than in the past. Breast cancer incidence rates in women decreased 3.5% per year from 2001 to 2004, the first decrease observed in 20 years. Colorectal cancer incidence and death rates and prostate cancer death rates declined, with colorectal cancer death rates dropping more sharply from 2002 through 2004. Overall, rates for AI/AN were lower than for NHW from 1999 through 2004 for most cancers, but they were higher for cancers of the stomach, liver, cervix, kidney, and gallbladder. Regional analyses, however, revealed high rates for AI/AN in the Northern and Southern Plains and Alaska. For cancers of the breast, colon and rectum, prostate, and cervix, AI/AN were less likely than NHW to be diagnosed at localized stages., Conclusions: For all races/ethnicities combined in the U.S., favorable trends in incidence and mortality were noted for lung and colorectal cancer in men and women and for breast cancer in women. For the AI/AN population, lower overall cancer incidence and death rates obscured important variations by geographic regions and less favorable healthcare access and socioeconomic status. Enhanced tobacco control and cancer screening, especially in the Northern and Southern Plains and Alaska, emerged as clear priorities.

Objectives: Recently, disparities related to ethnicity and rural place of residence for initial treatment and mortality of non-small cell lung cancer (NSCLC) have been reported. As a large proportion of residents in New Mexico are either Hispanic or reside in rural areas, we hypothesized that mortality of patients with early stage NSCLC would be higher in New Mexico compared to other areas of the country., Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Program registry to compare mortality from Stages 1A-2B NSCLC in New Mexico to other SEER registries between 1988-1997, and determined whether differences were related to demographics, tumor stage, place of residence, ethnicity, or receipt of surgical treatment. Data was collected from nine SEER registries functioning during the entire targeted period of 1988-1997., Results: Cases in the New Mexico Registry had a greater mortality risk (adjusted HR 1.22, CI 1.12-1.32) compared to cases enrolled in the other SEER registries. This higher risk was related to less cancer-directed surgery in New Mexico SEER patients, and a shift toward greater proportions of elderly and Stage 1B cases in New Mexico. Rural Stage 1B cases also exhibited greater risk than urban cases. Ethnic differences did not contribute to the higher mortality risk observed in New Mexico cases, although rural Hispanics had a higher mortality risk than urban Hispanics., Conclusions: These findings suggest a regional disparity in treatment and mortality risk for early stage NSCLC in New Mexico compared to the rest of the country.

Objective: The New Mexico Tumor Registry (NMTR) and Surveillance, Epidemiology and End Results (SEER) registries were utilized to determine (30+)-year trends in gestational trophoblastic disease and choriocarcinoma., Study Design: Age-adjusted incidence rates of gestational trophoblastic disease per 100,000 woman-years (1973-2003) and ratios per live births and pregnancies were calculated using data abstracted from the NMTR and state vital records. SEER data (1973-2002) were used to calculate age-adjusted incidence rates, estimated annual percentage change (EAPC) and relative survival rates for choriocarcinoma., Results: In New Mexico there were 1,153 cases affecting 377 non-Hispanic whites, 504 Hispanics and 241 American Indians, with respective incidence rates of 3.494, 5.150 and 9.991 (p < 0.0001). American Indian incidence rates decreased 53.3%, from 13.34 (1988-1992) to 6.23 (1998-2002). Within SEER (1973-2002), there were 504 gestational choriocarcinomas. The 30-year incidence rate was 0.132 and decreased by 37.7% (EAPC, -2.1% per year; p=0.0001)-by 40.1% for whites, 55.9% for blacks and 62.1% for others. However, over the previous 10 years, rates among blacks (0.097 vs. 0.259, p = 0.01) and for distant disease (0.044 vs. 0.071, p = 0.046) increased., Conclusion: Disparities in incidence rates by race/ethnicity in New Mexico are decreasing. An increase in rates among blacks and distant disease diagnosis may be the consequence of fewer regional trophoblastic centers in the United States.

As a background for understanding the increased incidence of melanoma, relevant information focuses on incidence, morality, environmental factors, host factors, and genetic factors. Incidence has increased dramatically; however, it is not clear to what extent changes in behavior, in the environment, or in early detection are involved. The major environmental factor, ultraviolet radiation exposure, shows surprisingly modest risks for developing melanoma, approximately 1.7-fold, and so focus is turning to interactions of exposure with host factors, including genetic factors. The major host factors associated with the development of melanoma include skin type and numbers of nevi (as well as atypical nevi). Genetic factors associated with familial melanoma have been well described and new attention, not yet validated, is being paid to low penetrant genes and their polymorphisms.

