Investigating the predictive value of whole-brain structural MR scans in autism: A pattern classification approach

Autistic spectrum disorder (ASD) is accompanied by subtle and spatially distributed differences in brain anatomy that are difficult to detect using conventional mass-univariate methods (e.g., VBM). These require correction for multiple comparisons and hence need relatively large samples to attain sufficient statistical power. Reports of neuroanatomical differences from relatively small studies are thus highly variable. Also, VBM does not provide predictive value, limiting its diagnostic value.Here, we examined neuroanatomical networks implicated in ASD using a whole-brain classification approach employing a support vector machine (SVM) and investigated the predictive value of structural MRI scans in adults with ASD. Subsequently, results were compared between SVM and VBM. We included 44 male adults; 22 diagnosed with ASD using “gold-standard” research interviews and 22 healthy matched controls.SVM identified spatially distributed networks discriminating between ASD and controls. These included the limbic, frontal-striatal, fronto-temporal, fronto-parietal and cerebellar systems. SVM applied to gray matter scans correctly classified ASD individuals at a specificity of 86.0% and a sensitivity of 88.0%. Cases (68.0%) were correctly classified using white matter anatomy. The distance from the separating hyperplane (i.e., the test margin) was significantly related to current symptom severity. In contrast, VBM revealed few significant between-group differences at conventional levels of statistical stringency.We therefore suggest that SVM can detect subtle and spatially distributed differences in brain networks between adults with ASD and controls. Also, these differences provide significant predictive power for group membership, which is related to symptom severity.     

In vivo hematopoietic effects of recombinant interleukin-1 alpha in mice: stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythropoietin

Interleukin-1 alpha (IL-1 alpha) is a macrophage-derived, multifunctional cytokine that broadly potentiates myelopoiesis and induces the synthesis of hematopoietic colony-stimulating factors (CSF) in vitro and in vivo. To evaluate the possibility for use of IL-1 alpha in ameliorating in vivo bone marrow suppression induced by drugs or radiation, we examined the in vivo effects of the cytokine on erythropoietic and other hematopoietic progenitor cells. Normal mice were treated with a single intraperitoneal (IP) injection of recombinant human IL-1 alpha at varying doses and were assayed at various times post-treatment. By six hours postinjection, a significant suppression of mature erythroid progenitors (CFU-E) was observed in animals treated with IL-1 alpha (0.5 micrograms/mouse), with maximum suppression of CFU-E and peripheral blood reticulocyte counts occurring at 24 hours. Decreases in peripheral blood hematocrit did not occur after a single IL-1 alpha injection but were observed after multiple injections of the cytokine. The suppressive effects of IL-1 alpha on late-stage erythropoiesis were abrogated by simultaneous administration of erythropoietin (EPO). At 48 hours post-treatment, a marked stimulation was observed in the numbers of spleen and marrow immature erythroid (BFU-E), macrophage (CFU-M), granulocyte (CFU-G), granulocyte- macrophage (CFU-GM), and megakaryocyte (CFU-meg) progenitor cells. These results demonstrate the potential use of IL-1 alpha as a generalized stimulator of hematopoiesis and show that the cytokine- induced suppression of late-stage erythropoiesis can be prevented by EPO.     

IgG, albumin, and sCD44 in whole-gut lavage fluid are useful clinical markers for assessing the presence and activity of pouchitis

Pouchitis is the most significant long-term complication in patients with ileoanal pouch anastomosis (IAP) and is especially frequent in patients with ulcerative colitis. There is an urgent need for simple and objective parameters to assess the presence and activity of pouchitis. Whole-gut lavage fluid (WGLF) was collected from 34 patients [8 with pouchitis (PDAI > or = 7 points) and 26 without pouchitis (Pouchitis Disease Activity Index, PDAI, < 7)]. Patients with active ulcerative colitis (n = 8) served as controls. Concentrations of IgG and sCD44 in WGLF were measured by enzyme-linked immunosorbent assays and those of albumin by immunoturbidimetry. Similar to the case in active ulcerative colitis, concentrations of IgG, albumin, and sCD44 in WGLF were significantly increased in acute pouchitis and reached high specificity (IgG 96%, albumin 96%, sCD44 100%) and acceptable sensitivity (75%) for the diagnosis of acute pouchitis. These parameters were also closely correlated with disease activity as determined by PDAI and endoscopic scoring indices. Assay of protein concentrations in WGLF is thus a simple and objective means for grading inflammation of the pouch and may be useful as a quantitative index of disease activity in clinical studies.     

