Fabrication and characterization of high-T/sub c/ SQUID magnetometer with damping resistance

Effects of damping resistance on current versus voltage (I-V) characteristics for high-T/sub c/ superconducting quantum interference devices (SQUIDs) were studied. In the transverse-type SQUID with coplanar strip lines, parasitic capacitance originating from the large dielectric constant of SrTiO/sub 3/ substrates can induce resonance structures on I-V curves and degrade the modulation voltage. In our simulations, it is shown that the modulation voltage is much improved by using damping resistance. However, the obtained experimental results for our SQUIDs with Au damping do not agree well with those in the simulations. The discrepancy is likely due to existence of the large contact resistance between Au and YBa/sub 2/Cu/sub 3/O/sub 7-/spl delta// films

Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism

Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin's effects on ASD remain unknown. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs-including rs53576 and rs2254298-were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD

Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways

Depression is a polygenic trait that causes extensive periods of disability. Previous genetic studies have identified common risk variants which have progressively increased in number with increasing sample sizes of the respective studies. Here, we conduct a genome-wide association study in 322,580 UK Biobank participants for three depression-related phenotypes: broad depression, probable major depressive disorder (MDD), and International Classification of Diseases (ICD, version 9 or 10)-coded MDD. We identify 17 independent loci that are significantly associated (P < 5 × 10−8) across the three phenotypes. The direction of effect of these loci is consistently replicated in an independent sample, with 14 loci likely representing novel findings. Gene sets are enriched in excitatory neurotransmission, mechanosensory behaviour, post synapse, neuron spine and dendrite functions. Our findings suggest that broad depression is the most tractable UK Biobank phenotype for discovering genes and gene sets that further our understanding of the biological pathways underlying depression

Meta-analysis of genome-wide association studies of anxiety disorders.

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.Molecular Psychiatry advance online publication, 12 January 2016; doi:10.1038/mp.2015.197

Treating patients with advanced rectal cancer and lateral pelvic lymph nodes with preoperative chemoradiotherapy based on pretreatment imaging

Yasunori Otowa, Kimihiro Yamashita, Kiyonori Kanemitsu, Yasuo Sumi, Masashi Yamamoto, Shingo Kanaji, Tatsuya Imanishi, Tetsu Nakamura, Satoshi Suzuki, Kenichi Tanaka, Yoshihiro Kakeji Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan Abstract: Preoperative chemoradiotherapy (CRT) and lateral pelvic lymph node (LPLN) dissection (LPLD) based on pretreatment imaging are performed to improve oncological outcomes at our institution. However, the advantage of LPLD following preoperative CRT in advanced rectal cancer remains unclear. The objective of the present study was to assess the validity of this approach. Thirty-two patients with advanced rectal cancer were included in the study. All patients were treated with preoperative CRT and curative operation. Of these, 16 patients who were treated between August 2005 and June 2008 underwent LPLD on both sides (LPLD group). Sixteen patients who were treated between July 2008 and January 2013 underwent LPLD only on the side with suspected LPLN metastasis determined by pretreatment imaging; in cases without LPLN metastasis, only total mesorectal excision was performed (limited-LPLD group). The overall survival and relapse-free survival between the LPLD and the limited-LPLD groups were compared. Preoperative CRT was able to lower clinical lymph node status in 50% of the cases. In addition, pathological lymph node status did not exceed the pretreatment clinical lymph node status stage in the LPLD group. There were no differences in the overall survival and relapse-free survival between the two groups (P=0.729 and P=0.874, respectively). We conclude that multi-imaging studies have a very low risk of overlooking pathologically positive LPLN metastases. Therefore, limited LPLD is a feasible strategy for patients with advanced rectal cancer and suspicious LPLN metastases based on pretreatment imaging. Keywords: neoadjuvant treatment, rectal cancer, chemoradiotherapy, lateral pelvic lymph node, MRI, C

Fabrication and characterization of high-T/sub c/ SQUID magnetometer with damping resistance

application/pdfEffects of damping resistance on current versus voltage (I-V) characteristics for high-T/sub c/ superconducting quantum interference devices (SQUIDs) were studied. In the transverse-type SQUID with coplanar strip lines, parasitic capacitance originating from the large dielectric constant of SrTiO/sub 3/ substrates can induce resonance structures on I-V curves and degrade the modulation voltage. In our simulations, it is shown that the modulation voltage is much improved by using damping resistance. However, the obtained experimental results for our SQUIDs with Au damping do not agree well with those in the simulations. The discrepancy is likely due to existence of the large contact resistance between Au and YBa/sub 2/Cu/sub 3/O/sub 7-/spl delta// films