Background: Elucidating gene regulatory networks is crucial for understanding normal cell physiology and complex pathologic phenotypes. Existing computational methods for the genome-wide "reverse engineering" of such networks have been successful only for lower eukaryotes with simple genomes. Here we present ARACNE, a novel algorithm, using microarray expression profiles, specifically designed to scale up to the complexity of regulatory networks in mammalian cells, yet general enough to address a wider range of network deconvolution problems. This method uses an information theoretic approach to eliminate the majority of indirect interactions inferred by co-expression methods., Results: We prove that ARACNE reconstructs the network exactly (asymptotically) if the effect of loops in the network topology is negligible, and we show that the algorithm works well in practice, even in the presence of numerous loops and complex topologies. We assess ARACNE's ability to reconstruct transcriptional regulatory networks using both a realistic synthetic dataset and a microarray dataset from human B cells. On synthetic datasets ARACNE achieves very low error rates and outperforms established methods, such as Relevance Networks and Bayesian Networks. Application to the deconvolution of genetic networks in human B cells demonstrates ARACNE's ability to infer validated transcriptional targets of the cMYC proto-oncogene. We also study the effects of misestimation of mutual information on network reconstruction, and show that algorithms based on mutual information ranking are more resilient to estimation errors., Conclusion: ARACNE shows promise in identifying direct transcriptional interactions in mammalian cellular networks, a problem that has challenged existing reverse engineering algorithms. This approach should enhance our ability to use microarray data to elucidate functional mechanisms that underlie cellular processes and to identify molecular targets of pharmacological compounds in mammalian cellular networks.

Purpose: Familial melanoma patients are reported to present with thinner melanomas, to be younger at the time of diagnosis, and to have a greater likelihood of developing multiple primary tumors. We sought to determine whether melanomas that occur in a familial setting demonstrate different prognostic and survival statistics relative to sporadic melanoma., Patients and Methods: This population-based study used the Utah Cancer Registry and Utah Population Database to objectively evaluate prognostic and survival statistics of the familial melanoma population. From 1973 to 1999, there were 7,785 cases of invasive melanoma identified through the Utah Cancer Registry. These were linked to the Utah Population Database, resulting in 2,659 subjects with family-history information from which a familiality score could be calculated. Cases scored in the top ninth percentile were assigned as high familial risk, and the remaining 91% were considered low familial risk., Results: Multivariate logistic-regression analysis found no association between sex, Breslow depth, Clark level, or survival and the familial status. Age at first diagnosis of invasive melanoma was slightly lower in the high-familial-risk group (57 v 60 years; P = .03). High-familial-risk subjects had more melanomas diagnosed at age 30 or younger (12% v 6%; P < .001). A significant difference in the overall number of individuals with two or more primary malignant melanomas was not detected among the groups (P = .2)., Conclusion: These data suggest that melanomas occurring in the context of an underlying inherited susceptibility do not have a significantly different biologic behavior.

Our goal is to cluster genes into transcriptional modules--sets of genes where similarity in expression is explained by common regulatory mechanisms at the transcriptional level. We want to learn modules from both time series gene expression data and genome-wide motif data that are now readily available for organisms such as S. cereviseae as a result of prior computational studies or experimental results. We present a generative probabilistic model for combining regulatory sequence and time series expression data to cluster genes into coherent transcriptional modules. Starting with a set of motifs representing known or putative regulatory elements (transcription factor binding sites) and the counts of occurrences of these motifs in each gene's promoter region, together with a time series expression profile for each gene, the learning algorithm uses expectation maximization to learn module assignments based on both types of data. We also present a technique based on the Jensen-Shannon entropy contributions of motifs in the learned model for associating the most significant motifs to each module. Thus, the algorithm gives a global approach for associating sets of regulatory elements to "modules" of genes with similar time series expression profiles. The model for expression data exploits our prior belief of smooth dependence on time by using statistical splines and is suitable for typical time course data sets with relatively few experiments. Moreover, the model is sufficiently interpretable that we can understand how both sequence data and expression data contribute to the cluster assignments, and how to interpolate between the two data sources. We present experimental results on the yeast cell cycle to validate our method and find that our combined expression and motif clustering algorithm discovers modules with both coherent expression and similar motif patterns, including binding motifs associated to known cell cycle transcription factors.

