Measurement of the ttbar Production Cross Section in ppbar collisions at sqrt s = 1.96 TeV in the All Hadronic Decay Mode

We report a measurement of the ttbar production cross section using the CDF-II detector at the Fermilab Tevatron. The analysis is performed using 311 pb-1 of ppbar collisions at sqrt(s)=1.96 TeV. The data consist of events selected with six or more hadronic jets with additional kinematic requirements. At least one of these jets must be identified as a b-quark jet by the reconstruction of a secondary vertex. The cross section is measured to be sigma(tbart)=7.5+-2.1(stat.)+3.3-2.2(syst.)+0.5-0.4(lumi.) pb, which is consistent with the standard model prediction.Comment: By CDF collaboratio

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The use of autologous free vascularized fibula grafts in reconstruction of the mobile spine following tumor resection: surgical technique and outcomes

OBJECTIVE Reconstruction of the mobile spine following total en bloc spondylectomy (TES) of one or multiple vertebral bodies in patients with malignant spinal tumors is a challenging procedure with high failure rates. A common reason for reconstructive failure is nonunion, which becomes more problematic when using local radiation therapy. Radiotherapy is an integral part of the management of primary malignant osseous tumors in the spine. Vascularized grafts may help prevent nonunion in the radiotherapy setting. The authors have utilized free vascularized fibular grafts (FVFGs) for reconstruction of the spine following TES. The purpose of this article is to describe the surgical technique for vascularized reconstruction of defects after TES. Additionally, the outcomes of consecutive cases treated with this technique are reported. METHODS Thirty-nine patients were treated at the authors' tertiary care institution for malignant tumors in the mobile spine using FVFG following TES between 2010 and 2018. Postoperative union, reoperations, complications, neurological outcome, and survival were reported. The median follow-up duration was 50 months (range 14-109 months). RESULTS The cohort consisted of 26 males (67%), and the median age was 58 years. Chordoma was the most prevalent tumor (67%), and the lumbar spine was most affected (46%). Complete union was seen in 26 patients (76%), the overall complication rate was 54%, and implant failure was the most common complication, with 13 patients (33%) affected. In 18 patients (46%), one or more reoperations were needed, and the fixation was surgically revised 15 times (42% of reoperations) in 10 patients (26%). A reconstruction below the L1 vertebra had a higher proportion of implant failure (67%; 8 of 12 patients) compared with higher resections (21%; 5 of 24 patients) (p = 0.011). Graft length, number of resected vertebrae, and docking the FVFG on the endplate or cancellous bone was not associated with union or implant failure on univariate analysis. CONCLUSIONS The FVFG is an effective reconstruction technique, particularly in the cervicothoracic spine. However, high implant failure rates in the lumbar spine have been seen, which occurred even in cases in which the graft completely healed. Methods to increase the weight-bearing capacity of the graft in the lumbar spine should be considered in these reconstructions. Overall, the rates of failure and revision surgery for FVFG compare with previous reports on reconstruction after TES

In vitro hemocompatibility evaluation of the HeartWare ventricular assist device under systemic, pediatric and pulmonary support conditions

The development of adult use right ventricular assist devices (RVADs) and pediatric left ventricular assist devices (pediatric LVADs) have significantly lagged behind compared to adult use left ventricular assist devices (LVADs). The HeartWare ventricular assist device (HVAD) intended to be used for adult's systemic support, is increasingly used off-label for adult pulmonary and pediatric systemic support. Due to different hemodynamics and physiology, however, the HVAD's hemocompatibility profiles can be drastically different when used in adult pulmonary circulation or in children, compared to its intended usage state, which could have a direct clinical and developmental relevance. Taking these considerations in mind, we sought to conduct in vitro hemocompatibility testing of HVAD in adult systemic, pediatric systemic and adult pulmonary support conditions. Two HVADs coupled to custom-built blood circulation loops were tested for 6 hours using bovine blood at 37°C under adult systemic, pediatric systemic, and adult pulmonary flow conditions (flow rate = 5.0, 2.5, and 4.5 L/min; differential pressure = 100, 69, and 20 mm Hg, respectively). Normalized index of hemolysis for adult systemic, pediatric systemic, and adult pulmonary conditions were 0.0083, 0.0039, and 0.0017 g/100 L, respectively. No significant difference was seen in platelet activation for these given conditions. High molecular weight von Willebrand factor multimer degradation was evident in all conditions (p < 0.05). In conclusion, alterations in the usage mode produce substantial differences in hemocompatibility of the HVAD. These findings would not only have clinical relevance but will also facilitate future adult use RVAD and pediatric LVAD development

