Brain imaging of the cortex in ADHD: a coordinated analysis of large-scale clinical and population-based samples

Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. Methods: Cortical thickness and surface area (based on the Desikan–Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707). Results: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen’s d=−0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample. Conclusions: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis

Erprobung und Versuchsergebnisse des PNP-Teströhrenspaltofens in der EVA-II-Anlage

For the development of a licensable steam reformer, arrangedand operated in the primary circuit of a HTR process heat plant,a steam reformer bundle with 18 full scale tubes and a nominalpower of 5 MJ/s was manufactured and successfully tested inthe EVA II-plant at KFA-Jülich. With these tests under normaloperation conditions and also under disturbances the thermal,process and mechanical design could be approved. The steam reformer test bundle was operated for a total timeof 5200 h. During a test time of 3230 h the temperature inthe helium inlet zone was in a temperature range above 900 °C. Temperature cycle experiments took additional 520 h, wherethe helium inlet temperature was cycled more than 100 timesfrom 960 °C to 630 °C to 960 °C. The process parameters werevaried in such a broad field, that most of today's foreseeableoperation conditions of nuclear heated steam reformersare included. Within this range the test bundle fulfilled theexpected data and the experimental results could be forecastedby computer simulation. The demounting of the bundle out of the steam reformer vesselwas done without any difficulty. The optical impression ofthe bundle was very well and was confirmed by measurement. For more intensive inspection after operation and material tests the bundle will be disassembled

Axon guidance of rat cortical neurons by microcontact printed gradients

Substrate-bound gradients expressed in numerous spatio-temporal patterns play a crucial role during the development of complex neural circuits. A deeper understanding of the axon guidance mechanism is provided by studying the effect of a defined substrate-bound cue on a confined neural network. In this study, we constructed a discontinuous substrate-bound gradient to control neuronal cell position, the path of neurite growth, and axon directionality. A variety of gradient patterns, with slight changes in slope, width, and length were designed and fabricated by microcontact printing using laminin/poly-l-lysine (PLL) or PLL alone. The gradients were tested for neurite growth and their impact on axon guidance of embryonic rat cortical neurons. The neurite length was determined and the axon was evaluated by Tau-1 immunostaining. We found that the microgradients of laminin/PLL and PLL directed neurons' adhesion, differentially controlled the neurite growth, and guided up to 84% of the axons. The effect of the protein micropattern on axon guidance and neurite growth depended on the protein and geometric parameters used. Our approach proved to be very successful in guiding axons of single multipolar neurons with very high efficiency. It could thereby be useful to engineer defined neural networks for analyzing signal processing of functional circuits, as well as to unravel fundamental questions of the axon guidance mechanism

HTR-Modul-Entwicklung. Schlussberichte zum F+E-Vorhaben ''Weiterentwicklung von Messgeraeten und elektronischen Bauteilen fuer Helium-Systeme''

Der Bericht enthaelt vier Beitraege, die einzeln in der Datenbank referiert sind: 1) Jod-Messung beim Druckentlastungsstoerfall; 2) Photometer zum Nachweis einer Dampferzeugerleckage; 3) Fuellstandsanzeiger fuer den Kugelbehaelter und 4) Abbrandmessanlage. (HP)The volume contains four reports which have been analysed for separate retrieval from the database. The reports deal with the following: 1. Iodine measurement in the event of a blowdown accident. 2. Photometer for detection of steam generator leaks. 3. Level indicator for the KLAK container. 4. Burnup measuring instruments. (HP)SIGLEAvailable from TIB Hannover: F93B1359+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Injured Podocytes Are Sensitized to Angiotensin II-Induced Calcium Signaling

Background Inhibition of angiotensin II (AngII) signaling, a therapeutic mainstay of glomerular kidney diseases, is thought to act primarily through regulating glomerular blood flow and reducing filtration pressure. Although extravascular actions of AngII have been suggested, a direct effect of Angll on podocytes has not been demonstrated in vivo. Methods To study the effects of AngII on podocyte calcium levels in vivo, we used intravital microscopy of the kidney in mice expressing the calcium indicator protein GCaMP3. Results In healthy animals, podocytes displayed limited responsiveness to AngII stimulation. In contrast, in animals subjected to either adriamycin-induced acute chemical injury or genetic deletion of the podocinencoding gene Nphs2, the consequent podocyte damage and proteinuria rendered the cells responsive to Angll and resulted in AngII-induced calcium transients in significantly more podocytes. The angiotensin type 1 receptor blocker losartan could fully inhibit this response. Also, responsiveness to AngII was at least partly mediated through the transient receptor potential channel 6, which has been implicated in podocyte calcium handling. Interestingly, loss of a single Nphs2 allele also increased podocytes' responsiveness to AngII signaling. This direct effect of AngII on injured podocytes results in increased calcium transients, which can further aggravate the underlying kidney disease. Conclusions Our discovery that podocytes become sensitized to AngII-induced calcium signaling upon injury might explain results from large, randomized, controlled trials in which improved renal outcomes occur only in the subgroup of patients with proteinuria, indicating podocyte damage. Our findings also emphasize the need to treat every patient with a glomerular disease with either an angiotensin-converting enzyme inhibitor or an angiotensin type 1 receptor blocker

Characterization of tumor-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma

The composition of tumor-infiltrating lymphocytes (TIL) reflects biology and immunogenicity of cancer. Here, we characterize T-cell subsets and expression of immune checkpoint molecules in head and neck squamous cell carcinoma (HNSCC). We analyzed TIL subsets in primary tumors (n = 34), blood (peripheral blood mononuclear cells (PBMC); n = 34) and non-cancerous mucosa (n = 7) of 34 treatment-naive HNSCC patients and PBMC of 15 healthy controls. Flow cytometry analyses revealed a highly variable T-cell infiltration mainly of an effector memory phenotype (CD45RA(-)/CCR7(-)). Naive T cells (CD45RA(+)/CCR7(+)) were decreased in the microenvironment compared to PBMC of patients, while regulatory T cells (CD4(+)/CD25(+)/CD127(low) and CD4(+)/CD39(+)) were elevated. Furthermore, we performed digital image analyses of entire cross sections of HNSCC to define the 'Immunoscore' (CD3(+) and CD8(+) cell infiltration in tumor core and invasive margin) and quantified MHC class I expression on tumor cells by immunohistochemistry. Immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) were increased in TILs compared to peripheral T cells in flow-cytometric analysis. Human papillomavirus (HPV) positive tumors showed higher numbers of TILs, but a similar composition of T-cell subsets and checkpoint molecule expression compared to HPV negative tumors. Taken together, the tumor microenvironment of HNSCC is characterized by a strong infiltration of regulatory T cells and high checkpoint molecule expression on T-cell subsets. In view of increasingly used immunotherapies, a detailed knowledge of TILs and checkpoint molecule expression on TILs is of high translational relevance