An eight-channel receive-only brain coil and table-top detunable volume transmit coil were developed and tested at 7 T for human imaging. Optimization of this device required attention to sources of interaction between the array elements, between the transmit and receive coils and minimization of common mode currents on the coaxial cables. Circular receive coils (85 mm dia.) were designed on a flexible former to fit tightly around the head and within a 270-mm diameter TEM transmit volume coil. In the near cortex, the array provided a fivefold increase in SNR compared to a TEM transmit-receive coil, a gain larger than that seen in comparable coils at 3 T. The higher SNR gain is likely due to strong dielectric effects, which cause the volume coil to perform poorly in the cortex compared to centrally. The sensitivity and coverage of the array is demonstrated with high-resolution images of the brain cortex.

Previous studies have shown that under some conditions, noise fluctuations in an fMRI time-course are dominated by physiological modulations of the image intensity with secondary contributions from thermal image noise and that these two sources scale differently with signal intensity, susceptibility weighting (TE) and field strength. The SNR of the fMRI time-course was found to be near its asymptotic limit for moderate spatial resolution measurements at 3 T with only marginal gains expected from acquisition at higher field strengths. In this study, we investigate the amplitude of image intensity fluctuations in the fMRI time-course at magnetic field strengths of 1.5 T, 3 T, and 7 T as a function of image resolution, flip angle and TE. The time-course SNR was a similar function of the image SNR regardless of whether the image SNR was modulated by flip angle, image resolution, or field strength. For spatial resolutions typical of those currently used in fMRI (e.g., 3 x 3 x 3 mm(3)), increases in image SNR obtained from 7 T acquisition produced only modest increases in time-course SNR. At this spatial resolution, the ratio of physiological noise to thermal image noise was 0.61, 0.89, and 2.23 for 1.5 T, 3 T, and 7 T. At a resolution of 1 x 1 x 3 mm(3), however, the physiological to thermal noise ratio was 0.34, 0.57, and 0.91 for 1.5 T, 3 T and 7 T for TE near T2*. Thus, by reducing the signal strength using higher image resolution, the ratio of physiologic to image noise could be reduced to a regime where increased sensitivity afforded by higher field strength still translated to improved SNR in the fMRI time-series.

We present a graph embedding space (i.e., a set of measures on graphs) for performing statistical analyses of networks. Key improvements over existing approaches include discovery of "motif hubs" (multiple overlapping significant subgraphs), computational efficiency relative to subgraph census, and flexibility (the method is easily generalizable to weighted and signed graphs). The embedding space is based on scalars, functionals of the adjacency matrix representing the network. Scalars are global, involving all nodes; although they can be related to subgraph enumeration, there is not a one-to-one mapping between scalars and subgraphs. Improvements in network randomization and significance testing--we learn the distribution rather than assuming Gaussianity--are also presented. The resulting algorithm establishes a systematic approach to the identification of the most significant scalars and suggests machine-learning techniques for network classification.

Background: Recent genomic and bioinformatic advances have motivated the development of numerous network models intending to describe graphs of biological, technological, and sociological origin. In most cases the success of a model has been evaluated by how well it reproduces a few key features of the real-world data, such as degree distributions, mean geodesic lengths, and clustering coefficients. Often pairs of models can reproduce these features with indistinguishable fidelity despite being generated by vastly different mechanisms. In such cases, these few target features are insufficient to distinguish which of the different models best describes real world networks of interest; moreover, it is not clear a priori that any of the presently-existing algorithms for network generation offers a predictive description of the networks inspiring them., Results: We present a method to assess systematically which of a set of proposed network generation algorithms gives the most accurate description of a given biological network. To derive discriminative classifiers, we construct a mapping from the set of all graphs to a high-dimensional (in principle infinite-dimensional) "word space". This map defines an input space for classification schemes which allow us to state unambiguously which models are most descriptive of a given network of interest. Our training sets include networks generated from 17 models either drawn from the literature or introduced in this work. We show that different duplication-mutation schemes best describe the E. coli genetic network, the S. cerevisiae protein interaction network, and the C. elegans neuronal network, out of a set of network models including a linear preferential attachment model and a small-world model., Conclusions: Our method is a first step towards systematizing network models and assessing their predictability, and we anticipate its usefulness for a number of communities.