GNAI1 and GNAI3 Reduce Colitis-Associated Tumorigenesis in Mice by Blocking IL6 Signaling and Down-regulating Expression of GNAI2

Background & Aims: Interleukin 6 (IL6) and tumor necrosis factor contribute to the development of colitis-associated cancer (CAC). We investigated these signaling pathways and the involvement of G protein subunit alpha i1 (GNAI1), GNAI2, and GNAI3 in the development of CAC in mice and humans. Methods: B6;129 wild-type (control) or mice with disruption of Gnai1, Gnai2, and/or Gnai3 or conditional disruption of Gnai2 in CD11c+ or epithelial cells were given dextran sulfate sodium (DSS) to induce colitis followed by azoxymethane (AOM) to induce carcinogenesis; some mice were given an antibody against IL6. Feces were collected from mice, and the compositions of microbiomes were analyzed by polymerase chain reactions. Dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) isolated from spleen and colon tissues were analyzed by flow cytometry. We performed immunoprecipitation and immunoblot analyses of colon tumor tissues, MDSCs, and mouse embryonic fibroblasts to study the expression levels of GNAI1, GNAI2, and GNAI3 and the interactions of GNAI1 and GNAI3 with proteins in the IL6 signaling pathway. We analyzed the expression of Gnai2 messenger RNA by CD11c+ cells in the colonic lamina propria by PrimeFlow, expression of IL6 in DCs by flow cytometry, and secretion of cytokines in sera and colon tissues by enzyme-linked immunosorbent assay. We obtained colon tumor and matched nontumor tissues from 83 patients with colorectal cancer having surgery in China and 35 patients with CAC in the United States. Mouse and human colon tissues were analyzed by histology, immunoblot, immunohistochemistry, and/or RNA-sequencing analyses. Results: GNAI1 and GNAI3 (GNAI1;3) double-knockout (DKO) mice developed more severe colitis after administration of DSS and significantly more colonic tumors than control mice after administration of AOM plus DSS. Development of increased tumors in DKO mice was not associated with changes in fecal microbiomes but was associated with activation of nuclear factor (NF) κB and signal transducer and activator of transcription (STAT) 3; increased levels of GNAI2, nitric oxide synthase 2, and IL6; increased numbers of CD4+ DCs and MDSCs; and decreased numbers of CD8+ DCs. IL6 was mainly produced by CD4+/CD11b+, but not CD8+, DCs in DKO mice. Injection of DKO mice with a blocking antibody against IL6 reduced the expansion of MDSCs and the number of tumors that developed after CAC induction. Incubation of MDSCs or mouse embryonic fibroblasts with IL6 induced activation of either NF-κB by a JAK2-TRAF6-TAK1-CHUK/IKKB signaling pathway or STAT3 by JAK2. This activation resulted in expression of GNAI2, IL6 signal transducer (IL6ST, also called GP130) and nitric oxide synthase 2, and expansion of MDSCs; the expression levels of these proteins and expansion of MDSCs were further increased by the absence of GNAI1;3 in cells and mice. Conditional disruption of Gnai2 in CD11c+ cells of DKO mice prevented activation of NF-κB and STAT3 and changes in numbers of DCs and MDSCs. Colon tumor tissues from patients with CAC had reduced levels of GNAI1 and GNAI3 and increased levels of GNAI2 compared with normal tissues. Further analysis of a public human colorectal tumor DNA microarray database (GSE39582) showed that