Surface versus needle electrodes in determination of motor conduction time to the external anal sphincter

Patients were referred to our neurophysiological department in order to investigate anorectal function. By the means of magnetic stimulation the total motor conduction can be determined. Only patients with normal latency of the pudendal nerve and normal EMG of the external anal sphincter were examined. Stimulation was carried out above the motor cortex with a MO between 80 and 100%. The recording was carried out in 22 patients with concentric needle electrodes and in the other 18 patients with surface electrodes. The mean latency in the group with surface electrodes was 19.4 ms (SD 1.7), and in the group with needle electrodes 23.4 ms (SD 4). Our results suggest, that in magnetic stimulation above the motor cortex and recording with a concentric needle electrode, the range and the mean was higher than with surface electrodes. In our opinion surface electrodes are preferable to needle electrodes in determining motor conduction time to the external anal sphincter.

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Résumé Qurante patients ont été adressés à notre département de Neurophysiologie dans le but d'investiguer la fonction ano-rectale. Par stimulation magnétique, le temps total de conduction motrice peut être déterminée. Seuls des patients avec un temps de latence du nerf honteux interne normal et avec un EMG du sphincter anal externe normal ont été étudiés. La stimulation avait été réalisée au-dessus du cortex moteur avec une MO allant de 80 à 110%. L'enregistrement a été réalisé chez 22 patients avec des aiguilles concentriques et chez 18 patients avec des électrodes de surface. Le temps de latence moyen dans le groupe de patients auxquels des électrodes de surface ont été appliquées était de 19,4 ms (DS 1,7) et dans le groupe investigué à l'aide d'électrodes concentriques de 23,4 ms (DS 4). Nos observations suggèrent que la stimulation magnétique au-dessus du cortex moteur et l'enregistrement des potentiels d'activités avec des aiguilles concentriques donnent des valeurs extrêmes et moyennes supérieures à ceux observés avec des électrodes de surface. A notre avis, des électrodes de surface sont préferables aux aiguilles dans la détermination du temps de conduction moteur au niveau du sphincter anal externe.

     

PCR Followed by Electrospray Ionization Mass Spectrometry for Broad-Range Identification of Fungal Pathogens

Invasive fungal infections are a significant cause of morbidity and mortality among immunocompromised patients. Early and accurate identification of these pathogens is central to direct therapy and to improve overall outcome. PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was evaluated as a novel means for identification of fungal pathogens. Using a database grounded by 60 ATCC reference strains, a total of 394 clinical fungal isolates (264 molds and 130 yeasts) were analyzed by PCR/ESI-MS; results were compared to phenotypic identification, and discrepant results were sequence confirmed. PCR/ESI-MS identified 81.4% of molds to either the genus or species level, with concordance rates of 89.7% and 87.4%, respectively, to phenotypic identification. Likewise, PCR/ESI-MS was able to identify 98.4% of yeasts to either the genus or species level, agreeing with 100% of phenotypic results at both the genus and species level. PCR/ESI-MS performed best with Aspergillus and Candida isolates, generating species-level identification in 94.4% and 99.2% of isolates, respectively. PCR/ESI-MS is a promising new technology for broad-range detection and identification of medically important fungal pathogens that cause invasive mycoses.     

Examining volumetric gradients based on the frustum surface ratio in the brain in autism spectrum disorder

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is accompanied by neurodevelopmental differences in regional cortical volume (CV), and a potential layer‐specific pathology. Conventional measures of CV, however, do not indicate how volume is distributed across cortical layers. In a sample of 92 typically developing (TD) controls and 92 adult individuals with ASD (aged 18–52 years), we examined volumetric gradients by quantifying the degree to which CV is weighted from the pial to the white surface of the brain. Overall, the spatial distribution of Frustum Surface Ratio (FSR) followed the gyral and sulcal pattern of the cortex and approximated a bimodal Gaussian distribution caused by a linear mixture of vertices on gyri and sulci. Measures of FSR were highly correlated with vertex‐wise estimates of mean curvature, sulcal depth, and pial surface area, although none of these features explained more than 76% variability in FSR on their own. Moreover, in ASD, we observed a pattern of predominant increases in the degree of FSR relative to TD controls, with an atypical neurodevelopmental trajectory. Our findings suggest a more outward‐weighted gradient of CV in ASD, which may indicate a larger contribution of supragranular layers to regional differences in CV.