Motivation: Studying gene regulatory mechanisms in simple model organisms through analysis of high-throughput genomic data has emerged as a central problem in computational biology. Most approaches in the literature have focused either on finding a few strong regulatory patterns or on learning descriptive models from training data. However, these approaches are not yet adequate for making accurate predictions about which genes will be up- or down-regulated in new or held-out experiments. By introducing a predictive methodology for this problem, we can use powerful tools from machine learning and assess the statistical significance of our predictions., Results: We present a novel classification-based method for learning to predict gene regulatory response. Our approach is motivated by the hypothesis that in simple organisms such as Saccharomyces cerevisiae, we can learn a decision rule for predicting whether a gene is up- or down-regulated in a particular experiment based on (1) the presence of binding site subsequences ('motifs') in the gene's regulatory region and (2) the expression levels of regulators such as transcription factors in the experiment ('parents'). Thus, our learning task integrates two qualitatively different data sources: genome-wide cDNA microarray data across multiple perturbation and mutant experiments along with motif profile data from regulatory sequences. We convert the regression task of predicting real-valued gene expression measurements to a classification task of predicting +1 and -1 labels, corresponding to up- and down-regulation beyond the levels of biological and measurement noise in microarray measurements. The learning algorithm employed is boosting with a margin-based generalization of decision trees, alternating decision trees. This large-margin classifier is sufficiently flexible to allow complex logical functions, yet sufficiently simple to give insight into the combinatorial mechanisms of gene regulation. We observe encouraging prediction accuracy on experiments based on the Gasch S.cerevisiae dataset, and we show that we can accurately predict up- and down-regulation on held-out experiments. We also show how to extract significant regulators, motifs and motif-regulator pairs from the learned models for various stress responses. Our method thus provides predictive hypotheses, suggests biological experiments, and provides interpretable insight into the structure of genetic regulatory networks., Availability: The MLJava package is available upon request to the authors. Supplementary: Additional results are available from http://www.cs.columbia.edu/compbio/geneclass

We study the relaxation dynamics of a semiflexible chain by introducing a time-dependent tension. The chain has one of its ends attached to a large bead, and the other end is fixed. We focus on the initial relaxation of the chain that is initially strongly stretched. Using a tension that is self-consistently determined, we obtain the evolution of the end-to-end distance with no free parameters. Our results are in good agreement with single molecule experiments on double stranded DNA.

Does gender by itself, or does gender's interaction with career variables, better explain the difference between women and men's careers in healthcare management? US healthcare managers were surveyed regarding career and personal experiences. Gender was statistically interacted with explanatory variables. Multiple regression with backwards selection systematically removed non-significant variables. All gender interaction variables were non-significant. Much of the literature proposes that work and career factors impact working women differently than working men. We find that while gender alone is a significant predictor of income, it does not significantly interact with other career variables.

Cytoarchitectonic fields of the human neocortex are defined by characteristic variations in the composition of a general six-layer structure. It is commonly accepted that these fields correspond to functionally homogeneous entities. Diligent techniques were developed to characterize cytoarchitectonic fields by staining sections of post-mortem brains and subsequent statistical evaluation. Fields were found to show a considerable interindividual variability in extent and relation to macroscopic anatomical landmarks. With upcoming new high-resolution magnetic resonance imaging (MRI) protocols, it appears worthwhile to examine the feasibility of characterizing the neocortical fine-structure from anatomical MRI scans, thus, defining neocortical fields by in vivo techniques. A fixated brain hemisphere was scanned at a resolution of approximately 0.3 mm. After correcting for intensity inhomogeneities in the dataset, the cortex boundaries (the white/grey matter and grey matter/background interfaces) were determined as a triangular mesh. Radial intensity profiles following the shortest path through the cortex were computed and characterized by a sparse set of features. A statistical similarity measure between features of different regions was defined, and served to define the extent of Brodmann's Areas 4, 17, 44 and 45 in this dataset.