low Gani1 and Gnai3 messenger RNA expression and high Gnai2 messenger RNA expression were significantly associated with decreased relapse-free survival. Conclusions: GNAI1;3 suppresses DSS-plus-AOM–induced colon tumor development in mice, whereas expression of GNAI2 in CD11c+ cells and IL6 in CD4+/CD11b+ DCs appears to promote these effects. Strategies to induce GNAI1;3, or block GNAI2 and IL6, might be developed for the prevention or therapy of CAC in patients.Fil: Li, Zhi-Wei. University Hawaii Cancer Research Center; Estados UnidosFil: Sun, Beicheng. No especifíca;Fil: Gong, Ting. University Hawaii Cancer Research Center; Estados UnidosFil: Guo, Sheng. University Hawaii Cancer Research Center; Estados UnidosFil: Zhang, Jianhua. University Hawaii Cancer Research Center; Estados UnidosFil: Wang, Junlong. University Hawaii Cancer Research Center; Estados UnidosFil: Sugawara, Atsushi. University of Hawaii; Estados UnidosFil: Jiang, Meisheng. University of California at Los Angeles; Estados UnidosFil: Yan, Junjun. No especifíca;Fil: Gurary, Alexandra. University of Hawaii; Estados UnidosFil: Zheng, Xin. University Hawaii Cancer Research Center; Estados UnidosFil: Gao, Bifeng. University Of Colorado Anschutz Medical Campus.; Estados UnidosFil: Xiao, Shu Yuan. University of Chicago; Estados UnidosFil: Chen, Wenlian. University Hawaii Cancer Research Center; Estados UnidosFil: Ma, Chi. University Hawaii Cancer Research Center; Estados UnidosFil: Farrar, Christine. University Hawaii Cancer Research Center; Estados UnidosFil: Zhu, Chenjun. University Hawaii Cancer Research Center; Estados UnidosFil: Chan, Owen T.M.. University Hawaii Cancer Research Center; Estados UnidosFil: Xin, Can. University Hawaii Cancer Research Center; Estados UnidosFil: Winnicki, Andrew. University Hawaii Cancer Research Center; Estados UnidosFil: Winnicki, John. University Hawaii Cancer Research Center; Estados UnidosFil: Tang, Mingxin. No especifíca;Fil: Park, Ryan. University Hawaii Cancer Research Center; Estados UnidosFil: Winnicki, Mary. University Hawaii Cancer Research Center; Estados UnidosFil: Diener, Katrina. University Of Colorado Anschutz Medical Campus.; Estados UnidosFil: Wang, Zhanwei. University Hawaii Cancer Research Center; Estados UnidosFil: Liu, Qicai. University Hawaii Cancer Research Center; Estados UnidosFil: Chu, Catherine H.. University Hawaii Cancer Research Center; Estados UnidosFil: Arter, Zhaohui L.. University Hawaii Cancer Research Center; Estados UnidosFil: Yue, Peibin. University Hawaii Cancer Research Center; Estados UnidosFil: Alpert, Lindsay. University of Chicago; Estados UnidosFil: Hui, George S.. No especifíca;Fil: Fei, Peiwen. University Hawaii Cancer Research Center; Estados UnidosFil: Turkson, James. University Hawaii Cancer Research Center; Estados UnidosFil: Yang, Wentian. No especifíca;Fil: Wu, Guangyu. Augusta University; GeorgiaFil: Tao, Ailin. Guangzhou Medical University; ChinaFil: Ramos, Joe W.. University Hawaii Cancer Research Center; Estados UnidosFil: Moisyadi, Stefan. No especifíca;Fil: Holcombe, Randall F.. University Hawaii Cancer Research Center; Estados UnidosFil: Jia, Wei. University Hawaii Cancer Research Center; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Zhou, Xiqiao. No especifíca;Fil: Chu, Wen-Ming. Guangzhou Medical University; China. University Hawaii Cancer Research Center; Estados Unido