Skin graft donor sites are partial-thickness wounds that are commonly managed with gauze-type dressings. As such, they often cause more pain and difficulty in healing than the graft-recipient site. A retrospective study was conducted to ascertain the effects of using a castor oil-balsam of Peru-trypsin containing ointment on skin graft donor sites in 36 consecutive patients (16 female, 20 male). All donor sites were epithelialized after 11 days (range 6 to 11 days, mean 8 days) and no wound complications were observed. Given these healing results and product ease of use, this particular formulation has become the facilities' current treatment of choice and further study is indicated and warranted.

Background and Purpose: Diffuse axonal injury is frequently accompanied by tissue tear hemorrhages. We examined whether high field strength T2*-weighted gradient-echo imaging performed during the chronic stage of traumatic brain injury may have advantages in the evaluation of diffuse axonal injury as compared with T1- and T2-weighted MR imaging., Methods: Prospective MR imaging of 66 patients (age range, 17-57 years) was performed using a 3-T system 3 to 292 months (median, 23.5 months) after traumatic brain injury. T1-, T2-, T2*-hypointense and T2-hyperintense foci of 1- to 15-mm diameter were registered in 10 brain regions by two readers separately. Foci that appeared hypointense both on the T1- and T2- and/or on the T2*-weighted images were defined as traumatic microbleeds., Results: For 46 (69.7%) of the patients, T2*-weighted gradient-echo imaging revealed traumatic microbleeds. Hyperintense foci were observed on the T2-weighted images of only 15 (22.7%) patients. T2*-weighted imaging showed significantly more traumatic microbleeds (P =.000) than did T1- and T2-weighted imaging. Interobserver agreement was strong (kappa = 0.79, tau = 0.749, P =.000). For 14 (21.2%) of the patients, T2*-weighted gradient-echo imaging revealed traumatic microbleeds in the corpus callosum, whereas for only two (3%), hyperintense callosal lesions were seen on the T2-weighted images. Although a significant correlation existed between the total amount and callosal appearance of traumatic microbleeds and Glasgow Coma Scale scores (P =.000), no correlation existed with extended Glasgow Outcome Scale scores., Conclusion: T2*-weighted gradient-echo imaging at high field strength is a useful tool for the evaluation of diffuse axonal injury during the chronic stage of traumatic brain injury. Diffuse axonal injury-related brain lesions are mainly hemorrhagic. The relevance of diffuse axonal injury for long-term clinical outcome is uncertain.

Successful survival in a competitive world requires the employment of efficient procedures for selecting new in preference to old information. Recent behavioral studies have shown that efficient selection is dependent not only on properties of new stimuli but also on an intentional bias that we can introduce against old stimuli. Event-related analysis of functional magnetic resonance imaging data from a task involving visual search across time as well as space indicates that the superior parietal lobule is specifically involved in processes leading to the efficient segmentation of old from new items, whereas the temporoparietal junction area and the ascending limb of the right intraparietal sulcus are involved in the detection of salient new items and in response preparation. The study provides evidence for the functional segregration of brain regions within the posterior parietal lobe.

Germinal vesicle (GV)-stage horse oocytes with diffuse chromatin are meiotically incompetent and degenerate in culture, whereas horse oocytes having condensed chromatin within the GV are meiotically competent. Degeneration of incompetent oocytes in culture may be related to premature GV breakdown, which could possibly be prevented by inhibition of m-phase protein activity. We examined the effects of 6-dimethylaminopurine (6-DMAP), butyrolactone and roscovitine on GV-stage horse oocytes. Culture in the presence of 2 mM 6-DMAP for 24 h suppressed meiosis (2% MI or MII compared with 38% for untreated oocytes). The proportion of GV-stage oocytes having condensed chromatin was not different between 6-DMAP culture and directly fixed controls; however, the proportion of oocytes with diffuse chromatin was significantly lower, and more oocytes with diffuse chromatin had atypical chromatin than did controls (p < 0.01). Culture with butyrolactone at 100 microM suppressed meiosis (5% MI + II). Again, this treatment maintained GV-stage oocytes having condensed chromatin, but the proportion of oocytes with diffuse chromatin was significantly reduced compared with directly fixed controls (p < 0.05). Culture with roscovitine at 25 microM was also effective in maintaining GV-stage oocytes having condensed chromatin; however, culture with 100 microM roscovitine did not suppress meiosis or maintain oocytes in the GV stage. These results indicate that meiosis in GV-stage horse oocytes having condensed chromatin may be suppressed by inhibitors of m-phase protein activity; however, oocytes originally having diffuse chromatin appear to degenerate in culture even in the presence of these inhibitors.

Enterprise resource planning (ERP) systems provide organizations with the opportunity to integrate individual, functionally-oriented information systems. Although much of the focus in the popular press has been placed on ERP systems in large for-profit organizations, small hospitals and clinics are candidates for ERP systems. Focusing information systems on critical success factors (CSFs) allows the organization to address a limited number of areas associated with performance. This limited number of factors can provide management with an insight into dimensions of information that must be addressed by a system. Focuses on CSFs for small health-care organizations. In addition, also considers factors critical to the implementation of health-care information systems. Presents two cases. The results indicate support for the continuing use of CSFs to help focus on the benefits of ERPs. Focusing on groups of tangible and intangible benefits can also assist the rural health-care organization in the use of ERPs.

The feasibility of recording event-related potentials (ERP) during functional MRI (fMRI) scanning using higher level cognitive stimuli was studied. Using responses to illusory figures in a visual oddball task, evoked potentials were obtained with their expected configurations and latencies. A rapid stimulation scheme using randomly varied trial lengths was employed, and class-wise characteristics of the hemodynamic response were obtained by a nonlinear analysis of the fMRI time series. Implications and limitations of conducting combined ERP-fMRI experiments using higher level cognitive stimuli are discussed. EEG/fMRI results revealed a sequential activation of striate and extrastriate occipital cortex along the ventral path of object processing for Kanizsa figures. Interestingly, Kanizsa figures activated the human motion area MT. Targets resulted in activations of frontal and parietal cortex which were not activated for standard stimuli., (Copyright 2001 Academic Press.)

The aim of this study was to adapt the balloon model for BOLD-based MR signal changes to a magnetic field strength of 3T and to examine its validity. The simultaneous measurement of BOLD and diffusion-weighted BOLD responses was performed. The amplitude of the BOLD peak was found to be similar for all subjects when a short visual stimulus of 6 sec was used. The rise-time to the BOLD peak and the shape and depth of the poststimulus undershoot varied significantly. A fit of the experimental BOLD responses was found to be possible by use of parameters within a reasonable physiological range. The relations between these parameters and their influence on the modeled BOLD responses is discussed. A prediction of the balloon model is the occurrence of a BOLD overshoot, i.e., a lag between the changes of the blood volume and the blood flow after the start of the stimulation. Experimental evidence for the existence of a BOLD overshoot is presented., (Copyright 2001 Wiley-Liss, Inc.)

When shaken vertically, a hanging chain displays a startling variety of distinct behaviors. We find experimentally that instabilities occur in tonguelike bands of parameter space, to swinging or rotating pendular motion, or to chaotic states. Mathematically, the dynamics are described by a nonlinear wave equation. A linear stability analysis predicts instabilities within the well-known resonance tongues; their boundaries agree very well with experiment. Full simulations of the 3D dynamics reproduce and elucidate many aspects of the experiment. The chain is also observed to tie knots in itself, some quite complex. This is beyond the reach of the current analysis and simulations.

A cognitive task can often be subdivided into several subprocesses, which follow a specific temporal order. Here, we report an event-related functional magnetic resonance imaging (fMRI) experiment on memory search, in which the temporal onset of search in primary memory was varied relative to retrieval from secondary memory. Furthermore, previous behavioral studies demonstrated that search times in primary memory depend on the number of items in a memory set, whereas retrieval from secondary memory is a set-size independent process. We analyzed the dependency of the blood oxygenation level dependent (BOLD)-response on the temporal onset of memory search on the one hand and on memory set size on the other hand to differentiate the contribution of retrieval from secondary memory, maintenance in primary memory, item search in primary memory, and response-related processes. The timing of activation followed cue presentation bilaterally in the middle frontal gyri (Brodmann area (BA) 9,46) and the inferior parts of the precentral gyri (BA6). In all other regions of interest (ROI), supplementary motor area (SMA), posterior parietal cortex, antero-superior insula, and primary motor cortex, the onset of activation was delayed with delayed probe presentation, ruling out participation in retrieval from secondary memory. The amplitude of the BOLD-response increased with increasing memory set size in all ROI except primary motor cortex and left posterior parietal cortex. All areas with cue-associated BOLD onset, suggesting involvement in retrieval, showed prolonged BOLD activation, suggesting that they also support maintenance of the retrieved information., (Copyright 2000 Wiley-Liss, Inc.)

PURPOSE: This paper presents a cross-sectional method for deriving age-specific hysterectomy prevalence. The influence of hysterectomy prevalence on uterine and ovarian cancer incidence rates and probabilities is illustrated.METHODS: Hysterectomy prevalence estimates are derived from cross-sectional data using a life table method. Analysis is based on hysterectomy data from the Utah Hospital Discharge Data Base and cancer cases recorded by the Utah Cancer Registry, 1995-1997.RESULTS: Correction for hysterectomy prevalence increases cancer incidence rates, more so at older ages, such that by ages 85 and older the increase is 92% for uterine cancers of the cervix and corpus, and 17% for ovarian cancer. Over the life span, correction for hysterectomy prevalence increases the estimated number per 100,000 developing these diseases by 195 (from 603 to 798) for uterine cervical cancer, 1,553 (from 2,580 to 4,133) for corpus uterine cancer, and 911 (1,674 to 2,585) for ovarian cancer.CONCLUSIONS: The utility of the cross-sectional method for deriving hysterectomy prevalence is that it does not require several years of data to obtain reasonable estimates. Correction for hysterectomy prevalence has a large effect on the cancer rates and probabilities, providing a more accurate representation of the risk and burden of these cancers.

Abnormalities in the brain of patients with thrombotic thrombocytopenic purpura (TTP) are infrequent on MRI, often reversible and mainly limited to symptomatic stages of the disease. We report a case in which high-resolution MRI demonstrated multiple persistent small cortical infarcts after clinical remission. High-resolution MRI investigations may detect clinically latent but permanent brain damage, and complement clinical judgement in guiding therapeutic decisions.

The feasibility of recording event-related potentials (ERP) during functional MRI (fMRI) scanning was studied. Using an alternating checkerboard stimulus in a blocked presentation, visually evoked potentials were obtained with their expected configuration and latencies. A clustered echoplanar imaging protocol was applied to observe the hemodynamic response due to the visual stimulus interleaved with measuring ERPs. Influences of the electrode/amplifier set up on MRI scanning and the scanning process on the recording of electrophysiological signals are reported and discussed. Artifacts overlaid on the electrophysiological recordings were corrected by post hoc filtering methods presented here. Implications and limitations of conducting combined ERP/fMRI experiments using higher-level cognitive stimuli are discussed. Magn Reson Med 44:277-282, 2000., (Copyright 2000 Wiley-Liss, Inc.)

The plasma membrane of eukaryotic cells differs in lipid composition from most of the internal organelles, presumably reflecting differences in many of its functions. In particular, the plasma membrane is rich in sphingolipids and sterols, one property of which is to decrease the permeability and increase the thickness of lipid bilayers. In this paper, we examine the length of transmembrane domains throughout the yeast secretory pathway. Although the transmembrane domains of cis and medial Golgi residents are similar to those of endoplasmic reticulum proteins, these domains lengthen substantially beyond the medial Golgi, suggesting a thickening of the bilayer. Yeast sphingolipids have particularly long acyl chains, and Aur1p, the inositol phosphorylceramide synthase that initiates yeast sphingolipid synthesis, was found to be located in the Golgi apparatus by both immunofluorescence and membrane fractionation, with its active site apparently in the Golgi lumen. Thus, it appears that sphingolipid synthesis in yeast takes place in the Golgi, separated from glycerophospholipid synthesis in the endoplasmic reticulum. A similar separation has been found in mammalian cells, and this conservation suggests that such an arrangement of enzymes within the secretory pathway could be important for the creation of bilayers of different thickness within the cell.

Introduction: High-dose therapy with haematopoietic progenitor cell support has increasingly been utilised for patients with haematological malignancies. Peripheral blood is the stem cell source of choice, however, various mobilisation strategies are used by different centres., Patients and Methods: Over a 2-year period, 52 patients with non-Hodgkin's lymphoma (median age 47 years, range 16-64 years) underwent peripheral blood progenitor cell mobilisation using G-CSF alone (16 microg/kg/day). The harvest was considered successful if > or =1 x 10(6) CD34(+) cells/kg were collected by leukapheresis. The histological subtypes of non-Hodgkin's lymphoma comprised: follicular (24 patients), diffuse large B-cell (14 patients), lymphoplasmacytoid (four patients), mantle cell (three patients), lymphoblastic lymphoma (one patient) and small lymphocytic lymphoma/chronic lymphocytic leukaemia (six patients). The median interval from diagnosis of non-Hodgkin's lymphoma to mobilisation was 27 months (range 2 months to 17 years). The median number of prior treatment episodes was 2 (range 1-5); 26 patients had received fludarabine alone or in combination. At the time of peripheral blood progenitor cell mobilisation, 20 patients were in 1st remission and 32 were in > or =2nd remission; 30 patients were in partial remission and 22 were in complete remission; the bone marrow was involved in nine patients., Results: Peripheral blood progenitor cell mobilisation/harvest was unsuccessful in 19 out of 52 (37%) patients (mobilisation: 18, harvest: 1). The factors associated with unsuccessful mobilisation or harvest were: prior fludarabine therapy (P=0.002), bone marrow involvement at diagnosis (P=0.002), bone marrow involvement anytime prior to mobilisation (P=0.02), histological diagnosis of follicular, mantle cell, or lymphoplasmacytoid lymphoma, or small lymphocytic lymphoma/chronic lymphocytic leukaemia (P=0.03) and female gender (P=0.04)., Conclusion: Although peripheral blood progenitor cells can be successfully mobilised and harvested from the majority of patients with non-Hodgkin's lymphoma after treatment with G-CSF alone, the latter is unsuccessful in approximately one-third of patients. These factors should be taken into account when patients are being considered for high-dose treatment.

When a switch between two tasks has to be carried out, performance is slower than in trials where the same task is performed repeatedly. This finding has been attributed to time-consuming control processes required for task switching. Previous results of other paradigms investigating cognitive control processes suggested that prefrontal cortex is involved in executive control. We used event-related fMRI to investigate prefrontal cortex involvement in task switching. Regions in the lateral prefrontal and premotor cortex bilaterally, the anterior insula bilaterally, the left intraparietal sulcus, the SMA/pre-SMA region and the cuneus/precuneus were activated by the task repetition condition and showed additional activation in the task switch condition. This confirmed the hypothesis that lateral prefrontal cortex is involved in task switching. However, the results also showed that this region is neither the only region involved in task switching nor a region specifically involved in task switching.

The inverse relationship between the radiofrequency (RF) power needed to transmit a 90 degree RF pulse, and the signal-to-noise ratio (SNR) available from a transmit-receive RF coil is well known. The theory is restated and a formula given for the signal-to-noise ratio from water, achievable from a single-shot MRI experiment, in terms of the net forward RF power needed for a rectangular 90 degree RF pulse of known shape and duration. The result is normalized to a signal bandwidth of 1 Hz and a sample mass of 1 g. The RF power information needed is available on most commercial scanners, as it is used to calculate specific absorption rates for RF tissue heating. The achievable SNR figure will normally be larger that that actually observed, mainly because of receiver noise, but also because of inaccuracies in setting RF pulse angles, and relaxation effects. Phantom experiments were performed on the transmit-receive RF head coil of a commercial MRI system at 0.95 T using a projection method. The measured SNR agreed with that expected from the formula for achievable SNR once a correction was made for the noise figure of the receiving chain. Comparisons of measured SNR figures with those calculated from RF power measurements are expected to be of value in acceptance testing and quality control.

Recently, event-related fMRI-experiments have been reported in which subsequent trials were separated by only 2 sec or less. Because the BOLD response needs 10 sec and longer to return to baseline, the event-related signal in these experiments has to be extracted from the overlapping responses elicited by successive trials. Usually it is assumed that this convolved signal is a summation of the overlapping BOLD responses. We tested this assumption by comparing event-related signals in conditions with little and with substantial BOLD overlap in two fMRI experiments of a task-switching paradigm. We analyzed the difference in the activational time course elicited by a critical task and a baseline task when trials of both tasks were separated by intertrial intervals of 15 sec or when the critical trials were embedded in a stream of baseline trials with ISI = 1 sec. The change of the BOLD signal elicited by the critical trials showed a high correspondence between both experiments in five out of six cortical ROI. Our data support the view that BOLD overlap leads to largely linear signal changes. In the present study, task-related increases in the BOLD response were detected equally well with substantial BOLD overlap as with mostly nonoverlapping BOLD responses.